AU2017235989B2 - Infusion systems including computer-facilitated maintenance and/or operation - Google Patents

Abstract

INFUSION SYSTEMS INCLUDING COMPUTER-FACILITATED MAINTENANCE AND/OR OPERATION Methods for setting up, maintaining and operating a radiopharmaceutical infusion system, that includes a radioisotope generator, are facilitated by a computer of the system. The computer includes pre-programmed instructions and a computer interface, for interaction with a user of the system, for example, in order to track contained volumes of eluant and/or 10 eluate, and/or to track time from completion of an elution performed by the system, and/or to calculate one or more system and/or injection parameters for quality control, and/or to perform purges of the system, and/or to facilitate diagnostic imaging. 15 Figure ID WO 2009/152323 PCTJUS2DO9/047031 C> Cr,) V-1 LO Io D to a- LOC1 cCr 0' rtyricirru t vrfl ) rllT13I

Description

IWUSKWSYSl EMSINCLUDING COMPUTER-FACILFWED.

MAIN IWANCE AND OR .OPERATION

RELAffiD APPLICA’HONS < 'The present application claims prioritv to the toiknt ing I .8. patent applieatimis: U.S. patent application serial No, 12 13~3to. fikxi June I?Vfi8; I ^!.S. patent application serial No. 12/137,363, filed June 11. 2608.1 .0. paunt apptic.b-ou serial No. 12/137,364, filed June 1L2008; and U.S. patent iipplkution serial No. 12/137,377, filed June IL 2008.

1Θ i'hc present application is a div Ntonal application derived fieri parent application number 200^257432 which is herein incorporated in N entirety by reference,

TECHN1UAL FIELD

T5 The present invention pertains to systems that generate and mfitse radiopharmaceuticals, and, more partieniarly, to systems incitidmg computer-: _: tociiito® maimenahce and/or operation;

RAUKGROl ND

Nuelear medicine employs radioactive material Ior therapy and diagnostic imaging. Positron emission tomography (ΡΒΓ) is one typerif diagnostic::imug:mg, which utilities doses of mdtopharmaceutical, tot exanplCirgcndtotodEyselutian Within a radioisotope generator, that are injected, ortotosed into a patient. The intosed dose of radiopharmaceutical is absorbed by cells of a target orgam of the patient, and emits mdiMiou, which is detected by a PET scanner, in order to generate ait 'miage of the organ. An example of a radioactive isotope, which may be used tor PET, is: Rttoidigm8:2 (produced by the decay of Strontium-82); and an example of a radioisotope generator which yields a saline solution of Rubidium-82, via elution, is the CardloGen82ίΦavailable from Bracco Diagnostics Inc. (Princeton, NJ). A ΡΕ Γ scanner in combination with infused doses of radiopharmaceuticals may also be employed to

2017235989 28 Sep 2017 quantity blood flow rate, tor example, through the coronary arteries of a patient.

Set up, maintenance and operational procedures for infusion systems that both generate and inject doses of radiopharmaceuticals are relatively involved in order to assure the safety and efficacy of each injected dose for the patient. E fficicncy in carrying out these procedures is highly desirable Ibr technical personnel, who work with the systems on a routine· basis and would like to avoid unnecessarily prolonged exposure to radioactive radiations. Thus there is a need for new system configurations that facilitate more efficient set up, maintenance and operation.

SUM MARY OF TH E IN V ENTION

In accordance with a first aspect of the present invention. there is provided a mo bile radioisotope generator system comprising:

a movable platform carrying an infusion tubing circuit, an activity detector, a dose calibrator. a computer, and a shielding assembly containing a strontium/rubidium i 5 radioisotope generator configured to generate a radioactive eluate via elution of an eluant.

the infusion tubing circuit including a tubing line connected between the slrontium/rubidium radioisotope generator and the dose .calibrator, and configured .to supply a portion of radioactive eluate to the dose calibrator.

the acth ity detector being positioned downstream of the slruniiunv'rnh'uiium radioisotope generator and configured to measure an activity of the radioactive eluate flowing through the infusion tubing circuit, and the computer being electronically coupled to the dioe calibratoj and configured to execute automated quality control testing using the dose calibrator.

in accordance with a second aspect of the present invention, there is provided a mobile radioisotope generator system comprising:

a shielding assembly configured to contain a strontiunVrubidium radioisotope generator that generates radioactive eluate via elution of an eluant and an infusion tubing circuit comprising an eluate tubing line configured to convey eluate from, fne ?0 stronthun/rabidium. radioisotope generator:

2017235989 28 Sep 2017 means for measuring an activity of the eluate flowing through the eluate tubing line;

means for receiving eluate from the eluate tubing line and calculating breakthrough activity witbin the eluate; and means tor receiving activity data from the means for measuring the activity of the eluate and also receiving breakthrough activity data from the means for receiving eluate and calculating breakthrough activity and controlling the mobik radioisotope generator system based on the received activity data and breakthrough activity data.

JO in accordance with a third aspect of the present invention. there is provided a method comprising:

delivering eluant to a strentium/rubidmm radioisotope generator carried by a movable cart and thereby generating radioactive eluate via elution;

measuring, with an activity detector carried by the movable cart, an activity of 15 the eluate within a tubing line of an infusing tubing circuit;

delivering a portion ofeluate via the tubing line to a dose calibrator carried by the movable -cart,, and performing quality control testing on the eluate delivered to the dose calibrator.

co In accordance with a fourth aspect of the present invention there is mo idod zk. system comprising:

a shielding asstmhh configured to contain a radioisotope generator th;u generates radioactive eluate via elution;

a computer carried by the shielding assembly, wherein the-computer is configured to receive a user input and. responsive to receiving the user input, control the radioisotope generator to generate a sample of eluate \ ia elution during breakthrough testing; and a dose calibrator electronically coupled to the computer and configured to measure an activity of the sample of eluate generated during breakthrough testing,

2017235989 28 Sep 2017

2b wherein the computer carried by the shielding assembly is configured to receive the activity data from the dose calibrator and calculate breakthrough test results.

In accordance with a fifth aspect of the present invention. there is provided A method comprising:

generating, with a radioisotope generator contained within a shielding assembly, a radioactive eluate via elution of an eluant;

measuring, with a dose· calibrator electronically coupled to a computer carried ;G by the shielding assembly, an activity of the radioactive eluate; ana determining, with the computer, an activity of rubidium-82 within the radioactive eluate,

BRIEF DECRLPTION OF THE DRAWINGS i 5 The following drawings are illustrative of particular embodiments of the present invention and thcretorc do not limit the scope of the invention. The drawings arc not to scale (unless so states) and are intended lor use in conjunction with the explanations in the following details description. Embodiments of the present invention will hereinafter he described in conjunctions with the appended drawings.

wherein like numerals denote like elements.

l-'igme IA k a first perspective view of an infusion system, accotding to embodiments of the present invention.

Figure 1B is another perspective view of a portion of a cabinet structure of the system

2017235989 28 Sep 2017 shoWA In Figure 1A, aeeording io some embodiments.

Figure IC is n second perspective view of the system shown in Figure 1 A, according to some embodiments,

5:

figure Η) is a 'vhemstic of an infusion circuit, .uuord’.ng Uj ^nne cmbudhmmw Ά the present mvmUmm

Figure IE is a perspective view of exemplary sample vial shielding that may be

Hi employed in eon junction with the infusion system of Figure 1 A.

Figm-e 2 A. Is; a perspective view of a shielding; assembly Wf an. infbsmn system,_: such: as that \ndwn in Figures ! A^C^aecordihg to some embodiments of the /present Invention, i s Figure 3B is a pempeetiv e view of a framework of the system _f according to some embodiments, with an enlarged detailed view of a component of the system,: according to some embodiments.

Figure 3 A is andtlter perspedti ve view of the shielding assembly she wn In F igure 2A, Jo

Figure '3'B is a perspective view of the infiision circuit, show in Figure 10, ccnSgnred, and mated, according to some embodiments.

Figure 3C Is A perspective view of a disposable infusion circuit subassembly,

J5 according to some embodiments,

U'H fol

2017235989 28 Sep 2017

Fi^irs.3D is a fiamc for the subas<>enfoly show in Figure 3 C_:. ng io some emtodimcnls.

I cure I ix r^Kui sx co foot f mu _t»n u >, f i o . oi ' fo ^v _v nuy bo nwleded in systems o·'the present invention, a coid rc fo sifoi.- w? >> h eer.s

Figure 5 A is a xdicmatie showing a first group of r.croxo x wroer foo.x fo <m the contofoer interface, according to some embodiments.

Fi-rore 5B is - pair of screen shots front the compote’· interface. v>b.c>. sox tdo mdse aborts 'dated to eluant x uluroe levels in χ reservoir of the system, according to some embodiments.

H} Figure 5C is a sch ematic showing a second group of successive screw· shots fium the compfoettfitfofimd. aceotding to some embodimenfo

Figure 6 is a schematic showing a third group of successive scree? < os .ten the computer interface, according to sow embodiments.

Figuros TA-G toe schematics Showing a fomthgfoiip oFsuccsfoiVn scroen shots j5 from the emuputer iuterfoee, according to some embodiments.

Figures 8A-B uro schematics showing a .Oh . group of wecossive sfoem· shuts from the computer interface according to some embodiments.

Figures 9A-C are schematics showing a sixth group of sfocessfoe .fotwi. shorn fem according to rome embtidimenis.

Figfod 10 is a schematic showing a seventh groupfof successive screfot shoto fiom the eowipnffo intfo&ce_t according tosonfo embodiment

Hgure 11 is. an exemplary report which m&y be generated by thewmpfoer tnetoded in mlnsion systems, according to some embodiments.

Figures 12A-B are schematics of altomfoiv© intostdiioircphshWmay be 35 employed by embodiments of the present invention.

Figure 1.2C is a schematic itatmting exemplary activity pro dies orinjeeted doses of a radiopharmaceutical.

DFrXfLHD DESCRIFnON

The following detailed description Is exemplary in nature and is nonn temfed to limit the suope, applicability, or configuration of ihe mventon m any way, Roihep the· foikm ing desenptior pro\ ices pniciic.il lUuMmhon* foi jmplemt.-m.ng cxempAry

2017235989 28 Sep 2017

WOi.2<WlS2323: Wettest embodiments. . ®firin| foe teaching provided hernia, those skilled m the art will meognme that many of the examples have suitable altemutries that can be utilized, f mure 1 Ai® fitet perspective view of an infusion system 10. according tv some embodiments ofthe pres® invenripn, w herein system 10 is shown supported by 5 a cabinet structure, whfoh includes a platform 113 (keen better in figure 3B) and a shell l:k shell 13 extends upward from a skirt 11, that ?urroanes pisiform : :3, to mrroimds ;m inrerier space in which a pornon of mfus’on syst-rin 10 h con-.uucd ( seen in Figure 1C). Shell may be formed from panels of injcctiou-molded polyurethane fitted together according m methods known to those skilled m the art. Figure 1A 10 illustrates the cabinet structure of system 10 .including a grip or handle 14, winch extends laterally from shell 13, in pmximiiy fo an upper surface 131 thereof. and a post 142. w Inch extends upward from $M 13,nmd to which a work surface, or tray 1 <> and a computer 17 ere, preferably, attached, viaw ergonomic. positionable mount. Vcmdnm to some embedments. compute: U :s eoup'ed to a em.tiv.ic¹ A) which is omuh® wifofo the interim-spacetstpTounded by shell 13: and. a monnor I C of computer Ϊ7 not only displays fodibatfons of system operation for a user of system W, but a® serves as a device for user input fo.g, touch _:s®en input). However, according to alternate anbodiments, another type of user 'ippat .device, known to those skilled m foe art_s may be employed' bycomputer 17, Other types of user input -devices M may be meludedj for example, a .keyboard, < series of οοηΙτοΓ buttons or levers, a bar code pfo-def for other reader of bedded informatbn^ a scanner,: a gompufor madab I e medium cuufoinisg pertimmt data, efo, Tbs user input dev® may be mowfodou the cabinet struehire of system; 10, as shown, Of may be :t$tfiered-^:,tk^rsipk^terftahWly?the user irmm device may be remote front system 10, for example, located m a separate 25 Control room. According to some additional embodimehts, another user input device, < for example, in addition to a touch screen of computer 17, may be remote from system W and used to start and stop in&foous, as well us to-monitor system operation both during quality control infusions and during patient infusions. Operation of system 10, which is facilitated by computer 17, will be described below, ip conjunction wuh •Ο FiguresA^.

Figure 1A forther illustrates two pairs of wheels IT T 122<mnmted io® ®derride of platform 113, fo make system 10 mobile; handle 14 isAhown heatedAt an elevation suitable for a person to grasp hi order to maneuver system 10. from one

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2017235989 28 Sep 2017 focatfon for annthtt; upon_: pairs of wheels 121. 122. According to amne pmterrtjd emlvthmeurs. oneot both pans of wheels 121. l-fe arc .a-tom, j'!> vmg s ’ onmon in a howzoei.A plane•(^wiXTS.orlSr-B^rovide additional flexibility for rnaumϊvering system 3Θ in rdativeiy tight spaces,

Figure IB is a perspective view of a portion of system 10, on x side 111 of the c-ibiurt stricture, which is io pioximuy io wheels 12b t igure IR ihu-urato's a let er <· pedal 125, which is located for activation by a foot of the person, who grasps haadio 14 to maneuver system 10. In a neutral position, pedal 125 allows wheels 12.¼ i 22 to rotate, and, if embodied as casters. to swivel freely. Pedal 125 may bo depressed to a W fest position wfochprevento a swiveling of wheels 122. according to those embodiments in which wheeis 122 arc custom, and maybe further depressed m brake Wheels 121,123 riom rolling and swiveling, upon reaching a desired location.

Accord fog to some embodimen% braking may be designed to slow system 10, for example, when rolling sfowg tin iiictine, arid, aecorditig; to yet further embodiments, 15 system 13 may mci-me a motor to power ηκ.η-emcut thereof.

figure IR further illustrates; a roar access panel foloffowl: b’-exmnpfo pFovidfo.g.aecess:to circuit boartisfe the aforetitenfiouedfoentfeterr -ru rod within... foe itferior space fed issurrounded by shell 13; Moptipnal fock ISfo fo secure pane! 174; tipnwer jack I II, for comccrrag system 10 to u revrer somce, and a pr mm 117 20 for ptoviding doenmefoatfon of each patient mfosfe' earned o.d Ip sj nrrr - 0. wm of sysfen quality control test resufe. In some embodiments, system 10 may further foehfoe ti power strip by which auxiifory equipment may be powercdynfe.fonemr more additional eleqtiieal eqnaeetors, or ports (not shown), which afe snppbfed by platform. .113 afe wy be integrated into shell 13, for feampfe:te profomity to jack .25 118 or printer 117; these electrical eonnecfors/portsAlfowlsysfen 10 to confefefoate;

with, other devices wd for nuclear imaging pfoeedurgs, forpxamplej a· RIST scannertcamertt, andfor for ccunhrg to an ir p ’w* ’ ethers. ?r d <r .e foe mtotarn. t_C' example, to link up withmonware ptogtams for various types or'dam. analysis, and/or to link to computers of consulting cliniciatis/physicians, and/or to link into service 30 providers tinfoor component suppliers data bases for sfeaneed.maintstitotoe and ^: inventory management

Figure 1A forther illustrates upper surfoee 131 pf shell 13 mcfodihg sfeefol openings 133,135,139 formed therein. Figure 1C is a partially exploded j ci >pvct v_PCf/tl $2409/047'751

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2017235989 28 Sep 2017 ’icfto’s\'>\n 10 9·\ι tern a p me ->2 w'lruui ι>ν> h> .

portion of upper .surface 131, which, when exposed. by lifting away a bin IS. that nuiti' .rerun .th,’m pc cmoeed *n>m <neWi epcoe ; '⁷ * >nce m hN<

Bl. Figure IC also provides a better view of another panel 13-4 which may be ntled «Wiiv from opening 139. Accordingto the illustrated embodiment, opening;.' i3va.tiG

13⁷ provide a user ofaystem 10 with independent access to separate portions of mfusion system 10, which-are contained within shell 13, for example. to set up ano mainta® system 10; and openings 133 and 135 provide passageways for tubing linos to pitas through she'd 13. Figure IC fmtiier illustrates an optional '•tu’.b ⁵ 02 'Wiv n, case of an emergency, may be activated to abort function Of system 10- w tth re'erence 10 Figures 1A and IC, it may be appreciated mat an arrangement of Imtmres formed m upper surface 131 of shell 13, in comtmcimn with bin 18, trav lb . vd computer 17. provide a relatively ergonomic and organized work Wa fer technical pewnnel who operate; system 10.

Tomina now to Figure ID, a schematic of an infusion ctreu-i .>00, which may be moorpofitied by system 10, is shown. Figure IM iildstmtes c treuj 1 300 generally divided into a first panTOOA, whitih mcludes components-.mounted outside shell 13, and a second part 3WB, which includes components mounted within the interior space

WWnded by shell 13. (Parts 300A and 300B are delineated by dotted lines in Figure 20 IDT Figure: ID further illustrates second pari 30® of circuit 300 including a portion.

contained within a shielding assembly 200, which· is designated schewhcaUy as a _: dashed fine. Some em'bgdmwnls of Shielding assembly 200 will be dpscnbeU in greater detail, in coni unction with Figures 2 A-B and 3A-B, belowAccording to the illustrated embodiment, circuit 3.00 includes: ay eluapt reservoir 15, for example, a bag, bottle or other container,. codtaming saline': ds the eluant, which is shown hanging fettm apost, or hanger -141 above upper surface IM of shell 13 m Figure 1A; a.syringe pump 33, for pumping the eluant from reservoir 15. and a pressure syringe 34 (or other device or sensor), for monitoring pumping pressure; a filter 37, which may .also serve ax a biibbleTrap,: for the pumped eluant;n radioisotope generator 2'1, through vzhich. the fit tered el uaat: t& pi ,m pec to create a radioactive: eluate, for example an eluate earrying RubidiMAi”82 that is genwted by the decay of Stmntium-S2, via elution, within a column of gen end 01 2': arc an adtvity detector 25, tor measuring the activity of the eiua’.c mscharged from genes mor I in

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2017235989 28 Sep 2017 order to preside to How of the eluate, via a divergence va.b e

35WP, reBhcrtoa waste bottle 23 or thwgh a patient line 305p, for example. w inject a dose of a patient. With reference back to Figure

A, patient line 305p is shown extending out from shell .13. through opening L>5, to a distal end thereof, which, according to some embodiments, includes a filter. Patient line 305pmay-.be coupled to another line that includes a patient injection needle (not Λι\ομ i'-'voA. jx..uu* me hBr tna\ *., „nap ed m i ctoe r c ^{> l}'' i which extei«isi^:fe^sa:?®ww,<^Wthcr acfc-vc substance, for example, a stress a gem; fee other Ore coup ed to the hue tlut tnchidcs the parent re cure's uvedhv re <rekr :o permit injection of the additional aebve substance.

Figure ID illustrates an eluant tubing limr301 urnpfed to reservoir 15 and to pump 33, and, with reference to Figures 1A-B, it may be appreciated feat opening I33 provides Ute passageway for tubmglitie 301 to enter the mterior space surrounded by shell 13. According to sonic preferred embodiments, opening 133 includes a grommst-tjpe-^al that preymts leakage pfpluant, whwh rmo spill from reservoir 15, into the Inferior space through opening 133, while 4110^ reg a sstoto assemble Omg line301 dreough opening 133. likewise opening 135, %<dh. provides^:a pastogeway :ret paiien < I aw 305p , may include a gtoinmei-tpe seal. According to _: some embodimems, shell 13 further supports holders to safelyteld, fer^: example,; dufipg: transport of system 10, portions of tubing lines that ex tend. Outward :thersfrum, tor example,; line 301 audfer line 305p,

Figure ID ferther Illustrates another eluant tubmg-line-302pUmp.:33. and a divergence valve 3 5BG, which may either direct pumped bluMt through· a ;tubing line 304, io generator 2.1,. or direct the pumped ©Inant through;a fewpassdubrng tine 303i directly to patient line 3O5p. Divergence yaM: 35BS, aS' w^LresdiWgencsi valve 35 WP, which directs eluate from, an eluate tubing line 305 either to a waste :lm& 305W or re patient Itoe 305p, may each be automatically operatediby a corresponding servomotor (not shown), coupled to the compiler (no*, shown} of system 10, which controller receives feedback from activity detector 25. When system 10 is ope rating lor automatic infusion, to deliver a dose of todiopharmaceuticaf to d patiem. lor example, Ru.bidfem-32 for diagnostic imaging.: diyergenee valve3'5BG isunitiallyPtot to direct eluant to generator 21 and divergence valve 35WP is set io direct eluate from generator Into waste bottle 23, until activity detector 25 detects the desired activity ot

2017235989 28 Sep 2017

WO 2809/152323 *< VS2‘Hf*> «4'831 the chafe, at which frw Ore foedbaek from activity dgteetor 25 causes the eoptfoher Ιό direct the corresponding servo-motor to re-set valve 35 WP for diverting the flow of eluate into patient line 305p. According to some efobodimenu, once a preoerihed volume of the eluate .has passed through patient line 505p, the eontrulicr directs the corresponding servomotor to re-$et divergence valve ,>5E>G tor diverting the flow ot eluant through by-pass line 303 and into patient tine 305p in order to flush, or push any eluate remaining in patient line 305p into the patient. According to some embodiments, the controller may also direct the cocrospon.bng servomotor to re-set divergence valve 35WP back toward waste bottle 23, prior to rhe flush through by-pass 10 Ime 303, hi order to prevent back frsv of ehutd. through tme 305. to^utd genetator

21, According to some preferred methods of operation, in certain situations, which will be described in greater detail below, eluant is pumped through by-puss line 303 immediatelv following the flow of the prescribed sofomc ot: oate into patient line 3O5p, at a higher speed, in ortfor to push foe oiu.re m pabcm Hut 3C5, thereby 15· Increasing aflowrate of the infection of chute out flofopasem hne 3l?hp and into patfont For example, onoethnprescribed votanie of eluate has fioued imo patient line 305p, and once divergence valve 35BGihWfo divert Bow t&wgh by-pass line 303. foe speed of pump 33 may bou^uBedto focrease foe flow rate of eluant foWtfosm apprexhnafoly -WfoLfoah and sppmxlmMdy 1OOmlfonfo.: T& method, fer increasing 20 : foe injection flow rate, is desjfobifo if a relatively high Bow foie is desired for ptfoeifo fufoction and A ffow rate through generator 21 is limited,; for exafoplfofo befow approximately TOmlfonfo, ntaxiinum (typical Bow fofo may be appfoxifoafoiy : bOfofofofo), in order to avoid an excessive back pressure created by foe ; cufofoh;0f generator 2:1 fo upstream portions of tubing circuit 300·: the expefoifofoack prssfore 25 codd damage filter 37 or otherwise irr^ede fiotvfhreugh ellmP tubfog/irpe:

Although not shown in Figure 1¾ a number of sensors,_: :for Wwplfo fo measure pressure and/ot flow velocity, mayfoe iifoorporated info efreui? 300, accordingfo some alternate embodiments, in order to monitor for Bow anonialies, for example, related to oceltisions/pfogs in circuit 300 and/or leaks, wdforfo pfovide foedbaek for 30 control of an activity level of infused doses of mdiophamuiCeuticaL Suitable sensors »«< ? e J >- Ό'·\’nt ww¹·· uc> to tiow' si 1 ed ., i eart I esο ^Λ <w metem that may be incorporated .into circuit 30fo include the hmova-Somcfo Model 205 dkmsiOiwUltrasonic liquid Flowfofoto that employs digital signal processing

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A ^{he Flocat LA 10-(.: dsffor.'trofo p-^>um Sow wisFc· (foie example of a pressure -sensor that may be empioyoo to eete-..r infusion circuit occlusions is the FRO / PressuroOcclusion Detector (available from 1NTROTEW of Edgewood, ΝΥ» a subsidiary of Magnetrol of Dowsers Grove, 11,.), 5 which enwioys pulse-type ultrasound; this sensor detects subtio changes m positive sub negative air pressure and produces a cntrespond'ngpa.v;o,e msv-mx : nur'et Ograi, wiped mayiea^fethe system controller and/or computer Π. On or more of this type of sensor may be; in corporatcd into infusion circuit 3ifo by simpjy titling tne sensor around any of foe tubing lines of infusion circuit 300; in fact, the PRO /

Prcssmr-fhvhHiori Detector may be a suitfo -m alternative to rmsvjw sj rng. 34 <>;

circuit 300. Other types of pressure sensors, for example, similar to those known m the sit lb? blood pressum monitoring:, uiay be employed in mtu&ion circusr SOU.

Svsifon/IO may anther include sensors fo detect Hum levels tn etuard reseiwir 15 and. waste botile 23. Some examples of such ssjwrs_?/whiifofoso smploy foe albremcntioocd pulse-type ultrasound. are foe Drip Chamber Liqu’d Level Sensor im<: the OLD Z Commutw Level Detector (both available from INTROTEK^);·· d’emJisth, to*· ιφρχ, c HPQ-Tpme mounte,.. ’’-u ^T* nod u ' ’ ‘•e x't (available from Ysmafoke Sensing Control foii), or an SL-630 Noiv iavww DisppsaiyyR<msabfr I.4?velSwfoih (avfolable from. Cosme*· feci *r iiavprauac, XY1 may be employed fo detect foe fluid levels. Alfomately or in addsuom »vstem 10 can jndufoi additwai mdiaiioA abdfor moisture detection..sea^rs, which: can detect leifos. With refereitce to Figure 1IX such sooshrs: ar© pfoforanly located ih- preefrfoity m Whip 3 H, 312,313, 314' aud 315 that j pin portions of cirefof 300 to one ahother. Some examples of leak detection sensors include, without limitaflop, · those fo the:

HFQ-I) leak detection sensor family, and the H’FF-DfldO flbefoptic leak detector (ah available from Yamutake Sensing Control. Ltd.). System ihmity runner mciudc additional sensors to detect contaminants and/or air bubbles within the tubing lines of circuit; examples of such sensors include· the Foifo-air Deteetipn (PA D) Sensor, mat eniploYS'£ulse-typd fot.msm.md for air bubble detection, and the Blood Component

Detector that employs optical sensing technology perform. Co lanmfory’'bW^::Sfod detection, of unwnfosd elements fo. the tubing lines (both avm fable: from

1.NTROTEKB),

2017235989 28 Sep 2017

I^s C IV Γ S20UW8 λ 05 s t<)

Aecordtog to those cmLodun.'i'is thui uu'udc any et the above sensois, tnv sensors are linked idife the cmitroller of system 10 and/or computer t v. eimcr of wmch mav pro* Je a signal to· a-user of system 10,. when, a flow anomaly is detected, and/or information to the user, via monitor 172, conesming fluid levds, pressure and-or (tow through ercuii 3<K). Computer 17-may be pro-progrsmrncd to display, tor example, onmonitor 172, a grapiiic of infusion circuit 300 wherein each zone ot the circuit. where an anomaly has bee® detected, ishighlighted, and/or to provide guidance. io the System user, for emrectmg the anomaly. It should be noted that the altcrnauw infusion circuits iUnstretcd to Figure» 12.A-.8, which will be described below, may also W include any or all Of these types of sensors.

With farther reference to Figure ID, it maybe appreciated that shidding assembly 200 encloses those portions of circuit 300 from which, radioactive mdiUtion may emanate, with the exception of that portion of patient line 305p, wtoch must extend otoiftom to rhe paiiwit tor m»>xton o m ου. ei to be vouptod to <ucHe-. sa op e uafr ,. ·. λ ί κ »crei ( below. Thus, tedmtoal psresrmef who operate system 40, are protected from radiation bs sb e dmg asMU-bb 200, except at ’ho-w a no. whto an oOioon o ux ng p <w . o’ when: miality control tests rectors collection of eluate mto sam pl e vi ats. Durhig mfusiems mid quality coairol Wsample collection, AU Wmfcal pewmrnl am typically^;in another room, or mherAlxe distanced from -.system· 10, · in owier -to avoid exposure tp mdia&m during &e inih&iOm and, according to some preierrop. mnbodlwms of the ^present mvemfeu. system 10 mditdes m imt-bne mourni hr informing technical personnel that an infosioh is about; to take place'cr. is talcing place. With reference back to Figures IA and IQ system fOisAhown^:ihciudingg|light projector 100,_; mounted on post .142, Accorduig to the· ulustmted embodiment, projecw 100,-.projects a light signal upward, fe nwimum wibility, when pump 33 is pumping eluimt end elmton is taking place within generator 21, or at all times when pump 33 is pumping eluant. According to some embodiments,;.the lighr. sigmd flashes onaud off when the eluate b: being diverted frtmi generator 21 into woe bottle 23,

30· .and the light signal shines steadily when the; eluate Is being diverted through patient line 305p, or visa versa. According to other embodimmQ: ^projector ;l 00 shines& light having a first.color,.tp indicate that eluate is-being diverted io waste ooltie 23, and then shines a light having a second, different color, to indicate that ctuato is being

PCT/USat^Wt 7031

Η directed ίο patient line 305p for infusion. Light projector 100 may further project a. utore rapidly risshing light, fix example, for approximately five seconds, once a peakbolus of radioactivity is detected in the eluate, to provide further information to technical personnel. Alternative means of informing technical personnel drai an infusion is taking place may also be incorporated by system 10, tor example, including audible alarms or other types of visible'Or ^:iwdable signals th at are apparent at a distance from system, including in the control room.

It should be noted that according to alternate embodiments, system lb includes an ^sdn board’ dose calibrator for quality control tests, ano circuit 300 is expanded to include dements foran automated coUcctton of eluate samples for activity mcasucracrns. vut tne oe board oxw. canbra.ot *roe> r Iraj to a ή”' to'¹ alternate embediments, a sample eofetfon reservoir is integrated into circuit 300, downrfroam of divergencewaive foWP'trnddn communication with tubing line 505P, ip order fo receive qualify control test samples of eluate, vta tubing Ime >05 P, »nu notu 15 the reservoir and the dose^c^^wtr^e-Ioc^ted in a separate shielded welt According to ..a wwi M of these altcmate embodiments, waste · Bottle 23 is configured to .receive the quality control test samples of eluate, via tifomg. lisc 30SW_sand a dose eahhrater is migrated into shtelding assembly 2dfo_: Quality conttofproccdiiw W bo described in'greater detail below, th conjunction with Figures 6-Wgp When maintenance of system 10 requites the emptying waste bottle 23, relatively, easy access to waste bottle 23 i&prOvided through opening 139 in top surface 131 pfshell 13.· It should be noted that technical personnel ^preferably trained to empty waste bottle 23 at timea when the:eluate, ebutofoed mwarftoMtfe 23_? has decayed suificimttly to ensure that the radioactivity therebt has felieti uctow s_{: ;} threshold to be safe. Opening 139 is preferably located at an_: eleyatios ot between approximately 2 feet and approximately 3 .feet'for example, npey mg 139>ay be at an elevalimt of approximately 24 Inches, with respect to a lower surface or platform 11 >, or at art efovatimt of approximately 32 inches, with respect: to a ground surface upon svhich wheels 121,122 rest According to the illustrated emlxtoimsm. opening 139 is 3(1 accessed by lifting panel 134; just within opening 139, a, shielded fid or .door 223

J ,a.ue Ώ mav pc Yfed wvav from a coimwitncs t o’ <mc>d’»g rose ably 230 ttvt contains waste bottle 23, With fenher reference to Figaro 1C. it may he uppocroued that opening 1W provides access to other portions of circuit 300 for addb soccl

2017235989 28 Sep 2017 mtenteitenee-procedures, such -as changing cut generator 2 i and/or other eomponents of cihmrt:3O0j a&.will be described below.

Fur those: embodiments ofsx'stcm IO e x% ολ , <u: muaed 4 v u)f>’>»tests are peffonned wd/or when system IP ts cnmloxx 4 tor tehnveh a 'F xo υ'-χ' operation, managementof waste may become burdensome, _:«x on OGutp to waste bottle 23 is greatly facilitated, as described above. Thus, m u,·!,? m xun itete waste management, some embodiments of system 10 may e** ploy a separation-system to scpxate sabs, including radioactive elements, fimn wsts tei e.mmrte. x m evapomnor orreve’se osmosis. in an evaporation type system, die oxc'· comrono n 10 of the waste is evaporated, while in a reverse osmosis type system rhe xvarcr is -epamted nom rhe ,sate, and, item any® confirmed to be non-r&dioacrivc, via a. radiation delectot, is pmed to adrain. According to some otter embodiments, circuit 3?X) maybe eontlgmoJ souhafthe waste may be used io purge air from the tubing tines thereof andtef to perform ttebyptes uteh that was described above, preferably after 15 the mdinateyity of the wteste;dmps tefeW a drifipal ttedshold.

Figures 1A and IC further h histral c 3. pair Of relatively shallow; external recesses 19¾ which are formed in upp^xurface 1.31 of shell 13, ter example, in onier to earch any spills from mfiteon system; one of mtews J90 is shown located m proximity to post, or hanger 141;, which holds reservoir 15, and m.ppjxiteity to 20 opening 133l thmugh which tuHngdinc. 301 p&sses. Another recess 192 i* shown termedte upper surface 131; a width arid depth of recess iFdmxy accommodate storage of technical dtemtenteiod associ sted With untesten system. 10, ter example,: a technical manual and/or maintenance records, Or printouts from printer ;! 17 /(Figure I Eh. With mferenes to Figute IC, upper surface 131 of shell .13 is shown to also 25 ineiude;addrtiouai recesses 101, which are each sized to hold a shielded test vial, 'which contains samples from infusion system 10, for example, ter breskihrOngh testing and/or calibration, which v.iU be described in greater detail, be-οχν, .An exemplary testwial shield is shown in Figure IE, The test vial shield of Figure IE is preferably termed from Tungsten rather than lead, for example, to reduce exposure m 30 lead, for -improved shielding, and to reduce th© weight of the shield. Figure ι E illustrates the test vial shield -including a handletosimpEly-ntatepulaiiouthereof but: dtemative configurations of test yiid shields have no handle — ter these; a sling, or strap, may be employed for handling.

WG

PCT/6S.2909/e-T<Gr

2017235989 28 Sep 2017

Addmonal recepteeles 180are shown fanned in bin 18, on either ».u a Imudfe -SC. which feeilitates removal of bin 18 away from shell 13. Techmeal persmmeimay, thus; conyenieutiy transport bin 18 to a storage area lor a collection ot supplies, for example, sharps, gloves, tubing lities, etc..., into one or more receptacles to.) thereof, and/or to a waste container where separate receptacles 1 $0 of bin IS may to emptied ^n'anste. sneb as packaging for the .ritom'wmxwi.'u aupp-.es Ό ex.cap e, depositeduhsreih during infusion procedures. According to some embodiments, one or moreuddilfonal: mcepfacies are formed in one or more disposal containers. for example. to contain, sharps aadfor radioactive waste (other than that conunnoh in waste i() bottle 231 which may teinmgrated into bm 18_s or otherwise fitted into, or ariached io shell 13. separate Som bin 18.

I y r' 2 X *> 1 f? qxen vicv. ci -hu ^!dr g 3-/'6; 20( o - * embodiments of the present invention. With reference io Figures IC and 2A, together, it may be appreciated that opening 137, in upper surface 131 of shell 13, provides acerss to a 114 or door 221 of a sidewall 201 of shielding a.xsemb'\ 2e0. <:ud skww.G 201 encloses a compartment sized to contain a radioisotope generator of system 10, ror example, generator 21,: previously introduced..· It should fee noiod tnat, according ?o .alternate embodiments, the compartment enclosed by sidcwali 20 is at to enougn to hold more th?mone generator, for example; to increase .system, epemtog ..erticiency tor rektovbly high yplmb® operation. In soiite ot these alternatetembodiments. tuotng tines 304 ami 305 are each branched tor parallel flow thmugh th^tniiitiple generators,: in which.case divergence valves may be employed to: alternate the Sow through: the: generators, one to a time. Is others of these totem ate embodinieptSj, the mtdtipip generators are connected in series/between, tubing line:304 and fobm^ime305. In addition, a reservoir for aecumulaimg eluate may be Included: m circurt:300, downstream' Of the generators and upstieatii of divergence yalye 35 W 0. in romunet-on With a second pump, in some cases. Embodiment inehtdmg multiple generators andtor an eluate reservoir and second pump can be empInyeitto better manage an actitoty- level of each dose, or patien t injection, tor example, m described below, in 30 cotettoction with Figures 12A-B.

According to th® embodiment illutorated in Figure 2A, opening 132 and door 221 allocated at a lower elevation, tor example. With respect to platform 113. than are opening 139 and lid 223, which provide access to the compartment being formed by a sidewall 203 of shielding assembly 200 to contain waste botoe 23. as previously described. Vi hen panes ’ 52 is separated from she'd 13. sen cw ?? 1 ofomto. yenerw.'· 21 maybe lifted out from an opening 231 (Bgfoc3A) which mates wiih door 221 of sidewall 201. A weight of generator 21, which /includes its own smesdmg, may be between approximately 23 and approximately 25 pounds, thus, according io some preferred embodiments of the present invention, rhe elc widen ol\ sen -<> onernngs 13/ and 231. with respect to the lowermost portion of the cabOwl structure·. w woaew. approximately I foot and approximately 2 feet, inorder io umbrat·.- λ enpxamm stance for technical personnel to lift generator 21 out from ihe eomp^rhnem. According to an exemplar,¹ embodiment when shielding a.xsvn>b:\ 100 is eonuiincd ro the cabinet structure of Figure 1A . openings 137 and 231 are locates «1 an ere' rnion of approximately 12 inches, with respect to the lower sunace ot pUtforo. >, 3. at an elevation of approximately 19 inches, wife respect to the ground surf.· c upon which wheels 121, 122 rest.. Figure K?hoccss/panel 132 including a security lock 138. which mates with a framework 19 of system 10, xboxsn in Figure 2B, in order to: .limit access to generator 21...

Figures 1C and 2A . fiiitoer/ilfosfrato: a lid or a door 225 of another sidewall 20 5 (Figure 3A) of shielding assembly 2Θ0, whichencloses wofoer wmpartment ibax is accessible ihrongh opeairig 13 7 of shell 13s and which is located aaj scent t he eoippxrtmeni encloaedby toilesvaU 201. Iidch of deters 2el, uw.5 are Sitown being attached by a cptresponding hinge H, and another door 227 to shown attached to sidewall. 203 by another hingeH. Figure 2A iftusteates reach Of fed 223 and doors 22.1,, 225,227 including a handle 232.212, 252 and:272,.rospdcriyeiy, for ihbvinglid 223 and dobra 221, 2.25,227, in order to provide access to the: corresponding compartmen ts, which can be seen in Figures 3 A·®. Fi gdre_: 2A: furthergllysrortea optional thumb screws 290, one securing lid 223 to sidewall 2B3 and girofoer securing door 221 to sidewall 201, or other means for securing the doorSi, which arc known tn those ski lied in the aft, maybe incorporated. Each -sidOWalbS^lj 203. 205 and the corresponding lid/door 223,221,225,227 thereof may be individually cast from 3¾¾ antimony lead, or fi'om other known shielding materials, and then assembled together acwriing to methods known to those skilled in the art.

AvxO'dmg >» ire ''.lusuatcd \ ntrod nw-u, curex 22. sw I mux - e ‘P‘ ¹¹ an upward direction, per arrows DwndC, and, wftb reference tuck to Figure iC, u

W0 2tWA52320

2017235989 28 Sep 2017

LW co’iponeut I¹⁵' is p yvntod to hold e„eb ot ireis 52L 2''^ o ,u op > C κο yr..

^iercbyfpwwnting doors *21, 225 from felling closed, which could pmchfcrush fingereof technical personnel and/or tubing lines of circuit M.K.1, v hen in the niiiist et a maintenance procedure. Figure 28 is a perspective view of framework 19 of the .5. cabinet structure of system 10, according to some embodiments, to which latch component 191 Is mounted; Figure 2B includes an enlargec detaueri v-ev, >.n later: eompon®pt;l9I, according to soOembodimcnis. Figure 2B illustrates latch ςοιηρουοηΐ Wl mcludmg a first pin 193. corresponding tn door 225, arc, a .worL n;n 195^ coraesponding todoorSTl; each pin 193, 195 includes a lever end 193A, 1938, respectively, ana a holding end 193B, 195B, respectively. An edge of each dem 221. 225, upon opening of doors 221, 225, may push past the holding cud 195B, 193B of the corresponding pin 195, 193, in a first direction, per arrow F, arid then mey rest against a respective side S95 and S93 of each end 195¾ 193B, mini the cnrrespnuuing lever end 195 A, 193A is roofed in a ebiinterfeiiitokwise direefiom per arrow cc, thereby moving ihe correspOfidifig Itoid&g end 19'B, 195B to make way lor the closing of doors 221, 225. Dores 221,225 being held by latch Icompommt 191 m an open pwtfea may be seen, m Figure: 3 A.

With farther reference to Figure 2A,:acemfeg to some preferred embodiments^ of the present fesentrou. sn edge of door 225 cwerBp* coot 22 ’ to present door,—ΐ 20 frptn being opened, per arrow D, if door 225 ranot opened,per arrow (.·> and an Cwge.

<door:227 overlaps an edge of dW 225 to prevent door 225 fibre being ppmed i.f door 227 is not opened, per arrow B; and an edge of lid 223 overlaps door .22 / to prevent door 227 from being opened if lid 223 is not opened, par wdw. A. Thus,: access to the compartment enclosed by sidewall 201 uhd corftaiutug.generator x-1 is :25 only systemntroslly allowed through a sequential opening· of lid 223 told doors 227;: 225,221, since, when generator 21 is replaced it is typOy desirable to also replace those portions of circuit 300 which are shielded behind lid 223 and doors 227, 225.

The routing of these portions of c ircui t 300 will be described in con itmelion with: Figures 3A-C.:

Figure SA is another perspective view of shielding assembly 20B uncording to some embodiments of the present ito cation. In Figure 3 A, Iro /2? and doors,— 1, ~25, and 227 are opened to provide a view into openings 233,235 anti 231 ot Mdewads: 203,205 and 301, respectively, and mto a passageway 207, umeh is tore.ru m

2017235989 28 Sep 2017 ®c wall 203, opposite the compartment, WhiChtoontalss waste bottle 23. .Passageway20'' w shown extending vertically along sidewall 203 and having a grooved o?; rension 2 s j formed in a perimeter:: surfocc of opening 233. An optional rcrainmg member 23?. fe example, formed fem: an efongate Strip of resilient plastic having a general iy c5 shape cross-sccuon, is shownbring nm®ed along u length of passageway 207 to hold lines 305w and 3O5p in place within passageway 207. Figure 3 A former illustrates a pair of passageways 25 lb and 25 lg, which are formed as grooves in a portion of sidewall 205. and another pair of passageways 215i and 2.15o, which are formed as giooves &a portion of sidewall 201. A routing of portions of tubing circmr 300 foigi® W) througb passageways 207,253b, 251c, 215i and 215o Ls shown in Figure 3B._: figure 3B illustrates tubing fine n)4 bemg touted though pas.w.gev, to \ 2'' a and 2i?i, eluate tubing fine 305· being touted through passsgev'ay 2.1 So, and both, waste line 305w and patientlihe: 30Sp befog routed riong passage w ·ο 207. Waste fine IS 3&5w M gforivp® U ®i-patient line 30Sp forther extends outWrd 'fem TOOJm npifeto extend outthrough openmgiSS fo upper surface 131 of shell 13 (Figure i A). According to the illustrated embodiment, each passagew® fomted:in shfoldfog assembly 200. by befog accessible: along a length thereof, can farililate a relatively easy routing of the:

20^: eoriespOi®ngtubing line-^eretoou^whm-tlie ^responding lid/door is open, and h depth of each passageway prevents pin®ng and/or erttshingof theeorresponding tubing line rnfoed Ihemtbrtmgh, when the eorresponarngdiridoor is closed down thereover. With further reference to Figures 3 ArB, it may be appredated that the compartment formed by ridewall 201 may have a shape mafehmg su exterior contour of generaw 21, such that generator 21 is fikeyed* tofoe^fopartimmt^·:® example,: to prev® ipstailafimt of an improper generator into system 10, andfor to facilit®: the proper ori®ation of genera tor 21 within the compartment for the proper routing oi' tubing lines. Alternately, or in addition, aecofeng to alteniate ®bndiments, if system 1 It includes it reader of encoded mformatiQn m e-omrnuuicaticn with computer 17, ah uulqite idmmfeatiim audfor data associated whh each gcr.er *rm may pro*id® tot example, in a bar code label or a.r^ofeqwnc5<identi.fic8iion:(SlFID) tag ihai is attached to each generator, so that the reader may transfer the:mfomMfou to:computer 17, when a generator is msralled, ip order to cither enable system uperatfou <n to

HO

2017235989 28 Sep 2017

Γ;

provide anfedicatrott to the user that tin. focorrect gettcrator has bsmt mstaucm Ot course a user of system 10- mtiyt tiitetnattily, rnamialiy enterinfomiatiori, that is provided on a generator label or marking, into computer 17, in order to either enable system 10, or to.r^^ybjfoc’dback from computer 17 that the; incorrect generator is installed.

f'^re 3 k ’ - me* sufe* a J 2(R mu'ea^a i' the m to ,e r ^>.

253, into which divergence valve 35WP is mounted, to be controlled by one ot the scnoiFouxoMroishoMP ofs>_ofunr 10, -red at o-permg 32? (or □.?«'< t> detoctoi 2? Activity detector 25 is mounted m a shielded well 255 that extendsaowti'ward from.

opening 3:25 (shown in Figure 3B), and, with rclmence to Figure 3B, tubing line 305 passes over opening 325so that detector 25 can dcteci an activity of foe fouatc, which passes thefehrough, Accofomg tosome embommoaw, foe posfomfeg, witbin the compartment enclosed by sidewall 205, of the cun tpnnents of the portion of tniasion cfemt300 wfefeare shown routed therein, is iacfeatod by providing the components fooufoed m a Stone 39 as a disposable subassembly 390, an emtxxiimcm oi which is illwmted by fogttifo 30¾

Figure 3C is a perspective view of subassembly 390, and Figure 3D iti a psrspefeve view of feme 39. Aecpfomgto the feme 30 foformed from mating trays 39A_fJ9B, for exfonpto, formed ilom a foermoforned pDsuc. which lit together to captuio. therebetween, are hold, iu feed relation to a perimeter edge of feme 39, divergence valve 35 WP and pocuvrs o: eluant tfemg lino 304, by-pass tifeng fem303, eluate tubing line 305, waste line 305 w Mid patient line 305p, Figure 30 illustrates the perimeter edge diGded into a fest side 391, a second side 392, opposite fest side 391. th third side 393, mending between:

first and second sides 391,392, and a fourth side 394^ opposite third side 393, Although Figure 3D shows trays 39A, 39B indfoiduatiy formed for totting fogefefo according to alternate embodfeents, mating trays of frame 39 may be parts of a continuous sheet of plastic folded over on itself

According to the illustrared embodiment, an end 404 A, of eluant line 3fok and an end 403, of by-pass fee 303 extend fem third side 393 of feme 39 to couple with divergence valve 35BO and an upstream section of eluant tubing line 30'2. Figure 3C :fta'ther illustrates au opposite end 404B of efoant line:extending fem first side 391 or feme 3fo alongside a ^similarly extending end 405 of eluate line 305,,and ends 40b and18

PCI !

2017235989 28 Sep 2017

1.520 to? of rutuxu hue H'fp and waste Hue 30iw. iwipcetivrly. eMcmfow, acr recvrc mie 392 of frame 39. Although ends 4 06, 40? are shown extending upward from n ay 39a, as they would within shielding assembly 200, it should be appreciated that the tubing lines of wit 300 are preferably llexible and would drop down under their own weight rather than extending upward, as shown* if -not supported. Referring back io Figure ID, in conjunction with Figure 3C, it can be seen that the aforementioned ltiJKv<^v> ptov doc hn coupLng ^ub^sensblv W nt' uru« to- ’*>n, M couples the section of eluant line 302 to filter 37; second fitting 312 couples cluam line fotooan Jo porter etunat» r 21, tl id Fton„ U >, wnnA m, u u^<» valve, couples eluate line 305 toran outlet port of generator 21; fourth fitting 314 couples waste ImeBObw to waste boh 1c 23; and fifth fitting 3.15 couples patuw he305p to ati extension thereof, which extends outside shell 13 (designated by me duded line). Each of the fittings Sil, 312, 313*314, 3.15 maybedfthe I-aer r»ye. may be a type suitable for relativelyother suitable type that is kupw to

As previously mentioned, when generator 21 is replaced, it is rypkfoly desirable .to also replace those portions of ci mult 300 'which are shielded bchind iid 223 and doors 227,225^ and, in those instances wherein system 10 is moved to « new site each day,^: fosse portions may fee replaced daily, -Thus, according to the illustrated Wbodiment, these portions : are conveniently held together by frame 39,_: as subassembly 390 m order to fonifitate relatively speedy removal and repteeeuwi, < while assuring it, proper assembly orientation,, via, fegistraifou with: features fomlcd M sidewall 205 (Figure 3A>; for example: registrationpf divergeites valve 35W^: with valve actuator receptacle 253, registration bf tubing line ends 403 and 404A with: passageways 251b and 251 g, respectively, wfotemfonbf tubing Ihre ends db^'B, and

405 with passageways 2151 and 215o, wpcctivcly, and registration of tubing line ends

406 and 407 with passageway 207.

With forther reference to Figure 3B_S other portions of tobfogylreuit 300 ere shewn. Figure 38 illustrates eluant tubingItae 301 extending from reservoir 15, outside of shell 13 (Figure 1 A), to syringe pump 33, which_::fr mounted to w: tmtuaimg, piatfonu 433, According to the illustrated embodiment, platform. 433 is aetpatedby another servomotor (not shown) of system Id, which is embroiled by the dbritroilet ano computer I 7 of system 10. to cause a plunger of pump ^3 to mose, per .urev I. so

2017235989 28 Sep 2017 as to draw u- eimmf, from rcservuir 15,tlwough tubing line SOT, and then to eauswtlm plunger to move m the opposite diwctionso us to pranpffeeiwA 302, to either generator 21 or to by-pass line 303 Although die illustrated embodiment includes syringe pump 33, other suitable pumps, knew a to iho<' \k -lied

S in the art. may be substituted for pump 33, m order to draw eluant front reserson 15 r io pcom toe Urn n* ^'mughoid eveur 300 \lthi a co, wxr Ό - e _x appreciated that divergence valve 35BG is fitted into another valve actuating receptacle mounted within shell 13 and coupled io yet another .servo-amor - not shown) of system 10.

Figure 3B further illustrates a filter holder 317 dial is mounted alongside an * ceno’ '•r ’'bee of -foe. t > to h.s d fiber 3 »’,I igum 1ϋ) m i. birg rw ^x<,l ', „> holder 317, like frame 39 for subassembly 390, may be formed from a tnenriohumcd plastic sheet; bbldcr 317 may have a elam-shell structure to enclose filter 3⁷ m an tmerior some sei allow tU^ag uno 302. on efihe: i>idc m ' ,ter > v>. vm m : com the interior space, m betweenopposing: sides of the bliim-s.heT -structure. Holder 317 is shown including an appendage 307 for hanging hoi de'· 317 from a sfoiicftn'e (riot shown) inside shell 13.

Turning nW fo Figures 4-9G details: concerning: computsr-fsoifiiafod operatic® of system 10 will be described, according fo sb me embodiments of the present

20' invention,.. As previpuxly mentioned, and with reference backto/Figufe/lA, computer O of system 10 includes monitor 172, which, prirfi^ablyi : hot duly displays mdicidfoi$ of system operation to inform a user of system,10) W is also :cWfigared. as a toacfr screen <o corm mpnt Iron' the user I sho'Jd K understood that comp pct ' ⁷ w coupled :tb the controller of system 10, which may be mounted within the interior . 25 space simwnded by shell 13:. Although Figure 1A shows compow O moimtedW post 142 of system 10, for direct hardwiring to the eontroUerof system: 10, according to some altemste embodiments, computer 17 is coupled to foe controller via a ftexi&klead thatallows computer 17 io be positioned srmiewhef mmoieiy fibm foose portions_: of system 10, fiom which radioactive radiation may emanate·; or, accordi-ig to some oilier embodiments computer 17 Is wirelessly coupled, for example.· via two-way telemetry, to the controller of system 10, for even greater flexibility in positioning ccnmutor 17, >o thai the operation of system 10 maybe monitored and ccmimilcd remotely, away from radioactive ngfiatfoo.

WO wsm S333S

AceordinKto some preferred ernbgfofoenty computer I~ is pm-prognnnmsO; to guide the user, via monitor .K’2, through procedures nccessaf’v to ma ut«in system th. to perform quality control tests on system 111, rnfo to operate system :C> lor ptmciu infusions, as well as to mteraci wifo tlwwer, viafoc ⁺oucb~xLrecn ^apaiuhty ot rumto 2,muim/metonreUrooemRbh-ue: s <* <rsk^w or .Cs' Ln > o e on and eluate contained within system 10, to track a time from completion or -erjca elution performed by system 10. io calculate one or more system parameters fortne quality cunfmi tests, and to perform various data operations. Computer 17 may atso no pre·· ?rogmmmcd to interact with the controller of system 10 in order to keep a runaifig tally or count of elutions per unit time, fora given gstiemtor employed by the system, and may farther categorize each of tlto counted elutions, for example, as bcmg aevcmmd either as a sample, for quality control testing, or as a dose, for patient injection. The elution count add categorization, along-with toeasurimwis made on each sample or dose, for example, activity level, volume, flow ra*···. 'to , may be maintained in a stored record on epfopui^d^i All or a portion .dt ir R .wt cd information, can be compiled ma mpott, to be printed locally , whor to co eleforbhicaUy frsnsforfed to a remote location, for «xample^yiasu internot connection to fochfo cal support personnel, suppliers, service provider, etc.,.., &, ptw owly dhseribed? Computer 17 im-iy further interact xvith the user audfor a reader of encoded informatibh, for example, a bar cod©header or a radfofrequeircy iaentiriC'ai.ion (RFID) tag reader, to afofo and Organize product.fofofmation colWed ffom a PtoOuct labeis/tags, cdtitrol, and/or confemmg i tut ibe proper components, for example, of the tubing circint, arid/or accessones; and/or solutions w being used in the system.

It should be undemtood that screen shots shown m Figures 4-9ό: areiexempfoty in natum and are presented to provide an outline of some methods of the present myendon in-which computer 17 focilitaies ths aforementioned procedures, without limiting the scope of the 'mvemioii to any partiefoar computer interface format. Computer 17 may also include & pre-programmed user manual, which: wy be viewed on monitor 172, either independent .of system operation or iucotyunetfen with aystoto_: operation, for example, via pop-up help screens. Although the English language is employed m the screen shots of figures 4-9C, st should be uudcmtoou that, accorurug

3ί to some embodiments. computer Π is pre-programmed to provide guidance re .30 multiple languages.

Figure.?4^; is<asereenshot of a main menu 470. which is presumed by computer 17 on monitor 172, according to some embodiments. Maia menu 470 metodes a listing of each comptoeUfotolfiated eperaiiun that may bo selected by (he user, once the user has togged on. .According to some multi-lingual embodiments. computer 17 presents a list of languages from which the user may select, prior to presenting main menu 470.

: Figure 5A is a schematic showing a series of screen shots which ^;ru hates a u-g to sereea 570, According to some einbodimetos^vyhen the userftoucb-solucw the data entry fields of screen 570 or 571, or of any of the otherscreens prosetoed herein, below, a virtual keyboard is displayed for touch-select data etory into the solecred data entry field; alternately, computer 17 may be augmented ..-with amuhe: ν,ρν o: det me ror user data entry, examples of which include, wfohont limhuttan, a peripheral keyboard device, a storage rnedtam ri.e. disk) reader. a scanner, a bar code reader (or other reader of encoded information). ahaud emlfrol (i.e. mouse, joy stick, etc.,. ,s. Although not shown, according to some esibodhnento, screen 570 may fortherinehfoe wmt’w' si 'tv envv fie .1 tn o hub tuc rer η- required to eute^T a _uwnx I e. κ »med o the^; gehefotor emp toyed; by system 1.0 m order to enable operetta® of system 10; the key may ba time sentotive, related to generator «toitaet terms. Of couree any -number of Ida in reqmrements may be employed, according to vario us embodiments, and may be presented dh multiple sequentially appearing screeds rather than -tm a single log:m screen.

After the user enters the appropriate information into: dataerriry Belds bf log in screen 570, computer IT presents a request for the user to c<m.firhy :fee wlume of eluant that Is within reservoir 15 (e.g. saline m saline bag), via a screen 5?1. and then brings up main menu 470. If the user detennhms thto the yoiame of cluanb sal me ss insufficient the user selects a menu item 573, to replace the saline bag. If system 10 includes an encoded information reader, such as a bar eode or RFID tog reader, confirmatfou that the selected reservoir is proper, Ι Α. contoius ife proper saline: solution, may be carried out by computer 17, prior w coanocting the reservoir into circuit: 300, by processing information read from a iabehtag attached to the reservoir. Alternatively, or in addition, tubing line 301 df circuit 300 may be proMded with a

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2017235989 28 Sep 2017 connector which only mates with the proper rype of reservoir 15. .to.cordmg to some emltodimcttts, system I0;Wy:fi^tfcwlpde an osmolarity or charge detector, which is located just downstreamof reservoir If : and is linked to computer 17, so Unit error message may bepresented on monitoj· 172 stating that the wrong osmolarity or 5 charge is detected in the eluant supplied by reservoir, indicating an improper solution.

One example of a charge detector that may be employed by system I 0 is the SeiCmt™ Conductivity Sensor (available from SciLog. Inc. of Middleton. Wf)

Once the reservoirfsaline bag is successfully replaced, computer 1 7 prompts the user to enter a quantity of saline contained by the new saline bag, via a screen 574.

ΐδ Alieuadciy, if vystetn 10 includes die atbrem.onttonedreader. ami th·: sa'.nc nwmdeva.ag bv Y w uncmfon.roon ispfos.coc. :U reto '•'n' a nb ironsfci rite quantity iufo^nation u> computer P, 3 bus, computer 1 ⁷ uses either the confirmed eiuantAaifoe volume^ via Screen: 571, or lhe newly entered clpunt saline volume as 3 baseline front which to track deptetten of reservoir volnme^i a activations of pump 33, in the operation bf system 10. With reference to Figure 5B. during me operation of system id,: when computer 17 detects foat the ehstett reservomsaline bag has been, depleted to a predetermmsrl volume threshold, sompnter I7 warns ths user, via a screen 577. If the user has disregarded screen:577 and sputinu fo: to deplete the saline bag, computer 17 detects when the salmo Bag.is empty and rwvidestindfeiefop.

of the same to ths user, via a Screen 578. Wrepfemsh the resetvon oJme %ig, toe user may either refill the rwttvoii?bag Of replace: the empty resetvotohag wttn a rail rosewfobag. According to some embddimeitts, System 10 automatically precludes any further operation of the system until foe resuryoir is replenished. .Ithhptild: ίχη noted that, as: previously mentioned, system .10 cap include a lluld level renscg coupled :25. to the eluant reservoir in order to detect when foe level of satine;drdps below a certain level.

In addition to fracking the volume ofelnant in reservoir IS, computer 1’7 also tracks a volume of the eluate which is discharged from gewator 21 i nto waste boh J e 23. With reference to Figure 5C, an item 583 is:provided:m mam menu 470, to bo selected by the user when the ^;u$er empties waste bottle: 23, When the user detects: item:

SB, computer 17 presents a screen 584, by which: foe user may effectively command: wnputer .17 to set a waste bottle level indicator to zero, once the user has emptied waste;bottie 2X 'Typically; the wx, when powering ep system 10 for opera-ion each

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2017235989 28 Sep 2017 day, wiS reither empty waste bottle 23, or confirm that wxuste bottle 23 was emptied at thp end ofOperation the previous day, and utilize Screen 584 to set the waste bottle level indicator to wn. Thus, computer 17, can track the filling of waste buttle 23 via monitoring of the operetion of pump 33 and divergeutc valve 35WP.. and provide an indication to the user when waste bohle 23 weds to be emptied, for example, via presentation of screen 584, in order to warr. the user that, unlcxs emptied rhe w-esto bottle will PvfoffoW. Aeeordingto some embodiments, system 10 automatically prechafe anyforther iteration of the system until the waste bottte Is emptied. Ac®3ard&t?fo:Wme'aietiiatBe itnbodimetts, u Hate fes, scnx> ere lx eo^kx re ^v 0 waste /retire, for example, as mentfonsdabove in cmyyncws with Figufo 10. m order to automteiealh detect wbra waste bottle is filled to a predetetmiiteU lv\ .'. c;c re provide, via computer 57, an indlcatkneto the user that waste bon c 23 seeds to Ire emptied and/or to automatically preclude operation of system 10 um.d the wastv Mile is emptied.

k· addition to the above mafore.·ancc steps related to ek-aat at id cl u ate volumes of system W,; the user of system 10 willtypically perform qualfiy control tests reach day, prior to any pari ent infusions. With reference to Figure; 6, according: to prefefed methods, prior -to performing the quality control tests (v.utHn^d fooowm ->>η uv.h Figures 7A-€ and 3A-B)_$ the user may select an hem 675 from main menu -7(1 te 20; order to direct system 10 to wash the column of generator 21. 'During the genciutpr coluw wash, which is ;pnrfbrmed by pumping a predeterarihed velum© of ciuant_s for ewnpte, approximately 50 milliliters, through generator 21; andfoto waste hottie 23« computer 17 provides an indication, via a screen 676, fofo -foe washes m pmuress Alsu, during the generator column wash, the system may pfedde a spreal u> indicate'· that eluate it being diverted to waste bottle 23, for example. If.ghtiptojectoriW (Figufo

TO) may prejeei a Hashing light signal, as previously described.

Figure 6 further iliWrates a screen 677, which is presented by computer 17 upon completion of the column wash, and which pro vides an indication of a time lapse since the completion of the wash, in terms of a time countdown, untd a stfeeqtten t elution process may be effectively carried out. While screen 677 is displayed, system 10 may be refilling, from reservoir 15, pump 33, which has a capacfty of apptexitnaiely 55 milliliters, aecofoing to some embodiments. Accotthug to some preferred embodiments of 'foe presentinvention, computer 17 starts a timer once any

2017235989 28 Sep 2017 plufife process is completed and informs the user of the time lapse, either in terr s .«f fe time copnidown (screen 677), or in terms of a time from completion of the e uh-m, for example, as wifi be described in conjunction with Figure 7B. According to an exctrolfa’y cnibodimtmu therein generator 71is foe Cetorofoen 8'.V thnsrefe i saline sohftKm of febidiian-82, produced by the decay of Stromium-82. via the elution, a fime required between feo effective elution processes is approxtnt zc / 0 minutes.

Once the appropriate amount of time lapsed, after rhe ehnion process ci generator column wash, a first quality control test may be performed. With reference 10 to Figure 7A. fewermay select, fem main menu 47fl. an item 773A. which directs computer Π to begin a setpteiice for breakfeough tesiiiig. According to some embodiments, in eofounfetoiwiih fe selecfton of item 773A, the user aiufe.es a needfo to an end of patientafihe SftSp and inserts the needle into to a test vial, for the cplfeetion of an eluate sampfetlterefem^ rfereYA, computer 17

J.fo mstrifes the user to infet tec rest . ialinto: a vial shield, which may be held in recess 101 of shell 13 ^Figure 1C);

Figure 7A ftxfeer illustrates a subsequent screen 775, by which cbmpwter 17 receives input, fem the user, for system 10 to start febreaktfoxjugh elntton, followed by ?8 screen 77$, which provides both an mdfeufoft that feefeion h in progress and ;2δ^: aft option for the user to abort the elution. As¹ previously described, the system may provide a signal'to Indicate that elufen is in progress, for example, light prqfeetor IW (Figure IC) may project a flashing light signal during that portion bf the cllftfoh process when eluate is diverted fem generator 21 through waste- line dflSw aud into waste bottle -23, and fen a steady light signal during that/portipp pf ferefotfoh .process 25 whenths eluate is diverted from generator 21 through patient fee 395 p and into the test vial, for example, once activity detector 25 detects a dose rate of approximately I.OmCi/sac in the eluate discharged fem generator 21, Another type of light signal, for oxampH.the more rapidly flashing light, as previously described may be projcqtod when a peak bolus of radioactivity is detected in she eluate,

U wi completion of the elution process for breaktfeough testing, computer I'7 presents a screen 77\ fewn in Figure 7B, which, like screen F'’, pros ides an indieatfonof a time lapse slope fecuinpfetfon of I he ehmon, but now in terms oi a time since cqmpletitm of the breakthrough phftfon process. When the user transfer^

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th e wl cbnM^ eluate Into a dose calibrator to mcas ure the activity of the sample, the user may make a note of the time lapse mdicamd on screen A .’. With further reference m rivure ?B, once the user has received t-ic acuvnv measure from the dose calibrator, the user proceeds to a screen 778, which imludea data entr y fields for the activity measure and the time between that at which the dose calibrator nieasnrerl the activity of the sample and that at which the elution was completed The user may enter the data via the touch -screen interface of monitor 172. or via any of the other aforementioned devices for user data entry. According to some alternate embodiments, computer 17 may receive the data, electromcaily, from die dose cuhbmtor, either vfa vtirdess commumcatimi or a cable cotmectimt.,

After the data & Wwed screen 779. from which the user moves back to main menu 470 to perform a system calibration, for example, as will be described in conjunction with Figures 8A-B. although the breakthrough testing is not completed. With reference back to Figure 7A, an item 1.5 773B is sltowa. ^mc^h<f^cd;_:W mam menu 470; item 773B may only be

773A,so asto_:perform· a second stage of bteaktiirough testing. In die second stage, the breakthrough of the sample of Warntolfected in the test is measured, ar a time o f approximately 60 min utes from the ecmplation of the elution that prod need the /20 sample. With reference to Figure 7C, after the user has selected item: 773B/ten main menu 470, m order to direct computer 17 toptovide breakthrough teSitesuittod screen 781 is displayed. Screen 781 includes^ for reference,, the values: previomsly efocted by the user in screen 778, along with another pair of dateetrtry fields into witich tr < awr is msfructed to enter the breakthrough reading of the sample at 60 minutes sm., we background radiation reading, respectively After the tiset enters this fremaitiing: mfortnaticn,.as described above, computer lAmay caicnbite and them display, on a screen 782, the breakthrough test results. According to the illustrated embodiment computer 17 also displays on screen. 782 pre-pmgrammed allowable iimits fbr the results., so that the user may verify that the breakthrough: test /results: amiteewptitetoe 3:0 with acceptable limits, before moving on to a patient mfosfon. According: to: some tettbodimentSjWystem 10 wil l not allow art infusion if tile results exceed the: acceptable :/ limits, and may. present a Screen explaining that the msltife are outside tlte:acceptable

2017235989 28 Sep 2017

WOWbfiaiSS? Ρ€Τ/υ$290$/047031 finite. the screen may furthct direct the user io contact tire generator .suppl ie·.. n r example, to order a replacement generator.

Ά \h teieierKA'Y figure ou.mg the afi re rem: ·η.οίΌ τ\ tn e ’ <. e,l while waiting to complete foebreakihrotigh testing, the user may perform calibration by selecting item 873 fiom main mete 470. Upon selection of item 873, oompa ter 17 presents a screen 874, which instructs the user to insert a new tost vial hsto an elution svlnhjde In add ten to mae m fee v u I i rae teeld, .he t m > ^reri'? o rei . patient tee 305p with a new patient line, and then aiu-tew·’ t need I. to the end of the now pattern hnc for insertion into the test vial, in order to collect an eluate sample tferefiom. Ater performing these steps, the user may move to screc'u $75, wherein a pliirafityofdatateiryfislds arepresen.tto, all or some of the fields may be filled in with pre-programmed default paramete's. which the user has an .option to change, if necessary. Once the user confirms entry of dcsircc param \is n r me calibration, the user pray eid<a eonteand,vis inferaerion with a subseqirev. re m et S76, re start the calibrate» elution.

With; reference to Figure SB, after computer I 7\state fife; etetfon pwessjto : screen 87 informs the user that rhe calf bratiou eiutfon is an progress and provider to option to abort the elate». As prevtously described, the system may provide an indication that elntert is m progress, for manpfe light prejector 10(1 (Figure IGfmgy Ji) project a ·.Hash mg light signal during tta: ptefou of fire elation process when eluate is diverted from generator 21 through waste hoc 3O5w and into waste bmtle 23, and then a Mtom tent sigrsl d. ..eg that port’on of toe e'utum process terer toi re uere^to.

has detected that a prescribed dose rate tlteshqid is reached, for example. 1 0 mCifeec,and the eluate is being diverted fem generator JD/through fee new pairest line, and into the test vial. Another type of light signal, for example, ihe m ore rapidly flashing light, as previously described, may be : projected wten mpenk bolfeof radrotofivity is detected m the eluate. Upon completion of the elution process for calibration, itomputer 17 presems a screen. 87$, which provides an indication of a t> W lapse sines the completion of the elution, in term of a ttee since: oompletfou of the calibration elution process, When the user fomsferx: ths vial rontenmg tte sampferof eluato into the dose calibrator, to measure the acrivity of the sample, the user may make a note of the time lapse indicated on screen 878. With further refere nce m Figure SB, once the user has received the activity measnre from the dose calibrator, the

W0 20W152323 user proceeds to axcreeu: F79, which includes data entry fields for the activity measure and the rime, wth reap® to the completion of elution. at which the dose ealibrafor measured ths activity of foe samp® Qneethe data is input by the user, as described above, computer mleufetes a calibration coefficient, or ratio, and presents the ratio on a scicen According to Figure 88, screen 880 further provides an indication of a cesirahlc r,mgc for foe calibration ratio and present's an upnoe fir foe use' to \'\Yt d e calculated ratio, in which case, the user may instruct computer 17 to recalculate the ratio.

As previously mentioned, sornc alternate ®bodimenta of the present invention, include an on board dose calibrator sothto foe entire sequence of saxnpte coiled ton and calculaiiou steps, which are. described above,-ininjunction with Figures 6-sB. fot the quality control procedures, may be automated. Phis automated alternative preferably includes screen shots, similar to some of those described above, which provide a user of the system Wife information at various stages over the course o: fee teuornatedprocedtessnd that provide the user withluppprtnnities to modify, override audfor abort: one or more stepsin the procedure. Regardtoss of the embodiment (i.e. whether svsfem lb emuiuvs an on board dose calibrator or noth computer 17 may

..... ...... x : P .· .·..........v Bather .coi lect all: quality control test parameters and. rpsuits into a stored record odfof compile a raport including all or some ofdfee param®rs:and-remits for:local prim out aud/br el set runic transfer to a remote locauon.

Wife reference to Fsguitfo to upon eomnkuon 01'the above dcite'foed mterry cot etd tovK tee utet m -> vct'o* a Uer* 9 ' . wn τ j.it menu 4”0 >. o*eet to ·. 1 .et system 10 to begin, a procedure for the generatfon aedrautomaiiefofesfenfofa radiopharmaeeutfeal infe a patient. As previously described;, system 10 tofu®the so that nuclear diagnostfc ifegmgAfeipotofe,: for example, a PET scanner, can create images of an organ of the patient, whfoh absorbs the ® iopharmaceutical, via detection of radioactive radiation, thereffom. According to Figure 9A., upon sei ecdon of item 971, computer .17 presents a screen 972 w hich? includes a data entry field for a pattest identification number. This id®iificaduu number that is entered by fee user is retained by computer 17,:½ corijunuiton w ith the pertinent system, parameters associated with the: patieut’S mfosion. After the user erne.\ Ute rat ent lecmdtoanon uuirnet J .ceb·, ne^! < »» co’' I⁷' tX'Ute’ to attach a now patient line and to purge the patient line of air. A subsequent screen

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974 presesucd. by computer 37 includes data entry fields by which rhe user may establish parameters for the automatic inthsion; ah or some of rhe fidds may be filled hr with pre-programmed default parameters, which the user has an option to change If necessary;

With reference to Figure 9B, if pump 33 does not contain enough cteant/saUns for the patiem infusion, computer 1'7 will present a wanting, via a screen 901. which h.dudes m up⁺reu tor foe user to tbre<'t Jn refilling of piece x Us .;..eri screen 902. Once pump 33 has been filled, computer 1? presents an indies lion to the user, via a screen 903. According to some embodiments, if the aror does not re-fill gump 33, yet attempts to proceed with an infusion, system 10 will preclude the irfoisfonandpresem another screen, that communicates to the uwr that no infusion is possible, if the pump is not refilled, mto asking the user to irfiti ;h< pump. m screen 901. When pump 33 contains a suffieiem volume of ehiarn for the patient mftefem, eohiptiter 17 presents a screen 975, which is shown in Figure 9ϋ, and allows the user to eutc;· a command for system 10 to start the; patient mfosiori. During the infusion,·, computer Ϊ7 provides the user with au indieation fhm the infusion is in process and. with a option for the user to abort the infeslou, via a sc-remi 976. As previously described, the system may provide an indication that an. c hition. is in progress, for example, tight project® 100 light signal during that:

portion of the elution process when eluate is diverted from generator 21 through waste tine 305 w and into waste buttle 23, and their a steady light signal during that portion of the elution precess when activity detector 25 has detected th at a prescribed .dose rate: threshold is reached, for example, 1.,0 mCi/see, and the efoatelis .befog diverted fiom· generator 2.1, through the new patient foie for ihffofou mto the patiem. Another type of fight signal, for example, the more rapidly flashing tight, previously describefo.may be projected when a peak bolus of radioactivity is detectedfinth® shfote. : Affite completion of the infusfon, a -screen^977 is displayed by computer 1? to inform the user of the completion of the infoslon and a time since the completion. QompanT 17 also displays a .summary of the tefusion, per screen 978.

With further reference io Figuro 9C, screen 976 shows as exsmpfory_: aciitoiy profile (activity - mtfosee, on y-axis, versus time ~ sec, on x-axis) for the ihfusioh/lnjeeted dose (designated between the two vertical lines), 'flmse skill edifi foe art will appreciate that foe shape of this profile depends upon rhe infusion flow rate.

2017235989 28 Sep 2017 for a given volume of fee dose. >vlneh flow rare is wntudfel. tot example, by tire speed at which, pomp 33',^y^-flwW^P^t:M9:pa*ic®t line, and upon the amount of Sb^ntii^^femsMfegfW'M’e-gStiex^WciMiMsAbsom'e of Bov,' rare control, activity profiles r.n.ay changc over the life of the generator. Fanheimorc, the peak bolus of radioactivity, particularly for injected doses feme rel riveh new generator, may exceed a saturation level of the imaging equipment, i e. PET treauuer. According to some preferred methods of the present invention, in order to maintain relatively consistent, and desirabie-tetfective, activity profiles for patient injections, over the hte of the generator, the operating speed of pump 33 may be varied (both over the course 10_: of a single injection andlfemfeeefen to .inject rent, acco rding to; feedback fem activity detector 25. Such a method may be implemented, via lUvoiptouLon refe'imre: quality cootrol text m which pump 33 is operated to drive fee. .hsmyto too ymreuto’· at a constant rate, in order to collect, into computed a pkrabtv of acuv to, eica-rec’t'crix fem activity dsteefe: 25;Me plurality of msasutements comprise a characteristic, or baseline activity profile fem w hreh the computer; J7 may calculate an appropriate flow nite profileto control a speed of pump33. /in order b> achieve the desirab letefeefive activity pfofiie. bi general, at the start of generator life, when Strofenm-82 is ptentifol, the pump is comtofed to drivefefiisiun flow at relatively tower rates, and, then, toward the end of gea^wr:hfei'wheti'tnp<. to‘v <<·%>.» m.

82 has been depleted* theptimp is conholledto drfire mfefon few . » η» ^,χ jxr rates. As was described Above, in cotfenmfon with Figure ID, If a desired infosiofolfoecfen flow late is relatively high, that is, high cfeagh to create too ntlteh back pressure, via flow through the column qf generator 21, by-pass line 303 :uw be: employed by adjusting divergence valve 3513G to'-feveiHIfete pfelwfit thfethfeigh after a fefeient volume has been pumped; through generator at a Infer few rate.

According to this method, once a dose of eluate, fem generator 21, haafewed;into patient line 305p* divergence valve 35BG is set to divert toedlow of eluant through bypass fee 303, and then pump speed is increased to pump eluant at a higher flow rate i ti order to push the dose out fem patient line 305p_:? for injection at tfe higfer few sate.

: 30 Consistency of activity profiles-among injected doses can greatly focilitete Meuse of PET scanning for the quantification of few. for example, in coronary perfusion studies, Altenistive fofufen eircuit eqnfigurations, operable according to alternative methods, to achieve consistency of activity profiles among injected doses, as wed as a

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Printer 117 (Figure IB) may be activated to print out a hard copy of foe mfasfon sum-nary, on which du patient itfonti.ficahori eumbe* and nemrem fexsion § Pud system parameters are alsoprinted, for reference. Alternatively. or in addition, according, to some embodiments. the summary may be downloaded <nm< a computer readable .storage device to be eiectronisallv transferred to one or more remote

·. **·· * computers and/or the summary may be automatically transferred to the one or more remote computers, via wireless communication or a cable canuectitm, for example, TO over an fofenxti network andfor the intemte. In order to protect private patient

Infimnatidn, the files may be encrypted for transmission over the internet, 3-he one m more remote xomputors may Lx. included, for example ir a Iwspxtol ι.Ίο.: 'anon system, and/or a billing system, and/or in a medical imaging sy>tem infusion parameters. for example, corresponding fo the activity profile, may a Iso be col i act cd and electron really transfoxrcd for analysis in cixfoinction withcaptured images. for example, in order fo qpautilv corowytoow, via .wspftware package that is loaded Into a System that includes the FliT Scanner.

With reference back to Figure 9A ths user may select an item 995, rtrom main, mend 479, in order have system 10 perform data operation todh· afo_::ati:hiving.a data 2G base of patient infusion iafomlatioa and quality ctaitroltest results., tfansmilting t patient infusion summary records to l;SB mass Storage deyicefoAnd various types Of data filtering, for example, according to date ranges -ahd/Or patient identification numbers, for example, to search fora particxdar set of data iatidtor to crimpllsfo summary report of related sets of data. Additionglly, certain mfofefeop,⁵ whiphiis·< 25 collected by computer 17 over the course of system operation, and whibfe defines systcan operation, may be transmitted to a local or remote«mputerfoed inventory system and/or to cxmiputets of technical support, personnel, mainten an cc A r fee ~ p roviders andfor suppliers of infusion ci rcuit etemenisfoontpttuenls, feet ch v *act' ,t. sting more efficient system operation and maintenance.

TO Turning now to Figure 10, an Item 981 for computer'faci>ituied purging of the tubu'g luaro ol system h» xs shown .nc,uded in mam menu a?0 Ys ran a use* icn 9h ,'ompmei > ” gmutro .he to select edlx’ an an putov ,x sxu e pin a?

.1 he direction ·provided by computer 17 is not explicitly hid out herein, for a saline

M

2017235989 28 Sep 2017 pu.pi. as oivceJuses lei sahiw nroamg snudJ be 'cue J> v ,τχ. s.\J e: -r the art, with reierenco to the schematic of mfipdm circuit 300 shown in Figure ID, A saline purge of circuit 300 is desired to assure dun uh the air is removed from circuit 300 when a new generator and/or a new complete or partial tubing set is installed. An air purge of the tubing lines of circuit 300 may be performed after removing reserve) r 15., by-passing generator 21, by connecting tubing, line 304 to tubing Hue. 305, and coupling park nr Hue 3O5p to a vial, for example, as is directed by the computer xt-mfacc, m set ecus 9^3 anri 9b I shown in I igure 10 The mi pur^c .s des.ml -c fo: blowing out the tubing lines, thereby removing all remaining eluant and -eluate., prior io installing anex generator and/orprior to/transporting system 10 from one site io another, Ifgemuator 21 is not depleted and will be used m system 10 al the new site, it is important to by-pass the generator prior to purging the robing lines of circuit 300 with, air, so that air is not blown across the generator, since air through generator 21 may compfomW both the fonetfon add the aseptic nature of generator 21.

According io preferred embodiments, once the user has followed the imuructfons presented in screens 983 and 984_: and selects to .start tho:air purge, for example. via screen 983, cximputer 17 directs the controller ofsystem 10 to carry out :a complete sir parge, in which pump 33 and divergence: valves 35BG arid 35WF are automatically controlled. The automated sir purge ptoferably includes the folio wing steps, which may be best understood withfeforeuee totitblng eireidt 300 in Figure ID:

pmhping atty remaining: volume of eluant left id pump 33, th tough lines 302, 304, 305 and 305¾¾ to waste bottle 23; refilling pump 33 witfimr endptsiriping the air through lines 302, 304,305 and 305w; into waste bottle 23 (ImesBQdand ^OSihayfrbsen previously connected directly to ope another, in order to by-pass gimetotbr 21; if generator 21 is depleted and will be replaced with a new geirerator; pumping dr through; generator .21 may be acceptable); refilling pump 33 with air: amt then pumping: a portion of the air through lines 302,304,305 imd 305p, into foe viat ^nd then s remaining portion of the air thtough lines 3O2_s 304,303 and 305p, ι«κ> the vial. Wlrh reference to Figure .1D and the previous description of divergsuee:Valves 35 BG,

35WP, it should, be understood how divergence valves 35BG, 35WP are automatically controlled to parry out the above steps.

The purge operations, which are fedlitiited by selecting item 9Sl_: .fr0m maih menu 47Q, may also be accessed via the selection of an item 901 for generator setup..

32:

WQ 2(»09/Ί52323

FCi

2017235989 28 Sep 2017

When the user selects item $)91, computer 17 may present an option for guidance in removing an old, depleted, generator and a set of tubing lines, prior to installing the new generator, or an option to just be guided in the nrst&Hation of the new generator According tosome enibotiimen.ts, comptiter 17 is preprogrammed to eal'.-udt·; m amount of activity left in a depleted generator, for example, by tracking activity of eluate over a life of the generator. At an end of the life of she generator, compute’ 17 may further compile, this information, along with other pertinent generator information, imo a report that may accompany a declaration of dangerous goods for shipping the depleted generator out for disposal or, in some cases, buck to the numafacturet for mvcsfeaij.cn An example of such a report i» ’St.owa ,u Figure 11 According to those embodiments of system:: 10 that include an encoded m&rmatian reader, computer 17 may eonfirm that the sew generator is proper by ρro cessi ng information: that is read:from an encoded label/tag attached thereto.

Figures l-SAfe are schematics of dtemative imusion citeuirx t HKfe 1300B that may be employed by system 10, in place .of circuit 300 (Figure 1D). accord! n g to some addifenai embodtments of the present fnyeniiom Circuits 1300 A, 13008 are : configured: id allow for alternative methods of operaf ion, to that previous iy described : for circuit 300, when a relatively even, or uniform level of activity tree? ear h inj acted dose, along with the relatively consistent level of activity from mjeutfou vo injection is desired, for example, in order to facilitate a qimtl&atidn of wrowry mcry blood few via PBT scanning. Figure 12C is a schfefeic illustrating activity profiles 1200A. .12008 for two injected doses, wherein profile 1200B has ambre unifonn level of activity than profile 12O0A; profile 12008 may be achieved vi a the 'operation: of circuits I300A, I30OB as described below,

Similar to circuit300 (Figure ID), dashed fines are shpwn in each of Figures I2A-B toindicate a general boandury of a shielding assembly for ..portions of each circuit 130QA-, 1300B. The shielding assembly for each of drenits 1300A, 13008 may be very similar, in most respects, to shielding; assembly A00, which is describcddboyci for system 10, and the elements of each of dromts 1300A, 13008 may be arranged with respect to their respective shielding and with respect to shell 13 of syst em 10 in a: similar manner to that described above for circuit 300.

Figure I2A illustrates circuit 13O0A including, like the previously described drcuit frGQ, eluant reservoir I p, pump 33. radioisotope generator 21, through which the

WO 200971S2323

2017235989 28 Sep 2017 filtered eluant is pumped to cream the radioactive eluate, activi·* detector 25. and waste bottle 23. Figure 12A further illustrates two filters 37 and two pressure transducers .1334 included in circuit .1300.4, Circuit Ι300Λ further includes by-pass tubing line 303, which is located downstream of divergence salve 3586, like in circuit 5 300, and which acwmmodates the previously described eluantisaline flush. Hero eve r.

in contrast to circuit 300, circuit 1300A further includes a lin^r/proportional vaivr.·

1335 integrated into by-paWflush line 303 so that circuit 1300A. may be operated, for example, according to pre-programmed parameters of computer 1 in conj unclion with feedback of information font activity detector 25, fn a · jor, troll·.,; hypa>.' of generator 21 in orde- to mn. e uaet wrlh eluate and, thereby rotero c a retire·, eh tmifbmi level of activity over each patient injectipiu for example, ,ι,'οο-ο,η^ ro profile I200B <n Figure 12(5. h sliould be noted Ito, imaddition to the rorere-ded mreing, a flow rate of each injection may be varied, it necessan.··, in ordvr to niainuikt a donsisteci activity level.

5 Figure 128 illustrates tefehlf 1300B: including, Ms the previously described circuit 300. eluant reservoir 15, pump 33, radioisotope^generator 21, activity dstectof^: 25_: and waste bottle 23, as well as the two and two: pressure transducers 1334, ax-in circuit I300A. hr cottoasfto ciwitx.SMiandllSfiQA,. circM 13O0B fisrthte includes an eluate reservoir 1350, which is shown located dOwnsirsani of generator

21, in between first and second fegments 305A_e 305B of the eluate -tubing lino,. It should be noted that a pump: Is combined with reservoir 13 50, for: example., similar to syringe pump 33* such that, when a divergence valve I335I0ds tot to aiidw fiuifi commumcatfon between reservoir 1350 and ttibmg line segment: 305Ά, the asspsimd pump may be operated to draw In a volume of ehiale, and<tlteti, when divergeinbe valve 133510 Is set to allow Suid communication between reservoir 135:0 add Wifig .Hue segment1305B, the pump may be operated to push the volume of eluate out through tubing line segment 305B for a pat ient Irg eciion, when di vergence valve 35WP Is set to direct flow into patient tine 305p, With/referetwhadtfo Figures 3ArB,_: si dewall 205 of shielding assembly 200 m ay be enlarged to fiuiher :Cnclpsc eluate:

reservoir 1350. For example, another shielded well, to house the eluate reservoih, may extend alongside well 255» in which activity detector 25^:is described,^:as Ming mounted. Fnrihermore, sidewal.1205 may include anbther valve actuator receptacle for

2017235989 28 Sep 2017

Jncrgencc valve 133510, similar to receptacle 255, shown In figure 3 X lei divergence valve 35WPi ('olteciton of discrete volumes of eluate, in a reservoir ; fov, mux l-efo c,<

achieve a more uniform activity les el over each injection, tor example, like hue of a protlk- 12WB in figure 12(5 and, according to preferred methods, feedback from activity deteelor 25 may be used to -.control the pump associated with reservoir 1.35(), in ojdet fox ary injection flow rate and. thcrcbx, mairtum., refer λ ch ^ous.sknc .rere.re'j level across multiple inieuiioiis, and, when necessary, to vary injection flow rate over id an individual infeeti<>n to maintam the uniform activity level, feedback from the pressure transducer 1334, that is downstream from detectoi 25, .uidmr irom a flow meter foot shewn} of circiiit 1300B wy also beiuspd to conuvd the varying of injection flow rate.

With further reference to Figures -12A*B, it should be noted that alternative eircuits may be configured to employ a eembinutian of the methods described for circuits 1300A and 2 300B, Itenhemiore, stsme iniusion circuits of the-preseni: invention, may employ multiple· generators 21, as mentioned above, in cpnjuwtfon with Figure 2A, to help maintain the relatively uniform level of anti vi ty over each · injection O and tits telatlvely consistent level' of activity from injection to infection;

In the foregoing detailed description, the invention liasbeen described Wife reference to specific enfoodlmeats. However, it may be appreciated that x orioas modi floations and changes can be made without departing from the scope of the invention as set forth;i n the appended claims.

In the claims which follow and in the preceding description of fee invention^ except where the context requires otherwise due to express language or necessary implication, the word .“comprise”-or variations such, as ⁴’compmes'· or 'comprising,” Is Mi used in an inclmive sense, i.e. to; specify the presence of the stated feci.ires but not to

2017235989 28 Sep 2017

34s precl u de the presence or add its on of further features in van bus erilbodinienfo of the invention.

It Is to be understood that, if any prior art pub*ie.men is teienvd to herein, tech reference does not ccrtstituteuu admission that the publication forms .1 part of the Common general knowledge in the art, in Austifeia or any other country.

Claims (29)

1. THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

   1. An infusion system on-board a cart comprising:

   a cabinet structure that comprises:

   a platform, an exterior shell that extends upwardly above the platform and has a front side; a rear side; two sidewalls connecting the front side to the rear side; and a top surface; wherein the platform and the exterior shell collectively define an interior space of the cabinet structure and wherein the interior space of the cabinet structure is configured to receive a strontium-rubidium radioisotope generator having an inlet tubing port configured to receive saline and an outlet tubing port configured to discharge a rubidium radioactive eluate, an opening through the exterior shell configured to provide access to the strontium-rubidium radioisotope generator within the interior space of the cabinet structure, and an opening through the top surface of the exterior shell configured to provide access for inserting a waste bottle into or removing the waste bottle from the interior space of the cabinet structure;

   a computer with a touch screen display configured to receive an input from a user for controlling operation of the infusion system, wherein the touch screen display is mounted on a vertical post having a top end extending above the cabinet structure;

   a first shielding compartment in the interior space of the cabinet structure having a first opening facing vertically upwardly through which the strontium-rubidium radioisotope generator can be inserted into and removed from the first shielding compartment;

   a first door accessible via the opening through the exterior shell, the first door being configured to provide access to the first shielding compartment and to close over the first opening;

   a second shielding compartment having a second opening facing vertically upwardly through which the waste bottle can be inserted into and removed from the second shielding compartment;

   a second door accessible via the opening through the top surface of the exterior shell, the second door being configured to provide access to the second shielding compartment and to close over the second opening;

   9531176_1 (GHMatters) P85620.AU.2 wherein the first opening is located at a lower elevation than the second opening; a radioactivity detector positioned to measure radioactivity of the rubidium radioactive eluate flowing through an eluate tubing line in fluid communication with the outlet tubing port of the strontium-rubidium radioisotope generator;

   a shielded well on-board the cart configured to receive an eluate reservoir, wherein the eluate reservoir is configured to receive a test sample; and wherein the computer of the infusion system is configured to:

   provide a stop button on the touch screen display to abort a function of the infusion system in response to a user input activating the stop button, pump saline from a saline reservoir positioned outside of the interior space of the cabinet structure into the strontium-rubidium radioisotope generator through the inlet tubing port of the strontium-rubidium radioisotope generator thereby generating the rubidium radioactive eluate that is discharged through the outlet tubing port, fill the eluate reservoir in the shielded well on-board the cart with the test sample of the rubidium radioactive eluate, determine a strontium breakthrough test result on the test sample filled into the eluate reservoir in the shielded well on-board the cart while the eluate reservoir remains in the shielded well on-board the cart, and not allow a patient infusion if the strontium breakthrough test result is greater than or equal to an allowed limit.
2. 2. The infusion system of claim 1, further comprising:

   the strontium-rubidium radioisotope generator in the first shielding compartment in the interior space of the cabinet structure, and the eluate reservoir located in the shielded well on-board the cart and in fluid communication with the eluate tubing line.
3. 3. The infusion system of claim 1, wherein the first shielding compartment comprises two tubing passageways formed in a perimeter surface of the first opening, and each of the two

   9531176_1 (GHMatters) P85620.AU.2 tubing passageways has a depth configured to prevent pinching or crushing of a corresponding tubing line routed therethrough when the first door is closed thereover.
4. 4. The infusion system of claim 1, wherein the function of the infusion system aborted in response to the user input activating the stop button is a patient infusion procedure.
5. 5. The infusion system of claim 1, further comprising a waste tubing line and a valve, wherein the waste tubing line is in fluid communication with the eluate tubing line and the waste bottle, and the valve is configured to control fluid flow between the eluate tubing line and the waste bottle via the waste tubing line.
6. 6. The infusion system of claim 1, wherein the cabinet structure has a lowermost portion and the platform has a lower surface, the first opening is at a first elevation, the second opening is at a second elevation, the first elevation is between approximately 1 foot and approximately 2 feet, with respect to the lowermost portion of the cabinet structure, and the second elevation is between approximately 2 feet and approximately 3 feet, with respect to the lower surface of the platform.
7. 7. The infusion system of claim 1, further comprising a dose calibrator in the shielded well on-board the cart and in communication with the computer to determine the strontium breakthrough test result.
8. 8. The infusion system of claim 1, wherein the computer of the infusion system is further configured to track a volume of the saline remaining in the saline reservoir and to alert the user via the touch screen display when the volume of the saline remaining in the saline reservoir is below a predetermined volume threshold.

   9531176_1 (GHMatters) P85620.AU.2
9. 9. The infusion system of claim 1, wherein the strontium breakthrough test result is for at least one of strontium-82 and strontium-85.
10. 10. The infusion system of claim 1, further comprising:

    a hanger configured to hold the saline reservoir at an elevation above the top surface of the exterior shell, a handle configured for the user to grasp in order to move the infusion system, four wheels mounted to an underside of the platform, a power inlet port for connecting the infusion system to a power source, and a printer configured to print a document concerning a patient infusion or a quality control test result generated by the infusion system;

    wherein:

    the first shielding compartment comprises two tubing passageways formed in a perimeter surface of the first opening, each of the two tubing passageways has a depth configured to prevent pinching or crushing of a corresponding tubing line routed therethrough when the first door is closed thereover, the first door is mounted via a hinge, access to an operation of the computer is regulated through a user login credential, the strontium breakthrough test result is for at least one of strontium-82 and strontium-85, and the exterior shell further includes a saline tubing opening configured for a saline tubing line to pass from the saline reservoir outside of the exterior shell to the interior space of the cabinet structure; and wherein the computer of the infusion system is further configured to:

    determine the strontium breakthrough test result on the test sample at least once a day, pump saline through the strontium-rubidium radioisotope generator at a rate less than approximately 70 ml/min,

    9531176_1 (GHMatters) P85620.AU.2 track a volume of the rubidium radioactive eluate discharged from the strontiumrubidium radioisotope generator to the waste bottle and to control the touch screen display to display a user screen guiding the user to empty the waste bottle, and track a volume of the saline remaining in the saline reservoir and to alert the user via the touch screen display when the volume of the saline remaining in the saline reservoir is below a predetermined volume threshold.
11. 11. The infusion system of claim 10, further comprising a dose calibrator located in the shielded well on-board the cart and in communication with the computer, wherein the dose calibrator is configured to determine the strontium breakthrough test result; and wherein the opening through the exterior shell configured to provide access to the strontium-rubidium radioisotope generator within the interior space of the cabinet structure is through the front side of the exterior shell.
12. 12. A method of using an infusion system on-board a cart to deliver a rubidium radioactive eluate comprising:

    installing a saline reservoir on the infusion system, wherein the infusion system comprises a platform and an exterior shell extending upwardly above the platform, and wherein the platform and the exterior shell collectively define an interior space of a cabinet structure;

    placing the saline reservoir in fluid communication through a saline tubing line with an inlet tubing port of a strontium-rubidium radioisotope generator located in a first shielding compartment in the interior space of the cabinet structure, wherein the strontium-rubidium radioisotope generator further comprises an outlet tubing port configured to discharge the rubidium radioactive eluate, and wherein the first shielding compartment has a first opening facing vertically upwardly;

    inserting a waste bottle into a second shielding compartment on-board the cart, wherein the second shielding compartment on-board the cart has a second opening facing vertically upwardly and being at a higher elevation than the first opening;

    placing the waste bottle in fluid communication with the outlet tubing port of the strontium-rubidium radioisotope generator through an eluate tubing line, wherein a computer

    9531176_1 (GHMatters) P85620.AU.2 on-board the cart is configured to control the fluid communication between the waste bottle and the outlet tubing port, and wherein the computer has a touch screen display mounted on a vertical post with a top end extending above the cabinet structure;

    inserting an eluate reservoir in a shielded well on-board the cart;

    placing the eluate reservoir in fluid communication with the eluate tubing line, wherein the computer is further configured to control the fluid communication between the eluate reservoir and the eluate tubing line;

    pumping a sample of the rubidium radioactive eluate into the eluate reservoir in the shielded well on-board the cart;

    measuring a radioactivity of the sample of the rubidium radioactive eluate flowing through the eluate tubing line with a radioactivity detector on-board the cart while the sample of the rubidium radioactive eluate is flowing through the eluate tubing line;

    measuring a calibration radioactivity of the sample pumped into the eluate reservoir in the shielded well on-board the cart while the eluate reservoir remains in the shielded well onboard the cart;

    comparing the radioactivity of the sample of the rubidium radioactive eluate flowing through the eluate tubing line measured by the radioactivity detector on-board the cart while the sample of the rubidium radioactive eluate is flowing through the eluate tubing line with the calibration radioactivity of the sample pumped into the eluate reservoir in the shielded well onboard the cart; and determining a strontium breakthrough test result on the sample pumped into the eluate reservoir in the shielded well on-board the cart while the eluate reservoir remains in the shielded well on-board the cart, wherein the computer of the infusion system is further configured to not allow a patient infusion if the strontium breakthrough test result is greater than or equal to an allowed limit.
13. 13. The method of claim 12, further comprising:

    placing the eluate tubing line in fluid communication with a patient, wherein the computer is further configured to control the fluid communication between the eluate tubing line and the patient;

    9531176_1 (GHMatters) P85620.AU.2 pumping a dose of the rubidium radioactive eluate to the patient; and flushing the rubidium radioactive eluate remaining in at least a portion of the eluate tubing line into the patient by pumping saline from the saline reservoir to the eluate tubing line through a by-pass line that by-passes the strontium-rubidium radioisotope generator, wherein the computer is further configured to control fluid communication via the by-pass line.
14. 14. The method of claim 12, wherein the cabinet structure has a lowermost portion and the platform has a lower surface, the first opening is at a first elevation, the second opening is at a second elevation, the first elevation is between approximately 1 foot and approximately 2 feet, with respect to the lowermost portion of the cabinet structure, and the second elevation is between approximately 2 feet and approximately 3 feet, with respect to the lower surface of the platform.
15. 15. The method of claim 12, wherein the saline tubing line and the eluate tubing line are routed through two tubing passageways formed in a perimeter surface of the first opening, wherein each of the two tubing passageways has a depth configured to prevent pinching or crushing of a corresponding tubing line routed therethrough when a first door is closed over the first opening.
16. 16. The method of claim 12, wherein the infusion system further comprises a dose calibrator in the shielded well on-board the cart, wherein the dose calibrator is in communication with the computer to determine the strontium breakthrough test result.
17. 17. The method of claim 12, further comprising:

    initiating a generator column wash through the touch screen display, wherein a predetermined amount of saline is pumped through the strontium-rubidium radioisotope generator and directed to the waste bottle during the generator column wash.

    9531176_1 (GHMatters) P85620.AU.2
18. 18. The method of claim 12, wherein the computer of the infusion system is further configured to track time passed from completion of pumping the sample of the rubidium radioactive eluate into the eluate reservoir to determining the strontium breakthrough test result.
19. 19. The method of claim 13, wherein the computer of the infusion system is further configured to present on the touch screen display a screen reminding a user to insert the eluate reservoir in the shielded well on-board the cart.
20. 20. The method of claim 12, wherein the saline reservoir is located outside of the interior space of the cabinet structure.
21. 21. The method of claim 13, wherein the computer of the infusion system is further configured to:

    present on the touch screen display a screen for starting the patient infusion by touching a button on the touch screen display;

    present on the touch screen display a screen reminding a user to insert the eluate reservoir in the shielded well on-board the cart;

    present on the touch screen display a screen indicating that the patient infusion is in process, wherein the screen indicating that the patient infusion is in process displays a stop button to abort the patient infusion; and present on the touch screen display the strontium breakthrough test result.
22. 22. A method of building an infusion system to deliver a rubidium radioactive eluate comprising:

    installing a first shielding compartment, a second shielding compartment, and a shielded well on a platform of a cart, wherein:

    the first shielding compartment has a first opening facing vertically upwardly, the first opening is configured for a strontium-rubidium radioisotope generator to be inserted into and removed from the first shielding compartment,

    9531176_1 (GHMatters) P85620.AU.2 the second shielding compartment has a second opening facing vertically upwardly, the second opening is configured for a waste bottle to be inserted into and removed from the second shielding compartment, the first opening is located at a lower elevation than the second opening, and the shielded well is configured to receive an eluate reservoir that is configured to receive a sample of the rubidium radioactive eluate;

    configuring a computer with a touch screen display for the infusion system to:

    fill the eluate reservoir in the shielded well on-board the cart with the sample of the rubidium radioactive eluate by pumping saline from a saline reservoir into the strontiumrubidium radioisotope generator via a saline tubing line thereby generating the rubidium radioactive eluate that is discharged through an eluate tubing line, determine a strontium breakthrough test result on the sample of the rubidium radioactive eluate filled into the eluate reservoir in the shielded well on-board the cart while the eluate reservoir remains in the shielded well on-board the cart, and not allow a patient infusion if the strontium breakthrough test result is greater than or equal to an allowed limit.
23. 23. The method of claim 22, further comprising configuring the computer to:

    measure a radioactivity of the sample of the rubidium radioactive eluate while the sample is flowing through the eluate tubing line to the eluate reservoir;

    measure a calibration radioactivity of the sample while the sample remains in the eluate reservoir in the shielded well on-board the cart; and compare the radioactivity of the sample measured while flowing through the eluate tubing line with the calibration radioactivity of the sample measured in the eluate reservoir in the shielded well on-board the cart.
24. 24. The method of claim 22, further comprising configuring the computer to:

    control a fluid communication between the strontium-rubidium radioisotope generator and the saline reservoir,

    9531176_1 (GHMatters) P85620.AU.2 control a fluid communication between the eluate tubing line and the eluate reservoir, control a fluid communication between the eluate tubing line and the waste bottle, place the eluate tubing line in fluid communication with a patient, pump a dose of the rubidium radioactive eluate to the patient; and flush the rubidium radioactive eluate remaining in at least a portion of the eluate tubing line into the patient by pumping saline from the saline reservoir to the eluate tubing line through a by-pass line that by-passes the strontium-rubidium radioisotope generator.
25. 25. The method of claim 22, further comprising installing an exterior shell extending upwardly above the platform, wherein:

    the exterior shell comprises a front side; a rear side; two sidewalls; and a top surface, the platform and the exterior shell collectively define an interior space of a cabinet structure, the cabinet structure has a lowermost portion and the platform has a lower surface, the first opening is at a first elevation, the second opening is at a second elevation, the first elevation is between approximately 1 foot and approximately 2 feet, with respect to the lowermost portion of the cabinet structure, and the second elevation is between approximately 2 feet and approximately 3 feet, with respect to the lower surface of the platform.
26. 26. The method of claim 22, wherein the infusion system is configured for the saline tubing line and the eluate tubing line to be routed through two tubing passageways formed in a perimeter surface of the first opening, wherein each of the two tubing passageways has a depth configured to prevent pinching or crushing of a corresponding tubing line routed therethrough when a first door is closed over the first opening.
27. 27. The method of claim 23, further comprising installing a dose calibrator in the shielded well on-board the cart, wherein the dose calibrator is in communication with the computer to

    9531176_1 (GHMatters) P85620.AU.2

    2017235989 26 Nov 2019 measure the strontium breakthrough test result and the calibration radioactivity of the sample pumped into the eluate reservoir.
28. 28. The method of claim 22, further comprising configuring the computer to:

    5 track a volume of saline remaining in the saline reservoir, and provide an alert via the touch screen display when the volume of saline remaining in the saline reservoir is below a predetermined volume threshold.
29. 29. The method of claim 22, further comprising configuring the computer to:

    10 track a volume of the rubidium radioactive eluate discharged from the strontiumrubidium radioisotope generator to the waste bottle, and present on the touch screen display a screen reminding a user to empty the waste bottle.