CN106977714A - Positive electron marking nano probe68Ga NOTA DGL Ac and preparation method thereof and purposes - Google Patents

Positive electron marking nano probe68Ga NOTA DGL Ac and preparation method thereof and purposes Download PDF

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CN106977714A
CN106977714A CN201710126684.3A CN201710126684A CN106977714A CN 106977714 A CN106977714 A CN 106977714A CN 201710126684 A CN201710126684 A CN 201710126684A CN 106977714 A CN106977714 A CN 106977714A
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王欣璐
尹吉林
杨玉婷
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General Hospital of Guangzhou Military Command
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Abstract

The invention discloses a kind of compound68Ga NOTA DGL Ac and preparation method thereof, the compound68Ga NOTA DGL Ac have very high radiochemicsl purity, good vitro stability and water solubility, are conducive to68Blood circulations of the Ga NOTA DGL Ac in mouse live body.It is of the present invention68Ga NOTA DGL Ac preparation method, by synthesizing tree-like macromolecular poly-D-lysine derivative DGL NOTA Ac, and uses positron radionuclide68Ga is marked, and explores a simple, positive electron marking nano molecular probe approach that quick, putting yield is high, passs to release for gene therapy, medicine and provides new research direction with bio-imaging.

Description

Positive electron marking nano probe68Ga-NOTA-DGL-Ac and preparation method thereof and purposes
Technical field
The present invention relates to positive electron marking nano probe68Ga-NOTA-DGL-Ac and preparation method thereof and purposes, belong to doctor Field.
Background technology
Nano material refers to one-dimensional space size<A 100nm class material, because its special volume and structure have it There are some special natures, such as good surface activity, hypotoxicity, catalytic capability are high and are difficult by internal and intracellular various enzyme drops Solution etc..The species of nano material is enriched very much, and the nano material for molecular imaging research field can be divided into organic and inorganic Two major classes, wherein organic nano material include dendrimers, liposome, micelle, ferritin etc.；Inorganic nano material includes amount Sub- point, iron oxide, gold nano grain, superparamagnetic rare earth ion etc..Dendrimer is to be ground by Michigan, United States chemistry for 1985 Study carefully Tomalia etc. and university of south florida the almost class novel high polymer material of stand-alone development simultaneously such as Newkome Material.It is born till now from it, although only short 30 years, due to its novel structure, unique performance and potentially should Received much concern with prospect.
Dendrimer poly-D-lysine (Dendrigraft poly-L-lysine, DGL) is newly developed in recent years one Dendrimer is planted, except possessing the shared characteristic of dendrimer, such as amphiphilic, internal cavities and lotus electropositive, also It is easy to be degraded into the amino acid of bioavailable, with good biocompatibility, antibiotic property, no immunogene, and hypotoxicity.This Outside, because structure is less crowded, their dendron shape framework can carry substantial amounts of molecule thing.For example DGL is recently as nanometer Magnetic resonance imaging contrast (after being mixed with Gd coordination compound), passs as the gene for passing through blood-brain barrier and releases carrier, or pass through lipid Body and cell membrane transporter, these examples show that this kind of novel macromolecule can be used for the application and development of most of dendritic macromole such as Gene therapy, medicine, which are passed, to be released and bio-imaging.
In recent years,68The positron emitter of Ga labeling polypeptides has begun to expansion should.68Ga is produced independent of accelerator, By68Ge/68Prepared by Ga generators, preparation method is easy, and more than 95% radioactive label yield can be reached in 15min, And68Ga half-life period is 67.6min, and its nucleic good properties, blood understands that comparatively fast, the radiation that patient is subject to is relatively fewer, because This turns into the primary study object that positron medicine is studied in recent years.For the radioactivity mark in dendrimer poly-D-lysine Note research is less, therefore this research is carried out68Discussions of the Ga to DGL labeling methods.
The content of the invention
A kind of new positive electron marking nano probe is provided it is an object of the invention to overcome drawbacks described above68Ga- NOTA-DGL-Ac, the probe has good stability and biocompatibility, can be circulated in intravital blood, putting yield Height, the preparation method of the positive electron marking nano molecular probe is simple, quick.
To achieve the above object, the technical scheme taken of the present invention is：A kind of compound68Ga-NOTA-DGL-Ac。
In addition, the present invention discloses a kind of compound68Ga-NOTA-DGL-Ac preparation method, it is used68Ga is to precursor DGL-NOTA-Ac carries out radioactive label, produces compound68Ga-NOTA-DGL-Ac。
It is preferred that, the compound68Ga-NOTA-DGL-Ac preparation method comprises the following steps：(1) appropriate dilute salt is taken Acid is eluted to germanium-gallium generator, collects eluent, chooses the maximum eluent of activity；(2) work obtained by step (1) Spend and sodium acetate solution is added in maximum eluent, adjust pH, be then added in DGL-NOTA-Ac sodium-acetate buffers；(3) Mixed solution obtained by step (2) is subjected to lucifuge reaction, reaction end is produced68Ga-NOTA-DGL-Ac。
It is preferred that, the concentration of watery hydrochloric acid is 0.05mol/L, the pouring eluted to germanium-gallium generator in the step (1) Wash flow rate 1ml/min.
It is preferred that, the concentration of sodium acetate solution is 1.0mol/L in the step (2).
It is preferred that, adjustment pH to 4.0-4.2 in the step (2).
It is preferred that, the condition that lucifuge is reacted in the step (3) is that lucifuge reacts 10min at 70 DEG C.
It is preferred that, the preparation method of the precursor DGL-NOTA-Ac comprises the following steps：(1) DGL G3 are dissolved in DMSO In, stir and evenly mix to being completely dissolved；(2) NOTA-NHS is dissolved in DMSO, stirred and evenly mixed to being completely dissolved；(3) by step (1) The middle DGL G3 dissolved are mixed with the NOTA-NHS dissolved in step (2), and lucifuge is reacted at room temperature；(4) then to Excessive triethylamine is added in mixed solution obtained by step (3), lucifuge is stirred at room temperature, then adds excessive acetic anhydride, Continue to react under same reaction conditions, reaction end produces precursor DGL-NOTA-Ac.
It is preferred that, the preparation method of the precursor DGL-NOTA-Ac is also included after step (5) reaction terminates in 0.5mol/ The precursor dialysed in L, pH=4.0 sodium-acetate buffer obtained by step (4), you can obtain purer precursor DGL-NOTA-Ac.
On the other hand, the present invention discloses a kind of compound68Ga-NOTA-DGL-Ac exists as positive electron marking nano probe Gene therapy, medicine pass the application released with bio-imaging.
The beneficial effects of the present invention are：Compound of the present invention68Ga-NOTA-DGL-Ac has very high top coal drawing Degree, good vitro stability and water solubility, are conducive to68Blood circulations of the Ga-NOTA-DGL-Ac in mouse live body.This hair It is bright described68Ga-NOTA-DGL-Ac preparation method, passes through synthesizing tree-like macromolecular poly-D-lysine derivative DGL-NOTA- Ac, and use positron radionuclide68Ga is marked, and explores a simple, positive electron marking nano point that quick, putting yield is high Sub- probe approach, passs to release for gene therapy, medicine and provides new research direction with bio-imaging.
Brief description of the drawings
Fig. 1 is that DGL-NOTA-Ac synthesizes schematic diagram；
Fig. 2 is DGL-NOTA-Ac ultraviolet absorptivity measurement result, and black arrow meaning is at 320nm；
Fig. 3 is DGL-NOTA-Ac Malvern nano particle size potentiometer testing result；
Fig. 4 is68Ga-NOTA-DGL-Ac paper chromatography testing result, wherein Rf( 68 Ga-NOTA-DGL-Ac)=38/200= 0.19, Rf( 68 Ga ions)=101/200=0.505；
Fig. 5 is68Ga-NOTA-DGL-Ac vitro stability experimental results；
Fig. 6 is68Ga-NOTA-DGL-Ac is in A459 cells and U87MG cellular uptakes and elution experiments result；
Fig. 7 is68Vivo biodistribution distribution results of the Ga-NOTA-DGL-Ac in normal mouse；
Fig. 8 is normal KM mouse through tail vein injection68120min Micro-PET are imaged after Ga-NOTA-DGL-Ac；
Fig. 9 is68Vivo biodistribution distribution results of the Ga-NOTA-DGL-Ac in lotus U87MG tumor mouses；
Figure 10 is68Ga-NOTA-DGL-Ac tumor bearing nude mice Micro-PET/CT image results, a is through tail vein injection68120min is imaged after Ga-NOTA-DGL-Ac, and b is intratumor injection68120min is imaged after Ga-NOTA-DGL-Ac, and arrow is signified For tumour.
Embodiment
To better illustrate the object, technical solutions and advantages of the present invention, below in conjunction with specific embodiment and accompanying drawing pair The present invention is described further.
1. materials and methods
1.1 precursor DGL-NOTA-Ac synthesis
Take 10mgDGL G3 to be dissolved in 6mL anhydrous DMSO, take 8.6mg NOTA-NHS to be dissolved in 20mL anhydrous DMSO In, both are mixed, at room temperature lucifuge stirring 24h.Reaction adds excessive triethylamine after terminating lucifuge is stirred at room temperature 0.5h, then adds excessive acetic anhydride, continues to react 24h under the same reaction conditions.React after terminating in 0.5mol/L pH Dialysed (3 days, liquid is changed altogether 5 times) in=4.0 sodium-acetate buffer, obtained concentration is 1mg/mL, wherein DGL-NOTA-Ac is closed It is as shown in Figure 1 into schematic diagram.
1.2 68Ga-NOTA-DGL-Ac preparation
0.05mol/L HCl 2.5ml are taken to elute germanium-gallium generator, flow rate 1ml/min collects eluent, often Branch 0.5ml totally 5.Activity detection is carried out respectively, is chosen 1 maximum eluent of activity, is added 32.5 μ L 1.0mol/L acetic acid Sodium solution, 4.0-4.2 is adjusted to by pH, then adds in 200 μ L DGL-NOTA-Ac sodium-acetate buffers that lucifuge is anti-at 70 DEG C 10min is answered, is produced68Ga-NOTA-DGL-Ac。
1.3 68Ga-NOTA-DGL-Ac identification and purifying
Label is identified using thin layer paper chromatography (Thin Layer Chromatography, TLC), separated Purifying uses PD10 purification columns.1 μ L label point samples are taken, solvent is 0.9% physiological saline.It is molten with 0.01mol/L PBS Liquid 25mL balances PD10 posts, adds 500 μ L reactant mixtures, is then eluted with 2mL 0.9% physiological saline.Take 5 EP Pipe, numbering is 1-5 respectively, and each EP pipes meet leacheate 0.5mL.After elution is finished, each EP pipes radioactive activity is measured, is picked and placeed Penetrating property activity highest leacheate carries out Radio-TLC and determines radiochemicsl purity, if radiochemicsl purity ＞ 99%, carries out external in vivo Thing is tested.
The measure of 1.4 basic physical and chemicals
The radioactive nano molecular probe of preparation is dissolved in PBS, it is visual observations its colors, clarity, transparent Degree, takes a small amount of sample to analyze its pH value with standard pH test paper.
1.5 lipids are determined
Take after isolating and purifying68The μ L of Ga-NOTA-DGL-Ac 10, be separately added into three EP pipe (containing 0.5mL n-octyl alcohols and 0.5mL 0.01mol/L PBS) in, be vortexed 2min at room temperature after sealing, and 3000r/min is centrifuged 5 minutes.With adding Sample rifle takes organic phase and each 10 μ L of aqueous phase to be placed in V counter tube from 3 EP pipes successively, carries out γ countings, in triplicate.With Formula Log P=Log (γ counts n-octyl alcohol/γ and counts PBS) calculate average Log P values.
1.6 68Ga-NOTA-DGL-Ac vitro stability evaluation
Take 20 μ L's (about 2.03MBq)68Ga-NOTA-DGL-Ac solution, be placed in 0.5mL PBS (pH=7.4, 0.01mol/L), 100 μ L are taken to determine its radiochemical purity after being incubated 30min, 60min, 90min and 120min at 37 DEG C, To observe its stability in PBS, in triplicate.To survey68Ga-NOTA-DGL-Ac solution is in calf serum Stability, is also incubated 30min, 60min, 90min and 120min at 37 DEG C, dilutes hyclone with isometric PBS afterwards, Be vortexed 2min at room temperature after sealing, centrifuges 5min under the conditions of 1000r/min, takes supernatant to be analyzed with Radio-TLC.
1.7 68Intakes and elution experiments of the Ga-NOTA-DGL-Ac in A549 and U87MG cells
(1) cellular uptake is tested：5 × 10 are added per hole in 24 orifice plates4Individual human A459 lung cancer cell line or human brain glue Make cell attachment after matter tumor cell strain U87MG, overnight incubation, culture medium is removed every other day, 5 μ L are added per hole and contain 185KBq68Ga- NOTA-DGL-Ac PBS solution, blank control group adds 5 μ LPBS solution and (is free of68Ga-NOTA-DGL), respectively at 37 DEG C It is incubated after 20min, 40min, 80mim and 120min, the PBS freezed per hole with 0.5mL is washed 3 times, then uses 0.25% tryptose Enzyme/0.02%EDTA vitellophags, is collected after cell suspension with the measurement radiocounting of γ calculating instruments.Cellular uptake data are whole After correction for attenuation with cell Percentage bound be percentage add dose form show, experiment set three it is parallel, be repeated 3 times.
(2) cell elution experiments：5 × 10 are added per hole in 24 orifice plates4Individual A549 or U87MG, at 37 DEG C with 185KBq/ holes68Ga-NOTA-DGL-Ac is incubated 1h jointly makes its abundant internalization.Then culture medium is removed, is rushed with the PBS of frost Wash 3 times, add serum-free medium and 0min, 20min, 40min, 80mim and 120min are incubated at 37 DEG C.Used afterwards per hole The PBS of 0.5mL frosts is rinsed 3 times, finally with 0.25% trypsase/0.02%EDTA vitellophags, is collected after cell suspension Radiocounting is measured with γ calculating instruments.Cell elution profile is all that percentage is added with Cellular retention rate after correction for attenuation Dosage represents, experiment set three it is parallel, be repeated 3 times.
1.8 68Vivo biodistribution credit cloth of the Ga-NOTA-DGL-Ac in normal mouse
12 hours fasting for solids and liquids of kunming mice, is marked to normal mouse, is grouped that (totally 12, be divided into 4 groups, often respectively Group 3), line label is entered to counting tube and is weighed.Syringe extracts 100 μ L tracers, radioactive activity is surveyed, by every syringe It is numbered, and numbers consistent with mouse number.With 2% isoflurane by mouse anesthesia, alcohol wipe mouse tail is then used, Through tail vein injection tracer.Blood is taken respectively at carrying out eyeball after tracer injection 5min, 30min, 60min and 120min, it The disconnected neck of row is put to death and major organs (heart, lung, liver,spleen,kidney, stomach, intestines, pancreas, brain, muscle, bone, fur) dissection afterwards, PBS bufferings Liquid is cleaned up dry after be respectively placed in the empty counting tube accordingly numbered.All counting tubes equipped with organs and tissues are claimed Weight, organs and tissues weight=gross weight-sky counting tube weight.γ meters are carried out to the counting tube equipped with organs and tissues with γ calculating instruments Number, calculates the radiocounting of per gram of tissue after correction for attenuation, is represented with per gram of tissue percentage injection dosage (ID%/g).
1.968Ga-NOTA-DGL-Ac is imaged in the Micro-PET of normal mouse
Micro-PET is gathered and graphical analysis is carried out with Siemens Inevon small animal position emission tomography (PET)s/CT.Normal mouse exists Through the μ L (12.7MBq) of tail vein injection 250 under chloraldurate solution intraperitoneal injection of anesthesia68Ga-NOTA-DGL-Ac, experiment is dynamic Thing is placed in prone position and is fixed, and the 120min collections still image after injection developer, scanning carries out data reconstruction after completing.
1.10 68Ga-NOTA-DGL-Ac is imaged in the Micro-PET of lotus U87MG tumor mouses
Lotus U87MG mice with tumor is under 2% isoflurane anesthesia respectively through tail vein and intratumor injection about 3.7MBq (100 μ Ci) And 1.11MBq (30 μ Ci)68Ga-NOTA-DGL-Ac, gathers quiet after developer 15min, 60min, 120min is injected State image.The region of interest of tumour and main organs is delineated on the coronal bit image of whole body in attenuation corrected, radioactivity is measured Uptake values, are represented with %ID/g, and PET imagings put to death the disconnected neck of animal row after terminating, it then follows animal welfare principle.
1.11 68Vivo biodistribution credit cloth of the Ga-NOTA-DGL-Ac in lotus U87MG tumor mouses
Every lotus U87MG tumor mouse is passed through into tail vein injection about 3.7MBq (100 μ under 2% isoflurane anesthesia state Ci)68Ga-NOTA-DGL-Ac.Disconnected neck is passed through after developer is injected 1 hour and puts to death lotus U87MG tumor mouses, dissects and separates swollen Knurl and main organs, and put it into and weighed after sky counting tube (gross weight), then with γ calculating instruments measurement activity meter Count, the radioactive uptake of tumour and normal internal organs is represented with ID%/g, specific experiment step such as 1.8.
2. conclusion
2.1 DGL-NOTA-Ac sign
DGL nano-carriers, NOTA-NHS and reacted DGL-NOTA lyophilized products respectively take 1mg, and the super of 2mL is dissolved in respectively Ultraviolet absorptivity detection is carried out in pure water.As a result show, nano-carrier DGL at 200-500nm wavelength without UV absorption, and NOTA-NHS has ultraviolet absorption peak at 320nm wavelength, and the product of synthesis ultraviolet inhale occurs in corresponding position 320nm or so Receive peak (Fig. 2), illustrate that DGL-NOTA-Ac is successfully synthesized, synthetic product DGL-NOTA-Ac is carried out to pass through Malvern nano particle size Potentiometer detects its particle size in water, and the particle size for as a result showing DGL-NOTA-Ac is (35.02 ± 1.53) nm (Fig. 3).
2.2 68Ga-NOTA-DGL-Ac mark and quality control
As shown in figure 4,68Ga-NOTA-DGL-Ac putting yield is put up to 96% after purifying column separating purification through PD10 Change purity and be more than 98%, pH value is the solution of colourless, transparent clarification between 4.0-4.2, without other heavy metal pollutions.Will 250 μ L's68Ga-NOTA-DGL-Ac probes are observed 7 days through (n=3) in the normal KM Mice Bodies of tail vein injection, do not occur KM The phenomenon of dead mouse, illustrates this nano-probe without overt toxicity.
2.3 lipids are determined
Lipid experiment is in order to measure its lipophilic degree, after measured68Ga-NOTA-DGL-Ac LogP=Log [(the average γ of lipid phase γ countings-background is counted)/(the average γ of aqueous phase γ countings-background is counted)]=- 1.62, illustrate this nanometer point Sub- probe is in hydrophily.
2.4 68Ga-NOTA-DGL-Ac Radio-TLC analyses and vitro stability experiment
Radio-TLC analysis results show, GaCl3RfIt is worth for 0.505,68Ga-NOTA-DGL-Ac RfIt is worth for 0.19. Vitro stability result of study is put as shown in figure 5, it stands 2h in 0.01mol/L pH value 7.4PBS solution and calf serum Change pure equal>95%.Above-mentioned experiment shows,68Ga-NOTA-DGL-Ac has preferable vitro stability, the ratio of the labeled compound Activity is 30GBq/ μm of ol.
2.5 cellular uptakes and elution experiments
To determine68Ga-NOTA-DGL-Ac cell is combined and Cellular retention characteristic, is carried out carefully with A549 and U87MG respectively Born of the same parents absorb and elution experiments.As a result show that A549 and U87MG cells can be combined fast and efficiently68Ga-NOTA-DGL-Ac, such as schemes Shown in 6, and as incubation time extends, developer is further enhanced to two kinds of cell binding forces, is peaked when being incubated 2h. In cell elution experiments,68Ga-NOTA-DGL-Ac shows as slowly declining with the extension of time in two kinds of cells, says It is bright68Ga-NOTA-DGL-Ac is drained slowly in the cell, and still has developer delay at 2h ends.
2.6 68Vivo biodistribution credit cloth of the Ga-NOTA-DGL-Ac in normal mouse
68Ga-NOTA-DGL-Ac normal kunming mice vivo biodistribution distribution results as shown in fig. 7, result is shown： Injection developer 30min after blood radioactivity be significantly lower than 5min, respectively for (3.43 ± 1.93) ID%/g and (8.73 ± 1.21) ID%/g, explanation68Ga-NOTA-DGL-Ac understands speed in blood.Injection developer 5min, 30min, After 60min and 120min, radioactive uptake is mainly gathered in liver and spleen, and radioactive uptake in liver prolonging over time Length has been raised, and the extension in spleen over time has declined.Double kidneys are relatively low in Each point in time radioactive uptake value, And liver is higher in Each point in time radioactive uptake value, explanation68Ga-NOTA-DGL-Ac is by liver metabolism, Er Feijing Kidney excretion.
2.7 68Ga-NOTA-DGL-Ac is imaged in the Micro-PET of normal mouse
68Micro-PET image results (figures of the Ga-NOTA-DGL-Ac in normal KM mouse after tail vein injection 120min 8) show, probe68Ga-NOTA-DGL-Ac is mainly distributed on liver, is secondly spleen, bladder absorbs on a small quantity, double kidneys and other are dirty Device has no obvious intake.
2.8 68Vivo biodistribution credit cloth of the Ga-NOTA-DGL-Ac in lotus U87MG tumor mouses
Nano molecular probe68Ga-NOTA-DGL-Ac is in U87MG tumor mouses after tail vein injection 1 hour, and it is in tumour Radioactive uptake degree in tissue and main organs is shown in Fig. 9.As a result show：Developer is injected after 1 hour, U87MG tumor groups Uptake values are knitted for (0.19 ± 0.02) ID%/g, less than other main organs tissues.Developer is taken the photograph in liver and spleen radioactivity Take higher, respectively (65.75 ± 0.10) ID%/g and (9.79 ± 0.58) ID%/g.
2.9 68Ga-NOTA-DGL-Ac is imaged in the Micro-PET of U87MG mice with tumor
Observable is imaged by Micro PET/CT68In internal medicine generations of the Ga-NOTA-DGL-Ac in U87MG mice with tumor, is dynamic Mechanical characteristic, from figure 10, it is seen that through tail vein injection68After Ga-NOTA-DGL-Ac, developer is mainly distributed on liver, secondly It is heart, knurl tubercle has no obvious intake.The uptake values difference of tumor tissue after injection developer 15min, 60min and 120min For (6.18 ± 1.44), (7.58 ± 1.88) and (5.93 ± 0.48).And intratumor injection result is shown, developer68Ga-NOTA- DGL-Ac is mainly distributed in knurl tubercle, and its hetero-organization of whole body and internal organs are showed no obvious intake.In intratumor injection developer After 15min, 60min and 120min, the uptake values of tumor tissue are (29.82 ± 1.88), (27.68 ± 3.78) and (27.28 respectively ±2.65)。
3. Analysis of conclusion
The present invention uses positron radionuclide by having synthesized dendrimer poly-D-lysine derivative DGL-NOTA-Ac68Ga has carried out pass flag, and this method explores one simple, that quick, putting yield is high positive electron marking nano molecule and visited Pin approach.Show in the Micro-PET imagings of the vivo biodistribution credit cloth and normal mouse of normal mouse,68Ga-NOTA- DGL-Ac nano moleculars probe is distributed mainly on liver and spleen in normal mice body, and other organs have no obvious metabolism.And Also show that nano-probe is mainly collected in liver and spleen in U87MG mice with tumor living imaging and vivo biodistribution credit cloth, swell Obvious intake is had no in knurl.Main cause may is that：1.68Ga-NOTA-DGL-Ac is as nano-probe, due to hydrodynamics It is (35.02 ± 1.53) nm to detect nanometer particle size, therefore the probe causes big in liver easily by reticuloendothelial system phagocytic Amount intake.2.68Ga-NOTA-DGL-Ac nano-probes have tumour passive targeting, cause tumor uptake and imaging effect to pay no attention to Think.
Later stage studies us and will be improved in terms of following two：1. choosing the less nano molecular of nano-scale is used as load Body, such as DGL-G2 so that the nano-scale after modification is adapted to gather in tumor locus, and it is netted that maximum possible reduces liver, spleen etc. The intake of endothelial system.2. increasing the tumor-targeting of nano-probe, glioma can be targetted in nano-sized surface modification RGD etc. Targeting peptides, increase its tumor-targeting.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than the present invention is protected The limitation of scope is protected, although being explained in detail with reference to preferred embodiment to the present invention, one of ordinary skill in the art should Understand, technical scheme can be modified or equivalent substitution, without departing from the essence of technical solution of the present invention.

Claims (10)

1. a kind of compound68Ga-NOTA-DGL-Ac。
2. a kind of preparation method of compound as claimed in claim 1, it is characterised in that use68Ga is to precursor DGL-NOTA-Ac Radioactive label is carried out, compound is produced68Ga-NOTA-DGL-Ac。
3. the preparation method of compound as claimed in claim 2, it is characterised in that the compound68Ga-NOTA-DGL-Ac's Preparation method comprises the following steps：(1) take appropriate watery hydrochloric acid to elute germanium-gallium generator, collect eluent, choose activity Maximum eluent；(2) sodium acetate solution is added into the maximum eluent of the activity obtained by step (1), adjusts pH, Ran Houjia Enter into DGL-NOTA-Ac sodium-acetate buffers；(3) mixed solution obtained by step (2) is subjected to lucifuge reaction, reaction end is 68Ga-NOTA-DGL-Ac。
4. the preparation method of compound as claimed in claim 3, it is characterised in that the concentration of watery hydrochloric acid is in the step (1) 0.05mol/L, the elution flow rate 1ml/min eluted to germanium-gallium generator.
5. the preparation method of compound as claimed in claim 3, it is characterised in that sodium acetate solution is dense in the step (2) Spend for 1.0mol/L.
6. the preparation method of compound as claimed in claim 3, it is characterised in that adjustment pH to 4.0- in the step (2) 4.2。
7. the preparation method of compound as claimed in claim 3, it is characterised in that the condition that lucifuge is reacted in the step (3) For the lucifuge reaction 10min at 70 DEG C.
8. the preparation method of compound as claimed in claim 2, it is characterised in that the preparation side of the precursor DGL-NOTA-Ac Method comprises the following steps：(1) DGL G3 are dissolved in DMSO, stirred and evenly mixed to being completely dissolved；(2) NOTA-NHS is dissolved in DMSO In, stir and evenly mix to being completely dissolved；(3) by the DGL G3 dissolved in step (1) and the middle NOTA-NHS dissolved of step (2) Mixed, lucifuge is reacted at room temperature；(4) excessive triethylamine and then into mixed solution obtained by step (3) is added, at room temperature Lucifuge is stirred, and then adds excessive acetic anhydride, continues to react under the same reaction conditions, and reaction end produces precursor DGL- NOTA-Ac。
9. the preparation method of compound as claimed in claim 8, it is characterised in that the preparation side of the precursor DGL-NOTA-Ac Method also includes dialysing obtained by step (4) in 0.5mol/L, pH=4.0 sodium-acetate buffer after step (5) reaction terminates Precursor, you can obtain purer precursor DGL-NOTA-Ac.
10. compound as claimed in claim 1 as positive electron marking nano probe gene therapy, medicine pass release and it is biological into Application as in.
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