WO2013144301A2 - Synthon composition - Google Patents

Synthon composition Download PDF

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Publication number
WO2013144301A2
WO2013144301A2 PCT/EP2013/056720 EP2013056720W WO2013144301A2 WO 2013144301 A2 WO2013144301 A2 WO 2013144301A2 EP 2013056720 W EP2013056720 W EP 2013056720W WO 2013144301 A2 WO2013144301 A2 WO 2013144301A2
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WO
WIPO (PCT)
Prior art keywords
formula
composition
compound
cassette
hydrogen
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Application number
PCT/EP2013/056720
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English (en)
French (fr)
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WO2013144301A3 (en
Inventor
Rajiv Bhalla
Alexander Jackson
Gareth Smith
Original Assignee
Ge Healthcare Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ge Healthcare Limited filed Critical Ge Healthcare Limited
Priority to JP2015502357A priority Critical patent/JP2015511620A/ja
Priority to EP13713853.3A priority patent/EP2830667A2/en
Priority to CN201380017419.1A priority patent/CN104168924A/zh
Priority to KR20147026773A priority patent/KR20140141604A/ko
Priority to US14/387,660 priority patent/US20160022845A1/en
Priority to IN6805DEN2014 priority patent/IN2014DN06805A/en
Priority to CA2866226A priority patent/CA2866226A1/en
Priority to AU2013241713A priority patent/AU2013241713A1/en
Publication of WO2013144301A2 publication Critical patent/WO2013144301A2/en
Publication of WO2013144301A3 publication Critical patent/WO2013144301A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/0497—Organic compounds conjugates with a carrier being an organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A61K51/1282—Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/001—Acyclic or carbocyclic compounds

Definitions

  • the present invention relates to an improved [ 18 F]labelled synthon composition, wherein the non-radioactive impurities in said composition have been found to be more straightforward to remove than with known compositions comprising said [ !8 F]labelled synthon.
  • the resultant purified [ l 8 F]labelled synthon therefore can be used in the production of a positron emission tomography (PET) tracer having improved properties for in vivo imaging.
  • PET positron emission tomography
  • the invention also includes methods of imaging and/or diagnosis using the radiopharmaceutical compositions described. Description of Related Art
  • Radiofluorination can be conveniently carried out via direct radiofluorination by reacting radiofluorine with a suitable precursor compound.
  • a suitable precursor compound for direct radiofluorination may comprise a group selected for example from N0 2 , trim ethyl ammoni urn (NMe 3 ), CI, Br, I, tosylate (OTs), mesylate (OMs), nosylate (ONs) and trill ate (OTf).
  • NMe 3 trim ethyl ammoni urn
  • CI tosylate
  • OMs mesylate
  • nosylate ONs
  • trill ate OTf
  • [ 18 F]labelled aldehydes including [ l 8 F]fiuoroben/aldehyde ([ 18 F]FBA), and their conjugation to amino-oxy functionalised cyclic ROD peptides.
  • Glaser et al describe that [ i8 F]FBA is obtained by radiofluorination of 4-/V,N,N-trimethylamrnonium benzaldehyde trifluoromcthanesulfonate as illustrated in the following reaction:
  • Impurities such as precursor, DMSO, Kryptofix-222 and hydrophilic by-products were said to be eluted to waste, and the [ 18 F]FBA subsequently eluted with ethanol.
  • the present inventors have, however, found that using the SPE method of Battle et al only some of the precursor is eluted to waste, and the remainder co-el utes when the
  • the present invention relates to a composition comprising an [ ! 8 F]labelled synthon wherein impurities which affect imaging in vivo and found in known compositions of said synthon are not present. Also provided is a rad i oph arm aceu t i cat composition obtained by means of said synthon.
  • the invention also includes methods of imaging and/or diagnosis using the radiopharmaceutical compositions described. Detailed Description of the Invention
  • the present invention provides a composition
  • a composition comprising: an [ 18 F]labelled synthon of Formula X: '*F -Ar x — X ! (X) wherein X 1 is CR'O wherein R 1 is hydrogen or C
  • each of Ar 5 and Ar 6 is a 6-membered aromatic ring comprising between 0-3 nitrogen heteroatoms; and, each of Z 1 and Z 2 is hydrogen or -CR'O as defined for Formula X.
  • composition refers to a chemical composition having the components listed, but that other, unspecified compounds or species may be present in addition.
  • a preferred subset can therefore be "a composition consisting essentially of, which means that the composition has the components listed without other compounds or species being present.
  • An “f " ' 8 F]labelled synthon” also known as an [ 18 F]labelled prosthetic group is a small molecule labelled with 18 F that may be coupled with a non-radioactive precursor compound to result in the desired [ 18 F]labelled product.
  • alkyl used either alone or as part o another group is defined as any straight, branched or cyclic, saturated or unsaturated C n H 2 n+i group.
  • 6-membered aromatic ring refers to an aromatic substitucnt based on benzene (C 6 H 6 ) comprising 0-3 nitrogen heteroatoms.
  • a "nitrogen hetcroatom” is a nitrogen that takes the place of a CM in the aromatic ring.
  • 6-membered aromatic rings of the invention include phenyl, pyridyl, and pyrimidyl.
  • non-radioactive compounds refers to any compound that comprises no radioactive atoms.
  • counter anion refers to an anion that accompanies a cationic species in order to maintain electric neutrality.
  • An "anion” is an ion with more electrons than protons, giving it a net negative charge. Any anion may be used as the counter anions.
  • Non-limiting examples include CF 3 S0 3 , PF 6 , BF 4 , and AsF 6 , S0 4 2 , and N0 3 .
  • X 1 is preferably -CR'O wherein R 1 is hydrogen or Ci -3 alkyl, and is most preferably -CHO.
  • Ar 1 is preferably phenyl or pyridyl, most preferably phenyl.
  • Ar 2 is preferably phenyl or pyridyl, most preferably phenyl.
  • Ar 3 and Ar 4 are preferably both phenyl or both pyridyl, most preferably both phenyl.
  • Y ! is preferably -CRO wherein R 1 is hydrogen or C
  • Y 2 and Y 3 are both preferably hydrogen.
  • Y 2 and Y 3 are alternatively preferably -CRO wherein R 1 is hydrogen or C , alkyl, and is most preferably - CHO.
  • a " is preferably selected from CF 3 SO 3 , PF 6 , BF 4 , and AsF 6 .
  • Ar 5 and Ar 6 are preferably either phenyl or pyridyl, most preferably phenyl.
  • Z 2 are preferably hydrogen or -CHO.
  • 1 is CR O wherein R 1 is hydrogen; and, Ar 1 is phenyl or pyridyl and is most preferably phenyl.
  • X 1 is CRO wherein R 1 is hydrogen
  • Ar' is phenyl
  • Ar 2 is phenyl or pyridyl
  • Ar 3 and Ar 4 are the same and are either both phenyl or both pyridyl; Y 1 is CRO wherein R 1 is hydrogen;
  • Y 2 and Y 3 are the same and are either both hydrogen or both CRO wherein R 1 is hydrogen; and, A " is selected from CF 3 SO 3 " , PF 6 , BF 4 , and AsF ( , ⁇ .
  • Ar 2 is phenyl
  • Ar 3 and Ar 4 are both phenyl
  • Y 1 is CRO wherein R 1 is hydrogen
  • Y 2 and Y 3 are both hydrogen;
  • a " is selected from CF 3 SO3 , PF 6 , BF 4 , and AsF 6 .
  • Ar 2 is phenyl
  • Ar 3 and Ar 4 are both phenyl
  • Y 1 is CRO wherein R 1 is hydrogen
  • Y 2 and Y 3 are both CRO wherein R 1 is hydrogen;
  • a " is selected from CF 3 SO 3 , PF 6 , BF 4 , and AsF 6 .
  • Ar 5 and Ar 6 are independently either phenyl or pyridyl
  • Z 1 and Z 2 are independently hydrogen or -CHO
  • said compound of Formula X is a compound of Formula Xa:
  • said compound of Formula Y is a compound of Formula Ya: wherein Y 1"3 are as defined for Formula Y; and, said compound of Formula Z is a compound of Formula Za:
  • X and Y are both located at the or/Ao-position. In an alternative preferred embodiment, it is preferred that X 1 and Y ! are both located at the para-position.
  • composition of the present invention is advantageous over known compositions that comprise a compound of Formula X.
  • One well-known compound of Formula X is [ 18 F]fluorobenzaldehyde ([ l 8 F]FBA), which is frequently used for the radiofluorination of peptides.
  • [ 18 F]fluorobenzaldehyde [ l 8 F]FBA
  • a major chemical impurity is formed:
  • the compounds of Formula Y and Formula Z are very straightforward to remove from the above-described composition of the present invention to provide pure compound of Formula X.
  • a compound of Formula X which does not include the major chemical impurity shown above can be used to obtain a radiofluorinated product having an improved purity profile.
  • composition of the present invention is obtained by the reaction of a compound of Formula Y with [ F] fluoride. Accordingly, in a second aspect of the present invention is provided a method to prepare the composition as defined for the first aspect of the invention wherein said method comprises:
  • Certain compounds of Formula Y may be obtained by use of methods known in the art. Crivello & Lam ( 1978 J Org Chem; 43(15): 3055-3058), Crivello (US4161478) and Yanez et al (2009 Chem Comm: 827-829) each provide teachings as to how to obtain a variety of compounds of Formula Y by reaction of a compound of Formula Z with a diaryliodonium salt of Formula Q as follows:
  • [ 18 F]Fluoride used in the method of the second aspect of the invention is normally obtained as an aqueous solution from the nuclear reaction 18 0(p,n) 18 F. Once it is made reactive by drying and by the addition of a cationic counterion and the removal of water 18 F " can be reacted with said compound of Formula Y.
  • the step of "drying" [ 18 F]fluoride comprises evaporation of water to result in anhydrous [ 18 F] fluoride. This drying step are suitably carried out by application of heat and use of a solvent such as acetonitrile to provide a lower boiling azeotrope.
  • a “cationic counterion” is a positively-charged counterion examples of which include large but soft metal ions such as rubidium or caesium, potassium compiexed with a cryptand, or tctraalkylammonium salts.
  • a preferred cationic counterion is a metal complex of a cryptand, most preferably wherein said metal is potassium and wherein said cryptand is Kryptofix 222.
  • purification refers to separation of the [ 18 F]labelled synthon of Formula X from the non-radioactive compounds of Formula Y and Formula Z comprised in the composition of the first aspect of the invention with the aim of obtaining pure
  • the purification step of the method of the invention is suitably carried out by chromatography or solid-phase extraction (SPE), wherein said chromatography is preferably high-performance liquid chromatography (HPLC). Purification is facilitated by virtue o the fact that the non-radioactive compounds of Formula Y are charged and as such easy to remove by ion exchange, and also that the non-radioactive compounds of Formula Z are more lipophilic than the
  • [ F] labelled synthon of Formula X and as such they can be removed using differential lipophilicity to purify using solid-phase extraction (SPE). Purification is even more straightforward where a symmetrical compound of Formula Y is used in the method as even fewer non-radioactive compounds are generated in the resultant composition.
  • SPE solid-phase extraction
  • the method of second aspect of the invention is preferably carried out on an automated synthesis apparatus.
  • automated synthesis apparatus is meant an automated module based on the principle of unit operations as described by Satyamurthy et al ( 1999 Clin Positr Imag; 2(5): 233-253).
  • the term 'unit operations means that complex processes are reduced to a series of simple operations or reactions, which can be applied to a range of materials.
  • Such automated synthesis apparatuses arc preferred for the method of the present invention especially when a radiopharmaceutical composition is desired. They are commercially available from a range of suppliers (Satyamurthy et al, above), including: GE Healthcare; CTI Inc; Ion Beam Applications S.A. (Chemin du Cyclotron 3, B- 1 348 Louvain-La- Ncuve, Belgium); Raytest (Germany) and Bioscan (USA).
  • a commercial automated synthesis apparatus also provides suitable containers for the liquid radioactive waste generated as a result of the radiopharmaceutical preparation.
  • Automated synthesis apparatuses are not typically provided with radiation shielding, since they are designed to be employed in a suitably configured radioactive work cell.
  • the radioactive work cell provides suitable radiation shielding to protect the operator from potential radiation dose, as well as ventilation to remove chemical and/or radioactive vapours.
  • the automated synthesis apparatus preferably comprises a cassette.
  • cassette is meant a piece of apparatus designed to fit removably and interchangeably onto an automated synthesis apparatus, in such a way that mechanical movement of moving parts of the synthesizer controls the operation of the cassette from outside the cassette, i.e. externally.
  • Suitable cassettes comprise a linear array ofvalves, each linked to a port where reagents or vials can be attached, by either needle puncture of an inverted septum-sealed vial, or by gas-tight, marrying joints.
  • Each valve has a male- fern ale joint which interfaces with a corresponding moving am of the automated synthesis apparatus. External rotation of the arm thus controls the opening or closing of the valve when the cassette is attached to the automated synthesis apparatus.
  • Additional moving parts of the automated synthesis apparatus are designed to clip onto syringe plunger tips, and thus raise or depress syringe barrels.
  • the cassette i versatile, typically having several positions where reagents can be attached, and several suitable for attachment of syringe vials of reagents or chromatography cartridges (e.g. for SPE).
  • the cassette always comprises a reaction vessel.
  • Such reaction vessels are preferably 0.5 to 10 mL, more preferably 0.5 to 5 mL and most preferably 0.5 to 4 mL in volume and are configured such that 3 or more ports of the cassette are connected thereto, to permit transfer of reagents or solvents from various ports on the cassette.
  • the cassette has 15 to 40 valves in a linear array, most preferably 20 to 30, with 25 being especially preferred.
  • the valves of the cassette are preferably each identical, and most preferably are 3 -way valves.
  • the cassettes are designed to be suitable for radiopharmaceutical manufacture and are therefore manufactured from materials which are of pharmaceutical grade and ideally also are resistant to radiolysis.
  • Preferred automated synthesis apparatuses of the present invention comprise a disposable or single use cassette which comprises all the reagents, reaction vessels and apparatus necessary to carry out the preparation of a given batch of radiofluorinated radiopharmaceutical .
  • the cassette means that the automated synthesis apparatus has the flexibility to be capable of making a variety of different radiopharmaceuticals with minimal risk of cross-contamination, by simply changing the cassette.
  • the cassette approach also has the advantages of: simplified set-up hence reduced risk of operator error; improved GMP (Good Manufacturing Practice) compliance; multi-tracer capability; rapid change between production runs; prc-run automated diagnostic checking o the cassette and reagents; automated barcode cross-check of chemical reagents vs the synthesis to be carried out: reagent traceability; single-use and hence no risk of cross-contamination, tamper and abuse resistance.
  • the present invention provides a method to prepare a composition comprising a positron emission tomography ( ET) tracer of Formula V:
  • the method of the third aspect of the invention is preferably carried out on an automated synthesis apparatus.
  • BTM biological tarReting molecule
  • the BTM may be of synthetic or natural origin, but is preferably synthetic.
  • synthetic has its conventional meaning, i.e. man-made as opposed to being isolated from natural sources e.g. from the mammalian body. Such compounds have the advantage that their manufacture and impurity profile can be fully controlled.
  • the molecular weight of the BTM is preferably up to 10000 Daltons.
  • the molecular weight is in the range 200 to 9000 Daltons, most preferably 300 to 8000 Daltons, with 400 to 6000 Daltons being especially preferred.
  • the molecular weight of the BTM is preferably up to 3000 Daltons, more preferably 200 to 2500 Daltons, most preferably 300 to 2000 Daltons, with 400 to 1500 Daltons being especially preferred.
  • peptide is meant a compound comprising two or more amino acids, as defined below, linked by a peptide bond (i.e. an amide bond linkin the amine of one amino acid to the carboxyl of another).
  • the BTM is an enzyme substrate, enzyme antagonist, enzyme agonist, enzyme inhibitor or receptor- binding compound it is preferably a non-peptide, and more preferably is synthetic.
  • non-peptide is meant a compound which does not comprise any peptide bonds, i.e. an amide bond between two amino acid residues.
  • the method of the third aspect is preferably carried out in a sterile manner, such that a pharmaceutical composition comprising said PET tracer of Formula V is obtained.
  • the radiopharmaceutical compositions of the present invention may be prepared by various methods:
  • kits methodology in which a sterile, non-radioactive kit formulation comprising a suitable precursor and optional excipients is reacted with a suitable supply of l 8 F;
  • composition refers to a composition comprising said PET tracer of Formula V together with a biocompatible carrier in a form suitable for mammalian administration.
  • compositions which are sterile, pyrogen- free, lacks compounds which produce toxic or adverse effects, and is formulated at a biocompatible pH (approximately pH 4.0 to 10.5).
  • Such compositions lack particulates which could risk causing emboli in vivo, and are formulated so that precipitation does not occur on contact with biological fluids (e.g. blood).
  • biological fluids e.g. blood
  • Such compositions also contain only biologically compatible excipients, and are preferably isotonic.
  • the “biocompatible carrier” is a fluid, especially a liquid, in which the PET tracer of Formula V can be suspended or preferably dissolved, such that the composition is physiologically tolerable, i.e. can be administered to the mammalian body without toxicity or undue discomfort.
  • the biocompatible carrier is suitably an injectable carrier liquid such as sterile, pyrogen-free water for injection; an aqueous solution such as saline (which may advantageously be balanced so that the final product for injection is isotonic); an aqueous buffer solution comprising a biocompatible buffering agent (e.g. phosphate buffer); an aqueous solution of one or more tonicity-adjusting substances (e.g.
  • biocompatible counterions e.g. glucose or sucrose
  • sugar alcohols e.g. sorbitol or mannitol
  • glycols e.g. glycerol
  • non-ionic polyol materials e.g. polyethyleneglycols, propylene glycols and the like.
  • the biocompatible carrier is pyrogen-free water for injection, isotonic saline or phosphate buffer.
  • the present invention provides a cassette for carrying out the method of the second aspect of the invention on an automated synthesis apparatus, said cassette comprising
  • the present invention provides a cassette for carrying out the method of the third aspect of the invention on an automated synthesis apparatus, said cassette comprising the features of the cassette as defined for the fourth aspect of the invention in addition to (iv) a vessel containing said compound of Formula W as defined for the third aspect of the invention,
  • a sixth aspect of the present invention is a pharmaceutical composition as defined hereinabove comprising the PET tracer of Formula V as defined for the third aspect of the invention wherein said pharmaceutical composition is obtained according to the method of the third aspect of the invention.
  • the present invention provides a method of imaging the human or animal body which comprises generating a PET image of at least a part of said body to which the pharmaceutical composition of the sixth aspect of the invention has distributed.
  • said method of imaging is carried out repeatedly to monitor the effect of treatment f a human or animal body with a drug, said imaging being effected before and after treatment with said drug, and optionally also during treatment with said drug.
  • said method of the seventh aspect of the invention can be understood as wherein said pharmaceutical composition has been previously administered to said body.
  • the present invention provides a method of diagnosis of the human or animal body which comprises the imaging method of the seventh aspect of the invention.
  • said eighth aspect can be understood to be the pharmaceutical composition of the sixth aspect of the invention for use in said method of diagnosis.
  • Example 1 describes the synthesis of an asymmetrical sulfonium precursor compound of the present invention.
  • Example 2 describes 18 F labelling of an asymmetric sulfonium precursor compound of the present invention. List of Abbreviations used in the Examples
  • [ 18 F] fluoride (370 MBq) was diluted with water ( 1 mL) and trapped a Waters QMA carb. Cartridge.
  • I 8 F] fluoride was eluted into a TRACERlabTM reaction vessel with a solution containing tetrabutylammonium carbonate in acetonitrile/water.
  • [ 18 F] fluoride solution was dried under vacuum and with a stream o nitrogen. (4- formylphenyl)diphenylsulfonium 2,2,2-trifluoroacetate (8.5 mg) in dimethylsulfoxide (1 ml) was added to the resultant [ 18 F] tetrabutylammonium fluoride residue and heated in the sealed reactor for 15 minutes at 130°C.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dispersion Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
PCT/EP2013/056720 2012-03-30 2013-03-28 Synthon composition WO2013144301A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
JP2015502357A JP2015511620A (ja) 2012-03-30 2013-03-28 シントン組成物
EP13713853.3A EP2830667A2 (en) 2012-03-30 2013-03-28 Synthon composition
CN201380017419.1A CN104168924A (zh) 2012-03-30 2013-03-28 容易纯化的合成子组合物
KR20147026773A KR20140141604A (ko) 2012-03-30 2013-03-28 용이하게 정제가능한 신톤 조성물
US14/387,660 US20160022845A1 (en) 2012-03-30 2013-03-28 Synthon composition
IN6805DEN2014 IN2014DN06805A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 2012-03-30 2013-03-28
CA2866226A CA2866226A1 (en) 2012-03-30 2013-03-28 Synthon composition
AU2013241713A AU2013241713A1 (en) 2012-03-30 2013-03-28 Easily purifiable synthon composition

Applications Claiming Priority (4)

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US201261617698P 2012-03-30 2012-03-30
US61/617,698 2012-03-30
GBGB1205703.0A GB201205703D0 (en) 2012-03-30 2012-03-30 Synthon composition
GB1205703.0 2012-03-30

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WO2013144301A2 true WO2013144301A2 (en) 2013-10-03
WO2013144301A3 WO2013144301A3 (en) 2013-11-21

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11077216B2 (en) 2014-06-30 2021-08-03 Ge Healthcare Limited Formulation and method of synthesis
US11534494B2 (en) 2011-12-21 2022-12-27 Ge Healthcare Limited Formulation and method of synthesis

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4161478A (en) 1974-05-02 1979-07-17 General Electric Company Photoinitiators
WO2004080492A1 (en) 2003-03-13 2004-09-23 Amersham Health As Methods of radiofluorination of biologically active vectors
WO2010066380A1 (en) 2008-12-12 2010-06-17 Bayer Schering Pharma Aktiengesellschaft Triaryl-sulphonium compounds, kit and methods for labeling positron emitting isotopes

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8257680B1 (en) * 2004-02-24 2012-09-04 The General Hospital Corporation Catalytic radiofluorination
EP2110367A1 (en) * 2008-04-14 2009-10-21 Bayer Schering Pharma Aktiengesellschaft Purification strategy for direct nucleophilic procedures
WO2011141515A1 (en) * 2010-05-14 2011-11-17 Bayer Pharma Aktiengesellschaft Diagnostic agents for amyloid beta imaging

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4161478A (en) 1974-05-02 1979-07-17 General Electric Company Photoinitiators
WO2004080492A1 (en) 2003-03-13 2004-09-23 Amersham Health As Methods of radiofluorination of biologically active vectors
WO2010066380A1 (en) 2008-12-12 2010-06-17 Bayer Schering Pharma Aktiengesellschaft Triaryl-sulphonium compounds, kit and methods for labeling positron emitting isotopes

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
BATTLE ET AL., J NUCL MED, vol. 52, no. 3, 2011, pages 424 - 430
CARROLL ET AL., J LABEL COMP RADIOPHARM, vol. 48, no. 7, 2005, pages 519 - 520
CRIVELLO; LAM, J ORGCHEM, vol. 43, no. 15, 1978, pages 3055 - 3058
GLASER ET AL., BIOCONJ CHEM, vol. 19, no. 4, 2008, pages 951 - 957
J FLUORINE CHEM, vol. 128, no. 2, 2007, pages 127 - 132
LEE ET AL., J LABEL COMP RADIOPHARM, vol. 48, 2005, pages 288
POETHKO ET AL., J NUC MED, vol. 45, 2004, pages 892 - 902
SATYAMURTHY ET AL., CLIN POSITR IMAG, vol. 2, no. 5, 1999, pages 233 - 253
SNYDER; KILBOUM: "Handbook of Radiopharmaceuticals, Radiochemistry and Applications", 2003, pages: 195 - 227
YANEZ ET AL., CHEM COMM, 2009, pages 827 - 829

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11534494B2 (en) 2011-12-21 2022-12-27 Ge Healthcare Limited Formulation and method of synthesis
US11077216B2 (en) 2014-06-30 2021-08-03 Ge Healthcare Limited Formulation and method of synthesis

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US20160022845A1 (en) 2016-01-28
CA2866226A1 (en) 2013-10-03
KR20140141604A (ko) 2014-12-10
AU2013241713A1 (en) 2014-10-02
CN104168924A (zh) 2014-11-26
GB201205703D0 (en) 2012-05-16
JP2015511620A (ja) 2015-04-20
IN2014DN06805A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 2015-06-26
EP2830667A2 (en) 2015-02-04
WO2013144301A3 (en) 2013-11-21

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