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WO1999018053A1 - Preparation de composes haloaromatiques radiomarques au moyen d'intermediaires a liaison polymere - Google Patents

Preparation de composes haloaromatiques radiomarques au moyen d'intermediaires a liaison polymere Download PDF

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Publication number
WO1999018053A1
WO1999018053A1 PCT/CA1998/000933 CA9800933W WO9918053A1 WO 1999018053 A1 WO1999018053 A1 WO 1999018053A1 CA 9800933 W CA9800933 W CA 9800933W WO 9918053 A1 WO9918053 A1 WO 9918053A1
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Prior art keywords
formula
compound
group
polymer
insoluble polymer
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/CA1998/000933
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English (en)
Inventor
Duncan H. Hunter
Xizhen Zhu
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University of Western Ontario
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University of Western Ontario
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Application filed by University of Western Ontario filed Critical University of Western Ontario
Priority to US09/529,017 priority Critical patent/US6461585B1/en
Priority to CA002345710A priority patent/CA2345710C/fr
Publication of WO1999018053A1 publication Critical patent/WO1999018053A1/fr
Anticipated expiration legal-status Critical
Priority to US11/850,306 priority patent/US7658910B2/en
Priority to US12/702,009 priority patent/US20100274052A1/en
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/30—Introducing nitrogen atoms or nitrogen-containing groups
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
    • C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/42—Introducing metal atoms or metal-containing groups

Definitions

  • This invention relates to the preparation of a radiopharmaceutical.
  • this invention relates to a process for the preparation a radiolabelled haloaromatic, as well as intermediate precursor compounds used in the process.
  • MIBG meta-iodobenzylguanidine
  • iodine atom when radiolabelled with the iodine atom, is used in nuclear medicine as either an imaging agent for diagnosis, or as a therapeutic agent for neural crest tumors such as neuroblastoma.
  • [ 123 I]MIBG provides diagnostic cardiac images as well as images of tumors.
  • the longer-lived [ 131 I]MIBG is used at much higher radiation and chemical doses for the treatment of tumors.
  • no-carrier-added [ 31 I]MIBG routes to no-carrier-added [ 31 I]MIBG have been developed which could reduce the chemical dose of MIBG by about a factor of 100.
  • Precursors to no- carrier-added [ 131 I]MIBG such as 3-tributylstannylbenzylamine 2 , 3- trimethylsilylbenzylguanidine 2 , and 3-trimethylstannylguanidinium 3 , have not found widespread application. These compounds have a short shelf life, and must be stored in a freezer shielded from light.
  • United States Patent No. 5,565,185 discloses a no-carrier-added process of radiolabelling MIBG by halodestannylation.
  • the process is disadvantageous in that a number of impurities remain in solution with the radiolabelled MIBG.
  • toxic tin by-products remain in solution and must be separated before the radiolabelled
  • MIBG is ready for use.
  • R 2 is selected from an alkyl group, an aryl group, a hydrogen atom, a halogen atom, a substituted oxygen atom, a substituted nitrogen atom, a substituted sulfur atom, a carbonyl group, a cyano group, an amino group, and a guanidino group.
  • X is selected from any suitable radiohalide, and is preferably selected from 123 l, 125 l, and 131 l.
  • the process comprises reacting an insoluble polymer compound (II) with a radiohalogen ion in the presence of an oxidant and a preferably organic solvent, where compound (II) has the formula:
  • R is an alkyl group, and is preferably a butyl group.
  • R 2 is as described above.
  • an intermediate insoluble polymer compound is provided.
  • the compound comprises the repeating unit formula:
  • R is selected from an alkyl group
  • R 2 is selected from an alkyl group, an aryl group, a hydrogen atom, a halogen atom, a substituted oxygen atom, a substituted nitrogen atom, a substituted sulfur atom, a carbonyl group, a cyano group, an amino group, and a guanidino group.
  • the process comprises reacting the compound of formula:
  • n is selected from 123, 125, and 131 ; the process comprising contacting a compound having the formula:
  • Fig. 1A shows the 119 Sn MAS NMR spectrum for Polymer 1 ;
  • Fig. 1 B shows the 119 Sn MAS NMR spectrum for Polymer 1 after hydrolysis
  • Fig. 1C shows the 119 Sn MAS NMR spectrum for Polymer 2
  • Fig. 1D shows the 119 Sn MAS NMR spectra for Polymer 3 recovered after iodination
  • Fig. 2 shows the HPLC analysis of the iodination products of reaction of Polymer 2 with cyanamide at selected reaction times.
  • the process provides for the radiohalogenation of a haloaromatic compound using a polymer-supported pharmaceutical, as follows: insohblepofyirEr rad pharrnaceudcai wherein:
  • R is an alkyl group, and is preferably a butyl group.
  • R 2 is selected from an alkyl group, an aryl group, a hydrogen atom, a halogen atom, a substituted oxygen atom, a substituted nitrogen atom, a substituted sulfur atom, a carbonyl group, a cyano group, an amino group, a guanidino group;
  • Nu is a nucleophile provided by the solvent or oxidant; and * X is selected from any suitable radiohalide, such as, for example, 131 l or 123 l.
  • a process is provided to synthesize no-carrier-added [ 131 I]MIBG or [ 123 I]MIBG using polymer-supported radiopharmaceutical precursors 4 .
  • An insoluble polymer is prepared in which the pharmaceutical to be radiohalogenated is bound to the polymer through a tin-aryl bond as illustrated above. Treatment with the radiohalide and an appropriate oxidant results in the release of the radiohalogenated pharmaceutical while unreacted polymer and polymer side- products remain insoluble and easily removed by filtration.
  • the polymer above is derived by reaction of the appropriate organolithium with a polymeric chlorostannane.
  • Polymer 1 described in detail below, is used as an intermediate compound to derive the polymers to be used in the radiohalogenation of a haloaromatic compound.
  • Polymer 2 is one such reagent derived from Polymer 1
  • Polymer 3 is the preferred polymer-supported 3-benzylguanidinium reagent for the preparation of no-carrier-added [ 13 I]MIBG or [ 123 I]MIBG. Polymers 2 and 3 are also described in detail below.
  • Polymer 1 has the following structural formula:
  • Polymer 1 The characteristics of Polymer 1 are preferably as follows:
  • Polymer 1 Samples of Polymer 1 were prepared as indicated above. Polymer 1 was characterized both chemically and spectroscopically. The availability of Sn-CI bonds was assessed by treatment of Polymer 1 with KOH in ethanol/THF at room temperature. Polymer 1 (201 mg) was soaked in 7 mL of absolute ethanol, 3 mL (3 mmol) of 1 M potassium hydroxide, and 1 mL of tetrahydrofuran for 24 h at room temperature. The polymer was filtered and washed with 70 % ethanol (5 x 5 mL). The ethanol and THF in the filtrate were removed on rotary evaporator and the residual liquid was transferred into a 50 mL volumetric flask and topped up to the mark with water.
  • Polymer 1 was also investigated by MAS NMR spectroscopy on samples that had been preswollen with chloroform which had the effect of sharpening the signals.
  • the 13 C NMR spectrum was consistent with the anticipated structure showing signals for all of the carbons.
  • the signals for the backbone CH and CH 2 and phenyl carbons were quite broad and indistinct.
  • the CH 2 -CH 2 carbons and the carbons on the butyl chains were readily assigned by analogy with non-polymeric species.
  • the 119 Sn NMR spectrum ( Figure 1A) showed but one peak at 148 ppm consistent with species of the general structure R 3 Sn-CI. This confirmed that all of the tin atoms were bonded to chlorine in spite of the apparent discrepancy in the hydrolysis results mentioned above.
  • Polymer 1 was preferably converted in two steps first into Polymer 2 which bears the 3-benzylammonium moiety and then into Polymer 3 functionalised with a 3-benzylguanidinium species.
  • Polymer 2 The characteristics of Polymer 2 were preferably as follows: • Solid-state MAS 13 C NMR spectrum: ⁇ 14.6 ( CH 3 ), 18.6 ( Sn-CH 2 . ), 27.7 (-CH 2 CH 2 CH 3 ), 28.6 ( -CH 2 CH 3 ), 42 ( broad, Ar-CH-, Ar-CH 2 - and backbone -CH 2 . ), 128 (broad, aryl CH), 144 ( broad, Aryl C )
  • the synthesis of Polymer 3 involved treatment of Polymer 2 with a large excess of cyanamide to convert the ammonium group into a guanidinium group, as illustrated below.
  • HPLC analysis showed 8 mol % of 3-iodobenzylamine hydrochloride, 17 mol % of MIBG and 75 mol % of 3-iodobenzylbiguanidinium nitrate (excluding dicyandiamide at 9.6 min ) with a retention times of 6.1 min, 11.2 min and 12.7 min respectively.
  • the solution was adjusted to pH ⁇ 9 with saturated sodium carbonate.
  • the upper aqueous solution was decanted from the oil which was separated. Water (5 mL) was added to the oil followed by 1 M nitric acid to a pH ⁇ 5. A lot of bubbles formed during the addition of nitric acid and the mixture turned into a clear solution at pH ⁇ 5. White crystals formed about 1 minute later.
  • the characteristics of the3-iodobenzylbiguanidinium nitrate were preferably as follows:
  • the filtrate was analyzed by HPLC.
  • the UV detector trace showed a large peak at the solvent front and several smaller peaks well before MIBG peak.
  • the corresponding radioactivity detector trace showed two peaks at 1.9 and 15.6 min which were confirmed by coinjection to be 131 l - ( 2.4 % ) and [ 131 I]MIBG (97.6%) respectively.
  • [ 123 I]MIBG was produced using lodobeadsTM as the oxidant, which resulted in a radiochemical yield of about 55 %. Since later experiments with Na 131 l showed that about 45 % of the radioactivity remained absorbed to the insoluble polymeric materials, this experiment demonstrates that Polymer 3 is an effective precursor to [ 123 I]MIBG. Similar results can also be expected with [ 125 I]MIBG.
  • the process produces no-carrier-added [ 131 I]MIBG in > 90 % radiochemical yield and high chemical purity. Isolation and purification are simple, involving just filtration and absorption and desorption onto a C18 Sep-PakTM cartridge. No-carrier-added material should avoid the potential pharmacological side effects accompanying the current method of production.
  • the process and precursor compounds, according to the present invention is useful in the field of nuclear medicine for the production of radiopharmaceutical compounds.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)

Abstract

L'invention concerne, dans un premier aspect, un procédé pour la préparation de composés haloaromatiques radiomarqués. Elle concerne également, dans un deuxième aspect, des composés polymères insolubles précurseurs intermédiaires utilisés dans la préparation des composés haloaromatiques radiomarqués, ainsi que des procédés pour la préparation de composés polymères insolubles précurseurs intermédiaires.
PCT/CA1998/000933 1997-10-02 1998-10-02 Preparation de composes haloaromatiques radiomarques au moyen d'intermediaires a liaison polymere Ceased WO1999018053A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US09/529,017 US6461585B1 (en) 1998-10-02 1998-10-02 Preparation of radiolabelled haloaromatics via polymer-bound intermediates
CA002345710A CA2345710C (fr) 1997-10-02 1998-10-02 Preparation de composes haloaromatiques radiomarques au moyen d'intermediaires a liaison polymere
US11/850,306 US7658910B2 (en) 1997-10-02 2007-09-05 Preparation of radiolabelled haloaromatics via polymer-bound intermediates
US12/702,009 US20100274052A1 (en) 1997-10-02 2010-02-08 Preparation of radiolabelled haloaromatics via polymer-bound intermediates

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US6088697P 1997-10-02 1997-10-02
US60/060,886 1997-10-02

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09529017 A-371-Of-International 1998-10-21
US10/224,261 Division US7273601B2 (en) 1997-10-02 2002-08-20 Preparation of radiolabelled haloaromatics via polymer-bound intermediates

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002070020A2 (fr) 2001-03-02 2002-09-12 University Of Western Ontario Precurseurs polymeres de composes radiomarques et methodes de fabrication et d'utilisation de ceux-ci
WO2004056399A3 (fr) * 2002-12-20 2004-09-23 Amersham Plc Fluoration en phase solide de benzothiazoles
WO2004098650A3 (fr) * 2003-05-02 2005-01-27 Univ Western Ontario Groupements prosthetiques utilisables dans la synthese des composes radiopharmaceutiques
WO2005095385A1 (fr) * 2004-03-02 2005-10-13 Aventis Pharmaceuticals Inc. Processus pour la preparation d'inhibiteurs de tryptase
WO2005107819A3 (fr) * 2004-05-11 2007-03-29 Hammersmith Imanet Ltd Procedes de purification
US7273601B2 (en) 2000-07-18 2007-09-25 The University Of Western Ontario Preparation of radiolabelled haloaromatics via polymer-bound intermediates
JP2010514786A (ja) * 2006-12-26 2010-05-06 ランセウス メディカル イメージング， インコーポレイテッド 心臓の神経支配を画像化するためのリガンド
EP1562640A4 (fr) * 2002-10-18 2010-07-07 Univ Mcmaster Procede de purification de composes radiomarques
EP2891657A1 (fr) 2014-01-07 2015-07-08 Centre National de la Recherche Scientifique (CNRS) Réactifs organostannane supportés par un liquide ionique pour la fabrication de composés radiopharmaceutiques
US9388125B2 (en) 2010-05-11 2016-07-12 Lantheus Medical Imaging, Inc. Compositions, methods, and systems for the synthesis and use of imaging agents
JP2019077703A (ja) * 2014-04-17 2019-05-23 イミューノメット セラピューティクス インコーポレイテッド グアニジン化合物、及びその用途

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0693467A1 (fr) * 1994-07-20 1996-01-24 Merck Frosst Canada Inc. Procédé pour la préparation de méta-halobenzylguanidine radiomarque

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0693467A1 (fr) * 1994-07-20 1996-01-24 Merck Frosst Canada Inc. Procédé pour la préparation de méta-halobenzylguanidine radiomarque

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
A. R. WAFELMAN: "Synthesis, radiolabelling and stability of radioiodinated m-iodobenzylguanidine, a review", APPLIED RADIATION AND ISOTOPES., vol. 45, no. 10, 1994, EXETER GB, pages 997 - 1007, XP002088255 *
G. VAIDYANATHAN: "No-carrier-added synthesis of meta-[131]iodobenzylguanidine", APPLIED RADIATION AND ISOTOPES., vol. 44, no. 3, 1993, EXETER GB, pages 621 - 628, XP002088254 *
P. A. CULBERT: "Polymer-supported radiopharmaceuticals: 123-I- and 131-I-labelled N-isopropyl-4-iodoamphetamine", REACTIVE POLYMERS, vol. 19, 1993, pages 247 - 253, XP002088253 *

Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7658910B2 (en) 1997-10-02 2010-02-09 The University Of Western Ontario Preparation of radiolabelled haloaromatics via polymer-bound intermediates
US7273601B2 (en) 2000-07-18 2007-09-25 The University Of Western Ontario Preparation of radiolabelled haloaromatics via polymer-bound intermediates
WO2002070020A3 (fr) * 2001-03-02 2003-05-30 Univ Western Ontario Precurseurs polymeres de composes radiomarques et methodes de fabrication et d'utilisation de ceux-ci
US9023317B2 (en) 2001-03-02 2015-05-05 University Of Western Ontario Polymer precursors of radiolabeled compounds, and methods of making and using the same
US8383083B2 (en) 2001-03-02 2013-02-26 University Of Western Ontario Polymer precursors of radiolabeled compounds, and methods of making and using the same
WO2002070020A2 (fr) 2001-03-02 2002-09-12 University Of Western Ontario Precurseurs polymeres de composes radiomarques et methodes de fabrication et d'utilisation de ceux-ci
US7018610B2 (en) 2001-03-02 2006-03-28 University Of Western Ontario Polymer precursors of radiolabeled compounds, and methods of making and using the same
EP2295475A1 (fr) 2001-03-02 2011-03-16 University of Western Ontario Precurseurs polymeres de composes radiomarques et methodes de fabrication et d'utilisation de ceux-ci
AU2002258100B2 (en) * 2001-03-02 2007-03-01 University Of Western Ontario Polymer precursors of radiolabeled compounds, and methods of making and using the same
EP1562640A4 (fr) * 2002-10-18 2010-07-07 Univ Mcmaster Procede de purification de composes radiomarques
US8323616B2 (en) 2002-12-20 2012-12-04 Ge Healthcare Limited Solid-phase fluorination of benzothiazoles
JP2006510705A (ja) * 2002-12-20 2006-03-30 ジーイー・ヘルスケア・リミテッド ベンゾチアゾール類の固相フッ素化
WO2004056399A3 (fr) * 2002-12-20 2004-09-23 Amersham Plc Fluoration en phase solide de benzothiazoles
US8697032B2 (en) 2003-05-02 2014-04-15 University Of Western Ontario Prosthetic groups attached to stannyl polymer in the synthesis of radiopharmaceuticals
CN100536926C (zh) * 2003-05-02 2009-09-09 西安大略省大学 合成放射性药物中连接至甲锡烷基聚合物的辅基
JP2006525311A (ja) * 2003-05-02 2006-11-09 ザ ユニバーシティー オブ ウェスタン オンタリオ 放射性医薬化合物の合成に有用な補欠分子族
JP2010265283A (ja) * 2003-05-02 2010-11-25 Univ Of Western Ontario 放射性医薬化合物の合成に有用な補欠分子族
WO2004098650A3 (fr) * 2003-05-02 2005-01-27 Univ Western Ontario Groupements prosthetiques utilisables dans la synthese des composes radiopharmaceutiques
US8435492B2 (en) 2003-05-02 2013-05-07 University Of Western Ontario Prosthetic groups attached to stannyl polymer in the synthesis of radiopharmaceuticals
CN101675997B (zh) * 2003-05-02 2013-07-17 西安大略省大学 合成放射性药物中连接至甲锡烷基聚合物的辅基
WO2005095385A1 (fr) * 2004-03-02 2005-10-13 Aventis Pharmaceuticals Inc. Processus pour la preparation d'inhibiteurs de tryptase
RU2378271C2 (ru) * 2004-03-02 2010-01-10 Авентис Фармасьютикалз Инк. Способы получения ингибиторов триптазы
EP2186782A1 (fr) * 2004-05-11 2010-05-19 GE Healthcare Limited Procédés pour la purification de produits radiomarques utilisant un capteur lié à un support solide
WO2005107819A3 (fr) * 2004-05-11 2007-03-29 Hammersmith Imanet Ltd Procedes de purification
US8221720B2 (en) 2004-05-11 2012-07-17 Hammersmith Imanet Limited Purification methods
US11241509B2 (en) 2006-12-26 2022-02-08 Lantheus Medical Imaging, Inc. Ligands for imaging cardiac innervation
US10010631B2 (en) 2006-12-26 2018-07-03 Lantheus Medical Imaging, Inc. Ligands for imaging cardiac innervation
US8491868B2 (en) 2006-12-26 2013-07-23 Lantheus Medical Imaging, Inc. Ligands for imaging cardiac innervation
US12324845B2 (en) 2006-12-26 2025-06-10 Lantheus Medical Imaging, Inc. Ligands for imaging cardiac innervation
JP2010514786A (ja) * 2006-12-26 2010-05-06 ランセウス メディカル イメージング， インコーポレイテッド 心臓の神経支配を画像化するためのリガンド
JP2014237679A (ja) * 2006-12-26 2014-12-18 ランセウス メディカル イメージング， インコーポレイテッド 心臓の神経支配を画像化するためのリガンド
US9388125B2 (en) 2010-05-11 2016-07-12 Lantheus Medical Imaging, Inc. Compositions, methods, and systems for the synthesis and use of imaging agents
US9682927B2 (en) 2010-05-11 2017-06-20 Lantheus Medical Imaging, Inc. Compositions, methods, and systems for the synthesis and use of imaging agents
US11174223B2 (en) 2010-05-11 2021-11-16 Lantheus Medical Imaging, Inc. Compositions, methods, and systems for the synthesis and use of imaging agents
WO2015104300A1 (fr) 2014-01-07 2015-07-16 Centre National De La Recherche Scientifique (Cnrs) Réactifs organostanniques supportés sur liquide ionique pour la production de composés radiopharmaceutiques
US9714261B2 (en) 2014-01-07 2017-07-25 Centre National De La Recherche Scientifique (Cnrs) Ionic liquid supported organotin reagents for the manufacturing of radiopharmaceuticals compounds
JP2017504658A (ja) * 2014-01-07 2017-02-09 センター ナショナル デ ラ リシェルシェ サイエンティフィック（シーエヌアールエス） 放射性医薬品化合物の製造のためのイオン性液体担持有機スズ試薬
EP2891657A1 (fr) 2014-01-07 2015-07-08 Centre National de la Recherche Scientifique (CNRS) Réactifs organostannane supportés par un liquide ionique pour la fabrication de composés radiopharmaceutiques
JP2019077703A (ja) * 2014-04-17 2019-05-23 イミューノメット セラピューティクス インコーポレイテッド グアニジン化合物、及びその用途
US11465989B2 (en) 2014-04-17 2022-10-11 ImmunoMet Therapeutics, Inc. Guanidine compounds and use thereof

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Publication number Publication date
CA2345710C (fr) 2008-12-30
CA2345710A1 (fr) 1999-04-15

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