Development of a positron emission tomography radiopharmaceutical for imaging thymidine kinase gene expression : Synthesis and in vitro evaluation of 9-{3-[18F] Fluoro-1-hydroxy-2-propoxymethyl guanine
[en] 9-[(3-fluoro-1-hydroxy-2-propoxy)methyl]guanine (FHPG) 2 has been labeled with fluorine-18 and evaluated in vitro as a potential radiotracer for mapping gene expression in vivo with positron emission tomography (PET).
Disciplines :
Biotechnology
Author, co-author :
Monclus, Michel
Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron
Cool, Vincent
Damhaut, Philippe
Velu, Thierry
Goldman, Serge
Language :
English
Title :
Development of a positron emission tomography radiopharmaceutical for imaging thymidine kinase gene expression : Synthesis and in vitro evaluation of 9-{3-[18F] Fluoro-1-hydroxy-2-propoxymethyl guanine
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Preparation of 9-{[1,3-di(p-toluenesulfonyloxy)-2-propoxy]methyl}guanine 3. To a suspension of DHPG 1 (255 mg, 1 mmole) in anhydrous pyridine (2 mL) was added with a syringe p-toluenesulfonyl chloride (955 mg, 5 mmoles) previously dissolved in anhydrous pyridine (1 mL). After addition, the suspension was allowed to stand at room temperature for 12 h. The solution was then poured in 1 M HCl/ice and then filtered. The crude material was purified by using column chromatography (SiO2, CH2Cl2/methanol: 9/1 and then CH2Cl2/methanol: 8/2) to afford pure ditosylate 3 (230 mg, 40%) as a solid mp 272-273°C (dec). 1H-NMR (250 MHz, DMSO-d6): δ 2.41 (s, 6H, CH3), 3.88 (dd, J=5.7, 10.6 Hz, 2H, CH2 (5′)), 4.02 (dd, J=3.5, 10.7 Hz, 2H, CH2 (3′)), 4.08-4.12 (m, 1H, CH (4′)), 5.28 (s, 2H, CH2), 6.57 (s, 1H, NH), 7.43 (d, J=8.25 Hz, 2H), 7.65 (d, J=7.8 Hz, 2H); HPLC-MS [M+H]+: 564
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