Syntheses of 5‐(2‐radiohaloethyl)‐ and 5‐(2‐radiohalovinyl)‐2′‐ deoxyuridines. Novel types of radiotracer for monitoring cancer gene therapy with PET

Syntheses of 5‐(2‐¹⁸F]fluoroethyl)‐ ( 1 ), 5‐(2‐⁸⁰Br]bromoethyl)‐ ( 2 ), un‐deprotected (E)‐5‐(2‐¹⁸F]fluorovinyl)‐ ( 3 ) and (E)‐5‐(2‐⁸⁰Br]bromovinyl)‐2′‐deoxyuridines ( 4 ) as the tracers for monitoring cancer gene therapy with positron emission tomography were described. Decay corrected radiochemical yield and synthesis time including labeling and HPLC purification from end of bombardment for 1 was 9.5% and 2 hours, respectively; yield and time for 2 was 16% and 2 hours, respectively. Chemical (approximate to radiochemical) yield and time for synthesis of 3 was 7.5% and 7 minutes, respectively. Radiochemical yield and synthesis time including labeling and HPLC purification of an analytical sample of 4 was 60% and 30 minutes, respectively. Both 2 and 4 received the side reactions during HPLC purification, i.e. ring closure and cleavage of glycosidic bond, respectively. Application of 2 and 4 needed to be confirmed by in vitro or in vivo experiments. Radiochemical yield of 1 could be optimized by employing a modified protocol for preparation of its precursor. The preparation of fluorovinyl counterparts had demonstrated the potential utility of the stannane, 3‐tolyl‐3′,5′‐di‐O‐acetyl‐(E)‐5‐(2‐stannylvinyl)‐2′‐deoxyuridine 7 . Copyright © 2003 John Wiley & Sons, Ltd.