Synthesis and biological evaluation of a lipophilic,fluorine‐18‐labeled 5‐ethynyl‐2′‐deoxyuridine derivative |
| |
Authors: | Satish K Chitneni Tom De Ruymaeker Jan Balzarini Alfons M Verbruggen Guy M Bormans |
| |
Institution: | 1. Laboratory for Radiopharmacy, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Leuven, Belgium;2. Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium |
| |
Abstract: | The synthesis and preliminary biological evaluation of a lipophilic, fluorine‐18‐labeled 5‐ethynyl‐2′‐deoxyuridine derivative 18F]‐ 3 is described. Initially, 5‐ethynyl‐2′‐deoxyuridine 5 was synthesized by coupling trimethylsilyl protected acetylene to 5‐iodo‐2′‐deoxyuridine 4 , followed by deprotection in alkaline conditions. Compound 5 was then reacted with 4‐(4′‐iodophenyl)phenol to give 5‐4(4′‐hydroxyphenyl)phenyl]ethynyl‐2′‐deoxyuridine 6 . Compound 6 was reacted with BrCH2CH F as alkylating agent to give stable or radiolabeled 3 . The crude products were purified using reversed phase‐high performance liquid chromatography to obtain compound 3 and 18F]‐ 3 in 33 and 7.4% yield (decay corrected), respectively. The synthesis time to obtain pure 18F]‐ 3 was about 60 min (starting from BrCH2CH F). The specific radioactivity of the tracer was between 74 and 222 GBq/µmol. The log P7.4 of 18F]‐ 3 was found to be 2.4. However, biodistribution study in normal mice showed low uptake of the tracer in the brain. The affinity of compounds 6 and 3 for varicella‐zoster virus thymidine kinase enzyme (VZV‐TK) was examined in vitro and the results revealed that the fluorinated analog 3 has a poor affinity for the enzyme in contrast to the phenol precursor 6 . Copyright © 2007 John Wiley & Sons, Ltd. |
| |
Keywords: | BCNAs VZV‐tk gene expression imaging PET |
|
|