Preparation of 5-[131I]Iodo- and 5-[211At]astato-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil by a halodestannylation reaction

To circumvent the in vivo instability of 5-iodo-2'-deoxyuridine (IUdR), a 2'-fluorine-substituted analogue, 5-iodo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (FIAU) recently has been introduced. To facilitate the preparation of radioiodinated FIAU as well as its astatinated analogue, a tin precursor, 5-trimethylstannyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (FTAU) was synthesized. Both [I-125/131]FIAU and 5-[At-211]astato-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (FAAU) were prepared from FTAU in more than 85% radiochemical yield under mild conditions. The in vitro serum stability of both fluorine-substituted derivatives was higher than that of the corresponding unsubstituted parents. The enhanced stability of fluorinated derivatives was even more apparent in whole blood. The uptake of [I-125]FIAU in D-247 MG human glioma cells in vitro was 20-fold higher than that of [I-125]IUdR over an activity concentration range of 5-100 kBq/mL; the uptake of FAAU was not significantly different from that of 5-[At-211]astato-2'-deoxyuridine (AUdR). Accumulation of radioiodine in mouse thyroid in vivo with [I-131]FIAU was fivefold lower than [I-125]IUdR, indicating that the former was less susceptible to deiodination. The tissue uptake of FAAU was similar to that reported for AUdR. NUCL MED BIOL 25;5: 487-496, 1998. (C) 1998 Elsevier Science Inc.