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

Abstract

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)ura cil (FTAU) was synthesized. Both [125/131I]FIAU and 5-[211At]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 [125I]FIAU in D-247 MG human glioma cells in vitro was 20-fold higher than that of [125I]IUdR over an activity concentration range of 5-100 kBq/mL; the uptake of FAAU was not significantly different from that of 5-[211At]astato-2'-deoxyuridine (AUdR). Accumulation of radioiodine in mouse thyroid in vivo with [131I]FIAU was fivefold lower than [125I]IUdR, indicating that the former was less susceptible to deiodination. The tissue uptake of FAAU was similar to that reported for AUdR.

• Authors: G Vaidyanathan, M R Zalutsky
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 25 Issue 5 Pg. 487-96 (Jul 1998) ISSN: 0969-8051 [Print] United States
• PMID: 9720667 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 5-(211-At)astato-1-(2-deoxy-2-fluoro-arabinofuranosyl)uracil
• Indicators and Reagents
• Iodine Radioisotopes
• Radiopharmaceuticals
• Arabinofuranosyluracil
• fialuridine
• Tin
• DNA

Topics

• Animals
• Arabinofuranosyluracil (analogs & derivatives, chemical synthesis, pharmacokinetics, pharmacology)
• Cell Line
• DNA (metabolism)
• Drug Stability
• Humans
• Indicators and Reagents
• Iodine Radioisotopes
• Isotope Labeling
• Mice
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics, pharmacology)
• Tin (chemistry)
• Tissue Distribution
• Tumor Cells, Cultured