Comparative radiopharmacokinetics of 18F-5-fluorouracil administered i.v. to rats bearing a mammary tumor

Abstract

In an attempt to compare the efficacy of various 5-fluorouracil (5-FU) regimens, we studied the kinetics of ¹⁸F-labeled and unlabeled 5-FU in rats. ¹⁸F-5-FU was synthesized in our laboratory and was administered in tracer doses to Fischer rats bearing either the 13762 or the R3230 mammary adenocarcinoma, and to Sprague-Dawley rats bearing the Walker-256 carcinosarcoma, with or without pre-treatment with a therapeutic dose of unlabeled 5-FU. In addition, the non-radioactive 5-FU was administered to control rats of both strains. All animals were followed for 70 min either by measuring their ¹⁸F blood levels continuously using an extracorporeal blood-loop, or by determining their 5-FU blood levels at discrete time intervals. The biphasic kinetic profile was characterized by determining α and β rate constants and their corresponding half-lives. Differences in ¹⁸F elimination, as measured by the area under the curve during the elimination phase, were observed between the pre-treated 13762-bearing rats and the untreated group bearing the same tumor. as well as the pre-treated non-tumored controls and both W-256-bearing groups. Such differences could reveal changes in the ability of those rats to metabolize 5-FU, and hence correlate to the level of active metabolite(s) available to their tumor sites.