PMID: 9187117Jun 1, 1997Paper

Studies on the metabolism of the novel antitumor agent [N-methyl-11C]N-[2-(dimethylamino)ethyl]acridine-4-carboxamide in rats and humans prior to phase I clinical trials

Cancer Research
S OsmanP M Price

Abstract

This study reports on the biodistribution and metabolism of the 11C-labeled novel antitumor agent N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA) (also known as NSC 601316) in rats (plasma and tissues) and humans (plasma). Information on plasma metabolites was uniquely obtained in humans prior to Phase I clinical trial following i.v. injection of [11C]DACA at tracer dose. DACA was labeled in the N-methyl position using no-carrier-added [11C]iodomethane. Rapid high-performance liquid chromatography methods were developed for metabolite analysis of [11C]DACA. The metabolism of [11C]DACA was investigated in patients by plasma sampling. The biodistribution and metabolism of [11C]DACA was investigated in rats by plasma sampling, sacrifice experiments with tissue analyses, and imaging using positron emission tomography scanning. Analysis of human plasma demonstrated rapid and extensive metabolism of [11C]DACA. The levels of [11C]DACA changed from 77 +/- 8% (SD) at 5 min to 25 +/- 5% at 45 min postinjection. Seven radioactive metabolites were observed in human plasma, and one was identified as [11C]DACA-N-oxide. Rapid clearance of 11C radioactivity from rat blood, plasma, and major organs was observed. The half-life of 11C rad...Continue Reading

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