Radiolabeled 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU) and 2'-fluoro-5-methyldeoxyuracil-beta -D-arabinofuranoside (FMAU) as tumor-imaging agents in mice

The purpose of the present study was to evaluate, in conjunction with the National Cancer Institute, the feasibility of using two thymidine analogs, 2'-fluorodeoxyuracil-beta-D-arabinofuranoside (FAU, NSC-678515) and 2'-fluoro-5-methyldeoxyuracil-beta-D-arabinofuranoside (FMAU, NSC-678516), as 18-fluorine-labeled positron emission tomography (PET) imaging agents. The in vivo distribution and DNA incorporation of [2-(14)C]FAU, [2-(14)C]FMAU, and [2-(14)C]thymidine (as a control) were studied in SCID mice bearing human xenografts of T-cell leukemia CCRF-CEM. Levels of drug-associated radioactivity in blood, tumor and normal tissues including liver, kidneys, heart, lungs, spleen, brain, and skeletal muscle were determined. At 1 h after dosing, radioactivity from all three compounds was distributed in a generally nonspecific manner, except that spleen and tumor tissue had relatively high concentrations of radioactivity from [(14)C]thymidine. At 4 h after dosing, the concentrations of radioactivity from [(14)C]thymidine and [(14)C]FMAU were relatively high in spleen and tumor tissue, and that from [(14)C]FAU was highest in tumor tissue. The tumor/skeletal muscle concentration ratios were 2.25+/-0.69 and 3.07+/-0.42 for [(14)C]FAU and [(14)C]FMAU, respectively. At 24 h after dosing, only spleen and tumor tissues contained appreciable amounts of radioactivity from either compound. In tumor tissue, the levels of radioactivity from [(14)C]FMAU were two- to threefold greater than those from [(14)C]thymidine or [(14)C]FAU. Examination of purified genomic DNA from tumor, liver, kidneys, brain, and skeletal muscle showed that, at 24 h after dosing, only DNA from tumor tissue contained appreciable concentrations of radioactivity. Radioactivity from [(14)C]FMAU in tumor DNA was 45% greater than that from [(14)C]thymidine and about threefold greater than that from [(14)C]FAU. The extent of accumulation of [(14)C]FMAU in tumor tissue and incorporation into tumor DNA indicate that [(18)F]FMAU could be useful as a functional PET tumor-imaging agent.