Tumor uptake of radiolabelled pyrimidine bases and pyrimidine nucleosides in animal models

The tritium-labelled acyclonucleoside, N-[2-(hydroxyethoxy)methyl]-5-[3H]methyluracil (3H-3), was synthesized for evaluation as a tumor diagnostic agent. 5-[3H]-methyluracil, 3H-1, was converted to the 2,4-bis-trimethylsilyl intermediate which was coupled with 2-acetoxyethoxymethyl bromide to afford 1-[(2-acetoxyethoxy)methyl-5-[3H]methyluracil (3H-2). Treatment of 3H-2 with sodium methoxide in methanol afforded 3H-3 (specific activity 188 MBq mmol-1). The tissue distribution of 3H-3 was examined in male BDF1 mice bearing Lewis Lung (LL) carcinomas. Long bone exhibited the highest tumor: tissue ratios. The kidney contained the highest radioactivity level relative to the tumor. This suggested a major urinary route of excretion. The major radioactive blood component (89.21%) was found to have a biological half-life of 0.19 min. The title compound is unsuitable for use as a diagnostic agent for LL carcinoma because of low tumor uptake and rapid urinary elimination of injected radioactivity from the body. (author)