Study of the toxicological effect of mitomycin C in mice: alteration on the biodistribution of radiopharmaceuticals used for renal evaluations

Mitomycin C (MMC) has been used as a component of many chemotherapeutic reg imens and some toxic effects of this substance have been reported. As it ha s been reported that the toxicological effect of a drug can alter the biodi stribution of radiopharmaceuticals and because patients on chemotherapeutic treatment can be submitted to a nuclear medicine procedure, we investigate d whether MMC could affect the uptake of Various technetium-99m (99mTc) rad iopharmaceuticals used for renal evaluations. The purpose of this study was to suggest a model to evaluate the toxic effect of substances in specific organs. Three doses of MMC (0.45 mg) were administered to mice (N=15). One hour after the last dose, 99mTc radiopharmaceuticals, 99mTc-diethylenetriam inepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA ) or 99mTc-glucoheptonic acid (99mTc-GHA), with activity of 7.4 MBq, were a lso administered in the treated group and in the control group (N=15). Afte r another 0.5 h, the animals were sacrificed. The organs were isolated, the 99mTc radiopharmaceutical uptake in the organs quantified in a well counte r and the percentages of radioactivity (%ATI) calculated. The results have shown that: (i) with 99mTc-DTPA, the %ATI increased in the pancreas, ovary, uterus, stomach, kidney, spleen, thymus, heart, lung, liver, thyroid and b one; (ii) with 99mTc-DMSA, the %ATI decreased in ah the organs except for t he brain; and (iii) with 99mTc-GHA, the %ATI increased in the liver and dec reased in the stomach, thymus, heart and thyroid. The effects of this chemo therapeutic drug on the biodistribution of these radiopharmaceuticals were statistically significant (Wilcoxon test, p <0.05) and could be explained b y the metabolization and/or therapeutic action of MMC. Studies with other r adiopharmaceuticals are in progress.