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 regimens and some toxic effects of this substance have been reported. As it has been reported that the toxicological effect of a drug can alter the biodistribution of radiopharmaceuticals and because patients on chemotherapeutic treatment can be submitted to a nuclear medicine procedure, we investigated whether MMC could affect the uptake of various technetium-99m (99mTc) radiopharmaceuticals 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-diethylenetriaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA) or 99mTc-glucoheptonic acid (99mTc-GHA), with activity of 7.4 MBq, were also administered in the treated group and in the control group (N=15). After another 0.5 h, the animals were sacrificed. The organs were isolated, the 99mTc radiopharmaceutical uptake in the organs quantified in a well counter 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 bone; (ii) with 99mTc-DMSA, the %ATI decreased in all the organs except for the brain; and (iii) with 99mTc-GHA, the %ATI increased in the liver and decreased in the stomach, thymus, heart and thyroid. The effects of this chemotherapeutic drug on the biodistribution of these radiopharmaceuticals were statistically significant (Wilcoxon test, p<0.05) and could be explained by the metabolization and/or therapeutic action of MMC. Studies with other radiopharmaceuticals are in progress.
Gomes
M L
ML
Departamento de Biofisica e Biometria, Universidade do Estado do Rio de Janeiro, RJ, Brazil.
de Mattos
D M
DM
de Souza Freitas
R
R
Bezerra
R J
RJ
Bernardo-Filho
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D007668:Kidney / Q000000981:diagnostic imaging* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016685:Mitomycin / Q000633:toxicity*; D009928:Organ Specificity / Q000187:drug effects; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D017556:Technetium Compounds / Q000493:pharmacokinetics*; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics; D016284:Technetium Tc 99m Pentetate / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
D019275:Radiopharmaceuticals; D017556:Technetium Compounds; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D016685:Mitomycin; D016284:Technetium Tc 99m Pentetate