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

Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ, 20551-030 Brazil; Universidade Federal do Rio de Janeiro, Hospital Clementino Fraga Filho, Av. Brigadeiro Trompowsky s/n, Cidade Universitaria, Rio de Janeiro, RJ, Brazil

D Mm de mattos

Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ, 20551-030 Brazil

R de souza freitas

Universidade Federal do Rio de Janeiro, Hospital Clementino Fraga Filho, Av. Brigadeiro Trompowsky s/n, Cidade Universitaria, Rio de Janeiro, RJ, Brazil

R Jac Bezerral

Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ, 20551-030 Brazil; Universidade Federal do Rio de Janeiro, Hospital Clementino Fraga Filho, Av. Brigadeiro Trompowsky s/n, Cidade Universitaria, Rio de Janeiro, RJ, Brazil

M Bernardo-Filho

Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ, 20551-030 Brazil; Universidade Federal do Rio de Janeiro, Hospital Clementino Fraga Filho, Av. Brigadeiro Trompowsky s/n, Cidade Universitaria, Rio de Janeiro, RJ, Brazil; Centro de Pesquisa Basica, Instituto Nacional de Cancer, Praga Cruz Vermelha, 23, Rio de Janeiro, RJ, 20230-130 Brazil

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-diethylene-triaminepentaacetic 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%YATI 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.

Key Words: mitomycin C • 99mTc radiopharmaceuticals • drug interaction • toxicolog

Human & Experimental Toxicology, Vol. 20, No. 4, 193-197 (2001)
DOI: 10.1191/096032701678766840


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