RESUMO
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.
Assuntos
Rim/diagnóstico por imagem , Rim/metabolismo , Mitomicina/toxicidade , Compostos Radiofarmacêuticos/farmacocinética , Compostos de Tecnécio/farmacocinética , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Especificidade de Órgãos/efeitos dos fármacos , Cintilografia , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Pentetato de Tecnécio Tc 99m/farmacocinética , Fatores de Tempo , Distribuição Tecidual/efeitos dos fármacosRESUMO
The effect of malnutrition on the biodistribution of radiopharmaceuticals is not known. We studied the biodistribution of 99Tcm-labelled sodium pertechnetate (Na99TcmO4) in two rat models of malnutrition. Three groups of 2-month-old rats were separated according to their diets: (1) control diet, 23% protein (C); (2) protein-restricted, receiving 8% protein (PR), both ad libitum; and (3) energy-restricted, receiving 60% of control diet (ER). After 21 days of the diet, 99Tcm was injected and the animals were killed after 30 min. The organs were isolated, their weight determined and the absolute per cent (%ID) and the per cent per gram injected dose (%ID x g(-1)) calculated. The %ID and %ID x g(-1) had a similar pattern, increasing in stomach and brain and decreasing in the thyroid, but did not change significantly in kidney, lung, liver, bone or testis in PR rats, except in the heart where the increase was only observed in the %ID x g(-1). In the ER group the %ID x g(-1) was decreased in the bone only, and did not change in the other organs. It is suggested that when using Na99TcmO4 scintigraphy in malnourished patients, the different patterns of distribution must be kept in mind.
Assuntos
Desnutrição Proteico-Calórica/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Pertecnetato Tc 99m de Sódio/farmacocinética , Animais , Dieta , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Proteínas Alimentares/farmacologia , Masculino , Ratos , Ratos Wistar , Distribuição TecidualRESUMO
Drug therapy can alter the biodistribution of radiopharmaceuticals. We studied the effect of mitomycin-C, a drug used in oncology, on the biodistribution in mice of 99Tcm-methylene diphosphonic acid (99Tcm-MDP). Three doses of mitomycin-C were administered. After the last dose, 99Tcm-MDP was injected and the animals were killed. The organs were isolated, their weight determined and the percent per gram injected dose (%ID/g) calculated. The %ID/g had increased in the pancreas, ovary, stomach, uterus, kidneys, spleen, thymus, heart, liver and lungs, but did not change significantly in thyroid, bone or brain. As a change in 99Tcm-MDP uptake by bone is not observed, a modification to bone scintigraphy is not required. As mitomycin-C treatment altered 99Tcm-MDP uptake in some organs, any hot spots should be evaluated carefully to avoid a misdiagnosis.