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

Abstract

<jats:p> 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&lt;0.05) and could be explained by the metabolization and/or therapeutic action of MMC. Studies with other radiopharmaceuticals are in progress. </jats:p>

Effect of a plant origin drug on the biodistribution of 99mTc-DTPA in Wistar albino rats

“…Some studies have suggested that radiolabeling of blood constituents with just 99m Tc could be performed to evaluate the biological effects of medicinal plant extracts (Moreno et al, 2004;Benarroz et al, 2008;Gomes et al, 2001;Abreu et al, 2006;Silva et al, 2006). Particularly Goncalves studied 99m Tc sodium pertechnetate and unpeeled Passiflora flavicarpa extract, labeling of blood components.…”

“…It may arise as a result of a variety of factors including the pharmacological action of the drug, physiochemical interactions between drugs and radiotracers, and competition for binding sites. It has already reported that the biodistribution of radiopharmaceuticals used in diagnostic imaging in nuclear medicine is also altered by including plant origin drugs (Hesslewood & Leung, 1994;Britto et al, 1998;Gomes et al, 2001;Mattos et al, 1999). It has been described that extracts of medicinal plants could interfere with the biodistribution of 99m Tc sodium pertechnetate particularly (Rebello et al, 2007;Rebello et al, 2008;Bernardo-Filho et al, 2005;Moreno et al, 2007;Jankovic & Djokic, 2005;Valenca et al, 2005).…”

Guidance for nuclear medicine staff on radiopharmaceuticals drug interaction

“…Iodide-sodium-131 Positive: reduce the uptake Dorr et al(1993) Octreotide Indium-pentetreotide-111 Positive: reduce the uptake Sampson (1993) Cyclosphosphamide; vincristine and cisplatin Gallium-67 Positive: alters the pharmacokinetics Khafagi et al(1989) Labetalol I-MIBG-131 Reduce uptake Gomes et al (2001) Mitomycin C 99m Tc radiopharmaceuticals, 99m Tc-diethylenetriaminepentaacetic acid (99mTc-DTPA), 99mTc-dimercaptosuccinic acid (99mTc-DMSA), 99mTc-glucioheptonic acid (99mTc-GHA) 99mTc-DTPA: Increased the uptake in pancreas, ovary, uterus, stomach, kidney, spleen, thymus, heart, lung, liver, thyroid and bone. 99mTc-DMSA: Decreased the uptake in all organs except brain 99mTc-GHA Increased the uptake in liver and decreased in stomach, thymus, heart and thyroid.…”

Radiopharmaceuticals drug interactions: a critical review

“…This would also decrease uptake of radioiodine into the thyroid gland (Sternthal et al 1980, Laurie et al 1992. Similarly, use of mitomycin C decreased the uptake of 99m Tc-GHA by the thyroid (Gomes et al 2001). …”

“…Labetalol, used for the treatment of pheocromacytoma, reduces the uptake of 131 Iodine-metaiodobenzylguanidine ( 131 Iodine-MIBG) in liver and spleen (Khafagi et al 1989). Gomes et al (2001) noted that mitomycin C increased the uptake of 99m Tc-DTPA by the spleen and liver and also increased the uptake of 99m Tc-GHA by the liver causing misdiagnosis and or a false positive result.…”