Effect of mitomycin‐C on the bioavailability of the radiopharmaceutical ^99mtechnetium–phytic acid in mice: a model to evaluate the toxicological effect of a chemical drug

Abstract

The many desirable characteristics of technetium-99m ((99m)Tc) have stimulated the development of labelling techniques for different molecular and cellular structures. It is generally accepted that a variety of factors can alter the biodistribution of radiopharmaceuticals and one such factor is drug therapy. Because patients on chemotherapeutic treatment receive a radiopharmaceutical in a nuclear medicine procedure, we have studied in Balb/c mice the effect of mitomycin-C on the biodistribution of the radiopharmaceutical (99m)Tc-phytic acid ((99m)Tc-PHY) used in hepatic scintigraphy. Mitomycin-C is an antineoplastic agent obtained from Streptomyces caesptosus and is used on the treatment of disseminated adenocarcinoma of the stomach or pancreas. Three doses of mitomycin-C were administered via the ocular plexus into Balb/c mice. One hour after the last dose, (99m)Tc-PHY was administered and the animals were sacrificed. The organs were isolated, the radioactivity was determined in a well counter and the percentages of radioactivity in the organs were calculated. The results have shown that the percentage radioactivity has been increased in stomach, spleen, lung, thyroid and bone, decreased in pancreas and thymus and not altered in ovary, uterus, kidney, heart, liver and brain. The changes in the distribution of (99m)Tc-PHY may be the result of metabolic processes and/or therapeutic actions produced by the administration of mitomycin-C.

Aqueous extract of the medicinal plant Mentha crispa alters the biodistribution of the radiopharmaceutical sodium pertechnetate in Wistar rats

“…Drug and radiation therapies as well as surgical interventions can also affect the biodistribution of radiobiocomplexes (Hladik et al, 1987;Gomes et al, 2002;Hesslewood and Leung, 1994). The interaction of drugs with radiobiocomplexes has also been studied, with both positive and negative results (Owunwanne et al, 1995).…”

“…Passos et al (2000; have also demonstrated that dietary conditions can interfere with the biodistribution of radiobiocomplex. Several authors have also reported that, due to their pharmacological properties, some chemical compounds can alter the biodistribution of various radiobiocomplexes (Brito et al, 1998;Diré et al, 2003;Gomes et al, 2002;Diré et al, 2001;Grigoleit and Grigoleit, 2005;Hesslewood and Leung, 1994;Aguiar et al, 2002;Gomes et al, 2001;Mattos et al, 1999;Mattos et al, 2001).…”

Abnormal Biologic Distribution Related to Normal Saline Among99mTc-Dimercaptosuccinic Acid Scans

“…Besides disease status, recent medication history was assessed for all patients to evaluate for possible interference and impact on the bioavailability of the radiopharmaceutical at abnormal sites and, therefore, on image quality. Gomes et al (12) and Bernardo et al (7) found evidence that the biodistribution of radiopharmaceuticals may be altered by patient medications. Medications such as ammonium chloride and sodium bicarbonate can reduce renal uptake and increase liver uptake (10).…”

Drug interaction with radiopharmaceuticals: a review

“…Vincristine is a chemotherapeutic drug used in several protocols in oncology and (i) in an animal model, this drug has increased significantly the uptake of the radiobiocomplex 99m Tc-DTPA (diethylenetriaminepentaacetic acid) by the thymus, ovary, uterus, spleen, kidneys, heart, stomach, lungs, liver and bone (Britto et al, 1998), (ii) it modified the bioavailability of the 99m Tc-phytate in Balb/c mice (Mattos et al, 1999a), (iii) it decreased the uptake of 99m Tc-MDP (methylenediphosphonic acid) by the uterus, ovary, spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, liver, pancreas, stomach, heart, brain and bone isolated from animals (Mattos et al, 1999b), (iv) it decreased the uptake of 99m Tc-PYP (sodium pyrophosphate) by the spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, lung, liver, pancreas, stomach, heart and brain, and it increased the uptake by the bone and thyroid in the treated animals (Mattos et al, 1999b), (v) it decreased the uptake of the 99m Tc-GHA (glucoheptonic acid) by the uterus, ovary, spleen, thymus, lymph nodes (inguinal and mesentheric), kidney and heart isolated from animals (Mattos et al, 2001), and (vi) it increased the blood pool of the radioactivity of Ga-67 citrate (Hladik III et al, 1987). In experiments with mice, mitomycin-C (i) increased the uptake of 99m Tc-MDP in thymus, ovary, uterus, heart, stomach, pancreas, kidneys, spleen and lungs (Gomes et al, 1998), (ii) altered the uptake of radiobiocomplexes used for renal evaluations (Gomes et al, 2001), (iii) modified the bioavailability of 99m Tc-PYP (Gomes et al, 2002b) and (iv) interfered in the bioavailability of the 99m Tc-phytic acid (Gomes et al, 2002c) Buchsbaum et al, 1992 have reported PET studies of drug interaction with brain regional glucose metabolism. Kumakura et al (2004) have used the PET with parametric mapping to measure the effect of levodopa on the net clearance of ( 18 F-fluor-fluorodopa to brain (K, ml/g/min).…”