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.
28 de setembro, 87, Rio de Janeiro, RJ, Brasil, 2055 1-030. bemardo@uerj.br key words: Sechiunz edule, blood cells, technetium-99m, biodistribution, morphometry.
summary.The evidence that drugs can affect radiolabeling or biodistribution of red cells in setting of nuclear medicine clinic has with to light only recently. A therapeutic drug can modify the nature/amount of technetium-99m ehTc) radiopharmaceutical bound to blood elements and this may result in a unexpected behavior of the radiopharmaceutical. Chayotte is used as food or as medication in popular medicine. We evaluated the influence of chayotte extract (macerated) on the biodistribution of sodium pertechnetate (gh"Tc04Na) in rats lVistar and on the morphometry of the red blood cells. The animals were treated during 60 days with chayotte extract. After that, Tc04Na was injected and the animals were sacrificed. The organs were isolated and counted in a well counter. The percentages of radioactivity (%AT0 in the organs were calculated. The analysis of the results have shown that there was a decrease of %AT1 in the lungs, stomach and thyroid. Histological preparations were carried out with the blood samples from the animals treated with chayotte during 15 days. Optical microscopy of red blood cells (RBC) showed important morphological alterations due to the treatment of the animals during 15 days with chayotte extract. The results could be justified by the metabolization of chayotte vegetable that could be capable to induce the generation of active metabolites with lesive properties in specific biological systems. The effects of the chayotte extract could also be due to a direct action of the compounds present in extract.
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.
Immunosuppressive therapy of solid organ transplantation has become more potent, effective and selective since the results of earlier use of prednisone and azathioprine post renal transplantation. Calcineurin inhibitors and mycophenolate mofetil have been important additions to the effective antirejection armamentarium. Today, cyclosporin, tacrolimus, azathioprine, mycophenolate and prednisone are all effective immunosuppressive agents and are the cornerstone of immunosuppressive protocols used posttransplant. However, the use of these agents is hindered by a 20% rate of rejection, lack of selectivity and a high rate of major adverse drug reactions which ultimately lead to a decrease in patient and graft survival. A number of clinical trials are underway to compare efficacy, safety and tolerability of different combination protocols to improve patient and allograft survival and decrease adverse drug reactions. Clinical knowledge of the pharmacology, pharmacokinetics, pharmacodynamics, adverse drug reactions and therapeutic drug monitoring of antirejection agents is essential for designing an effective immunosuppressive protocol for individual solid organ transplant recipients. The clinical application of pharmacotherapeutic principles into the clinical practice will improve both long-term patient and allograft survival while minimizing systemic toxicity of immunosuppressive drugs.
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.
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