A model to evaluate the biological effect of natural products: vincristine action on the biodistribution of radiopharmaceuticals in BALB/c female mice

Abstract

Natural products have been widely used by human beings. However, sometimes the biological effects of these products are not fully known. We are trying to develop a model to evaluate the toxicity of compounds employed as therapeutic drugs. This model is based on the capability of natural products to alter the biodistribution of radiopharmaceuticals labelled with technetium-99m (99mTc). The acceptance of 99mTc-labelled radiopharmaceuticals is so rapid and its current use so diverse that it is not possible to study this radionuclide's behaviour in the body more deeply. There is evidence that the biodistribution or the pharmacokinetics of radiopharmaceuticals can be modified by some drugs, by pathological states, by irradiation and by surgical procedures. A lack of knowledge of such factors can induce a misvisualization of the scintigraphic images, leading to a misdiagnosis. Vincristine is a natural product that has been employed in various chemotherapeutic protocols in oncology. We have studied the effect of vincristine on the distribution of [99mTc]methylenediphosphonic acid ([99mTc]MDP) in female mice. After the last dose of vincristine, [99mTc]MDP was injected, the animals were sacrificed and the percentage of radioactivity (%ATI) was determined in the isolated organs. The %ATI was significantly decreased in the uterus, ovary, spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, liver, pancreas, stomach, heart, brain and bone of the animals treated with the natural product. Several biological effects have been reported in patients treated with vincristine. These effects could justify the alterations in the uptake of the radiopharmaceutical in specific organs. Moreover, these results have shown that it is possible to employ this model to evaluate the toxicity of drugs.