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

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 thera peutic drugs. This model is based on the capability of natural products to alter the biodistribution of radiopharmaceuticals labelled with technetium- 99m (Tc-99m). The acceptance of Tc-99m-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 th e biodistribution or the pharmacokinetics of radiopharmaceuticals can be mo dified by some drugs, by pathological states, by irradiation and by surgica l procedures. A lack of knowledge of such factors can induce a misvisualiza tion of the scintigraphic images, leading to a misdiagnosis. Vincristine is a natural product that has been employed in various chemotherapeutic proto cols in oncology. We have studied the effect of vincristine on the distribu tion of [Tc-99m]methylenediphosphonic acid ([Tc-99m]MDP) in female mice. Af ter the last dose of vincristine, [Tc-99m]MDP was injected, the animals wer e sacrificed and the percentage of radioactivity (%ATI) was determined in t he isolated organs. The %ATI was significantly decreased in the uterus, ova ry, spleen, thymus, lymph nodes (inguinal and mesentheric), kidney, liver, pancreas, stomach, heart, brain and bone of the animals treated with the na tural product. Several biological effects have been reported in patients tr eated with vincristine. These effects could justify the alterations in the uptake of the radiopharmaceutical in specific organs. Moreover, these resul ts have shown that it is possible to employ this model to evaluate the toxi city of drugs. Copyright (C) 1999 John Wiley & Sons, Ltd.