D. M. M. Mattos

Effect of an extract of cauliflower (leaf) on the labeling of blood elements with technetium-99m and on the survival of Escherichia coli AB1157 submitted to the treatment with stannous chloride

The labeling of red blood cells (RBC) with technetium-99m (99mTc) depends on a reducing agent and stannous chloride (SnCl(2)) and is widely utilized. This labeling may also be altered by drugs, and SnCl(2) reduces the survival of Escherichia coli cultures. Cauliflower (Brassica oleracea L. var. botrytis) is used in folk medicine and we evaluated its influence on (i) the labeling of blood elements with 99mTc, and (ii) on the survival of an E. coli strain. Blood was withdrawn from rats that drank the extract of cauliflower (15 days). Blood was incubated with SnCl(2) and with 99mTc, as sodium pertechnetate, centrifuged and plasma (P) and RBC were isolated. Samples of P and RBC were also precipitated, centrifuged and soluble and insoluble fractions isolated. E. coli culture was treated with SnCl(2) in the presence of cauliflower. The extract of cauliflower did not alter the fixation of 99mTc on blood fractions; however, it abolished the lethal effect of SnCl(2) on the E. coli culture. We suggest that the substances present in the extract of cauliflower probably, would have redox property with different mechanisms of action. The oxidant action of the substances of the extract would not be strong enough to oxidise the stannous ions altering the 99mTc-labeling. However, the referred substances could oxidise these ions sufficiently to protect the E. coli culture against the lethal effect of the stannous ion.

A model to evaluate the biological effect of natural products: vincristine action 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 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. Copyright

Model to evaluate the toxic effect of drugs : vincristine effect in the mass of organs and in the distribution of radiopharmaceuticals in mice

There are evidences that the biodistribution of radiopharmaceuticals can be modified by some drugs. As chemotherapeutic drugs present important toxic effects, we studied the vincristine effect in the mass of organs and are trying to develop a model to evaluate the action of chemotherapeutic drug using the biodistribution of radiopharmaceuticals. Vincristine was administered (n=15) into female Balb/c mice, the organs isolated and their mass determined. To study the vincristine effect in the biodistribution of technetium-99m-dimercaptosuccinic acid (99mTc-DMSA) or technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA), vincristine (0.03 mg) was administered in the animals (n=15) in three doses. 99mTc-DMSA or 99mTc-DTPA was injected 1h after the last dose. After 0.5h, the animals were sacrificed and the percentage of radioactivity (%ATI) and the percentage of radioactivity per gram of tissue (%ATI/g) in each organ were calculated. The results have shown that the mass decreased significantly (Wilcoxon test, P<0.05) in thymus, spleen, ovary, uterus, kidneys, pancreas. The %ATI to 99mTc-DMSA increased in lung, pancreas, heart, thyroid, brain, and bone, and the %ATI/g increased in uterus, ovary, spleen, thymus, kidney, lung, liver, pancreas, heart, thyroid, brain and bone. To 99mTc-DTPA, the %ATI increased in uterus, ovary, spleen, thymus, kidney, lung, liver, stomach, heart and bone, and the %ATI/g increased in uterus, ovary, spleen, thymus, kidney, lung, liver, stomach, heart and bone. The results were statistically significant (Wilcoxon test). The results can be explained by the metabolization, therapeutic, toxicological or immunosupressive action of the vincristine. This model, probably, should be used to evaluate the toxic effect of various drugs.

Study of the binding of99mtechnetium-radiopharmaceuticals on blood cells and plasma proteins: evaluation using precipitation with trichloroacetic acid

Nuclear medicine uses radioactive tracers called radiopharmaceuticals to study the bloodflow, metabolism and morphology of an organ. Sodium pertechnetate (99mTcO4Na) and many 99mTc products are the most frequently radiopharmaceuticals used in nuclear medicine. Secure determination of the binding of 99mTc-radiopharmaceuticals to plasma (P) and blood cell (BC) constituents can help to understand the biodistribution of radiopharmaceuticals. The reported evaluations about the binding of radiopharmaceuticals on blood elements have shown that the results can not be easily compared. We decided to determine the gold standard concentration of trichloroacetic acid (TCA) to study the binding of radiopharmaceuticals on blood proteins: 99mTc-stannous colloid (99mTc-Sn-Colloid), sodium pertechnetate (99mTcO4Na), methylenediphosphonic acid (99mTc-MDP) and diisopropyliminodiacetic acid (99mTc-DISIDA). Blood of Wistar rats, was incubated with the radiopharmaceuticals for 5 minutes at room temperature, centrifuged and plasma (P) and blood cells (BC) were isolated. Samples of P and BC were also precipitated with TCA concentrations (0.1, 0.5, 1.0, 5.0, 10.0 and 20.0%) and soluble (SF) and insoluble fractions (IF) were isolated and counted. The percent radioactivity (%ATI) in IF-P depends on TCA concentration. It varies from 23.7 to 75.7 (99mTc-Sn-Colloid), from 7.8 to 26.2 (99mTcO4Na), from 10.7 to 40.4 (99mTc-MDP), from 52.2 to 60.7 (99mTc-DISIDA). The gold concentrations of TCA to study the binding of the studied radiopharmaceuticals in blood elements were revealed from the obtained results: (i) for 99mTc-Sn-Colloid in the IF-P is shown that there is no differences in the percent of radioactivity when TCA concentrations of 20 to 5.0 percent were used for precipitation, (ii) for 99mTcO4Na, 0.5 percent TCA concentration is the best one to precipitate the bound radiopharmaceutical, (iii) for 99mTc-MDP the % ATI increased from 10.7 to 40.4 with TCA concentrations from 0.1 to 5.0 percent and decreased from 40.4 to 23.8 with TCA concentrations from 5.0 to 20.0 percent and (iv) for 99mTc-DISIDA, the values of bound radioactivity are not dependent on TCA concentration in the range of 0.1 to 5.0 percent. The %ATI in IF-BC depends on TCA concentration and it varied for 99mTcO4Na (28.8 to 77.9), for 99mTc-MDP (68.8 to 83.7), for 99mTc-DISIDA (69.3 to 92.8). However, for 99mTc-Sn-Colloid, the %ATI in the insoluble fraction seems to be independent of the TCA concentration. The analysis of these results will contribute to understand the involved mechanisms on the binding of radiopharmaceuticals on blood elements. Copyright