RESUMO
PURPOSE: To evaluate the effect of hydroalcoholic extract of A. muricata on biodistribution of two radiopharmaceuticals: sodium phytate and dimercaptosuccinic acid (DMSA), both labeled with 99mtechnetium. METHODS: Twenty four Wistar rats were divided into two treated groups and two controls groups. The controls received water and the treated received 25mg/kg/day of A. muricata by gavage for ten days. One hour after the last dose, the first treated group received 99mTc-DMSA and the second sodium 99mTc-phytate (0.66MBq each group), both via orbital plexus. Controls followed the same protocol. Forty min later, all groups were sacrificed and the blood, kidney and bladder were isolated from the first treated group and the blood, spleen and liver isolated from the second treated group. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated using a gamma counter. RESULTS: The statistical analysis showed that there was a statistically significant decrease (p<0.05) in the uptake of %ATI/g in bladder (0.11±0.01and1.60±0.08), kidney (3.52±0.51and11.84±1.57) and blood (0.15±0.01and 0.54±0.05) between the treated group and control group, respectively. CONCLUSION: The A. muricata hydroalcoholic extract negatively influenced the uptake of 99mTc-DMSA in bladder, kidney and blood of rats.
Assuntos
Annona/química , Ácido Fítico/farmacocinética , Extratos Vegetais/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Animais , Interações Medicamentosas , Rim/efeitos dos fármacos , Masculino , Ácido Fítico/sangue , Extratos Vegetais/sangue , Compostos Radiofarmacêuticos/sangue , Ratos Wistar , Baço/efeitos dos fármacos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/sangue , Distribuição Tecidual , Bexiga Urinária/efeitos dos fármacosRESUMO
INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ((51)Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using (51)Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ((51)Cr-EDTA) and (99m)Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6+/-21.8 ml/kg/1.73 m(2) in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1+/-28.7 ml/kg/1.73m(2) in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6+/-14.8 ml/ kg/1.73m(2), p=0.001) and an insignificant change in the group without RAS (to 62.2+/-23.6 ml/kg/1.73m(2), p=0.68). Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA) did not show significant differences in differential renal function from baseline to post-captopril images in either group. CONCLUSIONS: Captopril induced a decrease in the GFR that could be quantitatively measured with (51)Cr-EDTA. The reduction is more pronounced in hypertensive patients with RAS.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Captopril/uso terapêutico , Quelantes , Ácido Edético , Taxa de Filtração Glomerular/efeitos da radiação , Hipertensão Renovascular/diagnóstico por imagem , Obstrução da Artéria Renal/fisiopatologia , Quelantes/farmacocinética , Ácido Edético/farmacocinética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Cintilografia , Obstrução da Artéria Renal/metabolismo , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinéticaRESUMO
Research for radiodiagnostic agents should considerate biological critical parameters which will give own contribution on the absorbed dose. The dimercaptosuccinic acid (DMSA) labeled with (99m)Tc(V) is a radiopharmaceutical which has well established role in medullar thyroid carcinoma and has been proposed in evaluation of bone metastasis. This work studied the biokinetics and dosimetry of (99m)Tc(V)-DMSA by animal model. The (99m)Tc(V)-DMSA was prepared from a (III)DMSA kit alkalized. Mice (n=5) received (99m)Tc(V)DMSA i.v., they were sacrificed (30 min, 1h, 5h and 12h), the organs excised and the activities measured by a gamma counter. The results were evaluated based on %activity/g and the absorbed dose was estimated (MIRDOSE 3.0 program) by extrapolation of data from animal to human scale. The results showed the majority of organs reached the top uptake at 30 min, the greatest kidney uptake was (4.81 +/- 1.38)% activity/g, while the bone presented its highest uptake at 1h (5.49+/- 0.47)% activity/g, after 1h all the organs had activity exponential decrease. The biokinetic profile of (99m)Tc(V)-DMSA was well established, allowing quantifying of residence time, and the radiation dose estimates were made for this agent. About the absorbed dose, the preliminary results showed higher value to bone, being the soft tissue dose relatively low.
Assuntos
Radiometria/métodos , Ácido Dimercaptossuccínico Tecnécio Tc 99m/química , Absorção , Animais , Camundongos , Metástase Neoplásica , Doses de Radiação , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/farmacocinética , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Fatores de Tempo , Distribuição TecidualRESUMO
OBJECTIVE: The aim of this study was to compare the renal function measured with either 99mTc-DTPA or 99mTc-EC dynamic scintigraphies with that measured using 99mTc-DMSA static scintigraphy. METHODS: the values of relative renal function measured in 111 renal dynamic scintigraphies performed either with 99mTc-DTPA (55 studies) or with 99mTc-EC (56 studies) were compared with the relative function measured using 99mTc-DMSA static scintigraphy performed within a 1-month period. The comparisons were performed using Wilcoxon signed rank test. The number of 99mTc-DTPA and 99mTc-EC studies that presented relative renal function different by more than 5% from that measured with 99mTc-DMSA, using chi square test were also compared. RESULTS: the relative renal function measured with 99mTc-EC is not statistically different from that measured with 99mTc-DMSA (p = 0.97). The relative renal function measured with 99mTc-DTPA was statistically different from that measured using 99mTc-DMSA, but with a borderline statistical significance (p = 0.05). The number of studies with relative renal function different by more than 5% from that measured with 99mTc-DMSA is higher for the 99mTc-DTPA scintigraphy (p = 0.04) than for 99mTc-EC. CONCLUSION: the relative renal function measured with 99mTc-EC dynamic scintigraphy is comparable with that measured with 99mTc-DMSA static scintigraphy, while the relative renal function measured with 99mTc-DTPA dynamic scintigraphy presents a significant statistical difference from that measured with 99mTc-DMSA static scintigraphy.
Assuntos
Compostos Radiofarmacêuticos , Obstrução da Artéria Renal/diagnóstico por imagem , Ácido Dimercaptossuccínico Tecnécio Tc 99m , Pentetato de Tecnécio Tc 99m , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Lactente , Recém-Nascido , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Pentetato de Tecnécio Tc 99m/farmacocinéticaRESUMO
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.
Assuntos
Modelos Biológicos , Tamanho do Órgão/efeitos dos fármacos , Compostos Radiofarmacêuticos/farmacocinética , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Pentetato de Tecnécio Tc 99m/farmacocinética , Vincristina/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Especificidade de Órgãos/efeitos dos fármacos , Testes de Toxicidade/métodosRESUMO
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-diethylenetriaminepentaacetic 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 %ATI 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.
Assuntos
Rim/diagnóstico por imagem , Rim/metabolismo , Mitomicina/toxicidade , Compostos Radiofarmacêuticos/farmacocinética , Compostos de Tecnécio/farmacocinética , Animais , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Especificidade de Órgãos/efeitos dos fármacos , Cintilografia , Ácido Dimercaptossuccínico Tecnécio Tc 99m/farmacocinética , Pentetato de Tecnécio Tc 99m/farmacocinética , Fatores de Tempo , Distribuição Tecidual/efeitos dos fármacosRESUMO
OBJECTIVE: Vincristine has been widely used in various chemotherapeutic protocols in oncology. The purpose of this study was to evaluate the effect of vincristine on the biodistribution of 99mTc-DMSA, 99mTc-GHA, and 99mTc-DTPA in Balb/c female mice. METHODS: Vincristine (0.03 mg, 0.3 mL) was injected into female isogenic Balb/c mice (n = 15), in 3 doses over an interval of 96 h. The 99mTc-DMSA, 99mTc-GHA, or 99mTc-DTPA (7.4 MBq) was administered after the last dose of vincristine. After 0.5 h the animals were killed rapidly. The organs (pancreas, thyroid, brain, thymus, ovary, uterus, spleen, kidney, heart, stomach, lung, liver, bone, and lymph nodes) were isolated and the radioactivity in each organ was counted in a NaI(Tl) well counter. The percentage of radioactivity (%) in each was calculated and compared with the control group. Statistical analysis was performed by Wilcoxon test (P < 0.05). RESULTS: The percentage of 99mTc-DMSA was increased in the lung, pancreas, heart, thyroid, brain, bone, and lymph nodes (inguinal and mesenteric). The percentage of 99mTc-GHA was decreased in the uterus, ovary, spleen, thymus, lymph nodes (inguinal and mesenteric), kidney, and heart. The percentage of 99mTc-DTPAwas increased in thymus, lymph nodes (inguinal and mesenteric), ovary, uterus, spleen, kidney, heart, stomach, lung, liver, and bone. CONCLUSION: The results could be explained by the metabolization, toxic effect, therapeutic, or immunosupressive action of the studied chemotherapeutic drug.