RESUMO
BACKGROUND: Estramustine phosphate (EMP) and estramustine binding protein antibody (EMBP-AB) accumulate in the mouse prostate. The distribution of radioiodinated EMBP-AB in tumor mice was investigated to assess its therapeutic potential against prostate cancer. MATERIALS AND METHODS: Mice with DU-145 prostate cancer xenografts received 243 microCi of I-125-labeled EMBP-AB (RI-EMBP-AB). The concentration of activity in different organs was measured 4 h after the injection. RESULTS: The blood contained 0.45% of the injected dose per gram, the prostate 2.4%, the testes 0.95% and the tumor 0.65%. Radioactivity in these organs decreased more rapidly than in other organs. The doses of radiation absorbed by the prostate and the tumor, assuming a 1 mCi injected dose, were 1.81 and 0.92 cGy, respectively. CONCLUSION: Most other organs would receive relatively high doses of radioactivity, were I-125 to be used in therapeutic doses. Therefore, RI-EMBP-AB is not beneficial in radionuclide treatment as compared to possible EMP applications.
Assuntos
Imunotoxinas/farmacocinética , Radioisótopos do Iodo/farmacocinética , Neoplasias da Próstata/metabolismo , Proteínas Secretadas pela Próstata/imunologia , Animais , Anticorpos/imunologia , Anticorpos/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta à Radiação , Humanos , Imunotoxinas/farmacologia , Radioisótopos do Iodo/administração & dosagem , Radioisótopos do Iodo/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias da Próstata/diagnóstico por imagem , Cintilografia , Distribuição Tecidual , Transplante HeterólogoRESUMO
BACKGROUND: Estramustine is an anti-mitotic cytostatic drug that also enhances the effect of radiotherapy. The mechanism of radiosensitization is not thoroughly known. Since both radiotherapy and estramustine induce apoptosis in prostate cancer cells, we conducted an experiment to show whether radiosensitization is mediated by apoptosis. MATERIALS AND METHODS: DU-145 human prostate cancer cells were xenografted to nude mice and treated with estramustine for 2 weeks and external radiation for 3 to 6 days (18 to 36 Gy). Tumor regression was measured mechanically and the rate of apoptosis defined by the amount of low molecular weight DNA fragmentation. Follow-up time was 1 to 18 days. RESULTS: The tumor size regressed in the group of mice receiving both radiotherapy and estramustine. Four weeks after the treatment, apoptosis was accentuated in the tumors treated with estramustine or radiation but not with their combination. CONCLUSION: Estramustine potentiates radiotherapy, but not by enhancing radiation-induced apoptosis.