RESUMO
The radiolanthanides (149)Pm, (166)Ho, and (177)Lu possess a range of half-lives and alpha(-) beta(-) energies for targeted radiotherapy of cancer. (149)Pm-, (166)Ho-, and (177)Lu-DOTA-biotin were pretargeted to LS174T colorectal tumors in nude mice with CC49 scFvSA antibody-streptavidin fusion protein. Tumor uptakes of (149)Pm (22.9% ID/g), (166)Ho (30.2% ID/g), and (177)Lu (35.4% ID/g) peaked at 1-4 h. Rapid blood disappearance was accompanied by urinary excretion of 59-66% ID within 1 h. Biodistributions of these agents show promise for pretargeted radioimmunotherapy of cancer.
Assuntos
Anticorpos Antineoplásicos/metabolismo , Biotina/análogos & derivados , Biotina/farmacocinética , Neoplasias do Colo/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Compostos Organometálicos/farmacocinética , Radioimunoterapia/métodos , Radioisótopos/farmacocinética , Estreptavidina/farmacocinética , Animais , Anticorpos Antineoplásicos/administração & dosagem , Biotina/administração & dosagem , Linhagem Celular Tumoral , Neoplasias do Colo/radioterapia , Hólmio/administração & dosagem , Hólmio/farmacocinética , Humanos , Fragmentos de Imunoglobulinas/administração & dosagem , Fragmentos de Imunoglobulinas/metabolismo , Injeções Intravenosas , Lutécio/administração & dosagem , Lutécio/farmacocinética , Taxa de Depuração Metabólica , Camundongos , Camundongos Nus , Especificidade de Órgãos , Compostos Organometálicos/administração & dosagem , Promécio/administração & dosagem , Promécio/farmacocinética , Radioisótopos/administração & dosagem , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/farmacocinética , Estreptavidina/administração & dosagem , Distribuição TecidualRESUMO
The nonstochastic radiobiological effects of combined alpha and beta irradiation of the lungs of rats from inhaled radionuclides were studied. Both respiratory functional morbidity at 18 mo and mortality from radiation pneumonitis within 18 mo after exposure were examined for rats exposed to the beta-emitter 147Pm, the alpha-emitter 238Pu, or both combined. The results were used to validate hazard-function models that were developed (1) for respiratory functional morbidity at 18 mo and (2) for lethality from radiation pneumonitis within 18 mo. Both models were found to adequately predict the experimental observations for chronic alpha plus beta irradiation of the lung. Based on this 18-mo study, a relative biological effectiveness of approximately seven was obtained for 238Pu alpha radiation compared to 147Pm beta radiation for both respiratory functional morbidity and lethality from radiation pneumonitis. However, the relative biological effectiveness for the alpha radiation is likely to increase with longer follow-up.