Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered intracerebrally in rats

B. Gonzalez, A. Casaco, P. Alvarez, M. Leon, M. Arteaga, A. Leon, E. Santana, A. Bada, R. Figueredo, R. Hernandez, N. Iznaga-Escobar, F. Gonzailez, R. Perez

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

11 Citas (Scopus)


Brain tumors are often incurable despite current aggressive treatment modalities. Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can maximize the radioisotope and Mab concentration to tumor sites while reducing systemic toxicity. h-R3 is a humanized antiepidermal growth factor receptor Mab that successfully targets the epidermal growth factor receptor, which is overexpressed in glioblastomas. We studied the acute local and systemic toxicity effects of intraventricular 188Re-h-R3 in rats. Forty rats were distributed into four groups with five animals of each sex in each group. A single 5-μI dose (2.5 μI into the left and 2.5 μl into the right lateral ventricles) of neutral solution containing 50 μgofh-R3 labeled with 49.5 ± 1.7,284 ± 13.7 or 579 ± 23.7 μCi of188Re were stereotactically administered to each animal. Control animals received vehicle alone. Each animal was observed twice daily for detection of toxicity signs. Body weights were recorded on days 0,7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out after completion of the study. All animals, but one, remained clinically stable. Toxicities included local radionecrosis, discrete increase in ALAT and creatinine blood values at higher dose level. We concluded that a single intraventricular administration of relatively large doses of188Re-h-R3 is tolerable and causes minimal local and systemic toxicity effects in rats. Nevertheless, further studies are necessary to discard learning and behavioral problems.

Idioma originalInglés
Páginas (desde-hasta)684-692
Número de páginas9
PublicaciónHuman and Experimental Toxicology
EstadoPublicada - 2000
Publicado de forma externa


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