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Human & Experimental Toxicology
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Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered intracerebrally in rats

B Gonzalez

Centro Nacional para la Produccion de Animales de Laboratorio, Havana, Cuba

A Casaco

Centro de Inmunologia Molecular, Havana, Cuba; Division of Immunopharmacology, Center of Molecular Immunology, 216 esq. a 15 Siboney, Playa, A. Postal 16040, Havana 11600, Cuba

P Alvarez

Centro Internacional de Restauracion Neurologica, Havana, Cuba

M Leon

Centro de Isotopos, Havana, Cuba

M Arteaga

A Leon

E Santana

A Bada

Centro Nacional para la Produccion de Animales de Laboratorio, Havana, Cuba

R Figueredo

Centro de Inmunologia Molecular, Havana, Cuba

R Hernandez

Centro de Isotopos, Havana, Cuba

N Iznaga-Escobar

Centro de Inmunologia Molecular, Havana, Cuba

F Gonzailez

Centro Nacional para la Produccion de Animales de Laboratorio, Havana, Cuba

R Perez

Centro de Inmunologia Molecular, Havana, Cuba

Brain tumors are often incurable despite current aggressive treatmentmodalities. Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can maximize the radioisotope and Mab concentration to tumor sites while reducing systemic toxicity. h 3 is a humanized antiepidemal 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 3 in rats. Forty rats were distributed into four groups with five animals of each sex in each group. A single 5-II dose (2.5 pl into the left and 2.5 MI into the right lateral ventricles) of neutral solution containing50pgofh-R31abeledwith49.5 t 1.7,284±13.7or 579±23.7 p Ci of 188Re were stereotactically administered to each animal. Control animals received vehicle alone. Each animal was observed twice daily for detection of toxicity signs. Bodyweights 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 of 188Re 3 is tolerable and causes minimal local and systemic toxicity effects in rats. Nevetheless, further studies are necessary to discard learning and behavioral problems.

Key Words: radiotoxicity • monoclonal antibody • cancer treatment • rhenium • h-R3

Human & Experimental Toxicology, Vol. 19, No. 12, 684-692 (2000)
DOI: 10.1191/096032700675323269
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