High dose of h-R3, an anti-epidermal growth factor receptor monoclonal antibody labeled with¹⁸⁸rhenium following intravenous injection into rats

Radioimmunotherapy (RAIT) is a promising new therapeutic modality for the treatment of a variety of malignancies. Humanized monoclonal antibody (MAb) h-R3 is a product, developed at the Center of Molecular Immunology in Havana, Cuba, that was labeled with rhenium 188 (¹⁸⁸Re) (Center of Molecular Immunology in Havana, Cuba). It can be used in the treatment of neoplasia of transformed cerebral cells that overexpress epidermal growth factor receptor (EGF-R). The acute local and systemic toxicity effects of single intravenous dose of ¹⁸⁸Re labeled or unlabeled MAb h-R3 in 100 Sprague-Dawley rats were studied. The rats were distributed into 5 groups of 20 animals (10 male, 10 female) from a mean dose of 14.20 mCi/m² on 20 μg/100 μL/animal to a mean dose of 41.86 mCi/m² on 60 μg/300 μL/animal. Standard endpoints were collected at various times after administration (ie, days 0, 14, 28, 42, 56, and 70). Endpoints included clinical observations, an abbreviated neurological assessment, body weight, hematology and clinical chemistry parameters, and, at the study termination, necropsy examination, organ weight, and histological evaluations. RAIT did not show toxic effects in the bone marrow or in peripheral blood, only an increase of alkaline phosphatase and a decrease of liver weight when compared with the control group. It was concluded that the proposed phase I clinical trial can be planned under the hypothesis of locoregional administration of ¹⁸⁸Re-h-R3 with intensive medical management.This phase I trial can be used to enhance antitumor effects with minimum toxicity to normal tissue in patients who have grade III/IV astrocytomas who were treated previously with conventional therapies.