Effect of 67Cu-2IT-BAT-Lym-1 Therapy on BCL-2 Gene and Protein Expression in a Lymphoma Mouse Model

Radioimmunotherapy using monoclonal antibodies against tumor-associated antigens has been particularly promising in the treatment of radiosensitive malignancies such as lymphoma. 67 Cu has excellent physical and biochemical properties for radioimmunotherapy. 67 Cu-2IT-BAT-Lym-1 has been used in preclinical and clinical trials, where an exceptionally long residence time of 67 Cu on tumor was observed. BCL-2 , a proto-oncogene that promotes cell survival by blocking apoptotic cell death, is overexpressed in most B-cell lymphomas including Raji human Burkitt9s lymphoma cells. In this study, therapeutic efficacy and BCL-2 gene and protein expression levels were examined in Raji xenografts in mice after 67 Cu-2IT-BAT-Lym-1 radioimmunotherapy. 67 Cu-2IT-BAT-Lym-1 therapy induced a response rate (complete and partial responses) of ∼50%. BCL-2 gene expression was decreased 3 h after radioimmunotherapy, followed by a decrease in Bcl-2 protein by 24 h. Decreases in BCL-2 gene and protein expression preceding observations of 67 Cu-2IT-BAT-Lym-1 therapeutic effect suggest that down-regulation of BCL-2 leaves cells more likely to be killed by low dose-rate radiation from radioimmunotherapy.