Validation of Bi-213-alpha radioimmunotherapy for multiple myeloma

The efficacy of radioimmunotherapy (RIT) with beta emitters has been clinic ally demonstrated in the treatment of refractory forms of lymphoma. alpha-e mitting radionuclides with a short half-life are also good potential candid ates for RIT directed at tumor targets easily accessible to radioimmunoconj ugate molecules and small enough to benefit from the short range of alpha p articles (<100 mu m). The purpose of this study was to demonstrate the feas ibility of ex vivo purging of multiple myeloma-invaded bone marrow. Tumor c ells were targeted by a specific monoclonal antibody (B-B4) coupled to Bi-2 13 by a chelating agent (pentaacetic triamine diethylene p-aminobenzyl acid ). The efficacy of alpha-RIT was assessed in vitro by analysis of thymidine incorporation, cell mortality, apoptosis of myeloma cells, and the study o f nonspecific irradiation of hematopoietic cell lines not recognized by B-B 4-pentaacetic triamine diethylene p-aminobenzyl acid immunoconjugate. High dose-dependent cell mortality of myeloma cells was found with radiolabeled B-B4, and this mortality was total at 30 kBq/10(5) cells. Cells were found in apoptotic state at rates of up to 40% for a dose of 7.4 kBq/10(5) cells. Nonspecific mortality was low compared with specific mortality (up to 1%).