In vitro and preclinical testing of Bi-213-labeled antimelanoma monoclonal antibody 9.2.27

NUCL 81

Syed M Abbas Rizvi, Yong Li, Chand Raja, and Barry J. Allen. Center for Experimental Radiation Oncology (CERO), St. George Hospital, Gray Street, Kogarah, NSW 2217, Sydney, Australia
Antimelanoma antibody 9.2.27 was labeled with Bi-213 - an alpha emitter with 46-minute half-life. Labeling was done using two different chelators namely cyclic dianhydride of DTPA (Cy-DTPA) and CHX-A" - DTPA. Stability of the labeled product was compared (by serum stability and DTPA challenge tests) for two chelators and was found to be similar. In vivo dose tolerance was tested up to 12 mCi / kg. Maximum tolerated dose (MTD) was found to be ~10mCi/kg. Tumours at various stages of growth (2, 4, 8, 16 and 26-days post inoculation) were given local intra-lesional Bi-213 - labeled-9.2.27 injections. At 2-days post-inoculation, complete tumour inhibition was observed whereas progressive response (inhibition or delay) was obtained with later time points. Systemic injections showed a significant delay in tumour growth compared to controls. These encouraging results are the basis of an ongoing phase-I dose escalation trial of intra-lesional targeted alpha therapy in patients with advanced melanoma.