Chemoradiotherapy of Cancer: Boronated Antibodies and Boron-Containing Derivatives of Chlorpromazine and Porphyrins for Neutron Capture Therapy

摘要

Monoclonal antibodies directed against tumor associated antigens have been proposed for the selective targeting of malignant cells with boron-10. The purpose of this task was to optimize the conditions for linking a large number of boron atoms to antibody molecules without compromising the antibody's immunoreactivity. There has been a need to develop methodologies for the separation, purification and characterization of such immunoconjugates prior to their evaluation both under in vitro and in vivo conditions. During this project period, much of the effort has concentrated on MoAb 17-1A which is directed against human colorectal cancer. The observed selective concentration of chlorpromazine in melanotic tissue and its high localization in murine melanoma indicated that boronated analogues of chlorpromazine potentially could be used to deliver sufficient concentration of boron-10 for BNCT of melanomas. Five boronated promazines have been synthesized and fully characterized. The phthalocyanines, as with various porphyrins, have been shown to be incorporated to a significant extent in malignant tumors. As a consequence, we have undertaken the synthesis of boron-containing phthalocyanines. Initial efforts have concentrated on the sulfonation of copper phthalocyanine by chlorosulfonation followed by reaction with aminocarboranes such as p-amino-phenylcarborane. We have achieved an average of 18 boron atoms per phthalocyanine molecule. 1 fig. (ERA citation 13:031198)