Studies Related to Antibody-Mediated Boron Delivery for BNCT

Of the many methods of selective boron delivery to tumor presently under consideration, the use of boron-labeled tumor-targeted monoclonal antibodies (Mabs) and their immunoreactive fragments appears to offer the most general, but complex, approach.1–4 Assuming that tumor cells generally carry 106 characteristic antigenic sites of any one type and that there are approximately 109 cells per gram of tumor, one calculates that about 600 10B atoms must be attach d to each individual Mab molecule (if all antigenic sites are complexed) for each 10 ppm of 10B supplied to tumor. Rather than randomly attack IgG Mab molecules with a large number of relatively small boron-containing conjugation reagent molecules we have chosen to assemble a series of discrete, precisely synthesized oligomeric reagents (“trailers”) each of which contains a fixed number of B-atoms up to approximately 200. These oligomeric reagents would carry a radioactive or fluorescent group for analytical purposes attached to a terminal-NH2 group of their chain and the remaining -COOH terminus would be free for conjugation with the lysine e-NH2 groups of Mab protein. Two types of oligomeric trailer reagents are envisioned; hydrophilic peptides and polyamides. Both types of reagent are prepared using the solid-supported synthesis methods of Merrifield.5 Figure 1 illustrates two typical a-amino acids which contain the hydrophobic closo-1,2-C2B10H11-cage and the corresponding hydrophilic [nido-7,8-C2B9H11-]-cage fragment. These amino acids are designated closo-CB and nido-CB,respectively, throughout this paper.