Studies Related to Antibody-Mediated Boron Delivery for BNCT

Abstract

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 ε-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.