Neutron-capture therapy of human cancer: in vitro results on the preparation of boron-labeled antibodies to carcinoembryonic antigen.

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Abstract
Two samples of 2-phenyl-1,2-dicarba-closo-[1-3H]dodecaborane(12) were prepared by treating 1-lithio-2-phenyl-1,2-dicarba-closo-dodecarborane(12)with 3H2O (0.1 and 5.0 Ci/ml, respectively). These tritiated phenylcarborane samples were subsequently converted to corresponding samples of p-[1,2-dicarba-closo-[1-3H]dodecarboran(12)-2-yl]benzenediazonium ion ([3H]DBD) suitable for azo-coupling reactions. Reaction of the 2 tritiated diazonium ion samples with 2-napthol resulted in the formation of an azo dye (.epsilon. = 1.98 .times. 104 M-1 cm-1 at 485 nm). Experiments relating absorbance to 3H activity proved the 2 [3H]DBD sources to have 3.81 .times. 1011 and 2.45 .times. 1013 cpm of 3H/mol of tritiated carborane substitutent. Purified antibodies to carcinoembryonic antigen were coupled to the [3H]DBD, and after extensive dialysis, the average number of carborane moieties per antibody molecule was determined by measuring the 3H activity associated with a known protein concentration. Further examination of these tritiated carborane-labeled antibodies by affinity chromatography proved that B labeling did not destroy their immunoreactivity. Correlations of azo-coupling conditions (reactant ratios, pH) with immunoreactivity and antibody protein recovery are presented. [The potential use of B-containing compounds in cancer therapy is based on the nuclear property to 10B to absorb thermal neutrons. The disintegration products are charged particles that have a range in tissue of < 10 .mu.m, which is comparable to the diameter of an erythrocyte. Thus, the radiation dose from these particles would be confined to a single cell or its immediate neighbors. B conjugated to antitumor antibodies might be an effective means of targeting the neutron-capture therapy to cancer tissue.].