A TARGETING MODEL OF BORON NEUTRON-CAPTURE THERAPY TO HEPATOMA-CELLS IN-VIVO WITH A BORONATED ANTI-(ALPHA-FETOPROTEIN) MONOCLONAL-ANTIBODY

We described previously that B-10 atoms delivered by monoclonal antibo dy (mAb) exerted a cytotoxic effect on AH66 cells in a dose-dependent manner upon thermal neutron irradiation in vitro. In the present study , the delivering capacity of boronated anti-(alpha-fetoprotein) (AFP) mAb to carry B-10 atoms to AFP-producing tumor xenografts in nude mice was determined. Boronated mAb was prepared by conjugating 50 mM B-10 compound to an anti-AFP mAb (2 mg/ml) using N-succinimidyl-3-) (2-pyri dyldithio) propionate. The number of B-10 atoms conjugated directly to the mAb was estimated to be 459/antibody by prompt gamma-ray spectrom etry. Boron concentrations in tumor tissue obtained 12, 24, 72, and 12 0 h after injection of 3.0 mg B-10-conjugated anti-AFP mAb were 11.10/-3.12 (SD, n=6), 29.30+/-5.11, 33.02+/-11.8, and 12.91+/-5.62 ppm res pectively. For control B-10-conjugated anti-dinitrophenol (DNP) mAb, t he values were 9.59+/-0.99, 10.37+/-2.86, 10.00+/-2.95, and 8.83+/-4.7 1 ppm respectively. The concentrations in blood were less than 0.40+/- 0.10 ppm with anti-AFP mAb and less than 0.51+/-0.15 ppm with anti-DNP mAb at each sampling time (12, 24, 72, and 120 h). The number of B-10 atoms delivered to the tumor cells was calculated to be 0.62x10(9), 1 .63x10(9), 1.84x10(9) and 0.72x10(9) at each sampling time after injec tion of B-10-anti-AFP mAb. The amount of B-10 atoms necessary for effe ctive boron neutron-capture therapy was estimated to be 10(9)/tumor ce ll. We were able to carry 1.84x10(9) B-10 atoms to AH66 tumor cells by using B-10-anti-AFP mAb. The accumulation reached its peak 72 h after injection. These data indicated that the B-10-conjugated antitumor mA b could deliver a sufficient amount of B-10 atoms to the tumor cells t o induce cytotoxic effects 72 h after injection upon thermal neutron i rradiation.