Preliminary study for application of anti-alpha-fetoprotein monoclonal antibody to boron-neutron capture therapy.
Boron-neutron capture therapy (BNCT) has been applied clinically, especially in brain-neuro surgery. We intended to expand the application of BNCT for the treatment of abdominal cancers and tried to determine whether MoAb (monoclonal antibody) against AFP (alpha-fetoprotein) could be useful tool to deliver boron-10 (10B) to AH-66 hepatoma cells for BNCT. Firstly, MoAb was boronated by mixing with 10B-compound (Cs2 10B12H11SH) by using N-succinimidyl 3(2-pyridyldithio)propionate (SPDP). Numbers of 10B atoms bound to an antibody molecule were in proportion to the dose of 10B-compound added, and maximum number of 10B atoms conjugated to an antibody molecule was approximately 1240. Secondly, using this boronated MoAb, 10B was delivered to AH-66 cells, and 11 X 10(9) 10B atoms were estimated to be on and/or in an AH-66 cell. After the irradiation with thermal neutron, boronated AH-66 cells showed decreasing uptake of [3H]TdR in proportion to the number of 10B atoms bound to and/or incorporated into the tumor cells. These results indicate that 10B atoms delivered by MoAb exert cytotoxic effect on AH-66 cells in a dose dependent manner by thermal neutron irradiation.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001895:Boron / Q000627:therapeutic use*; D002460:Cell Line; D004261:DNA Replication; D007554:Isotopes; D008114:Liver Neoplasms, Experimental / Q000628:therapy*; D009502:Neutrons; D051381:Rats; D011919:Rats, Inbred Strains; D000509:alpha-Fetoproteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007554:Isotopes; D000509:alpha-Fetoproteins; D001895:Boron