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 10B atoms delivered by monoclonal antibody (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 10B atoms to AFP-producing tumor xenografts in nude mice was determined. Boronated mAb was prepared by conjugating 50 mM 10B compound to an anti-AFP mAb (2 mg/ml) using N-succinimidyl-3-) (2-pyridyldithio) propionate. The number of 10B atoms conjugated directly to the mAb was estimated to be 459/antibody by prompt gamma-ray spectrometry. Boron concentrations in tumor tissue obtained 12, 24, 72, and 120 h after injection of 3.0 mg 10B-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 respectively. For control 10B-conjugated anti-dinitrophenol (DNP) mAb, the values were 9.59 +/- 0.99, 10.37 +/- 2.86, 10.00 +/- 2.95, and 8.83 +/- 4.71 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 10B atoms delivered to the tumor cells was calculated to be 0.62 x 10(9), 1.63 x 10(9), 1.84 x 10(9) and 0.72 x 10(9) at each sampling time after injection of 10B-anti-AFP mAb. The amount of 10B atoms necessary for effective boron neutron-capture therapy was estimated to be 10(9)/tumor cell. We were able to carry 1.84 x 10(9) 10B atoms to AH66 tumor cells by using 10B-anti-AFP mAb. The accumulation reached its peak 72 h after injection. These data indicated that the 10B-conjugated antitumor mAb could deliver a sufficient amount of 10B atoms to the tumor cells to induce cytotoxic effects 72 h after injection upon thermal neutron irradiation.
Yanagië
H
H
Department of Clinical Oncology, University of Tokyo, Japan.
Fujii
Y
Y
Sekiguchi
M
M
Nariuchi
H
H
Kobayashi
T
T
Kanda
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use; D001895:Boron / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016754:Boron Neutron Capture Therapy; D004140:Dinitrophenols / Q000276:immunology / Q000627:therapeutic use; D004797:Enzyme-Linked Immunosorbent Assay; D000922:Immunotoxins / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D007554:Isotopes; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism* / Q000532:radiotherapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008954:Models, Biological; D051381:Rats; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D000509:alpha-Fetoproteins / Q000096:biosynthesis / Q000276:immunology* / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D004140:Dinitrophenols; D000922:Immunotoxins; D007554:Isotopes; D000509:alpha-Fetoproteins; D001895:Boron