Thermal neutron capture therapy of malignant melanoma using 10B-monoclonal antibodies: in vitro and in vivo analysis.
We have established methods of targeting a sufficient number of 10B atoms on human melanoma cells to allow selective destruction of the cancer cells by thermal neutron irradiation. Thermal neutron capture therapy (NCT)1-3 requires the presence of at least 10(9) 10B atoms on each target cell for specific killing of that cell without injuring normal tissues. In order to accumulate an adequate number of 10B atoms on target cells, we first created an effective compound containing 12 atoms of 10B per molecule (10B12-chlorpromazine) and 10B-dopa analogue (10B1-paraboronophenylalanine). In the present study, about three molecules of our newly synthesized 10B12-compound were conjugated to an avidin molecule. The resulting 10B38.5-avidin compound can be specifically directed to human melanoma cells by biotinated monoclonal antibodies (MAbs) specific for the cells. We were able to accumulate 2.6 x 10(8) 10B atoms on a melanoma cell using this method. Cultured human melanoma cells treated with 10B-avidin-biotin-MAb (10B-AB-MAb) were selectively damaged by thermal neutron irradiation in vitro. This is the first study to indicate that thermal neutrons selectively damage target cells boronated by MAbs.
Komura
A
A
Department of Dermatology, School of Medicine, Kobe University, Japan.
Nakagawa
T
T
Ichihashi
M
M
Mishima
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D001360:Avidin; D001895:Boron / Q000008:administration & dosage* / Q000528:radiation effects; D001896:Boron Compounds / Q000008:administration & dosage; D002746:Chlorpromazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004337:Drug Carriers; D005720:Gamma Rays / Q000627:therapeutic use; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000532:radiotherapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009502:Neutrons / Q000627:therapeutic use*; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000528:radiation effects
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D001896:Boron Compounds; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D001360:Avidin; D010649:Phenylalanine; D001895:Boron; D002746:Chlorpromazine; C033685:4-boronophenylalanine