Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.
Immunoliposomes were prepared by conjugating anti-carcinoembryonic antigen (CEA) monoclonal antibody with liposomes containing [10B]compound. These immunoliposomes were shown to bind selectively to human pancreatic carcinoma cells (AsPC-1) bearing CEA on their surface. The cytotoxic effects of locally injected [10B]compound, multilamellar liposomes containing [10B]compound or [10B]immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with [10B]solution, 10B-containing liposomes or [10B]immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Injection of [10B]immunoliposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation.
Yanagië
H
H
Department of Surgery, Institute of Medical Science, University of Tokyo, Minata-ku, Japan.
Tomita
T
T
Kobayashi
H
H
Fujii
Y
Y
Nonaka
Y
Y
Saegusa
Y
Y
Hasumi
K
K
Eriguchi
M
M
Kobayashi
T
T
Ono
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001895:Boron / Q000008:administration & dosage / Q000627:therapeutic use; D001896:Boron Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D002272:Carcinoembryonic Antigen / Q000276:immunology; D002455:Cell Division / Q000528:radiation effects; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000627:therapeutic use; D015552:Injections, Intralesional; D007554:Isotopes; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D012996:Solutions; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D001896:Boron Compounds; D002272:Carcinoembryonic Antigen; D000922:Immunotoxins; D007554:Isotopes; D008081:Liposomes; D012996:Solutions; D001895:Boron