Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;75(5):660–665. doi: 10.1038/bjc.1997.118

Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.

H Yanagië 1, T Tomita 1, H Kobayashi 1, Y Fujii 1, Y Nonaka 1, Y Saegusa 1, K Hasumi 1, M Eriguchi 1, T Kobayashi 1, K Ono 1
PMCID: PMC2063329  PMID: 9043021

Abstract

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.

Full text

PDF
660

Images in this article

662Figure 2
on p.662

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bangham A. D., Standish M. M., Watkins J. C. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol. 1965 Aug;13(1):238–252. doi: 10.1016/s0022-2836(65)80093-6. [DOI] [PubMed] [Google Scholar]
  2. Barbet J., Machy P., Leserman L. D. Monoclonal antibody covalently coupled to liposomes: specific targeting to cells. J Supramol Struct Cell Biochem. 1981;16(3):243–258. doi: 10.1002/jsscb.1981.380160305. [DOI] [PubMed] [Google Scholar]
  3. Chen W. H., Horoszewicz J. S., Leong S. S., Shimano T., Penetrante R., Sanders W. H., Berjian R., Douglass H. O., Martin E. W., Chu T. M. Human pancreatic adenocarcinoma: in vitro and in vivo morphology of a new tumor line established from ascites. In Vitro. 1982 Jan;18(1):24–34. doi: 10.1007/BF02796382. [DOI] [PubMed] [Google Scholar]
  4. Coderre J. A., Glass J. D., Fairchild R. G., Micca P. L., Fand I., Joel D. D. Selective delivery of boron by the melanin precursor analogue p-boronophenylalanine to tumors other than melanoma. Cancer Res. 1990 Jan 1;50(1):138–141. [PubMed] [Google Scholar]
  5. Coderre J., Rubin P., Freedman A., Hansen J., Wooding T. S., Jr, Joel D., Gash D. Selective ablation of rat brain tumors by boron neutron capture therapy. Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1067–1077. doi: 10.1016/0360-3016(94)90480-4. [DOI] [PubMed] [Google Scholar]
  6. Dorn R. V., 3rd Boron neutron capture therapy (BNCT): a radiation oncology perspective. Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1189–1201. doi: 10.1016/0360-3016(94)90494-4. [DOI] [PubMed] [Google Scholar]
  7. GOLD P., FREEDMAN S. O. DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES. J Exp Med. 1965 Mar 1;121:439–462. doi: 10.1084/jem.121.3.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gabizon A., Papahadjopoulos D. Liposome formulations with prolonged circulation time in blood and enhanced uptake by tumors. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6949–6953. doi: 10.1073/pnas.85.18.6949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hashimoto Y., Sugawara M., Masuko T., Hojo H. Antitumor effect of actinomycin D entrapped in liposomes bearing subunits of tumor-specific monoclonal immunoglobulin M antibody. Cancer Res. 1983 Nov;43(11):5328–5334. [PubMed] [Google Scholar]
  10. Hasuike Y., Okamura J., Furukawa J., Naoi M., Takata N., Maruyama H., Kinuta M., Yayoi E., Oi H., Okamoto S. Efficacy of combination treatment--(TAE with adriamycin and ethanol)--for hepatocellular carcinoma. Cancer Chemother Pharmacol. 1992;31 (Suppl):S30–S34. doi: 10.1007/BF00687101. [DOI] [PubMed] [Google Scholar]
  11. Hatanaka H., Nakagawa Y. Clinical results of long-surviving brain tumor patients who underwent boron neutron capture therapy. Int J Radiat Oncol Biol Phys. 1994 Mar 30;28(5):1061–1066. doi: 10.1016/0360-3016(94)90479-0. [DOI] [PubMed] [Google Scholar]
  12. Hill J. S., Kahl S. B., Kaye A. H., Stylli S. S., Koo M. S., Gonzales M. F., Vardaxis N. J., Johnson C. I. Selective tumor uptake of a boronated porphyrin in an animal model of cerebral glioma. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1785–1789. doi: 10.1073/pnas.89.5.1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hughes B. J., Kennel S., Lee R., Huang L. Monoclonal antibody targeting of liposomes to mouse lung in vivo. Cancer Res. 1989 Nov 15;49(22):6214–6220. [PubMed] [Google Scholar]
  14. Joel D. D., Fairchild R. G., Laissue J. A., Saraf S. K., Kalef-Ezra J. A., Slatkin D. N. Boron neutron capture therapy of intracerebral rat gliosarcomas. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9808–9812. doi: 10.1073/pnas.87.24.9808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Joel D., Slatkin D., Fairchild R., Micca P., Nawrocky M. Pharmacokinetics and tissue distribution of the sulfhydryl boranes (monomer and dimer) in glioma-bearing rats. Strahlenther Onkol. 1989 Feb-Mar;165(2-3):167–170. [PubMed] [Google Scholar]
  16. Kato T., Nemoto R., Mori H., Takahashi M., Tamakawa Y., Harada M. Arterial chemoembolization with microencapsulated anticancer drug. An approach to selective cancer chemotherapy with sustained effects. JAMA. 1981 Mar 20;245(11):1123–1127. [PubMed] [Google Scholar]
  17. Konno H., Suzuki H., Tadakuma T., Kumai K., Yasuda T., Kubota T., Ohta S., Nagaike K., Hosokawa S., Ishibiki K. Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein monoclonal antibody. Cancer Res. 1987 Aug 15;47(16):4471–4477. [PubMed] [Google Scholar]
  18. Kruger P. G. Some Biological Effects of Nuclear Disintegration Products on Neoplastic Tissue. Proc Natl Acad Sci U S A. 1940 Mar 15;26(3):181–192. doi: 10.1073/pnas.26.3.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leserman L. D., Machy P., Barbet J. Cell-specific drug transfer from liposomes bearing monoclonal antibodies. Nature. 1981 Sep 17;293(5829):226–228. doi: 10.1038/293226a0. [DOI] [PubMed] [Google Scholar]
  20. Mishima Y., Honda C., Ichihashi M., Obara H., Hiratsuka J., Fukuda H., Karashima H., Kobayashi T., Kanda K., Yoshino K. Treatment of malignant melanoma by single thermal neutron capture therapy with melanoma-seeking 10B-compound. Lancet. 1989 Aug 12;2(8659):388–389. doi: 10.1016/s0140-6736(89)90567-9. [DOI] [PubMed] [Google Scholar]
  21. Singh M., Ghose T., Faulkner G., Kralovec J., Mezei M. Targeting of methotrexate-containing liposomes with a monoclonal antibody against human renal cancer. Cancer Res. 1989 Jul 15;49(14):3976–3984. [PubMed] [Google Scholar]
  22. Yanagië H., Tomita T., Kobayashi H., Fujii Y., Takahashi T., Hasumi K., Nariuchi H., Sekiguchi M. Application of boronated anti-CEA immunoliposome to tumour cell growth inhibition in in vitro boron neutron capture therapy model. Br J Cancer. 1991 Apr;63(4):522–526. doi: 10.1038/bjc.1991.124. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES