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In Vitro Killing of Melanoma by Liposome-Delivered Intracellular Irradiation

In Vitro Killing of Melanoma by Liposome-Delivered Intracellular Irradiation Abstract • To better understand and optimize the mechanism of alpha particle killing of tumors, an in vitro model utilizing liposomes as carrier vehicles was developed to study the killing of melanoma via intracellular α-irradiation. The radionuclide 212Pb (lead), with its 10.6-hour half-life and α-emitting daughter 212Bi (bismuth), was encapsulated in liposomes to achieve the intracellular irradiation of melanoma cells in culture. In dose-response experiments, B16F10 mouse melanoma cells were incubated with liposomes212Pb/212Bi bound to dextran 70. Plating efficiency and growth of the melanoma cells cultured on gridded petri dishes after incubation were compared with controls at 24 and 48 hours. Greater than 85% cell killing occurred by 48 hours, with administered radioactivity levels of 1.6 dpm/μmol of lipid/cell, which corresponds to intracellular delivery of five to seven alpha particles per cell. These alpha doses can be exceeded in vivo with recirculation or in a perfusion circuit, and more efficient cytotoxic action may be possible. (Arch Surg 1987;122:1417-1420) References 1. Schlom J: Basic principles and applications of monoclonal antibodies in the management of carcinomas . Cancer Res 1986;46:3225-3238. 2. Barendsen GW, Beusker TLJ, Vergroesen AJ, et al: Effects of different ionizing radiations on human cells in tissue culture: II. Biological experiments . Radiat Res 1960;13:841-849.Crossref 3. Kozak RW, Atcher RW, Gansow OA, et al: Bismuth-212–labeled anti-Tac monoclonal antibody: Alpha-particle—emitting radionuclides as modalities for radioimmunotherapy . Proc Natl Acad Sci USA 1986;83:474-478.Crossref 4. Vaughan ATM, Bateman WJ, Brown G, et al: The specific inhibition of cellular clonogenic proliferation using At-211 labelled lectins and antibodies . Int J Nucl Med Biol 1982;9:167-171.Crossref 5. Potter DA, Gorschboth CM, Schneider PD: Liposome uptake by melanoma: In vitro comparison with hepatocytes . J Surg Res 1984;39:157-163.Crossref 6. Hill AS, Schneider PD, Chelton KC, et al: Murine model for intracellular therapeutic radiation of melanoma . Surg Forum 1986;37:425-427. 7. Lloyd EL, Gemmell MA, Henning CB, et al: Cell survival following multiple-track alpha particle irradiation . Int J Radiat Biol 1979;35:23-31.Crossref 8. Munro TR: The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts . Radiat Res 1970;42:451-470.Crossref 9. Zidenberg-Cherr S, Parks NJ, Keen CL: Tissue and subcellular distribution of bismuth radiotracer in the rat: Considerations of cytotoxicity and microdosimetry for bismuth radiopharmaceuticals. Radiat Res, in press. 10. Mishra AC, Chelton KC, Parks NJ: Design and operation of a generator system for studies of reactions activated by nuclear transformation and synthesis of alpha-emitting radiopharmaceutical compounds. Read before the 192nd American Chemical Society Meeting, Anaheim, Calif, Sept 9, 1986. 11. Papahadjopoulos D, Szoka F: Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation . Proc Natl Acad Sci USA 1978;75:4194-4198.Crossref 12. Fidler IJ, Kripke ML: Metastasis resulting from preexisting variant cells within a malignant tumor . Science 1977;197:893-895.Crossref 13. Poste G: Drug-targeting in cancer therapy , in Gregoriadis G, Poste G, Senior J, et al (eds): Receptor-Mediated Targeting of Drugs . New York, Plenum Press, 1984, pp 427-474. 14. Pihl A, Godal A, Fodstad O: Abrin and ricin immunotoxins against melanoma: Toxicity related to binding, internalization, and processing . Br J Cancer 1985;52:652. 15. Rosenow MK, Zucchini GL, Bridwell PM, et al: Properties of liposomes containing Pb-212 . Int J Nucl Med Biol 1983;10:189-197.Crossref 16. Weinstein NJ, Yoshikami S, Henkert P, et al: Liposome-cell interactions: Transfer and intracellular release of a trapped fluorescent marker . Science 1977;195:489-492.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Surgery American Medical Association

In Vitro Killing of Melanoma by Liposome-Delivered Intracellular Irradiation

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Publisher
American Medical Association
Copyright
Copyright © 1987 American Medical Association. All Rights Reserved.
ISSN
0004-0010
eISSN
1538-3644
DOI
10.1001/archsurg.1987.01400240063011
Publisher site
See Article on Publisher Site

Abstract

Abstract • To better understand and optimize the mechanism of alpha particle killing of tumors, an in vitro model utilizing liposomes as carrier vehicles was developed to study the killing of melanoma via intracellular α-irradiation. The radionuclide 212Pb (lead), with its 10.6-hour half-life and α-emitting daughter 212Bi (bismuth), was encapsulated in liposomes to achieve the intracellular irradiation of melanoma cells in culture. In dose-response experiments, B16F10 mouse melanoma cells were incubated with liposomes212Pb/212Bi bound to dextran 70. Plating efficiency and growth of the melanoma cells cultured on gridded petri dishes after incubation were compared with controls at 24 and 48 hours. Greater than 85% cell killing occurred by 48 hours, with administered radioactivity levels of 1.6 dpm/μmol of lipid/cell, which corresponds to intracellular delivery of five to seven alpha particles per cell. These alpha doses can be exceeded in vivo with recirculation or in a perfusion circuit, and more efficient cytotoxic action may be possible. (Arch Surg 1987;122:1417-1420) References 1. Schlom J: Basic principles and applications of monoclonal antibodies in the management of carcinomas . Cancer Res 1986;46:3225-3238. 2. Barendsen GW, Beusker TLJ, Vergroesen AJ, et al: Effects of different ionizing radiations on human cells in tissue culture: II. Biological experiments . Radiat Res 1960;13:841-849.Crossref 3. Kozak RW, Atcher RW, Gansow OA, et al: Bismuth-212–labeled anti-Tac monoclonal antibody: Alpha-particle—emitting radionuclides as modalities for radioimmunotherapy . Proc Natl Acad Sci USA 1986;83:474-478.Crossref 4. Vaughan ATM, Bateman WJ, Brown G, et al: The specific inhibition of cellular clonogenic proliferation using At-211 labelled lectins and antibodies . Int J Nucl Med Biol 1982;9:167-171.Crossref 5. Potter DA, Gorschboth CM, Schneider PD: Liposome uptake by melanoma: In vitro comparison with hepatocytes . J Surg Res 1984;39:157-163.Crossref 6. Hill AS, Schneider PD, Chelton KC, et al: Murine model for intracellular therapeutic radiation of melanoma . Surg Forum 1986;37:425-427. 7. Lloyd EL, Gemmell MA, Henning CB, et al: Cell survival following multiple-track alpha particle irradiation . Int J Radiat Biol 1979;35:23-31.Crossref 8. Munro TR: The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts . Radiat Res 1970;42:451-470.Crossref 9. Zidenberg-Cherr S, Parks NJ, Keen CL: Tissue and subcellular distribution of bismuth radiotracer in the rat: Considerations of cytotoxicity and microdosimetry for bismuth radiopharmaceuticals. Radiat Res, in press. 10. Mishra AC, Chelton KC, Parks NJ: Design and operation of a generator system for studies of reactions activated by nuclear transformation and synthesis of alpha-emitting radiopharmaceutical compounds. Read before the 192nd American Chemical Society Meeting, Anaheim, Calif, Sept 9, 1986. 11. Papahadjopoulos D, Szoka F: Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation . Proc Natl Acad Sci USA 1978;75:4194-4198.Crossref 12. Fidler IJ, Kripke ML: Metastasis resulting from preexisting variant cells within a malignant tumor . Science 1977;197:893-895.Crossref 13. Poste G: Drug-targeting in cancer therapy , in Gregoriadis G, Poste G, Senior J, et al (eds): Receptor-Mediated Targeting of Drugs . New York, Plenum Press, 1984, pp 427-474. 14. Pihl A, Godal A, Fodstad O: Abrin and ricin immunotoxins against melanoma: Toxicity related to binding, internalization, and processing . Br J Cancer 1985;52:652. 15. Rosenow MK, Zucchini GL, Bridwell PM, et al: Properties of liposomes containing Pb-212 . Int J Nucl Med Biol 1983;10:189-197.Crossref 16. Weinstein NJ, Yoshikami S, Henkert P, et al: Liposome-cell interactions: Transfer and intracellular release of a trapped fluorescent marker . Science 1977;195:489-492.Crossref

Journal

Archives of SurgeryAmerican Medical Association

Published: Dec 1, 1987

References