In vitro killing of melanoma by liposome-delivered intracellular irradiation.
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 alpha-irradiation. The radionuclide 212Pb (lead), with its 10.6-hour half-life and alpha-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 liposomes 212Pb/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/mumol 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.
Department of Surgery, University of California, Davis.
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Pikul
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Parks
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Schneider
D000512:Alpha Particles; D000818:Animals; D001729:Bismuth / Q000627:therapeutic use; D001918:Brachytherapy / Q000379:methods; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D006207:Half-Life; D007856:Lead Radioisotopes / Q000627:therapeutic use; D008081:Liposomes / Q000008:administration & dosage*; D008546:Melanoma, Experimental / Q000532:radiotherapy*; D051379:Mice; D014677:Pharmaceutical Vehicles; D011868:Radioisotopes / Q000627:therapeutic use; D013997:Time Factors; D014407:Tumor Cells, Cultured
D007856:Lead Radioisotopes; D008081:Liposomes; D014677:Pharmaceutical Vehicles; D011868:Radioisotopes; D001729:Bismuth