Pikul S S, Parks N J, Schneider P D
Department of Surgery, University of California, Davis.
Arch Surg. 1987 Dec;122(12):1417-20. doi: 10.1001/archsurg.1987.01400240063011.
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.
为了更好地理解和优化α粒子杀伤肿瘤的机制，开发了一种以脂质体作为载体的体外模型，用于研究通过细胞内α辐射对黑色素瘤的杀伤作用。放射性核素212Pb（铅）及其半衰期为10.6小时且发射α粒子的子体212Bi（铋）被包裹在脂质体中，以实现对培养的黑色素瘤细胞的细胞内辐射。在剂量反应实验中，将与葡聚糖70结合的脂质体212Pb/212Bi与B16F10小鼠黑色素瘤细胞一起孵育。将孵育后在网格化培养皿上培养的黑色素瘤细胞的铺板效率和生长情况与24小时和48小时后的对照组进行比较。在48小时时，脂质/细胞的放射性活度水平为1.6 dpm/μmol，细胞杀伤率超过85%，这相当于每个细胞细胞内递送五到七个α粒子。在体内通过再循环或在灌注回路中，这些α剂量是可以超过的，并且可能会有更有效的细胞毒性作用。
