Vaidyanathan G, Zalutsky M R
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
Phys Med Biol. 1996 Oct;41(10):1915-31. doi: 10.1088/0031-9155/41/10/005.
Radionuclides such as 211At and 212Bi which decay by the emission of alpha-particles are attractive for certain applications of targeted radiotherapy. The tissue penetration of 212Bi and 211At alpha-particles is equivalent to only a few cell diameters, offering the possibility of combining cell-specific targeting with radiation of similar range. Unlike the beta-particles emitted by radionuclides such as 131I and 90Y, alpha-particles are radiation of high linear energy transfer and thus greater biological effectiveness. Several approaches have been explored for targeted radiotherapy with 212Bi- and 211At-labelled substances including colloids, monoclonal antibodies, metabolic precursors, receptor-avid ligands and other lower molecular weight molecules. An additional agent which exemplifies the promise of alpha-emitting radiopharmaceuticals is meta-[211At]astatobenzylguanidine. The toxicity of this compound under single-cell conditions, determined both by [3H]thymidine incorporation and by limiting dilution clonogenic assays, for human neuroblastoma cells is of the order of 1000 times higher than that of meta-[131I] iodobenzylguanidine. For meta-[211At] astatobenzylguanidine, the Do value was equivalent to only 6-7 211At atoms bound per cell. These results suggest that meta-[211At] astatobenzylguanidine might be valuable for the targeted radiotherapy of micrometastatic neuroblastomas.
诸如通过发射α粒子衰变的211At和212Bi等放射性核素在靶向放射治疗的某些应用中具有吸引力。212Bi和211At的α粒子在组织中的穿透深度仅相当于几个细胞直径，这为将细胞特异性靶向与类似射程的辐射相结合提供了可能性。与131I和90Y等放射性核素发射的β粒子不同，α粒子是高线性能量传递的辐射，因此具有更高的生物学效应。已经探索了几种用212Bi和211At标记的物质进行靶向放射治疗的方法，这些物质包括胶体、单克隆抗体、代谢前体、受体亲和配体和其他低分子量分子。一种体现发射α粒子的放射性药物前景的额外药物是间位-[211At]砹苄基胍。通过[3H]胸苷掺入法和极限稀释克隆形成试验测定，这种化合物在单细胞条件下对人神经母细胞瘤细胞的毒性比间位-[131I]碘苄基胍高约1000倍。对于间位-[211At]砹苄基胍，Do值仅相当于每个细胞结合6-7个211At原子。这些结果表明，间位-[211At]砹苄基胍可能对微转移性神经母细胞瘤的靶向放射治疗有价值。
