Targeted therapy using alpha emitters

Radionuclides such as At-211 and Bi-212 which decay by the emission of alpha-particles are attractive for certain applications of targeted radiotherapy. The tissue penetration of Bi-212 and At-211 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 B-particles emitted by radionuclides such as I-131 and Y-90, alpha-particles are radiation of high linear energy transfer and thus greater biological effectiveness. Several approaches have been explored for targeted radiotherapy with Bi-212 and At-211-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-[At-211]astatobenzylguanidine. The toxicity of this compound under single-cell conditions, determined both by [H-3]thymidine incorporation and by limiting dilution clonogenic assays, for human neuroblastoma cells is of the order of 1000 times higher than that of meta-[I-131]iodobenzylguanidine, For meta-[At-211]astatobenzylguanidine, the D-0 value was equivalent to only 6-7 At-211 atoms bound per cell. These results suggest that meta-[At-211]astatobenzylguanidine might be valuable for the targeted radiotherapy of micrometastatic neuroblastomas.