Targeted therapy using alpha emitters.
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.
Department of Radiology, Duke University Medical Center, Durham, NC 27710, USA.
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Vaidyanathan
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Zalutsky
D000512:Alpha Particles; D000911:Antibodies, Monoclonal; D001246:Astatine / Q000627:therapeutic use*; D001729:Bismuth / Q000627:therapeutic use; D017357:Cyclotrons; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000379:methods; D011868:Radioisotopes / Q000627:therapeutic use*; D011878:Radiotherapy / Q000379:methods*
D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D001729:Bismuth; D001246:Astatine