Harnessing α-Emitting Radionuclides for Therapy: Radiolabeling Method Review

Abstract

Targeted α-therapy (TAT) is an emerging powerful tool treating latestage cancers for which therapeutic options are limited. At the core of TAT are targeted radiopharmaceuticals, where isotopes are paired with targeting vectors to enable tissue- or cell-specific delivery of α-emitters. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and DTPA (diethylenetriamine pentaacetic acid) are commonly used to chelate metallic radionuclides but have limitations. Significant efforts are underway to develop effective stable chelators for α-emitters and are at various stages of development and community adoption. Isotopes such as149Tb,212/213Bi, 212Pb (for212Bi), 225Ac, and226/227Th have found suitable chelators, although further studies, especially in vivo studies, are required. For others, including223Ra, 230U, and, arguably211At, the ideal chemistry remains elusive. This review summarizes the methods reported to date for the incorporation of149Tb,211At, 212/213Bi,212Pb (for212Bi),223Ra,225Ac,226/227Th, and 230U into radiopharmaceuticals, with a focus on new discoveries and remaining challenges. COPYRIGHT