Harnessing <b>α</b>-Emitting Radionuclides for Therapy: Radiolabeling Method Review
Hua Yang, Justin J. Wilson, Chris Orvig, Yawen Li, D. Scott Wilbur, Caterina F. Ramogida, Valery Radchenko, Paul Schaffer
Abstract
Targeted a-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 a-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 a-emitters and are at various stages of development and community adoption. Isotopes such as 149 Tb, 212/213 Bi, 212 Pb (for 212 Bi), 225 Ac, and 226/227 Th have found suitable chelators, although further studies, especially in vivo studies, are required. For others, including 223 Ra, 230 U, and, arguably 211 At, the ideal chemistry remains elusive. This review summarizes the methods reported to date for the incorporation of 149 Tb, 211 At, 212/213 Bi, 212 Pb (for 212 Bi), 223 Ra, 225 Ac, 226/227 Th, and 230 U into radiopharmaceuticals, with a focus on new discoveries and remaining challenges.