Harnessing α-Emitting Radionuclides for Therapy: Radiolabeling Method Review

Targeted alpha-therapy (TAT) is an emerging powerful tool treating late-stage 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 Tb-149 , Bi-212/213 , (212)pb (for Bi-212), adoption. Isotopes such as (225)AC, and Th-226/227 have found suitable chelators, although further studies, especially in vivo studies, are required. For others, including Ra-223, U-230 and, arguably At-211, the ideal chemistry remains elusive. This review summarizes the methods reported to date for the incorporation of Tb-149, At-211, Bi-212/213, Pb-212 (for Bi-212), Ra-223, Ra-225, Ac-225, Th-226/227, and U-230 into radiopharmaceuticals, with a focus on new discoveries and remaining challenges.

Automated summary

Targeted alpha-therapy is a promising tool for treating late-stage cancers. By using targeted radiopharmaceuticals, tissue- or cell-specific delivery of a-emitters can be achieved. Researchers are currently focusing on developing effective stable chelators for a-emitters, but there are still challenges to overcome.