Wet harvesting of no-carrier-added 211At from an irradiated 209Bi target for radiopharmaceutical applications

Astatine-211 is one of the most promising -emitters for targeted cancer radiotherapy. However, research and clinical trials involving ²¹¹At-labeled radiopharmaceuticals have often been impeded due to the irregular and sometimes inconveniently low recovery yields obtained by the currently used dry distillation procedure. Therefore, a wet harvesting procedure isolating ²¹¹At from an irradiated ²⁰⁹Bi target was explored. The procedure involves target dissolution in concentrated HNO₃ and extraction of the high oxidation state ²¹¹At activity with butyl or isopropyl ether. This method resulted in consistent and nearly quantitative yields. The activity was re-extracted in aqueous phase and applied to NIS6 UVW human glioma cells transfected with cDNA encoding the human sodium/iodide symporter (NIS). The significant and specific uptake of ²¹¹At activity by these cells suggests that in the ether phase, high oxidation state ²¹¹At is reduced to [²¹¹At]astatide anion. The synthesis of the first astatinated organic compound derived from wet harvested ²¹¹At, 3-astatobenzoic acid (ABA), was achieved.This work was supported by Grants EB002980, CA42324 and CA91927 from the U.S. National Institutes of Health. Special thanks go to Michael Dailey and Shawn Murphy from the Duke University Medical Center PET Cyclotron Department for providing us with ²¹¹At activities and to Kevin Alston for the preparation of the bismuth targets. NIS cDNA was kindly gifted by Dr. Sissy M. Jhiang from Ohio State University, Columbus, Ohio.     

Wet harvesting of no-carrier-added 211At from an irradiated 209Bi target for radiopharmaceutical applications

Astatine-211 is one of the most promising -emitters for targeted cancer radiotherapy. However, research and clinical trials involving ²¹¹At-labeled radiopharmaceuticals have often been impeded due to the irregular and sometimes inconveniently low recovery yields obtained by the currently used dry distillation procedure. Therefore, a wet harvesting procedure isolating ²¹¹At from an irradiated ²⁰⁹Bi target was explored. The procedure involves target dissolution in concentrated HNO₃ and extraction of the high oxidation state ²¹¹At activity with butyl or isopropyl ether. This method resulted in consistent and nearly quantitative yields. The activity was re-extracted in aqueous phase and applied to NIS6 UVW human glioma cells transfected with cDNA encoding the human sodium/iodide symporter (NIS). The significant and specific uptake of ²¹¹At activity by these cells suggests that in the ether phase, high oxidation state ²¹¹At is reduced to [²¹¹At]astatide anion. The synthesis of the first astatinated organic compound derived from wet harvested ²¹¹At, 3-astatobenzoic acid (ABA), was achieved.This work was supported by Grants EB002980, CA42324 and CA91927 from the U.S. National Institutes of Health. Special thanks go to Michael Dailey and Shawn Murphy from the Duke University Medical Center PET Cyclotron Department for providing us with ²¹¹At activities and to Kevin Alston for the preparation of the bismuth targets. NIS cDNA was kindly gifted by Dr. Sissy M. Jhiang from Ohio State University, Columbus, Ohio.