Production, purification and formulation of nanoradiopharmaceutical with 211At: An emerging candidate for targeted alpha therapy

Introduction Astatine-211 has attained significant interest in the recent times as a promising radioisotope for targeted alpha therapy (TAT) of cancer. In this study, we report the production of At-211 via Bi-209 (alpha, 2n) At-211 reaction in a cyclotron and development of a facile radiochemical separation procedure to isolate At-211 for formulation of nanoradiopharmaceuticals. Methods Natural bismuth oxide target in pelletized form wrapped in Al foil was irradiated with 30 MeV alpha-beam in an AVF cyclotron. The irradiated target was dissolved in 2 M HNO3 followed by selective precipitation of Bi as Bi(OH)(3) under alkaline condition. The radiochemically separated At-211 was used for labeling cyclic RGD peptide conjugated gold nanoparticles (Au-RGD NPs) by surface adsorption. The radiochemical stability of At-211-Au-RGD NPs was evaluated in phosphate buffered saline (PBS) and human serum media. Results The batch yield of At-211 at the end of irradiation was similar to 6 MBq.mu A(-1).h(-1). After radiochemical separation, similar to 80 % of At-211 could be retrieved with >99.9 % radionuclidic purity. Au-RGD NPs (particle size 8.4 +/- 0.8 nm) could be labeled with At-211 with >99 % radiolabeling yield. The radiolabeled nanoparticles retained their integrity in PBS and human serum media over a period of 21 h. Conclusions The present strategy simplifies At-211 production in terms of purification and would increase affordable access to this radioisotope for TAT of cancer.