Production, purification and formulation of nanoradiopharmaceutical with At: 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 via Bi (α, 2n) At reaction in a cyclotron and development of a facile radiochemical separation procedure to isolate At for formulation of nanoradiopharmaceuticals.

Methods: Natural bismuth oxide target in pelletized form wrapped in Al foil was irradiated with 30 MeV α-beam in an AVF cyclotron. The irradiated target was dissolved in 2 M HNO followed by selective precipitation of Bi as Bi(OH) under alkaline condition. The radiochemically separated At was used for labeling cyclic RGD peptide conjugated gold nanoparticles (Au-RGD NPs) by surface adsorption. The radiochemical stability of At-Au-RGD NPs was evaluated in phosphate buffered saline (PBS) and human serum media.

Results: The batch yield of At at the end of irradiation was ∼6 MBq.μA.h. After radiochemical separation, ∼80 % of At could be retrieved with >99.9 % radionuclidic purity. Au-RGD NPs (particle size 8.4±0.8 nm) could be labeled with At 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 production in terms of purification and would increase affordable access to this radioisotope for TAT of cancer.