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

Abstract

IntroductionAstatine-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 211At via 209Bi (α, 2n) 211At reaction in a cyclotron and development of a facile radiochemical separation procedure to isolate 211At for formulation of nanoradiopharmaceuticals. MethodsNatural 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 HNO3 followed by selective precipitation of Bi as Bi(OH)3 under alkaline condition. The radiochemically separated 211At was used for labeling cyclic RGD peptide conjugated gold nanoparticles (Au-RGD NPs) by surface adsorption. The radiochemical stability of 211At-Au-RGD NPs was evaluated in phosphate buffered saline (PBS) and human serum media. ResultsThe batch yield of 211At at the end of irradiation was ∼6 MBq.μA−1.h−1. After radiochemical separation, ∼80 % of 211At could be retrieved with >99.9 % radionuclidic purity. Au-RGD NPs (particle size 8.4±0.8 nm) could be labeled with 211At with >99 % radiolabeling yield. The radiolabeled nanoparticles retained their integrity in PBS and human serum media over a period of 21 h. ConclusionsThe present strategy simplifies 211At production in terms of purification and would increase affordable access to this radioisotope for TAT of cancer.