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 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.

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 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.

Results

The 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.

Conclusions

The present strategy simplifies ²¹¹At production in terms of purification and would increase affordable access to this radioisotope for TAT of cancer.