An automated process for astatine-211 isolation from irradiated bismuth targets using a tellurium-packed column

666 Objectives: The objective of this research effort was to evaluate automation of a facile method for isolation of 211At from irradiated bismuth targets using tellurium-packed columns (Te-column). 211At is an attractive radionuclide for targeted alpha therapy (TAT) due to its physical properties; 7.21 h half-life, minimal high energy gamma-ray emission and 100% alpha emission. Highly efficient and robust automated 211At isolation systems are required for improving its availability and to facilitate clinical studies of 211At-labeled TAT agents. Methods: Chromatographic conditions for manually separating 211At using Te-columns were optimized using small amounts, i.e. ≤37 MBq (≤1 mCi), of 211At based on the early studies of Bochvarova and co-workers1. In evaluations of the automated system, targets containing ~0.96 GBq (~26 mCi) of 211At were dissolved in 10 M HNO3 using an in-line dissolution chamber2 and the resultant solution was routed into a 250-mL reaction vessel. Then an NH2OH·HCl solution was added dropwise into the reaction vessel to destroy the nitrate ions, followed by a HCl solution to reconstitute the 211At/Bi mixture to 1.5 M HCl solution. Subsequently, the Te-column was loaded with the 211At/Bi mixture, washed with 1.5 M HCl and H2O. Finally, 211At was eluted using 5 mL of 2 M NaOH. In the automated system, Hamilton Microlab 500 Series Diluter/Dispenser dual-syringe pump and Modular Valve Positioners controlled by the Microlab 500 Control Software were used for routing and delivering all the liquids. The radiochemical purity of the 211At was assessed using radio-HPLC and radio-iTLC. The 211At obtained was used to radiolabel isothiocyanato-phenethyl-closo-decaborate(2-) (B10-NCS)-conjugated antibodies after adjusting the pH to ~7.0. The concentrations of Bi and Te in 211At solutions and astatinated antibodies were determined using ICP-MS. Results: The automated isolation process took less than 2 h, and 211At isolated yields (after attenuation and decay correction) of 88-95% were achieved. Radio-HPLC analyses showed that ≥ 99% of the 211At in the final product was astatide. Astatination yields of B10-conjugated antibody were high (77-95%) and the concentration of Bi and Te in the size-exclusion column purified final product was less than 0.031 and 0.19 ppm, respectively. Conclusions: An efficient automated process that uses Te-columns for separating 211At from irradiated Bi targets has been developed. The purified 211At is of high radiochemical purity and suitable for B10-conjugated antibody astatination reactions. Acknowledgments: The authors gratefully acknowledge the staff of the U.W. Medical Cyclotron Facility, especially E.F. Dorman and R.C. Emery, for assistance in obtaining irradiated bismuth targets. We thank the Isotope Research & Development program, Office of Science, United States Department of Energy for funding this research (DE-SC0013618 & DE-SC0018013). References: 1. M. Bochvarova, D. K. T., I. Dudova, Yu. V. Norseev, and V. A. Khalkin, Investigation of Columns Filled with Crystalline Tellurium for the Production of Radiochemically Pure Preparations of Astatine. Translated from Radiokhimiya 1972,14 (6), 858-865. 2. O’Hara, M. J., Krzysko, A. J., Niver, C. M., Morrison, S. S., Owsley, S. L., Hamlin, D. K., Dorman, E. F., and Wilbur, D.S, An automated flow system incorporating in-line acid dissolution of bismuth metal from a cyclotron irradiated target assembly for use in the isolation of astatine-211. Applied Radiation and Isotopes 2017,122 (Supplement C), 202-210.