Development of a preclinical 211Rn/211At generator system for targeted alpha therapy research with 211At

Introduction: The availability of At-211 for targeted alpha therapy research can be increased by the Rn-211/At-211 generator system, whereby At-211 is produced by Rn-211 electron capture decay. This study demonstrated the feasibility of using generator-produced At-211 to label monoclonal antibody (BC8, anti-human CD45) for preclinical use, following isolation from the Po-207 contamination also produced by these generators (by Rn-211 a-decay). Methods: Rn-211 was produced by Fr-211 electron capture decay following mass separated ion beam implantation and chemically isolated in liquid alkane hydrocarbon (dodecane). 21 At HI produced by the resulting Rn-211 source was extracted in strong base (2 N NaOH) and purified by granular Te columns. BC8-810 (antibody conjugated with closo-decaborate(2-)) was labeled with generator-produced At-211 and purified by PD-10 columns. Results: Aqueous solutions extracted from the generator were found to contain At-211 and Po-207, isolated from Rn-211. High radionuclidic purity was obtained for At-211 eluted from Te columns, from which BC8-810 monoclonal antibody was successfully labeled. If not removed, Po-207 was found to significantly contaminate the final At-211-BC8-B10 product. High yield efficiencies (decay-corrected, n = 3) were achieved for 211At extraction from the generator (86% +/- 7%), Te column purification (70% +/- 10%), and antibody labeling (76% +/- 2%). Conclusions: The experimental Rn-211/(211) At. HE generator was shown to be well-suited for preclinical At-211-based research. Advances in knowledge: We believe that these experiments have furthered the knowledge-base for expanding accessibility to At-211 using the Rn-211/(211) At generator system. Implications for patient care: As established by this work, the Rn-211/(211) At generator has the capability of facilitating preclinical evaluations of At-211-based therapies. (C) 2017 Elsevier Inc. All rights reserved.