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

IntroductionThe availability of 211At for targeted alpha therapy research can be increased by the 211Rn/211At generator system, whereby 211At is produced by 211Rn electron capture decay. This study demonstrated the feasibility of using generator-produced 211At to label monoclonal antibody (BC8, anti-human CD45) for preclinical use, following isolation from the 207Po contamination also produced by these generators (by 211Rn α-decay).Methods211Rn was produced by 211Fr electron capture decay following mass separated ion beam implantation and chemically isolated in liquid alkane hydrocarbon (dodecane). 211At produced by the resulting 211Rn source was extracted in strong base (2 N NaOH) and purified by granular Te columns. BC8-B10 (antibody conjugated with closo-decaborate(2-)) was labeled with generator-produced 211At and purified by PD-10 columns.ResultsAqueous solutions extracted from the generator were found to contain 211At and 207Po, isolated from 211Rn. High radionuclidic purity was obtained for 211At eluted from Te columns, from which BC8-B10 monoclonal antibody was successfully labeled. If not removed, 207Po was found to significantly contaminate the final 211At-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%).ConclusionsThe experimental 211Rn/211At generator was shown to be well-suited for preclinical 211At-based research.Advances in knowledgeWe believe that these experiments have furthered the knowledge-base for expanding accessibility to 211At using the 211Rn/211At generator system.Implications for patient careAs established by this work, the 211Rn/211At generator has the capability of facilitating preclinical evaluations of 211At-based therapies.