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

INTRODUCTION: The availability of211 At for targeted alpha therapy research can be increased by the211 Rn/211 At generator system, whereby211 At is produced by211 Rn electron capture decay. This study demonstrated the feasibility of using generator-produced211 At to label monoclonal antibody (BC8, anti-human CD45) for preclinical use, following isolation from the207 Po contamination also produced by these generators (by211 Rn α-decay).

METHODS: 211 Rn was produced by211 Fr electron capture decay following mass separated ion beam implantation and chemically isolated in liquid alkane hydrocarbon (dodecane).211 At produced by the resulting211 Rn source was extracted in strong base (2N NaOH) and purified by granular Te columns. BC8-B10 (antibody conjugated with closo-decaborate(2-)) was labeled with generator-produced211 At and purified by PD-10 columns.

RESULTS: Aqueous solutions extracted from the generator were found to contain211 At and207 Po, isolated from211 Rn. High radionuclidic purity was obtained for211 At eluted from Te columns, from which BC8-B10 monoclonal antibody was successfully labeled. If not removed,207 Po was found to significantly contaminate the final211 At-BC8-B10 product. High yield efficiencies (decay-corrected, n=3) were achieved for211 At extraction from the generator (86%±7%), Te column purification (70%±10%), and antibody labeling (76%±2%).

CONCLUSIONS: The experimental211 Rn/211 At generator was shown to be well-suited for preclinical211 At-based research.

ADVANCES IN KNOWLEDGE: We believe that these experiments have furthered the knowledge-base for expanding accessibility to211 At using the211 Rn/211 At generator system.

IMPLICATIONS FOR PATIENT CARE: As established by this work, the211 Rn/211 At generator has the capability of facilitating preclinical evaluations of211 At-based therapies.