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

The 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).

²¹¹Rn 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 (2N 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.

Aqueous 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%).

The experimental ²¹¹Rn/²¹¹At generator was shown to be well-suited for preclinical ²¹¹At-based research.

We believe that these experiments have furthered the knowledge-base for expanding accessibility to ²¹¹At using the ²¹¹Rn/²¹¹At generator system.

As established by this work, the ²¹¹Rn/²¹¹At generator has the capability of facilitating preclinical evaluations of ²¹¹At-based therapies.