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

INTRODUCTION

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

METHODS

Rn was produced by Fr electron capture decay following mass separated ion beam implantation and chemically isolated in liquid alkane hydrocarbon (dodecane). At produced by the resulting 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-produced At and purified by PD-10 columns.

RESULTS

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

CONCLUSIONS

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

ADVANCES IN KNOWLEDGE

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

IMPLICATIONS FOR PATIENT CARE

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