Labeling Monoclonal Antibody with α-emitting ²¹¹At at High Activity Levels via a Tin Precursor

In a previous clinical study, the authors evaluated the potential of antitenascin C monoclonal antibody (mAb) 81C6 labeled with ²¹¹At via the prosthetic agent N-succinimidyl 3-[²¹¹At]astatobenzoate (SAB) for the treatment of primary brain tumors. Although encouraging results were obtained, labeling chemistry failed while attempting to escalate the dose to 370 MBq. The goal of the current study was to develop a revised procedure less susceptible to radiolysis-mediated effects on ²¹¹At labeling that would be suitable for use at higher activity levels of this α-emitter. Addition of N-chlorosuccinimide to the methanol used to remove the ²¹¹At from the cryotrap after bismuth target distillation was done to thwart radiolytic decomposition of reactive ²¹¹At and the tin precursor. A series of 11 reactions were performed to produce SAB at initial ²¹¹At activity levels of 0.31-2.74 GBq from 50 μg of N-succinimidyl 3-trimethylstannylbenzoate (Me-STB), which was then reacted with murine 81C6 mAb without purification of the SAB intermediate. Radiochemical purity, immunoreactive fraction, sterility, and apyrogenicity of the ²¹¹At-labeled 81C6 preparations were evaluated. Murine 81C6 mAb was successfully labeled with ²¹¹At using these revised procedures with improved radiochemical yields and decreased overall synthesis time compared with the original clinical labeling procedure. With 2.74 GBq of ²¹¹At, it was possible to produce 1.0 GBq of ²¹¹At-labeled 81C6 with an immunoreactive fraction of 92%. These revised procedures permit production of ²¹¹At-labeled mAbs suitable for use at clinically relevant activity levels.