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

Background: In a previous clinical study, the authors evaluated the potential of antitenascin C monoclonal antibody (mAb) 81C6 labeled with ²¹¹ At via the prosthetic agent N -succinimidyl 3-[ ²¹¹ At]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 ²¹¹ At labeling that would be suitable for use at higher activity levels of this α-emitter. Materials and Methods: Addition of N -chlorosuccinimide to the methanol used to remove the ²¹¹ At from the cryotrap after bismuth target distillation was done to thwart radiolytic decomposition of reactive ²¹¹ At and the tin precursor. A series of 11 reactions were performed to produce SAB at initial ²¹¹ At 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 ²¹¹ At-labeled 81C6 preparations were evaluated. Results: Murine 81C6 mAb was successfully labeled with ²¹¹ At using these revised procedures with improved radiochemical yields and decreased overall synthesis time compared with the original clinical labeling procedure. Conclusions: With 2.74 GBq of ²¹¹ At, it was possible to produce 1.0 GBq of ²¹¹ At-labeled 81C6 with an immunoreactive fraction of 92%. These revised procedures permit production of ²¹¹ At-labeled mAbs suitable for use at clinically relevant activity levels.