Development of [62Zn/62Cu]-DOTA-rituximab as a possible novel in vivo PET generator for anti-CD20 antigen imaging

Abstract

Abstract In this study, zinc-62 was prepared at radiopharmaceutical grade (for 62Zn/62Cu generator production) using natCu(p, xn) reaction with the production yield of 5.9 mCi/μAh at 30 MeV proton energy (radiochemical separation yield >95%, radionuclidic purity >99% and radiochemical purity >99%). In the next step, rituximab was successively labeled with [62Zn]-ZnCl2 after conjugation with p-SCN-Bz-DOTA followed by molecular filtration and determination of the average number of DOTA conjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (>97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of [62Zn]-DOTA-rituximab (in final formulation, and human serum) were determined 1–8 h as well as biodistribution studies in wild-type rats followed by coincidence imaging for 6 h. However, the accumulation of the radiolabeled antibody was not consistent with the former reported rituximab conjugates. [62Zn]-labeled monoclonal antibodies and fragments can be prepared as potential in vivo PET generators for molecular imaging however, the search for application of stable zinc complexes must be continued.