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

Author:

Gholipour Nazila1,Jalilian Amir R.2,Fazaeli Yousef2,Sabzevari Omid3,Moradkhani Sedigheh2,Bolourinovin Fateme2,Khalaj Ali4

Affiliation:

1. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2. Nuclear Science and Technology Research Institute (NSTRI), Tehran, Postal code: 14155-1339, Iran

3. Department of Toxicology and Pharmacology, Faculty of Pharmacy,Tehran University of Medical Sciences, Tehran, Iran

4. Department of Medical Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

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.

Publisher

Walter de Gruyter GmbH

Subject

Physical and Theoretical Chemistry

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