Comparison of bifunctional chelates for (64)Cu antibody imaging

• Published in: European journal of nuclear medicine and molecular imaging 2010-11, Vol.37 (11), p.2117-2126
• Main Authors: Ferreira, Cara L, Yapp, Donald T T, Crisp, Sarah, Sutherland, Brent W, Ng, Sylvia S W, Gleave, Martin, Bensimon, Corinne, Jurek, Paul, Kiefer, Garry E
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - metabolism; Antibodies, Monoclonal, Humanized; Cell Line, Tumor; Chelating Agents - chemistry; Chlorobenzenes - chemistry; Copper Radioisotopes - chemistry; Cross-Linking Reagents - chemistry; Humans; Isothiocyanates - chemistry; Mice; Molecular Imaging - methods; Positron-Emission Tomography; Reproducibility of Results; Trastuzumab
• ISSN: 1619-7089
• DOI: 10.1007/s00259-010-1506-1

Improved bifunctional chelates (BFCs) are needed to facilitate efficient (64)Cu radiolabeling of monoclonal antibodies (mAbs) under mild conditions and to yield stable, target-specific agents. The utility of two novel BFCs, 1-Oxa-4,7,10-triazacyclododecane-5-S-(4-isothiocyanatobenzyl)-4,7,10-triacetic acid (p-SCN-Bn-Oxo-DO3A) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-4-S-(4-isothiocyanatobenzyl)-3,6,9-triacetic acid (p-SCN-Bn-PCTA), for mAb imaging with (64)Cu were compared to the commonly used S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). The BFCs were conjugated to trastuzumab, which targets the HER2/neu receptor. (64)Cu radiolabeling of the conjugates was optimized. Receptor binding was analyzed using flow cytometry and radioassays. Finally, PET imaging and biodistribution studies were done in mice bearing either HER2/neu-positive or HER2/neu-negative tumors. (64)Cu-Oxo-DO3A- and PCTA-trastuzumab were prepared at room temperature in >95% radiochemical yield (RCY) in