Improved production, and evaluation of Cu-67 for tumor radioimmunotherapy

Copper-67 is a radionuclide of great interest for radioimmunotherapy. We report labeling and biodistribution results with the anti-CEA F(ab`){sub 2} monoclonal antibody (MAb). The anti-CEA F(ab`){sub 2} MAb was conjugated with 1,4,7,10-tetraazacyclodo-decane-and 1,4,8,11-tetraazacyclotetradecane-N,N`,N``,N```-tetraacetic acid (DOTA and TETA) using their mono NHS esters. The ligands were synthesized using a simple large scale method and the MAb conjugates were labeled with Cu-67 (90{plus_minus}5% yield, 98% in-vitro serum stability at 4d, and immunoreactivity 80{plus_minus}10%). Data in tumor (LS-174 T cells) xenografted nude mice showed similar tumor uptake (% ID/g) for both DOTA and TETA at 24h (32.4 vs 35.7) and 96h (14.6 vs 17.1). The DOTA conjugate showed slightly higher liver uptake (24h: 14.7 vs 10.4; 96h: 7.05 vs 5.3) and blood uptake (24h: 6.16 vs 4.73; 96h: 0.72 vs 0.46) while the TETA conjugate showed higher kidney uptake (24h: 12.8 vs 4.8; 96h: 8.6 vs 4.1). These results are quite favorable and warrant further study of these Cu-67-MAb conjugates for radioimmunotherapy.