Targeting of renal carcinoma with 67/64CU-labeled anti-L1-CAM antibody chCE7:: selection of copper ligands and PET imaging

In order to optimize radiocopper labeling of anti-L1-CAM antibody chCE7, five bifunctional copper chelators were synthesized and characterized (CPTA-N-hydoxysuccinimide, DO3A-L-p-isothiocyanato-phenylalanine, DOTA-PA-L-p-isocyanato-phenylalanine, DOTA-glycyl-L-p-isocyanato-phenylalanine and DOTA-triglycyl-L-p-isocyanato-phenylalanine). Substitution with more than 11 chelators per antibody molecule was found to influence immunoreactivity and biodistributions of Cu-67-MAb chCE7 significantly. CPTA-labeled antibody achieved the best tumor to normal tissue ratios when biodistributions of the different Cu-67-chCE7 conjugates were assessed in tumor-bearing mice. High resolution PET imaging with Cu-64-CPTA-labeled MAb chCE7 showed uptake in lymph nodes and heterogeneous distribution in tumor xenografts. (C) 2003 Elsevier Inc. All rights reserved.