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

Nucl Med Biol. 2003 May;30(4):417-27. doi: 10.1016/s0969-8051(03)00019-2.

Abstract

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 (67)Cu-MAb chCE7 significantly. CPTA-labeled antibody achieved the best tumor to normal tissue ratios when biodistributions of the different (67)Cu-chCE7 conjugates were assessed in tumor-bearing mice. High resolution PET imaging with (64)Cu-CPTA-labeled MAb chCE7 showed uptake in lymph nodes and heterogeneous distribution in tumor xenografts.

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / radiotherapy
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / metabolism
  • Chelating Agents / pharmacokinetics
  • Copper Radioisotopes
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / radiotherapy
  • Ligands
  • Mice
  • Radioimmunotherapy / methods*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / metabolism
  • Radiopharmaceuticals / pharmacokinetics
  • Structure-Activity Relationship
  • Tissue Distribution
  • Tomography, Emission-Computed

Substances

  • Chelating Agents
  • Copper Radioisotopes
  • Ligands
  • Radiopharmaceuticals