title: Targeting of renal carcinoma with 67/64Cu-labeled anti-L1-CAM antibody chCE7: selection of copper ligands and PET imaging.
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.
authors.affiliation: Center for Radiopharmaceutical Science ETH-PSI-USZ, Paul Scherrer Institute, CH-5232 Villigen, Switzerland.
authors.forename: Kurt
authors.initials: K
authors.lastname: Zimmermann
authors.forename: Jürgen
authors.initials: J
authors.lastname: Grünberg
authors.forename: Michael
authors.initials: M
authors.lastname: Honer
authors.forename: Simon
authors.initials: S
authors.lastname: Ametamey
authors.forename: P August
authors.initials: PA
authors.lastname: Schubiger
authors.forename: Ilse
authors.initials: I
authors.lastname: Novak-Hofer
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000532:radiotherapy; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D003301:Copper Radioisotopes; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000532:radiotherapy; D008024:Ligands; D051379:Mice; D016499:Radioimmunotherapy / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D008024:Ligands; D019275:Radiopharmaceuticals