A triglycine linker improves tumor uptake and biodistributions of 67-Cu-labeled anti-neuroblastoma MAb chCE7 F(ab')2 fragments.
The peptide-linked copper chelators CPTA-triglycyl-L-p-isothiocyanato-phenylalanine (CPTA-R1-NCS) as well as DOTA-triglycyl-L-p-isocyanato-phenylalanine (DOTA-R1-NCS) were synthesized and coupled to F(ab')2 fragments of the anti-neuroblastoma monoclonal antibody (MAb) chCE7. 67Cu-labeled conjugates were compared with the original CPTA- and DO3A-F(ab')2 in vitro and in vivo in mice bearing neuroblastoma xenografts. With the CPTA-R1-F(ab')2, biodistributions were improved, because radioactivity present in the kidney was reduced. With the DOTA-R1-F(ab')2, clearance from the blood was slower and tumor uptake was higher compared with the other conjugates. DOTA-R1-F(ab')2 achieved the best tumor/tissue ratios.
Zimmermann
K
K
Center for Radiopharmaceutical Sciences, Paul Scherrer Institute, Villigen-Psi, Switzerland.
Gianollini
S
S
Schubiger
P A
PA
Novak-Hofer
I
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000378:metabolism*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003301:Copper Radioisotopes; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000493:pharmacokinetics; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry*; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C035647:glycyl-glycyl-glycine