A triglycine linker improves tumor uptake and biodistributions of 67-Cu-labeled anti-neuroblastoma MAb chCE7 F(ab')2 fragments.

Abstract

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.

• Authors: K Zimmermann, S Gianollini, P A Schubiger, I Novak-Hofer
• Journal: Nuclear medicine and biology (Nucl Med Biol) Vol. 26 Issue 8 Pg. 943-50 (Nov 1999) ISSN: 0969-8051 [Print] United States
• PMID: 10708309 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Copper Radioisotopes
• Immunoconjugates
• Immunoglobulin Fab Fragments
• Ligands
• Oligopeptides
• Radiopharmaceuticals
• glycyl-glycyl-glycine

Topics

• Animals
• Antibodies, Monoclonal (chemistry, pharmacokinetics)
• Brain Neoplasms (metabolism)
• Chromatography, Gel
• Chromatography, High Pressure Liquid
• Chromatography, Thin Layer
• Copper Radioisotopes
• Humans
• Immunoconjugates (chemistry, pharmacokinetics)
• Immunoglobulin Fab Fragments (chemistry)
• Ligands
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neuroblastoma (metabolism)
• Oligopeptides (chemistry)
• Radiopharmaceuticals (chemistry, pharmacokinetics)
• Spectrophotometry, Ultraviolet
• Tissue Distribution