RESUMEN

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.

Asunto(s)

Anticuerpos Monoclonales/farmacocinética , Neoplasias Encefálicas/metabolismo , Fragmentos Fab de Inmunoglobulinas/química , Neuroblastoma/metabolismo , Oligopéptidos/química , Radiofármacos/farmacocinética , Animales , Anticuerpos Monoclonales/química , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Cromatografía en Capa Delgada , Radioisótopos de Cobre , Humanos , Inmunoconjugados/química , Inmunoconjugados/farmacocinética , Ligandos , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Radiofármacos/química , Espectrofotometría Ultravioleta , Distribución Tisular