Cu-64-Labeled multifunctional dendrimers for targeted tumor PET imaging

We report the use of multifunctional folic acid (FA)-modified dendrimers as a platform to radiolabel with Cu-64 for PET imaging of folate receptor (FR)-expressing tumors. In this study, amine-terminated generation 5 (G5) poly(amidoamine) dendrimers were sequentially modified with fluorescein isothiocyanate (FI), FA, and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), followed by acetylation of the remaining dendrimer terminal amines. The as-formed multifunctional DOTA-FA-FI-G5 center dot NHAc dendrimers were then radiolabeled with Cu-64 via the DOTA chelation. We show that the FA modification renders the dendrimers with targeting specificity to cancer cells overexpressing FR in vitro. Importantly, the radiolabeled Cu-64-DOTA-FA-FI-G5 center dot NHAc dendrimers can be used as a nanoprobe for specific targeting of FRoverexpressing cancer cells in vitro and targeted microPET imaging of the FR-expressing xenografted tumor model in vivo. The developed Cu-64-labeled multifunctional dendrimeric nanoprobe may hold great promise to be used for targeted PET imaging of different types of FR-expressing cancer.