Synthesis and biological evaluation of (68) Ga-labeled Pteroyl-Lys conjugates for folate receptor-targeted tumor imaging

In order to develop novel (68) Ga-labeled PET tracers for folate receptor imaging, two DOTA-conjugated Pteroyl-Lys derivatives, Pteroyl-Lys-DOTA and Pteroyl-Lys-DAV-DOTA, were designed, synthesized and radiolabeled with (68) Ga. Biological evaluations of the two radiotracers were performed with FR-positive KB cell line and athymic nude mice bearing KB tumors. Both (68) Ga-DOTA-Lys-Pteroyl and (68) Ga-DOTA-DAV-Lys-Pteroyl exhibited receptor specific binding in KB cells in vitro. The tumor uptake values of (68) Ga-DOTA-Lys-Pteroyl and (68) Ga-DOTA-DAV-Lys-Pteroy were 10.06 ± 0.59%ID/g and 11.05 ± 0.60%ID/g at 2 h post-injection, respectively. Flank KB tumor was clearly visualized with (68) Ga-DOTA-DAV-Lys-Pteroyl by Micro-PET imaging at 2 h post-injection, suggesting the feasibility of using (68) Ga-labeled Pteroyl-Lys conjugates as a novel class of FR targeted probes.