(18) F labeled RGD-A7R peptide for dual integrin and VEGF-targeted tumor imaging in mice bearing U87MG tumors.

Abstract

The aim of this study is to develop a novel Arg-Gly-Asp acid (RGD) and Ala-Thr-Trp-Leu-Pro-Pro-Arg (ATWLPPR A7R) peptide-containing ligand for (18) F labeling as αvβ3 and vascular endothelial growth factor receptor-targeted imaging agent. (18) F-RGD-A7R was prepared by conjugation with (18) F-SFB. The final product was purified by high-performance liquid chromatography and tested in vitro and in vivo. Cell-binding assays of RGD-A7R, RGD and RGD-A7R, A7R were tested in U87MG cells ((125) I-RGDyK and (125) I-A7RY as radioligand, respectively). Preliminary biodistribution of the (18) F-RGD-A7R was also evaluated. The RGD-A7R had good integrin binding affinity (50% inhibitory concentration (IC50 ) = 21.67 and 23.68 nM, slightly lower than unmodified RGD (40.02 nM) and A7R (50.18 nM)). The radiotracer had receptor-mediated activity accumulation in U87MG tumor (1.90 ± 0.34 percentage of injected dose per gram (%ID/g) at 0.5 h postinjection), which is known to be integrin positive. After blocking with RGD-A7R, the tumor uptake was reduced to 0.47 ± 0.06 %ID/g at 0.5 h postinjection. (18) F-RGD-A7R exhibited dual receptor targeting properties both in vitro and in vivo. The favorable characterizations of (18) F-RGD-A7RY, such as convenient synthesis, high specific activity, and high tumor uptake, warrant its further investigation for clinical cancer imaging.