Radiosynthesis and evaluation of ~(188)Re-c(RGDyK)-His as a novel radiotherapeutic agent for integrin α_vβ_3 targeting tumour

摘要

The successes of noninvasive methods to visualize and quantify integrin α_vβ_3 expression in vivo have paved the way for radiolabeling anti-integrin therapy in clinic. Arginine-glycine-aspartice (RGD) peptide and related derivatives labeled with radionuclides for radiotherapy, which specifically targeting integrin α_vβ_3-positive tumors, could be used to treat these tumors. We have labeled c(RGDyK)-His, a RGD derivative, with ~(188)Re and the radio-therapy efficiency has been evaluated in model nude mice. c(RGDyK)-His was labeled with ~(188)Re by chelating with [~(188)Re(CO)_3(H_2O)_3]~+ under a slightly basic condition. The in vitro specific binding affinity to U87 MG cell lines and the biodistribution of ~(188)Re-c(RGDyK)-His in the animal tumor models was measured. The inhibitory effects of ~(188)Re-c(RGDyK)-His were observed more than 1 month, and evaluated by microPET/CT imaging with ~(18)F-FDG. Results of in vivo, cell uptake demonstrated ~(188)Re-c(RGDyK)-His had a high specific binding affinity to receptor integrin α_vβ_3. In biodistribution experiment, ~(188)Re-c(RGDyK)-His was accumulated in the tumor and cleared fast from the normal tissues. In radiotherapy study, tumor growth inhibition was significantly higher in the treatment groups than in the control groups. These studies showed that ~(188)Re-c(RGDyK)-His could be effectively used for integrin α_vβ_3 targeting therapy. This may offer a potential therapeutic strategy for the treatment of integrinpositive tumors in clini