Radiosynthesis and evaluation of 188Re-c(RGDyK)-His as a novel radiotherapeutic agent for integrin αvβ3 targeting tumour
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The successes of noninvasive methods to visualize and quantify integrin αvβ3 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 radio-therapy, which specifically targeting integrin αvβ3-positive tumors, could be used to treat these tumors. We have labeled c(RGDyK)-His, a RGD derivative, with 188Re and the radio-therapy efficiency has been evaluated in model nude mice. c(RGDyK)-His was labeled with 188Re by chelating with [188Re(CO)3(H2O)3]+ under a slightly basic condition. The in vitro specific binding affinity to U87 MG cell lines and the biodistribution of 188Re-c(RGDyK)-His in the animal tumor models was measured. The inhibitory effects of 188Re-c(RGDyK)-His were observed more than 1 month, and evaluated by microPET/CT imaging with 18F-FDG. Results of in vivo, cell uptake demonstrated 188Re-c(RGDyK)-His had a high specific binding affinity to receptor integrin αvβ3. In biodistribution experiment, 188Re-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 188Re-c(RGDyK)-His could be effectively used for integrin αvβ3 targeting therapy. This may offer a potential therapeutic strategy for the treatment of integrin-positive tumors in clinic.
Keywords188Re-c(RGDyK)-His Integrin Targeting therapy MicroPET/CT
This work was supported Natural Science Foundation of China under Contract No. 81101066.
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