Radiosynthesis and evaluation of Re-188-c(RGDyK)-His as a novel radiotherapeutic agent for integrin alpha(v)beta(3) targeting tumour
- 医学院－已发表论文 
The successes of noninvasive methods to visualize and quantify integrin alpha(v)beta(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 alpha(v)beta(3)-positive tumors, could be used to treat these tumors. We have labeled c(RGDyK)-His, a RGD derivative, with Re-188 and the radio-therapy efficiency has been evaluated in model nude mice. c(RGDyK)-His was labeled with Re-188 by chelating with [Re-188(CO)(3)(H2O)(3)](+) under a slightly basic condition. The in vitro specific binding affinity to U87 MG cell lines and the biodistribution of Re-188-c(RGDyK)-His in the animal tumor models was measured. The inhibitory effects of Re-188-c(RGDyK)-His were observed more than 1 month, and evaluated by microPET/CT imaging with F-18-FDG. Results of in vivo, cell uptake demonstrated Re-188-c(RGDyK)-His had a high specific binding affinity to receptor integrin alpha(v)beta(3). In biodistribution experiment, Re-188-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 Re-188-c(RGDyK)-His could be effectively used for integrin alpha(v)beta(3) targeting therapy. This may offer a potential therapeutic strategy for the treatment of integrin-positive tumors in clinic.