Design and Activity Determination of Cyclic RGD Peptide and Preparation of ~(99)Tc~m Labeled Cyclic RGD Dimer

This paper was to design a cyclic RGD peptide tumor inhibitor with high affinity to integrin ανβ3 receptor by molecular docking technique.cRGD molecular library was built and an optimal structure of cRGD peptide with the lowest score that was Cy s-Arg-Gly-Asp-(D)Ser-Cy]s was screened out using the function of DOCK procedure of the V-life software.Based on the moiety a dimer linked by Tyr-(D)Ser-Lys-(D)Ser-Ser and with a side chain Gly-Gly-(D)Ala-Gly on Lys was synthesisized and 99Tcm-cRGD dimer was prepared.Its radiolabeled efficiency,stability,water-soluble and affinity in vitro were evaluated.Under the reaction condition of room temperature,1 g/L SnCl2·2H2O and the 30 min of reaction time,labeling efficiency reachs(87.42±3.21)%.After Sephadex G10 purification,the radiochemical purity is no less than 95%.In both mediums of saline and fresh human serum,the radiochemical purity keeps high stability in room temperature and 37 ℃.Then the equilibrium dissociation constant(Kd) on U87 human glioma cells was determined.After the reconstruction of the cRGD dimer,it possesses higher water-soluble and affinity,octanol-water partition coefficient lg P value is-1.96±0.01 and Kd value is(0.089±0.052)×10-9 mol/L.cRGD peptide screened by computer-aided drug design(CADD) system can bind to integrin ανβ3 specifically,and be a promising radiotracer for integrin ανβ3-positive tumors imaging.