A new cyclic RGD peptide dimer for integrin αvβ3 imaging.

OBJECTIVE To design a new Arg-Gly-Asp (RGD) peptide that can specifically bind integrin αvβ3 and evaluate the possibility of using 131I-labeled peptide for imaging αvβ3-positive tumors. MATERIALS AND METHODS The structure of the RGD monomer was selected using V-life software. Based on the RGD monomer, a dimer of cyclic RGD [c(RGD)2] linked by Tyr-(D)Ser-Lys-(D)Ser-Ser with a Gly-Gly-(D)Ala-Gly side chain on the lysine residue was synthesized. 131I-c(RGD)2 was synthesized using the chloramine-T (ChT) method, and the octanol-water partition coefficient was experimentally measured. To evaluate its binding affinity and selectivity, its equilibrium dissociation constant (Kd) with U87 MG glioma cells was measured in vitro, while whole body imaging and biodistribution were assessed in vivo in mice bearing U87 MG xenografts. RESULTS The optimal structure of the monomer was cyclic [-Cys-Arg-Gly-Asp-(D)Ser-Cys-]. The 131I-c(RGD)2 molecule exhibited good stability and was highly hydrophilic. The Kd value was (3.87 ± 0.05) × 10(-9) M, suggesting a high αvβ3-binding affinity and specificity. The tumors were clearly visualized at 3 and 6 h post-injection. Biodistribution data of the 131I-c(RGD)2 molecule showed rapid clearance from the blood and predominant accumulation in the tumor and kidney. The tumor-to-normal tissue (T/NT) ratio increased over time. At 24 h post-injection, the tumor-to-liver, tumor-to-muscle, and tumor-to-blood ratios were 4.92, 4.29, and 5.00, respectively. CONCLUSIONS These results suggest that the 131I-c(RGD)2 molecule may serve as a promising tracer for the detection of αvβ3-positive tumors.