title: A new cyclic RGD peptide dimer for integrin αvβ3 imaging.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Nuclear Medicine, Peking University First Hospital, Beijing, China. china__doctor@163.com.
authors.forename: H
authors.initials: H
authors.lastname: Ma
authors.forename: P
authors.initials: P
authors.lastname: Hao
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Ma
authors.forename: P
authors.initials: P
authors.lastname: Yan
authors.forename: R-F
authors.initials: RF
authors.lastname: Wang
authors.forename: C-L
authors.initials: CL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging / Q000379:methods; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D014018:Tissue Distribution / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid