title: Comparison of three dimeric 18F-AlF-NOTA-RGD tracers.
abstract: OBJECTIVE
  RGD peptide-based radiotracers are well established as integrin αvβ3 imaging probes to evaluate tumor angiogenesis or tissue remodeling after ischemia or infarction. In order to optimize the labeling process and pharmacokinetics of the imaging probes, we synthesized three dimeric RGD peptides with or without PEGylation and performed in vivo screening.
  
  
  METHODS
  Radiolabeling was achieved through the reaction of F-18 aluminum-fluoride complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Three imaging probes were synthesized as (18)F-AlF-NOTA-E[c(RGDfK)]2, (18)F-AlF-NOTA-PEG4-E[c(RGDfK)]2, and (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2. The receptor binding affinity was determined by competitive cell binding assay, and the stability was evaluated by mouse serum incubation. Tumor uptake and whole body distribution of the three tracers were compared through direct tissue sampling and PET quantification of U87MG tumor-bearing mice.
  
  
  RESULTS
  All three compounds remained intact after 120 min incubation with mouse serum. They all had a rapid and relatively high tracer uptake in U87MG tumors with good target-to-background ratios. Compared with the other two tracers, (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2 had the highest tumor uptake and the lowest accumulation in the liver. The integrin receptor specificity was confirmed by co-injection of unlabeled dimeric RGD peptide.
  
  
  CONCLUSIONS
  The rapid one-step radiolabeling strategy by the complexation of (18)F-aluminum fluoride with NOTA-peptide conjugates was successfully applied to synthesize three dimeric RGD peptides. Among the three probes developed, (18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2 with relatively low liver uptake and high tumor accumulation appears to be a promising candidate for further translational research.
authors: Department of Biomedical Engineering, and Wuhan National Laboratory for Optoelectronics(WNLO), Huazhong University of Science and Technology, Wuhan, 430074, China.
authors: Jinxia
authors: J
authors: Guo
authors: Lixin
authors: L
authors: Lang
authors: Shuo
authors: S
authors: Hu
authors: Ning
authors: N
authors: Guo
authors: Lei
authors: L
authors: Zhu
authors: Zhongchan
authors: Z
authors: Sun
authors: Ying
authors: Y
authors: Ma
authors: Dale O
authors: DO
authors: Kiesewetter
authors: Gang
authors: G
authors: Niu
authors: Qingguo
authors: Q
authors: Xie
authors: Xiaoyuan
authors: X
authors: Chen
mesh_terms: D017607:Aluminum Compounds / Q000097:blood / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D019281:Dimerization; D005459:Fluorides / Q000097:blood / Q000737:chemistry; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds / Q000097:blood / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring; D006801:Humans; D051379:Mice; D009842:Oligopeptides / Q000097:blood / Q000737:chemistry; D009928:Organ Specificity; D011849:Radioactive Tracers; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D017607:Aluminum Compounds; D005462:Fluorine Radioisotopes; D006571:Heterocyclic Compounds; D006573:Heterocyclic Compounds, 1-Ring; D009842:Oligopeptides; D011849:Radioactive Tracers; C048993:1,4,7-triazacyclononane-N,N',N''-triacetic acid; C047981:arginyl-glycyl-aspartic acid; D005459:Fluorides; C032311:aluminum fluoride
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