title: First experience with clinical-grade ([18F]FPP(RGD₂): an automated multi-step radiosynthesis for clinical PET studies.
abstract: OBJECTIVE
  A reliable and routine process to introduce a new ¹⁸F-labeled dimeric RGD-peptide tracer ([¹⁸F]FPP(RGD₂) for noninvasive imaging of α(v)β₃ expression in tumors needed to be developed so the tracer could be evaluated for the first time in man. Clinical-grade [¹⁸F]FPP(RGD)₂ was screened in mouse prior to our first pilot study in human.
  
  
  METHODS
  [¹⁸F]FPP(RGD)₂ was synthesized by coupling 4-nitrophenyl-2-[¹⁸F]fluoropropionate ([¹⁸F]NPE) with the dimeric RGD-peptide (PEG₃-c(RGDyK)₂). Imaging studies with [¹⁸F]FPP(RGD)₂ in normal mice and a healthy human volunteer were carried out using small animal and clinical PET scanners, respectively.
  
  
  RESULTS
  Through optimization of each radiosynthetic step, [¹⁸F]FPP(RGD)₂ was obtained with RCYs of 16.9 ± 2.7% (n = 8, EOB) and specific radioactivity of 114 ± 72 GBq/μmol (3.08 ± 1.95 Ci/μmol; n = 8, EOB) after 170 min of radiosynthesis. In our mouse studies, high radioactivity uptake was only observed in the kidneys and bladder with the clinical-grade tracer. Favorable [¹⁸F]FPP(RGD)₂ biodistribution in human studies, with low background signal in the head, neck, and thorax, showed the potential applications of this RGD-peptide tracer for detecting and monitoring tumor growth and metastasis.
  
  
  CONCLUSIONS
  A reliable, routine, and automated radiosynthesis of clinical-grade [¹⁸F]FPP(RGD)₂ was established. PET imaging in a healthy human volunteer illustrates that [¹⁸F]FPP(RGD)₂ possesses desirable pharmacokinetic properties for clinical noninvasive imaging of α(v)β₃ expression. Further imaging studies using [¹⁸F]FPP(RGD)₂ in patient volunteers are now under active investigation.
authors.affiliation: Molecular Imaging Program at Stanford (MIPS), Departments of Radiology and Bioengineering, Bio-X Program, Stanford University School of Medicine, Stanford, CA 94305, USA. chinf@stanford.edu
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.forename: Bin
authors.initials: B
authors.lastname: Shen
authors.forename: Shuanglong
authors.initials: S
authors.lastname: Liu
authors.forename: Rhona A
authors.initials: RA
authors.lastname: Berganos
authors.forename: Edwin
authors.initials: E
authors.lastname: Chang
authors.forename: Erik
authors.initials: E
authors.lastname: Mittra
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C574086:FPP(RGD)2; D005462:Fluorine Radioisotopes; D009842:Oligopeptides; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid