title: Synthesis and preliminary evaluation of an ¹⁸F-labeled oleic acid analog for PET imaging of fatty acid uptake and metabolism.
abstract: BACKGROUND
  Imaging fatty acid uptake and utilization has broad impact in investigating myocardial diseases, hepatic functions, tumor progression, and the metabolic state of adipose tissue. The SPECT tracer (123)I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) is a clinically used nuclear medicine tracer to image myocardial uptake of fatty acid. Although ((18)F-5) has been in clinical use for PET imaging of adipose tissue as well as the myocardium, here we developed a click oleate analog to compare to FTO, with the goal of improved stability to defluorination and suitability for imaging myocardial uptake and oxidation of fatty acids.
  
  
  METHODS
  A rapid and convenient synthetic approach for a precursor to a (18)F-labeled oleate analog using click chemistry was developed and evaluated for PET imaging in fasted mice.
  
  
  RESULTS
  The overall yield for the preparation of the labeling precursor of the clicked oleate analog was 12%. This precursor was efficiently radiolabeled with F-18 in 17% non-decay-corrected radiochemical yield. PET/CT imaging and biodistribution results show that this fatty acid analog had reasonable heart uptake (0.94±0.28 %ID/g at 0.5 h p.i.) and heart-to-muscle ratio (2.05±0.39 at 0.5h p.i.) and is a potential lead for developing new PET tracers to image fatty acid uptake and utilization using click chemistry methodologies. The synthetic route to FTO was optimized to three steps from known starting materials.
  
  
  CONCLUSIONS
  While the uptake of the clicked oleic acid analog was sufficient for visualizing the myocardium in mice, the preliminary metabolism data suggest that only a fraction of the uptake was due to fatty acid beta-oxidation. Studies are under way to explore the uptake/oxidation mechanism and kinetics.
authors.affiliation: Department of Radiology.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Radiology.
authors.forename: Neale Scott
authors.initials: NS
authors.lastname: Mason
authors.affiliation: Department of Radiology; Department of Pharmacology and Chemical Biology; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15219, USA.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.affiliation: Department of Radiology. Electronic address: edwardsw@upmc.edu.
authors.forename: Wilson Barry
authors.initials: WB
authors.lastname: Edwards
mesh_terms: D000818:Animals; D001692:Biological Transport; D060326:Chemistry Techniques, Synthetic; D005227:Fatty Acids / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D019301:Oleic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
chemical_list: D005227:Fatty Acids; D005462:Fluorine Radioisotopes; D019301:Oleic Acid
keywords: (18)F; Fatty acid; Metabolism; Oleic acid; PET