Synthesis and evaluation of 15-(4-(2-[¹⁸F]Fluoroethoxy)phenyl)pentadecanoic acid: a potential PET tracer for studying myocardial fatty acid metabolism

Bioconjug Chem. 2010 Dec 15;21(12):2313-9. doi: 10.1021/bc100343h. Epub 2010 Nov 11.

Abstract

15-(4-(2-[¹⁸F]fluoroethoxy)phenyl)pentadecanoic acid ([¹⁸F]7) was synthesized as a PET probe for assessing myocardial fatty acid metabolism. The radiosynthesis of [¹⁸F]7 was accomplished using a two-step reaction, starting with the corresponding tosylate ester, methyl 15-(4-(2-(tosyloxy)ethoxy)phenyl)pentadecanoate (5), and gave the radiolabeled fatty acid, [¹⁸F]7 in a radiolabeling yield of 55-60% and a specific activity of >2000 Ci/mmol (decay corrected to EOB). The biological evaluation of [¹⁸F]7 in rats displayed high uptake in heart (1.94%ID/g at 5 min), which was higher than the uptake (%ID/g) in blood, lung, muscle, pancreas, and brain. MicroPET studies of [¹⁸F]7 in Sprague-Dawley rats demonstrated excellent images of the myocardium when compared with [¹¹C]palmitate images in the same animal. Moreover, the tracer kinetics of [¹⁸F]7 paralleled those seen with [¹¹C]palmitate, with an early peak followed by biphasic washout. When compared to [¹¹C]palmitate, [¹⁸F]7 exhibited a slower early clearance (0.17 ± 0.01 vs 0.30 ± 0.02, P < 0.0001) and a significantly higher late clearance (0.0030 ± 0.0005 vs 0.0006 ± 0.00013, P < 0.01). These initial studies suggest that [¹⁸F]7 could be a potentially useful clinical PET tracer to assess abnormal myocardial fatty acid metabolism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carbon Isotopes / chemistry
  • Carbon Isotopes / metabolism
  • Ethyl Ethers / chemistry
  • Ethyl Ethers / metabolism
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism*
  • Fatty Acids / pharmacokinetics
  • Fluorine Radioisotopes / chemistry
  • Fluorine Radioisotopes / pharmacokinetics*
  • Isotope Labeling / methods
  • Lipid Metabolism
  • Male
  • Myocardium / metabolism*
  • Organ Specificity
  • Palmitic Acid / chemistry
  • Palmitic Acid / metabolism
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution

Substances

  • Carbon Isotopes
  • Ethyl Ethers
  • Fatty Acids
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Palmitic Acid
  • pentadecanoic acid