Synthesis and binding affinity of a fluorine-substituted peroxisome proliferator-activated gamma (PPARgamma) ligand as a potential positron emission tomography (PET) imaging agent

Bioconjug Chem. 2007 Mar-Apr;18(2):507-13. doi: 10.1021/bc060190o. Epub 2007 Feb 20.

Abstract

The peroxisome proliferator-activated receptor gamma (PPARgamma) is an important regulator of lipid metabolism and the differentiation of pre-adipocytes. Thus, imaging PPARgamma in vivo using positron-emission tomography (PET) might be useful in assessing lipid metabolism disorders and identifying tumor cell differentiation. A fluorine-substituted PPARgamma ligand from tyrosine-benzophenone class, compound 1, has a very high affinity for PPARgamma receptor (Ki = 0.14 nM). To develop this compound as a PPARgamma PET imaging agent, we investigated synthetic routes suitable for its labeling with the short-lived PET radionuclide fluorine-18 (t1/2 = 110 min). To obtain the high specific activity material needed for receptor imaging with this isotope, reactions need to proceed efficiently, within a short time, starting from fluoride ion at the tracer level. The most promising approach involves introduction of fluorine into a suitable benzophenone precursor, followed by efficient coupling of this intermediate with the heterocyclic tyrosine component using a copper-catalyzed Ullmann-type condensation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Benzophenones / chemistry
  • Fluorine / chemistry*
  • Fluorine Radioisotopes
  • Ligands
  • PPAR gamma / chemical synthesis*
  • PPAR gamma / chemistry
  • PPAR gamma / metabolism*
  • Positron-Emission Tomography*
  • Protein Binding
  • Rosiglitazone
  • Thiazolidinediones / metabolism
  • Tyrosine / chemistry

Substances

  • Benzophenones
  • Fluorine Radioisotopes
  • Ligands
  • PPAR gamma
  • Thiazolidinediones
  • Rosiglitazone
  • Fluorine
  • Tyrosine
  • benzophenone