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

Byung Chul Lee, Kyo Chul Lee, Hsiaoju Lee, Robert H. Mach, John A. Katzenellenbogen

Research output: Contribution to journalArticlepeer-review

Abstract

The peroxisome proliferator-activated receptor γ (PPARγ) is an important regulator of lipid metabolism and the differentiation of pre-adipocytes. Thus, imaging PPARγ in vivo using positron-emission tomography (PET) might be useful in assessing lipid metabolism disorders and identifying tumor cell differentiation. A fluorine-substituted PPARγ ligand from tyrosine-benzophenone class, compound 1, has a very high affinity for PPARγ receptor (Ki = 0.14 nM). To develop this compound as a PPARγ 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.

Original languageEnglish (US)
Pages (from-to)507-513
Number of pages7
JournalBioconjugate Chemistry
Volume18
Issue number2
DOIs
StatePublished - Mar 2007

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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