Synthesis and evaluation of 18F-labeled PPARγ antagonists

Hsiaoju Lee, Delphine L. Chen, Justin M. Rothfuss, Michael J. Welch, Robert J. Gropler, Robert H. Mach

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Introduction: Peroxisome proliferator-activated receptor gamma (PPARγ) transcriptionally modulates fat metabolism and also plays a role in pathological conditions such as cancer, neurodegenerative disease and inflammation. PPARγ imaging agents are potential tools for investigating these diseases. Methods: Four analogs of GW9662, a PPARγ antagonist, with different fluorine-containing substituents at the para-position of the aniline ring were synthesized and evaluated using two different receptor binding assays for measuring PPARγ affinity. Micro-positron emission tomography (PET) imaging studies were performed in a transgenic mouse model having a heart-specific overexpression of PPARγ. Results: All four analogs were found to have binding affinities that were comparable to or better than the reference antagonist, GW9662, using a scintillation proximity assay (SPA). However, only the chloro-based analogs (compounds 3 and 4) had activity in a whole-cell assay measuring activation of the PPARγ/retinoid X receptor complex. The microPET imaging studies in an MHC-PPARγ transgenic mouse model showed high uptake and PPARγ-specific binding for the irreversible antagonist [ 18F]3, whereas the corresponding reversible methoxy analog ([ 18F]5) displayed only nonspecific uptake in heart. Conclusions: The results of this preliminary study show that the irreversible antagonist [ 18F]3 may represent a novel strategy for imaging PPARγ in vivo with PET.

Original languageEnglish
Pages (from-to)77-87
Number of pages11
JournalNuclear Medicine and Biology
Issue number1
StatePublished - Jan 2012


  • Antagonist
  • Imaging agent
  • PPARγ
  • Peroxisome proliferator-activated receptor-γ


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