Peroxisome proliferator-activated receptor alpha (PPAR-α) is a ligand-activated nuclear receptor transcription factor that regulates the fatty acid β-oxidation. An in vitro assay identified the p-methoxy phenyl ureido thiobutyric acid derivative KSM-01 (IC50 = 0.28 ± 0.09 nM) having a higher affinity to activate PPAR-α than the PPAR-α agonist GW7647 (IC50 = 0.46 ± 0.19 nM). In this study, we report the synthesis and initial in vivo evaluation of [11C]KSM-01. The radiosynthesis was carried out by first alkylating the corresponding p-phenol precursor with [11C]MeI in DMF using NaOH, followed by deprotection of the t-butyl ester group by TFA, yielding [11C]KSM-01. SUV analysis of dynamic micro PET/CT imaging data showed that [11C]KSM-01 accumulation was ∼2.0-fold greater in cardiac-specific PPAR-α overexpressing transgenic mice compared to wild-type littermates. The post-PET biodistribution studies were consistent with these results and demonstrated 2.5-fold greater radiotracer uptake in the heart of transgenic mice compared to the wild-type littermates. These results demonstrate the potential utility of PPAR-α agonists as PET radiopharmaceuticals.

Original languageEnglish
Pages (from-to)6233-6236
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Issue number19
StatePublished - Oct 1 2012


  • Cardiomyopathy
  • PET imaging
  • Peroxisome proliferator-activated receptor alpha (PPAR-α)
  • Ureido thioisobutyric acid (TiBA)
  • β-Oxidation


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