Structure dependence of long-chain [18F]fluorothia fatty acids as myocardial fatty acid oxidation probes

Mukesh K. Pandey, Anthony P. Belanger, Shuyan Wang, Timothy R. Degrado

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

In vivo imaging of regional fatty acid oxidation (FAO) rates would have considerable potential for evaluation of mammalian diseases. We have synthesized and evaluated 18F-labeled thia fatty acid analogues as metabolically trapped FAO probes to understand the effect of chain length, degree of unsaturation, and placement of the thia substituent on myocardial uptake and retention. 18-[18F]Fluoro-4-thia-(9Z)-octadec-9-enoic acid (3) showed excellent heart/background radioactivity concentration ratios along with highest retention in heart and liver. Pretreatment of rats with the CPT-1 inhibitor, POCA, caused >80% reduction in myocardial uptake of 16-[ 18F]fluoro-4-thiahexadecanoic acid (2) and 3, indicating high specificity for FAO. In contrast, 18-[18F]fluoro-4-thiaoctadecanoic acid (4) showed dramatically reduced myocardial uptake and blunted response to POCA. 18-[18F]Fluoro-6-thiaoctadecanoic acid (5) showed moderate myocardial uptake and no sensitivity of myocardial uptake to POCA. The results demonstrate relationships between structures of 18F-labeled thia fatty acid and uptake and their utility as FAO probes in various tissues.

Original languageEnglish (US)
Pages (from-to)10674-10684
Number of pages11
JournalJournal of Medicinal Chemistry
Volume55
Issue number23
DOIs
StatePublished - Dec 13 2012

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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