Fluorine-18 labeled thia fatty acids for PET imaging of fatty acid oxidation in heart and cancer

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11 Scopus citations

Abstract

Myocardial fatty acid oxidation (FAO) imaging is a noninvasive technique that can measure FAO rates in tissues for research applications in animals and humans, as well as clinical applications in managing patients with metabolic disorders. FAO imaging has great potential in diagnosis and monitoring of patients with ischemic heart disease, cardiomyopathies, myocarditis, acute coronary syndrome, and heart failure. Applications of FAO imaging in oncology and endocrinology are also highly anticipated. For over 20 years, our laboratory has investigated fluorine-18 labeled thia-substituted fatty acid analogs as positron emission tomography (PET) probes of myocardial FAO. These FAO probes share a common design motif of metabolic trapping in the myocardium subsequent to their commitment to the mitochondrial FAO pathway, in analogy to the design of 2-[18F]fluoro-2-deoxy-D-glucose (FDG) as a metabolically trapped probe of glucose transport and phosphorylation. This mini-review describes the development of these FAO probes, from the seminal 6-thia substituted analog, 14-[18F]fluoro-6-thia-heptadecanoate (FTHA), to the most recently developed oleate-based FAO analog, 18-[18F]fluoro-4-thia-oleate (FTO). It is shown that small changes in thia fatty acid analog structure can exert profound differences in the biodisposition and specificity of these probes to indicate myocardial FAO, particularly in conditions of oxygen deprivation. The potential of these probes for imaging of FAO in cancer is supported by initial uptake studies in cultured cancer cells. Thus, 18F-labeled thia fatty acid analogs have significant potential to play an important role as clinical PET probes of FAO in cardiovascular diseases, oncology, and future anticipated applications in endocrinology and neurology.

Original languageEnglish (US)
Pages (from-to)15-19
Number of pages5
JournalHeart and Metabolism
Issue number51
StatePublished - Dec 12 2011

Keywords

  • FTHA
  • FTO
  • FTP
  • Fatty acid oxidation
  • PET
  • Thia fatty acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

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