18-[F]Fluoro-4-thia-oleate

β-Oxidation of long-chain fatty acids is the major (60%–80%) aerobic process for energy production in the heart, liver, and skeletal muscle. Abnormalities of fatty acid oxidation (FAO) are associated with several cardiovascular diseases, neurodegeneration, fatty liver, and diabetes (1-5). Myocardium has a high mitochondrial content because of high energy usage. Carnitine palmitoyltransferases (CPT1 and CPT2) mediate transfer of fatty acids into the mitochondrial matrix for β-oxidation (6, 7). Various radiolabeled, thia-substituted, fatty acid analogs have been found to be metabolically trapped in the myocardial mitochondria (8-10). 4-Thia fatty acids are oxidized in the mitochondria to 4-thia-enoyl-CoAs, which cannot be further metabolized and trapped (protein-bound) in the mitochondria. Oleate (18:1) is preferentially oxidized relative to palmitate (16:0) and stearate (18:0) by the mitochondrial FAO (11). DeGrado et al. (12) have synthesized 18-[F]fluoro-4-thia-oleate ([F]FTO) for evaluation as a positron emission tomography (PET) agent of FAO.