| Summary: | The world-wide high incidence of non-alcoholic fatty liver disease (NAFLD) is of concern for its progression to insulin resistance, steatohepatitis and cardiovascular disease (CVD). The increased uptake of fatty acids in critical organs plays a major role in NAFLD progression. Male <i>Ceacam1<sup>−/−</sup></i> mice that develop NAFLD, insulin resistance and CVD on normal chow are a potential model for studying the dysregulation of fatty acid uptake. [<sup>18</sup>F]fluoro-4-thia-oleate ([<sup>18</sup>F]FTO) was chosen as a fatty acid reporter because of its higher uptake and retention in the heart in an animal model of CVD. Male wild-type (WT) or <i>Ceacam1<sup>−/−</sup></i> mice fasted 4–6 h were administered [<sup>18</sup>F]FTO i.v., and dynamic PET scans were conducted in an MR/PET small animal imaging system along with terminal tissue biodistributions. Quantitative heart image analysis revealed significantly higher uptake at 35 min in <i>Ceacam1<sup>−/</sup><sup>−</sup></i> (6.0 ± 1.0% ID/cc) vs. WT (3.9 ± 0.6% ID/cc) mice (<i>p</i> = 0.006). Ex vivo heart uptake/retention (% ID/organ) was 2.82 ± 0.45 for <i>Ceacam1<sup>−/</sup><sup>−</sup></i> mice vs. 1.66 ± 0.45 for WT mice (<i>p</i> < 0.01). Higher kidney and pancreas uptake/retention in <i>Ceacam1<sup>−/</sup><sup>−</sup></i> was also evident, and the excretion of [<sup>18</sup>F]FTO into the duodenum was observed for both WT and <i>Ceacam1<sup>−/</sup><sup>−</sup></i> mice starting at 10 min. This study suggests that the administration of [<sup>18</sup>F]FTO as a marker of fatty acid uptake and retention may be an important tool in analyzing the effect of NAFLD on lipid dysregulation in the heart.
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