Assessment of Fatty Acid Uptake by PET/MRI Imaging Under Fasting and Postprandial Conditions-A Repeatability Study in People with T2DM and Obesity

Background: Changes in fatty acid metabolism are an important component of the pathogenesis of type 2 diabetes mellitus (T2DM). Fatty acid uptake in tissues can be measured with positron emission tomography (PET) imaging, employing the fatty acid analogue 18F-FTHA radiotracer. We aimed to evaluate the repeatability of assessments of fatty acid uptake in tissues with a new whole-body PET/MRI (magnetic resonance) imaging method in people with obesity with or without T2DM. Methods: 17 completers underwent 4 repeated examinations under standardised conditions, twice under fasting and twice postprandially (PP). Tissue-specific fatty acid uptake (FAU) and uptake rate was measured using 18F-FTHA and dynamic whole-body PET/MRI in skeletal muscle, subcutaneous and visceral adipose tissues (SAT, VAT), myocardium and brain. Free fatty acid levels were measured over time. The repeatability of PET measurements under fasting, and under PP, was assessed by calculating the intraclass correlation coefficient (ICC 2,1) along with its 95 % confidence intervals; ICC ≥ 0.75 indicates excellent, 0.6 - 0.74 good, 0.4 - 0.59 fair and <0.4 poor reliability. Results: In the fasted state, repeatability of the net uptake rate in muscle tissue was found to be excellent, ICC 0.91 (0.78 - 0.96) and good in myocardium, ICC 0.64 (0.27-0.86). Repeatability of FAU in other tissues was at least fair (ICC SAT 0.80 (0.54-0.91), VAT 0.64 (0.27-0.85), brain 0.75 (0.46-0.90). In the PP experiments, variability increased especially for the FAU estimates, but the repeatability of the uptake rate was acceptable (ICC >0.4) for most investigated tissues, and good for muscle (ICC 0.73 (0.42-0.89). Conclusion: 18F-FTHA-PET/MRI provides information on tissue-specific fatty acid uptake with good reliability, and excellent repeatability for the muscle under fasting. The method has potential to provide insights in monitoring and evaluating treatment effects in interventional trials. Disclosure I.Laitinen: Employee; Antaros Medical. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Z.Milicevic: Employee; Eli Lilly and Company. L.Johansson: Employee; Antaros Medical, Stock/Shareholder; Antaros Medical. P.Nuutila: None. S.Ekström: Employee; Antaros Medical. H.Haraldsson: Employee; Antaros Medical. S.Pierrou: Stock/Shareholder; AstraZeneca. K.Kalliokoski: Consultant; Synektik S.A., Stock/Shareholder; Faron Pharmaceuticals Oy, CRST Oy. M.Kiugel: None. M.Scheinin: Consultant; Orion Pharma, Employee; Clinical Research Services Turku - CRST Oy, Other Relationship; Antaros Medical AB, Biogen, Boehringer Ingelheim International GmbH, Falk GmbH and Co Kg, Imbria, Novartis AG, Novo Nordisk A/S, Provention Bio, Inc., Stock/Shareholder; Clinical Research Services Turku - CRST Oy. S.Southekal: Employee; Eli Lilly and Company. M.Lu: None.