Using positron emission tomography to study human ketone body metabolism: A review Nadia Bouteldja c , Lone Thing Andersen a , Niels Møller b , Lars Christian Gormsen a, ⁎ a Department of Nuclear Medicine & PET Center, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark b Department of Endocrinology, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark c Department of Radiology, Hospital of Southwest Denmark, 6700 Esbjerg, Denmark ARTICLE INFO ABSTRACT Article history: Received 8 May 2014 Accepted 2 August 2014 Ketone bodies – 3-hydroxybutyrate and acetoacetate – are important fuel substrates, which can be oxidized by most tissues in the body. They are synthesized in the liver and are derived from fatty acids released from adipose tissue. Intriguingly, under conditions of stress such as fasting, arterio-venous catheterization studies have shown that the brain switches from the use of almost 100% glucose to the use of > 50–60% ketone bodies. A similar adaptive mechanism is observed in the heart, where fasting induces a shift toward ketone body uptake that provides the myocardium with an alternate fuel source and also favorably affects myocardial contractility. Within the past years there has been a renewed interest in ketone bodies and the possible beneficial effects of fasting/semi-fasting/exercising and other “ketogenic” regimens have received much attention. In this perspective, it is promising that positron emission tomography (PET) techniques with isotopically labeled ketone bodies, fatty acids and glucose offer an opportunity to study interactions between ketone body, fatty acid and glucose metabolism in tissues such as the brain and heart. PET scans are non-invasive and thus eliminates the need to place catheters in vascular territories not easily accessible. The short half-life of e.g. 11C-labeled PET tracers even allows multiple scans on the same study day and reduces the total radiation burden associated with the procedure. This short review aims to give an overview of current knowledge on ketone body metabolism obtained by PET studies and discusses the methodological challenges and perspectives involved in PET ketone body research. © 2014 Elsevier Inc. All rights reserved. Keywords: Ketone bodies PET Cardiac metabolism Fasting 1. Introduction Ketone bodies are produced by the liver when excess acetyl-CoA accumulates as a result of increased fatty acid oxidation and decreased glucose oxidation, and serve as important fuel sources during metabolic stress such as fasting and starvation. Ketogenesis is regulated by the supply of ketogenic precursors, primarily free fatty acids (FFAs), to the METABOLISM CLINICAL AND EXPERIMENTAL XX (2014) XXX – XXX Abbreviations: 3HBD, R-3HB dehydrogenase; AT, acetoacetyl thiolase; AcAc, acetoacetate; ATP, adenosine triphosphate; BBB, blood– brain barrier; CBF, cerebral blood flow; CMR, cerebral metabolic rate; CoA, coenzyme A; CPT1, carnithine pamitoyl transporter 1; FDG, fluorodeoxyglucose; FFA, free fatty acid; GLUT, glucose transporter; HMG-CoA, 3-hydroxy-3-methylglutaryl-coenzyme A; HL, HMG-CoA Lyase; LC, lumped constant; MCT, monocarboxylic acid transporter; mHS, mitochondrial HMG-CoA synthase; OHB, beta-hydroxybutyrate; PET, positron emission tomography; PDH, pyruvate dehydrogenase; SAT, succinylCoA:acetoacetate CoA transferase; SUV, standardized uptake value; TCA, tricarboxylic acid; T2, mitochondrial AcAcCoA thiolase. ⁎ Corresponding author. E-mail address: larsgorm@rm.dk (L.C. Gormsen). N.B., L.T.A., N.M. and L.C.G. have no disclosures. http://dx.doi.org/10.1016/j.metabol.2014.08.001 0026-0495/© 2014 Elsevier Inc. All rights reserved. Available online at www.sciencedirect.com Metabolism www.metabolismjournal.com Please cite this article as: Bouteldja N, et al, Using positron emission tomography to study human ketone body metabolism: A review, Metabolism (2014), http://dx.doi.org/10.1016/j.metabol.2014.08.001