Intravenous and Oral Whole Body Ketone Dosimetry, Biodistribution, Metabolite Correction and Kinetics Studied by (R)-[1-11C]ß-Hydroxybutyrate ([11C]OHB) PET in Healthy Humans

Abstract

Abstract Background: Ketones are increasingly recognized as an important and possibly oxygen sparing source of energy in vital organs such as the heart, the brain and the kidneys. Drug treatments, dietary regimens and oral ketone drinks designed to deliver ketones for organ and tissue energy production have therefore gained popularity. However, whether ingested ketones are taken up by various extra-cerebral tissues and to what extent is still largely unexplored. It was therefore the aim of this study to use positron emission tomography (PET) to explore the whole body dosimetry, biodistribution and kinetics of the ketone tracer (R)-[1-11C]b-hydroxybutyrate ([11C]OHB). Six healthy subjects (3 women and 3 men) underwent dynamic PET studies after both intravenous (90 minutes) and oral (120 minutes) administration of [11C]OHB. Dosimetry estimates of [11C]OHB was calculated using OLINDA/EXM software, biodistribution was assessed visually and [11C]OHB tissue kinetics were obtained using an arterial input function and tissue time-activity curves. Results: Radiation dosimetry yielded effective doses of 3.28 Sv/MBq (intravenous administration) and 12.51 Sv/MBq (oral administration). Intravenous administration of [11C]OHB resulted in avid radiotracer uptake in the heart, liver, and kidneys, whereas lesser uptake was observed in the salivary glands, pancreas, skeletal muscle and red marrow. Only minimal uptake was noted in the brain. Oral ingestion of the tracer resulted in rapid radiotracer appearance in the blood and radiotracer uptake in the heart, liver and kidneys. In general, [11C]OHB tissue kinetics after intravenous administration were best described by a reversible 2-tissue compartmental model. Conclusion: The PET radiotracer [11C]OHB is highly suitable for imaging ketone uptake in all physiologically relevant tissues. It is therefore a safe and non-invasive imaging tool to investigate organ and tissue ketone metabolism in both patients and healthy subjects. Trial registration: Clinical trials, NCT0523812, Registered February 10th 2022, https://clinicaltrials.gov/ct2/show/NCT05232812?cond=NCT05232812&draw=2&rank=1.