A ketogenic diet lowers myocardial fatty acid oxidation but does not affect oxygen consumption: a study in overweight humans.

OBJECTIVE: A ketogenic diet (KD) characterized by very low carbohydrate intake and high fat consumption may simultaneously induce weight loss and be cardioprotective. The "thrifty substrate hypothesis" posits that ketone bodies are more energy efficient compared with other cardiac oxidative substrates such as fatty acids. This work aimed to study whether a KD with presumed increased myocardial ketone body utilization reduces cardiac fatty acid uptake and oxidation, resulting in decreased myocardial oxygen consumption (MVO2 ). METHODS: This randomized controlled crossover trial examined 11 individuals with overweight or obesity on two occasions: (1) after a KD and (2) after a standard diet. Myocardial free fatty acid (FFA) oxidation, uptake, and esterification rate were measured using dynamic [11 C]palmitate positron emission tomography (PET)/computed tomography, whereas MVO2 and myocardial external efficiency (MEE) were measured using dynamic [11 C]acetate PET. RESULTS: The KD increased plasma ß-hydroxybutyrate, reduced myocardial FFA oxidation (p < 0.01) and uptake (p = 0.03), and increased FFA esterification (p = 0.03). No changes were observed in MVO2 (p = 0.2) or MEE (p = 0.87). CONCLUSIONS: A KD significantly reduced myocardial FFA uptake and oxidation, presumably by increasing ketone body oxidation. However, this change in cardiac substrate utilization did not improve MVO2 , speaking against the thrifty substrate hypothesis.

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.

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]ß-hydroxybutyrate ([11C]OHB). Six healthy subjects (3 women and 3 men) underwent dynamic PET studies after both intravenous (90 min) and oral (120 min) 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 [Formula: see text]Sv/MBq (intravenous administration) and 12.51 [Formula: see text]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 shows promising potential in providing imaging data on ketone uptake in various physiologically relevant tissues. As a result, it may serve as a safe and non-invasive imaging tool for exploring ketone metabolism in organs and tissues of both patients and healthy individuals. Trial registration Clinical trials, NCT0523812, Registered February 10th 2022, https://clinicaltrials.gov/ct2/show/NCT05232812?cond=NCT05232812&draw=2&rank=1 .

Myocardial perfusion imaging by 15O-H2O positron emission tomography predicts clinical revascularization procedures in symptomatic patients with previous coronary artery bypass graft.

Aims: We wanted to assess if 15O-H2O myocardial perfusion imaging (MPI) in a clinical setting can predict referral to coronary artery catheterization [coronary angiography (CAG)], execution of percutaneous coronary intervention (PCI), and post-PCI angina relief for patients with angina and previous coronary artery bypass graft (CABG). Methods and results: We analysed 172 symptomatic CABG patients referred for 15O-H2O positron emission tomography (PET) MPI at Aarhus University Hospital Department of Nuclear Medicine & PET Centre, of which five did not complete the scan. In total, 145 (87%) enrolled patients had an abnormal MPI. Of these, 86/145 (59%) underwent CAG within 3 months; however, no PET parameters predicted referral to CAG. During the CAG, 25/86 (29%) patients were revascularized by PCI. Relative flow reserve (RFR) (0.49 vs. 0.54 P = 0.03), vessel-specific myocardial blood flow (MBF) (1.53 vs. 1.88 mL/g/min, P < 0.01), and vessel-specific myocardial flow reserve (MFR) (1.73 vs. 2.13, P < 0.01) were significantly lower in patients revascularized by PCI. Receiver operating characteristic analysis of the vessel-specific parameters yielded optimal cutoffs of 1.36 mL/g/min (MBF) and 1.28 (MFR) to predict PCI. Angina relief was experienced by 18/24 (75%) of the patients who underwent PCI. Myocardial blood flow was an excellent predictor of angina relief on both a global [area under the curve (AUC) = 0.85, P < 0.01] and vessel-specific (AUC = 0.90, P < 0.01) level with optimal cutoff levels of 1.99 mL/g/min and 1.85 mL/g/min, respectively. Conclusion: For CABG patients, RFR, vessel-specific MBF, and vessel-specific MFR measured by 15O-H2O PET MPI predict whether subsequent CAG will result in PCI. Additionally, global and vessel-specific MBF values predict post-PCI angina relief.

Clinical use of cardiac 18 F-FDG viability PET: a retrospective study of 44 patients undergoing post-test revascularization.

The coupling between coronary artery disease and the development of ischemic heart failure is well-established. For these patients, assessment of potentially viable but dysfunctional myocardial tissue (hibernation) is considered critical to guide optimal surgical treatment. Assessment with positron emission tomography (PET) theoretically provides measurements of hibernating tissue and maximal myocardial glucose uptake (MGU) in all cardiac territories. However, the clinical benefits of these measures are not thoroughly studied. We therefore aimed to investigate whether cardiac viability testing with combined Rubidium-82 (82Rb) and 18F-fluorodeoxyglucose (18F-FDG) predicts post-intervention improvement in left ventricle ejection fraction (LVEF) and survival. This retrospective study consisted of 131 patients with ischemic heart failure referred for dynamic 82Rb/18F-FDG PET viability testing prior to revascularization. The FDG viability scan was done during a hyperinsulinemic-euglycemic clamp and included PET measures static FDG hibernation and absolute MGU as well as myocardial blood flow and coronary flow reserve. In total, 44/131 patients undergoing viability testing were subsequently revascularized. Following revascularization, 26 patients had LVEF improvement of at least 5% while 18 patients had no improvement. A poor correlation between areas of intervention and areas of hibernation was observed. Receiver operating characteristics for all PET metrics did not predict improvement in LVEF. Furthermore, hibernation failed to predict survival regardless of whether patients underwent subsequent revascularization. Dynamic viability PET metrics (hibernation and MGU) do not predict post-intervention improvement in LVEF or overall survival in ischemic heart failure patients undergoing revascularization. In a clinical setting, the value of these measurements may therefore be limited. Kindly check and confirm the Given names and Family names for all the authors.All names are correct!

Early acquisition of [18F]FDOPA PET/CT imaging in patients with recurrent or residual medullary thyroid cancer is safe-and slightly better!

PURPOSE: The aim of this study was to compare early (15 min) and late (60 min) [18F]FDOPA PET/CT acquisition times in the detection of recurrence/residual disease in medullary thyroid cancer (MTC) patients. MATERIALS AND METHODS: Thirty-two dual-phase [18F]FDOPA PET scans were retrospectively reviewed. Scan indications were (1) suspected recurrence of MTC, (2) treatment monitoring, or (3) restaging. In four scans, no final verification could be obtained, and one scan was excluded due to non-consistency with the acquisition protocol. Images were analyzed visually and semiquantitatively (using SUVmax). On both per-scan and per-lesion basis, early (median time 15 min) and late (median time 60 min) acquisition were compared by number and SUVmax of detected MTC lesions, and a washout rate between the two acquisitions was calculated. Sensitivity and specificity of early and late acquisition were also compared. RESULTS: Out of the 27 eligible PET scans, twenty were classified as PET positive and 7 as PET negative. By subsequent histology and/or combination of imaging and clinical data during follow-up, the MTC diagnosis was verified, showing a scan-based sensitivity and specificity of 100% and 87.5%, respectively, for the early acquisition, and for the late acquisition both were 100%. However, there were no statistically significant difference in detection rate between the two acquisitions. Lesions on the early acquisition were significantly more intense compared to lesions on the late acquisition (median washout rate of - 33% (- 57 to + 50%)). CONCLUSION: Our study confirms that it is safe to omit the late [18F]FDOPA PET/CT acquisition in the detection of recurrent/residual MTC.