Cerebral and myocardial kinetics of [ 11 C]acetoacetate and [ 11 C]β-hydroxybutyrate: A comparative crossover study in healthy rats.

Autor: Kjærulff MLG; Department of Clinical Medicine - Nuclear Medicine & PET, Aarhus University, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark; Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Denmark. Electronic address: metkju@clin.au.dk., Luong TV; Department of Clinical Medicine - Nuclear Medicine & PET, Aarhus University, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark; Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Denmark., Richard G; Centre d'imagerie Moléculaire de Sherbrooke, Sherbrooke, Québec, Canada; Centre de Recherche du CHUS, Sherbrooke, Québec, Canada., St-Pierre V; Department of Medicine and Research Center on Aging, Université de Sherbrooke, Sherbrooke, Québec, Canada., Søndergaard E; Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark; Department of Clinical Medicine - Medical/Steno Aarhus Research Laboratory, Aarhus University, Denmark., Møller N; Department of Clinical Medicine - Medical/Steno Aarhus Research Laboratory, Aarhus University, Denmark; Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark., Gormsen LC; Department of Clinical Medicine - Nuclear Medicine & PET, Aarhus University, Denmark; Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Denmark., Tremblay S; Centre d'imagerie Moléculaire de Sherbrooke, Sherbrooke, Québec, Canada; Centre de Recherche du CHUS, Sherbrooke, Québec, Canada., Croteau E; Centre d'imagerie Moléculaire de Sherbrooke, Sherbrooke, Québec, Canada; Centre de Recherche du CHUS, Sherbrooke, Québec, Canada., Cunnane SC; Department of Medicine and Research Center on Aging, Université de Sherbrooke, Sherbrooke, Québec, Canada.
Jazyk: angličtina
Zdroj: Nuclear medicine and biology [Nucl Med Biol] 2024 Nov-Dec; Vol. 138-139, pp. 108967. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.nucmedbio.2024.108967
Abstrakt: Background: Ketone metabolism has been studied using positron emission tomography (PET) with the radiotracers [ 11 C]acetoacetate and [ 11 C]β-hydroxybutyrate. However, whether these two radiotracers actually yield equivalent estimates of cerebral and myocardial ketone metabolism has not yet been investigated. This study aimed to investigate and compare the kinetics of both tracers in the brain and heart of healthy rats under varying levels of circulating ketones at baseline and after a single-dose exogenous ketone ester (KE) supplement.
Methods: Six healthy Sprague-Dawley rats each underwent two scans with each tracer: one following oral KE administration and one with a placebo. Cerebral kinetic parameters (K i , V T , and cerebral metabolic rate (CMR)) were obtained using the Patlak method, whereas myocardial kinetic parameters (K 1 , k 2 , and V T ) were derived using a 1-tissue compartment model. Parameters were compared through mixed-effects, correlation, and Bland-Altman analyses.
Results: Global CMR increased 3-4-fold in the KE group versus placebo, with strong positive correlations between CMR and plasma ketone levels for both tracers. Correlations between [ 11 C]acetoacetate and [ 11 C]β-hydroxybutyrate were moderate and non-significant for relative cerebral uptake expressed as K i (ρ = 0.40) and for V T (ρ = 0.38) but strongly positive for absolute uptake, CMR (r = 0.84), with a non-significant mean bias of -0.03. In contrast, myocardial kinetics showed only non-significant weak to moderate correlations between the radiotracers (K 1 (r = 0.04), k 2 (r = -0.27), and V T (ρ = 0.43)), with no systematic biases.
Conclusion: [ 11 C]acetoacetate and [ 11 C]β-hydroxybutyrate can be used interchangeably for measuring global CMR in healthy rats but differ in certain cerebral and myocardial kinetics. Whether these findings are generalizable to pathological conditions warrants further studies to explore the kinetics of these tracers in disease models.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stephen C. Cunnane consults for Nestlé Health Science and Cerecin. He has received financial support and materials for research from Nestlé Health Science. His research has also been funded by the Alzheimer Association USA. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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