Mette Louise Gram Kjærulff , Thien Vinh Luong , Gabriel Richard , Valérie St-Pierre , Esben Søndergaard , Niels Møller , Lars Christian Gormsen , Sébastien Tremblay , Etienne Croteau , Stephen C. Cunnane
{"title":"[11C]乙酰乙酸酯和[11C]β-羟丁酸的大脑和心肌动力学：健康大鼠的交叉对比研究。","authors":"Mette Louise Gram Kjærulff , Thien Vinh Luong , Gabriel Richard , Valérie St-Pierre , Esben Søndergaard , Niels Møller , Lars Christian Gormsen , Sébastien Tremblay , Etienne Croteau , Stephen C. Cunnane","doi":"10.1016/j.nucmedbio.2024.108967","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Ketone metabolism has been studied using positron emission tomography (PET) with the radiotracers [<sup>11</sup>C]acetoacetate and [<sup>11</sup>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.</div></div><div><h3>Methods</h3><div>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 (<em>K</em><sub>i</sub>, <em>V</em><sub>T</sub>, and cerebral metabolic rate (CMR)) were obtained using the Patlak method, whereas myocardial kinetic parameters (<em>K</em><sub>1</sub>, <em>k</em><sub>2</sub>, and <em>V</em><sub>T</sub>) were derived using a 1-tissue compartment model. Parameters were compared through mixed-effects, correlation, and Bland-Altman analyses.</div></div><div><h3>Results</h3><div>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 [<sup>11</sup>C]acetoacetate and [<sup>11</sup>C]β-hydroxybutyrate were moderate and non-significant for relative cerebral uptake expressed as <em>K</em><sub>i</sub> (ρ = 0.40) and for <em>V</em><sub>T</sub> (ρ = 0.38) but strongly positive for absolute uptake, CMR (<em>r</em> = 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 (<em>K</em><sub>1</sub> (<em>r</em> = 0.04), <em>k</em><sub>2</sub> (<em>r</em> = −0.27), and <em>V</em><sub>T</sub> (ρ = 0.43)), with no systematic biases.</div></div><div><h3>Conclusion</h3><div>[<sup>11</sup>C]acetoacetate and [<sup>11</sup>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.</div></div>","PeriodicalId":19363,"journal":{"name":"Nuclear medicine and biology","volume":"138 ","pages":"Article 108967"},"PeriodicalIF":3.6000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cerebral and myocardial kinetics of [11C]acetoacetate and [11C]β-hydroxybutyrate: A comparative crossover study in healthy rats\",\"authors\":\"Mette Louise Gram Kjærulff , Thien Vinh Luong , Gabriel Richard , Valérie St-Pierre , Esben Søndergaard , Niels Møller , Lars Christian Gormsen , Sébastien Tremblay , Etienne Croteau , Stephen C. Cunnane\",\"doi\":\"10.1016/j.nucmedbio.2024.108967\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Ketone metabolism has been studied using positron emission tomography (PET) with the radiotracers [<sup>11</sup>C]acetoacetate and [<sup>11</sup>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.</div></div><div><h3>Methods</h3><div>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 (<em>K</em><sub>i</sub>, <em>V</em><sub>T</sub>, and cerebral metabolic rate (CMR)) were obtained using the Patlak method, whereas myocardial kinetic parameters (<em>K</em><sub>1</sub>, <em>k</em><sub>2</sub>, and <em>V</em><sub>T</sub>) were derived using a 1-tissue compartment model. Parameters were compared through mixed-effects, correlation, and Bland-Altman analyses.</div></div><div><h3>Results</h3><div>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 [<sup>11</sup>C]acetoacetate and [<sup>11</sup>C]β-hydroxybutyrate were moderate and non-significant for relative cerebral uptake expressed as <em>K</em><sub>i</sub> (ρ = 0.40) and for <em>V</em><sub>T</sub> (ρ = 0.38) but strongly positive for absolute uptake, CMR (<em>r</em> = 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 (<em>K</em><sub>1</sub> (<em>r</em> = 0.04), <em>k</em><sub>2</sub> (<em>r</em> = −0.27), and <em>V</em><sub>T</sub> (ρ = 0.43)), with no systematic biases.</div></div><div><h3>Conclusion</h3><div>[<sup>11</sup>C]acetoacetate and [<sup>11</sup>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.</div></div>\",\"PeriodicalId\":19363,\"journal\":{\"name\":\"Nuclear medicine and biology\",\"volume\":\"138 \",\"pages\":\"Article 108967\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nuclear medicine and biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0969805124000933\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nuclear medicine and biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969805124000933","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
Cerebral and myocardial kinetics of [11C]acetoacetate and [11C]β-hydroxybutyrate: A comparative crossover study in healthy rats
Background
Ketone metabolism has been studied using positron emission tomography (PET) with the radiotracers [11C]acetoacetate and [11C]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 (Ki, VT, and cerebral metabolic rate (CMR)) were obtained using the Patlak method, whereas myocardial kinetic parameters (K1, k2, and VT) 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 [11C]acetoacetate and [11C]β-hydroxybutyrate were moderate and non-significant for relative cerebral uptake expressed as Ki (ρ = 0.40) and for VT (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 (K1 (r = 0.04), k2 (r = −0.27), and VT (ρ = 0.43)), with no systematic biases.
Conclusion
[11C]acetoacetate and [11C]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.
期刊介绍：
Nuclear Medicine and Biology publishes original research addressing all aspects of radiopharmaceutical science: synthesis, in vitro and ex vivo studies, in vivo biodistribution by dissection or imaging, radiopharmacology, radiopharmacy, and translational clinical studies of new targeted radiotracers. The importance of the target to an unmet clinical need should be the first consideration. If the synthesis of a new radiopharmaceutical is submitted without in vitro or in vivo data, then the uniqueness of the chemistry must be emphasized.
These multidisciplinary studies should validate the mechanism of localization whether the probe is based on binding to a receptor, enzyme, tumor antigen, or another well-defined target. The studies should be aimed at evaluating how the chemical and radiopharmaceutical properties affect pharmacokinetics, pharmacodynamics, or therapeutic efficacy. Ideally, the study would address the sensitivity of the probe to changes in disease or treatment, although studies validating mechanism alone are acceptable. Radiopharmacy practice, addressing the issues of preparation, automation, quality control, dispensing, and regulations applicable to qualification and administration of radiopharmaceuticals to humans, is an important aspect of the developmental process, but only if the study has a significant impact on the field.
Contributions on the subject of therapeutic radiopharmaceuticals also are appropriate provided that the specificity of labeled compound localization and therapeutic effect have been addressed.
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