[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。

IF 3.6 4区医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Nuclear medicine and biology Pub Date : 2024-11-01 DOI:10.1016/j.nucmedbio.2024.108967

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}

引用次数: 0

摘要

背景：利用正电子发射断层扫描（PET）和放射性同位素[11C]乙酰乙酸酯和[11C]β-羟丁酸对酮代谢进行了研究。然而，这两种放射性核素是否能实际得出大脑和心肌酮体代谢的等效估计值尚未进行研究。本研究旨在调查和比较健康大鼠在不同水平的循环酮基线和单剂量外源性酮酯（KE）补充后大脑和心脏中这两种示踪剂的动力学：六只健康的 Sprague-Dawley 大鼠分别接受了两次示踪剂扫描：一次是在口服 KE 之后，另一次是在口服安慰剂之后。大脑动力学参数（Ki、VT 和大脑代谢率 (CMR)）采用 Patlak 方法获得，而心肌动力学参数（K1、k2 和 VT）则采用 1 组织分区模型获得。通过混合效应分析、相关分析和 Bland-Altman 分析对参数进行比较：结果：与安慰剂相比，KE 组的整体 CMR 增加了 3-4 倍，两种示踪剂的 CMR 与血浆酮体水平之间均存在很强的正相关性。[11C]乙酰乙酸酯和[11C]β-羟基丁酸之间的相关性为中等，在以 Ki 表示的相对脑摄取量（ρ = 0.40）和 VT（ρ = 0.38）方面不显著，但在绝对摄取量 CMR 方面呈强正相关（r = 0.84），平均偏差为-0.03，不显著。与此相反，心肌动力学显示放射性同位素（K1 (r = 0.04)、k2 (r = -0.27) 和 VT (ρ = 0.43)）之间只有非显著的弱到中等程度的相关性，没有系统性偏差：结论：[11C]乙酰乙酸盐和[11C]β-羟基丁酸盐可互换用于测量健康大鼠的整体 CMR，但在某些大脑和心肌动力学方面存在差异。这些发现是否可用于病理情况，还有待进一步研究，以探索这些示踪剂在疾病模型中的动力学。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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

查看原文本刊更多论文

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 (K_i, V_T, and cerebral metabolic rate (CMR)) were obtained using the Patlak method, whereas myocardial kinetic parameters (K₁, k₂, 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 [¹¹C]acetoacetate and [¹¹C]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 (K₁ (r = 0.04), k₂ (r = −0.27), and V_T (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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Nuclear medicine and biology 医学-核医学

CiteScore

6.00

自引率

9.70%

发文量

479

审稿时长

51 days

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.