[11C]PK11195-PET Brain Imaging of the Mitochondrial Translocator Protein in Mitochondrial Disease

Author:

van den Ameele JelleORCID,Hong Young T.,Manavaki RoidoORCID,Kouli AntoninaORCID,Biggs Heather,MacIntyre Zoe,Horvath Rita,Yu-Wai-Man PatrickORCID,Reid Evan,Williams-Gray Caroline H.ORCID,Bullmore Ed T.ORCID,Aigbirhio Franklin I.ORCID,Fryer Tim D.,Chinnery Patrick F.

Abstract

ObjectiveTo explore the possibilities of radioligands against the mitochondrial outer membrane translocator protein (TSPO) as biomarkers for mitochondrial disease, we performed brain PET-MRI with [11C]PK11195 in 14 patients with genetically confirmed mitochondrial disease and 33 matched controls.MethodsCase–control study of brain PET-MRI with the TSPO radioligand [11C]PK11195.ResultsForty-six percent of symptomatic patients had volumes of abnormal radiotracer binding greater than the 95th percentile in controls. [11C]PK11195 binding was generally greater in gray matter and significantly decreased in white matter. This was most striking in patients with nuclear TYMP or mitochondrial m.3243A>G MT-TL1 mutations, in keeping with differences in mitochondrial density seen postmortem. Some regional binding patterns corresponded to clinical presentation and underlying mutation, even in the absence of structural changes on MRI. This was most obvious for the cerebellum, where patients with ataxia had decreased binding in the cerebellar cortex, but not necessarily volume loss. Overall, there was a positive correlation between aberrant [11C]PK11195 binding and clinical severity.ConclusionThese findings endorse the use of PET imaging with TSPO radioligands as a noninvasive in vivo biomarker of mitochondrial pathology.Classification of EvidenceThis study provides Class III evidence that brain PET-MRI with TSPO radioligands identifies mitochondrial pathology.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Neurology (clinical)

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3