van den Ameele Jelle, Hong Young T, Manavaki Roido, Kouli Antonina, Biggs Heather, MacIntyre Zoe, Horvath Rita, Yu-Wai-Man Patrick, Reid Evan, Williams-Gray Caroline H, Bullmore Ed T, Aigbirhio Franklin I, Fryer Tim D, Chinnery Patrick F
From the Departments of Clinical Neurosciences (J.v.d.A., Y.T.H., A.K., H.B., Z.M., R.H., P.Y.-W.M., C.H.W.-G., F.I.A., T.D.F., P.F.C.), Radiology (R.M.), Medical Genetics (E.R.), and Psychiatry (E.T.B.), Cambridge Institute for Medical Research (E.R.), Cambridge Biomedical Campus, and MRC Mitochondrial Biology Unit (J.v.d.A., P.F.C.), University of Cambridge; Moorfields Eye Hospital NHS Foundation Trust (P.Y.-W.M.); and Institute of Ophthalmology (P.Y.-W.M.), University College London, UK.
Neurology. 2021 May 31;96(22):e2761-e2773. doi: 10.1212/WNL.0000000000012033.
To explore the possibilities of radioligands against the mitochondrial outer membrane translocator protein (TSPO) as biomarkers for mitochondrial disease, we performed brain PET-MRI with [C]PK11195 in 14 patients with genetically confirmed mitochondrial disease and 33 matched controls.
Case-control study of brain PET-MRI with the TSPO radioligand [C]PK11195.
Forty-six percent of symptomatic patients had volumes of abnormal radiotracer binding greater than the 95th percentile in controls. [C]PK11195 binding was generally greater in gray matter and significantly decreased in white matter. This was most striking in patients with nuclear or mitochondrial m.3243A>G 1 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 [C]PK11195 binding and clinical severity.
These findings endorse the use of PET imaging with TSPO radioligands as a noninvasive in vivo biomarker of mitochondrial pathology.
This study provides Class III evidence that brain PET-MRI with TSPO radioligands identifies mitochondrial pathology.
为了探索针对线粒体外膜转位蛋白（TSPO）的放射性配体作为线粒体疾病生物标志物的可能性，我们对14例经基因确诊的线粒体疾病患者和33例匹配的对照者进行了[C]PK11195脑PET-MRI检查。
采用TSPO放射性配体[C]PK11195进行脑PET-MRI的病例对照研究。
46%有症状的患者放射性示踪剂异常结合体积大于对照者的第95百分位数。[C]PK11195结合在灰质中通常更高，在白质中显著降低。这在核或线粒体m.3243A>G 1突变患者中最为明显，与死后观察到的线粒体密度差异一致。即使在MRI上没有结构变化的情况下，一些区域结合模式也与临床表现和潜在突变相对应。这在小脑最为明显，共济失调患者小脑皮质结合减少，但不一定有体积损失。总体而言，异常的[C]PK11195结合与临床严重程度呈正相关。
这些发现支持使用TSPO放射性配体进行PET成像作为线粒体病理学的非侵入性体内生物标志物。
本研究提供了III类证据，即使用TSPO放射性配体的脑PET-MRI可识别线粒体病理学。
