[11C]PK11195-PET brain imaging of the mitochondrial translocator protein in mitochondrial disease

Jelle van den Ameele, Young Hong, Roido Manavaki, Antonina Kouli, Heather Biggs, Zoe MacIntyre, Rita Horvath, Patrick Yu-Wai-Man, Evan Reid, Caroline H. Williams-Gray, Ed T. Bullmore, Franklin I. Aigbirhio, Tim D. Fryer, Patrick F. Chinnery. [11C]PK11195-PET Brain Imaging of the Mitochondrial Translocator Protein in Mitochondrial Disease Neurology Jun 2021, 96 (22) e2761-e2773; DOI: 10.1212/WNL.0000000000012033 

Abstract

Objective 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 [11C]PK11195 in 14 patients with genetically confirmed mitochondrial disease and 33 matched controls. 

Methods Case–control study of brain PET-MRI with the TSPO radioligand [11C]PK11195. 

Results Forty-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. 

Conclusion These findings endorse the use of PET imaging with TSPO radioligands as a noninvasive in vivo biomarker of mitochondrial pathology. 

Classification of Evidence This study provides Class III evidence that brain PET-MRI with TSPO radioligands identifies mitochondrial pathology.