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

Abstract

ObjectiveTo explore the possibilities of radioligands against the mitochondrial outer membrane protein TSPO as biomarkers for mitochondrial disease, we performed PET (PET)-MR brain imaging with [11C]PK11195 in 14 patients with genetically confirmed mitochondrial disease and 33 matched controls.MethodsA case-control study of PET-MR imaging 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 grey 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 post mortem. 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 non-invasive in vivo biomarker of mitochondrial pathology.Classification of evidenceThis study provides Class III evidence that PET-MR brain imaging with TSPO radioligands identifies mitochondrial pathology.

Mitochondria drive microglial NRLP3 inflammasome activation via TSPO

“…Previous results have endorsed the potential of TSPO as an in vivo biomarker of mitochondrial pathology for PET imaging [30]. To further validate TSPO as a viable pharmacological target to reduce pathological neuroinflammatory conditions, we tested the effect of a recently developed, highly specific TSPO ligand, namely 18 F- GE-180 (S-N, N-diethyl-9-[2-18F-fluoroethyl]-5-methoxy 2,3,4,9-tetrahydro-1H- carbazole-4-carboxamide).…”

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

“…In the article “[ 11 C]PK11195-PET Brain Imaging of the Mitochondrial Translocator Protein in Mitochondrial Disease” by van den Ameele et al, 1 panels E, H, K, and N of Figure 4 should be labeled “Patient < controls.” A corrected version of Figure 4 is available at links.lww.com/WNL/B478. The editorial staff regret the error.…”