Data from: 11C-PK11195-PET brain imaging of the mitochondrial translocator protein in mitochondrial disease

Objective: To explore the possibilities of radioligands against the
mitochondrial outer membrane protein TSPO as biomarkers for mitochondrial
disease, we performed positron emission tomography (PET)-MR brain imaging
with [11C]PK11195 in 14 patients with genetically confirmed mitochondrial
disease and 33 matched controls.   
Methods: A case-control study of PET-MR imaging with the TSPO
radioligand [11C]PK11195.  Results: 46% 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.  Conclusion: These findings endorse the use of PET
imaging with TSPO radioligands as a non-invasive in
vivo biomarker of mitochondrial pathology. Classification of
Evidence: This study provides Class III evidence that PET-MR
brain imaging with TSPO radioligands identifies mitochondrial pathology.