In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration.
Corticobasal degeneration (CBD) is a neurodegenerative parkinsonian disorder of unknown cause that shows considerable clinical heterogeneity. In CBD, activated microglia have been shown to be associated closely with the extensive tau pathology found in the affected basal ganglia, brainstem nuclei, and cortical regions. We report on the use of [(11)C](R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) (PK11195) positron emission tomography (PET), a marker of peripheral benzodiazepine binding sites (PBBS) that are expressed by activated microglia, to demonstrate in vivo the degree and distribution of glial response to the degenerative process in 4 patients with CBD. Compared with normal age-matched controls, the CBD patient group showed significantly increased mean [(11)C](R)-PK11195 binding in the caudate nucleus, putamen, substantia nigra, pons, pre- and postcentral gyrus, and the frontal lobe. [11C](R)-PK11195 PET reveals a pattern of increased microglial activation in CBD patients involving cortical regions and the basal ganglia that corresponds well with the known distribution of neuropathological changes, which may therefore help to characterize in vivo the underlying disease activity in CBD.
Gerhard
Alexander
A
MRC Clinical Sciences Center and Division of Neuroscience, Faculty of Medicine, Imperial College, London, United Kingdom. alexander.gerhard@csc.mrc.ac.uk
Watts
Justin
J
Trender-Gerhard
Iris
I
Turkheimer
Federico
F
Banati
Richard B
RB
Bhatia
Kailash
K
Brooks
David J
DJ
D000368:Aged; D001479:Basal Ganglia / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D002540:Cerebral Cortex / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D006801:Humans; D007546:Isoquinolines; D008297:Male; D017628:Microglia / Q000000981:diagnostic imaging* / Q000473:pathology*; D008875:Middle Aged; D009410:Nerve Degeneration / Q000000981:diagnostic imaging* / Q000473:pathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
D007546:Isoquinolines; D019275:Radiopharmaceuticals; C037850:PK 11195