In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive supranuclear palsy.
Progressive supranuclear palsy (PSP) is a neurodegenerative disease presenting with voluntary gaze difficulties, early falls, and Parkinsonism. Neuronal loss, associated with intracellular neurofibrillary tangles and activated microglia, is found targeting the basal ganglia, brainstem nuclei, and frontal cortex. [11C](R)-PK11195 PET is a marker of peripheral benzodiazepine binding sites (PBBS) expressed by activated microglia. We have used [11C](R)-PK11195 PET to demonstrate in vivo the degree and distribution of the glial response to the degenerative process in four patients with PSP. Compared to normal age-matched controls, the PSP patient group showed significantly increased mean [11C](R)-PK11195 binding in the basal ganglia, midbrain, the frontal lobe, and the cerebellum. Two of the patients were rescanned after 6 to 10 months and during that time the level of microglial activation remained stable. [11C](R)-PK11195 PET reveals a pattern of increased microglial activation in PSP patients involving cortical and subcortical regions that corresponds well with the known distribution of neuropathological changes. [11C](R)-PK11195 PET, therefore, may help in characterizing in vivo the underlying disease activity in PSP.
Gerhard
Alexander
A
MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, and National Hospital for Neurology and Neurosurgery, London, United Kingdom. alexander.gerhard@csc.mrc.ac.uk
Trender-Gerhard
Iris
I
Turkheimer
Federico
F
Quinn
Niall P
NP
Bhatia
Kailash P
KP
Brooks
David J
DJ
D000368:Aged; D001479:Basal Ganglia / Q000000981:diagnostic imaging / Q000503:physiopathology; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000503:physiopathology; D002250:Carbon Radioisotopes; D016923:Cell Death / Q000502:physiology; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007546:Isoquinolines; D008279:Magnetic Resonance Imaging; D008297:Male; D017628:Microglia / Q000000981:diagnostic imaging* / Q000502:physiology; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000000981:diagnostic imaging / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D011877:Radionuclide Imaging; D011963:Receptors, GABA-A / Q000502:physiology; D012016:Reference Values; D013237:Stereoisomerism; D013494:Supranuclear Palsy, Progressive / Q000000981:diagnostic imaging* / Q000503:physiopathology
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; C037850:PK 11195