In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson's disease.
Idiopathic Parkinson's disease (PD) is a neurodegenerative disorder associated with akinesia, tremor and rigidity. While the characteristic Lewy body pathology targets pigmented and other brainstem nuclei at post-mortem, activated microglia are found in both subcortical and cortical areas. [11C](R)-PK11195 is a positron emission tomography (PET) marker of peripheral benzodiazepine sites (PBBS), which are selectively expressed by activated microglia. We examined 18 PD patients clinically and with [11C](R)-PK11195 and [18F]-dopa PET. Compared to 11 normal controls, the PD patients showed significantly increased mean levels of [11C](R)-PK11195 binding in the pons, basal ganglia and frontal and temporal cortical regions. Eight PD patients were examined longitudinally, and their [11C](R)-PK11195 signal remained stable over 2 years. Levels of microglial activation did not correlate with clinical severity or putamen [18F]-dopa uptake. Our in vivo findings confirm that widespread microglial activation is associated with the pathological process in PD. The absence of significant longitudinal changes suggests that microglia are activated early in the disease process, and levels then remain relatively static, possibly driving the disease via cytokine release.
Gerhard
Alexander
A
MRC Clinical Sciences Centre and Division of Neuroscience, Faculty of Medicine, Imperial College, London, UK. alexander.gerhard@csc.mrc.ac.uk
Pavese
Nicola
N
Hotton
Gary
G
Turkheimer
Federico
F
Es
Meltem
M
Hammers
Alexander
A
Eggert
Karla
K
Oertel
Wolfgang
W
Banati
Richard B
RB
Brooks
David J
DJ
D000368:Aged; D001569:Benzodiazepines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003952:Diagnostic Imaging; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000378:metabolism*; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism*; D049268:Positron-Emission Tomography
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D001569:Benzodiazepines; C037850:PK 11195