PET of peripheral benzodiazepine binding sites in the microgliosis of Alzheimer's disease.
Animal and human autoradiographic studies have shown increased in vitro binding of the peripheral benzodiazepine binding site antagonist PK 11195 in areas of microgliosis, including the temporal association cortex of patients with Alzheimer's disease. To further elucidate the role of cellular inflammation and microgliosis in Alzheimer's disease during life, we used PET and [11C]PK 11195, a peripheral benzodiazepine receptor ligand known to bind avidly to microglia.


METHODS
Eight patients with a diagnosis of probable Alzheimer's disease underwent PET of the brain using [11C]PK 11195 and, for comparison, with [18F]FDG to determine cerebral glucose metabolism. Uptake of [11C]PK 11195 in various brain regions was expressed relative to that in the cerebellum and compared to values determined in one normal elderly subject and in clinically and anatomically unaffected hemispheres of seven patients with small unilateral gliomas.


RESULTS
No increases in peripheral benzodiazepine binding were identified in patients with probable Alzheimer's disease, and binding was lowest in regions that were most hypometabolic.


CONCLUSIONS
The peripheral benzodiazepine binding sites associated with microgliosis and cellular inflammation in Alzheimer's disease at postmortem are undetectable by PET using [11C]PK 11195 in patients with mild-to-moderate dementia.
Groom
G N
GN
Division of Nuclear Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028, USA.
Junck
L
L
Foster
N L
NL
Frey
K A
KA
Kuhl
D E
DE
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D003847:Deoxyglucose / Q000031:analogs & derivatives; D005260:Female; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007546:Isoquinolines; D008297:Male; D017628:Microglia / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011963:Receptors, GABA-A / Q000032:analysis*; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D007546:Isoquinolines; D011963:Receptors, GABA-A; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; C037850:PK 11195