Imaging of amyloid deposition in human brain using positron emission tomography and [18F]FACT: comparison with [11C]PIB.
OBJECTIVE
The characteristic neuropathological changes in Alzheimer's disease (AD) are deposition of amyloid senile plaques and neurofibrillary tangles. The (18)F-labeled amyloid tracer, [(18)F]2-[(2-{(E)-2-[2-(dimethylamino)-1,3-thiazol-5-yl]vinyl}-1,3-benzoxazol-6-yl)oxy]-3-fluoropropan-1-ol (FACT), one of the benzoxazole derivatives, was recently developed. In the present study, deposition of amyloid senile plaques was measured by positron emission tomography (PET) with both [(11)C]Pittsburgh compound B (PIB) and [(18)F]FACT in the same subjects, and the regional uptakes of both radiotracers were directly compared.


METHODS
Two PET scans, one of each with [(11)C]PIB and [(18)F]FACT, were performed sequentially on six normal control subjects, two mild cognitive impairment (MCI) patients, and six AD patients. The standardized uptake value ratio of brain regions to the cerebellum was calculated with partial volume correction using magnetic resonance (MR) images to remove the effects of white matter accumulation.


RESULTS
No significant differences in the cerebral cortical uptake were observed between normal control subjects and AD patients in [(18)F]FACT studies without partial volume correction, while significant differences were observed in [(11)C]PIB. After partial volume correction, the cerebral cortical uptake was significantly larger in AD patients than in normal control subjects for [(18)F]FACT studies as well as [(11)C]PIB. Relatively lower uptakes of [(11)C]PIB in distribution were observed in the medial side of the temporal cortex and in the occipital cortex as compared with [(18)F]FACT. Relatively higher uptake of [(11)C]PIB in distribution was observed in the frontal and parietal cortices.


CONCLUSIONS
Since [(18)F]FACT might bind more preferentially to dense-cored amyloid deposition, regional differences in cerebral cortical uptake between [(11)C]PIB and [(18)F]FACT might be due to differences in regional distribution between diffuse and dense-cored amyloid plaque shown in the autoradiographic and histochemical assays of postmortem AD brain sections.
Hiroshi
H
Ito
Hitoshi
H
Shinotoh
Hitoshi
H
Shimada
Michie
M
Miyoshi
Kazuhiko
K
Yanai
Nobuyuki
N
Okamura
Harumasa
H
Takano
Hidehiko
H
Takahashi
Ryosuke
R
Arakawa
Fumitoshi
F
Kodaka
Maiko
M
Ono
Yoko
Y
Eguchi
Makoto
M
Higuchi
Toshimitsu
T
Fukumura
Tetsuya
T
Suhara
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000814:Aniline Compounds; D052160:Benzothiazoles / Q000493:pharmacokinetics; D001583:Benzoxazoles / Q000494:pharmacology; D001921:Brain / Q000000981:diagnostic imaging* / Q000473:pathology; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013844:Thiazoles / Q000494:pharmacology; D014018:Tissue Distribution
C000593009:2-((2-(2-(2-(dimethylamino)-1,3-thiazol-5-yl)vinyl)-1,3-benzoxazol-6-yl)oxy)-3-fluoropropan-1-ol; C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D001583:Benzoxazoles; D019275:Radiopharmaceuticals; D013844:Thiazoles