In vivo detection of prion amyloid plaques using [(11)C]BF-227 PET.
OBJECTIVE
In vivo detection of pathological prion protein (PrP) in the brain is potentially useful for the diagnosis of transmissible spongiform encephalopathies (TSEs). However, there are no non-invasive ante-mortem means for detection of pathological PrP deposition in the brain. The purpose of this study is to evaluate the amyloid imaging tracer BF-227 with positron emission tomography (PET) for the non-invasive detection of PrP amyloid in the brain.


METHODS
The binding ability of BF-227 to PrP amyloid was investigated using autoradiography and fluorescence microscopy. Five patients with TSEs, including three patients with Gerstmann-Sträussler-Scheinker disease (GSS) and two patients with sporadic Creutzfeldt-Jakob disease (CJD), underwent [(11)C]BF-227 PET scans. Results were compared with data from 10 normal controls and 17 patients with Alzheimer's disease (AD). The regional to pons standardized uptake value ratio was calculated as an index of BF-227 retention.


RESULTS
Binding of BF-227 to PrP plaques was confirmed using brain samples from autopsy-confirmed GSS cases. In clinical PET study, significantly higher retention of BF-227 was detected in the cerebellum, thalamus and lateral temporal cortex of GSS patients compared to that in the corresponding tissues of normal controls. GSS patients also showed higher retention of BF-227 in the cerebellum, thalamus and medial temporal cortex compared to AD patients. In contrast, the two CJD patients showed no obvious retention of BF-227 in the brain.


CONCLUSIONS
Although [(11)C]BF-227 is a non-specific imaging marker of cerebral amyloidosis, it is useful for in vivo detection of PrP plaques in the human brain in GSS, based on the regional distribution of the tracer. PET amyloid imaging might provide a means for both early diagnosis and non-invasive disease monitoring of certain forms of TSEs.
Okamura
Nobuyuki
N
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Shiga
Yusei
Y
Furumoto
Shozo
S
Tashiro
Manabu
M
Tsuboi
Yoshio
Y
Furukawa
Katsutoshi
K
Yanai
Kazuhiko
K
Iwata
Ren
R
Arai
Hiroyuki
H
Kudo
Yukitsuka
Y
Itoyama
Yasuhito
Y
Doh-ura
Katsumi
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001345:Autoradiography; D001583:Benzoxazoles; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017096:Prion Diseases / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000378:metabolism*; D013844:Thiazoles
C516779:2-(2-(2-dimethylaminothiazol-5-yl)ethenyl)-6-(2-(fluoro)ethoxy)benzoxazole; D001583:Benzoxazoles; D002250:Carbon Radioisotopes; D011328:Prions; D013844:Thiazoles