Quantitative analysis of amyloid deposition in human brain using PET and a new imaging probe [11C]BF-227

Manabu Tashiro, K. Kumagai, N. Okamura, S. Furumoto, K. Furukawa, Y. Funaki, M. Maruyama, Y. Kimura, M. Itoh, R. Iwata, Y. Kudo, H. Arai, K. Yanai

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Introduction: In vivo detection of amyloid deposits would be useful for early diagnosis of Alzheimer's disease (AD). A new imaging probe, 2-[2-(2-Dimethylaminothiazol-5-yl)ethenyl]-6-[2-(fluoro)ethoxy]benzoxazole (BF-227), that was picked up out of hundreds of candidate compounds through systematic evaluation using animals, was [11C]-labeled for clinical evaluation. In vivo amyloid imaging using the [11C]BF-227 was successfully conducted in AD patients at Tohoku University (Ref.). The purpose of the present study is to examine the method for quantitative analysis of amyloid deposition in human brain using PET and [11C]BF-227. Methods: Eleven healthy controls (M:F=8:3; mean age: 56.3 +/- 15.0 y.o.) and ten AD patients (M:F=4:6; 73.3 +/- 7.7 y.o.) were studied. Dynamic PET images were obtained for 60 min (23 sequential scans). Blood samples were obtained through arterialized veins as well as through radial arteries in only one case for each subgroup. The all cases were studied with PET and FDG as well. Regions of interest were placed on various cortical and subcortical regions based on the coregistered MRI images. The whole data were analyzed using tissue time-activity curves, corrected for partial volume effects due to white matter and cerebrospinal space, and metabolite-corrected plasma time-activity curves. Ratio of distribution volume (DVR: each region/cerebellum) were calculated using Logan graphical method, and additionally using full kinetic analysis based on three-compartment model in the cases with arterial sampling data. Results: In AD patients, [11C]BF-227 displayed significantly higher DVR values than in controls in various cortical regions such as the cingulate, frontal, temporal, parietal and occipital regions (i.e. temporal; control vs. AD: 1.16 +/- 0.05 vs. 1.29 +/- 0.06, respectively)(p< 0.001). Further analysis revealed that the highest retention of [11C]BF-227 was observed in the temporoparietal association area, the predilected site for dense amyloid plaque depositions, which was corresponding to the hypometabolic area observed in the FDG study. Conclusion: These findings demonstrated that [11C]BF-227 was a promising PET probe and that Logan graphical method can be used for evaluation of dense amyloid deposits in AD patients.

Original languageEnglish
Pages (from-to)PO02-03U
JournalJournal of Cerebral Blood Flow and Metabolism
Issue numberSUPPL. 1
Publication statusPublished - 2007 Nov 13


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