Amyloid Imaging in Alzheimer Disease Using PET with [F-18]Fact: A Neuritic Plaque Imaging?

Objectives: The characteristic neuropathologic changes in Alzheimer disease (AD) are deposition of amyloid senile plaques and neurofibrillary tangles. [C-11]BF227, a benxoxazole derivative, has been developed for in vivo imaging of amyloid senile plaques [1], which has been considered to bind more preferentially to dense-cored amyloid deposition than [C-11]PIB. The fluorine-18 labeled amyloid tracer, [F-18]2-[(2-{(E)-2-[2-(dimethylamino)-1,3-thiazol-5-yl]vinyl}-1,3-benzoxazol-6-yl)oxy]-3-fluoropropan-1-ol (Fluorinated Amyloid imaging Compound of Tohoku University; [F-18]FACT), which is one of benxoxazole derivatives and has similar structure with [C-11]BF227, has recently been developed. In the present study, deposition of amyloid senile plaques was measured by PET with both [C-11]PIB and [F-18]FACT in same subjects, and the regional uptake of both radiotracers were directly compared.Methods: Two PET scans with [C-11]PIB and [F-18]FACT were performed sequentially on 6 normal control (NC) subjects, 2 mild cognitive impairment (MCI) patients, and 6 AD patients. The standardized uptake value (SUV) was calculated from time-integrated radioactivity with the integration intervals of 50 to 70 min and 40 to 60 min for [C-11]PIB and [F-18]FACT, respectively. Since SUV are affected by the non-specific accumulation of radiotracer in the white matter, the SUV per gray matter fraction in an ROI were calculated using MR images as follows:SUV = SUVgray•TFgray + SUVwhite•TFwhite.where SUVgray and SUVwhite are SUV in gray and white matter, respectively. TFgray and TFwhite are the tissue fraction of gray and matter, respectively, which are determined from MR images. The SUVgray were calculated by assuming SUVwhite to be equal to SUV in the centrum semiovale. The SUVgray ratio (SUVR) of brain regions to cerebellum was calculated.Results: The SUVR of [C-11]PIB for cerebral cortical regions in NC subjects and AD patients were 1.15-1.40 and 3.10-4.91 in average, respectively. The SUVR of [F-18]FACT for cerebral cortical regions in NC subjects and AD patients were 1.22-1.33 and 1.58-1.70 in average, respectively. Significant positive correlations were observed between SUVR of [C-11]PIB and [F-18]FACT in all brain regions. Relatively lower uptake of [C-11]PIB in distribution were observed in the medial side of temporal cortex and occipital cortex as compared with [F-18]FACT. Relatively higher uptake of [C-11]PIB in distribution was observed in the frontal and parietal cortices.Conclusions: Since [F-18]FACT has similar structure with [C-11]BF227, it might also bind more preferentially to dense-cored amyloid deposition. [C-11]PIB might bind to both diffuse and dense-cored amyloid plaques, and therefore such regional differences in cerebral cortical uptake between [C-11]PIB and [F-18]FACT might be due to differences in regional distribution between diffuse and dense-cored amyloid plaques. A histopathological study showed that diffuse amyloid plaque was not prominent in the occipital lobe as compared with the frontal and temporal lobe [2], corresponding to the present results. Because neuropathology in AD are characterized by cortical neuritic plaque containing dense-cored amyloid deposition [3], selective radiotracer for neuritic amyloid plaque might be useful to distinguish normal aging process from AD.References:[1] Kudo Y, et al. J Nucl Med 2007; 48: 553-561.[2] Yamaguchi H, et al. Acta Neuropathol 1988; 77: 113-119.[3] Price JL. Neurobiol Aging 1997; 18: S67-70.Brain 201