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  • Title: 18F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia.
    Author: Higashi T, Nishii R, Kagawa S, Kishibe Y, Takahashi M, Okina T, Suzuki N, Hasegawa H, Nagahama Y, Ishizu K, Oishi N, Kimura H, Watanabe H, Ono M, Saji H, Yamauchi H.
    Journal: Ann Nucl Med; 2018 Apr; 32(3):206-216. PubMed ID: 29388083.
    Abstract:
    OBJECTIVE: Recently, we developed a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine (18F-FPYBF-2) (Ono et al., J Med Chem 54:2971-9, 2011). The aim of this study was to assess the feasibility of 18F-FPYBF-2 as an amyloid imaging PET tracer in a first clinical study with healthy volunteers and patients with various dementia and in comparative dual tracer study using 11C-Pittsburgh Compound B (11C-PiB). METHODS: 61 healthy volunteers (age: 53.7 ± 13.1 years old; 19 male and 42 female; age range 24-79) and 55 patients with suspected dementia [Alzheimer's Disease (AD); early AD: n = 19 and moderate stage AD: n = 8, other dementia: n = 9, mild cognitive impairment (MCI): n = 16, cognitively normal: n = 3] for first clinical study underwent static head PET/CT scan using 18 F - FPYBF-2 at 50-70 min after injection. 13 volunteers and 14 patients also underwent dynamic PET scan at 0-50 min at the same instant. 16 subjects (volunteers: n = 5, patients with dementia: n = 11) (age: 66.3 ± 14.2 years old; 10 males and 6 females) were evaluated for comparative study (50-70 min after injection) using 18F-FPYBF-2 and 11C-PiB on separate days, respectively. Quantitative analysis of mean cortical uptake was calculated using Mean Cortical Index of SUVR (standardized uptake value ratio) based on the established method for 11C-PiB analysis using cerebellar cortex as control. RESULTS: Studies with healthy volunteers showed that 18F-FPYBF-2 uptake was mainly observed in cerebral white matter and that average Mean Cortical Index at 50-70 min was low and stable (1.066 ± 0.069) basically independent from age or gender. In patients with AD, 18F-FPYBF-2 uptake was observed both in cerebral white and gray matter, and Mean Cortical Index was significantly higher (early AD: 1.288 ± 0.134, moderate AD: 1.342 ± 0.191) than those of volunteers and other dementia (1.018 ± 0.057). In comparative study, the results of 18F-FPYBF-2 PET/CT were comparable with those of 11C-PiB, and the Mean Cortical Index (18F-FPYBF-2: 1.173 ± 0.215; 11C-PiB: 1.435 ± 0.474) showed direct proportional relationship with each other (p < 0.0001). CONCLUSIONS: Our first clinical study suggest that 18F-FPYBF-2 is a useful PET tracer for the evaluation of β-amyloid deposition and that quantitative analysis of Mean Cortical Index of SUVR is a reliable diagnostic tool for the diagnosis of AD.
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