(18)F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia

OBJECTIVE: Recently, we developed a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N-methylpyridin-2-amine ((18)F-FPYBF-2) (Ono et al., J Med Chem 54:2971–9, 2011). The aim of this study was to assess the feasibility of (18)F-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 (11)C-Pittsburgh Compound B ((11)C-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 (18)F-FPYBF-2 and (11)C-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 (11)C-PiB analysis using cerebellar cortex as control. RESULTS: Studies with healthy volunteers showed that (18)F-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, (18)F-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 (18)F-FPYBF-2 PET/CT were comparable with those of (11)C-PiB, and the Mean Cortical Index ((18)F-FPYBF-2: 1.173 ± 0.215; (11)C-PiB: 1.435 ± 0.474) showed direct proportional relationship with each other (p < 0.0001). CONCLUSIONS: Our first clinical study suggest that (18)F-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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12149-018-1236-1) contains supplementary material, which is available to authorized users.