¹⁸F-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-(2-¹⁸F-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.