Design, synthesis, and preliminary evaluation of [F]-aryl flurosulfates PET radiotracers via SuFEx methods for β-amyloid plaques in Alzheimer's disease.

[F]BAY-94-9172, [F]AV-45, and [F]GE-067 were FDA approved positron emission tomography (PET) imaging radiotracer of β-amyloid plaques (Aβ) in Alzheimer's disease (AD). However, the radiochemical synthesis requires multi-step reactions and complex procedure. Recently, a protocol for radiochemical synthesis of sulfur fluoride exchange (SuFEx) using ultrafast F/F isotopic exchange had been reported. We developed three pairs of novel F-labeled radiotracers by the "SuFEx" method for PET imaging Aβ plaques. The F labeling reaction can be completed quickly (30 s) at room temperature and purified using solid-phase extraction (SPE). The radiochemical purity (RCP) of the products was all greater than 95 %. In vitro fluorescent staining using Aβ-transgenesis mice section preliminary verified the affinity of tracers with Aβ. Competitive binding assay displayed high affinity of tracers for towards artificial Aβ aggregates (K values ranging from 3.53 ± 0.39 to 42.0 ± 4.24 nM). In vivo biodistribution and Micro-PET imaging showed that [F]-Sulfur Fluoride β-Amyloid ([F]SFA 1-6) could penetration the blood-brain barrier (BBB) in wild-type mice, and [F]SFA 5-6 had a high initial brain uptake value (3.65 ± 0.9 % and 5.07 ± 0.1 % ID/g, respectively) and a fast washout (Brain uptake = 4.15 and 4.61, respectively) from the brain. In vitro autoradiography demonstrated the affinity of the [F]SFA 5-6 to Aβ plaques in AD human brain tissues. Our results suggested that [F]SFA maybe a potential PET radiotracers for detecting Aβ in Alzheimer's disease.