Design, synthesis, and preliminary evaluation of [18F]-aryl flurosulfates PET radiotracers via SuFEx methods for β-amyloid plaques in Alzheimer's disease. (1st December 2022)

• Record Type: Journal Article
• Authors: He, Yunlin; Zhu, Xingxing; Wang, Kaixuan; Xie, Jikui; Zhu, Zehua; Ni, Ming; Wang, Shicun; Xie, Qiang
• Is Part Of: Bioorganic & medicinal chemistry. Volume 75(2022)
• Publication Date: 2022-12-01
• Subjects: Fluorine-18 -- Sulfur fluoride exchange (SuFEx) -- Aβ plaques -- PET -- Brain imaging -- Alzheimer's disease; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2022.117087
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: The radiochemical synthesis method of SuFEx can be completed in 30 s at room temperature. Three pairs of new PET radiotracers were successfully synthesized and evaluated in vivo . [ 18 F]SFA 3 –6 had high affinity and sensitivity with A β plaques in AD human brain tissues. [ 18 F]SFA 5 –6 had a high initial brain uptake value and a fast metabolic rate from wild-type mice brains. Abstract: [ 18 F]BAY-94-9172, [ 18 F]AV-45, and [ 18 F]GE-067 were FDA approved positron emission tomography (PET) imaging radiotracer of β-amyloid plaques (A β ) 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 19 F/ 18 F isotopic exchange had been reported. We developed three pairs of novel 18 F-labeled radiotracers by the "SuFEx" method for PET imaging A β plaques. The 18 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 A β -transgenesis mice section preliminary verified the affinity of tracers with A β . Competitive binding assay displayed high affinity of tracers for towards artificial A β 1-42 aggregates ( K i values ranging from 3.53 ± 0.39 to 42.0 ± 4.24 nM). In vivo biodistribution and Micro-PET imaging showed that [ 18 F]-S ulfur F luoride β-A myloid ([ 18 F]SFA 1 –6 ) could penetration the blood–brain barrier (BBB) in wild-type mice, and [ 18 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 uptake2 min/60 min = 4.15 and 4.61, respectively) from the brain. In vitro autoradiography demonstrated the affinity of the [ 18 F]SFA 5 –6 to A β plaques in AD human brain tissues. Our results suggested that [ 18 F]SFA maybe a potential PET radiotracers for detecting A β in Alzheimer's disease.