Synthesis and Initial Characterization of a Reversible, Selective 18F-Labeled Radiotracer for Human Butyrylcholinesterase

• DOI: 10.1007/s11307-021-01584-2
• Publication Date: 2021-03-03T17:06:29Z
• Authors: Christian Gentzsch; Xinyu Chen; Philipp Spatz; Urban Košak; Damijan Knez; Naoko Nose; Stanislav Gobec; Takahiro Higuchi; Michael Decker
• Keywords: Radiosynthesis; Butyrylcholinesterase; Dissociation constant; IC50; Ex vivo; Specific activity; PET Imaging; Human brain; Radioligand

Abstract Purpose A neuropathological hallmark of Alzheimer’s disease (AD) is the presence amyloid-β (Aβ) plaques in brain, which are observed a significant number cognitively normal, older adults as well. In AD, butyrylcholinesterase (BChE) becomes associated with β aggregates, making it promising target for imaging probes to support diagnosis AD. this study, we present synthesis, radiochemistry, vitro and preliminary ex vivo investigations selective, reversible BChE inhibitor PET-tracer evaluation an AD diagnostic. Procedures Radiolabeling was achieved by fluorination respective tosylated precursor using K[ 18 F]. IC 50 values fluorinated compound were obtained colorimetric assay recombinant, human ( h ) BChE. Dissociation constants determined measuring activity different concentrations inhibitor. Results Radiofluorination tosylate gave desired radiotracer average radiochemical yield 20 ± 3 %. Identity > 95.5 % purity confirmed HPLC TLC autoradiography. The inhibitory potency Ellman’s value 118.3 19.6 nM. measured kinetic experiments revealed lower affinity binding acylated enzyme K 2 = 68.0 nM) comparison free 1 32.9 nM). Conclusions reversibly acting, selective synthetically easily accessible retains potential on Radiosynthesis F labeling tosylates feasible reasonable time frame good yield.