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

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