Radioiodinated 9-fluorenone derivatives for imaging ?7-nicotinic acetylcholine receptors.

ABSTRACT: A series of 9H-fluoren-9-one substituents were synthesized and evaluated for imaging cerebral ?7-nAChRs. Meta-iodine substituted 9-fluorenone 5 with high binding affinity (K i = 9.3 nM) and selectivity was radiolabeled with 125I. Fully in vitro and in vivo studies of [125I]5 have been performed. [125I]5 exhibited well brain uptake with a peak concentration of 7.5 ± 0.9% ID/g in mice brains. Moreover, ex vivo autoradiography studies and micro single-photon emission computed tomography (micro-SPECT/CT) dynamic imaging in mice confirmed its in vivo imaging properties. Besides, molecular docking and MD studies were also performed to interpret the binding mechanisms of the two series of ligands towards ?7-nAChRs. To conclude, the meta-iodine substituted 9-fluorenone [125I]5 could be a promising tracer for imaging ?7-nAChRs.

SUBMITTER: Gao H 

PROVIDER: S-EPMC7451070 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature