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Oligoethyleneoxy-Modified 99mTc-Labeled β‑Amyloid Imaging Probes with Improved Brain Pharmacokinetics for Single-Photon Emission Computed Tomography

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posted on 2018-01-05, 00:00 authored by Xiaoyang Zhang, Yaqin Hou, Cheng Peng, Chu Wang, Xiang Wang, Zhigang Liang, Jing Lu, Baian Chen, Jiapei Dai, Boli Liu, Mengchao Cui
An oligoethyleneoxy linker was introduced for conjugation between 99mTc/Re-bis­(amino­ethane­thiol) (BAT) and β-amyloid (Aβ) binding scaffolds. Rhenium complexes exhibited high to moderate binding affinity to Aβ1–42 aggregates and efficient fluorescent staining to Aβ plaques in brain tissue. After radiolabeling, the 99mTc-labeled probes revealed improved brain pharmacokinetics in normal ICR mice. Probe [99mTc]15 with potent binding affinity (Ki = 13.4 nM) and the highest initial brain uptake (2.10% ID/g at 2 min) in normal ICR mice was evaluated further. In vitro autoradiography showed specific labeling of Aβ plaques by [99mTc]15 in transgenic (Tg) mouse brain tissue. Ex vivo autoradiography further demonstrated its efficient labeling of Aβ plaques in a living Tg mouse. In vivo single photon emission computed tomography (SPECT)/CT imaging in six rhesus monkeys revealed remarkably improved brain uptakes (1.94–2.63% ID within 20 min) of [99mTc]15, making it highly potential to be used in humans for Aβ plaques imaging in the brain.