99mTc-Labeled 2‑Arylbenzothiazoles: Aβ Imaging Probes with Favorable Brain Pharmacokinetics for Single-Photon Emission Computed Tomography

A series of 2-arylbenzothiazole derivatives conjugated with bis­(aminoethanethiol) (BAT) chelating groups were designed and synthesized. A competitive binding assay-based screening was used to select seven rhenium complexes with potent binding affinity toward Aβ1–42 aggregates (K i < 50 nM) for 9...

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Veröffentlicht in:Bioconjugate chemistry 2016-10, Vol.27 (10), p.2493-2504
Hauptverfasser: Zhang, Xiaoyang, Yu, Pingrong, Yang, Yanping, Hou, Yaqin, Peng, Cheng, Liang, Zhigang, Lu, Jing, Chen, Baian, Dai, Jiapei, Liu, Boli, Cui, Mengchao
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Sprache:eng
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Zusammenfassung:A series of 2-arylbenzothiazole derivatives conjugated with bis­(aminoethanethiol) (BAT) chelating groups were designed and synthesized. A competitive binding assay-based screening was used to select seven rhenium complexes with potent binding affinity toward Aβ1–42 aggregates (K i < 50 nM) for 99mTc labeling and further evaluation. The 99mTc-labeled probes showed good affinity and specificity to Aβ plaques in Tg mouse brain tissue in in vitro autoradiography studies. Moreover, [99mTc]14b exhibited favorable brain pharmacokinetics in normal mice (2.11% ID/g at 2 min and 0.62% ID/g at 60 min). Ex vivo autoradiography revealed extensive labeling of Aβ plaques by [99mTc]14b in the brain of Tg mice. Furthermore, we performed the first single-photon emission computed tomography (SPECT) imaging study in nonhuman primates with 99mTc-labeled Aβ probes. The semiquantitative data showed that [99mTc]14b penetrated the brains of rhesus monkeys. These results indicate that [99mTc]14b could be utilized as a SPECT imaging probe for Aβ plaques.
ISSN:1043-1802
1520-4812
DOI:10.1021/acs.bioconjchem.6b00444