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 Aβ1-42aggregates (Ki< 50 nM) for99mTc labeling and further evaluation. The99mTc-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 with99mTc-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.
Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University , Beijing 100875, China.
Xiaoyang
X
Zhang
Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University , Beijing 100875, China.
Pingrong
P
Yu
Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University , Beijing 100875, China.
Yanping
Y
Yang
Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University , Beijing 100053, China.
Yaqin
Y
Hou
Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University , Beijing 100053, China.
Cheng
C
Peng
Department of Nuclear Medicine, Xuanwu Hospital, Capital Medical University , Beijing 100053, China.
Zhigang
Z
Liang
Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University , Beijing 100069, China.
Jing
J
Lu
Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University , Beijing 100069, China.
Baian
B
Chen
Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities , Wuhan 430074, China.
Jiapei
J
Dai
Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University , Beijing 100875, China.
Boli
B
Liu
Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University , Beijing 100875, China.
Mengchao
M
Cui