Subjects: Nuclear Science and Technology >> Nuclear Materials and Techniques submitted time 2023-06-18 Cooperative journals: 《Nuclear Science and Techniques》
KONG Yan-Yan
SI Zhan
ZHANG Zheng-Wei
GUAN Yi-Hui
CAO Guo-Xian
XUE Fang-Ping
HUA Feng-Chun
WU Ping
ZHAO Jun
ZHU Jian-Hua
LI Cong
CHEN Jian
QIAN Jun
Abstract： Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimer’s disease (AD). The existence of neurofibrillary tangles (NFTs) consisting of tau protein are one kind of the pathological features of AD, and its level of severity is correlated with the stage of AD. However, no clinically approved positron emission tomography (PET) probe is currently available for selective imaging of neurofibrillary tangles on patients. In this paper, we report our studies on biological characteristics of [18F]-THK523 as a novel tau imaging probe. With low molecular weight, [18F]-THK523 is stable, electrically neutral, lipophilic and non-mass concentration-dependent. Preliminary biological studies have shown the excellent properties of [18F]-THK523 as brain imaging tracer for further research.
Subjects: Nuclear Science and Technology >> Nuclear Materials and Techniques submitted time 2023-06-18 Cooperative journals: 《Nuclear Science and Techniques》
KONG Yan-Yan
SI Zhan
CAO Guo-Xian
ZHANG Zheng-Wei
WU Ping
XUE Fang-Ping
DU Fu-Qiang
ZHU Jian-Hua
LI Cong
CHEN Jian
GUAN Yi-Hui
Abstract： Extensive accumulation of neurofibrillary tangles (NFTs) consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimer’s disease. However, no PET probe is currently available for selective detection of NFTs in the living human brain. [18F]-THK523 was developed as a potential in vivo imaging probe for tau pathology. In this paper, we report a new protected precursor, 2-((2-(4-(( tert-butoxycarbonyl)amino)phenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate (THK-7), instead of 2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate (BF241), and an improved automated radiosynthesis of [18F]-THK523 and the study on chemical kinetics of the labeling reaction of [18F]-THK523, with high-yield (70±5%, n=6, decay-corrected to end of bombardment), and high radiochemical purity (>90%) and specific activity (2.5 ± 0.5 Ci/μmol) from protected precursor on fully automated module at the end of radiosynthesis (45–55 min). The chemical kinetics for [18F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.
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