分类: 核科学技术 >> 核材料与工艺技术 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: Reliable and non-invasive diagnostic tools are highly valuable for successful therapeutic strategies for the treatment of Alzheimers 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.
分类: 核科学技术 >> 核材料与工艺技术 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: Extensive accumulation of neurofibrillary tangles (NFTs) consistently correlate with the degree of cognitive impairment and neuronal circuitry deterioration associated with Alzheimers 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 (705%, n=6, decay-corrected to end of bombardment), and high radiochemical purity (>90%) and specific activity (2.5 0.5 Ci/mol) from protected precursor on fully automated module at the end of radiosynthesis (4555 min). The chemical kinetics for [18F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.
分类: 核科学技术 >> 核材料与工艺技术 提交时间: 2023-06-18 合作期刊: 《Nuclear Science and Techniques》
摘要: The 4,5-dioxo-4,5-dihydro-1H-pyrrolo(2,3-f)quinoline-2,7,9-tricarboxylic acid 2-ethyl ester 7,9-dimethyl ester (PQQE) was synthesized on the basis of Pyrroloquinoline quinine (PQQ). 99mTc-PQQE was prepared using stannous fluoride (SnF2) as reducing agent. Biological characteristics of 99mTc-PQQE include lipophilic and the charge properties were compared to 99mTc-PQQ. The biodistributions of 99mTc-PQQE in mice and brain regional distribution were performed. In vivo distribution of 99mTc-PQQE in mice indicates that the concentration ratio of drug and blood increases steadily over time. The major radioactivity may be metabolized by the hepatic and renal system. The elimination-phase half-time (t1/2) results indicate that the residence time of 99mTc-PQQE (203.92) in the body is twice as long as 99mTc-PQQ (100.45). The uptake of 99mTc-PQQE in brain was improved due to the ameliorating of charge and lipophilicity. The highest total regional brain uptake of 99mTc-PQQE was in the frontal lobe and hippocampus, where the NMDA receptor is very abundant. 99mTc-PQQE had a good target to nontarget ratio (hippocampus/cerebellum) which preserved a higher value (peak 4.0 at 120 min) from 60 min to 180 min after injection. In vitro autoradiographic results are in close agreement with the regional brain map. The enrichment can be blocked by N-methyl-D-aspartate receptor (NMDAR) redox modulatory site antagonists-ebselen (EB). This work suggests that 99mTc-PQQE has some specific targeting to the NMDA receptor.