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 i...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.[^(18)F]-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 of2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(BF241),and an improved automated radiosynfhesis of[^(18)F]-THK523 and the study on chemical kinetics of the labeling reaction of[^(18)F]-THK523,with high-yield(70±5%,n=6,decay-corrected to end of bombardment),and high radiochemical purity(>90%)and specific activity(2.5±0.5Ci/umol)from protected precursor on fully automated module at the end of radiosynthesis(45-55 min).The chemical kinetics for[^(18)F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.展开更多
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 p...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.展开更多
基金Supported by National Natural Science Foundation of China(Nos.81271516 and 81371625)Program of Shanghai Science and Technology Commission(Nos.13JC1401503 and 14DZ1930402)+1 种基金the exchange program fund of doctoral student under the office for Graduate Medical EducationFudan University and Shanghai Municipal Health and Family Planning Commission(No.2013313)
文摘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.[^(18)F]-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 of2-((2-(4-aminophenyl)quinolin-6-yl)oxy)ethyl 4-methylbenzenesulfonate(BF241),and an improved automated radiosynfhesis of[^(18)F]-THK523 and the study on chemical kinetics of the labeling reaction of[^(18)F]-THK523,with high-yield(70±5%,n=6,decay-corrected to end of bombardment),and high radiochemical purity(>90%)and specific activity(2.5±0.5Ci/umol)from protected precursor on fully automated module at the end of radiosynthesis(45-55 min).The chemical kinetics for[^(18)F]-THK523 demonstrates that nucleophilic substitution can be carried out easily with protected precursor.
基金Supported by National Natural Science Foundation of China(Nos.81271516 and 81371625)Program of Shanghai Science and Technology Commission(Nos.13JC1401503 and 14DZ1930402)+1 种基金Shanghai Municipal Health and Family Planning Commission(No.2013313)Exchange Programme Foundation of Doctoral Student under the Office for Graduate Medical Education,Fudan University
文摘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.
