Abnormal Tau deposition is a crucial pathological hallmark of various neurodegenerative disorders defined as tauopathies,of which Alzheimer’s disease is the most prominent one.To date,a large number of chemical entit...Abnormal Tau deposition is a crucial pathological hallmark of various neurodegenerative disorders defined as tauopathies,of which Alzheimer’s disease is the most prominent one.To date,a large number of chemical entities with different structures have been developed as Tau imaging tracers for the early diagnosis of tauopathies.Several of them with excellent bio-properties are currently being assessed in clinical trials,and more recently,the Tauvid^(TM)([^(18)F]Flortaucipir,also known as[^(18)F]AV1451 or[^(18)F]T807)as the first Tau tracer was approved by the U.S.Food and Drug Administration in 2020.This review summarized the latest development of Tau tracers and analyzed their chemical structures,with particular attention to the effects of chemical structures on biological properties.In addition,we also discuss the limitations of current Tau imaging tracers,issues that need attention in the development of new tracers,and possible future directions.展开更多
We have discovered and synthesized a series of indole-based derivatives as novel sigma-2(σ_(2))receptor ligands.Two ligands with high σ_(2) receptor affinity and subtype selectivity were then radiolabeled with F-18 ...We have discovered and synthesized a series of indole-based derivatives as novel sigma-2(σ_(2))receptor ligands.Two ligands with high σ_(2) receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities,and evaluated in rodents.In biodistribution studies in male ICR mice,radioligand[18F]9,or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[18F]fluoroethoxy)-1H-indole,was found to display high brain uptake and high brain-to-blood ratio.Pretreatment of animals with the selective σ_(2) receptor ligand CM398 led to significant reductions in both brain uptake(29%-54%)and brain-to-blood ratio(60%-88%)of the radioligand in a dose-dependent manner,indicating high and saturable specific binding of[18F]9 to σ_(2) receptors in the brain.Further,ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of[18F]9 in the brain that is consistent with the distribution pattern of σ_(2) receptors.Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for[18F]9 in the rat brain,along with appropriate tissue kinetics.Taken together,results from our current study indicated the novel radioligand[18F]9 as the first highly specific and promising imaging agent for σ_(2) receptors in the brain.展开更多
基金funded by the National Natural Science Foundation of China(Nos.U1967221,22022601)。
文摘Abnormal Tau deposition is a crucial pathological hallmark of various neurodegenerative disorders defined as tauopathies,of which Alzheimer’s disease is the most prominent one.To date,a large number of chemical entities with different structures have been developed as Tau imaging tracers for the early diagnosis of tauopathies.Several of them with excellent bio-properties are currently being assessed in clinical trials,and more recently,the Tauvid^(TM)([^(18)F]Flortaucipir,also known as[^(18)F]AV1451 or[^(18)F]T807)as the first Tau tracer was approved by the U.S.Food and Drug Administration in 2020.This review summarized the latest development of Tau tracers and analyzed their chemical structures,with particular attention to the effects of chemical structures on biological properties.In addition,we also discuss the limitations of current Tau imaging tracers,issues that need attention in the development of new tracers,and possible future directions.
基金supported by the National Natural Science Foundation of China(No.21876013)Beijing Natural Science Foundation(7212203,China)。
文摘We have discovered and synthesized a series of indole-based derivatives as novel sigma-2(σ_(2))receptor ligands.Two ligands with high σ_(2) receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities,and evaluated in rodents.In biodistribution studies in male ICR mice,radioligand[18F]9,or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[18F]fluoroethoxy)-1H-indole,was found to display high brain uptake and high brain-to-blood ratio.Pretreatment of animals with the selective σ_(2) receptor ligand CM398 led to significant reductions in both brain uptake(29%-54%)and brain-to-blood ratio(60%-88%)of the radioligand in a dose-dependent manner,indicating high and saturable specific binding of[18F]9 to σ_(2) receptors in the brain.Further,ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of[18F]9 in the brain that is consistent with the distribution pattern of σ_(2) receptors.Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for[18F]9 in the rat brain,along with appropriate tissue kinetics.Taken together,results from our current study indicated the novel radioligand[18F]9 as the first highly specific and promising imaging agent for σ_(2) receptors in the brain.
