No-carrier-added 6-[^18F] fluoro-L-DOPA(6-FDOPA) was synthesized via a multistep procedure from a commercial available precursor,6-nitroveratraldehyde,The total synthesis time was 75min,with a radiochemical yield of (...No-carrier-added 6-[^18F] fluoro-L-DOPA(6-FDOPA) was synthesized via a multistep procedure from a commercial available precursor,6-nitroveratraldehyde,The total synthesis time was 75min,with a radiochemical yield of (10±3)%,high radiochemical purity(>99%) and high enantiomeric purity(>95%).The biodistributions of 6-FDOPA in normal and unilateral PD model rats were measured.The results from normal rats showed the expected high concentration of radioactivity in striatum and low distrbutions in cerebrum,cortex and cerebellum.The ration of the radioactivity in striatum to cerebellum reached a peak value(5.9) at 60 min.In unilateral PD model rate.whose substania nigra of the right side had been damaged by pre-treated with 6-OHDA,the radioactive concentration in striatum of the damaged side was significantly lower than that of the undamaged side or that of both sides in striatum of control groups.展开更多
The synthesis of 3, 4-dihydroxy- 6- bromo- phenyl- L- alanine (6- Br- L- dopa ), preparation of 3,4-dihydroxy-6-[ Br] bromo-phenyl-L-alanine(6-77 Br-bromo-L-dopa) and its distribution study in mouse brain are describe...The synthesis of 3, 4-dihydroxy- 6- bromo- phenyl- L- alanine (6- Br- L- dopa ), preparation of 3,4-dihydroxy-6-[ Br] bromo-phenyl-L-alanine(6-77 Br-bromo-L-dopa) and its distribution study in mouse brain are described. The radiochemical yield and radiochemical purity of 6- Br-bromo-L-dopa were 8.5 % and 93 %, respectively. Its distribution in mouse brain after one hour injection indicates that it does pass blood brain barrier. The ratio of uptake in striatum to that in cerebellum was 2.45±0.12. The results appeared that 6- Br-bromo-L-dopa could be used as brain tracer for visualizing dopamine-containing brain structures by using single photon tomography.展开更多
BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopam...BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits. OBJECTIVE： To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed. METHODS： The authors＇ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed. RESULTS： An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine （L-dopa）. These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D 1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements （walking） and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements. CONCLUSIONS： The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.展开更多
基金Supported by the National Nature Sciences Foundation(10075073)
文摘No-carrier-added 6-[^18F] fluoro-L-DOPA(6-FDOPA) was synthesized via a multistep procedure from a commercial available precursor,6-nitroveratraldehyde,The total synthesis time was 75min,with a radiochemical yield of (10±3)%,high radiochemical purity(>99%) and high enantiomeric purity(>95%).The biodistributions of 6-FDOPA in normal and unilateral PD model rats were measured.The results from normal rats showed the expected high concentration of radioactivity in striatum and low distrbutions in cerebrum,cortex and cerebellum.The ration of the radioactivity in striatum to cerebellum reached a peak value(5.9) at 60 min.In unilateral PD model rate.whose substania nigra of the right side had been damaged by pre-treated with 6-OHDA,the radioactive concentration in striatum of the damaged side was significantly lower than that of the undamaged side or that of both sides in striatum of control groups.
文摘The synthesis of 3, 4-dihydroxy- 6- bromo- phenyl- L- alanine (6- Br- L- dopa ), preparation of 3,4-dihydroxy-6-[ Br] bromo-phenyl-L-alanine(6-77 Br-bromo-L-dopa) and its distribution study in mouse brain are described. The radiochemical yield and radiochemical purity of 6- Br-bromo-L-dopa were 8.5 % and 93 %, respectively. Its distribution in mouse brain after one hour injection indicates that it does pass blood brain barrier. The ratio of uptake in striatum to that in cerebellum was 2.45±0.12. The results appeared that 6- Br-bromo-L-dopa could be used as brain tracer for visualizing dopamine-containing brain structures by using single photon tomography.
文摘BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits. OBJECTIVE： To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed. METHODS： The authors＇ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed. RESULTS： An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine （L-dopa）. These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D 1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements （walking） and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements. CONCLUSIONS： The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.
