| Parkinson's disease(PD) is a common neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra and loss of its nerve terminal in the basal ganglia, especially in the striatum. PD consists of a syndrome including tremor, rigidity, bradykinesia and postural abnormalities. The binding of dopamine transporter can serve as a marker for investigating dopaminergic function. Our study concentrates dopamine transporter receptor PET imaging of experimental and clinical study on Parkinson's disease, which involves 3 parts as follows. Part I. Preparation of dopamine transporter imaging agent 18F-FP-(CIT and its studies on PET imaging in small animalsObjective To prepare [18F]N-3-fluoropropyl-2-(-carbomethoxy-3-(-(4-iodophenyl) nortropane(18F-FP-(CIT) as dopamine transporter(DAT) imaging agent by a one-step procedure and to study the regional brain DAT binding site in small animal using Siemens/CTI ECAT HR+ PET scanner. Methods 18F-FP-(CIT was prepared based on nucleophilic fluorination of mesylate with K18F/K2.2.2.(Kryptofix) via single-step method. Dynamic scans were carried out at 15min, 30min, 60min, 90min and 2h after injection of 22.2-55.5MBq 18F-FP-(CIT in 4 normal cats. The changes of distribution of 18F-FP-βCIT in brain with time elapse were observed, and striatum/cerebellum ratio was calculated. Hemi-Parkinson's disease cat model , rats and mice were also performed with 18F-FP-(CIT PET imaging. Results The total radiochemical synthesis time was 100-135min, the overall radiochemical yield from stating synthesis was 0.47%-15.31%. The average radiochemical purity was 93.9% by HPLC. Retention time(tR) of 18F-FP-(CIT was 3.38±0.20min. In early stage (within 30min), 18F-FP-βCIT accumulation in cortical, striatum, thalamus, and cerebellum was showed clearly. The radioactivity in cortical, thalamus and cerebellum exhibited decrease with time. The radioactivity mainly accumulated in striatum areas. The striatum-to-cerebellum ratio was 2.59±0.16 at 30min, 2.73±0.23 at 60min, 2.52±0.13 at 90min and 2.08±0.11 at 120min respectively. Conclusion These results show that 18F-FP-(CIT is a valuble PET imaging agent for dopamine transporter. Some brain receptor research on small animal such as cat and rat may be possible by using Siemens/CTI ECAT HR+ PET system.Part II. Preliminary clinical study on 18F-FP-(-CIT PET dopamine transporter imaging in Parkinson's DiseaseObjective To evaluate the value of [18F]N-3-fluoropropyl-2-(- carbomethoxy-3-(-(4-iodophenyl) nortropane(18F-FP-(-CIT) PET imaging in patients with Parkinson's disease(PD). Methods PET with [18F]-FP-β-CIT was studied in 6 healthy volunteers, 21 parkinsonian patients with early stage and 10 ones with advanced stage. Of them,8 PD cases and 6 control subjects were both performed dynamic PET scans at 15min, 30min, 60min, 2h and 3h after injection of 74-111MBq 18F-FP-(-CIT. The changes of distribution of 18F-FP-β-CIT in brain with time elapse were observed, and (ROI-cerebellum)/cerebellum ratio was calculated. The correlation between DAT binding in striatum and UPDRS motor scores was determined in the parkinsonian patients. Results In early phase (within 30 min), 18F-FP-β-CIT accumulation in cortical, basal gangalia, thalamus, and cerebellum was showed clearly. The radioactivity in cortical, thalamus and cerebellum exhibited decrease with time. The radioactivity mainly accumulated in the caudate and putamen areas. The striatum-to-cerebellum ratio was 3.71-5.41 (4.24(0.63) at 2-3h. In early stage of PD patients, the uptake of 18F-FP-β-CIT in the posterior putamen contralateral to the predominant symptoms was more severely affected than in the anterior putamen or the caudate nucleus. As the disease progresses, bilateral basal gangalia and the caudate nucleus would be affected. In the patients with early stage(Hoehn&Yahr 1-2), the binding uptake in the posterior putamen, anterior putamen and caudate was reduced to 23.6% , 43.8%, 71.8% of the control value respectively, and mor...
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