<sup> 11 </ Sup> C-cft Pet Imaging Of Brain Dopamine Transporters In Parkinson's Disease Diagnosis In Value

Parkinson's disease(PD) is the second common neurodegenerative disorder mainly occurring in the elderly.Its manifestation is caused by the degeneration of dopaminergic neurons in substantial nigra and the loss of dopamine in the striatum.So far,the diagnosis of PD is assessed primarily based on its clinical symptoms and signs, which appear only after a loss of approximately 50-80%of dopaminergic neurons in nigra.If there is approaches available for making earlier diagnosis and objectively monitoring progression of PD,it will facilitate introduction of potential neuroprotective treatments at earlier stage,and more likely postpone the deterioration of this movement disorder.ObjectivesTo evaluate the 2β-carbomethoxy-3β-(4-fluorophenyl)-(N-¹¹C-methyl)tropane (¹¹C-CFT) dopamine transporter(DAT) PET imaging in diagnosing PD at early stage and assessing the severity of PD.MethodsSixteen patients with PD and five age-matched healthy controls were enrolled in this study.Among patients with PD,ten patients were at early stage(Hoehn&Yahr stageⅠ-Ⅱ) and six developed into advanced stage(Hoehn&Yahr stageⅢ-Ⅳ).One hour after injection of ¹¹C-CFT,¹¹C-CFT DAT PET imaging were performed and analyzed for all above subjects.The three adjacent slices where the striatum was best seen were used to calculate the redioactive uptake ratio by applying the region of interest(ROI) analysis,including the subregions of caudate nucleus,anterior putamen and posterior putamen.The ratio of(ROI-cerebellum)/cerebellum was measured and compared among different groups,and evaluated by correlation analysis with United Parkinson Disease rating scale motor score(UPDRSⅢ),as well as sub-scores for tremor,rigidity and bradykinesia.Statistical parametric mapping (SPM) comparison of ¹¹C-CFT uptake between early or advanced PD and the control group was also performed by using SPM analysis.Results1.In healthy control group,¹¹C-CFT DAT PET imaging was symmetrical in striatum of both sides with high signal-to-noise ratio,and no significant difference of ¹¹C-CFT uptake was found at the subregions of caudate nucleus, anterior and posterior putamen.2.In the PD group at early stage,there was a significant decrease in ¹¹C-CFT uptake in striatum,which reduced to 51.9%of the control mean in caudate nucleus,to 37.9%of that in anterior putamen and 25.7%in posterior putamen.The reductions occurred in both the contralateral and ipsilateral striatum,localized predominantly on the contralateral side.In 8 hemi-parkinsonian patients with early disease(Hoehn&Yahr stage 1 or 1.5) the reduction in the ¹¹C-CFT uptake was reduced in the ipsilateral caudate nucleus to 59.3%of the mean control value,anterior putamen to 45.5%and posterior putamen to 36.1%.The corresponding figures in the contralateral side were to 50.0%at caudate nucleus,34.8%at anterior putamen,and 19.6%at posterior putamen respectively.3.In the PD patients at advanced stage,the above corresponding figure were reduced to 34.8%,21.0%and 13.2%in the caudate nucleus,anterior and posterior putamen respectively.No significant difference was found between the contralateral and ipsilateral striatum.4.The reduction in ¹¹C-CFT uptake was more pronounced in those patients with more severe disability.The correlations between UPDRSⅢscores and ¹¹C-CFT uptake was significant in the caudate nucleus(r=-0.5401,p=0.0308), anterior putaman(r=-0.6468,p=0.0068),and posterior putamen(r=-0.7119, p=0.0020) respectively.There was a significant negative correlation ¹¹C-CFT uptake at putamen with the hypokinesia and rigidity sub-scores,however, there was no significant correlation observed with the tremor sub-score of the UPDRSⅢ.5.By means of SPM analysis,there was a significant reduction of DAT binding in the contralateral striatum of PD patients with early stage and in the bilateral striatum of patients with advanced stage,especially in posterior putamen and putamen contralateral to the affected limbs.Conclusions¹¹C-CFT could be served as a sensitive biomarker for detecting nigrostriatal dysfunction in PD at early stage and evaluating the severity of PD.