Study Of Dopamine Transporter Imaging In The Different Stages Of Parkinson's Disease

Background: Parkinson's disease(PD) is a chronic progressive neurodegenerativedisorder which usually occurred in the senior people. Along with our populationold age, its disease incidence rate assumes the tendency of year by year increase.Nowadays, the PD diagnosis still is the clinical diagnosis and not difficult to makeaccording to the onset after middle age, typical symptom and the reaction to dopaagents. However, the symptoms are usually untypical for the early stage patients,especially before the onset of tremor. The diagnosis for these patients, therefore, isusually very difficult. No characteristic signs can be found in CT or MRI studiesat the early stage of PD either. The coincident rate of clinical and pathologicaldiagnosis is only 80%, because of lacking reliable, sensitive and specific probes.In recent years, the SPECT cerebral dopamine transporter imaging brings out anew method for the early diagnosis of PD. The semi-quantitative analysis ofstriatum/background plays an important role in the diagnosis of PD, patient'scondition monitoring and the differential diagnosis of PD and Parkinson'ssyndrome as well. However, for the late stage patients, the localization of thestriatum is still difficult, and very few reports can be found in this field, nosemi-quantitative method is available.Purpose:1. Test the uptake function of ^99mTc-TRODAT-1 in striatum and semi-quantitativeanalysis of striatum/cerebellum in the patients of different PD stages and innormal subjects.2. Evaluate the correlation between striatum/cerebellum value and UPDRS score.3. Apply the experimental result to the clinical work, so as to improve theaccuracy and the reliability of the diagnosis.Method: Separately to the PD patient 58 cases (13 cases in H-Y stageâ… , 9 casesin stage 1.5, 15 cases in stageâ…¡, 10 cases in stage 2.5,7 cases in stageâ…¢, 4 casesin stageâ…£) and the comparison group 13 cases, we took ^99mTc-TRODAT-1SPECT/CT brain hybrid fusion imaging. Preparing ^99mTc-TRODAT-1 by adding fresh ^99mTCO₄ 1110MBq(30 mCi) into a TRODAT-1 kit, shaking steadily, heatingin the boiling water for 30 min, then taking out and letting it cool down in theroom temperature, we got the ^99mTc-TRODAT-1. The subject was injected^99mTc-TRODAT-1 1110MBq (30mCi) intravenously 30 min after 1ml NaIsolution was given orally. The image acquisition was performed 2hr later using adual-head SPECT/CT (GE Discovery VH). Gathering Parameters: FanBeamcollimator, energy peak 140Kev, window width 20%. After the SPECT imaging,the X-ray CT transmission scan was performed with the subject in same position.Regions of interest of the striatum (including caudate and putamen)in both sides,cerebellum, occipital lobe, frontal lobe were delineated. The count ratios ofstratum/cerebellum, putamen/cerebellum and caudate/cerebellum, striatum/occipital lobe and striatum/frontal lobe were then calculated.Results:1. The images in normal subject showed symmetrical radioactive accumulation inboth sides of striatum, with clear and sharp border, of symmetry in shape and size,in the transversal images. The head of caudate nucleus is large localized in front,while the putamen is a little smaller localized in the back, like a "comma" inshape. No significant differences in the uptake of ^99mTc-TRODAT-1 were found inboth sides of striatum (t=0.533, P=0.604＞0.05).2. The SPECT images of PD patients in stageâ… showed intact contour but theradio-distribution is sparser. Although some symptoms occurred only on one sideof the limbs to some patients, the uptake of ^99mTc-TRODAT-1 reduced bilaterally.The uptake of ^99mTc-TRODAT-1 in the ipsilateral striatum decreased alsocompared to the normal subjects. PD patients in stageâ…¡showed defectivecontour of the striatum, the radioactivity distributed obviously sparse, or evenradioactive defect can be seen. The ratio of striatum/cerebellum showedsignificant differences between the normal sbujects and PD patients in differentstage. No significant differences of striatum/cerebellum were found between stage2.5 and stageâ…¢(P=0.146), nor between stageâ…¢and stageâ…£(P=0.284).There was significant difference in striatum/cerebellum ratio among the patients in the other stages.3. Significant difference in striatum/cerebellum ratio was found between thestriatum contralateral and ipsilateral to the limbs with symptoms or more affected,no matter the patients were in stageâ… , stage 1.5, stage 2 or stage 2.5. Greater lossof striatal uptake were found in the contralateral limbs. For late stage PD patients(H-Y stageâ…¢orâ…£), however, no significant difference in striatum/cerebellumratio between contralateral and ipsilateral limbs was found.4. There was no significant difference in the uptake of ^99mTc-TRODAT-1 betweenputamen and caudate in normal subjects. For PD patients in early stage, lessuptake was seen in bilateral putamen than in caudate for patients.5. As disease develops, the uptake of ^99mTc-TRODAT-1 in striatum decreasedprominently. A negative correlation between the uptake of ^99mTC-TRODAT-1with UPDRS score(r=-0.827, P＜0.001) was found.6. The higher the age in normal subjects, the less uptake of ^99mTc-TRODAT-1 instriatum. No correlation between the age and the uptake in PD patients (r=-0.186)was found.Conclusions: TRODAT-1 shows high affinity with dopamine transporter, also hashigh specificity and selectivity. It hardly binds to other transporter, and will not beaffected by nonspecific uptake. It is a potential tool for the evaluation of DATfunction and density in striatum. ^99mTc-TRODAT-1 SPECT imaging is helpful forthe early diagnosis of PD. DAT function and density in putamen are first suffersinjury, then is the caudate, and implicates the entire striatum. DAT function anddensity decrease more obviously in the contralateral side with limb symptom thanin the opposite side for the early-middle stage PD patients. The uptake of ^99mTc-TRODAT-1 in striatum is a beneficial complement to the UPDRS score inthe ssessment of the disease severity and monitoring PD progress.