| Title:Study of TRODAT-1 imaging for early diagnose in patients with Parkinson's Disease. University: Southeast UniversityObjective:To develop 99mTc labeled dopamine transporter (DAT) imaging agent99mTc-(2β-[N,N,-bis(2-mercaptoethyl)ethylenediamino]methyl,3β-(4-chlorophenyl)tropane(TRODAT-1) for evaluating changes of DAT in patients with Parkinson's Disease.Methods: Experimental One (Fabrication of animal model): There were three groups,including control group,PD group and generalized cerebral infarction group . Unilateral smashing that one handred and six rats received a unilateral injection of 6-hydroxydopamine(6-OHDA)into the substanti anigra pars compacta(SNc) and injecting autothrombo into carotid artery of twenty-two SD rats were used .Behavioral changes were investigated 1,7,14,21d after leision. Experimental Two(Pathology of PD model): Immunocytochemistry and electron microscope was used. Experimental Two(Study nuclear and image medicine): 99mTc-TRODAT-1 distribution in normal rat body and striatum was observed and the uptakes in sound side and smashed side of PD rats (14 day after lesion)striatum and in two sides of multiple infarction rats striatum were compared 0.5,1.0,2.0,4.0 hour after injected 37MBq(2ml) 99mTc-TRODAT-1 into caudal vein of normal group and PD group. After injected 740MBq(2ml) 99mTc-TRODAT-1 into caudal vein of three group , autoradiography was performed. After several days , MRI was performed in normal group and PD group of untreated .Results: Experimental One:Two fabrication of animal model is successful .Fifty-two and twenty-two is successful PD and generalized cerebral infarction model . Experimental Two: By immunohistochemistry observation,male cells(Dopamine neur cells)obviouse decrease,1,7,14,21d after lesion,lose <55%,55-65%,75-85%,>85%, in the same as praxiology。Electron microscope card show that lesion side of PD model it is thus clear tha impaired dopamine neur cell,but comparing two normal picture,dopamine receptor is no special under electron microscope. Experimental Three : 99mTc-TRODAT-1 distribution in normal rats body and brain resuits is that uptake tite of ST/CB ,ST/CX,ST/HP is 1.74,1.26,1.15;2.38, 1.76,2.06;4.25, 2.55,3.10;3.01,2.17,2.45(0.5,1.0,2.0,4.0h after injection)that exhibited obvious uptake in striatum.And PD rats results exhibited that the uptake was less in normal striatum than in smashed striatum obviously(uptake tite of ST/CB is in results). Autoradiography results show that corpus striatum of normal uptake is obviously higher than cerebral cortex,their odds is 2.52, two sides corpus striatum of normal model odds is 1.02,which is no obvious difference. Generalized cerebral infarction group is resemble with nomal group in autoradiography. Sound side up take of PD model is obviously higher than lesion side,that odds is 2.19,2.51,4.12,5.21 (1,7,14,21d after lesion, 2h after injection)。In MRI,normal model is no different with PD model.Conclusion :The methods of two fabrication of animal model is reliable. 99mTc-TRODAT-1might safe and neutnal , stable , produced easely ,specific , so it's SPECT imaging can provide a beneficial evidence for PD disease early diagnose.
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