^99Tc^m—TRODAT-1脑SPECT用于体质指数与纹状体多巴胺转运蛋白相互关系的研究

目的 探讨BMI与人脑纹状体DAT的相互关系及对99Tcm-TRODAT-1脑SPECT显像的影响.方法 31名健康志愿者（男16名,女15名）分别进行颅脑MRI和99Tcm-TRODAT-1脑SPECT显像.对SPECT图像进行三维重建,参照MRI图像,在SPECT图像横断面纹状体（ST）显示最清楚的连续4层图像上对脑左、右ST（LST、RST）分别进行ROI勾画,取小脑（CB）作为本底参考区,分别计算ST/CB、LST/CB和RST/CB的放射性摄取比值.采用SPSS 15.0软件,分别对ST/CB、LST/CB、RST/CB与BMI、年龄进行Pearson相关性分析;然后以BMI、年龄为自变量,ST/CB为因变量进行多因素回归分析.结果 31名健康志愿者99Tcm-TRODAT-1脑SPECT显像示双侧ST左右对称,放射性前部高于后部.其ST/CB、LST/CB和RST/CB的平均值分别为1.71±0.16,1.70±0.16和1.72±0.17;女性ST/CB、LST/CB和RST/CB的平均值分别为1.74±0.18,1.71±0.19和1.76±0.19;男性ST/CB、LST/CB和RST/CB的平均值分别为1.68±0.14,1.68±0.13和1.69±0.15.ST/CB、LST/CB和RST/CB与BMI均呈负相关（r=-0.53,-0.57,-0.47,P均＜0.05）.ST/CB与年龄呈负相关（r=-0.39,P=0.03）.多因素回归分析发现仅BMI为显著影响因素（回归系数β=-0.53,t=-3.36,P=0.002）.结论 健康人脑ST DAT水平随着BMI、年龄的增高而呈降低趋势.女性STDAT水平略高于男性.提示在99Tcm-TRODAT-1脑SPECT显像中,不但要考虑年龄、性别等影响因素,而且要注意BMI也是重要影响因素.     

中枢多巴胺转运蛋白显像剂^99Tc^m—TRODAT—1

^99Tc^m－TRODAT－1是一种新型中枢多巴胺转运蛋白显像剂，其SPECT显像在帕金森氏病的早期诊断中具有重要的临床价值。章综述了近年来^99Tc^m－TRODAT－1的生化及其标记制备、动物实验、显像方案和临床前研究方面的进展，展示了^99Tc^m－TRODAT－1在临床有良好的应用前景。     

多巴胺转运蛋白显像剂

目的研究多巴胺转运蛋白(DAT)显像剂99Tcm-2β-[N,N'-双(2-巯乙基)乙撑二胺基]甲基,3β-(4-氯苯基)托烷(TRODAT-1)用于帕金森病(PD)早期诊断的价值。方法制备99Tcm-TRODAT-1,用2β-羧甲基,3β-(4-碘苯基)托烷(β-CIT)阻断DAT后,观察大鼠脑内分布、兔血药清除动力学、异常毒性实验、正常及PD模型鼠的放射自显影图并对志愿者进行显像。结果制备的99TcmM-TRODAT-1放化纯大于90％,室温下放置6h稳定;用β-CIT阻断后大鼠纹状体的特异性摄取即纹状体与小脑放射性计数差除以小脑放射性计数为0.12(对照组为3.45),表明β-CIT对99Tcm-TRODAT-1有明显的竞争抑制作用。血药清除动力学研究表明它的分布半衰期T1/2(α)=1.2min,消除半衰期T1/2(β)=368min。模型鼠的放射自显影结果表明纹状体的特异摄取随着给药(神经毒素)总量的增加而减少,并有良好的线性关系(r=-0.9792)。正常猴断层显像在3个断面上基底节均有明显高于周围组织的摄取,单侧PD模型猴显像示健侧纹状体与小脑的比值(1.56)明显高于损毁侧比值(O.94)。志愿者脑断层图像清晰,患侧纹状体对99Tcm-TRODAT-1摄取较正常侧减低,其显像结果分析与临床表现相吻合。结论99Tcm-TRODAT-1制备方便,体外稳定,毒性低,用于人非常安全;纹状体与小脑、大脑皮质的比值高,有利于获得清晰的图像。     

多巴胺转运蛋白显像剂^99Tc^m—TRODAT—1临床前药理研究

目的 研究多巴胺转运蛋白（DAT）显像剂^99Tc^m－2β-[N,N‘-双（2－巯乙基）乙撑二胺基]甲基,3β-（4-氯苯基）托烷（TRODAT－1）用于帕金森病（PD）早期诊断的价值。方法 制备^99Tc^m－TRODAT－1,用2β－羧甲基,3β-（4-碘苯基）托烷（β－CIT）阻断DAT后,观察大鼠脑内分布、兔血药清除动力学、异常毒性实验、正常及PD模型 的放射自显影图并对志愿者进行显像。结果 制备的^99Tc^m－TRODAT－1放化纯大于90％,室温下h稳定;用β－CIT阻断后大鼠纹状体的特异性摄取即纹状体与离放射性计数差除以小脑放射性计数为0.12（对照组为3.45）,表明β－CIT对^99Tc^m－TRODAT－1有明显的竞争抑制作用。血药清除动力学研究表明它的分布半衰期T1／2（α)=1.2min,消除半衰期T1／2（β）=368min。模型鼠的放射自显影结果表明纹状体的特异摄取随着给药（神经毒素）总量的增加而减少,并有良好的线性关系（r=-0.9792）。正常猴断层显像在3个断面上基底节均有明显高于周围组织的摄取,单侧PD模型猴显像示健侧纹状体与小脑的比值（1.56）明显高于损毁侧比值（0.94）。志愿者脑断层单侧PD模型猴显像示健侧纹状体与小脑的比值（1.56）明显高于损毁侧比值（0.94）。志愿者脑断层图像清晰,患侧纹状体对^99Tc^m－TRODAT－1摄取较正常侧减低,其显像结果分析与临床表现相吻合。结论 ^99Tc^m－TRODAT－1制备方便,体外稳定,毒性低,用于人非常安全;纹状体与小脑、大脑皮质的比值高,有利于获得清晰的图像。     

脑多巴胺转运蛋白显像剂99Tcm-TRODAT-1的SPECT显像

目的探讨脑多巴胺转运蛋白显像剂99Tcm-2β-[N,N′-双(2-巯乙基)乙撑二胺基]甲基,3β-(4-氯苯基)托烷(TRODAT-1)SPECT显像对帕金森病(PD)的诊断价值.方法对30例PD患者及16例健康志愿者行99Tcm-TRODAT-1脑SPECT显像.用2种半定量方法分析①应用感兴趣区(ROI)技术计算双侧横断面、矢状面纹状体(ST)/小脑(CB)放射性摄取比值(ST/CB);②取横断面基底节,将其划分成左、右ST,左、右尾状核和左、右壳核6个ROI,CB和枕叶皮质(OC)作为本底参考区,计算基底节ROI的放射性摄取比值[ROI/(CB+OC/2)].结果对照组横断面、矢状面左、右侧ST/CB分别为1.55±0.15、1.58±0.14和1.62±0.17、1.69±0.16.PD患者ST/CB和ROI/(CB+OC/2)均比对照组明显减低,差异有显著性(P＜0.001).计算矢状面双侧ST/CB更合理.根据ROI/(CB+OC/2)可获得基底节各神经核团放射性分布半定量数据.结论99Tcm-TRODAT-1脑SPECT显像是诊断PD的有效方法.     

脑多巴胺转运蛋白显像剂99Tcm-TRODAT-1的标记研究

目的研究99Tcm-2β-[N,N′-双(2-巯乙基)乙撑二胺基]甲基,3β-(4-氯苯基)托烷(TRODAT-1)显像剂的标记方法和放化纯(Rp).方法 TRODAT-1(液体)3批共37支.在TRODAT-1瓶中加入PBS 液、EDTA液、SnCl2 、GH液和不同放射性浓度的99TcmO-4注射液,煮沸30 min.99Tcm-TRODAT-1注射液Rp测定采用萃取剂-显像法,并用99Tcm-双半胱乙酯(ECD)比照.结果 34支99Tcm-TRODAT-1 Rp>85.03%,平均Rp=(87.70±1.94)%,另3支Rp<65.23%,平均Rp=(60.14±0.27)%,放射性浓度皆<7.4 GBq/ml.结论用TRODAT-1(液体)制备99Tcm-TRODAT-1注射液成功率达92%,放射性浓度对99Tcm-TRODAT-1的Rp影响不大.     

中枢多巴胺转运蛋白显像剂99Tcm-TRODAT-1

99Tcm-TRODAT-1是一种新型中枢多巴胺转运蛋白显像剂,其SPECT显像在帕金森氏病的早期诊断中具有重要的临床价值.文章综述了近年来99Tcm-TRODAT-1的生化及其标记制备、动物实验、显像方案和临床前研究方面的进展,展示了99Tcm-TRODAT-1在临床有良好的应用前景.     

新配方99TCm-TRODAT-1药盒的研制

目的 制备标记率＞90%的99Tcm-2β-[N,N'-双(2-巯乙基)乙撑二胺基]甲基-3β-(4-氯苯基)托烷(TRODAT-1)药盒,并研究药盒中各组分含量与pH值对其标记率的影响.方法 按每支药盒含TRODAT-1 50μg、SnCl2·2H2O 70μg、EDTA-2Na 1.0 mg、Na2HPO4·12H2O 17.6 mg,KH2PO42.37 mg和葡庚糖酸钠(GH)10 mg制备药盒,用上行薄层色谱法测定标记率;保持其他组分含量不变,分别改变TRODAT-1、SnCl2,EDTA-2Na和GH的用量,并测定标记率;保持其他组分含量不变,调节pH缓冲剂的用量,使药盒在不同的pH值下标记,测定标记率.结果 制备的药盒标记率＞90%,稳定性好.药盒中各组分含量在下列范围内标记率＞90%TRODAT-1 20～200 μg、SnCl2 4～100 μg、EDTA-2Na 0.5～2.0 mg、GH 1～20 mg、pH值4.5～8.3.结论 可成功制备标记率＞90%的TRODAT-1药盒,其稳定性较好.     

99Tcm-TRODAT-1脑SPECT用于体质指数与纹状体多巴胺转运蛋白相互关系的研究

Objective To assess the relationship between the BMI and the brain DAT, and the influence of BMI on the brain SPECT imaging with 99Tcm-TRODAT-1. Methods MRI and 99Tcm-TRODAT-1SPECT imaging were performed in 31 healthy volunteers(16 males and 15 females), and then the three-dimensional reconstruction of SPECT images were completed. Based on the MRI images, right striatum (RST) and the left striatum (LST) were drawn as ROI on the 4 most clearly consecutive transverse slices.The cerebellum (CB) was taken as the background reference area and the corresponding uptake ratios of ST/CB, LST/CB and RST/CB were calculated. The Pearson correlation tests for radio-uptake ratios (ST/CB, LST/CB, RST/CB), BMI and age were performed, Then multiple linear regression analysis using ST/CB as dependent variable and BMI and age as independent variables was performed. SPSS 15.0 was used in data analysis. Results The ST imaging was symmetrical. The radioactivity was higher in the ST front area than that of the back area. The average uptake ratios of ST/CB, LST/CB, RST/CB were 1.71±0.16,1.70 ± 0. 16 and 1.72±0.17 respectively, in which the three ratios of the female were 1.74 ± 0. 18, 1.71±0. 19 and 1.76 ± 0. 19 respectively and those of the male were 1.68 t 0. 14, 1.68 ± 0. 13 and 1.69± 0.15respectively. ST/CB, LST/CB and RST/CB were negatively correlated with patients'BMI (r = -0. 53,-0.57,-0.47, all P＜0.05). The ST/CB was negatively correlated with patients' age(r=-0.39, P=0. 03). The multiple linear regression analysis showed that the BMI was significant independent variable (β=-0.53, t= -3.36, P=0. 002). Conclusions TheSTDAT,evel may decrease as patients' BMI and age increase. Females' DAT level is slightly higher than males'. For ST DAT imaging, age, gender and BMI should be all taken into consideration.     

抽动秽语综合征的脑^99Tc^m-TRODAT-1SPECT显像

目的 利用^99Tc^m-TRODAT-1 SPECT脑显像观察抽动秽语综合征（TS）患者纹状体DAT的结合能力,探讨纹状体^99Tc^m-TRODAT-1的摄取率与年龄、病程及抽动严重性之间的关系.方法 选取未经治疗的TS患者18例：男14例,女4例,年龄（24±10）岁;性别、年龄匹配的健康对照者8名.所有受检者按体质量静脉注射^99Tc^m-TRODAT-1 11.1～14.8 MBq/kg,2.5 h后行脑SPECT显像.分别在双侧纹状体及进一步划分的尾状核和壳核勾画感兴趣区,以小脑为本底,计算纹状体/小脑放射性比值,该值反映纹状体对99Tcm-TRODAT-1的摄取率.采用独立样本t检验将TS患者与对照组的99Tcm-TRODAT-1摄取率进行比较;采用Pearson相关分析将患者摄取率与年龄、病程、抽动严重性等做进一步相关分析.结果 TS患者双侧纹状体对99Tcm-TRODAT-1的摄取率明显高于对照组（2.17±0.23与1.87±0.24,t=2.957,P＜0.05）,且分布对称;纹状体摄取率与患者年龄（r=-0.320,P＞0.05）、抽动严重性（r=0.345,P＞0.05）无关,但与病程呈负相关（r=-0.483,P＜0.05）,病程越短,摄取率越高.结论 未经治疗的TS患者DAT功能活性较对照组明显增强;DAT活性增高程度与病程呈负相关.99Tcm-TRODAT-1 SPECT脑显像可作为初诊TS患者确诊的客观依据.     

The role of dopamine transporter imaging agent [Tc]TRODAT-1 in hemi-parkinsonism rat brain

This study aims to investigate the relationship between the determination of dopamine level by high performance liquid chromatography (HPLC) with electrochemical detection (ECD) and the detection of dopamine transporter (DAT) counts using autoradiography with DAT image agent [^99mTc]TRODAT-1. For striatal lesions, pretreatment of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle shows that autoradiogaphic labeling of striatum region is reduced to near-background level. Using HPLC with ECD, unilateral 6-OHDA treatment is associated with significant (p < 0. 0002) reductions of dopamine levels. For the striatum of the 6-OHDA-lesioned side, dopamine content and DAT counts are reduced to 97% and 90%, respectively. Thus, our observation indicates a potential of using [^99mTc]TRODAT-1 for the evaluation of animal DAT.     

抽动秽语综合征的脑99Tcm-TRODAT-1SPECT显像

Objective To observe dopamine transporter (DAT) binding capacity using 99Tcm-TRODAT-1 in drug-naive patients with Tourette's syndrome (TS) on SPECT imaging, and explore possible correlations between 99Tcm-TRODAT-1 uptake ratio and TS patient's age, disease duration, and tic severity.Methods Eighteen drug-naive TS patients, male 14, female 4, as well as 8 age- and gender-matched healthy subjects were recruited. Brain SPECT imaging was performed 2. 5 h after intravenous injection of 11.1 - 14.8 MBq/kg 99Tcm-TRODAT-1. ROI was drawn on the striatum including its sub-regions of caudate and putamen, with cerebellum as the background. Striatum/cerebellum ratio was calculated. Comparisons of the ratios between TS patients and controls were carried out by independent-sample t-test. Pearson correlation analysis was performed between DAT uptake ratios of striatum and patients' age, disease duration, tic severity. Results Compared with the control, higher symmetrically striatum uptake of 99Tcm-TRODAT-1 in TS patients was observed (2.17±0.23 vs 1.87±0.24, t =2.957, P＜0.05). Age (r= -0.320, P＞0.05)and tic severity(r = 0. 345, P ＞ 0.05) scores were not significantly correlated with specific uptake ratios measured in the striatum. But there was significant negative correlation between disease duration and the specific uptake ratios (r = - 0. 483, P ＜ 0. 05). Conclusions 99 Tcm-TRODAT-1 SPECT imaging may play an adjuvant role for initial evaluation of untreated TS.     

早期帕金森病患者脑99Tcm-TRODAT-1 SPECT显像研究

目的　探讨脑多巴胺转运蛋白 (DAT) 99Tcm 2 β [N ,N′ 双 (2 巯乙基 )乙撑二胺基 ]甲基 ,3 β (4 氯苯基 )托烷 (TRODAT 1)SPECT显像在帕金森病 (PD)早期诊断中的临床应用价值。 方法　对10例正常对照者及 50例早期PD患者行脑DAT99Tcm TRODAT 1SPECT显像 ,利用感兴趣区技术计算纹状体 (ST)与枕叶 (OC)、额叶 (FC)的放射性比值 [(ST -OC) OC ,(ST -FC) FC]。结果　对照组双侧ST摄取差异无显著性。早期PD患者双侧 (ST -OC) OC和 (ST -FC) FC较对照组明显降低 ;起病肢体对侧 (ST -OC) OC和 (ST -FC) FC比起病肢体同侧均明显降低 (P均 <0 0 0 1)。PDHoehn Yahr(H Y)Ⅰ级患者病变肢体对侧及同侧 (ST -FC) FC较对照组均明显降低 (P均 <0 0 5)。早期PD患者起病肢体对侧ST摄取与病程及H Y分级呈明显相关。结论　脑99Tcm TRODAT 1SPECT显像有助于PD的早期诊断