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.     

^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.     

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.     

不同显像时间窗对11C-CFT PET/CT显像测多巴胺转运蛋白分布半定量值的影响

目的 通过11C-甲基-N-2β-甲基酯-3β-(4-氟苯基)托烷(CFT) PET/CT显像,观察不同显像时间窗基底节区DAT分布的半定量值,寻找最佳显像时间窗并分析不同年龄和性别间的DAT分布差异.方法 将31名[男20名,女11名,平均年龄(55.7±2.3)岁]知情同意的健康受试者按随机区组法分为年龄匹配的3组,分别在注射11 C-CFT后40～60 min、60～ 80 min和80～100 min进行PET/CT静态显像,计算机自动勾画ROI,获得不同显像时间窗内尾状核及壳核DAT分布的半定量值(尾状核或壳核放射性计数/顶枕叶放射性计数-1),使用单因素方差分析及最小显著差异t检验对不同脑区半定量值进行比较.采用两独立样本t检验比较不同年龄(≥60岁和＜60岁)和性别患者最佳显像时间窗内尾状核及壳核半定量值的差异.结果 左侧尾状核(2.08±0.06、1.75±0.07和1.77±0.12)、右侧壳核前部(2.33±0.06、1.95±0.09和2.08±0.12)、双侧壳核后部(左:1.88±0.06、1.55±0.88和1.72±0.09,右:1.98±0.07、1.61±0.09和1.69±0.12)的DAT分布半定量值在3个时间窗内的差异具有统计学意义(F=3.588、3.345、4.479和3.557,均P＜0.05).其中,40 ～ 60 min显像与60～80 min相比,左侧尾状核、右侧壳核前部、双侧壳核后部半定量值差异具有统计学意义(均P＜0.05);与80～100 min相比,左侧尾状核半定量值差异具有统计学意义(P＜0.05).而60～ 80 min与80～ 100 min显像差异均不具有统计学意义(均P＞0.05).＜60岁的健康人尾状核、壳核DAT分布半定量值高于≥60岁者(t值分别为-3.260、-3.090、-3.270、-3.190、-2.270及-3.110,均P＜0.05);不同性别尾状核及壳核DAT分布差异均无统计学意义(t值分别为0.367、0.522、0.144、0.524、0.166及0.004,均P＞0.05).结论 脑内11C-CFT在注射后60 min达到稳定,11 C-CFT PET/CT显像检测DAT分布的最佳显像时间窗为注射后60～80 min;≥60岁和＜60岁健康人的DAT分布有差异.显像时间窗的统一和不同年龄段的半定量正常值的建立,有助于11C-CFT PET/CT显像在PD诊断方面的临床应用.     

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。     

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.     

多巴胺D2受体乃131I-epidepride显像对帕金森病的临床研究

目的 评价多巴胺D2受体显像剂131I-(s)-(-)-N-[(1-乙基-2-吡咯烷基)甲基]-5-碘-2,3-二甲氧基苯甲酰胺(epidepride)对帕金森病(PD)的临床应用价值.方法 PD患者38例(H/YⅠ～Ⅳ级,病程4个月～6年),健康对照组12例,静脉注射131I-epidepride 18.5 MBq 3 h后行SPECT显像,并应用感兴趣区(ROI)技术计算纹状体/枕叶放射性(ST/OC)比值,分析ST/OC比值与PD患者临床严重程度的相关性.采用SPSS 10.0软件对数据进行校正t检验,配对t检验及Spearman相关分析.结果 对照组131I-epidepride显像示双侧纹状体内有高度放射性浓聚,纹状体显示清晰,双侧基本对称,额叶、颞叶、顶叶、枕叶及小脑放射性较低.与健康对照组比较,PD患者ST内131I-epide-pride浓聚增加,但差异无统计学意义.早期PD患者(H/Y Ⅰ级)病侧肢体的对侧ST放射性显著增加、体积增大(壳核尤为显著),与同侧ST相比差异有统计学意义(t=7.89,P＜0.05).ST/OC比值与PD临床严重程度(H/Y分级)无明显相关性(r=0.12,P＞0.05).结论 多巴胺D2受体131I-Epi-depride SPECT显像有助于了解PD患者ST内突触后膜的多巴胺D2受体变化,PD患者D2上调,在偏侧PD中以病变对侧壳核尤为显著.ST/OC比值与PD临床严重程度无相关性.     

新生猪缺氧缺血性脑损伤模型纹状体多巴胺转运蛋白PET/CT显像

目的 利用PET/CT观察新生猪缺氧缺血(HI)性脑损伤纹状体(ST) DAT的变化,探讨DAT在判断HI性脑损伤程度中的价值.方法 制备新生猪HI脑损伤模型(n=20),为模型组;另取5头新生猪作为对照组.予猪颈静脉注射11C-N-2β-甲基酯-3β-(4-氟-苯基)托烷(CFT) 55.5 ～74.0 MBq/只,行PET/CT显像,观察新生猪的DAT变化,计算ST/枕叶(OC)比值.模型组按显像时间分为HI后0～6h、20 ～24 h、44 ～48 h、68～72 h显像亚组,显像完毕即刻处死各组猪,取大脑行病理分析.采用单因素方差分析和Pearson直线相关分析行数据比较.结果 11C-CFT在大脑皮质、小脑及ST放射性分布较高,脑白质放射性分布较低.随着时间延长,大脑皮质、小脑放射性明显减低,而ST显示仍清晰.HI后0～6h,ST DAT功能上调,ST/OC比值为1.34±0.04,与对照组比较差异有统计学意义(1.18 ±0.06,F=4.658,P＜0.05),其余时间组ST/OC比值分别为1.27±0.01、1.27±0.10和1.18±0.05.HI后各时间点病理示DAT免疫阳性神经元数量[(13±3)、(13±4)、(8±3)和(4±4)个/高倍视野]与11C-CFT PET示ST/OC比值呈正相关(r=0.844,P＜0.05).结论 11C-CFTPET/CT能够准确反映HI性脑损伤ST DAT的动态变化,且DAT的变化与缺血损伤的程度有关.     

99 Tcm-ECD SPECT显像定位致

目的探讨99Tcm-双半胱乙酯(ECD) SPECT显像对原发性癫致灶定位的价值.方法经临床和头皮脑电图(EEG)诊断为癫的34例患者行SPECT发作间期及发作期局部脑血流(rCBF)显像,以确定致灶.结果 22例患者发作间期rCBF显像出现rCBF灌注减低,28例发作期显示血流灌注增加,两期吻合的部位确定为致灶,据此行伽玛刀治疗.结论 SPECT对致灶定位有很大价值.     

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.     

慢性实验性帕金森病模型猴多巴胺转运蛋白显像研究

目的　探讨多巴胺系统功能显像对帕金森病 (PD)的诊断价值。方法　对 5只正常猴及 6只经颈动脉注射 1 甲基 4 苯基 1,2 ,3,6 四氢吡啶 (MPTP) 30个月的PD模型猴进行99Tcm 2 β [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 ,经图像处理 ,计算正常及PD模型猴纹状体特异摄取比值 (SURs)。结果　正常猴纹状体在 30 ,6 0 ,12 0 ,15 0 ,180及 2 4 0minSURs分别为 0 5 4 9,0 792 ,0 84 8,0 96 5 ,0 96 9和 0 96 4 ;MPTP模型猴 3h双侧纹状体比值 [健侧 (左侧 ,L) 损毁侧 (右侧 ,R) (L R) =1 32 8± 0 30 8]明显高于对照猴 (L R =1 0 16± 0 0 12 ,t=9 87,P <0 0 5 ) ;损毁侧纹状体 枕叶摄取比值为 0 385± 0 32 6 ,明显低于对侧 (0 795± 0 4 2 6 )及对照猴 (R :0 790± 0 2 4 4 ,L :0 819± 0 2 4 9;t分别为 8 5 6 ,9 4 2和 8 93,P均 <0 0 5 )。结论　99Tcm TRODAT 1SPECT脑显像能反映PD模型猴脑多巴胺能突触前功能的变化。     

多巴胺转运蛋白显像剂^99Tc^m—TRODAT-1药盒及注射液的质量控制

目的对自制多巴胺转运蛋白显像剂^99Tcm-TRODAT-1药盒及注射液进行质量控制研究。方法对3批^99Tc^m-TRODAT-1药盒及注射液进行澄清度、pH值、氯化亚锡与TRODAT-1含量、标记率、放化纯、半衰期测定,无菌以及细菌内毒素检查,可见异物、不溶性微粒检查,并分析药盒在不同存放环境下的稳定性。结果^99Tc^m-TRODAT-1药盒澄清度好,pH值为5．9±0．1,药盒中氯化亚锡与TRODAT-1含量稳定,标记率大于95％。药盒在0-4℃下6个月、室温（20～25℃）下10d内稳定性好。注射液澄清透明、pH值在5．5～7．0之间,放化纯≥95％,室温（20～25℃）下8h内放化纯〉90％。药盒及注射液无菌、细菌内毒素检查合格。结论自制的^99Tc^m-TRODAT-1药盒及注射液的质量控制方法简便易行,药盒及注射液质量符合临床应用要求。     

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     

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.     

Dopamine transporter imaging with [123I]FP-CIT SPECT: potential effects of drugs

Background [¹²³I]N-ω-fluoropropyl-2β-carbomethoxy-3β-{4-iodophenyl}nortropane ([¹²³I]FP-CIT) single photon emission computed tomography (SPECT) is a frequently and routinely used technique to detect or exclude dopaminergic degeneration by imaging the dopamine transporter (DAT) in parkinsonian and demented patients. This technique is also used in scientific studies in humans, as well as in preclinical studies to assess the availability of DAT binding in the striatum. In routine clinical studies, but also in scientific studies, patients are frequently on medication and sometimes even use drugs of abuse. Moreover, in preclinical studies, animals will be anesthetized. Prescribed drugs, drugs of abuse, and anesthetics may influence the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Discussion Here, we discuss the basic principle of how drugs and anesthetics might influence the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. We also review drugs which are likely to have a significant influence on the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Additionally, we discuss the evidence as to whether frequently prescribed drugs in parkinsonian and demented patients may have an influence on the visual interpretation and/or quantification of [¹²³I]FP-CIT SPECT scans. Finally, we discuss our recommendations as to which drugs should be ideally withdrawn before performing a [¹²³I]FP-CIT SPECT scan for routine clinical purposes. The decision to withdraw any medication must always be made by the specialist in charge of the patient’s care and taking into account the pros and cons of doing so.