Striatal dopamine transporter function in dementia with Lewy bodies and Parkinson's disease

The aim of this study was to compare parkinsonian features and loss of striatal dopamine transporter (DAT) function in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD), matched for age and disease duration. Twenty patients with DLB, 24 PD patients and 10 matched controls were examined with SPET using a dual-head camera and the dopamine-transporter ligand ¹²³I-#-CIT (148 MBq). Moreover, in a subgroup of patients (16 DLB and 20 PD patients), subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) - motor examination (ME) subscale were obtained during "practical off", i.e. 12 h following withdrawal of antiparkinsonian therapy. Compared with controls, striatal/cerebellar (S/C) ratios of DAT binding were significantly reduced in both DLB and PD, deficits being more marked in DLB patients (controls 7.2ǃ.2, DLB 3.3ǃ, PD 4.2ǃ.4; means-SD). The side-to-side differences in the S/C ratios were lower in the DLB group and the controls than in PD patients (0.4ǂ.4, 0.2ǂ.2 and 0.6ǂ.3, respectively, P<0.05). The total UPDRS-ME scores during practical-off were significantly higher in the DLB than in the PD group (41.2ᆠ.7 vs 26.6ᆣ.3, P<0.01). The side-to-side differences of the summed UPDRS extremity subscores were smaller in the DLB than in the PD group (2.2DŽ.3 vs 7.4Dž.9, P<0.0001). Our findings suggest that parkinsonism evolves largely symmetrically and progresses more rapidly with more severe loss of striatal dopamine transporter function in DLB compared to PD. Whether these findings are helpful in the differential diagnosis of DLB and PD needs to be examined in further studies.     

Striatal dopamine transporter function in dementia with Lewy bodies and Parkinson's disease.

The aim of this study was to compare parkinsonian features and loss of striatal dopamine transporter (DAT) function in patients with dementia with Lewy bodies (DLB) and Parkinson's disease (PD), matched for age and disease duration. Twenty patients with DLB. 24 PD patients and 10 matched controls were examined with SPET using a dual-head camera and the dopamine-transporter ligand 123I-beta-CIT (148 MBq). Moreover, in a subgroup of patients (16 DLB and 20 PD patients), subscores of the Unified Parkinson's Disease Rating Scale (UPDRS)-motor examination (ME) subscale were obtained during "practical off", i.e. 12 h following withdrawal of antiparkinsonian therapy. Compared with controls, striatal/cerebellar (S/C) ratios of DAT binding were significantly reduced in both DLB and PD, deficits being more marked in DLB patients (controls 7.2 +/- 1.2, DLB 3.3 +/- 1, PD 4.2 +/- 1.4; means +/- SD). The side-to-side differences in the S/C ratios were lower in the DLB group and the controls than in PD patients (0.4 +/- 0.4. 0.2 +/- 0.2 and 0.6 +/- 0.3, respectively, P<0.05). The total UPDRS-ME scores during practical-off were significantly higher in the DLB than in the PD group (41.2 +/- 12.7 vs 26.6 +/- 15.3, P<0.01). The side-to-side differences of the summed UPDRS extremity subscores were smaller in the DLB than in the PD group (2.2 +/- 2.3 vs 7.4 +/- 3.9, P<0.0001). Our findings suggest that parkinsonism evolves largely symmetrically and progresses more rapidly with more severe loss of striatal dopamine transporter function in DLB compared to PD. Whether these findings are helpful in the differential diagnosis of DLB and PD needs to be examined in further studies.     

Striatal dopamine transporter imaging correlates with anxiety and depression symptoms in Parkinson's disease.

We studied the correlation of striatal dopamine transporter (DAT) imaging with anxiety and depression symptoms in Parkinson's disease (PD). METHODS: Patients with idiopathic PD (n = 76) and age-matched healthy volunteers (n = 46) underwent SPECT brain scans with (99m)Tc-TRODAT-1, a radiolabeled tropane that selectively binds to the DAT. TRODAT-1 distribution volume ratios, a reflection of DAT availability, were calculated from the SPECT scan data for 6 regions of interest (ROIs) in the caudate and putamen. The association between neuropsychiatric symptoms (anxiety, depression, and fatigue) and DAT availability was explored for both subject groups, and the impact of disease severity on this association was examined in the PD group. RESULTS: PD patients showed lower DAT availability than did healthy volunteers in all examined regions (for all ROIs, P < 0.001). In PD patients, higher individual affective measures (for anxiety, r = -0.30 and P = 0.01; and for depression, r = -0.24 and P = 0.05) and total affect scores (r = -0.31; P = 0.01) were associated with diminished left anterior putamen DAT availability. The association between total affect scores and DAT availability was present only in the subset of patients with less severe PD (r = -0.35; P = 0.04), but subjects with the highest DAT availability did not show high total affect scores. No association between neuropsychiatric measures and DAT availability was found in the controls. CONCLUSION: These preliminary findings suggest that decreased DAT availability may be necessary for but not invariably associated with the development of affective symptoms in PD. This suggestion is consistent with previous research showing a link between depression and basal ganglia impairment, particularly involving the left hemisphere, and extends this finding to include anxiety.     

Decreased dopamine transporter binding in Machado-Joseph disease.

The aim of this study was to use 99mTc-TRODAT-1 brain SPECT for investigation of the binding of dopamine transporter (DAT) in the nigrostriatal dopaminergic pathway of symptomatic Machado-Joseph disease (MJD) and to compare the results with the abnormal cytidylate, adenylate, and guanylate (CAG) expansion in the MJD1 gene and other clinical factors. METHODS: Ten symptomatic MJD patients (8 women, 2 men; age range, 20-71 y; mean age +/- SD, 36.4 +/- 10.6 y; mean duration of illness, 9.8 +/- 5.4 y) and 21 healthy volunteers (age range, 24-71 y; mean age, 47.6 +/- 20.1 y) were examined. Brain SPECT images were acquired 4 h after injection. The ratio of specific to nonspecific nigrostriatal 99mTc-TRODAT-1 binding was measured and compared with the clinical symptoms, duration of illness, and size of abnormal expanded CAG repeats. RESULTS: All nigrostriatal 99mTc-TRODAT-1 ratios were significantly lower in MJD patients than in healthy volunteers (P < 0.05). Discriminant function analysis of all MJD patients showed that the decreased binding of 99mTc-TRODAT-1 in the putamen was not significantly different from that in the caudate nucleus. Eight of 10 MJD patients had significantly decreased 99mTc-TRODAT-1 uptake. Of these 8, 2 had extrapyramidal signs and 6 had no obvious extrapyramidal signs. The other 2 patients, who had normal 99mTc-TRODAT-1 uptake, had no obvious extrapyramidal signs. CONCLUSION: Our findings indicate that 99mTc-TRODAT-1 brain SPECT is an appropriate method for evaluating damage to the nigrostriatal DAT in symptomatic MJD patients with and without extrapyramidal signs. The decreased binding of 99mTc-TRODAT-1 in the nigrostriatal dopaminergic pathway in symptomatic MJD patients correlates with the phenotype of extrapyramidal signs but not with the abnormal CAG repeat length, age at disease onset, or disease duration.     

Loss of dopamine transporter binding in Parkinson's disease follows a single exponential rather than linear decline.

Imaging of L-dopa uptake or dopamine transporter binding can monitor the progression of Parkinson's disease. Most follow-up studies have provided data best fitted by a linear decline of their outcome measure. However, in these studies, patients were repeatedly scanned during their first years after a diagnosis had been established. METHODS: We followed 6 patients with early Parkinson's disease for 7.5 y using 123I-labeled N-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane and SPECT. RESULTS: Loss of dopamine transporter binding was best fitted using a single exponential approximation. A 63% loss (tau [time constant tau]) was calculated as 5.18 +/- 7.62 y in the putamen and 10.62 +/- 31.4 y in the caudate nucleus when a 3-parameter fit was used. CONCLUSION: These data approximate, for what is to our knowledge the first time, the decline of dopamine transporter binding as expected in biologic systems and may allow for models that correct for exponential decline to be developed and for disease-modifying effects in patients with advanced disease to be determined.     

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.     

小鼠帕金森病模型多巴胺转运体、脑血流灌注与葡萄糖代谢变化

目的联合观察不同剂量1甲基4苯基1,2,3,6四氢吡啶(MPTP)对小鼠多巴胺神经系统、局部脑血流灌注和葡萄糖代谢的损伤效应。方法8周龄雄性C57BL6小鼠,按体重腹腔注射0～80mgkg的MPTP,10d后用免疫组织化学法测定黑质酪氨酸羟化酶(TH)阳性细胞数,放射自显影法测定尾壳核多巴胺转运体(DAT)相对含量、尾壳核和丘脑局部血流量与葡萄糖代谢水平。结果随MPTP用量增加,DAT损耗和TH阳性细胞数减少程度均加重,两者呈正相关(r=0.998,P<0.05)。其中80mgkg组平均DAT损耗达79.8%(P<0.001),TH阳性细胞数减少达54.1%(P<0.001)。尾壳核和丘脑局部血流量在各组之间差异无显著性(P>0.2)。尾壳核、丘脑葡萄糖代谢在80mgkg组分别下降了3.0%和5.4%(P<0.05)。结论MPTP引起黑质多巴胺神经元和尾壳核DAT丧失存在明显剂量效应关系,尾壳核和丘脑的局部血流灌注变化不明显,葡萄糖代谢在高剂量组有轻微下降。     

Quantification of dopamine transporter by 123I-PE2I SPECT and the noninvasive Logan graphical method in Parkinson's disease.

(E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methyl-phenyl) nortropane (PE2I), a cocaine analog, is a new, highly specific tracer for imaging dopamine transporter labeled with (123)I for in vivo SPECT. Its reversible binding on dopamine transporter and its rapid kinetics allow quantification of its binding potential according to a 3-compartment model. For quantification of distribution volume of reversible tracer, Logan developed a noninvasive and graphical method that allows accurate estimation of binding potential. In this study, we performed (123)I-PE2I SPECT on healthy volunteers and patients with Parkinson's disease (PD) to validate the Logan graphical method for quantification of (123)I-PE2I binding and to analyze the relationship between (123)I-PE2I SPECT and clinical features of this frequent degenerative disease. METHODS: Eight PD patients (3 women, 5 men; mean age, 64 +/- 7.9 y; disease duration range, 1-8 y, Hoehn and Yahr stage range, 1-2.5) and 8 age-matched healthy volunteers (4 women, 4 men; mean age, 61.5 +/- 9.5 y) were included in 2 centers and studied with SPECT. Four sequential SPECT imaging sessions of 15-min duration were performed from 5 to 65 min after bolus injection of 140 +/- 30 MBq of (123)I-PE2I. RESULTS: The kinetics of PE2I in healthy volunteers and PD patients were rapid, and the Logan graphical method allowed quantification of distribution volume ratio (DVR) in the caudate nucleus and putamen. (123)I-PE2I striatal specific binding was significantly reduced in PD patients, compared with healthy volunteers, in the caudate and putamen. The decrease of DVR in the putamen was significantly and inversely correlated to disease duration and Hoehn and Yahr stage. In asymmetric PD patients, (123)I-PE2I uptake was significantly more reduced in the putamen contralateral to the side with predominant clinical symptoms. However, (123)I-PE2I uptake was also significantly reduced in the ipsilateral putamen, compared with that in healthy volunteers, suggesting that (123)I-PE2I SPECT can detect nigrostriatal degeneration before the appearance of clinical symptoms. CONCLUSION: Our data indicate that the Logan graphical method is accurate for noninvasive quantification of PE2I and that (123)I-PE2I SPECT is a useful quantitative method for accurate estimation of nigrostriatal dopaminergic nerve terminal degeneration. The close relationships between SPECT findings and clinical data suggest that this method is useful for objectively following the progression of PD and for assessing the effect of potential neuroprotective treatments. Finally, our findings suggest that (123)I-PE2I SPECT can be used for preclinical and early diagnosis of PD.     

Relationship between clinical features of Parkinson's disease and presynaptic dopamine transporter binding assessed with [123I]IPT and single-photon emission tomography

IPT [N-(3-iodopropen-2-yl)-2-carbome-thoxy-3-(4-chlorophenyl) tropane] is a new cocain analogue which allows the presynaptic dopamine transporters to be imaged with single-photon emission tomography (SPET) as early as 1–2 h post injection. In the present study [¹²³I]IPT SPET was performed in patients with Parkinson's disease (PD) to analyse the relationship between specific dopamine tansporter binding and clinical features of the disease. Twenty-six PD patients (Hoehn and Yahr stages I-IV, age range 40–79 years) and eight age-matched controls were studied. SPET imaging was performed 90–120 min after injection of 160–185 MBq [¹²³I]IPT using a triple-head camera. For semiquantitative evaluation of specific [¹²³I]IPT binding, ratios between caudate, putamen and background regions were calculated. Specific [¹²³I]IPT uptake was significantly reduced in PD patients compared to controls. Most patients showed a marked asymmetry with a more pronounced decrease in [¹²³I]IPT binding on the side contralateral to the predominant clinical findings. The putamen was always more affected than the caudate. [¹²³I]IPT binding was significantly correlated with disease duration (r=–0.7,P<0.0001) but not with the age of PD patients (r=–0.10,P=0.61). Specific [¹²³I]IPT uptake in the caudate and putamen, and putamen to caudate ratios, decreased with increasing Hoehn and Yahr stage. Our findings indicate that [¹²³I]IPT SPET may be a useful technique to estimate the extent of nigrostriatal degeneration in PD patients. Close relationships between striatal [¹²³I]IPT binding and clinical features of the disease suggest that this method can be used to objectively follow the course and progression of PD. The reduced putamen to caudate ratios observed even in patients with mild, newly recognized symptoms indicate that particularly this parameter may help to establish the correct diagnosis in the early course of PD.     

帕金森病脑部葡萄糖代谢和脑多巴胺转运体PET显像特点的临床研究

目的 探讨18F-FDG脑代谢联合11C-甲基-N-2β-甲基酯-3β（4-F苯基）托烷（11C-CFT）脑多巴胺转运体（DAT）PET双显像在帕金森病（PD）诊断与病情严重程度评估中的应用价值。 方法 对55例不同严重程度的PD患者及30名健康对照者分别行18F-FDG脑代谢显像和11C-CFT脑DAT PET显像检查,通过勾画ROI,比较PET图像中不同严重程度的PD患者与健康对照者中脑基底节区葡萄糖代谢及DAT分布的差异,分析18F-FDG PET、11C-CFT PET显像在不同严重程度PD评估中的作用及特点。 结果 与健康对照者相比,18F-FDG PET显像中PD患者脑葡萄糖代谢改变主要为双侧基底节区壳核对称性代谢增高,同时部分患者伴有大脑皮质不同程度代谢减低;11C-CFT PET显像中PD患者双侧尾状核、壳核前、中、后部表现为DAT分布不同程度减低。单侧症状者或双侧症状者均以患侧对侧基底节区壳核DAT分布减低明显,并以壳核后部DAT分布减低为著。 结论 18F-FDG PET联合11C-CFT PET双显像在PD诊断及病情严重程度评估中有应用价值。     

Long-term monitoring of gait in Parkinson's disease

A new system for long-term monitoring of gait in Parkinson's disease (PD) has been developed and validated. The characteristics of every stride taken over 10-h epochs were acquired using a lightweight ankle-mounted sensor array that transmitted data wirelessly to a small pocket PC at a rate of 100 Hz. Stride was calculated from the vertical linear acceleration and pitch angular velocity of the leg with an accuracy of 5 cm. Results from PD patients (5) demonstrate the effectiveness of long-term monitoring of gait in a natural environment. The small, variable stride length characteristic of Parkinsonian gait, and fluctuations of efficacy associated with levodopa therapy, such as delayed onset, wearing off, and the 'off/on' effect, could reliably be detected from long-term changes in stride length.     

18F-FP-β-CIT PET脑显像在早期诊断帕金森病中的意义

目的 探讨多巴胺转运蛋白(DAT)PET显像在早期诊断帕金森病(PD)及评估其严重度中的意义。方法 以^18F—N—(3—氟丙基)—2β—甲酯基—3β—(4′—碘苯基)去甲基托烷(FP—β—CIT)为显像剂，对4例正常对照者、21例早期PD和10例晚期PD患者基底节区DAT进行PET显像，比较3组间基底节不同组成区DAT的差异，并判断其与临床严重程度的相关性。结果 在尾状核、前壳核、后壳核区，早期PD组的DAT均显著降低，分别降至对照组相应部位的71．8％、43．8％及23．6％，起病肢体对侧基底节DAT显著低于起病肢体同侧基底节DAT，早期偏侧PD患者起病肢体同侧(亚临床)基底节DAT显著低于对照者；晚期PD组则分别降至对照组的51．9％、31．8％及15．8％。这些区域的DAT与统一帕金森病评定量表(UPDRS)运动评分呈显著负相关，r分别为-0．423、-0.421、-0．532。结论 ^18F-FP—β—CIT PET显俊右助于PD的早期诊断及评估其严重度。     

帕金森患者脑多巴胺转运体11C-CFT PET/CT显像特点的分析

目的 探讨帕金森病（PD）患者11C-2β-甲氧甲酰-3β-（4-氟苯基）托烷（CFT）脑多巴胺转运体（DAT）PET/CT显像的特点,分析其对PD的临床诊断价值。 方法 回顾性分析2018年8月至2021年2月于贵州医科大学附属医院行11C-CFT PET/CT脑显像且经临床确诊的41例原发性PD患者的临床资料和影像学资料,其中男性21例、女性20例,年龄34~81岁（57.6±12.2）岁。根据Hoehn-Yahr（H-Y）分级将PD患者分为早期PD组（19例）和晚期PD组（22例）。同时纳入与PD组患者年龄匹配的8名健康受检者作为正常对照组,其中男性4名、女性4名,年龄42~72（61.0±9.8）岁。通过勾画感兴趣区（ROI）得到双侧尾状核、壳核及小脑3个层面的11C-CFT摄取值,按相应公式计算双侧尾状核、壳核、新纹状体的11C-CFT摄取值和不对称指数、壳核与尾状核摄取值的比值。计量资料的比较采用两独立样本t检验;计数资料的比较采用卡方检验;采用Pearson相关性分析评价PD患者新纹状体及各亚区DAT分布与各临床指标之间的相关性。 结果 在11C-CFT PET/CT脑显像中,PD组双侧尾状核放射性分布呈稍降低但尚均匀,双侧壳核放射性分布呈不同程度的降低或稀疏缺损。其中,早期PD组患者双侧壳核放射性分布呈不对称性降低或缺损;晚期PD组患者双侧壳核放射性分布呈较对称性稀疏缺损。与正常对照组比较,PD组新纹状体11C-CFT摄取值减低,且差异有统计学意义（12.29±2.75 对 7.69±2.42,t=4.818,P<0.01）;PD组不对称指数增高,且在壳核中表现最显著,差异有统计学意义（0.06±0.08 对 0.14±0.09,t=2.184,P<0.05）;PD组壳核与尾状核摄取值的比值降低,且差异有统计学意义（1.13±0.13 对 0.74±0.21,t=4.929,P<0.01）。与早期PD组比较,晚期PD组在新纹状体的摄取值降低最明显,且差异有统计学意义（8.50±1.77 对 6.99±2.71,t=2.070,P<0.05）,晚期PD组在尾状核、壳核不对称指数之间的差异均有统计学意义（0.06±0.06 对 0.11±0.08、0.18±0.10 对 0.11±0.07,t=2.251、2.858,均P<0.05）。PD患者新纹状体11C-CFT摄取值与年龄、起病年龄、H-Y分级均呈负相关（r=?0.444、?0.514、?0.426,均P<0.01）,与壳核11C-CFT摄取不对称指数呈正相关（r=0.331,P<0.05）。PD患者尾状核11C-CFT摄取值与年龄、起病年龄、H-Y分级均呈负相关（r=?0.537、?0.581、?0.380,均P<0.05）,与壳核不对称指数呈正相关（r=0.410,P<0.01）;PD患者壳核11C-CFT摄取值与起病年龄、H-Y分级均呈负相关（r=?0.353、?0.453,均P<0.05）,与病程、壳核与尾状核摄取值的比值均呈正相关（r=0.322、0.396,均P<0.05）。 结论 PD患者DAT在11C-CFT PET/CT脑显像上主要表现为双侧尾状核及壳核的放射性分布降低,11C-CFT PET/CT脑DAT显像有助于PD的诊断及其严重程度的评估。     

Quantification of 123I-PE2I binding to dopamine transporter with SPECT after bolus and bolus/infusion.

The aim of the present study was to describe a method combining easy implementation in a clinical setting with accuracy and precision in quantification of 123I-labeled N-(3-iodoprop-(2E)-enyl)-2beta-carboxymethoxy-3beta-(4'-methylphenyl)nortropane (PE2I) binding to brain dopamine transporter. METHODS: Five healthy subjects (mean age, 50 y; range, 40-68 y) were studied twice. In the first experiment, dynamic SPECT data and arterial plasma input curves obtained after 123I-PE2I bolus injection were assessed using Logan, kinetic, transient equilibrium, and peak equilibrium analyses. Accurate and precise determination of BP1 (binding potential times the free fraction in the metabolite-corrected plasma compartment) and BP2 (binding potential times the free fraction in the intracerebral nonspecifically bound compartment) was achieved using Logan analysis and kinetic analysis, with a total study time of 90 min. In the second experiment, (123)I-PE2I was administrated as a combined bolus and constant infusion. The bolus was equivalent to 2.7 h of constant infusion. RESULTS: The bolus-to-infusion ratio of 2.7 h was based on the average terminal clearance rate from plasma in the bolus experiments. Steady state was attained in brain and plasma within 2 h, and time-activity curves remained constant for another 2 h. Even when an average bolus-to-infusion ratio was used, the striatal BP1 and BP2 values calculated with kinetic analysis (BP1 = 21.1 +/- 1.1; BP2 = 4.1 +/- 0.4) did not significantly differ from those calculated with bolus/infusion analysis (BP1 = 21.0 +/- 1.2; BP2 = 4.3 +/- 0.3). Computer simulations confirmed that a 2-fold difference in terminal clearance rate from plasma translates into only a 10% difference in BP1 and BP2 calculated from 120 to 180 min after tracer administration. CONCLUSION: The bolus/infusion approach allows accurate and precise quantification of 123I-PE2I binding to dopamine transporter and is easily implemented in a clinical setting.     

Assessment of 11C-PE2I binding to the neuronal dopamine transporter in humans with the high-spatial-resolution PET scanner HRRT.

The high-resolution research tomograph (HRRT), dedicated to brain imaging, may offer new perspectives for identifying small brain nuclei that remain neglected by the spatial resolution of conventional scanners. However, the use of HRRT for neuroimaging applications still needs to be fully assessed. The present study aimed at evaluating the HRRT for measurement of the dopamine transporter (DAT) binding to validate its quantification and explore the gain induced by the increased spatial resolution in comparison with conventional PET scanners. METHODS: Fifteen and 11 healthy subjects were examined using the selective DAT radioligand (11)C-PE2I with HRRT and HR+ scanners, respectively. Quantification of the DAT binding was assessed by the calculation of binding potential (BP) values using the simplified reference tissue model in anatomic regions of interest (ROIs) defined on the dorsal striatum and in a standardized ROI defined on the midbrain. RESULTS: Quantification of (11)C-PE2I binding to the DAT measured in the midbrain and striatum with both scanners at the same spatial resolution (smoothed HRRT images) exhibited similar BP values and intersubject variability, thus validating the quantification of DAT binding on the HRRT. For age-paired comparison, BP values of subjects examined with HRRT were significantly higher than those of the subjects examined with HR+. The increase ranged from 29% in the caudate and 35% in the putamen to 92% in the midbrain. The decline in DAT binding with age in the striatum was in good agreement between both scanners and literature, whereas no significant decrease in DAT binding with age was observed in the midbrain with either HRRT or HR+. CONCLUSION: HRRT allows quantitative measurements of neurotransmission processes in small brain nuclei and allows recovering higher values as compared with coarser spatial resolution PET scanners. High-spatial-resolution PET appears promising for a more accurate detection of neurobiologic modifications and also for the exploration of subtle modifications in small and complex brain structures largely affected by the partial-volume effect.     

Quantitative analyses of regional [11C]PE2I binding to the dopamine transporter in the human brain: a PET study

Purpose The dopamine transporter (DAT) is a plasma membrane protein of central interest in the pathophysiology of neuropsychiatric disorders and is known to be a target for psychostimulant drugs. [¹¹C]PE2I is a new radioligand which binds selectively and with moderate affinity to central DAT, as has been demonstrated in vitro by autoradiography and in vivo by positron emission tomography (PET). The aims of the present PET study were to quantify regional [¹¹C]PE2I binding to DAT in the human brain and to compare quantitative methods with regard to suitability for applied clinical studies.Methods One PET measurement was performed in each of eight healthy male subjects. The binding potential (BP) values were obtained by applying kinetic compartment analysis, which uses the metabolite-corrected arterial plasma curve as an input function. They were compared with the BP values quantified by two reference tissue approaches, using cerebellum as a reference region representing free and non-specific radioligand binding.Results The radioactivity concentration was highest in the striatum, lower in the midbrain and very low in the cerebellum. The regional [¹¹C]PE2I binding could be interpreted by kinetic compartment models. However, the BP values in the striatum obtained by the compartment analyses were about 30% higher than the BP values obtained using reference tissue methods. We suggest that the difference may be explained by the inaccurate metabolite correction, small amounts of radioactive metabolites that could account for the presence of non-specific binding in the cerebellum and insufficient data acquisition time.Conclusion The reference methods may be used to quantify [¹¹C]PE2I binding in clinical studies, assuming that non-specific binding in the cerebellum does not vary between subjects and that an extended data acquisition time is employed. Moreover, the study corroborates the previous observation that [¹¹C]PE2I is advantageous for PET examination of DAT binding in the midbrain, a region from which dopaminergic innervation originates and which is of central interest for the pathophysiology of several neuropsychiatric disorders.     

Evaluation of [I]β-CIT binding with SPECT in controls, early and late Parkinson's disease

The main neuropathological feature in Parkinson's disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (β-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [¹²³I]-β-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [¹²³I]-β-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.     

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。