多巴胺转运蛋白PET成像在建立帕金森病大鼠模型中的作用

目的研究多巴胺转运蛋白(11C-β-CYF)PET成像技术在判别帕金森病(PD)大鼠模型中的作用.材料和方法22只成功的PD大鼠模型分别进行11C-β-CFT PET显像,ROI方法测量模型大鼠两侧纹状体/小脑比值并进行统计分析,比较两侧有无显著性差异.正常与模型大鼠分别进行TH免疫组化染色.结果模型大鼠毁损侧纹状体放射性明显下降(P=0.000).同时模型大鼠TH染色黑质处阳性神经元数量减少.结论PET多巴胺转运蛋白成像可结合行为学观察作为证实模型成功的检验方法之一,为基础研究及临床诊断PD提供了一种分子成像工具.     

11C-Raclopride的快速制备及生物学评价

目的 建立快速制备11C-雷氯必利(Raclopride)的方法,并对其进行生物学评价.方法 采用固相萃取法制备11C-Raclopride,即用11C-三氟甲基磺酰基甲烷(CH3-Triflate)与去甲基(Nor)-Raclopride反应得粗产品,用水稀释粗产品,将其转移到Sep-Pak C18反相柱,冲洗反相柱,再用乙醇淋洗得11C-Raclopride.研究正常SD大鼠体内11C-Raclopride分布,并行阻断剂(螺环哌啶酮)阻断后显像.制备食蟹猴帕金森病(PD)模型,行PET显像.结果 11C-Raclopride放化纯＞95%,比活度＞8 GBq/μmol,合成效率为60%,从11CO2到11C-Raclopride的合成时间为16 min.大鼠注射11C-Raclo pride 30 min后纹状体/小脑、纹状体/额叶皮质放射性摄取比值分别为4.67和6.20.Raclopride和螺环哌啶酮明显阻断了纹状体摄取11C-Raclopride,而Nor-Raclopride则不明显.PD模型猴11C-Raclo-pride PET显像示实验侧放射性高于对侧,出现D2受体上调.结论 固相萃取法制备11C-Raclopride速度快,放化纯高.动物显像表明11C-Raclopride能满足临床需求.     

帕金森病模型猴11C-Raclopride多巴胺D2受体PET脑显像

目的探讨亚临床期和临床期帕金森病(PD)脑多巴胺D2受体(D2R)功能变化特征.方法建立亚临床期和临床期PD猴模型,合成多巴胺D2R PET显像剂11C-Raclopfide.对4只健康猴、4只亚临床期和2只临床期PD模型猴分别进行11C-Raclopride D2R PET脑显像.利用感兴趣区(ROI)技术半定量分析纹状体D2R功能.结果健康猴11C-Raclopride PET脑显像放射性浓聚于双侧纹状体,左右对称,双侧纹状体/小脑放射性比值无明显差异(5.06±0.79,5.03±0.78,t=0.704,P＞0.05).亚临床期PD猴11C-Raclopride PET脑显像双侧纹状体/小脑放射性比值无明显差异(5.03±O.83,4.98±0.77,t=0.926,P＞0.05).与健康猴比较,纹状体/小脑放射性比值差异无显著性(5.00±0.74,5.04±0.72,t=1.016,P＞0.05).临床期PD猴11C-Raclopride PET脑显像双侧纹状体放射性分布不对称,2只临床期PD猴右侧比左侧纹状体/小脑放射性比值分别增高19.69%和22.68%.毁损侧(右侧)纹状体D2R功能发生上调.结论PD亚临床期脑内纹状体D2R功能无明显变化,临床期毁损侧D2R功能出现上调.     

多巴胺转运蛋白PET成像诊断帕金森病

目的探讨多巴胺转运蛋白(DAT)显像诊断帕金森病的价值.材料和方法对18例正常人、31例晚期帕金森病(PD)患者分别进行11C-β-CFT PET显像,采用感兴趣区(ROI)及统计参数图(SPM)进行分析,比较正常组与PD组之间的差异.结果ROI显示PD组尾状核及壳核各区域DAT摄取明显低于对照组,重侧基底节DAT减少较对侧明显,重侧的尾状核头、体及壳核前、中、后的区域内CFT摄取值分别为轻侧的94.6%、87.0%、89.6%、91.8%、95.4%.SPM图像显示DAT减低区域主要集中在两侧尾状核、壳核区域,以壳核中后部减低为著,重侧DAT减低区域明显大于轻侧.结论11C-β-CFT PET显像能够客观显示帕金森病DAT不对称性代谢改变的区域,有助于帕金森病的诊断和疗效评价.SPM分析为一种更全面、准确的统计方法.     

偏侧帕金森病患者葡萄糖代谢与多巴胺转运蛋白PET显像

目的 评价葡萄糖代谢与多巴胺转运蛋白PET显像在偏侧帕金森病(PD)患者诊断中的价值。方法 正常对照组16例。偏侧PD患者34例，Hoehn—YahrⅠ～Ⅱ级。其中16例偏侧(右侧肢体)PD患者进行^18F—脱氧葡萄糖(FDG)PET显像，18例偏侧(右侧或左侧)PD患者进行^18F-N—(3—氟丙基)—2β—甲酯基—3β—(4′—碘苯基)去甲基托烷(FP—β—CIT)显像，6例患者同时进行两种显像。静脉注射^18F—FDG 185～259MBq 30min后进行脑三维采集，结果应用感兴趣区(ROI)半定量分析和统计参数地图(SPM)分析。^18F—FP—β—CIT显像于注射后2～3h进行，计算(各ROI计数—小脑计数）小脑计数比值。结果 PD组与对照组比较，患侧肢体对侧基底节葡萄糖代谢减低，但差异无显著性。SPM分析结果示，PD患者与对照组比较，葡萄糖代谢减低位于左侧前额叶、中额叶、下额叶及左侧中颞叶，而摄取增加区域除双侧额叶中央前回、双侧顶叶楔前叶、左侧枕叶外，还累及左侧丘脑。偏侧PD患者豆状核后部^18F—FP—β—CIT摄取显著减低，且不仅见于症状对侧豆状核，同侧豆状核后部也可见摄取减低。结论 ^18F—FDG PET显像对PD的早期诊断无特异性。^18F—FP—β—CIT可早期发现PD纹状体多巴胺转运蛋白的变化，有助于PD的早期诊断和鉴别诊断；与^18F—FDG PET显像结合，可显示大脑皮层的葡萄糖代谢变化。     

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。     

6-18F-DOPA合成改进及动物实验

目的研究6-18F-多巴(DOPA)的合成改进及其在大鼠体内和偏侧帕金森病(PD)大鼠模型脑内生物分布.方法以6-硝基胡椒醛为前体,经亲核氟化、二碘硅烷在柱还原碘化、手性相转移催化烷基化及水解4步反应合成6-18F-DOPA,测定大鼠体内和偏侧PD大鼠模型脑内6-18F-DOPA生物分布.结果 6-18F-DOPA总放化产率为5%～18%(未经时间衰减校正),总合成时间<110 min,放化纯度>98%,对映纯度>97%.正常大鼠肾脏、血液、纹状体和海马对6-18F-DOPA摄取较高,但前两者对6-18F-DOPA清除快,而后两者对6-18F-DOPA滞留时间长,且具有较高纹状体/皮质和纹状体/小脑放射性比值.与假手术对照组和偏侧PD大鼠模型未损毁侧(左侧)比较,偏侧PD大鼠模型损毁侧(右侧)纹状体对6-18F-DOPA摄取显著下降,且具有较低纹状体/皮质和纹状体/小脑放射性比值(P<0.05).结论提供了简便实用的6-18F-DOPA合成方法,制备的6-18F-DOPA可用于动物及PD患者PET显像.     

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。     

18F-FDG PET/CT评价兔VX2移植瘤对顺铂化疗的早期反应

目的 探讨18F-FDG PET/CT评价兔VX2移植瘤顺铂化疗早期反应的最佳时间,观察移植瘤摄取FDG的变化规律及其与病理变化的相关性.方法 将30只VX2荷瘤兔按随机数字表法分为5组,每组6只.化疗组在按体质量静脉注射顺铂(7 mg/kg)化疗前和化疗后6、12、24及36h分别行18F-FDG PET/CT显像;对照组用等体积的生理盐水进行干预;勾画ROI,计算SUVmax、T/NT.采用HE染色观察肿瘤细胞坏死率,TUNEL法检测细胞凋亡.统计学分析采用配对t检验、Games-Howell检验及曲线相关分析.结果 对照组干预后SUVmax为9.77±2.45,明显高于干预前(6.58±1.67;t=-5.480,P＜0.05),干预后T/NT为29.34±3.31,明显低于干预前(52.93±3.90;t=17.593,P＜0.05).化疗组化疗后6 h 18F-FDG摄取减低,SUVmax平均减低率为(11.83±8.89)％,T/NT平均减低率为(59.00±8.22)％,与对照组间的差异有统计学意义(均P＜0.05).化疗后24 h 18F-FDG摄取减低最明显,SUVmax平均减低率为(42.33±33.80)％,T/NT平均减低率为(83.50±7.69)％,与对照组和化疗后6h显像组间的差异均有统计学意义(均P＜0.05).SUVmax和T/NT变化率与凋亡指数呈正相关(r=0.750、0.794,均P＜0.05),与肿瘤细胞坏死率亦呈正相关(r=0.804、0.874,均P＜0.05).结论 18F-FDG PET/CT能够灵敏检测早期化疗反应,化疗后24 h是最佳早期化疗反应评价时间点.     

统计参数图和ROI联合应用在多巴胺转运蛋白PET显像分析中的价值

目的 探讨联合应用统计参数图(SPM)和感兴趣区(ROI)方法在帕金森病(PD)患者多巴胺转运蛋白(DAT)PET图像分析中的价值.方法 临床确诊的41例PD患者,其中23例早期(Hoehn-Yahr Ⅰ～Ⅱ级),年龄(56.2±8.1)岁;18例晚期(Hoehn-Yahr Ⅲ～Ⅳ级),年龄(59.1±7.6)岁.健康对照组12名,年龄(58.84±7.2)岁.分别进行18F-N-(3-氟丙基)-2β-甲酯基-3β-(4'-碘苯基)去甲基托烷(FP-β-CIT)PET显像,对所获得的脑PET图像分别进行ROI及SPM分析.结果 应用ROI方法,与健康对照组相比,在23例早期PD患者中,尾状核、前壳核和后壳核的DAT分别减少29.1%、53.2%和76.0%;18例晚期PD患者的尾状核、前壳核和后壳核的DAT分别减少48.0%、65.5%和83.5%.SPM分析可直观显示,早期和晚期PD双侧壳核DAT较健康对照组减少,尤其是患肢的对侧壳核和后壳核区域.结论 PD患者纹状体内18F-FP-CIT的摄取显著降低,尤以患肢的对侧壳核最为明显;联合应用SPM和ROI方法有助于DAT PET图像的综合分析.     

In-vivo PET imaging of implanted human retinal pigment epithelium cells in a Parkinson's disease rat model

BACKGROUND AND AIM: Researchers find that monitoring the differentiation of implanted cells in vivo is difficult. This study was designed to show that it is possible to track the efficacy of transplanted human retinal pigment epithelial cells (RPE cells) in a rat model of Parkinson's disease by using positron emission tomography (PET). METHODS: RPE cells or normal saline were injected into striatum of the injured side of the rat model in treated and control groups, respectively. PET imaging of both groups was undertaken before transplantation and at intervals afterwards, using C-raclopride and C-beta-CFT as the markers. Observation of the rats' behaviour and immunofluorescence confocal microscopy were also used to prove the PET results. RESULTS: PET studies showed increased accumulation of C-raclopride and decreased C-beta-CFT in the injured side of striatum in both groups. C-raclopride decreased along with a concomitant increase of C-beta-CFT after transplantation in the treated group. The changes shown by the PET studies paralleled the behavioural states and confocal microscopy observations in the treated animals. CONCLUSION: These results suggest that even a clinical PET scanner could, to a certain extent, provide some information on the existence and in-vivo differentiation of RPE cells in a rat model of Parkinson's disease.     

Modulation of dopaminergic and glutamatergic brain function: PET studies on parkinsonian rats.

Degeneration of dopaminergic neurons of the substantia nigra pars compacta is a cardinal feature of Parkinson's disease (PD). Although uncertain, the pathology has been suggested to derive from a malfunction of the complex interaction between dopaminergic and metabotropic glutamate receptors (mGluRs). To further address this issue, we investigated the imaging profile and expression of dopamine D(2) receptors and mGluRs in a classic parkinsonian rodent model induced by the toxin 6-hydroxydopamine. METHODS: Adult male Sprague-Dawley rats (250-300 g) received a stereotaxic injection of 8 mug/2 muL of 6-hydroxydopamine (n = 6) or saline solution (n = 4) in the right medial forebrain bundle. Small-animal PET was performed on all rats 4 wk after the surgical procedure to assess dopamine transporter (DAT) status using (11)C-2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane (CFT), as well as dopamine D(2) receptor and mGluR(5) modulation using (11)C-raclopride and 2-(11)C-methyl-6-(2-phenylethynyl)-pyridine ((11)C-MPEP), respectively. Behavioral studies were also conducted 6 wk after lesioning by d-amphetamine challenge. Immunohistochemistry and Western blotting were carried out at 8 wk after lesioning to confirm dopamine fiber, neuronal loss, and level of striatal mGluR(5) expression. RESULTS: PET images showed decreased (11)C-CFT binding on the lesioned side, including the structures of the striatum, hippocampus, and cortex, compared with the contralateral intact side. Interestingly, dopamine D(2) receptors and mGluR(5) upregulation were observed in the right striatum, hippocampus, and cortex, using (11)C-raclopride and (11)C-MPEP, respectively. A negative correlation was also found between the percentage change in mGluR(5) expression and DAT function. Finally, tyrosine hydroxylase immunoreactivity confirmed both dopamine fiber loss (t test, P < 0.01) and neuronal loss (t test, P < 0.01) on the lesioned side. These changes were accompanied by a strongly enhanced mGluR(5) expression in the right striatum of the lesioned side analyzed by Western plot. CONCLUSION: These findings support the existence of compensatory mechanisms in nigrostriatal dopamine degeneration and provide new insights that help further dissect some of the pathways underlying neurodegeneration. In addition, these results reconfirm that PET is a valuable tool for multilevel receptor studies, significantly contributing to the understanding of pathogenic mechanisms and ultimately opening new avenues in the study of neuroprotective approaches toward PD.     

Validation of cardiac 123I-MIBG scintigraphy in patients with Parkinson’s disease who were diagnosed with dopamine PET

Purpose  

The aim of this study was to evaluate the diagnostic potential of cardiac ¹²³I-labelled metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy in idiopathic Parkinson’s disease (PD). The diagnosis was confirmed by positron emission tomography (PET) imaging with ¹¹C-labelled 2β-carbomethoxy-3β-(4-fluorophenyl)-tropane (¹¹C-CFT) and ¹¹C-raclopride (together designated as dopamine PET).     

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。     

Effects of hypoxic-ischemic brain injury on striatal dopamine transporter in newborn piglets: evaluation of 11C-CFT PET/CT for DAT quantification

IntroductionAlterations of dopamine in striatal presynaptic terminals play an important role in the hypoxic–ischemic (HI) brain injury. Quantification of DAT levels in the presynaptic site using ¹¹C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (¹¹C-CFT) with positron emission tomography (PET) was applied in studies for Parkinson's disease. The current study investigated the changes in striatal DAT following HI brain injury in newborn piglets using ¹¹C-CFT PET.MethodsNewborn piglets were subjected to occlusion of bilateral common carotid arteries for 30 min and simultaneous peripheral hypoxia. Brain DAT imaging was performed using PET/CT with ¹¹C-CFT as the probe in each group (including the control group and HI insult groups). Brain tissues were collected for DAT immunohistochemical (IHC) analysis at each time point post the PET/CT procedure. Sham controls had some operation without HI procedure.ResultsA few minutes after intravenous injection of ¹¹C-CFT, radioactive signals for DAT clearly appeared in the cortical area, striatum and cerebellum of newborn piglets of sham control group and HI insult groups. HI brain insult markedly increased striatal DAT at an early period (P<.05 vs. sham controls) when neuronal pathological changes were mild. Changes in striatal DAT were absent at later period post-HI insult when neuronal injury became more severe. ¹¹C-CFT PET imaging data and IHC DAT staining data were highly correlated (r=0.844, P<.05).ConclusionsHI brain injury resulted in a transient increase in striatal DAT. ¹¹C-CFT PET/CT imaging data reflected the dynamic changes of DAT in the striatum in vivo.     

SIC, an intracerebral beta(+)-range-sensitive probe for radiopharmacology investigations in small laboratory animals: binding studies with (11)C-raclopride.

Our aim was to show the ability of a recently developed beta(+)-range-sensitive intracerebral probe (SIC) to measure, in vivo, the binding of radioligands in small animals. METHODS: The potential of the device for pharmacokinetic studies was evaluated by measurement of the dynamic striatal binding of (11)C-raclopride, a well-documented D(2) dopaminergic receptor ligand, in rat brain after intravenous injection of the labeled compound. The effects of preinjection of the unlabeled ligand (raclopride, 2 mg/kg intravenously) and of increasing the synaptic dopamine level (amphetamine treatment, 1 mg/kg intravenously) or of depleting synaptic dopamine (reserpine pretreatment, 5 mg/kg intraperitoneally) on in vivo (11)C-raclopride binding were monitored by SIC. RESULTS: The radioactivity curves measured as a function of time were reproducible and consistent with previous studies using PET imaging (ratio of striatum to cerebellum, 2.6 +/- 0.3 after 20 min). Further studies showed significant displacement of (11)C-raclopride by its stable analog. Finally, the device proved its capacity to accurately detect changes in (11)C-raclopride binding after a sudden (amphetamine) or a gradual (reserpine) modulation of endogenous dopamine levels. CONCLUSION: These results show that the new device can monitor binding of PET ligands in anesthetized rodents in vivo, with high temporal resolution.     

Reproducibility of 11C-raclopride binding in the rat brain measured with the microPET R4: effects of scatter correction and tracer specific activity.

A new generation of commercial animal PET cameras may accelerate drug development by streamlining preclinical testing in laboratory animals. However, little information on the feasibility of using these machines for quantitative PET in small animals is available. Here we investigate the reproducibility of microPET imaging of (11)C-raclopride in the rat brain and the effects of tracer-specific activity and photon scatter correction on measures of D2 receptor (D2R) availability. METHODS: Sprague-Dawley rats (422 +/- 29 g; n = 7) were anesthetized with ketamine/xylazine and catheterized for tail vein injection of (11)C-raclopride. Each animal was positioned prone in the microPET, centering the head in the field of view. MicroPET data was collected for 60 min-starting at (11)C-raclopride injection-and binned into 24 time frames (6 x 10 s, 3 x 20 s, 8 x 60 s, 4 x 200 s, 3 x 600 s). In 3 studies, (11)C-raclopride was administered a second time in the same animal, with 2-4 h between injections. In a fourth animal, raclopride (1 mg/kg) was coinjected with (11)C-raclopride for the second injection. Three rats received a single dose of (11)C-raclopride. The range of doses for all studies was 6.11-18.54 MBq (165-501 micro Ci). The specific activity at injection was 4.07-48.1 GBq/ micro mol (0.11-1.3 Ci/ micro mol). Region-of-interest analysis was performed and the distribution volume ratio (DVR) was computed for striatum/cerebellum using sinograms uncorrected and corrected for scatter using a tail-fit method. RESULTS: Test-retest results showed that the (11)C-raclopride microPET DVR was reproducible (change in DVR = -8.3% +/- 4.4%). The average DVR from 6 rats injected with high specific activity (<4 nmol/kg) was 2.43 +/- 0.19 (coefficient of variation = 8%). The DVR for the blocking study was 1.23. The DVR depended on the mass of tracer (11)C-raclopride injected for doses >1.5 nmol/kg. Scatter fractions within the rat head were approximately 25%-45% resulting in an average increase of DVR of 3.5% (range, 0%-10%) after correction. CONCLUSION: This study shows that the (11)C-raclopride microPET-derived DVR is reproducible and suitable for studying D2R availability in the rat brain. MicroPET sensitivity was sufficient to determine reproducible DVRs from (11)C-raclopride injections of 9.25 MBq (approximately 250 micro Ci). However, the effect of tracer mass on the DVR should be considered for studies using more than approximately 1-2 nmol/kg raclopride, and scatter correction has a measurable impact on the results.     

Striatal D2 receptor availability after shunting in idiopathic normal pressure hydrocephalus.

Gait disturbance in idiopathic normal pressure hydrocephalus (iNPH) is reminiscent of parkinsonism. Our recent PET study showed reduction in postsynaptic D(2) receptor binding concomitant with a normality of presynaptic dopamine transporter binding. Here, we investigated the plasticity of D(2) receptor in treating iNPH patients with ventriculoperitoneal (VP) shunting using PET with (11)C-raclopride and discuss the contribution of D(2) receptor to the pathophysiology of iNPH. METHODS: Eight iNPH patients participated in this study. After evaluation of their neuropsychologic abilities, all patients underwent 3-dimensional MRI and quantitative PET measurements twice before and 1 mo after VP shunting. MRI-based morphometric analyses were performed to examine postoperative variations of the ventricles. Estimation of binding potential (BP) for (11)C-raclopride was based on Logan plot analysis. Region-of-interest analysis was used to examine changes in (11)C-raclopride BP in the striatum. A 2-tailed paired t test was used for evaluating changes in PET and MRI parameters between conditions, and correlation analysis was used to investigate clinicopathophysiologic relevance (clinical vs. in vivo findings). RESULTS: Clinical evaluation revealed significant recovery in a 5-m back-and-forth navigation test and an affect test and a mild increase in Mini-Mental State Examination scores after VP shunting. Significant postoperative increases in (11)C-raclopride BP were found in the nucleus accumbens and dorsal putamen, and the increases were significantly associated with emotional (Spearman rank r = 0.66, P < 0.05) and navigational improvement (r = 0.72, P < 0.05), respectively. The (11)C-raclopride BP increase in the striaum as a whole correlated significantly with improvement in general cognitive ability. There was a mild ventricular shrinkage after surgery, albeit there was no correlation of its size with clinical and PET parameters. CONCLUSION: Striatal upregulation of D(2) receptor after VP shunting is associated with amelioration of hypokinetic gait disturbance and anhedonic mentation in iNPH patients, indicating that the effect of VP shunting may reside in noninhibition of functionally suppressed D(2) receptor in the striatum. D(2) receptor responsiveness may indicate a mechanism for iNPH pathophysiology.     

Sequential H(2)(15)O PET studies in baboons: before and after amphetamine.

PET and (11)C-raclopride have been used to assess dopamine activity in vivo using a paradigm that involved d-amphetamine (AMPH)-induced endogenous dopamine release that led to reductions (relative to baseline) in the (11)C-raclopride-specific binding parameter (binding potential). A common assumption in bolus injection PET studies of this type is that cerebral blood flow (CBF) does not vary during the scan. The goal of this work was to examine the effect of AMPH administration on sequential PET measures of CBF. METHODS: Eight dynamic H(2)(15)O PET scans were acquired with arterial blood sampling in 6 baboons: 4 scans before AMPH (over 60 min) and 4 scans after AMPH (over 60 min) (0.6 mg/kg AMPH). Magnetic resonance images (coregistered to PET) were used to define regions of interest that included cortex, striatum (including subregions), and cerebellum. Data were analyzed using a 1-tissue compartment model. CBF was assessed through K(1) (mL/mL/min). RESULTS: Temporal patterns of the CBF alterations were similar across regions for each baboon. For 5 of 6 baboons, a general pattern of an initial increase in K(1) was observed after AMPH that gradually declined toward baseline, after minimizing anesthesia-induced variability in the in vivo measures. Although these alterations after AMPH were statistically significant in particular subcortical regions and cerebellum, such changes would not likely influence measures of (11)C-raclopride binding potential to a significant extent. CONCLUSION: These data support previous PET studies for which constant blood flow was assumed during the bolus PET (11)C-raclopride/AMPH experiment across striatal subregions, while underscoring the importance of considering effects of anesthesia when interpreting in vivo imaging parameters.