11C-PIB PET在不同时期阿尔茨海默病中的研究进展

阿尔茨海默病(AD)作为神经变性病, 起病隐袭, 早期诊断困难。β淀粉样蛋白(Aβ)沉积形成的老年斑是其特征性病理改变, 并且发生在疾病的早期阶段。N-[11C]甲基-2-4′-甲基氨基苯基-6-羟基苯并噻唑(11C-PIB)作为Aβ特异性的分子探针, 能够无创、实时、定量地监测脑内纤维状Aβ的变化。因此, 明确PIB在不同时期AD中的分布特点, 对AD的早期诊断、抗Aβ治疗的人群筛选以及疗效监测方面都具有重要意义。该文就近年来11C-PIB PET在不同时期AD中的应用作一综述。     

纳米技术在阿尔兹海默病诊断中的研究进展

阿尔兹海默病（AD）是一种常见的神经退行性疾病,临床表现以渐进性认知和记忆功能减退等为特征,在疾病晚期可严重影响患者的身心健康和生活质量。AD的早期诊断仍是全球面临的重大难题之一。β淀粉样肽（Aβ）沉积形成的Aβ斑块和Tau蛋白过度磷酸化形成的神经原纤维缠结为AD的标志性病理改变,Aβ和Tau蛋白的检测对实现AD早期诊断至关重要。近年来,纳米技术发展迅速,基于纳米技术的Aβ或Tau蛋白靶向检测为AD的早期诊断提供了可能。笔者对基于纳米技术的AD诊断研究进行综述。     

阿尔茨海默病分子影像探针的研究进展

阿尔茨海默病（AD）是一种进行性神经退行性疾病。β淀粉样蛋白（Aβ）沉积和过度磷酸化的Tau蛋白形成的神经原纤维缠结（NFT）是该病的病理学特征。在过去的20年中,分子影像探针在AD的诊疗中取得了很大进展,其作用已经超越了传统的脑灌注和葡萄糖代谢显像。与Aβ或NFT特异性结合的分子影像探针可成为准确和早期诊断AD的有价值工具,且其已被提出作为最近修订的临床诊断标准中的生物标志物。笔者主要对Aβ和NFT分子影像探针的研究进展进行综述。     

阿尔茨海默病相关正电子显像剂的研究进展

阿尔茨海默病（AD）是老年人群中最常见的神经退行性疾病之一,其症状始于轻微的记忆困难,逐渐演变为认知功能障碍、复杂的日常活动功能障碍等。目前AD的早期诊断和鉴别诊断仍具有一定的挑战性,而β淀粉样蛋白（Aβ）和Tau蛋白等生物标志物在AD诊断中的作用越来越重要。笔者就AD诊断相关的正电子显像剂进行综述,以期让更多的医务工作者了解新的核医学显像技术,从而对AD进行早期诊断和治疗,延缓病情的恶化。     

正电子显像剂11C-匹兹堡化合物B的化学合成及其临床应用

阿尔茨海默病(AD)是一种严重影响老年人生活质量的常见疾病.11C-匹兹堡化合物B(11C-PIB)作为新型B-淀粉样蛋白(Aβ)正电子显像剂,能够特异性地检出AD的特征性病理学改变,为AD的早期诊断、早期治疗乃至疗效评价提供了潜在的可能性.     

磁共振新技术在阿尔茨海默病研究中的应用

阿尔茨海默病（AD）,又称老年性痴呆,随着年龄的增长和人口的老龄化,发病率呈增高趋势。近年来,随着磁共振在临床的广泛应用,扩散加权成像、扩散张量成像、质子磁共振波谱成像、β-淀粉样蛋白的MR检测等在早期诊断AD上的优势逐步体现。就MR新技术在AD诊断中的价值予以综述。     

多巴胺转运蛋白显像剂11C-β-CFT在帕金森病中的应用研究

帕金森病(PD)是全球第二大最常见的神经退行性疾病, 与患者年龄、激素水平、生活习惯及基因遗传等相关因素密切相关, 且与大脑多巴胺能神经元的结构和功能差异有关。常规的影像学检查在PD的早期发现、预后评估、术前分级等方面存在一些不足。11C-甲基-N-2β-甲基酯-3β-(4-氟-苯基)托烷(11C-β-CFT)是一种多巴胺转运蛋白正电子显像剂, 与多巴胺转运体的结合具有高度特异性, 同时受患者治疗药物因素的干扰较小, 是一种良好的临床诊断类的显像剂。目前, 11C-β-CFT已应用于人类神经病学方面疾病的研究, 如精神分裂症、PD等, 11C-β-CFT PET显像可以评价疾病病理、生理过程, 便于临床诊断及监测疾病治疗效果等。笔者就近年来11C-β-CFT PET显像在PD中的应用作一综述。     

18F-AV1451 PET在阿尔茨海默病中的临床研究进展

阿尔茨海默病（AD）是一种起病隐匿的神经退行性疾病,其主要病理学特征为β淀粉样蛋白沉积形成的老年斑和Tau蛋白异常聚集形成的神经原纤维缠结。使用特异性靶向Tau蛋白的PET分子探针可完成AD的无创精准检测,为AD的早期诊断、疾病进展监测、发病机制和认知功能研究等提供一种有效的检测手段。笔者以18F-AV1451为代表,对Tau蛋白PET显像在AD中的临床研究进展进行综述。     

静息态脑功能成像在阿尔茨海默病早期诊断的研究进展

阿尔茨海默病（AD）是一种以进行性认知功能障碍和行为损害为特征的中枢神经系统退行性疾病,起病隐匿,早期诊断较为困难。目前国内外研究者利用各种成像技术对AD的早期诊断进行了大量相关研究。近年来,静息态脑功能成像作为一种崭新的成像技术出现并得到迅速发展。其因分析方法多样、实用性强、被试依从性高等优点而广泛应用于AD的研究中。就静息态脑功能成像特别是其不同的分析方法在AD早期诊断中的应用进行综述。     

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。     

阿尔茨海默病的放射性分子显像探针研究进展

阿尔茨海默病(AD)是引起痴呆的最常见类型之一,其主要病理改变包括由β-淀粉样蛋白构成的老年斑、神经原纤维缠结。在体观察AD脑内的β-淀粉样蛋白沉积,可为AD的诊断、疗效观察和治疗药物的研究提供很大帮助。目前已合成数种标记β-淀粉样蛋白的放射性探针并开始用于PET对AD患者脑内老年斑的在体显像研究,并显示出潜在的临床应用价值。AD的放射性分子显像探针仍需进一步研究,使其不仅适用于PET,而且还可以满足SPECT的显像要求。     

新型斑块显像剂18F-W372在阿尔茨海默病中的应用

目的 通过比较18F-7-甲氧基-2(6-氟-18吡啶-3-yl)咪唑[2,1-β]-8-吡啶噻唑(18F-W372)和11C-匹兹堡化合物B(11C-PIB)在AD患者和健康老年志愿者(HC)的动态影像,评价新型斑块显像剂18F-W372的临床应用价值.方法 8例AD患者,年龄(64.00±8.81)岁,男∶女=1∶7;9名HC,年龄(64.78±4.02)岁,男∶女=4∶5;2名青年志愿者,男29岁,女25岁.静脉注射18F-W372和11C-PIB后,进行40 min连续动态PET数据采集.计算每个受试者SUV以及皮质/小脑SUV比率(SUVR),获得2种示踪剂TAC.应用秩和检验及两样本t检验进行统计学处理.结果 AD患者简易智力状态检查量表(MMSE)评分低于HC,为19.13±4.05与28.89±0.78(T=36.00,P＜0.01).AD与HC受试者年龄(H=28.50,P＞0.05)及受教育程度(H=35.50,P＞0.05)差异无统计学意义.18F-W372能够快速通过血脑屏障并迅速廓清.AD患者在皮质区域出现18F-W372摄取,而青年志愿者仅有少量摄取.给药40 min内,18F-W372和11C-PIB在AD患者皮质/小脑SUVR进行性增加,但后者更加明显.两者均出现白质区放射性浓聚,但18F-W372在白质的摄取明显高于皮质.35～40 min时,AD患者和HC11C-PIB和18F-W372皮质/小脑SUVR分别为1.48±0.22与1.06±0.04(t=5.58,P＜0.001)和1.31±0.08与1.17±0.06(t=3.78,P＜0.01).结论 18F-W372与11C-PIB具有相似分布模式,在注射18F-W372 40 min内SUVR在AD患者与HC间有差异,但视觉上病灶欠清晰.18F-W372作为斑块显像剂临床应用有待进一步深入研究.     

阿尔茨海默病患者基于体素形态学的CT和磁共振影像的比较研究

目的：探讨基于体素形态学的CT和磁共振（MR）影像对阿尔茨海默病（AD）患者的诊断价值。方法 AD患者和健康志愿者各5例,用3．0 T的扫描仪行MR检查,用3D矢状磁化预备快速梯度回波序列获取3D数据。1月后,所有参与者行正电子发射计算机断层显像（PET/CT）检查;然后静脉注射11C-PIB 600 MBq,并再次行PET/CT检查。完毕后,用统计参数图-8（SPM8）软件对MRI和PET/CT影像进行重建,并将两者进行比较分析。结果和志愿者相比,不管是MR还是PET/CT影像,AD患者两侧颞叶区域灰质均明显减少（P＜0．001）;与MR影像对比,PET/CT影像所示的变化区域更大。结论基于体素形态学的CT和MR影像均可对AD患者进行准确的诊断,但CT的敏感性更高。     

Voxel-based analysis of 11C-PIB scans for diagnosing Alzheimer's disease

The positron emission tomography (PET) radioligand N-methyl-11C-2-(4-methylaminophenyl)-6-hydroxybenzothiazole (also known as 11C-6-OH-BTA-1 or 11C-PIB) binds to amyloid-beta (Abeta), which accumulates pathologically in Alzheimer's disease (AD). Although 11C-PIB accumulation is greater in patients with AD than in healthy controls at a group level, the optimal method for discriminating between these 2 groups has, to our knowledge, not been established. We assessed the use of data-determined standardized voxels of interest (VOIs) to improve the classification capability of 11C-PIB scans on patients with AD. METHODS: A total of 16 controls and 14 AD age-matched patients were recruited. All subjects underwent a 11C-PIB scan and structural MRI. Binding potential (a measure of amyloid burden) was calculated for each voxel using the Logan graphical method with cerebellar gray matter as the reference region. Voxel maps were then partial-volume corrected and spatially normalized by MRI onto a standardized template. The subjects were divided into 2 cohorts. The first cohort (control, 12; AD, 9) was used for statistical parametric mapping analysis and delineation of data-based VOIs. These VOIs were tested in the second cohort (control, 4; AD, 5) of subjects. RESULTS: Statistical parametric mapping analysis revealed significant differences between control and AD groups. The VOI map determined from the first cohort resulted in complete separation between the control and the AD subjects in the second cohort (P < 0.02). Binding potential values based on this VOI were in the same range as other reported individual and mean cortical VOI results. CONCLUSION: A standardized VOI template that is optimized for control or AD group discrimination provides excellent separation of control and AD subjects on the basis of 11C-PIB uptake. This VOI template can serve as a potential replacement for manual VOI delineation and can eventually be fully automated, facilitating potential use in a clinical setting. To facilitate independent analysis and validation with more and a broader variety of subjects, this VOI template and the software for processing will be made available through the Internet.     

Visual assessment versus quantitative assessment of 11C-PIB PET and 18F-FDG PET for detection of Alzheimer's disease.

Amyloid-beta (Abeta) imaging with N-methyl-(11)C-2-(4'-methylamino-phenyl)-6-hydroxy-benzothiazole ((11)C-6-OH-BTA-1; also known as (11)C-PIB) shows a robust increase in cortical binding in Alzheimer's disease (AD). The aim of this study was to explore the clinical potential of Abeta imaging for the diagnosis of AD by comparison of the accuracy of visual reading of (11)C-PIB images with quantitative analysis and (18)F-FDG. METHODS: Fifteen AD patients (age, 71.1 +/- 11.3 y [mean +/- SD]; mini-mental state examination [MMSE], 18.9 +/- 9.3 [mean +/- SD]) and 25 healthy control (HC) subjects (age, 71.9 +/- 6.82 y; MMSE >or= 28) underwent 90-min dynamic (11)C-PIB PET and 20-min static (18)F-FDG PET. (11)C-PIB images, generated from data acquired between 40 and 70 min after injection, and (18)F-FDG images were rated separately by 2 readers as normal, possible AD, or probable AD. Quantitative analyses used the distribution volume ratio (DVR) of frontal cortex, parietotemporal cortex, posterior cingulate, and caudate nucleus for (11)C-PIB and standardized uptake value ratio (SUVR) of parietotemporal cortex and posterior cingulate for (18)F-FDG, using cerebellar cortex as the reference region. Receiver-operating-characteristic (ROC) analysis was performed to compare the accuracy of quantitative measures. To determine the effect of age on diagnostic accuracy, the median age of the AD subjects (74 y) was chosen to separate the cohort into younger (64.4 +/- 5.8 y) and older (78.6 +/- 4.1 y) groups. RESULTS: Visual agreement between readers was excellent for (11)C-PIB (kappa = 0.90) and good for (18)F-FDG (kappa = 0.56). (11)C-PIB was more accurate than (18)F-FDG both on visual reading (accuracy, 90% vs. 70%, P = 0.05) and ROC analysis (95% vs. 83%, P = 0.02). Accuracy declined more with (18)F-FDG than with (11)C-PIB in the older group. CONCLUSION: Visual analysis of (11)C-PIB images appears more accurate than visual reading of (18)F-FDG for identification of AD and has accuracy similar to quantitative analysis of a 90-min dynamic scan. The accuracy of (11)C-PIB PET is limited by cortical binding in some healthy elderly subjects, consistent with postmortem studies of cerebral Abeta. Longitudinal follow-up is required to determine if this represents detection of preclinical AD.     

脑脊液生物标志物与 11C-PIB PET/CT显像对阿尔茨海默病的诊断准确率及相关性研究

目的:探讨脑脊液生物标志物与 11C-匹兹堡化合物B （PIB）PET/CT显像在阿尔茨海默病（AD）中的诊断准确率及相关性,确定脑脊液生物标志物诊断AD的最佳临界值。 方法:回顾性分析2011年1月至2020年3月在北部战区总医院行 11C-PIB PET/CT显像和腰椎穿刺的66名...     

Comparison of dual-biomarker PIB-PET and dual-tracer PET in AD diagnosis

Objectives

To identify the optimal time window for capturing perfusion information from early ¹¹C-PIB imaging frames (perfusion PIB, ¹¹C-pPIB) and to compare the performance of ¹⁸F-FDG PET and "dual biomarker" ¹¹C-PIB PET [¹¹C-pPIB and amyloid PIB (¹¹C-aPIB)] for classification of AD, MCI and CN subjects.

Methods

Forty subjects (14 CN, 12 MCI and 14 AD patients) underwent ¹⁸F-FDG and ¹¹C-PIB PET studies. Pearson correlation between the ¹⁸F-FDG image and sum of early ¹¹C-PIB frames was maximised to identify the optimal time window for ¹¹C-pPIB. The classification power of imaging parameters was evaluated with a leave-one-out validation.

Results

A 7-min time window yielded the highest correlation between ¹⁸F-FDG and ¹¹C-pPIB. ¹¹C-pPIB and ¹⁸F-FDG images shared a similar radioactive distribution pattern. ¹⁸F-FDG performed better than ¹¹C-pPIB for the classification of both AD vs. CN and MCI vs. CN. ¹¹C-pPIB?+?¹¹C-aPIB and ¹⁸F-FDG?+?¹¹C-aPIB yielded the highest classification accuracy for the classification of AD vs. CN, and ¹⁸F-FDG?+?¹¹C-aPIB had the best classification performance for the classification of MCI vs. CN.

Conclusion

C-pPIB could serve as a useful biomarker of rCBF for measuring neural activity and improve the diagnostic power of PET for AD in conjunction with ¹¹C-aPIB. ¹⁸F-FDG and ¹¹C-PIB dual-tracer PET examination could better detect MCI.

Key Points

? Dual-tracer PET examination provides neurofunctional and neuropathological information for AD diagnosis. ? The identified optimal 11C-pPIB time frames had highest correlation with 18F-FDG. ? 11C-pPIB images shared a similar radioactive distribution pattern with 18F-FDG images. ? 11C-pPIB can provide neurofunctional information. ? Dual-tracer PET examination could better detect MCI.     

Biodistribution and radiation dosimetry of the amyloid imaging agent 11C-PIB in humans.

We investigated the biodistribution and radiation dosimetry of the PET amyloid imaging agent (11)C-PIB ((11)C-6-OH-BTA-1) (where BTA is benzothiazole) in humans. Previous radiation exposure estimates have been based on animal experiments. A dosimetry study in humans is essential for a balanced risk-benefit assessment of (11)C-PIB PET studies. METHODS: We used data from 16 different (11)C-PIB PET scans on healthy volunteers to estimate radiation exposure. Six of these scans were dynamic imaging over the abdominal region: 3 covering the upper abdomen and 3 covering the middle abdomen. On average, 489 MBq of (11)C-PIB (range, 416-606 MBq) were injected intravenously, and dynamic emission scans were recorded for up to 40 min. Two subjects had whole-body imaging over the entire body to illustrate the biodistribution. PET brain scans and blood and urine radioactivity measurements from our previous (11)C-PIB studies were also analyzed. Thirteen source organs and the remainder of the body were studied to estimate residence times and mean radiation-absorbed doses. The MIRD method was used to calculate the radiation exposure of selected target organs and the body as a whole. RESULTS: There is a high degree of consistency between our human data and previous biodistribution information based on baboons. In our study, the highest radiation-absorbed doses were received by the gallbladder wall (41.5 microGy/MBq), liver (19.0 microGy/MBq), urinary bladder wall (16.6 microGy/MBq), kidneys (12.6 microGy/MBq), and upper large intestine wall (9.0 microGy/MBq). The hepatobiliary and renal systems were the major routes of clearance and excretion, with approximately 20% of the injected radioactivity being excreted into urine. The effective radiation dose was 4.74 microSv/MBq. CONCLUSION: The established clinical dose of (11)C-PIB required for 3-dimensional PET amyloid imaging has an acceptable effective radiation dose. This dose is comparable with the average exposure expected in other PET brain receptor tracer studies. (11)C-PIB is rapidly cleared from the body, largely by the kidneys. From the viewpoint of radiation safety, these results support the use of (11)C-PIB in clinical PET studies.     

Neuroimaging and early diagnosis of Alzheimer disease: a look to the future

Alzheimer disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. Current consensus statements have emphasized the need for early recognition and the fact that a diagnosis of AD can be made with high accuracy by using clinical, neuropsychologic, and imaging assessments. Magnetic resonance (MR) or computed tomographic (CT) imaging is recommended for the routine evaluation of AD. Coronal MR images can be useful to document or quantify atrophy of the hippocampus and entorhinal cortex, both of which occur early in the disease process. Both volumetric and subtraction MR techniques can be used to quantify and monitor dementia progression and rates of regional atrophy. MR measures are also increasingly being used to monitor treatment effects in clinical trials of cognitive enhancers and antidementia agents. Positron emission tomography (PET) and single photon emission CT offer value in the differential diagnosis of AD from other cortical and subcortical dementias and may also offer prognostic value. In addition, PET studies have demonstrated that subtle abnormalities may be apparent in the prodromal stages of AD and in subjects who carry susceptibility genes. PET ligands are in late-stage development for demonstration of amyloid plaques, and human studies have already begun. Functional MR-based memory challenge tests are in development as well.