-
阿尔茨海默病(Alzheimer disease,AD)是一种中枢神经系统变性疾病,起病隐匿,呈进行性发展,主要表现为渐进性记忆障碍、认知功能障碍、人格改变及语言障碍等神经精神症状,严重影响社交、职业与生活能力。随着全球人口老龄化日趋严重,AD患者的绝对人数和比例持续增加,成为严重影响社会和经济发展的重大问题之一。目前确诊AD唯一可靠的方法是脑组织的病理学检查,临床难以实施,因此急需一种无创性的、能够早期诊断AD、动态监测疾病发展与实时评价AD治疗效果的有效方法,PET以及PET显像剂的快速发展为实现这一目标提供了理想手段[1]。通过10余年的发展,PET扫描速度与解剖分辨率明显提高,最新一代PET/MRI设备即将投入临床使用,将为AD早期诊断与疗效评价提供全新临床分子影像平台。PET显像价值依赖于示踪剂的发展,近年来,AD相关PET正电子药物发展迅速,本文就此类正电子药物的应用与研究进展做一综述,希望为AD分子显像提供参考。
阿尔茨海默病PET正电子药物应用与研究进展
Application and research progress of PET positron tracers associated with Alzheimer disease
-
摘要: 阿尔茨海默病(AD)严重危害人们的身心健康。伴随PET分子成像的发展,出现了一系列针对AD的正电子药物,其中匹兹堡化合物B(PIB)及其衍生物类PET正电子药物研究最为成熟,部分已获准应用于临床,在AD诊断与治疗方面显示出重要价值。随着人们对AD发生机制研究的不断深入,近年又相继出现了包括蛋白类、受体类以及肽类在内的更多种类AD相关PET正电子药物。该文就此类正电子药物的应用与研究进展做一综述。
-
关键词:
- 阿尔茨海默病 /
- 正电子发射断层显像术 /
- 正电子药物
Abstract: Alzheimer disease(AD) harms human being′s health seriously.With the development progress of PET molecular imaging, a series of PET positron tracers associated with AD appeard.Among them, pittsburgh compound-B(PIB) and PIB derivatives are studied more deeply and part of them have been used in clinic which are showing great value in diagnosis and therapy of AD.Recently, with the deeper research of AD mechanism, more kinds of PET tracers related to AD are developed, including protein, receptor and peptide radiotracers.This article reviews the current application and research progress of those PET positron tracers which associated with AD.-
Key words:
- Alzheimer disease /
- Positron-emission tomography /
- Radiotracer
-
[1] McKhann GM, Knopman DS, Chertkow H, et al.The diagnosis of dementia due to Alzheimer′s disease: recommendations from the National Institute on Aging-Alzheimer′s Association workgroups on diagnostic guidelines for Alzheimer′s disease[J].Alzheimers Dement, 2011, 7(3): 263-269. [2] Colletier JP, Laganowsky A, Landau M, et al.Molecular basis for amyloid-beta polymorphism[J].Proc Natl Acad Sci USA, 2011, 108(41): 16938-16943. [3] Jeong JS, Ansaloni A, Mezzenga R, et al.Novel mechanistic insight into the molecular basis of amyloid polymorphism and secondary nucleation during amyloid formation[J].J Mol Biol, 2013, 425(10): 1765-1781. [4] Kawahara M.Neurotoxicity of β-amyloid protein: oligomerization, channel formation, and calcium dyshomeostasis[J].Curr Pharm Des, 2010, 16(25): 2779-2789. [5] Hatashita S, Yamasaki H.Clinically different stages of Alzheimer′s disease associated by amyloid deposition with [11C]-PIB PET imaging[J].J Alzheimers Dis, 2010, 21(3): 995-1003. [6] Vandenberghe R, Van Laere K, Ivanoiu A, et al.18F-flutemetamol amyloid imaging in Alzheimer disease and mild cognitive impairment: a phase 2 trial[J].Ann Neurol, 2010, 68(3): 319-329. [7] Hsiao IT, Huang CC, Hsieh CJ, et al.Correlation of early-phase 18F-florbetapir(AV-45/Amyvid) PET images to FDG images: preliminary studies[J].Eur J Nucl Med Mol Imaging, 2012, 39(4): 613-620. [8] Becker GA, Ichise M, Barthel H, et al.PET quantification of 18F-florbetaben binding to β-amyloid deposits in human brains[J].J Nucl Med, 2013, 54(5): 723-731. [9] Tauber C, Beaufils E, Hommet C, et al.Brain [18F]FDDNP binding and glucose metabolism in advanced elderly healthy subjects and Alzheimer's disease patients[J].J Alzheimers Dis, 2013, 36(2): 311-320. [10] Okamura N, Furumoto S, Harada R, et al.Novel 18F-Labeled arylquinoline derivatives for noninvasive imaging of tau pathology in Alzheimer disease[J].J Nucl Med, 2013, 54(8): 1420-1427. [11] Mathis CA, Bacskai BJ, Kajdasz ST, et al.A lipophilic thioflavin-T derivative for positron emission tomography(PET) imaging of amyloid in brain[J].Bioorg Med Chem Lett, 2002, 12(3): 295-298. [12] Kemppainen NM, Scheinin NM, Koivunen J, et al.Five-year follow-up of 11C-PIB uptake in Alzheimer′s disease and MCI[J].Eur J Nucl Med Mol Imaging, 2014, 41(2): 283-289. [13] Clark CM, Schneider JA, Bedell BJ, et al.Use of florbetapir-PET for imaging beta-amyloid pathology[J].JAMA, 2011, 305(3): 275-283. [14] Rinne JO, Wong DF, Wolk DA, et al. [18F]Flutemetamol PET imaging and cortical biopsy histopathology for fibrillar amyloid β detection in living subjects with normal pressure hydrocephalus: pooled analysis of four studies[J].Acta Neuropathol, 2012, 124(6): 833-845. [15] Hatashita S, Yamasaki H, Suzuki Y, et al. [18F]Flutemetamol amyloid-beta PET imaging compared with [11C]PIB across the spectrum of Alzheimer′s disease[J].Eur J Nucl Med Mol Imaging, 2014, 41(2): 290-300. [16] Barthel H, Gertz HJ, Dresel S, et al.Cerebral amyloid-beta PET with florbetaben (18F) in patients with Alzheimer′s disease and healthy controls: a multicentre phase 2 diagnostic study[J].Lancet Neurol, 2011, 10(5): 424-435. [17] Rominger A, Brendel M, Burgold S, et al.Longitudinal assessment of cerebral β-amyloid deposition in mice overexpressing Swedish mutant β-amyloid precursor protein using 18F-florbetaben PET[J].J Nucl Med, 2013, 54(7): 1127-1134. [18] Thompson PW, Ye L, Morgenstern JL, et al.Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer′s disease pathologies[J].J Neurochem, 2009, 109(2): 623-630. [19] Ercoli LM, Siddarth P, Kepe V, et al.Differential FDDNP PET patternsin nondemented middle-aged and older adults[J].Am J Geriatr Psychiatry, 2009, 17(5): 397-406. [20] Tolboom N, Yaqub M, van der Flier WM, et al.Detection of Alzheimer pathology in vivo using both 11C-PIB and 18F-FDDNP PET[J].J Nucl Med, 2009, 50(2): 191-197. [21] Tolboom N, van der Flier WM, Boverhoff J, et al.Molecular imaging in the diagnosis of Alzheimer's disease: visual assessment of [11C] PIB and[18F] FDDNP PET images[J].J Neurol Neurosurg Psychiatry, 2010, 81(8): 882-884. [22] Ossenkoppele R, Tolboom N, Foster-Dingley JC, et al.Longitudinal imaging of Alzheimer pathology using [11C] PIB, [18F] FDDNP and [18F] FDG PET[J].Eur J Nucl Med Mol Imaging, 2012, 39(6): 990-1000. [23] Fodero-Tavoletti MT, Okamura N, Furumoto S, et al.18F-THK523: a novel in vivo tau imaging ligand for Alzheimer's disease[J].Brain, 2011, 134(4): 1089-1000. [24] Chien DT, Bahri S, Szardenings AK, et al.Early clinical PET imaging results with the novel PHF-tau radioligand[F-18]-T807[J].J Alzheimers Dis, 2013, 34(2): 457-468. [25] Van Camp N, Boisgard R, Kuhnast B, et al.In vivo imaging of neuroinflammation: a comparative study between [18F]PBR111, [11C]CLINME and [11C]PK11195 in an acute rodent model[J].Eur J Nucl Med Mol Imaging, 2010, 37(5): 962-972. [26] Wang M, Gao M, Miller KD, et al.Synthesis of [11C]PBR06 and [18F]PBR06 as agents for positron emission tomographic(PET)imaging of the translocator protein(TSPO)[J].Steroids, 2011, 76(12): 1331-1340. [27] Damont A, Boisgard R, Kuhnast B, et al.Synthesis of 6- [18F] fluoro-PBR28, a novel radiotracer for imaging the TSPO 18 kDa with PET[J].Bioorg Med Chem Lett, 2011, 21(16): 4819-4822. [28] Wilms H, Claasen J, Röhl C, et al.Involvement of benzodiazepine receptors in neuroinflammatory and neurodegenerative diseases: evidence from activated microglial cells in vitro[J].Neurobiol Dis, 2003, 14(3): 417-424. [29] Pascual B, Prieto E, Arbizu J, et al.Decreased carbon-11-flumazenil binding in early Alzheimer's disease[J].Brain, 2012, 135(Pt 9): 2817-2825. [30] Wong DF, Waterhouse R, Kuwabara H, et al.18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry[J].J Nucl Med, 2013, 54(3): 388-396. [31] Constantinescu CC, Garcia A, Mirbolooki MR, et al.Evaluation of [18F] Nifene biodistribution and dosimetry based on whole-body PET imaging of mice[J].Nucl Med Biol, 2013, 40(2): 289-294. [32] Kuwabara H, Wong DF, Gao Y, et al.PET Imaging of nicotinic acetylcholine receptors in baboons with 18F-AZAN, a radioligand with improved brain kinetics[J].J Nucl Med, 2012, 53(1): 121-129. [33] Bucerius J, Manka C, Schmaljohann J, et al.Feasibility of [18F]-2-Fluoro-A85380-PET imaging of human vascular nicotinic acetylcholine receptors in vivo[J].JACC Cardiovasc Imaging, 2012, 5(5): 528-536.
计量
- 文章访问数: 2898
- HTML全文浏览量: 1877
- PDF下载量: 6