Development of positron emission tomography β-amyloid plaque imaging agents.
Development of positron emission tomography β-amyloid plaque imaging agents.
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DOI：
10.1053/j.semnuclmed.2012.07.001
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发表时间：
2012-11
影响因子：
4.9
通讯作者：
Klunk WE
中科院分区：
文献类型：
--
作者：
Mathis CA;Mason NS;Lopresti BJ;Klunk WE
100年来，β-淀粉样蛋白（Aβ）斑块和神经原纤维缠结（nft）被认为是阿尔茨海默病（AD）的神经病理学标志，它们的存在或不存在只能在死后通过染色和染料来确定这些微观结构。大约10年前，第一个成功的a β斑块特异性正电子发射断层扫描（PET）成像研究在临床诊断为可能AD的活的人类受试者中进行，使用11c标记的放射性药物匹兹堡化合物B （PiB）。设计PiB的实验室研究和临床前评估比第一次人类PiB PET研究早十年开始，涉及不同已知染料的化学修饰，这些染料特异性地结合到包含淀粉样蛋白原纤维（如β斑块，nft， β-突触核蛋白沉积物和朊病毒）的扩展β-皱褶片上。这些临床前研究是在匹兹堡大学的实验室进行的，从刚果红衍生物开始，然后是金胺G衍生物，然后是x系列化合物，最后是硫黄素- t的中性衍生物。本文介绍了不同衍生物作为人脑中β斑块和神经原纤维缠结成像的候选PET放射配体的体外和体内评价，以及判断候选放射配体的具体评价标准。从这些研究中得出了PiB，这是一种PET放射性配体，它选择性地、高亲和力地仅与纤维状的a β结合。PiB已在世界各地的许多不同的人类研究方案中使用，并已证明在临床诊断可能的AD前多年评估受试者的Aβ斑块状态是有用的。近年来，长寿命的18f放射性标记的a β选择性放射性药物已被开发出来。这些显像剂的全部临床影响可能会通过识别症状前受试者来实现，这些受试者将受益于早期药物治疗和未来的疾病改善性阿尔茨海默病治疗。
For 100 years, β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) have been recognized as the neuropathological hallmarks of Alzheimer’s disease (AD), and their presence or absence could only be assessed postmortem using stains and dyes that identified these microscopic structures. Approximately 10 years ago, the first successful Aβ plaque–specific positron emission tomography (PET) imaging study was conducted in a living human subject clinically diagnosed with probable AD using the 11C-labeled radiopharmaceutical Pittsburgh Compound B (PiB). Laboratory studies and preclinical evaluations to design PiB began a decade earlier than the first human PiB PET study and involved chemical modifications of different well-known dyes that bound specifically to the extended β-pleated sheets that comprise the fibrils of amyloid proteins such as Aβ plaques, NFTs, β-synuclein deposits, and prions. These preclinical studies were conducted in our laboratories at the University of Pittsburgh, starting with Congo red derivatives, followed by Chrysamine G derivatives, followed by X-series compounds, and finally with neutral derivatives of thioflavin-T. The in vitro and in vivo evaluations of the different derivatives as candidate PET radioligands for imaging Aβ plaques and neurofibrillary tangles in human brain are described in this review, along with the specific evaluation criteria by which the candidate radioligands were judged. Out of these studies came PiB, a PET radioligand that binds selectively and with high affinity to only fibrillar forms of Aβ. PiB has been used in many different human research protocols throughout the world and has demonstrated the usefulness of assessing the Aβ plaque status of subjects many years before the clinical diagnosis of probable AD. Recently, longer-lived 18F-radiolabeled Aβ-selective radiopharmaceuticals have been developed. It is likely that the full clinical impact of these imaging agents will be realized by identifying presymptomatic subjects who would benefit from early drug treatments with future disease-modifying AD therapeutics.
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影响因子：
12.7
作者：
Ikonomovic MD;Abrahamson EE;Price JC;Hamilton RL;Mathis CA;Paljug WR;Debnath ML;Cohen AD;Mizukami K;DeKosky ST;Lopez OL;Klunk WE
通讯作者：
Klunk WE
影响因子：
3.7
作者：
Arnold, Steven E.;Hyman, Bradley T.;Van Hoesen, Gary W.
通讯作者：
Van Hoesen, Gary W.
影响因子：
--
作者：
Aizenstein, Howard Jay;Nebes, Robert D.;Saxton, Judith A.;Price, Julie C.;Mathis, Chester A.;Tsopelas, Nicholas D.;Ziolko, Scott K.;James, Jeffrey A.;Snitz, Beth E.;Houck, Patricia R.;Bi, Wenzhu;Cohen, Ann D.;Lopresti, Brian J.;DeKosky, Steven T.;Halligan, Edythe M.;Klunk, William E.
通讯作者：
Klunk, William E.
影响因子：
56.9
作者：
FARDE, L;HALL, H;SEDVALL, G
通讯作者：
SEDVALL, G
影响因子：
--
作者：
Bacskai, Brian J.;Frosch, Matthew P.;Growdon, John H.
通讯作者：
Growdon, John H.