用于阿尔茨海默病突触密度、乙酰胆碱转运体、AMPA-tarp-γ8 和毒蕈碱 M4 受体成像的 PET 放射性同位素体外评估。

IF 2 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING American journal of nuclear medicine and molecular imaging Pub Date : 2024-02-20 eCollection Date: 2024-01-01
Faustine d'Orchymont, Andrea Narvaez, Roger Raymond, Pallavi Sachdev, Arnaud Charil, Stephen Krause, Neil Vasdev
{"title":"用于阿尔茨海默病突触密度、乙酰胆碱转运体、AMPA-tarp-γ8 和毒蕈碱 M4 受体成像的 PET 放射性同位素体外评估。","authors":"Faustine d'Orchymont, Andrea Narvaez, Roger Raymond, Pallavi Sachdev, Arnaud Charil, Stephen Krause, Neil Vasdev","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Several therapeutics and biomarkers that target Alzheimer's disease (AD) are under development. Our clinical positron emission tomography (PET) research programs are interested in six radiopharmaceuticals to image patients with AD and related dementias, specifically [<sup>11</sup>C]UCB-J and [<sup>18</sup>F]SynVesT-1 for synaptic vesicle glycoprotein 2A as a marker of synaptic density, two vesicular acetylcholine transporter PET radiotracers: [<sup>18</sup>F]FEOBV and [<sup>18</sup>F]VAT, as well as the transmembrane AMPA receptor regulatory protein (TARP)-γ8 tracer, [<sup>18</sup>F]JNJ-64511070, and the muscarinic acetylcholine receptor (mAChR) M4 tracer [<sup>11</sup>C]MK-6884. The goal of this study was to compare all six radiotracers (labeled with tritium or <sup>18</sup>F) by measuring their density variability in pathologically diagnosed cases of AD, mild cognitive impairment (MCI) and normal healthy volunteer (NHV) human brains, using thin-section <i>in vitro</i> autoradiography (ARG). Region of interest analysis was used to quantify radioligand binding density and determine whether the radioligands provide a signal-to-noise ratio optimal for showing changes in binding. Our preliminary study confirmed that all six radiotracers show specific binding in MCI and AD. An expected decrease in their respective target density in human AD hippocampus tissues compared to NHV was observed with [<sup>3</sup>H]UCB-J, [<sup>3</sup>H]SynVesT-1, [<sup>3</sup>H]JNJ-64511070, and [<sup>3</sup>H]MK-6884. This preliminary study will be used to guide human PET imaging of SV2A, TARP-γ8 and the mAChR M4 subtype for imaging in AD and related dementias.</p>","PeriodicalId":7572,"journal":{"name":"American journal of nuclear medicine and molecular imaging","volume":null,"pages":null},"PeriodicalIF":2.0000,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944377/pdf/","citationCount":"0","resultStr":"{\"title\":\"In vitro evaluation of PET radiotracers for imaging synaptic density, the acetylcholine transporter, AMPA-tarp-γ8 and muscarinic M4 receptors in Alzheimer's disease.\",\"authors\":\"Faustine d'Orchymont, Andrea Narvaez, Roger Raymond, Pallavi Sachdev, Arnaud Charil, Stephen Krause, Neil Vasdev\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Several therapeutics and biomarkers that target Alzheimer's disease (AD) are under development. Our clinical positron emission tomography (PET) research programs are interested in six radiopharmaceuticals to image patients with AD and related dementias, specifically [<sup>11</sup>C]UCB-J and [<sup>18</sup>F]SynVesT-1 for synaptic vesicle glycoprotein 2A as a marker of synaptic density, two vesicular acetylcholine transporter PET radiotracers: [<sup>18</sup>F]FEOBV and [<sup>18</sup>F]VAT, as well as the transmembrane AMPA receptor regulatory protein (TARP)-γ8 tracer, [<sup>18</sup>F]JNJ-64511070, and the muscarinic acetylcholine receptor (mAChR) M4 tracer [<sup>11</sup>C]MK-6884. The goal of this study was to compare all six radiotracers (labeled with tritium or <sup>18</sup>F) by measuring their density variability in pathologically diagnosed cases of AD, mild cognitive impairment (MCI) and normal healthy volunteer (NHV) human brains, using thin-section <i>in vitro</i> autoradiography (ARG). Region of interest analysis was used to quantify radioligand binding density and determine whether the radioligands provide a signal-to-noise ratio optimal for showing changes in binding. Our preliminary study confirmed that all six radiotracers show specific binding in MCI and AD. An expected decrease in their respective target density in human AD hippocampus tissues compared to NHV was observed with [<sup>3</sup>H]UCB-J, [<sup>3</sup>H]SynVesT-1, [<sup>3</sup>H]JNJ-64511070, and [<sup>3</sup>H]MK-6884. This preliminary study will be used to guide human PET imaging of SV2A, TARP-γ8 and the mAChR M4 subtype for imaging in AD and related dementias.</p>\",\"PeriodicalId\":7572,\"journal\":{\"name\":\"American journal of nuclear medicine and molecular imaging\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-02-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10944377/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of nuclear medicine and molecular imaging\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of nuclear medicine and molecular imaging","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING","Score":null,"Total":0}
引用次数: 0

摘要

目前正在开发几种针对阿尔茨海默病(AD)的治疗药物和生物标记物。我们的临床正电子发射断层扫描(PET)研究项目对六种放射性药物很感兴趣,这些药物可用于对阿尔茨海默病和相关痴呆症患者进行成像,特别是用于突触囊泡糖蛋白 2A 的[11C]UCB-J 和[18F]SynVesT-1(作为突触密度的标记)、两种囊泡乙酰胆碱转运体 PET 放射性racers:[18F]FEOBV和[18F]VAT,以及跨膜AMPA受体调节蛋白(TARP)-γ8示踪剂[18F]JNJ-64511070和毒蕈碱乙酰胆碱受体(mAChR)M4示踪剂[11C]MK-6884。本研究的目的是利用薄片体外自显影(ARG)技术,通过测量病理诊断的 AD、轻度认知障碍(MCI)和正常健康志愿者(NHV)人脑中这六种放射性掺杂剂(用氚或 18F 标记)的密度变化,对它们进行比较。感兴趣区分析用于量化放射性配体的结合密度,并确定放射性配体是否能提供显示结合变化的最佳信噪比。我们的初步研究证实,所有六种放射性配体在 MCI 和 AD 中都有特异性结合。与NHV相比,[3H]UCB-J、[3H]SynVesT-1、[3H]JNJ-64511070和[3H]MK-6884在人类AD海马组织中的各自靶密度出现了预期的下降。这项初步研究将用于指导对 SV2A、TARP-γ8 和 mAChR M4 亚型进行人体 PET 成像,以对注意力缺失症和相关痴呆症进行成像。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
In vitro evaluation of PET radiotracers for imaging synaptic density, the acetylcholine transporter, AMPA-tarp-γ8 and muscarinic M4 receptors in Alzheimer's disease.

Several therapeutics and biomarkers that target Alzheimer's disease (AD) are under development. Our clinical positron emission tomography (PET) research programs are interested in six radiopharmaceuticals to image patients with AD and related dementias, specifically [11C]UCB-J and [18F]SynVesT-1 for synaptic vesicle glycoprotein 2A as a marker of synaptic density, two vesicular acetylcholine transporter PET radiotracers: [18F]FEOBV and [18F]VAT, as well as the transmembrane AMPA receptor regulatory protein (TARP)-γ8 tracer, [18F]JNJ-64511070, and the muscarinic acetylcholine receptor (mAChR) M4 tracer [11C]MK-6884. The goal of this study was to compare all six radiotracers (labeled with tritium or 18F) by measuring their density variability in pathologically diagnosed cases of AD, mild cognitive impairment (MCI) and normal healthy volunteer (NHV) human brains, using thin-section in vitro autoradiography (ARG). Region of interest analysis was used to quantify radioligand binding density and determine whether the radioligands provide a signal-to-noise ratio optimal for showing changes in binding. Our preliminary study confirmed that all six radiotracers show specific binding in MCI and AD. An expected decrease in their respective target density in human AD hippocampus tissues compared to NHV was observed with [3H]UCB-J, [3H]SynVesT-1, [3H]JNJ-64511070, and [3H]MK-6884. This preliminary study will be used to guide human PET imaging of SV2A, TARP-γ8 and the mAChR M4 subtype for imaging in AD and related dementias.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
American journal of nuclear medicine and molecular imaging
American journal of nuclear medicine and molecular imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
自引率
4.00%
发文量
4
期刊介绍: The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.
期刊最新文献
A radioactive and fluorescent dual modality cysteine cathepsin-B activity-based probe for the detection and treatment evaluation in rheumatoid arthritis. Accurate brain pharmacokinetic parametric imaging using the blood input function extracted from the cavernous sinus. Analysis of bone single-photon emission CT/CT and diffusion-weighted MR imaging in medication-related osteonecrosis of the jaw: focusing on the correlation between standardized uptake values and apparent diffusion coefficient values. Hemodynamic characteristics of vertebrobasilar artery fenestration combined with vertebrobasilar dolichoectasia: a study based on magnetic resonance angiography. Radiomics-based model for prediction of TGF-β1 expression in head and neck squamous cell carcinoma.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1