正电子发射断层扫描 2 型大麻素受体检测中枢神经系统炎症。
Positron emission tomography of type 2 cannabinoid receptors for detecting inflammation in the central nervous system.
机构信息
Department of Chemistry and Applied Biosciences, Center for Radiopharmaceutical Sciences of ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Zurich, 8093, Switzerland.
Department of Nuclear Medicine, University Hospital Zurich, Zurich, 8091, Switzerland.
出版信息
Acta Pharmacol Sin. 2019 Mar;40(3):351-357. doi: 10.1038/s41401-018-0035-5. Epub 2018 Jun 19.
Abstract
Cannabinoid receptor CB (CBR) is upregulated on activated microglia and astrocytes in the brain under inflammatory conditions and plays important roles in many neurological diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and ischemic stroke. The advent of positron emission tomography (PET) using CBR radiotracers has enabled the visualization of CBR distribution in vivo in animal models of central nervous system inflammation, however translation to humans has been less successful. Several novel CBR radiotracers have been developed and evaluated to quantify microglial activation. In this review, we summarize the recent preclinical and clinical imaging results of CBR PET tracers and discuss the prospects of CBR imaging using PET.
摘要
大麻素受体 CB（CBR）在炎症条件下在大脑中活化的小胶质细胞和星形胶质细胞上上调，并在许多神经疾病中发挥重要作用，如阿尔茨海默病、肌萎缩侧索硬化症和缺血性中风。正电子发射断层扫描（PET）使用 CBR 放射性示踪剂的出现使中枢神经系统炎症动物模型中 CBR 分布的可视化成为可能，然而向人类的转化则不太成功。已经开发和评估了几种新型 CBR 放射性示踪剂来定量测量小胶质细胞的激活。在这篇综述中，我们总结了 CBR PET 示踪剂的最新临床前和临床成像结果，并讨论了使用 PET 进行 CBR 成像的前景。
相似文献
1
Positron emission tomography of type 2 cannabinoid receptors for detecting inflammation in the central nervous system.正电子发射断层扫描 2 型大麻素受体检测中枢神经系统炎症。
Acta Pharmacol Sin. 2019 Mar;40(3):351-357. doi: 10.1038/s41401-018-0035-5. Epub 2018 Jun 19.
2
Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer's disease.阿尔茨海默病中2型大麻素受体的体内可用性降低。
Eur J Nucl Med Mol Imaging. 2016 Nov;43(12):2219-2227. doi: 10.1007/s00259-016-3457-7. Epub 2016 Aug 3.
3
Upregulation of cannabinoid receptor type 2, but not TSPO, in senescence-accelerated neuroinflammation in mice: a positron emission tomography study.大麻素受体 2 的上调，而非 TSPO，在小鼠加速衰老的神经炎症中：一项正电子发射断层扫描研究。
J Neuroinflammation. 2019 Nov 10;16(1):208. doi: 10.1186/s12974-019-1604-3.
4
PET imaging of cannabinoid type 2 receptors with [C]A-836339 did not evidence changes following neuroinflammation in rats.使用[C]A-836339对大鼠2型大麻素受体进行正电子发射断层扫描（PET）成像，未发现神经炎症后有变化迹象。
J Cereb Blood Flow Metab. 2017 Mar;37(3):1163-1178. doi: 10.1177/0271678X16685105. Epub 2017 Jan 12.
5
Radioligands for positron emission tomography imaging of cannabinoid type 2 receptor.用于大麻素2型受体正电子发射断层显像的放射性配体。
J Labelled Comp Radiopharm. 2018 Mar;61(3):299-308. doi: 10.1002/jlcr.3579. Epub 2017 Dec 29.
6
CB2 Receptor in Microglia: The Guardian of Self-Control.小胶质细胞中的 CB2 受体：自我控制的守护者。
Int J Mol Sci. 2020 Dec 22;22(1):19. doi: 10.3390/ijms22010019.
7
From Structure-Activity Relationships on Thiazole Derivatives to the In Vivo Evaluation of a New Radiotracer for Cannabinoid Subtype 2 PET Imaging.从噻唑衍生物的构效关系到新型大麻素 2 型受体 PET 显像放射性示踪剂的体内评价。
Mol Pharm. 2017 Nov 6;14(11):4064-4078. doi: 10.1021/acs.molpharmaceut.7b00746. Epub 2017 Oct 18.
8
Cannabinoid type 2 receptor activation downregulates stroke-induced classic and alternative brain macrophage/microglial activation concomitant to neuroprotection.大麻素 2 型受体激活下调卒中诱导的经典和替代型脑巨噬细胞/小胶质细胞激活，同时发挥神经保护作用。
Stroke. 2012 Jan;43(1):211-9. doi: 10.1161/STROKEAHA.111.631044. Epub 2011 Oct 20.
9
Synthesis, Structure-Activity Relationships, Radiofluorination, and Biological Evaluation of [F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET.[F]RM365 的合成、构效关系、放射性标记及作为正电子发射断层扫描（PET）脑内人源大麻素受体 2（CB2R）显像剂的生物学评价
J Med Chem. 2023 Oct 26;66(20):13991-14010. doi: 10.1021/acs.jmedchem.3c01035. Epub 2023 Oct 10.
10
Cannabinoid Receptor 2 Alters Social Memory and Microglial Activity in an Age-Dependent Manner.大麻素受体 2 以年龄依赖的方式改变社交记忆和小胶质细胞活性。
Molecules. 2021 Oct 2;26(19):5984. doi: 10.3390/molecules26195984.
引用本文的文献
1
Development of Carborane-Based Benzothiazole Analogues as Cannabinoid Receptor Type 2 (CBR) Ligands.基于碳硼烷的苯并噻唑类似物作为2型大麻素受体（CBR）配体的开发。
ACS Omega. 2025 Aug 13;10(33):38264-38271. doi: 10.1021/acsomega.5c06508. eCollection 2025 Aug 26.
2
Biomarkers and therapeutic strategies targeting microglia in neurodegenerative diseases: current status and future directions.神经退行性疾病中靶向小胶质细胞的生物标志物与治疗策略：现状与未来方向
Mol Neurodegener. 2025 Jul 10;20(1):82. doi: 10.1186/s13024-025-00867-4.
3
Translational Preclinical PET Imaging and Metabolic Evaluation of a New Cannabinoid 2 Receptor (CBR) Radioligand, ()--(3-(2-(2-[F]Fluoroethoxy)ethyl)-4,5-dimethylthiazol-2(3)-ylidene)-2,2,3,3-tetramethylcyclopropane-1-carboxamide.一种新型大麻素2型受体（CBR）放射性配体（）--(3-(2-(2-[¹⁸F]氟乙氧基)乙基)-4,5-二甲基噻唑-2(3)-亚基)-2,2,3,3-四甲基环丙烷-1-甲酰胺的转化临床前PET成像与代谢评估
ACS Pharmacol Transl Sci. 2024 Sep 13;7(10):3144-3154. doi: 10.1021/acsptsci.4c00348. eCollection 2024 Oct 11.
4
Emerging roles of cannabinoid receptor CB2 receptor in the central nervous system: therapeutic target for CNS disorders.大麻素受体 CB2 受体在中枢神经系统中的新兴作用：中枢神经系统疾病的治疗靶点。
Psychopharmacology (Berl). 2024 Oct;241(10):1939-1954. doi: 10.1007/s00213-024-06683-w. Epub 2024 Sep 12.
5
Cannabinoid CB2 receptors and hypersensitivity to methamphetamine: Vulnerability to schizophrenia.大麻素 CB2 受体与对甲基苯丙胺的敏感性：精神分裂症易感性。
Prog Neuropsychopharmacol Biol Psychiatry. 2024 Mar 2;130:110924. doi: 10.1016/j.pnpbp.2023.110924. Epub 2023 Dec 20.
6
Synthesis, Structure-Activity Relationships, Radiofluorination, and Biological Evaluation of [F]RM365, a Novel Radioligand for Imaging the Human Cannabinoid Receptor Type 2 (CB2R) in the Brain with PET.[F]RM365 的合成、构效关系、放射性标记及作为正电子发射断层扫描（PET）脑内人源大麻素受体 2（CB2R）显像剂的生物学评价
J Med Chem. 2023 Oct 26;66(20):13991-14010. doi: 10.1021/acs.jmedchem.3c01035. Epub 2023 Oct 10.
7
Development of the High-Affinity Carborane-Based Cannabinoid Receptor Type 2 PET Ligand [F]LUZ5-.高亲和力基于碳硼烷的大麻素受体 2 PET 配体[F]LUZ5-的研制。
J Med Chem. 2023 Apr 13;66(7):5242-5260. doi: 10.1021/acs.jmedchem.3c00195. Epub 2023 Mar 21.
8
Evaluation of cannabinoid type 2 receptor expression and pyridine-based radiotracers in brains from a mouse model of Alzheimer's disease.阿尔茨海默病小鼠模型大脑中2型大麻素受体表达及吡啶基放射性示踪剂的评估
Front Aging Neurosci. 2022 Sep 30;14:1018610. doi: 10.3389/fnagi.2022.1018610. eCollection 2022.
9
Expression of the Adenosine A-A Receptor Heteromer in Different Brain Regions and Marked Upregulation in the Microglia of the Transgenic APP Alzheimer's Disease Model.腺苷A-A受体异聚体在不同脑区的表达及在转基因APP阿尔茨海默病模型小胶质细胞中的显著上调
Biomedicines. 2022 Jan 19;10(2):214. doi: 10.3390/biomedicines10020214.
10
Positron Emission Tomography in Animal Models of Tauopathies.正电子发射断层扫描在tau蛋白病动物模型中的应用
Front Aging Neurosci. 2022 Jan 10;13:761913. doi: 10.3389/fnagi.2021.761913. eCollection 2021.
本文引用的文献
1
Evaluation of 4-oxo-quinoline-based CB2 PET radioligands in R6/2 chorea huntington mouse model and human ALS spinal cord tissue.评估基于 4-氧代喹啉的 CB2 PET 放射性配体在 R6/2 亨廷顿舞蹈病小鼠模型和人类 ALS 脊髓组织中的应用。
Eur J Med Chem. 2018 Feb 10;145:746-759. doi: 10.1016/j.ejmech.2017.12.097. Epub 2018 Jan 5.
2
Radioligands for positron emission tomography imaging of cannabinoid type 2 receptor.用于大麻素2型受体正电子发射断层显像的放射性配体。
J Labelled Comp Radiopharm. 2018 Mar;61(3):299-308. doi: 10.1002/jlcr.3579. Epub 2017 Dec 29.
3
From Structure-Activity Relationships on Thiazole Derivatives to the In Vivo Evaluation of a New Radiotracer for Cannabinoid Subtype 2 PET Imaging.从噻唑衍生物的构效关系到新型大麻素 2 型受体 PET 显像放射性示踪剂的体内评价。
Mol Pharm. 2017 Nov 6;14(11):4064-4078. doi: 10.1021/acs.molpharmaceut.7b00746. Epub 2017 Oct 18.
4
Microglia turnover with aging and in an Alzheimer's model via long-term in vivo single-cell imaging.通过长期在体单细胞成像研究衰老和阿尔茨海默病模型中小胶质细胞的更替。
Nat Neurosci. 2017 Oct;20(10):1371-1376. doi: 10.1038/nn.4631. Epub 2017 Aug 28.
5
Transcriptomic analysis of purified human cortical microglia reveals age-associated changes.人类皮质小胶质细胞的转录组分析揭示了与年龄相关的变化。
Nat Neurosci. 2017 Aug;20(8):1162-1171. doi: 10.1038/nn.4597. Epub 2017 Jul 3.
6
Activation of CB receptor system restores cognitive capacity and hippocampal Sox2 expression in a transgenic mouse model of Alzheimer's disease.CB 受体系统的激活可恢复阿尔茨海默病转基因小鼠模型的认知能力和海马 Sox2 表达。
Eur J Pharmacol. 2017 Sep 15;811:12-20. doi: 10.1016/j.ejphar.2017.05.044. Epub 2017 May 25.
7
Loss of 'homeostatic' microglia and patterns of their activation in active multiple sclerosis.“稳态”小胶质细胞的丧失及其在活动性多发性硬化症中的激活模式。
Brain. 2017 Jul 1;140(7):1900-1913. doi: 10.1093/brain/awx113.
8
Development of Highly Affine and Selective Fluorinated Cannabinoid Type 2 Receptor Ligands.高亲和力和选择性的氟化大麻素2型受体配体的研发
ACS Med Chem Lett. 2017 Apr 28;8(5):566-571. doi: 10.1021/acsmedchemlett.7b00129. eCollection 2017 May 11.
9
Translocator Protein-18 kDa (TSPO) Positron Emission Tomography (PET) Imaging and Its Clinical Impact in Neurodegenerative Diseases.18 kDa转位蛋白（TSPO）正电子发射断层扫描（PET）成像及其在神经退行性疾病中的临床影响
Int J Mol Sci. 2017 Apr 7;18(4):785. doi: 10.3390/ijms18040785.
10
In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: a positron emission tomography study.大鼠缺血性脑卒中后神经炎症早期体内转运体18 kDa外周苯二氮䓬受体（TSPO）和大麻素2型受体的可用性：一项正电子发射断层扫描研究
J Neuroinflammation. 2017 Mar 29;14(1):69. doi: 10.1186/s12974-017-0851-4.
Zotero 插件