Endocannabinoid System
We have contributed several review articles in the Positron Emission Tomography (PET) ligand development and neuroimaging application of endocannabinoid system (ECS). These reviews serve to not only summarize recent advancements in the development of PET radioligands and their applications in neuroimaging of the ECS but also offers critical analysis and commentary on each promising chemotype. It concludes with a look into future perspectives in this field.
The ECS is known to be widely distributed in various tissues and organs within both the central and peripheral nervous systems, playing a pivotal role in numerous physiological activities. Beyond that, the ECS is implicated in the development and progression of various neuropsychiatric disorders and neurodegenerative diseases. The use of PET tracers provides a means for noninvasive imaging with quantitative data, enabling the real-time tracking of biological processes in vivo. In light of this, a multitude of radioligands has been created to visualize ECS biodistribution and expression in both healthy and pathological conditions, as well as to investigate the relationship between the ECS and the progression of these diseases.
Selected review articles from our publication:
112. Varlow, C., Boileau, I., Wey, H-Y., Liang, S. H. and Vasdev, N. “Classics in Neuroimaging: Imaging the Endocannabnoid Pathway with PET” ACS Chemical Neuroscience, 2020, 11, 1855-1862. https://pubmed.ncbi.nlm.nih.gov/32559067/
119. Hou, L.; Rong, J.; Haider, A.; Ogasawara, D.; Varlow, C.; Schafroth, M. A.; Mu, L.; Gan, J.; Xu, H.; Fowler, C. J.; Zhang, M-R.; Vasdev, N.; Ametamey, S.; Cravatt, B. F.; Wang, L. and Liang, S. H. “Positron Emission Tomography Imaging of the Endocannabinoid System: Opportunities and Challenges in Radiotracer Development” Journal of Medicinal Chemistry, 2021, accepted. https://pubmed.ncbi.nlm.nih.gov/33379862/
Neuroinflammation
We have contributed several review articles in PET ligand development and application of neuroinflammation, including biological targets such as traditional TSPO and beyond. These reviews not only cover the basic concepts of neuroinflammation including its pathogenesis and relevance to pains, tumors and neurodegenerative diseases, but also summarize recent progress and medicinal chemistry of small molecule neuroinflammation PET probe development as well as their applications in disease models and patients. In addition, major challenges of existing probes and future opportunities will be discussed.
Selected review articles from our publication:
116. Zhang, L.; Hu, K.; Shao, T.; Hou, L.; Zhang, S.; Ye, W.; Josephson, L.; Meyer, J. H.; Zhang, M.-R.; Vasdev, N.; Wang, J.; Xu, H.; Wang, L. and Liang, S. H. “Recent developments on PET radiotracers for TSPO and their applications in neuroimaging” Acta Pharmaceutica Sinica B, 2021, 11, 373-393. https://pubmed.ncbi.nlm.nih.gov/33643818/
133. Chen, Z.;Haider, A.; Chen, J.; Xiao, Z.; Gobbi, L.; Honer, M.; Grether, U.; Arnold, S.; Josephson, L. and Liang, S. H. “The repertoire of small molecule PET probes for neuroinflammation imaging: challenges and opportunities beyond TSPO”, Journal of Medicinal Chemistry, 2021, accepted. Link: https://pubmed.ncbi.nlm.nih.gov/34905377/
Ionotropic Glutamate Receptors
We have contributed several review articles in PET ligand development and application of imaging Ionotropic glutamate receptors (iGluRs). iGluRs are ligand-gated ion channels that mediate excitatory neurotransmission within the mammalian central nervous system (CNS). iGluRs can be divided into three main distinct families: N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors. iGluRs play critical roles in both neural development and neurodegeneration, and their aberrant activity is implicated in a broad spectrum of brain dysfunctions including epilepsy, ischemic stroke and neurodegenerative diseases. Mapping the molecular event of iGluRs by PET would provide meaningful and valuable information on in vivo quantifying the concentration of iGluRs, as well as investigate the distribution and pharmacology of these receptors in physiological and pathological conditions. To this end, past decades have witnessed the remarkable development of PET tracers targeting different iGluRs including NMDA and AMPA receptors, and several of them have advanced to clinical imaging studies.
Selected review articles from our publication:
45. Kassenbrock, A.; Vasdev, N. & Liang, S. H. “Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors” Curr. Top. Med. Chem. 2016, 16, 1830-42. [full-text]
82. Fu, H., Chen, Z., Josephson, L., Li, Z. and Liang, S. H. “Positron Emission Tomography (PET) Ligand Development for Ionotropic Glutamate Receptors: Challenges and Opportunities for Radiotracer Targeting N-methyl-D-aspartate (NMDA), alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) and Kainate Receptors” Journal of Medicinal Chemistry, 2019, 62, 403-419. DOI: https://pubmed.ncbi.nlm.nih.gov/30110164/. PMID: 30110164
Metabotropic Glutamate Receptors
in preparation
Phosphodiesterases (PDEs)
We have contributed several review articles in PET ligand development and application of imaging cyclic nucleotide phosphodiesterase system. Cells recognize chemical and physical extracellular signals through intracellular concentration changes of two second messengers, cyclic adenosine 3′, 5′-monophosphate (cAMP) and cyclic guanosine 3′, 5′-monophosphate (cGMP). In all cells, the concentration of cAMP and/or cGMP is regulated by the activity of cyclic nucleotide phosphodiesterase (PDEs) that catalyze the degradation of these two second messengers. Thus, PDEs could regulate a wide range of biological processes affecting the nervous system, the cardiovascular system, fertility, immunity, cancer and metabolism in the central nervous system and peripheral tissues. PET tracers can provide quantitative information from noninvasive imaging and allow for tracking real-time biological processes in vivo. In this context, numerous radioligands have been developed for visualizing PDEs biodistribution and expression in physiological and pathological conditions, as well as for determining the relationship between PDEs quantification and disease progression.
Selected review articles from our publication:
126. Sun, J.; Xiao, Z.; Haider, A.; Gebhard, C.; Xu, H.; Luo, H. B.; Zhang, H. T.; Josephson, L.; Wang, L. and Liang, S. H. “Advances in Cyclic Nucleotide Phosphodiesterase-Targeted PET Imaging and Drug Discovery”, Journal of Medicinal Chemistry, 2021, accepted. DOI:
https://pubmed.ncbi.nlm.nih.gov/34042442/
Serotonin Receptors
We have contributed several review articles in PET ligand development and application of imaging 5HT receptors (Serotonin system). The serotonin (5-hydroxytryptamine, 5-HT) system is one of the oldest neurotransmitter/hormone systems in evolution. Currently, 14 structurally and pharmacologically distinct mammalian 5-HT receptor subtypes have been described. In central nervous system (CNS), serotonin and its receptors (5-HTRs) play key roles in the pathophysiology of a variety of neuropsychiatric and neurodegenerative disorders, which renders them attractive diagnostic and therapeutic targets. In addition, 5-HT is also highly distributed outside the CNS, and affects a variety of physiologic processes in diverse organs such as cardiovascular function and gastrointestinal functions. PET, a noninvasive molecular imaging, has been widely used for the quantification of neuroreceptor binding and release of neurotransmitters, and measuring enzyme binding, which has gained great achievement in early diagnosis and evaluation of therapy effects of the disease. In this context, many PET radioligands have been developed for visualizing 5-HTRs’ biodistribution and expression in physiological and pathological conditions, and lots of clinical achievements have been obtained with several excellent PET tracers.
Selected review articles from our publication:
142. Fu, H.; Rong, J.; Chen, Z.; Zhou, J.; Collier, T. and Liang, S. H. “Positron Emission Tomography (PET) Imaging Tracers for Serotonin Receptors”, Journal of Medicinal Chemistry, 2022, accepted. Link: https://doi.org/10.1021/acs.jmedchem.2c00633