Recent developments on PET radiotracers for TSPO and their applications in neuroimaging
The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial c...
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| Language: | English |
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Elsevier
2021-02-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383520306894 |
| _version_ | 1818417720867160064 |
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| author | Lingling Zhang Kuan Hu Tuo Shao Lu Hou Shaojuan Zhang Weijian Ye Lee Josephson Jeffrey H. Meyer Ming-Rong Zhang Neil Vasdev Jinghao Wang Hao Xu Lu Wang Steven H. Liang |
| author_facet | Lingling Zhang Kuan Hu Tuo Shao Lu Hou Shaojuan Zhang Weijian Ye Lee Josephson Jeffrey H. Meyer Ming-Rong Zhang Neil Vasdev Jinghao Wang Hao Xu Lu Wang Steven H. Liang |
| author_sort | Lingling Zhang |
| collection | DOAJ |
| description | The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases. |
| first_indexed | 2024-12-14T12:11:16Z |
| format | Article |
| id | doaj.art-f41bf533ef0c495f89c741de8840c7ea |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-14T12:11:16Z |
| publishDate | 2021-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-f41bf533ef0c495f89c741de8840c7ea2022-12-21T23:01:44ZengElsevierActa Pharmaceutica Sinica B2211-38352021-02-01112373393Recent developments on PET radiotracers for TSPO and their applications in neuroimagingLingling Zhang0Kuan Hu1Tuo Shao2Lu Hou3Shaojuan Zhang4Weijian Ye5Lee Josephson6Jeffrey H. Meyer7Ming-Rong Zhang8Neil Vasdev9Jinghao Wang10Hao Xu11Lu Wang12Steven H. Liang13Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Department of Neurology, the First Affiliated Hospital of Jinan University, Guangzhou 510630, ChinaDepartment of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, JapanDivision of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USACenter of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, ChinaCenter of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, ChinaCenter of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, ChinaDivision of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USAAzrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health & Department of Psychiatry, University of Toronto, Toronto ON M5T 1R8, CanadaDepartment of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, JapanDivision of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA; Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health & Department of Psychiatry, University of Toronto, Toronto ON M5T 1R8, CanadaDepartment of Pharmacy, the First Affiliated Hospital of Jinan University, Guangzhou 510630, ChinaCenter of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Corresponding authors.Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine and PET/CT-MRI Center, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA; Corresponding authors.Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA; Corresponding authors.The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial membrane in steroidogenic cells. Brain TSPO expression is relatively low under physiological conditions, but is upregulated in response to glial cell activation. As the primary index of neuroinflammation, TSPO is implicated in the pathogenesis and progression of numerous neuropsychiatric disorders and neurodegenerative diseases, including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), major depressive disorder (MDD) and obsessive compulsive disorder (OCD). In this context, numerous TSPO-targeted positron emission tomography (PET) tracers have been developed. Among them, several radioligands have advanced to clinical research studies. In this review, we will overview the recent development of TSPO PET tracers, focusing on the radioligand design, radioisotope labeling, pharmacokinetics, and PET imaging evaluation. Additionally, we will consider current limitations, as well as translational potential for future application of TSPO radiopharmaceuticals. This review aims to not only present the challenges in current TSPO PET imaging, but to also provide a new perspective on TSPO targeted PET tracer discovery efforts. Addressing these challenges will facilitate the translation of TSPO in clinical studies of neuroinflammation associated with central nervous system diseases.http://www.sciencedirect.com/science/article/pii/S2211383520306894TSPOMicroglial activationNeuroinflammationPositron emission tomography (PET)CNS disorders |
| spellingShingle | Lingling Zhang Kuan Hu Tuo Shao Lu Hou Shaojuan Zhang Weijian Ye Lee Josephson Jeffrey H. Meyer Ming-Rong Zhang Neil Vasdev Jinghao Wang Hao Xu Lu Wang Steven H. Liang Recent developments on PET radiotracers for TSPO and their applications in neuroimaging Acta Pharmaceutica Sinica B TSPO Microglial activation Neuroinflammation Positron emission tomography (PET) CNS disorders |
| title | Recent developments on PET radiotracers for TSPO and their applications in neuroimaging |
| title_full | Recent developments on PET radiotracers for TSPO and their applications in neuroimaging |
| title_fullStr | Recent developments on PET radiotracers for TSPO and their applications in neuroimaging |
| title_full_unstemmed | Recent developments on PET radiotracers for TSPO and their applications in neuroimaging |
| title_short | Recent developments on PET radiotracers for TSPO and their applications in neuroimaging |
| title_sort | recent developments on pet radiotracers for tspo and their applications in neuroimaging |
| topic | TSPO Microglial activation Neuroinflammation Positron emission tomography (PET) CNS disorders |
| url | http://www.sciencedirect.com/science/article/pii/S2211383520306894 |
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