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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| Published in | Acta pharmaceutica Sinica. B Vol. 11; no. 2; pp. 373 - 393 |
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| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier B.V
01.02.2021
Elsevier |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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.
The 18 kDa translocator protein (TSPO) expression in the central nervous system is upregulated in response to glial cell activation. There is a great potential for the future application of TSPO radioligands as diagnostic and prognostic tools, as well as for assessing therapeutic interventions for neurologic diseases. [Display omitted] |
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| AbstractList | 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. 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. The 18 kDa translocator protein (TSPO) expression in the central nervous system is upregulated in response to glial cell activation. There is a great potential for the future application of TSPO radioligands as diagnostic and prognostic tools, as well as for assessing therapeutic interventions for neurologic diseases. Image 1 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.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. 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. The 18 kDa translocator protein (TSPO) expression in the central nervous system is upregulated in response to glial cell activation. There is a great potential for the future application of TSPO radioligands as diagnostic and prognostic tools, as well as for assessing therapeutic interventions for neurologic diseases. [Display omitted] |
| Author | Xu, Hao Hou, Lu Wang, Jinghao Zhang, Lingling Hu, Kuan Ye, Weijian Meyer, Jeffrey H. Zhang, Ming-Rong Wang, Lu Vasdev, Neil Shao, Tuo Josephson, Lee Zhang, Shaojuan Liang, Steven H. |
| Author_xml | – sequence: 1 givenname: Lingling surname: Zhang fullname: Zhang, Lingling organization: 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 – sequence: 2 givenname: Kuan orcidid: 0000-0003-2448-2254 surname: Hu fullname: Hu, Kuan organization: Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan – sequence: 3 givenname: Tuo surname: Shao fullname: Shao, Tuo organization: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA – sequence: 4 givenname: Lu surname: Hou fullname: Hou, Lu organization: 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 – sequence: 5 givenname: Shaojuan surname: Zhang fullname: Zhang, Shaojuan organization: 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 – sequence: 6 givenname: Weijian surname: Ye fullname: Ye, Weijian organization: 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 – sequence: 7 givenname: Lee surname: Josephson fullname: Josephson, Lee organization: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA – sequence: 8 givenname: Jeffrey H. surname: Meyer fullname: Meyer, Jeffrey H. organization: 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, Canada – sequence: 9 givenname: Ming-Rong surname: Zhang fullname: Zhang, Ming-Rong organization: Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba 263-8555, Japan – sequence: 10 givenname: Neil orcidid: 0000-0002-2087-5125 surname: Vasdev fullname: Vasdev, Neil organization: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA – sequence: 11 givenname: Jinghao surname: Wang fullname: Wang, Jinghao organization: Department of Pharmacy, the First Affiliated Hospital of Jinan University, Guangzhou 510630, China – sequence: 12 givenname: Hao surname: Xu fullname: Xu, Hao email: txh@jnu.edu.cn organization: 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 – sequence: 13 givenname: Lu surname: Wang fullname: Wang, Lu email: l_wang1009@jnu.edu.cn organization: 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 – sequence: 14 givenname: Steven H. orcidid: 0000-0003-1413-6315 surname: Liang fullname: Liang, Steven H. email: liang.steven@mgh.harvard.edu organization: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital & Department of Radiology, Harvard Medical School, Boston, MA 02114, USA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33643818$$D View this record in MEDLINE/PubMed |
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| Keywords | AMPA BBB ALS MDD dMCAO RCYs QA TSPO TBI BPND HSE NAA/Cr PBR AD BcTSPO MS PKA IMM fP EP PSP OMM MAB PCA TBAH SUV FTD ROS SUVR CNS disorders DLB PRAX-1 SAH PAP7 VT RRMS BMSC CBD MRI SAR ANT CNS Am TLE BP CRAC LPS P2X7R SA SNL PDD d.c. RCYs KA MMSE SNR MSA Microglial activation Positron emission tomography (PET) HAB Neuroinflammation PpIX p.i MAO-B LAB n.d.c. RCYs OCD MCI PD VDAC HD PET SCIDY Am, molar activities DLB, Lewy body dementias RCYs, radiochemical yields fP, plasma free fraction MCI, mild cognitive impairment SA, specific activity PDD, PD dementia SCIDY, spirocyclic iodonium ylide SAR, structure–activity relationship CRAC, cholesterol recognition amino acid consensus sequence HSE, herpes simplex encephalitis MAB, mixed-affinity binding NAA/Cr, N-acetylaspartate/creatine MMSE, mini-mental state examination PAP7, RIa-associated protein PBR, peripheral benzodiazepine receptor SNL, selective neuronal loss p.i., post-injection HAB, high-affinity binding OMM, outer mitochondrial membrane PET, positron emission tomography IMM, inner mitochondrial membrane FTD, frontotemporal dementia d.c. RCYs, decay-corrected radiochemical yields MSA, multiple system atrophy PD, Parkinson's disease LAB, low-affinity binding AD, Alzheimer's disease TBI, traumatic brain injury LPS, lipopolysaccharide BPND, non-displaceable binding potential BcTSPO, Bacillus cereus TSPO PKA, protein kinase A PpIX, protoporphyrin IX KA, kainic acid TSPO, translocator protein VT, distribution volume TBAH, tetrabutyl ammonium hydroxide n.d.c. RCYs, non-decay-corrected radiochemical yields TLE, temporal lobe epilepsy P2X7R, purinergic receptor P2X7 ALS, amyotrophic lateral sclerosis PRAX-1, PBR-associated protein 1 SUVR, standard uptake volume ratio dMCAO, distal middle cerebral artery occlusion BP, binding potential VDAC, voltage-dependent anion channel ANT, adenine nucleotide transporter BMSC, bone marrow stromal cells EP, epilepsy ROS, reactive oxygen species MDD, major depressive disorder AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid SUV, standard uptake volume HD, Huntington's disease QA, quinolinic acid BBB, blood‒brain barrier CBD, corticobasal degeneration PCA, posterior cortical atrophy MS, multiple sclerosis MRI, magnetic resonance imaging CNS, central nervous system OCD, obsessive compulsive disorder PSP, progressive supranuclear palsy SAH, subarachnoid hemorrhage MAO-B, monoamine oxidase B SNR, signal to noise ratio RRMS, relapsing remitting multiple sclerosis |
| Language | English |
| License | This is an open access article under the CC BY-NC-ND license. 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
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| Snippet | The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial... The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is predominately localized to the outer mitochondrial... |
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| SubjectTerms | CNS disorders Microglial activation Neuroinflammation Positron emission tomography (PET) Review TSPO |
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| Title | Recent developments on PET radiotracers for TSPO and their applications in neuroimaging |
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