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Published in: Nuclear Medicine and Molecular Imaging 6/2019

01-12-2019 | Alzheimer's Disease | Perspective

Perspectives in TSPO PET Imaging for Neurologic Diseases

Author: Yoo Sung Song

Published in: Nuclear Medicine and Molecular Imaging | Issue 6/2019

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Abstract

The translocator protein (18 kDa) (TSPO) is a mitochondrial transmembrane protein, which has brought attention as a neuroinflammatory biomarker. Positron emission tomography (PET) imaging studies have been done for several decades, since neuroinflammation has been implicated as an important pathophysiology of several common neurologic disorders. However, despite numerous previous studies with positive findings, its clinical significance is not yet clear. Various attempts to overcome the limitations are ongoing, in order to bring acceptance for use in clinics.
Literature
1.
go back to reference Papadopoulos V, Baraldi M, Guilarte TR, et al. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci. 2006;27:402–9.CrossRef Papadopoulos V, Baraldi M, Guilarte TR, et al. Translocator protein (18 kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci. 2006;27:402–9.CrossRef
2.
go back to reference Casellas P, Galiegue S, Basile AS. Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int. 2002;40:475–86.CrossRef Casellas P, Galiegue S, Basile AS. Peripheral benzodiazepine receptors and mitochondrial function. Neurochem Int. 2002;40:475–86.CrossRef
3.
go back to reference Maezawa I, Zimin PI, Wulff H, Jin LW. Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity. J Biol Chem. 2011;286:3693–706.CrossRef Maezawa I, Zimin PI, Wulff H, Jin LW. Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity. J Biol Chem. 2011;286:3693–706.CrossRef
4.
go back to reference Morales I, Jimenez JM, Mancilla M, Maccioni RB. Tau oligomers and fibrils induce activation of microglial cells. J Alzheimers Dis. 2013;37:849–56.CrossRef Morales I, Jimenez JM, Mancilla M, Maccioni RB. Tau oligomers and fibrils induce activation of microglial cells. J Alzheimers Dis. 2013;37:849–56.CrossRef
5.
go back to reference Edison P, Archer HA, Gerhard A, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32:412–9.CrossRef Edison P, Archer HA, Gerhard A, et al. Microglia, amyloid, and cognition in Alzheimer’s disease: an [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008;32:412–9.CrossRef
6.
go back to reference Yokokura M, Mori N, Yagi S, et al. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2011;38:343–51.CrossRef Yokokura M, Mori N, Yagi S, et al. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur J Nucl Med Mol Imaging. 2011;38:343–51.CrossRef
7.
go back to reference Wiley CA, Lopresti BJ, Venneti S, et al. Carbon 11-labeled Pittsburgh compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol. 2009;66:60–7.CrossRef Wiley CA, Lopresti BJ, Venneti S, et al. Carbon 11-labeled Pittsburgh compound B and carbon 11-labeled (R)-PK11195 positron emission tomographic imaging in Alzheimer disease. Arch Neurol. 2009;66:60–7.CrossRef
8.
go back to reference Schuitemaker A, Kropholler MA, Boellaard R, et al. Microglial activation in Alzheimer’s disease: an (R)-[11C]PK11195 positron emission tomography study. Neurobiol Aging. 2013;34:128–36.CrossRef Schuitemaker A, Kropholler MA, Boellaard R, et al. Microglial activation in Alzheimer’s disease: an (R)-[11C]PK11195 positron emission tomography study. Neurobiol Aging. 2013;34:128–36.CrossRef
9.
go back to reference Stefaniak J, O’Brien J. Imaging of neuroinflammation in dementia: a review. J Neurol Neurosurg Psychiatry. 2016;87:21–8.CrossRef Stefaniak J, O’Brien J. Imaging of neuroinflammation in dementia: a review. J Neurol Neurosurg Psychiatry. 2016;87:21–8.CrossRef
10.
go back to reference Carter SF, Scholl M, Almkvist O, et al. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med. 2012;53:37–46.CrossRef Carter SF, Scholl M, Almkvist O, et al. Evidence for astrocytosis in prodromal Alzheimer disease provided by 11C-deuterium-L-deprenyl: a multitracer PET paradigm combining 11C-Pittsburgh compound B and 18F-FDG. J Nucl Med. 2012;53:37–46.CrossRef
11.
go back to reference Kreisl WC, Lyoo CH, McGwier M, et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease. Brain. 2013;136:2228–38.CrossRef Kreisl WC, Lyoo CH, McGwier M, et al. In vivo radioligand binding to translocator protein correlates with severity of Alzheimer’s disease. Brain. 2013;136:2228–38.CrossRef
12.
go back to reference Iannaccone S, Cerami C, Alessio M, et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord. 2013;19:47–52.CrossRef Iannaccone S, Cerami C, Alessio M, et al. In vivo microglia activation in very early dementia with Lewy bodies, comparison with Parkinson’s disease. Parkinsonism Relat Disord. 2013;19:47–52.CrossRef
13.
go back to reference Cagnin A, Rossor M, Sampson EL, et al. In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol. 2004;56:894–7.CrossRef Cagnin A, Rossor M, Sampson EL, et al. In vivo detection of microglial activation in frontotemporal dementia. Ann Neurol. 2004;56:894–7.CrossRef
14.
go back to reference Gerhard A, Watts J, Trender-Gerhard I, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration. Mov Disord. 2004;19:1221–6.CrossRef Gerhard A, Watts J, Trender-Gerhard I, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in corticobasal degeneration. Mov Disord. 2004;19:1221–6.CrossRef
15.
go back to reference Gerhard A, Trender-Gerhard I, Turkheimer F, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive supranuclear palsy. Mov Disord. 2006;21:89–93.CrossRef Gerhard A, Trender-Gerhard I, Turkheimer F, et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in progressive supranuclear palsy. Mov Disord. 2006;21:89–93.CrossRef
16.
go back to reference Gerhard A, Banati RB, Goerres GB, et al. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology. 2003;61:686–9.CrossRef Gerhard A, Banati RB, Goerres GB, et al. [11C](R)-PK11195 PET imaging of microglial activation in multiple system atrophy. Neurology. 2003;61:686–9.CrossRef
17.
go back to reference Dodel R, Spottke A, Gerhard A, et al. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [11C] (R)-PK11195 PET (MEMSA-trial). Mov Disord. 2010;25:97–107.CrossRef Dodel R, Spottke A, Gerhard A, et al. Minocycline 1-year therapy in multiple-system-atrophy: effect on clinical symptoms and [11C] (R)-PK11195 PET (MEMSA-trial). Mov Disord. 2010;25:97–107.CrossRef
18.
go back to reference Koshimori Y, Ko JH, Mizrahi R, et al. Imaging striatal microglial activation in patients with Parkinson’s disease. PLoS One. 2015;10:e0138721.CrossRef Koshimori Y, Ko JH, Mizrahi R, et al. Imaging striatal microglial activation in patients with Parkinson’s disease. PLoS One. 2015;10:e0138721.CrossRef
19.
go back to reference Gulyas B, Toth M, Schain M, et al. Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: a PET study with the TSPO molecular imaging biomarker [11C]vinpocetine. J Neurol Sci. 2012;320:110–7.CrossRef Gulyas B, Toth M, Schain M, et al. Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: a PET study with the TSPO molecular imaging biomarker [11C]vinpocetine. J Neurol Sci. 2012;320:110–7.CrossRef
20.
go back to reference Thiel A, Radlinska BA, Paquette C, et al. The temporal dynamics of poststroke neuroinflammation: a longitudinal diffusion tensor imaging-guided PET study with 11C-PK11195 in acute subcortical stroke. J Nucl Med. 2010;51:1404–12.CrossRef Thiel A, Radlinska BA, Paquette C, et al. The temporal dynamics of poststroke neuroinflammation: a longitudinal diffusion tensor imaging-guided PET study with 11C-PK11195 in acute subcortical stroke. J Nucl Med. 2010;51:1404–12.CrossRef
21.
go back to reference Gulyas B, Toth M, Vas A, et al. Visualising neuroinflammation in post-stroke patients: a comparative PET study with the TSPO molecular imaging biomarkers [11C]PK11195 and [11C]vinpocetine. Curr Radiopharm. 2012;5:19–28.CrossRef Gulyas B, Toth M, Vas A, et al. Visualising neuroinflammation in post-stroke patients: a comparative PET study with the TSPO molecular imaging biomarkers [11C]PK11195 and [11C]vinpocetine. Curr Radiopharm. 2012;5:19–28.CrossRef
22.
go back to reference Block F, Dihne M, Loos M. Inflammation in areas of remote changes following focal brain lesion. Prog Neurobiol. 2005;75:342–65.CrossRef Block F, Dihne M, Loos M. Inflammation in areas of remote changes following focal brain lesion. Prog Neurobiol. 2005;75:342–65.CrossRef
23.
go back to reference Owen DR, Yeo AJ, Gunn RN, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012;32:1–5.CrossRef Owen DR, Yeo AJ, Gunn RN, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012;32:1–5.CrossRef
24.
go back to reference Murail S, Robert JC, Coic YM, et al. Secondary and tertiary structures of the transmembrane domains of the translocator protein TSPO determined by NMR. Stabilization of the TSPO tertiary fold upon ligand binding. Biochim Biophys Acta. 1778;2008:1375–81. Murail S, Robert JC, Coic YM, et al. Secondary and tertiary structures of the transmembrane domains of the translocator protein TSPO determined by NMR. Stabilization of the TSPO tertiary fold upon ligand binding. Biochim Biophys Acta. 1778;2008:1375–81.
25.
go back to reference Li F, Liu J, Zheng Y, et al. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science. 2015;347:555–8.CrossRef Li F, Liu J, Zheng Y, et al. Crystal structures of translocator protein (TSPO) and mutant mimic of a human polymorphism. Science. 2015;347:555–8.CrossRef
26.
go back to reference Tiwari AK, Ji B, Yui J, et al. [18F]FEBMP: positron emission tomography imaging of TSPO in a model of neuroinflammation in rats, and in vitro autoradiograms of the human brain. Theranostics. 2015;5:961–9.CrossRef Tiwari AK, Ji B, Yui J, et al. [18F]FEBMP: positron emission tomography imaging of TSPO in a model of neuroinflammation in rats, and in vitro autoradiograms of the human brain. Theranostics. 2015;5:961–9.CrossRef
27.
go back to reference Fan Z, Calsolaro V, Atkinson RA, et al. Flutriciclamide (18F-GE180) PET: first-in-human PET study of novel third-generation in vivo marker of human translocator protein. J Nucl Med. 2016;57:1753–9.CrossRef Fan Z, Calsolaro V, Atkinson RA, et al. Flutriciclamide (18F-GE180) PET: first-in-human PET study of novel third-generation in vivo marker of human translocator protein. J Nucl Med. 2016;57:1753–9.CrossRef
28.
go back to reference Colasanti A, Owen DR, Grozeva D, et al. Bipolar disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa translocator protein (TSPO). Psychoneuroendocrinology. 2013;38:2826–9.CrossRef Colasanti A, Owen DR, Grozeva D, et al. Bipolar disorder is associated with the rs6971 polymorphism in the gene encoding 18 kDa translocator protein (TSPO). Psychoneuroendocrinology. 2013;38:2826–9.CrossRef
29.
go back to reference Nakamura K, Yamada K, Iwayama Y, et al. Evidence that variation in the peripheral benzodiazepine receptor (PBR) gene influences susceptibility to panic disorder. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:222–6.CrossRef Nakamura K, Yamada K, Iwayama Y, et al. Evidence that variation in the peripheral benzodiazepine receptor (PBR) gene influences susceptibility to panic disorder. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:222–6.CrossRef
30.
go back to reference Lockhart A, Davis B, Matthews JC, et al. The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant alpha1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker. Nucl Med Biol. 2003;30:199–206.CrossRef Lockhart A, Davis B, Matthews JC, et al. The peripheral benzodiazepine receptor ligand PK11195 binds with high affinity to the acute phase reactant alpha1-acid glycoprotein: implications for the use of the ligand as a CNS inflammatory marker. Nucl Med Biol. 2003;30:199–206.CrossRef
31.
go back to reference Turkheimer FE, Rizzo G, Bloomfield PS, et al. The methodology of TSPO imaging with positron emission tomography. Biochem Soc Trans. 2015;43:586–92.CrossRef Turkheimer FE, Rizzo G, Bloomfield PS, et al. The methodology of TSPO imaging with positron emission tomography. Biochem Soc Trans. 2015;43:586–92.CrossRef
32.
go back to reference Rizzo G, Veronese M, Tonietto M, et al. Kinetic modeling without accounting for the vascular component impairs the quantification of [11C]PBR28 brain PET data. J Cereb Blood Flow Metab. 2014;34:1060–9.CrossRef Rizzo G, Veronese M, Tonietto M, et al. Kinetic modeling without accounting for the vascular component impairs the quantification of [11C]PBR28 brain PET data. J Cereb Blood Flow Metab. 2014;34:1060–9.CrossRef
33.
go back to reference Owen DR, Guo Q, Rabiner EA, Gunn RN. The impact of the rs6971 polymorphism in TSPO for quantification and study design. Clin Transl Imaging 2015;3:417–22.CrossRef Owen DR, Guo Q, Rabiner EA, Gunn RN. The impact of the rs6971 polymorphism in TSPO for quantification and study design. Clin Transl Imaging 2015;3:417–22.CrossRef
34.
go back to reference Lyoo CH, Ikawa M, Liow JS, et al. Cerebellum can serve as a pseudo-reference region in Alzheimer disease to detect neuroinflammation measured with PET radioligand binding to translocator protein. J Nucl Med. 2015;56:701–6.CrossRef Lyoo CH, Ikawa M, Liow JS, et al. Cerebellum can serve as a pseudo-reference region in Alzheimer disease to detect neuroinflammation measured with PET radioligand binding to translocator protein. J Nucl Med. 2015;56:701–6.CrossRef
35.
go back to reference Moon BS, Kim BS, Park C, et al. [18F]Fluoromethyl-PBR28 as a potential radiotracer for TSPO: preclinical comparison with [11C]PBR28 in a rat model of neuroinflammation. Bioconjug Chem. 2014;25:442–50.CrossRef Moon BS, Kim BS, Park C, et al. [18F]Fluoromethyl-PBR28 as a potential radiotracer for TSPO: preclinical comparison with [11C]PBR28 in a rat model of neuroinflammation. Bioconjug Chem. 2014;25:442–50.CrossRef
Metadata
Title
Perspectives in TSPO PET Imaging for Neurologic Diseases
Author
Yoo Sung Song
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
Nuclear Medicine and Molecular Imaging / Issue 6/2019
Print ISSN: 1869-3474
Electronic ISSN: 1869-3482
DOI
https://doi.org/10.1007/s13139-019-00620-y

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