In Vivo Assessment of Brain White Matter Inflammation in Multiple Sclerosis with18F-PBR111 PET
Open accessAbstract
UNLABELLED: PET radioligand binding to the 18-kD translocator protein (TSPO) in the brains of patients with multiple sclerosis (MS) primarily reflects activated microglia and macrophages. We previously developed genetic stratification for accurate quantitative estimation of TSPO using second-generation PET radioligands. In this study, we used (18)F-PBR111 PET and MR imaging to measure relative binding in the lesional, perilesional, and surrounding normal-appearing white matter of MS patients, as an index of the innate immune response. METHODS: (18)F-PBR111 binding was quantified in 11 MS patients and 11 age-matched healthy volunteers, stratified according to the rs6971 TSPO gene polymorphism. Fluid-attenuated inversion recovery and magnetization transfer ratio (MTR) MR imaging were used to segment the white matter in MS patients as lesions, perilesional volumes, nonlesional white matter with reduced MTR, and nonlesional white matter with normal MTR. RESULTS: (18)F-PBR111 binding was higher in the white matter lesions and perilesional volumes of MS patients than in white matter of healthy controls (P < 0.05). Although there was substantial heterogeneity in binding between different lesions, a within-subject analysis showed higher (18)F-PBR111 binding in MS lesions (P < 0.05) and in perilesional (P < 0.05) and nonlesional white matter with reduced MTR (P < 0.005) than in nonlesional white matter with a normal MTR. A positive correlation was observed between the mean (18)F-PBR111 volume of distribution increase in lesions relative to nonlesional white matter with a normal MTR and the MS severity score (Spearman ρ = 0.62, P < 0.05). CONCLUSION: This study demonstrates that quantitative TSPO PET with a second-generation radioligand can be used to characterize innate immune responses in MS in vivo and provides further evidence supporting an association between the white matter TSPO PET signal in lesions and disease severity. Our approach is practical for extension to studies of the role of the innate immune response in MS for differentiation of antiinflammatory effects of new medicines and their longer term impact on clinical outcome.
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TSPO has become recognized as a marker of in vivo neuroinflammation.
“and thus has become recognized as a marker of in vivo neuroinflammation (Banati et al., 2000; Venneti et al., 2006; Colasanti et al., 2014).”
From A quantitative neuropathological assessment of translocator protein expression in multiple sclerosis (2019) · cites this paper as Colasanti et al., 2014
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Cosenza‐Nashat, M., Zhao, M. ‐., Suh, H. ‐., Morgan, J., Natividad, R., Morgello, S., & Lee, S. C. (2009) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2008.01006.x · Cited by 459 · cited 3× · see citing works
“An immunohistochemical analysis of postmortem MS brain tissue was largely consistent with these findings, suggesting that most cells expressing TSPO in acute MS lesions were macrophages or microglia (9), although it should be cautioned that antibody-based localization of the TSPO peptide and expression of the binding…”
BackgroundResultAge and gender effects on microglia and astrocyte numbers in brains of mice
Mouton, P. R., Long, J. M., Lei, D.-L., Howard, V., Jucker, M., Calhoun, M. E., & Ingram, D. K. (2002) · Brain Research · doi:10.1016/s0006-8993(02)03475-3 · Cited by 320 · see citing works
Versijpt, J., Debruyne, J. C., Van Laere, K. J., De Vos, F., Keppens, J., Strijckmans, K., Achten, E., Slegers, G., Dierckx, R. A., Korf, J., et al. (2005) · Multiple Sclerosis Journal · doi:10.1191/1352458505ms1140oa · Cited by 126 · see citing works
Flagged first, then by citations
Research works printed but not linked: 37
- Henderson AP, Barnett MH, Parratt JD, Prineas JW. Multiple sclerosis: distribution of inflammatory cells in newly forming lesions. Ann Neurol. 2009;66:739-753.
- Marik C, Felts PA, Bauer J, Lassmann H, Smith KJ. Lesion genesis in a subset of patients with multiple sclerosis: a role for innate immunity? Brain. 2007;130:2800- 2815.
- van Horssen J, Singh S, van der Pol S, et al. Clusters of activated microglia in normal-appearing white matter show signs of innate immune activation. J Neuro- inflammation. 2012;9:156.
- Kutzelnigg A, Lucchinetti CF, Stadelmann C, et al. Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005;128:2705-2712.
- De Groot CJ, Bergers E, Kamphorst W, et al. Post-mortem MRI-guided sampling of multiple sclerosis brain lesions: increased yield of active demyelinating and (p)reactive lesions. Brain. 2001;124:1635-1645.
- Gouw AA, Seewann A, van der Flier WM, et al. Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry. 2011;82:126-135.
- Moll NM, Rietsch AM, Thomas S, et al. Multiple sclerosis normal-appearing white matter: pathology-imaging correlations. Ann Neurol. 2011;70:764-773.
- Banati RB, Newcombe J, Gunn RN, et al. The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain. 2000;123:2321-2337.
- Debruyne JC, Versijpt J, Van Laere KJ, et al. PET visualization of microglia in multiple sclerosis patients using [ 11 C]PK11195. Eur J Neurol. 2003;10:257-264.
- Vowinckel E, Reutens D, Becher B, et al. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neurosci Res. 1997;50:345-353.
- Vas A, Shchukin Y, Karrenbauer VD, et al. Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [ 11 C]vinpocetine and [ 11 C]PK11195 in patients. J Neurol Sci. 2008;264:9-17.
- Chauveau F, Boutin H, Van Camp N, Dolle F, Tavitian B. Nuclear imaging of neuroinflammation: a comprehensive review of [ 11 C]PK11195 challengers. Eur J Nucl Med Mol Imaging. 2008;35:2304-2319.
- Oh U, Fujita M, Ikonomidou VN, et al. Translocator protein PET imaging for glial activation in multiple sclerosis. J Neuroimmune Pharmacol. 2011;6:354-361.
- Takano A, Piehl F, Hillert J, et al. In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [ 18 F]FEDAA1106. EJNMMI Res. 2013;3:30.
- 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.
- Fookes CJ, Pham TQ, Mattner F, et al. Synthesis and biological evaluation of substituted [ 18 F]imidazo[1,2-a]pyridines and [ F]pyrazolo[1,5-a]pyrimidines for the study of the peripheral benzodiazepine receptor using positron emission tomography. J Med Chem. 2008;51:3700-3712.
- Mattner F, Staykova M, Berghofer P, et al. Central nervous system expression and PET imaging of the translocator protein in relapsing-remitting experimental autoimmune encephalomyelitis. J Nucl Med. 2013;54:291-298.
- Guo Q, Colasanti A, Owen DR, et al. Quantification of the specific translocator protein signal of [ 18 F]PBR111 in healthy humans: a genetic polymorphism effect on in vivo binding. J Nucl Med. 2013;54:1915-1923.
- Filippi M, Rocca MA, Barkhof F, et al. Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol. 2012;11:349-360.
- Roxburgh RH, Seaman SR, Masterman T, et al. Multiple sclerosis severity score: using disability and disease duration to rate disease severity. Neurology. 2005;64:1144-1151.
- Gunn RN, Gunn SR, Cunningham VJ. Positron emission tomography compart- mental models. J Cereb Blood Flow Metab. 2001;21:635-652.
- Logan J, Fowler JS, Volkow ND, et al. Graphical analysis of reversible radioligand binding from time-activity measurements applied to [N-11 C-methyl]-(-)-cocaine PET studies in human subjects. J Cereb Blood Flow Metab. 1990;10:740-747.
- Giannetti P, Politis M, Su P, et al. Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: an in vivo [ 11 C](R)-PK11195- PET pilot study. Neurobiol Dis. 2014;65:203-210.
- Venneti S, Wang G, Nguyen J, Wiley CA. The positron emission tomography ligand DAA1106 binds with high affinity to activated microglia in human neu- rological disorders. J Neuropathol Exp Neurol. 2008;67:1001-1010.
- Owen DR, Howell OW, Tang SP, et al. Two binding sites for [ 3 H]PBR28 in human brain: implications for TSPO PET imaging of neuroinflammation. J Cereb Blood Flow Metab. 2010;30:1608-1618.
- Trapp BD, Bo L, Mork S, Chang A. Pathogenesis of tissue injury in MS lesions. J Neuroimmunol. 1999;98:49-56.
- Boyle EA, McGeer PL. Cellular immune response in multiple sclerosis plaques. Am J Pathol. 1990;137:575-584.
- Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000;47:707-717.
- Brück W, Stadelmann C. The spectrum of multiple sclerosis: new lessons from pathology. Curr Opin Neurol. 2005;18:221-224.
- Smith KJ, Lassmann H. The role of nitric oxide in multiple sclerosis. Lancet Neurol. 2002;1:232-241.
- Singh S, Metz I, Amor S, van der Valk P, Stadelmann C, Bruck W. Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons. Acta Neuropathol. 2013;125:595-608.
- Yaqub M, van Berckel BN, Schuitemaker A, et al. Optimization of supervised cluster analysis for extracting reference tissue input curves in (R)-[ 11 C]PK11195 brain PET studies. J Cereb Blood Flow Metab. 2012;32:1600-1608.
- Ratchford JN, Endres CJ, Hammoud DA, et al. Decreased microglial activation in MS patients treated with glatiramer acetate. J Neurol. 2012;259:1199-1205.
- Schwarz JM, Sholar PW, Bilbo SD. Sex differences in microglial colonization of the developing rat brain. J Neurochem. 2012;120:948-963.
- Berkovich A, Ferrarese C, Cavaletti G, et al. Topology of two DBI receptors in human lymphocytes. Life Sci. 1993;52:1265-1277.
- Turkheimer FE, Edison P, Pavese N, et al. Reference and target region modeling of [ 11 C]-(R)-PK11195 brain studies. J Nucl Med. 2007;48:158-167.
- Canat X, Carayon P, Bouaboula M, et al. Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells. Life Sci. 1993;52:107-118.
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“MRI techniques, such as diffusion tension imaging, PET studies with radioligands of activated microglia, and pathological studies have demonstrated abnormalities in NAWM [25, 26].”
Background11C-PBR28 and 18F-PBR111 Detect White Matter Inflammatory Heterogeneity in Multiple Sclerosis
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“Recent studies have highlighted more diffuse uptake (13,14).”
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“Findings from MS studies using later generation TSPO ligands were also in accordance with the above described findings (66, 72).”
ResultHagens, M., Golla, S. S. V., Janssen, B., Vugts, D., Beaino, W., Windhorst, A., O'Brien-Brown, J., Kassiou, M., Schuit, R., Schwarte, L., et al. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04550-x · Cited by 66 · see citing works
Unterrainer, M., Mahler, C. F., Vomacka, L., Lindner, S., Havla, J. B., Brendel, M., Böning, G., Ertl-Wagner, B. B., Kümpfel, T., Milenkovic, V. M., et al. (2018) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-018-3974-7 · Cited by 78 · see citing works
“Second, asMR imaging does not detect a specific aspect of parenchymal inflammation, it generally provides only a binary and not a quantitative assessment of the activity status of a given lesion [8].”
BackgroundResultVomacka, L., Albert, N., Lindner, S., Unterrainer, M., Mahler, C., Brendel, M., Ermoschkin, L., Gosewisch, A., Brunegraf, A., Buckley, C. J., et al. (2017) · EJNMMI Research · doi:10.1186/s13550-017-0340-x · Cited by 63 · see citing works
“Both [(18)F]PBR111 and [(11)C]PBR28 showed an increased VT in some lesions with CE in MRI [24, 28, 29].”
Hamzaoui, M., Garcia, J., Boffa, G., Lazzarotto, A., Absinta, M., Ricigliano, V. A. G., Soulier, T., Tonietto, M., Gervais, P., Bissery, A., et al. (2023) · Annals of Neurology · doi:10.1002/ana.26657 · Cited by 69 · see citing works
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“In accordance with the results with [(11)C]PBR28, a study with [(18)F]PBR111 [67], where the subjects were matched according to their TSPO binding genotype, showed that the TSPO binding was increased in the T2 lesional and perilesional WM of RRMS patients (n = 11) when compared to healthy controls (n = 11), and the ra…”
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“Similarly, depressive symptoms in MS can be partially explained by functional connectivity of the hippocampus combined with imaging of PET ligands based on 8-kDa translocator protein (TSPO), sensitive to the activation of microglia, and thus to acute inflammation (Colasanti et al., 2014).”
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“T2 lesions display somewhat higher overall binding in the lesion center compared to T1 lesions [55,58].”
BackgroundChauveau, F., Becker, G., & Boutin, H. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05425-w · Cited by 45 · see citing works
“derived classification (active/inactive) of chronic lesions or black holes [103, 109].”
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“fluid-attenuated inversion recovery (FLAIR) hyperintense regions compared with non-lesional regions with highMTR.(35) Higher uptake of (18)F-PBR111 is suggestive of a pathological”
BackgroundPET imaging in multiple sclerosis
Faria, D. D. P., Copray, S. C. V. M., Buchpiguel, C. A., Dierckx, R., & de Vries, E. F. J. (2014) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-014-9544-2 · Cited by 37 · see citing works
Supervised clustering for TSPO PET imaging
Schubert, J., Tonietto, M., Turkheimer, F., Zanotti-Fregonara, P., & Veronese, M. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05309-z · Cited by 40 · see citing works
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“…in patients with MS (Colasanti et al. 2016) and increased NAWM binding which inversely correlated with magnetization transfer ratio, suggesting a potential link between microglial activation and demyelination in regions that appear normal on routine T2-weighted images (Colasanti et al. 2014).”
BackgroundRecent imaging advances in neurology
Rocchi, L., Niccolini, F., & Politis, M. (2015) · Journal of Neurology · doi:10.1007/s00415-015-7711-x · Cited by 39 · see citing works
“Within-subject analysis showed higher [(18)F]PBR111 binding in WM lesions and perilesional regions compared to the normal WM, which was associated with worse disability scores [144].”
BackgroundScott, G. P. T., Mahmud, M., Owen, D. R., & Johnson, M. R. (2017) · Seizure · doi:10.1016/j.seizure.2016.10.023 · Cited by 37 · see citing works
“Human studies using these secondgeneration ligands have demonstrated increased TSPO expression in a variety of CNS disorders, including Alzheimer’s disease [37], amyotrophic lateral sclerosis [34], and multiple sclerosis [38].”
BackgroundSelf-citationWang, W., Zhang, L., Zhang, X., Xue, R., Li, L., Zhao, W., Fu, Q., Mi, W., & Li, Y.-F. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00384 · Cited by 36 · see citing works
“The number of entries and the time spent in the target quadrant were recorded, with a cut-off time of 60 s. Enzyme-Linked Immunosorbent Assay (ELISA) Concentrations of IL-1β (Biosource, Invitrogen, USA), TNF-α (Biosource, Invitrogen, USA), IL-6 (Biosource, Invitrogen, USA) and allopregnanolone (Arbor Assays, Ann Arbor…”
BackgroundInfluentialZinnhardt, B., Belloy, M., Fricke, I. B., Orije, J., Guglielmetti, C., Hermann, S., Wagner, S., Schäfers, M., Van der Linden, A., & Jacobs, A. H. (2019) · Theranostics · doi:10.7150/thno.32461 · Cited by 30 · see citing works
“Second generation TSPO ligands may even allow to visualize the heterogeneity of inflammatory lesions in MS as well as give additional information to conventional MRI [7, 58].”
BackgroundDatta, G., Violante, I., Scott, G., Zimmerman, G., Santos-Ribeiro, A., Rabiner, E., Gunn, R., Malik, O., Ciccarelli, O., Nicholas, R., et al. (2016) · Multiple Sclerosis · doi:10.1177/1352458516681504 · Cited by 35 · see citing works
Self-citationMeijer, K., Muhlert, N., Cercignani, M., Sethi, V., Ron, M., Thompson, A., Miller, D. H., Chard, D., Geurts, J., & Ciccarelli, O. (2016) · Multiple Sclerosis · doi:10.1177/1352458515622694 · Cited by 35 · see citing works
Self-citationArbo, B. D., Benetti, F., García-Segura, L., & Ribeiro, M. (2015) · Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2015.07.007 · Cited by 35 · see citing works
“injury and inflammation, as well as in several neur opathological conditions including stroke and neurodegenerative disorders such as Alzh eimer’s disease (AD), Parkinson’s disease, Huntington’s disease, multiple sclerosis a nd amyotrophic lateral sclerosis [2, 41-43].”
TSPO Radioligands for Neuroinflammation: An Overview
Salerno, S., Viviano, M., Baglini, E., Poggetti, V., Giorgini, D., Castagnoli, J., Barresi, E., Castellano, S., Settimo, F. D., & Taliani, S. (2024) · Molecules · doi:10.3390/molecules29174212 · Cited by 33 · see citing works
“[ 18 F]PBR111 ( 25 , Figure 6, Table 1) has undergone extensive evaluation in both preclinical experiments [56] and clinical trials to study pathologies such as AD and MS.”
BackgroundMustafi, S., Harezlak, J., Kodiweera, C., Randolph, J. S., Ford, J. C., Wishart, H., & Wu, Y.-C. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.243716 · Cited by 33 · see citing works
“Similar to (Colasanti et al., 2014), the perilesion WM voxels were generated by intersecting dilated lesion masks and the WM mask.”
Gliosis and Neurodegenerative Diseases: The Role of PET and MR Imaging
Cavaliere, C., Tramontano, L., Fiorenza, D., Alfano, V., Aiello, M., & Salvatore, M. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00075 · Cited by 40 · see citing works
Airas, L., Rissanen, E., & Rinne, J. (2017) · Multiple Sclerosis · doi:10.1177/1352458516674568 · Cited by 32 · see citing works
PET Evaluation of Microglial Activation in Non-neurodegenerative Brain Diseases
Ghadery, C., Best, L. A., Pavese, N., Tai, Y., & Strafella, A. P. (2019) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-019-0951-x · Cited by 34 · see citing works
Poutiainen, P., Jaronen, M., Quintana, F. J., & Brownell, A. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00085 · Cited by 31 · see citing works
“[ 18 F]FDG has some valuable characteristics for monitoring cognitive and mental dysfunctions associated with MS (Paulesu et al., 1996; Zarei, 2003; Buck et al., 2012; Colasanti et al., 2014).”
BackgroundBelloli, S., Zanotti, L., Murtaj, V., Mazzon, C., Grigoli, G. D., Monterisi, C., Masiello, V., Iaccarino, L., Cappelli, A., Poliani, P., et al. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-017-1044-x · Cited by 29 · see citing works
“in 2000 and then confirmed in other clinical studies [12, 31].”
ResultThe translocator protein (18 kDa) and its role in neuropsychiatric disorders
Barichello, T., Simões, L. R., Collodel, A., Giridharan, V. V., Dal‐Pizzol, F., Macêdo, D. S., & Quevedo, J. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.10.010 · Cited by 29 · see citing works
“In a large-scale case–control study, rs6971 polymorphism in the gene encoding TSPO was associated with bipolar disorder (Colasanti et al., 2014).”
Matthews, P. M., & Datta, G. (2015) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2015.1032240 · Cited by 28 · see citing works
“Similar results were reported using [(18)F]PBR111 in a separate cohort [55].”
BackgroundMethodResultInfluentialSelf-citationNovel MRI and PET markers of neuroinflammation in multiple sclerosis.
Hagens, M., van Berckel, B. N., & Barkhof, F. (2016) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000326 · Cited by 28 · see citing works
Molecular and Metabolic Imaging in Multiple Sclerosis
Moccia, M., & Ciccarelli, O. (2017) · Neuroimaging Clinics of North America · doi:10.1016/j.nic.2016.12.005 · Cited by 28 · see citing works
Self-citationPrimary Progressive Multiple Sclerosis—A Key to Understanding and Managing Disease Progression
Sempik, I., Dziadkowiak, E., Moreira, H., Zimny, A., & Pokryszko‐Dragan, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168751 · Cited by 25 · see citing works
“…visualization of cortical damage and ribbon-like subpial demyelination (ultra-high magnetic field resolution (>7 T) chronic neuroinflammation [96,102,103] measures of global and regional CNS atrophy loss of cerebral structure volume diffuse neurodegeneration with axonal loss [100–105]…”
BackgroundBeaino, W., Janssen, B., Kooijman, E., Vos, R., Schuit, R., O'Brien-Brown, J., Kassiou, M., Hof, B. J. V. H., Vugts, D., de Vries, H. D., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01962-7 · Cited by 23 · see citing works
Singhal, T., O’Connor, K., Dubey, S., Belanger, A. P., Hurwitz, S., Chu, R., Tauhid, S., Kijewski, M. F., DiCarli, M. F., Weiner, H. L., et al. (2018) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000002179 · Cited by 27 · see citing works
Eberl, S., Katsifis, A., Peyronneau, M. A., Wen, L., Henderson, D., Loc'h, C., Greguric, I., Verschuer, J., Pham, T., Lam, P., et al. (2017) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-016-3517-z · Cited by 21 · see citing works
Kovbasyuk, Z., Tefera, E., Li, C., Baete, S., & Steriade, C. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03598-x · Cited by 20 · see citing works
“Although several studies have failed to find differences in [ 11 C]PK11195 uptake in MS patients compared to HCs [99, 100] second-and third-generation radioligands including [ 18 F]PBR06, [ 18 F]PBR111, and [ 18 F]GE-180 have shown promise in tracking MS-related glial activation [80, 101, 102].”
Sheikhi, K., Ghaderi, S., Firouzi, H., Rahimibarghani, S., Shabani, E., Afkhami, H., & Yarahmadi, A. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1517369 · Cited by 20 · see citing works
Beaurain, M., Salabert, A., Ribeiro, M. J., Arlicot, N., Damier, P., Jeune, F. L., Démonet, J., & Payoux, P. (2019) · Frontiers in Medicine · doi:10.3389/fmed.2019.00268 · Cited by 26 · see citing works
Advanced imaging tools to investigate multiple sclerosis pathology.
Bodini, B., Louapre, C., & Stankoff, B. (2015) · Presse medicale · doi:10.1016/j.lpm.2015.02.011 · Cited by 19 · see citing works
“The results obtained in MS remain so far disappointing as the first pilot studies did not reveal major differences between patients and controls [104].”
ResultCrosstalk between CD64+MHCII+ macrophages and CD4+ T cells drives joint pathology during chikungunya
Lum, F., Chan, Y., Teo, T.-H., Becht, E., Amrun, S. N., Teng, K., Hartimath, S., Yeo, N. K., Yee, W.-X., Ang, N., et al. (2024) · EMBO Molecular Medicine · doi:10.1038/s44321-024-00028-y · Cited by 18 · see citing works
“However, it is important to note that TSPO can also be expressed by fi broblast-like synoviocytes (FLS) (Narayan et al, 2018), which play a pathogenic role in rheumatoid arthritis (Bartok and Firestein, 2010) Notably, increased proportion in clusters 7, 8, and 12 re fl ected a corresponding decreased proportion of clust…”
TSPO-PET Imaging to Assess Cerebral Microglial Activation in Multiple Sclerosis
Weiner, H. L., Bakshi, R., & Singhal, T. (2017) · Seminars in Neurology · doi:10.1055/s-0037-1608715 · Cited by 18 · see citing works
Concussion: Beyond the Cascade
Neumann, K. D., Broshek, D. K., Newman, B. T., Druzgal, T. J., Kundu, B. K., & Resch, J. E. (2023) · Cells · doi:10.3390/cells12172128 · Cited by 14 · see citing works
Chaney, A. M., Cropper, H. C., Jain, P., Wilson, E. N., Simonetta, F., Johnson, E. M., Alam, I. S., Patterson, I. T. J., Swarovski, M. S., Stevens, M. Y., et al. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.abm6267 · Cited by 14 · see citing works
Bond, D., Andreazza, A., Torres, I., Honer, W., Lam, R. W., & Yatham, L. (2022) · Journal of Affective Disorders · doi:10.1016/j.jad.2022.09.044 · Cited by 11 · see citing works
Manning, K. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.001 · Cited by 8 · see citing works
Advances in Imaging Multiple Sclerosis
Caverzasi, E., Cordano, C., Hauser, S. L., Henry, R. G., & Bischof, A. (2017) · Seminars in Neurology · doi:10.1055/s-0037-1607278 · Cited by 6 · see citing works
PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation
Goggi, J., Claser, C., Hartimath, S., Hor, P. X., Tan, P., Ramasamy, B., Rahman, H. A., Cheng, P., Chang, Z.-W., Nguee, S., et al. (2021) · Infection and Immunity · doi:10.1128/iai.00024-21 · Cited by 7 · see citing works
Toscano, S., Spelman, T., Ozakbas, S., Alroughani, R., Chisari, C., Fermo, S. L., Prat, A., Girard, M., Duquette, P., Izquierdo, G., et al. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00552 · Cited by 6 · see citing works
García, D. V., Doorduin, J., Faria, D. D. P., Dierckx, R., & de Vries, E. D. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9741-x · Cited by 6 · see citing works
“…2012; Xie et al. 2012; Mattner et al. 2013; de Paula Faria et al. 2014a, b; Airas et al. 2015) and patients (Debruyne et al. 2003; Versijpt et al. 2005; Oh et al. 2011; Politis et al. 2012; Takano et al. 2013; Colasanti et al. 2014; Rissanen et al. 2014; Park et al. 2015; Giannetti et al. 2015).”
BackgroundCerebrovascular and microglial states are not altered by functional neuroinflammatory gene variant
Felsky, D., Jager, P. L. D., Schneider, J. A., Arfanakis, K., Fleischman, D. A., Arvanitakis, Z., Honer, W. G., Pouget, J. G., Mizrahi, R., Pollock, B. G., et al. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x15626719 · Cited by 6 · see citing works
The Future of PET Imaging in Multiple Sclerosis: Characterisation of Individual White Matter Lesions
van der Weijden, C. W. J., Meilof, J. F., van der Hoorn, A., de Vries, E. F. J., & Baron, W. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134439 · Cited by 4 · see citing works
Reversing binding sensitivity to A147T translocator protein.
Vo, S., Banister, S. D., Freelander, I., Werry, E., Reekie, T., Ittner, L., & Kassiou, M. (2020) · RSC Medicinal Chemistry · doi:10.1039/c9md00580c · Cited by 4 · see citing works
Badiuk, S., Thiessen, J., Vareki, S. M., Foster, P., Chen, J. Z. Y., & Wong, E. (2022) · Physics and Imaging in Radiation Oncology · doi:10.1016/j.phro.2022.02.016 · Cited by 3 · see citing works
Tang, S., Harrison, D., Bardhoshi, A., Cureton, R., Yan, X., Parcon, P. A., Morse, C., Ecker, C., Choi, S., Pike, V. W., et al. (2025) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1177/0271678x251332490 · Cited by 2 · see citing works
Radiation dosimetry of the 18 kDa translocator protein ligand [18F]PBR111 in humans.
Tournier, B., Mansouri, Z., Salimi, Y., Ceyzériat, K., Mathoux, G., Richard-Lepouriel, H., Zullino, D., Bois, F., Zaidi, H., Garibotto, V., et al. (2025) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2025.109011 · Cited by 2 · see citing works
Crescenzo, F., Marastoni, D., Pisani, A. I., Tamanti, A., Dapor, C., Colombi, A., Brillo, A., Magliozzi, R., Pizzini, F. B., Castellaro, M., et al. (2021) · Diagnostics · doi:10.3390/diagnostics11040686 · Cited by 1 · see citing works
Piri, R., Valta, M., Lempainen, J., Ivaska, L., Ezer, S., Kere, J., Katayama, S., & Peltola, V. (2026) · Communications Medicine · doi:10.1038/s43856-025-01370-z · Cited by 1
Yu, M.-H., Sun, Y.-H., Lalush, D., Mihalik, J., Yap, P., & Liu, M. (2026) · arXiv.org · doi:10.48550/arxiv.2602.21345 · Cited by 1
“Brain positron emission tomography (PET) is a powerful imaging modality that enables the in vivo visualization of various molecular targets, including β -amyloid deposition with 11 C-PIB (PIB), tau pathology with 18 F-AV1451 (TAU) [1]–[4], and neuroinflammatory activity with 18 F-PBR111 (PBR) [5].”
York, E., Thrippleton, M., Meijboom, R., Hunt, D., & Waldman, A. (2021) · medRxiv · doi:10.1101/2021.07.14.21260512 · Cited by 1
Assessment of 18F-PBR-111 in the Cuprizone Mouse Model of Multiple Sclerosis
Jewells, V., Yuan, H., Merrill, J. R., Frank, J. E., Patel, A., Cohen, S. M., Giglio, B. C., Feinberg, N. N., Matsushima, G., & Li, Z.-B. (2021) · Diagnostics · doi:10.3390/diagnostics11050786 · Cited by 1 · see citing works
“Although not currently FDA approved, 18F-PBR-111 has been evaluated in humans and has demonstrated a positive correlation between uptake of 18F-PBR111 and MS lesion score [15].”
BackgroundPET in Neurological and Psychiatric Disorders: Technologic Advances and Clinical Applications
Matusch, A., & Kroll, T. (2016) · Springer eBooks · doi:10.1007/978-3-319-40070-9_20 · Cited by 1 · see citing works
Evaluating the Clinical Utility of TSPO-PET in MS and the Influence of Methodological Heterogeneity
Neishaboori, A. M., Agarwal, M., Kalinsky, A., Lofaso, J. P., Rampilla, G., Kras, E. A., Nagy, S. C., Cooper, J. G., Ai, S., Zhang, C. K., et al. (2026) · Neurology Neuroimmunology & Neuroinflammation · doi:10.1212/nxi.0000000000200658
“%) included LAB participants with second-generation TSPO-PET tracers without strat-i fi cation, 26,e2,e31,e33 and 1 included patients with clinically isolated syndrome 25 ; thus, these studies were rated as high risk in patient selection applicability.”
PET Imaging in Multiple Sclerosis
van der Weijden, C. W. J., Meilof, J., & de Vries, E. D. (2020) · PET and SPECT in Neurology · doi:10.1007/978-3-030-53168-3_33
Water Homeostasis Dysfunctions and Edema in Neuroinflammatory Disease
Petry, K. G., & Bikfalvi, A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-803196-4.00018-7
Colasanti, A. (2014) · Spiral (Imperial College London) · doi:10.25560/25285
“, 2013) and, in MS patients in vivo, is increased in brain areas that T2-weighted MRI identifies as lesions (Colasanti et al., 2014) (see Chapter 4).”
BackgroundSelf-citation
- Authors
- Colasanti, A., Guo, Q., Muhlert, N., Giannetti, P., Onega, M., Newbould, R. D., Ciccarelli, O., Rison, S., Thomas, C., Nicholas, R., Muraro, P. A., Malik, O., Owen, D. R., Piccini, P., Gunn, R. N., Rabiner, E. A., & Matthews, P. M.
- Affiliations
- Imperial College London (GB)
- King's College London (GB)
- UCL Queen Square Institute of Neurology (GB)
- Imperial College Healthcare NHS Trust (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- ORCID
- Venue
- Journal of Nuclear Medicine
- Publisher
- Society of Nuclear Medicine
- Published
- 2014-06-05
- Volume
- 55
- Issue
- 7
- Pages
- 1112-1118
- ISSN
- 0161-5505 (ISSN-L)
- 2159-662X
- OpenAlex
- W2167600849
- Cited by
- 100
- References
- 0
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 10 · 2020: 7 · 2019: 11 · 2018: 6 · 2017: 14 · 2016: 14 · 2015: 11 · 2014: 2
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Nuclear Medicine (publishedVersion)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Australian Nuclear Science and Technology Organisation
- Wellcome Trust
- National Institute for Health and Care Research (CL-2013-17-003, CL-2011-21-002)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- multiple sclerosis, translocator protein (TSPO), white matter inflammation, innate immune response, microglial activation, macrophages, normal-appearing white matter, disease severity, magnetization transfer ratio, lesion quantification
- MeSH terms
- Adult, Aged, Female, Humans, Inflammation, Macrophages, Male, Middle Aged, Multiple Sclerosis, Pyridines, Reproducibility of Results, Case-Control Studies, Microglia, Positron-Emission Tomography, White Matter
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