[11C]-PBR28 positron emission tomography signal as an imaging marker of joint inflammation in knee osteoarthritis.
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
28 Nov 2023
28 Nov 2023
Historique:
received:
14
08
2023
accepted:
24
10
2023
medline:
28
11
2023
pubmed:
28
11
2023
entrez:
28
11
2023
Statut:
aheadofprint
Résumé
Although inflammation is known to play a role in knee osteoarthritis (KOA), inflammation-specific imaging is not routinely performed. In this article, we evaluate the role of joint inflammation, measured using [11C]-PBR28, a radioligand for the inflammatory marker 18-kDa translocator protein (TSPO), in KOA. Twenty-one KOA patients and 11 healthy controls (HC) underwent positron emission tomography/magnetic resonance imaging (PET/MRI) knee imaging with the TSPO ligand [11C]-PBR28. Standardized uptake values were extracted from regions-of-interest (ROIs) semiautomatically segmented from MRI data, and compared across groups (HC, KOA) and subgroups (unilateral/bilateral KOA symptoms), across knees (most vs least painful), and against clinical variables (eg, pain and Kellgren-Lawrence [KL] grades). Overall, KOA patients demonstrated elevated [11C]-PBR28 binding across all knee ROIs, compared with HC (all P's < 0.005). Specifically, PET signal was significantly elevated in both knees in patients with bilateral KOA symptoms (both P's < 0.01), and in the symptomatic knee (P < 0.05), but not the asymptomatic knee (P = 0.95) of patients with unilateral KOA symptoms. Positron emission tomography signal was higher in the most vs least painful knee (P < 0.001), and the difference in pain ratings across knees was proportional to the difference in PET signal (r = 0.74, P < 0.001). Kellgren-Lawrence grades neither correlated with PET signal (left knee r = 0.32, P = 0.19; right knee r = 0.18, P = 0.45) nor pain (r = 0.39, P = 0.07). The current results support further exploration of [11C]-PBR28 PET signal as an imaging marker candidate for KOA and a link between joint inflammation and osteoarthritis-related pain severity.
Identifiants
pubmed: 38015622
doi: 10.1097/j.pain.0000000000003114
pii: 00006396-990000000-00464
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCCIH NIH HHS
ID : P01-AT009965
Pays : United States
Organisme : NCCIH NIH HHS
ID : R61-AT009306
Pays : United States
Organisme : NCCIH NIH HHS
ID : R33-AT009306
Pays : United States
Organisme : NCCIH NIH HHS
ID : R01-AT007550
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01-AR064367
Pays : United States
Informations de copyright
Copyright © 2023 International Association for the Study of Pain.
Références
Ahmed AS, Gedin P, Hugo A, Bakalkin G, Kanar A, Hart DA, Druid H, Svensson C, Kosek E. Activation of NF-κB in synovium versus cartilage from patients with advanced knee osteoarthritis: a potential contributor to inflammatory aspects of disease progression. J Immunol 2018;201:1918–27.
Alam MM, Lee J, Lee S-Y. Recent progress in the development of TSPO PET ligands for neuroinflammation imaging in neurological diseases. Nucl Med Mol Imaging 2017;51:283–96.
Albrecht DS, Ahmed SU, Kettner NW, Borra RJH, Cohen-Adad J, Deng H, Houle TT, Opalacz A, Roth SA, Melo MFV, Chen L, Mao J, Hooker JM, Loggia ML, Zhang Y. Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients. PAIN 2018;159:968–77.
Albrecht DS, Forsberg A, Sandström A, Bergan C, Kadetoff D, Protsenko E, Lampa J, Lee YC, Höglund CO, Catana C, Cervenka S, Akeju O, Lekander M, Cohen G, Halldin C, Taylor N, Kim M, Hooker JM, Edwards RR, Napadow V, Kosek E, Loggia ML. Brain glial activation in fibromyalgia—a multi-site positron emission tomography investigation. Brain Behav Immun 2019;75:72–83.
Albrecht DS, Mainero C, Ichijo E, Ward N, Granziera C, Zürcher NR, Akeju O, Bonnier G, Price J, Hooker JM, Napadow V, Loggia ML, Hadjikhani N. Imaging of neuroinflammation in migraine with aura: a [11C]PBR28 PET/MRI study. Neurology 2019;92:e2038–50.
Alshelh Z, Albrecht DS, Bergan C, Akeju O, Clauw DJ, Conboy L, Edwards RR, Kim M, Lee YC, Protsenko E, Napadow V, Sullivan K, Loggia ML. In-vivo imaging of neuroinflammation in veterans with gulf war illness. Brain Behav Immun 2020;87:498–507.
Alshelh Z, Brusaferri L, Saha A, Morrissey E, Knight P, Kim M, Zhang Y, Hooker JM, Albrecht D, Torrado-Carvajal A, Placzek MS, Akeju O, Price J, Edwards RR, Lee J, Sclocco R, Catana C, Napadow V, Loggia ML. Neuroimmune signatures in chronic low back pain subtypes. Brain 2022;145:1098–110.
Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation Study of Womac: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol 1988;15:1833–40.
Bonsack F, Sukumari-Ramesh S. TSPO: an evolutionarily conserved protein with elusive functions. Int J Mol Sci 2018;19:1694.
Braestrup C, Squires RF. Specific benzodiazepine receptors in rat brain characterized by high-affinity (3H)diazepam binding. Proc Natl Acad Sci USA 1977;74:3805–9.
Brown AK, Fujita M, Fujimura Y, Liow J-S, Stabin M, Ryu YH, Imaizumi M, Hong J, Pike VW, Innis RB. Radiation dosimetry and biodistribution in monkey and man of 11C-PBR28: a PET radioligand to image inflammation. J Nucl Med 2007;48:2072–9.
Canat X, Carayon P, Bouaboula M, Cahard D, Shire D, Roque C, Le Fur G, Casellas P. Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells. Life Sci 1993;52:107–18.
Clow A, Glover V, Sandler M. Triazolam, an anomalous benzodiazepine receptor ligand: in vitro characterization of alprazolam and triazolam binding. J Neurochem 1985;45:621–5.
Cosenza-Nashat M, Zhao M-L, Suh H-S, Morgan J, Natividad R, Morgello S, Lee SC. Expression of the translocator protein of 18 kDa by microglia, macrophages and astrocytes based on immunohistochemical localization in abnormal human brain. Neuropathol Appl Neurobiol 2009;35:306–28.
Dakin SG, Coles M, Sherlock JP, Powrie F, Carr AJ, Buckley CD. Pathogenic stromal cells as therapeutic targets in joint inflammation. Nat Rev Rheumatol 2018;14:714–26.
Dupont A-C, Largeau B, Santiago Ribeiro M, Guilloteau D, Tronel C, Arlicot N. Translocator protein-18 kDa (TSPO) positron emission tomography (PET) imaging and its clinical impact in neurodegenerative diseases. Int J Mol Sci 2017;18:785.
Gehlert DR, Yamamura HI, Wamsley JK. Autoradiographic localization of “peripheral-type” benzodiazepine binding sites in the rat brain, heart and kidney. Naunyn Schmiedebergs Arch Pharmacol 1985;328:454–60.
Han D, Fang Y, Tan X, Jiang H, Gong X, Wang X, Hong W, Tu J, Wei W. The emerging role of fibroblast‐like synoviocytes‐mediated synovitis in osteoarthritis: an update. J Cell Mol Med 2020;24:9518–32.
Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet 2019;393:1745–59.
Kalk NJ, Owen DR, Tyacke RJ, Reynolds R, Rabiner EA, Lingford-hughes AR, Parker CA. Are prescribed benzodiazepines likely to affect the availability of the 18 kDa translocator protein (TSPO) in PET studies?. Synapse 2013;67:909–12.
Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier J-P, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011;7:33–42.
Kraus VB, McDaniel G, Huebner JL, Stabler TV, Pieper CF, Shipes SW, Petry NA, Low PS, Shen J, McNearney TA, Mitchell P. Direct in vivo evidence of activated macrophages in human osteoarthritis. Osteoarthritis Cartilage 2016;24:1613–21.
Kreisl WC, Jenko KJ, Hines CS, Lyoo CH, Corona W, Morse CL, Zoghbi SS, Hyde T, Kleinman JE, Pike VW, McMahon FJ, Innis RB; Biomarkers Consortium PET Radioligand Project Team. The biomarkers consortium PET radioligand project team. A genetic polymorphism for translocator protein 18 Kda affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation. J Cereb Blood Flow Metab 2013;33:53–8.
Lavisse S, Guillermier M, Hérard AS, Petit F, Delahaye M, Van Camp N, Ben Haim L, Lebon V, Remy P, Dollé F, Delzescaux T, Bonvento G, Hantraye P, Escartin C. Reactive astrocytes overexpress TSPO and are detected by TSPO positron emission tomography imaging. J Neurosci 2012;32:10809–18.
Liu B, Zhang M, Zhao J, Zheng M, Yang H. Imbalance of M1/M2 macrophages is linked to severity level of knee osteoarthritis. Exp Ther Med 2018;16:5009–14.
Loggia ML, Chonde DB, Akeju O, Arabasz G, Catana C, Edwards RR, Hill E, Hsu S, Izquierdo-Garcia D, Ji R-R, Riley M, Wasan AD, Zürcher NR, Albrecht DS, Vangel MG, Rosen BR, Napadow V, Hooker JM. Evidence for brain glial activation in chronic pain patients. Brain 2015;138:604–15.
Narayan N, Mandhair H, Smyth E, Dakin SG, Kiriakidis S, Wells L, Owen D, Sabokbar A, Taylor P. The macrophage marker translocator protein (TSPO) is down-regulated on pro-inflammatory ‘M1’ human macrophages. PLoS One 2017;12:e0185767.
Narayan N, Owen DR, Mandhair H, Smyth E, Carlucci F, Saleem A, Gunn RN, Rabiner EA, Wells L, Dakin SG, Sabokbar A, Taylor PC. Translocator protein as an imaging marker of macrophage and stromal activation in rheumatoid arthritis pannus. J Nucl Med 2018;59:1125–32.
Nutma E, Gebro E, Marzin MC, van der Valk P, Matthews PM, Owen DR, Amor S. Activated microglia do not increase 18 kDa translocator protein (TSPO) expression in the multiple sclerosis brain. Glia 2021;69:2447–58.
Owen DR, Narayan N, Wells L, Healy L, Smyth E, Rabiner EA, Galloway D, Williams JB, Lehr J, Mandhair H, Peferoen LA, Taylor PC, Amor S, Antel JP, Matthews PM, Moore CS. Pro-inflammatory activation of primary microglia and macrophages increases 18 kDa translocator protein expression in rodents but not humans. J Cereb Blood Flow Metab 2017;37:2679–90.
Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, Rhodes C, Pulford DJ, Bennacef I, Parker CA, St Jean PL, Cardon LR, Mooser VE, Matthews PM, Rabiner EA, Rubio JP. 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.
Palada V, Siddiqah Ahmed A, Hugo A, Radojčić MR, Svensson CI, Kosek E. Expression of mitochondrial TSPO and FAM173B is associated with inflammation and symptoms in patients with painful knee osteoarthritis. Rheumatology 2021;60:1724–33.
Papadopoulos V, Baraldi M, Guilarte TR, Knudsen TB, Lacapère JJ, Lindemann P, Norenberg MD, Nutt D, Weizman A, Zhang M-R, Gavish M. Translocator protein (18kDa): new nomenclature for the peripheral-type benzodiazepine receptor based on its structure and molecular function. Trends Pharmacol Sci 2006;27:402–9.
Princeton rehabilitation WOMAC form. 2023. Available at: https://www.princetonhcs.org/-/media/files/forms/princeton-rehabilitation/womac.pdf. Accessed April 7, 2023.
Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, Sokolove J. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol 2016;12:580–92.
Roemer FW, Kwoh CK, Hannon MJ, Hunter DJ, Eckstein F, Fujii T, Boudreau RM, Guermazi A. What comes first? Multitissue involvement leading to radiographic osteoarthritis: magnetic resonance imaging-based trajectory analysis over four years in the osteoarthritis initiative: trajectory of tissue damage leading to knee OA. Arthritis Rheumatol 2015;67:2085–96.
Sanchez-Lopez E, Coras R, Torres A, Lane NE, Guma M. Synovial inflammation in osteoarthritis progression. Nat Rev Rheumatol 2022;18:258–75.
Son KM, Hong JI, Kim D-H, Jang D-G, Crema MD, Kim HA. Absence of pain in subjects with advanced radiographic knee osteoarthritis. BMC Musculoskelet Disord 2020;21:640.
Weerasekera A, Morrissey E, Kim M, Saha A, Lin Y, Alshelh Z, Torrado-Carvajal A, Albrecht D, Akeju O, Kwon Y-M, Bedair H, Chen AF, Napadow V, Schreiber K, Ratai E-M, Edwards RR, Loggia ML. Thalamic neurometabolite alterations in patients with knee osteoarthritis before and after total knee replacement. PAIN 2021;162:2014–23.
Yoder KK, Nho K, Risacher SL, Kim S, Shen L, Saykin AJ. Influence of TSPO genotype on 11 C-PBR28 standardized uptake values. J Nucl Med 2013;54:1320–2.
Zhang H, Cai D, Bai X. Macrophages regulate the progression of osteoarthritis. Osteoarthritis Cartilage 2020;28:555–61.
Zhang Y, Nevitt M, Niu J, Lewis C, Torner J, Guermazi A, Roemer F, McCulloch C, Felson DT. Fluctuation of knee pain and changes in bone marrow lesions, effusions, and synovitis on magnetic resonance imaging. Arthritis Rheum 2011;63:691–9.