Skip to main content

Advertisement

SpringerLink
Log in

PET imaging in multiple sclerosis

  • INVITED REVIEW
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

Positron emission tomography (PET) is a non-invasive technique for quantitative imaging of biochemical and physiological processes in animals and humans. PET uses probes labeled with a radioactive isotope, called PET tracers, which can bind to or be converted by a specific biological target and thus can be applied to detect and monitor different aspects of diseases. The number of applications of PET imaging in multiple sclerosis is still limited. Clinical studies using PET are basically focused on monitoring changes in glucose metabolism and the presence of activated microglia/macrophages in sclerotic lesions. In preclinical studies, PET imaging of targets for other processes, like demyelination and remyelination, has been investigated and may soon be translated to clinical applications. Moreover, more PET tracers that could be relevant for MS are available now, but have not been studied in this context yet. In this review, we summarize the PET imaging studies performed in multiple sclerosis up to now. In addition, we will identify potential applications of PET imaging of processes or targets that are of interest to MS research, but have yet remained largely unexplored.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abourbeh G, Thézé B, Maroy R, Dubois A, Brulon V, Fontyn Y, Dollé F, Tavitian B, Boisgard R (2012) Imaging microglial/macrophage activation in spinal cords of experimental autoimmune encephalomyelitis rats by positron emission tomography using the mitochondrial 18 kDa translocator protein radioligand [18 F] DTPA-714. J Neurosci 32:5728–5736

    CAS  PubMed  Google Scholar 

  • Ahmed I, Sk B, Pavese N, Ramlackhansing A, Turheimer F, Hotton G, Hammers A, Brooks DJ (2011) Glutamate NMDA receptor dysregulation in Parkinson’s disease with dyskinesias. Brain 134:979–986

    PubMed  Google Scholar 

  • Bajramovic JJ, Plomp AC, Goes A et al (2000) Presentation to T cells of alpha b-crystallin in ms lesions, an early event following inflammatory demyelination. J Immunol 164:4359–4366

    CAS  PubMed  Google Scholar 

  • Bakshi R, Miletich RS, Kinkel PR, Emmet ML, Kinkel WR (1998) High-resolution fluorodeoxyglucose positron emission tomography shows both global and regional cerebral hypometabolism in multiple sclerosis. J Neuroimaging 8:228–34

    CAS  PubMed  Google Scholar 

  • Banati RB, Newcombe J, Gunn RN et al (2000) The peripheral benzodiazepine binding site in the brain in multiple sclerosis: quantitative in vivo imaging of microglia as a measure of disease activity. Brain 123(Pt 11):2321–2337

    PubMed  Google Scholar 

  • Berding G, Schneider U, Gielow P, Buchert R, Donnerstag F, Brandau W, Knapp WH, Emrich HM, Müller-Vahl K (2006). Feasibility of central cannabinoid CB1 receptor imaging with [124I] AM281 PET demonstrated in a schizophrenic patient Psychiatry Res; 147:249–256.

  • Blinkenberg M, Rune K, Jønsson A, Holm S, Jensen CV, Paulson OB et al (1996) Cerebral metabolism in a case of multiple sclerosis with acute mental disorder. Acta Neurol Scand 94:310–313

    CAS  PubMed  Google Scholar 

  • Blinkenberg M, Jensen CV, Holm S, Paulson OB, Sorensen OS (1999) A longitudinal study of cerebral glucose metabolism, MRI, and disability in patients with MS. Neurology 53:149–53

    CAS  PubMed  Google Scholar 

  • Bolcaen J, Acou M, Mertens K, Hallaert G, Van den Broecke C, Achten E, Goethals I (2013) Structural and metabolic features of two different variants of multiple sclerosis: a PET/MRI study. J Neuroimaging 23:431–436

    PubMed  Google Scholar 

  • Brück W (2005) Clinical implications of neuropathological findings in multiple sclerosis. J Neurol 252:10–14

    Google Scholar 

  • Buck D, Förschler A, Lapa C, Schuster T, Vollmar P, Korn T, Nessler S, Stadelmann C, Drzezga A, Buck AK, Wester HJ, Zimmer C, Krause BJ, Hemmer B (2012) 18F-FDG PET detects inflammatory infiltrates in spinal cord experimental autoimmune encephalomyelitis lesions. J Nucl Med 53:1269–76

    CAS  PubMed  Google Scholar 

  • Burns HD, Van Laere K, Sanabria-Bohórquez S (2007) [18F] MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor. Proc Natl Acad Sci 104(23):9800–9805

    CAS  PubMed Central  PubMed  Google Scholar 

  • Carlson NG, Hill KE, Tsunoda I, Fujinami RS, Rose JW (2006) The pathologic role for COX-2 in apoptotic oligodendrocytes in virus induced demeylination disease:implications for multiple sclerosis. J Neuroimmunol 174:21–31

    CAS  PubMed  Google Scholar 

  • Carlson NG, Rojas MA, Redd JW, Tang P, Wood B, Hill KE, Rose JW (2010) Cyclooxygenase-2 expression in oligodendrocytes increases sensitivity to excitotoxic death. J Neuroinflammation 7:25

    PubMed Central  PubMed  Google Scholar 

  • Ceccarini J, De Hert M, Van Winkel R, Peuskens J, Bormans G, Kranaster L, Enning F, Koethe D, Leweke FM, Van Laere K (2013) Increased ventral striatal CB1 receptor binding is related to negative symptoms in drug-free patients with schizophrenia. Neuroimage 79:304–312

    CAS  PubMed  Google Scholar 

  • Chen SJ, Wnag YL, Fan HC, Lo WT, Wang CC, Sytwu HK (2012) Current status of the immunomodulation and immunomediated therapeutic strategies for multiple sclerosis. Clin Dev Immunol 2012:970789

    PubMed Central  PubMed  Google Scholar 

  • Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517

    CAS  PubMed  Google Scholar 

  • Confavreux C, Hutchinson M, Hours MM, Cortinovis-Tourniaire P, Moreau T (1998) Rate of pregnancy-related relapse in multiple sclerosis. Preg in Multiple Sclerosis Group N Engl J Med 339:285–291

    CAS  Google Scholar 

  • de Paula F, De Vries EF, Sijbesma JW, Dierckx RA, Buchpiguel CA, Copray S (2014a) PET imaging of demyelination and remyelination in the cuprizone mouse model for multiple sclerosis: a comparison between [11C] CIC and [11C] MeDAS. Neuroimage 87:395–402

  • de Paula Faria D, Copray S, Sijbesma JW, Willemsen AT, Buchpiguel CA, Dierckx RA, de Vries EF (2014b). PET imaging of focal demyelination and remyelination in a rat model of multiple sclerosis: comparison of [11C] MeDAS, [11C] CIC and [11C] PIB. Eur J Nucl Med Mol Imaging; Feb 6. [Epub ahead of print].

  • de Vries EFJ, van Waarde A, Buursma AR, Vaalburg W (2003) Synthesis and in vivo evaluation of 18F-desbromo-DuP-697 as a PET tracer for cyclooxygenase-2 expression. J Nucl Med 44(10):1700–1706

    PubMed  Google Scholar 

  • de Vries EFJ, Doorduin J, Dierckx RAJO, van Waarde A (2008a) Evaluation of [(11) C] rofecoxib as PET tracer for cyclooxygenase 2 overexpression in rat models of inflammation. Nucl Med Biol 35(1):35–42

    PubMed  Google Scholar 

  • de Vries EF, Doorduin J, Vellinga NA, van Waarde A, Dierckx RA, Klein HC (2008b) Can celecoxib affect P-glycoprotein-mediated drug efflux? A microPET study Nucl Med Biol 35:459–66

    Google Scholar 

  • Debruyne JC, Versijpt J, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, Achten E, Slegers G, Dierckx RA, Korf J, De Reuck JL (2003) PET visualization of microglia in multiple sclerosis patients using [11C] PK11195. Eur J Neurol 10:257–64

    CAS  PubMed  Google Scholar 

  • Derfuss T (2012) Personalized medicine in multiple sclerosis: hope or reality? BMC Medicine 10:116

    PubMed Central  PubMed  Google Scholar 

  • Dijkers EC, Kosterink JG, Rademaker AP, Perk LR, van Dongen GA, Bart J, de Jong JR, de Vries EG, Lub-de Hooge MN (2009) Development and characterization of clinical-grade 89Zr-trastuzumab for HER2/neu immunoPET imaging. J Nucl Med 50:974–81

    CAS  PubMed  Google Scholar 

  • Doorduin J, de Vries EFJ, Dierckx RA, Klein HC (2008) PET imaging of the peripheral benzodiazepine receptor: monitoring disease progress and therapy in neurodegenerative disorders. Curr Pharm Des 14:3297–3315

    CAS  PubMed  Google Scholar 

  • Evens N, Muccioli GG, Houbrechts N, Lambert DM, Verbruggen AM, Van Laere K, Bormans GM (2009) Synthesis and biological evaluation of carbon-11- and fluorine-18-labeled 2-oxoquinoline derivatives for type 2 cannabinoid receptor positron emission tomography imaging. Nucl Med Biol 36(4):455–465

    CAS  PubMed  Google Scholar 

  • Fillippi M, Rocca MA (2011) MR imaging of multiple sclerosis. Radiology 259:659–681

    Google Scholar 

  • Fodero-Tavoletti MT, Rowe CC, Maclean CA, Leone L, Li QX, Masters CL, Cappai R, Villemagne VL (2009) Characterization of PIB binding to white matter in Alzheimer disease and other dementias. J Nucl Med 50:198–204

    PubMed  Google Scholar 

  • Fukumitsu N, Ishii K, Kimura Y, Oda K, Hashimoto M, Suzuki M, Ishiwata K (2008) Adenosine A (1) receptors using 8-dicyclopropylmethyl-1-[(11) C] methyl-3-propylxanthine PET in Alzheimer’s disease. Ann Nucl Med 22:841–7

    PubMed  Google Scholar 

  • Gajofatto A, Bongianni M, Zanusso G, Bianchi MR, Turatti M, Benedetti MD, Monaco S (2013). Clinical and biomarker assessment of demyelinating events suggesting multiple sclerosis. Acta Neurol Scand; Apr 1. doi: 10.1111/ane.12123. [Epub ahead of print]

  • Gomez O, Arevalo-Martin A, Garcia-Ovejero D, Ortega-Gutierrez S, Cisneros JA, Almazan G, Sanchez-Rodrigues MS, Molina-Holgado F, Molina-Holgado E (2010) The constitutive production of the endocannabinoid 2-arachidonoylglycerol participates in oligodendrocyte differentiation. Glia 58:1913–1927

    PubMed  Google Scholar 

  • Greene Y, Tariot P, Wishart H, Cox C, Holt CJ, Schwid S et al (2000) A 12-week, open trial of donepezil hydrochloride in patients with multiple sclerosis and associated cognitive impairments. J Clin Psychopharmacol 20:350–356

    CAS  PubMed  Google Scholar 

  • Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, Hauser S, Waubant E, Vollmer T, Panitch H, Zhang J, Chin P, Smith CH, OLYMPUS trial group (2009) Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter. Trial Ann Neurol 66(4):460–471

    CAS  Google Scholar 

  • Honce JM (2013) Gray matter pathology in MS: neuroimaging and clinical correlations. Multi Scler Int 2013:627870

    Google Scholar 

  • Ishiwata K, Kimura Y, de Vries EFJ, Elsinga PH (2007) PET tracers for mapping adenosine receptors as probes for diagnosis of CNS disorders. Cent Nerv Syst Agents Med Chem 7:57–77

    CAS  Google Scholar 

  • Johnston JB, Silva C, Gonzalez G, Holden J, Warren KG, Metz LM, Power C (2001) Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis. Ann Neurol 49:650–8

    CAS  PubMed  Google Scholar 

  • Jonson SD, Welch MJ (1999) Synthesis, biological evaluation, and baboon PET imaging of the potential adrenal imaging agent cholesteryl-p-[18 F] fluorobenzoate. Nucl Med Biol 26:131–138

    CAS  PubMed  Google Scholar 

  • Káradóttir R, Attwell D (2007) Neurotransmitter receptors in the life and death of oligodendrocytes. Neuroscience 145:1426–1438

    PubMed Central  PubMed  Google Scholar 

  • Khayum MAK, de Vries EFJ, Glaudemans AWJM, Dierckx RAJO, Doorduin J (2014). In Vivo Imaging of Brain Estrogen Receptors in Rats: A 16α-18 F-Fluoro-17β-Estradiol PET Study. J Nucl Med. [Epub ahead of print].

  • Kimura Y, Ishii K, Fukumitsu N, Oda K, Sasaki T, Kawamura K, Ishiwata K (2004) Quantitative analysis of adenosine A1 receptors in human brain using positron emission tomography and [1-methyl-11C] 8-dicyclopropylmethyl-1-methyl-3-propylxanthine. Nucl Med Biol 31:975–81

    CAS  PubMed  Google Scholar 

  • Kreisl WC, Jenko KJ, Hines CS, Lyoo CH, Corona W, Morse CL, Zoghbi SS, Hyde T, Kleinman JE, Pike VW, McMahon FJ, Innis RB (2013) A genetic polymorphism for translocator protein 18kDa affects both in vitro and in vivo radioligand binding in human brain to this putative biomarker of neuroinflammation. J Cereb Blood Flow Metab 33:53–8

    CAS  PubMed Central  PubMed  Google Scholar 

  • Krupp L, Christodoulou C, Melville P, Scherl WF, MacAllister WS, Elkins LE (2004) Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology 63:1579–1585

    CAS  PubMed  Google Scholar 

  • Kumar S, Patel R, Moore S, Crawford DK, Suwanna N, Mangiardi M, Tiwari-Wooodruff SK (2013) Estrogen receptor â ligand therapy activates PI3K/Akt/mTOR signaling in oligodendrocytes and promotes remyelination in a mouse model for multiple sclerosis. Neurobiol Dis 56:131–144

    CAS  PubMed  Google Scholar 

  • Lassman H (2013) Pathology and disease mechanisms in different stages of multiple sclerosis. J Neurol Sci. doi:10.1016/j.jns.2013.05.010

    Google Scholar 

  • Lassman H, van Horssen J (2011) The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett 585:3715–3723

    Google Scholar 

  • Laube M, Kniess T, Pietzsch J (2013) Radiolabeled COX-2 inhibitors for non-invasive visualization of COX-2 expression and activity–a critical update. Molecules 18(6):6311–6355

    CAS  PubMed  Google Scholar 

  • Luessi F, Siffrin V, Zipp F (2012) Neurodegeneration in multiple sclerosis: novel treatment strategies. Expert Ver Neurother 12:1061–1076

    CAS  Google Scholar 

  • Maresz K, Pryce G, Ponomarev E, Marsicano G, Croxford J et al (2007) Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat Med 13:492–497

    CAS  PubMed  Google Scholar 

  • Matthews PM (2009) Brain imaging of multiple sclerosis: the next 10 years. Neuroimag Clin N Am 19:101–112

    Google Scholar 

  • Mattner F, Staykova M, Berghofer P, Wong HJ, Fordham S, Callaghan P, Jackson T, Pham T, Gregoire MC, Zahra D, Rahardjo G, Linares D, Katsifis A (2013) Central nervous system expression and PET imaging of the translocator protein in relapsing-remitting experimental autoimmune encephalomyelitis. J Nucl Med 54:291–298

    CAS  PubMed  Google Scholar 

  • McCarthy TJ, Sheriff AU, Graneto MJ, Talley JJ, Welch MJ (2002) Radiosynthesis, in vitro validation, and in vivo evaluation of 18 F-labeled COX-1 and COX-2 inhibitors. J Nucl Med 43(1):117–124

    CAS  PubMed  Google Scholar 

  • McDonald WI, Ron MA (1999) Multiple sclerosis: the disease and its manifestations. Philos Trans R Soc Lond B Biol Sci 354:1615–22

  • McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, McFarland HF, Paty DW, Polman CH, Reingold SC, Sandberg-Wollheim M, Sibley W, Thompson A, van der Noort S, Weinshenker BY, Wolinsky JS (2001) Recommended diagnostic criteria for multiple sclerosis: Guidelines from the Intenational Panel on the Diagnosis of Multiple sclerosis. Ann Neurol 50:121–127

    CAS  PubMed  Google Scholar 

  • McGinnity CO, Hammers A, Barros DAR, Luthra SK, Jones PA, Trigg W et al (2014) Initial Evaluation of 18 F-GE-179, a putative PET tracer for activated N-Methyl d-Aspartate receptors. J Nucl Med 55:423–430

    CAS  PubMed  Google Scholar 

  • Minghetti L (2004) Cycloooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol 63:901–910.

  • Molina-Holgado E, Vela JM, Arevalo-Martin A, Almazan G, Molina-Holgado F, Borell J, Guaza C (2002) Cannabinoids promote oligodendrocyte progenitor survival: involvemente of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. J Neurosci 22:9742–9753

    CAS  PubMed  Google Scholar 

  • Moresco RM, Casati R, Lucignani G, Carpinelli A, Schmidt K, Todde S, Colombo F, Fazio F (1995) Systemic and cerebral kinetics of 16 alpha [18 F] fluoro-17 beta-estradiol: a ligand for the in vivo assessment of estrogen receptor binding parameters. J Cereb Blood Flow Metab 15:301–311

    CAS  PubMed  Google Scholar 

  • Nelissen K, Mulder M, Smets I, Timmermans S, Smeets K, Ameloot M, Hendriks JJ (2012) Liver X receptors regulate cholesterol homeostasis in oligodendrocytes. J Neurosci Res 90:60–71

    CAS  PubMed  Google Scholar 

  • Oh U, Fujita M, Ikonomidou VN, Evangelou IE, Matsuura E, Harberts E, Fujimura Y, Richert ND, Ohayon J, Pike VW, Zhang Y, Zoghbi SS, Innis RB, Jacobson S (2011) Translocator protein PET imaging for glial activation in multiple sclerosis. J Neuro Phar 6:354–61

    Google Scholar 

  • Orr AG, Orr AL, Li XJ, Gross RE, Traynelis SF (2009) Adenosine A (2A) receptor mediates microglial process retraction. Nat Neurosci 12:872–878

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ousman SS, Tomooka BH, van Noort JM, Wawrousek EF, O’Connor KC, Hafler DA, Sobel RA, Robinson WH, Steinman L (2007) Protective and therapeutic role for alphaB-crystallin in autoimmune demyelination. Nature 448:474–479

    CAS  PubMed  Google Scholar 

  • Padma MV, Adineh M, Pugar K, Mukherjee J, Satter M, Shi B, Dunigan K, Bidwell K, Ezzeddine B, Mantil J (2005) Functional imaging of a large demyelinating lesion. J Clin Neurosci 12(2):176–8

    CAS  PubMed  Google Scholar 

  • Paulesu E, Perani D, Fazio F, Comi G, Pozzilli C, Martinelli V, Filippi M, Bettinardi V, Sirabian G, Passafiume D, Anzini A, Lenzi GL, Canal N, Fieschi C (1996) Functional basis of memory impairment in multiple sclerosis: a [18 F] FDG PET study. Neuroimage 4:87–96

    CAS  PubMed  Google Scholar 

  • Pettersson K, Gustafsson JA (2001) Role of estrogen receptor beta in estrogen action. Annu Rev Physiol 63:165–92

    CAS  PubMed  Google Scholar 

  • Pittock SJ, Lucchinetti CF (2007) The pathology of MS. New insights and potential clinical applications. Neurologist 13:45–56

    PubMed  Google Scholar 

  • Politis M, Gianetti P, Su P, Turkheiner F, Keihaninejad S, Wu K, Waldman A, Malik O, Matthews PM, Reynolds R, Nicholas R, Piccini P (2012) Increased PK11195 PET binding in the córtex with MS correlates with disability. Neurology 79:523–530

    PubMed Central  PubMed  Google Scholar 

  • Popescu BFG, Lucchinetti CF (2012) Pathology of demeylinating diseases. Annu Rev Pathol Mech Dis 7:185–217

    CAS  Google Scholar 

  • Prabhakaran J, Underwood MD, Parsey RV, Arango V, Majo VJ, Simpson NR, Van Heertum R, Mann JJ, Kumar JS (2007) Synthesis and in vivo evaluation of [18 F]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide as a PET imaging probe for COX-2 expression Bioorg Med Chem;15 (4):1802–1807.

  • Prentice RL, Manson JE, Langer RD, Anderson GL, Pettinger M, Jackson RD, Johnson KC, Kuller LH, Lane DS, Wactawski-Wende J, Brzyski R, Allison M, Ockene J, Sarto G, Rossouw JE (2009) Benefits and risks of postmenopausal hormone therapy when it is initiate soon after menopause. Am J Epidemiol 170:12–23

    PubMed Central  PubMed  Google Scholar 

  • Ratchford JN, Endres CJ, Hammoud DA, Pomper MG, Shiee N, McGready J, Pham DL, Calabresi PA (2012) Decreased microglial activation in MS patients treated with glatiramer acetate. J Neurol 259:1199–1205

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ribeiro R, Yu F, Wen J, Vana A, Zhang Y (2013). Therapeutic potential of a novel cannabinoid agent CB52 in the mouse modelof experimental encephalomyelitis. Neuroscience. [Epub ahead of print].

  • Rissanen E, Virta JR, Paavilainen T, Tuisku J, Helin S, Luoto P, Parkkola R, Rinne JO, Airas (2013). Adenosine A2A receptors in secondary progressive multiple sclerosis: a [11C] TMSX brain PET study. J Cereb Blood Flow Metab. [Epub ahead of print].

  • Rodgers JM, Robinson AP, Miller SD (2013) Strategies for protecting oligodendrocytes and enhancing remyelination in multiple sclerosis. Discov Med 16:53–63

    PubMed Central  PubMed  Google Scholar 

  • Rojas S, Martín A, Pareto D, Herance JR, Abad S, Ruíz A, Flotats N, Gispert JD, Llop J, Gómez-Vallejo V, Planas AM (2011) Positron emission tomography with 11C-flumazenil in the rat shows preservation of binding sites during the acute phase after 2 h-transient focal ischemia. Neuroscience 182:208–216

    CAS  PubMed  Google Scholar 

  • Rom S, Persidsky Y (2013) Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation. J Neuroimmune Pharmacol 8:608–20

    PubMed Central  PubMed  Google Scholar 

  • Rommer P, Dudesek A, Stüve O, Zettl U (2013) Monoclonal Antibodies in Treatment of Multiple Sclerosis. Clin Exp Immunol. doi:10.1111/cei.12197

    Google Scholar 

  • Rose JW, Foley J, Carlson N (2008) Monoclonal antibody treatments for multiple sclerosis. Curr Neurol Neurosci Rep 8(5):419–426

    CAS  PubMed  Google Scholar 

  • Rossi S, Studer V, Motta C, De Chiara V, Barbieri F, Bernardi G, Centonze D (2012) Inflammation inhibits GABA transmission in multiple sclerosis. Mult Scler 18:1633–1635

    PubMed  Google Scholar 

  • Saher G, Brugger B, Lappe-Siefke C, Mobius W, Tozawa R, Wehr MC, Wieland F, Ishibashi S, Nave KA (2005) High cholesterol level isessential for myelin membrane growth. Nat Neurosci 8:468–475

    CAS  PubMed  Google Scholar 

  • Sahraian MA, Eshaghi A (2010) Role of MRI in diagnosis and treatment of multiple sclerosis. Clin Neurol Neurosurg 112:609–615

    PubMed  Google Scholar 

  • Sand IBK, Lublin FD (2013) Diagnosis and differential diagnosis of multiple sclerosis. Continuum (Minneap Minn) 19:922–943

    Google Scholar 

  • Schiepers C, Van Hecke P, Vandenberghe R, Van Oostende S, Dupont P, Demaerel P, Bormans G, Carton H (1997) Positron emission tomography, magnetic resonance imaging and proton NMR spectroscopy of white matter in multiple sclerosis. Mult Scler 3:8–17

    CAS  PubMed  Google Scholar 

  • Shukuri M, Takashima-Hirano M, Tokuda K, Takashima T, Matsumura K, Inoue O, Doi H, Suzuki M, Watanabe Y, Onoe H (2011) In vivo expression of cyclooxygenase-1 in activated microglia and macrophages during neuroinflammation visualized by PET with 11C-ketoprofen methyl Ester. J Nucl Med 52(7):1094–1101

    PubMed  Google Scholar 

  • Sicotte NL, Liva SM, Klutch R, Pfeiffer P, Bouvier S, Odesa S, Wu TC, Voskuhl RR (2002) Treatment of multiple sclerosis with the pregnancy hormone estriol. Ann Neurol 52:421–428

    CAS  PubMed  Google Scholar 

  • Sobrio F, Gilbert G, Perrio C, Barré L, Debruyne D (2010) PET and SPECT imaging of the NMDA receptor system: an overview of radiotracer development. Mini Rev Med Chem 10:870–86

    CAS  PubMed  Google Scholar 

  • Solbrig MV, Fan Y, Hermanowicz N, Morgese MG, Giuffrida A (2010) A synthetic cannabinoid agonist promotes oligodendrogliogenisis during viral encephalitis in rats. Exp Neurol 226:231–241

    CAS  PubMed Central  PubMed  Google Scholar 

  • Spence RD, Hamby ME, Umeda E, Itoh N, Du S, Wisdom AJ, Cao Y, Bondar G, Lam J, Ao Y, Sandoval F, Suriany S, Sofroniew MV, Voskuhl RR (2011) Neuroprotection mediated through estrogen receptor-alpha in astrocytes. Proc Natl Acad Sci 108:8867–8872

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stankoff B, Wang Y, Bottlaender M, Aigrot MS, Dolle F, Wu C, Feinstein D, Huang GF, Semah F, Mathis CA, Klunk W, Gould RM, Lubetzki C, Zalc B (2006) Imaging of CNS myelin by positron emission tomography. PNAS 103:9304–9309

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stankoff B, Freeman L, Aigrot MS, Chardain A, Dollé F, Willinas A, Galanaud D, Armand L, Lehericy S, Lubetzki C, Zalc B, Botlaender M (2011) Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [Methyl-11C]-2-(40-Methylaminophenyl)-6-Hydroxybenzothiazole. Ann Neurol 69:673–680

    CAS  PubMed  Google Scholar 

  • Stuart M, Bergstrom L (2011) Pregnancy and multiple sclerosis. J Midwifery Womens healthy 56:41–47

    Google Scholar 

  • Stys PK, Lipton SA (2007) White matter NMDA receptors: an unexpected new therapeutic target? Pharmacol Scie 28:561–566

    CAS  Google Scholar 

  • Stys PK, Zamponi GW, van Minnen J, Geurts JJG (2012) Will the real multiple sclerosis please stand up? Nat Rev Neurosci 13:507–514

    CAS  PubMed  Google Scholar 

  • Sun X, Tanaka M, Kondo S, Okamoto K, Hirai S (1998) Clinical significance of reduced cerebral metabolism in multiple sclerosis: a combined PET and MRI study. Ann Nucl Med 12:89–94

    CAS  PubMed  Google Scholar 

  • Takano A, Piehl F, Hillert J, Varrone A, Nag S, Gulyás B, Stenkrona P, Villemagne VL, Rowe CC, Macdonell R, Tawil NA, Kucinski T, Zimmermann T, Schultze-Mosgau M, Thiele A, Hoffmann A, Halldin C (2013) In vivo TSPO imaging in patients with multiple sclerosis: a brain PET study with [18 F] FEDAA1106. EJNMMI Res 3:30

    PubMed Central  PubMed  Google Scholar 

  • Tameh AA, Clarner T, Beyer C, Atlasi MA, Hassanzadeh G, Naderian H (2013). Regional regulation of glutamate signaling during cuprizone-induced demeylination in the brain. Annals of Anatomy. [Epub ahead of print].

  • Tsao J, Heilman K (2005) Donepezil improved memory in multiple sclerosis in a randomized clinical trial. Neurology 64:1823

    PubMed  Google Scholar 

  • Tsutsui S, Schnermann J, Noorbakhsh F, Henry S, Yong VW, Winston BW, Warren K, Power C (2004) A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. J Neurosci 24:1521–1529

    CAS  PubMed  Google Scholar 

  • Tsutsui S, Vergote D, Shariat N, Warren K, Ferguson SS, Power C (2008). Glucocorticoids regulate innate immunity in a model of multiple sclerosis: reciprocal interactions between the A1 adenosine receptor and beta-arrestin-1 in monocytoid cells FASEB J; 22:786–796.

  • Uddin MJ, Crews BC, Ghebreselasie K, Huda I, Kingsley PJ, Ansari MS, Tantawy MN, Reese J, Marnett LJ (2011) Fluorinated COX-2 inhibitors as agents in PET imaging of inflammation and cancer. Cancer Prev Res 4(10):1536–1545

    CAS  Google Scholar 

  • van den Hoff J (2005) Principles of quantitative positron emission tomography. Amino Acids 29:341–353

    PubMed  Google Scholar 

  • Van Laere K, Goffin K, Casteels C, Dupont P, Mortelmans L, de Hoon J, Bormans G (2008) Gender-dependent increases with healthy aging of the human cerebral cannabinoid-type 1 receptor binding using [(18) F] MK-9470 PET. Neuroimage 39(4):1533–1541

    PubMed  Google Scholar 

  • van Noort JM, Bsibsi M, Gerritsen WH, van der Valk P, Bajramovic JJ, Steinman L, Amor S (2010) Alphab-crystallin is a target for adaptive immune responses and a trigger of innate responses in preactive multiple sclerosis lesions. J Neuropathol Exp Neurol 69:694–703

    PubMed  Google Scholar 

  • Vas A, Shchukin Y, Karrenbauer VD, Cselényi Z, Kostulas K, Hillert J, Savic I, Takano A, Halldin C, Gulyás B (2008) Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C] vinpocetine and [11C] PK11195 in patients. J Neurol Sci 264:9–17

    CAS  PubMed  Google Scholar 

  • Versijpt J, Debruyne JC, Van Laere KJ, De Vos F, Keppens J, Strijckmans K, Achten E, Slegers G, Dierckx RA, Korf J, De Reuck JL (2005) Microglial imaging with positron emission tomography and atrophy measurements with magnetic resonance imaging in multiple sclerosis: a correlative study. Mult Scler 11:127–34

    CAS  PubMed  Google Scholar 

  • Vincenzi F, Corciulo C, Targa M, Merighi S, Gessi S, Cassetta I, Gentile M, Granieri E, Borea PA, Varani K (2013) Multiple sclerosis lymphocytes upregulated A2A adenosine receptors that are anti-inflammatory when stimulated. Eur J Immunol 43:2206–2216

    CAS  PubMed  Google Scholar 

  • Virta JR, Laatu S, Parkkola R, Oikonen V, Rinne JO, Ruutiainen J (2011) Cerebral acetylcholinesterase activity is not decreased in MS patients with cognitive impairment. Mult Scler 17:931–938

    PubMed  Google Scholar 

  • Vowinckel E, Reutens D, Becher B, Verge G, Evans A, Owens T, Antel JP (1997) PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis. J Neurosci Res 50:345–53

    CAS  PubMed  Google Scholar 

  • Wadsak W, Mitterhauser M (2010) Basics and principles of radiopharmaceuticals for PET/CT. Eur J Radiol 73:461–469

    CAS  PubMed  Google Scholar 

  • Wang Y, Wu C, Caprariello AV, Somoza E, Zhu W, Wang C, Miller RH (2009) In vivo quantification of myelin changes in the vertebrate nervous system. J Neurosc 29:14663–14669

    CAS  Google Scholar 

  • Wisdom AJ, Cao Y, Itoh N, Spence RD, Voskuhl RR (2013) Estrogen receptor β ligand treatment after disease onset is neuroprotective in the multiple sclerosis model. J Neurosci Res 91:901–908

    CAS  PubMed  Google Scholar 

  • Wu C, Tian D, Feng Y, Polak P, Wei J, Sharp A, Stankoff B, Lubetzki C, Zalc B, Mufson EJ, Gould RM, Feinstein DL, Wang Y (2006) A novel fluorescent probe that is brain permeable and selectively binds to myelin. J Histochem Cytochem 54:997–1004

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu C, Wang C, Popescu DC, Zhu W, Somoza EA, Zhu J, Condie AG, Flask CA, Miller RH, Macklin W, Wang Y (2010) A novel PET marker for in vivo quantification of myelination. Bioorg Med Chem 18:8592–8599

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu C, Li F, Niu G, Chen X (2013a) PET imaging of inflammation biomarkers. Theranostics 3:448–466

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu C, Zhu J, Baeslak J, Zaremba A, Hecker J, Kraso J, Matthews PM, Miller RH, Wang Y (2013b) Longitudinal PET imaging for monitoring myelin repair in the spinal cord. Ann Neurol 74:688–98

    CAS  PubMed  Google Scholar 

  • Xie L, Yamasaki T, Ichimaru N, Yui J, Kawamura K, Kumata K, Hatori A, Nonomura N, Zhang MR, Li XK, Takahara S (2012) [(11) C] DAC-PET for noninvasively monitoring neuroinflammation and immunosuppressive therapy efficacy in rat experimental autoimmune encephalomyelitis model. J Neuro Pharmacol 7:231–42

    Google Scholar 

  • Xu P, Li D, Tang X, Bao X, Huang J, Tang Y, Yang Y, Xu H, Fan X (2013). LXR Agonists: New potential therapeutic drug for neurodegenerative diseases. Mol Neurobiol [Epub ahead of print].

  • Zajicek JP, Apostu VI (2011) Role of cannabinoids in multiple sclerosis. CNS Drugs 25:187–201

    CAS  PubMed  Google Scholar 

  • Zanzonico P (2012) Principles of nuclear medicine imaging: Planar, SPECT, PET, multi-modality, and autoradiography systems. Radiation Reseach 177:349–364

    CAS  Google Scholar 

  • Zhao Y, Robins E, Turton D, Brady F, Luthra SK, Arstad E (2006) Synthesis and characterization of N-(2-chloro-5-methylthiophenyl)-N0-(3-methylthiophenyl)-N0-[11C] methylguanidine [11C] CNS 5161, a candidate PET tracer for functional imaging of NMDA receptors. J Label Compd Radiopharm 49:163–170

    CAS  Google Scholar 

Download references

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Daniele de Paula Faria, Rudi Dierckx & Erik de Vries

  2. Department of Neuroscience, University of Groningen, University Medical Center Groningen, A. Deusinglaan 1 9713 AV, Groningen, The Netherlands

    Daniele de Paula Faria & Sjef Copray

  3. Center of Nuclear Medicine, University of Sao Paulo, University of Sao Paulo Medical School, Sao Paulo, Brazil

    Daniele de Paula Faria & Carlos Buchpiguel

Authors
  1. Daniele de Paula Faria
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sjef Copray
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos Buchpiguel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rudi Dierckx
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Erik de Vries
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sjef Copray.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

de Paula Faria, D., Copray, S., Buchpiguel, C. et al. PET imaging in multiple sclerosis. J Neuroimmune Pharmacol 9, 468–482 (2014). https://doi.org/10.1007/s11481-014-9544-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-014-9544-2

Keywords

Search

Navigation