Positron emission tomography (PET) gives an opportunity to quantitate the expression of specific molecular targets in vivo and longitudinally in brain and thus enhances our possibilities to understand and follow up multiple sclerosis (MS)-related pathology. For successful PET imaging, one needs a relevant target molecule within the brain, to which a blood–brain barrier–penetrating specific radioligand will bind. 18-kDa translocator protein (TSPO)-binding radioligands have been used to detect activated microglial cells at different stages of MS, and remyelination has been measured using amyloid PET. Several PET ligands for the detection of other inflammatory targets, besides TSPO, have been developed but not yet been used for imaging MS patients. Finally, synaptic density evaluation has been successfully tested in human subjects and gives opportunities for the evaluation of the development of cortical and deep gray matter pathology in MS. This review will discuss PET imaging modalities relevant for MS today.
McDonaldWICompstonAEdanGet al. Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol2001; 50: 121–127.
2.
WattjesMPSteenwijkMDStangelM.MRI in the diagnosis and monitoring of multiple sclerosis: An update. Clin Neuroradiol2015; 25(Suppl. 2): 157–165.
3.
EnzingerCBarkhofFCiccarelliOet al. Nonconventional MRI and microstructural cerebral changes in multiple sclerosis. Nat Rev Neurol2015; 11: 676–686.
4.
WakeHMoorhouseAJNabekuraJ.Functions of microglia in the central nervous system—Beyond the immune response. Neuron Glia Biol2011; 7: 47–53.
5.
MosserCABaptistaSArnouxIet al. Microglia in CNS development: Shaping the brain for the future. Prog Neurobiol2017; 149–150: 1–20.
6.
NimmerjahnAKirchhoffFHelmchenF.Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science2005; 308: 1314–1318.
7.
BocheDPerryVHNicollJA.Review: Activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol2013; 39: 3–18.
8.
CherryJDOlschowkaJAO’BanionMK.Neuroinflammation and M2 microglia: The good, the bad, and the inflamed. J Neuroinflammation2014; 11: 98.
9.
LiuGJMiddletonRJHattyCRet al. The 18 kDa translocator protein, microglia and neuroinflammation. Brain Pathol2014; 24: 631–653.
10.
BeckersLOryDGericIet al. Increased expression of translocator protein (TSPO) marks pro-inflammatory microglia but does not predict neurodegeneration. Mol Imaging Biol2018; 20: 94–102.
11.
OwenDRMatthewsPM.Imaging brain microglial activation using positron emission tomography and translocator protein-specific radioligands. Int Rev Neurobiol2011; 101: 19–39.
12.
OwenDRYeoAJGunnRNet al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab2012; 32: 1–5.
13.
MizrahiRRusjanPMKennedyJet al. Translocator protein (18 kDa) polymorphism (rs6971) explains in-vivo brain binding affinity of the PET radioligand [(18)F]-FEPPA. J Cereb Blood Flow Metab2012; 32: 968–972.
14.
IkawaMLohithTGShresthaSet al. 11C-ER176, a radioligand for 18-kDa translocator protein, has adequate sensitivity to robustly image all three affinity genotypes in human brain. J Nucl Med2017; 58: 320–325.
15.
RissanenETuiskuJRokkaJet al. In vivo detection of diffuse inflammation in secondary progressive multiple sclerosis using PET imaging and the radioligand 11C-PK11195. J Nucl Med2014; 55: 939–944.
16.
RissanenETuiskuJVahlbergTet al. Microglial activation, white matter tract damage, and disability in MS. Neurol Neuroimmunol Neuroinflamm2018; 5: e443.
17.
AlamMMLeeJLeeSY.Recent progress in the development of TSPO PET ligands for neuroinflammation imaging in neurological diseases. Nucl Med Mol Imaging2017; 51: 283–296.
18.
AirasLNylundMRissanenE.Evaluation of microglial activation in multiple sclerosis patients using positron emission tomography. Front Neurol2018; 9: 181.
19.
AirasLRissanenERinneJ.Imaging of microglial activation in MS using PET: Research use and potential future clinical application. Mult Scler2017; 23: 496–504.
20.
ChiurchiùVvan der SteltMCentonzeDet al. The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases. Prog Neurobiol2018; 160: 82–100.
21.
SavonenkoAVMelnikovaTWangYet al. Cannabinoid CB2 receptors in a mouse model of Aβ amyloidosis: Immunohistochemical analysis and suitability as a PET biomarker of neuroinflammation. PLoS ONE2015; 10: e0129618.
22.
LourbopoulosAGrigoriadisNLagoudakiRet al. Administration of 2-arachidonoylglycerol ameliorates both acute and chronic experimental autoimmune encephalomyelitis. Brain Res2011; 1390: 126–141.
23.
Fernandez-SuarezDCelorrioMRiezu-BojJIet al. Monoacylglycerol lipase inhibitor JZL184 is neuroprotective and alters glial cell phenotype in the chronic MPTP mouse model. Neurobiol Aging2014; 35: 2603–2616.
WittingAWalterLWackerJet al. P2X7 receptors control 2-arachidonoylglycerol production by microglial cells. Proc Natl Acad Sci U S A2004; 101: 3214–3219.
26.
HosoyaTFukumotoDKakiuchiTet al. In vivo TSPO and cannabinoid receptor type 2 availability early in post-stroke neuroinflammation in rats: A positron emission tomography study. J Neuroinflammation2017; 14: 69.
27.
AhmadRPostnovABormansGet al. Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer’s disease. Eur J Nucl Med Mol Imaging2016; 43: 2219–2227.
28.
AhmadRKooleMEvensNet al. Whole-body biodistribution and radiation dosimetry of the cannabinoid type 2 receptor ligand [11C]-NE40 in healthy subjects. Mol Imaging Biol2013; 15: 384–390.
29.
BurnstockG.Purinergic signalling: Therapeutic developments. Front Pharmacol2017; 8: 661.
30.
FieldsRDBurnstockG.Purinergic signalling in neuron-glia interactions. Nat Rev Neurosci2006; 7: 423–436.
31.
ZimmermannHZebischMStraterN.Cellular function and molecular structure of ecto-nucleotidases. Purinergic Signal2012; 8: 437–502.
32.
Del PuertoAWandosellFGarridoJJ. Neuronal and glial purinergic receptors functions in neuron development and brain disease. Front Cell Neurosci2013; 7: 197.
33.
CekicCLindenJ.Purinergic regulation of the immune system. Nat Rev Immunol2016; 16: 177–192.
34.
OhtaASitkovskyM.Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature2001; 414: 916–920.
VuorimaaARissanenEAirasL.In vivo PET imaging of adenosine 2A receptors in neuroinflammatory and neurodegenerative disease. Contrast Media Mol Imaging2017; 2017: 6975841.
37.
MishinaMIshiwataKNaganawaMet al. Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson’s disease patients. PLoS ONE2011; 6: e17338.
38.
RissanenEVirtaJRPaavilainenTet al. Adenosine A2A receptors in secondary progressive multiple sclerosis: A [(11)C]TMSX brain PET study. J Cereb Blood Flow Metab2013; 33: 1394–1401.
39.
BarretOHannestadJValaCet al. Characterization in humans of 18F-MNI-444, a PET radiotracer for brain adenosine 2A receptors. J Nucl Med2015; 56: 586–591.
40.
MorescoRMToddeSBelloliSet al. In vivo imaging of adenosine A2A receptors in rat and primate brain using [11C]SCH442416. Eur J Nucl Med Mol Imaging2005; 32: 405–413.
41.
GrachevIDDoderMBrooksDJet al. Quantitative in vivo imaging of adenosine A2A receptors in the human brain using 11C-SCH442416 PET: A pilot study. J Diagn Imaging Ther2014; 1: 1–19.
42.
KhanapurSvan WaardeADierckxRAet al. Preclinical evaluation and quantification of (18)F-fluoroethyl and (18)F-fluoropropyl analogs of SCH442416 as radioligands for PET imaging of the adenosine A2A receptor in rat brain. J Nucl Med2017; 58: 466–472.
43.
ZhouXKhanapurSde JongJRet al. In vivo evaluation of [(11)C]preladenant positron emission tomography for quantification of adenosine A2A receptors in the rat brain. J Cereb Blood Flow Metab2017; 37: 577–589.
44.
ZhouXBoellaardRIshiwataKet al. In vivo evaluation of (11)C-preladenant for PET imaging of adenosine A2A receptors in the conscious monkey. J Nucl Med2017; 58: 762–767.
45.
SakataMIshibashiKImaiMet al. Initial evaluation of an adenosine A2A receptor ligand, (11)C-preladenant, in healthy human subjects. J Nucl Med2017; 58: 1464–1470.
46.
IllesPKhanTMRubiniP.Neuronal P2X7 receptors revisited: Do they really exist?J Neurosci2017; 37: 7049–7062.
47.
Miras-PortugalMTSebastian-SerranoAde Diego GarciaLet al. Neuronal P2X7 receptor: Involvement in neuronal physiology and pathology. J Neurosci2017; 37: 7063–7072.
48.
MonifMReidCAPowellKLet al. The P2X7 receptor drives microglial activation and proliferation: A trophic role for P2X7R pore. J Neurosci2009; 29: 3781–3791.
49.
FranceschiniACapeceMChiozziPet al. The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB J2015; 29: 2450–2461.
50.
MariathasanSWeissDSNewtonKet al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature2006; 440: 228–232.
51.
BeainoWJanssenBKooijGet al. Purinergic receptors P2Y12R and P2X7R: Potential targets for PET imaging of microglia phenotypes in multiple sclerosis. J Neuroinflammation2017; 14: 259.
52.
YiangouYFacerPDurrenbergerPet al.COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol2006; 6: 12.
53.
AmadioSParisiCPirasEet al. Modulation of P2X7 receptor during inflammation in multiple sclerosis. Front Immunol2017; 8: 1529.
54.
JanssenBVugtsDJFunkeUet al. Synthesis and initial preclinical evaluation of the P2X7 receptor antagonist [(1)(1)C]A-740003 as a novel tracer of neuroinflammation. J Labelled Comp Radiopharm2014; 57: 509–516.
55.
FantoniERDal BenDFalzoniSet al. Design, synthesis and evaluation in an LPS rodent model of neuroinflammation of a novel 18F-labelled PET tracer targeting P2X7. EJNMMI Res2017; 7: 31.
56.
OryDCelenSGijsbersRet al. Preclinical evaluation of a P2X7 receptor-selective radiotracer: PET studies in a rat model with local overexpression of the human P2X7 receptor and in nonhuman primates. J Nucl Med2016; 57: 1436–1441.
57.
TerritoPRMeyerJAPetersJSet al. Characterization of 11C-GSK1482160 for targeting the P2X7 receptor as a biomarker for neuroinflammation. J Nucl Med2017; 58: 458–465.
58.
HanJLiuHLiuCet al. Pharmacologic characterizations of a P2X7 receptor-specific radioligand, [11C]GSK1482160 for neuroinflammatory response. Nucl Med Commun2017; 38: 372–382.
59.
JanssenBVugtsDJWilkinsonSMet al. Identification of the allosteric P2X7 receptor antagonist [(11)C]SMW139 as a PET tracer of microglial activation. Sci Rep2018; 8: 6580.
60.
INMIND. Imaging of neuroinflammation in neurodegenerative diseases (Final Report Summary). Münster: Westfälische Wilhelms-Universität Münster, 2017.
61.
GaoMWangMGlick-WilsonBEet al. Synthesis and preliminary biological evaluation of a novel P2X7R radioligand [18F]IUR-1601. Bioorg Med Chem Lett2018; 28: 1603–1609.
62.
FerrariDPizziraniCAdinolfiEet al. The P2X7 receptor: A key player in IL-1 processing and release. J Immunol2006; 176: 3877–3883.
63.
XuXJBoumechacheMRobinsonLEet al. Splice variants of the P2X7 receptor reveal differential agonist dependence and functional coupling with pannexin-1. J Cell Sci2012; 125: 3776–3789.
64.
MooreCSAseARKinsaraAet al. P2Y12 expression and function in alternatively activated human microglia. Neurol Neuroimmunol Neuroinflamm2015; 2: e80.
65.
AmadioSParisiCMontilliCet al. P2Y(12) receptor on the verge of a neuroinflammatory breakdown. Mediators Inflamm2014; 2014: 975849.
66.
AmadioSMontilliCMagliozziRet al. P2Y12 receptor protein in cortical gray matter lesions in multiple sclerosis. Cereb Cortex2010; 20: 1263–1273.
67.
MildnerAHuangHRadkeJet al. P2Y12 receptor is expressed on human microglia under physiological conditions throughout development and is sensitive to neuroinflammatory diseases. Glia2017; 65: 375–387.
68.
Matias-GuiuJAOreja-GuevaraCCabrera-MartinMNet al. Amyloid proteins and their role in multiple sclerosis. Considerations in the use of amyloid-PET imaging. Front Neurol2016; 7: 53.
69.
StankoffBFreemanLAigrotMSet al. Imaging central nervous system myelin by positron emission tomography in multiple sclerosis using [methyl-11C]-2-(4’-methylaminophenyl)- 6-hydroxybenzothiazole. Ann Neurol2011; 69: 673–680.
70.
BodiniBVeroneseMGarcia-LorenzoDet al. Dynamic imaging of individual remyelination profiles in multiple sclerosis. Ann Neurol. Epub ahead of print 18 February 2016. DOI: 10.1002/ana.24620.
71.
MallikSSamsonRSWheeler-KingshottCAet al. Imaging outcomes for trials of remyelination in multiple sclerosis. J Neurol Neurosurg Psychiatry2014; 85: 1396–1404.
72.
Faria DdePCopraySSijbesmaJWet al. 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 Imaging2014; 41: 995–1003.
73.
ZeydanBLoweVJSchwarzCGet al. Pittsburgh compound-B PET white matter imaging and cognitive function in late multiple sclerosis. Mult Scler2017; 24: 739–749.
74.
WuCZhuJBaeslackJet al. Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord. Ann Neurol2013; 74: 688–698.
75.
BrugarolasPSanchez-RodriguezJETsaiHMet al. Development of a PET radioligand for potassium channels to image CNS demyelination. Sci Rep2018; 8: 607.
76.
JurgensTJafariMKreutzfeldtMet al. Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis. Brain2016; 139: 39–46.
77.
FinnemaSJNabulsiNBMercierJet al. Kinetic evaluation and test-retest reproducibility of [(11)C]UCB-J, a novel radioligand for positron emission tomography imaging of synaptic vesicle glycoprotein 2A in humans. J Cereb Blood Flow Metab. Epub ahead of print 1 January 2017. DOI: 10.1177/0271678x17724947.
78.
FinnemaSJNabulsiNBEidTet al. Imaging synaptic density in the living human brain. Sci Transl Med2016; 8: 348ra396.
79.
KawamataJShimohamaS.Stimulating nicotinic receptors trigger multiple pathways attenuating cytotoxicity in models of Alzheimer’s and Parkinson’s diseases. J Alzheimers Dis2011; 24(Suppl. 2): 95–109.
80.
MartinASzczupakBGomez-VallejoVet al. In vivo PET imaging of the α4β2 nicotinic acetylcholine receptor as a marker for brain inflammation after cerebral ischemia. J Neurosci2015; 35: 5998–6009.
81.
PatelHMcIntireJRyanSet al. Anti-inflammatory effects of astroglial α7 nicotinic acetylcholine receptors are mediated by inhibition of the NF-κB pathway and activation of the Nrf2 pathway. J Neuroinflammation2017; 14: 192.
82.
O’NeillMJMurrayTKLakicsVet al. The role of neuronal nicotinic acetylcholine receptors in acute and chronic neurodegeneration. Curr Drug Targets CNS Neurol Disord2002; 1: 399–411.
83.
SchmaljohannJMinneropMKarwathPet al. Imaging of central nAChReceptors with 2-[18F]F-A85380: Optimized synthesis and in vitro evaluation in Alzheimer’s disease. Appl Radiat Isot2004; 61: 1235–1240.
84.
SchmaljohannJGundischDMinneropMet al. In vitro evaluation of nicotinic acetylcholine receptors with 2-[18F]F-A85380 in Parkinson’s disease. Nucl Med Biol2006; 33: 305–309.
85.
SabriOBeckerG-AMeyerPMet al. First-in-human PET quantification study of cerebral α4β2* nicotinic acetylcholine receptors using the novel specific radioligand (-)-[(18)F]Flubatine. NeuroImage2015; 118: 199–208.
86.
KuwabaraHGaoYStabinMet al. Imaging α4β2 nicotinic acetylcholine receptors (nAChRs) in baboons with [18F]XTRA, a radioligand with improved specific binding in extra-thalamic regions. Mol Imaging Biol2017; 19: 280–288.
87.
CoughlinJMSlaniaSDuYet al. 18F-XTRA PET for enhanced imaging of the extrathalamic α4β2 nicotinic acetylcholine receptor. J Nucl Med. Epub ahead of print 1 March 2018. DOI: 10.2967/jnumed.117.205492.
88.
BetthauserTJHillmerATLaoPJet al. Human biodistribution and dosimetry of [18F]nifene, an α4β2* nicotinic acetylcholine receptor PET tracer. Nucl Med Biol2017; 55: 7–11.
89.
MukherjeeJLaoPJBetthauserTJet al. Human brain imaging of nicotinic acetylcholine α4β2* receptors using [(18) F]Nifene: Selectivity, functional activity, toxicity, aging effects, gender effects, and extrathalamic pathways. J Comp Neurol2018; 526: 80–95.
90.
WongDFKuwabaraHPomperMet al. Human brain imaging of α7 nAChR with [(18)F]ASEM: A new PET radiotracer for neuropsychiatry and determination of drug occupancy. Mol Imaging Biol2014; 16: 730–738.
91.
HillmerATLiSZhengMQet al. PET imaging of α7 nicotinic acetylcholine receptors: A comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans. Eur J Nucl Med Mol Imaging2017; 44: 1042–1050.
92.
AïdSBosettiF.Targeting cyclooxygenases-1 and -2 in neuroinflammation: Therapeutic implications. Biochimie2011; 93: 46–51.
93.
OhnishiASendaMYamaneTet al. Human whole-body biodistribution and dosimetry of a new PET tracer, [11C]ketoprofen methyl ester, for imagings of neuroinflammation. Nucl Med Biol2014; 41: 594–599.
94.
ShukuriMMawatariAOhnoMet al. Detection of cyclooxygenase-1 in activated microglia during amyloid plaque progression: PET studies in Alzheimer’s disease model mice. J Nucl Med2016; 57: 291–296.
95.
OhnishiASendaMYamaneTet al. Exploratory human PET study of the effectiveness of (11)C-ketoprofen methyl ester, a potential biomarker of neuroinflammatory processes in Alzheimer’s disease. Nucl Med Biol2016; 43: 438–444.
96.
OhlKTenbrockKKippM.Oxidative stress in multiple sclerosis: Central and peripheral mode of action. Exp Neurol2016; 277: 58–67.
PaganiMNobiliFMorbelliSet al. Early identification of MCI converting to AD: A FDG PET study. Eur J Nucl Med Mol Imaging2017; 44: 2042–2052.
99.
WebsterJMMortonCAJohnsonBFet al. Functional imaging of oxidative stress with a novel PET imaging agent, 18F-5-fluoro-L-aminosuberic acid. J Nucl Med2014; 55: 657–664.
100.
OkamuraTOkadaMKikuchiTet al. A 11C-labeled 1,4-dihydroquinoline derivative as a potential PET tracer for imaging of redox status in mouse brain. J Cereb Blood Flow Metab2015; 35: 1930–1936.
101.
TsukadaHNishiyamaSFukumotoDet al. Novel PET probes 18F-BCPP-EF and 18F-BCPP-BF for mitochondrial complex I: A PET study in comparison with 18F-BMS-747158-02 in rat brain. J Nucl Med2014; 55: 473–480.
102.
TsukadaHOhbaHKanazawaMet al. Evaluation of 18F-BCPP-EF for mitochondrial complex 1 imaging in the brain of conscious monkeys using PET. Eur J Nucl Med Mol Imaging2014; 41: 755–763.
103.
IkawaMOkazawaHKudoTet al. Evaluation of striatal oxidative stress in patients with Parkinson’s disease using [62Cu]ATSM PET. Nucl Med Biol2011; 38: 945–951.
104.
IkawaMOkazawaHTsujikawaTet al. Increased oxidative stress is related to disease severity in the ALS motor cortex: A PET study. Neurology2015; 84: 2033–2039.
105.
HerreroPLaforestRShoghiKet al. Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans. J Nucl Med2012; 53: 994–1001.
HouCHsiehCJLiSet al. Development of a positron emission tomography radiotracer for imaging elevated levels of superoxide in neuroinflammation. ACS Chem Neurosci2018; 9: 578–586.
108.
Puig-KrogerASierra-FilardiEDominguez-SotoAet al. Folate receptor beta is expressed by tumor-associated macrophages and constitutes a marker for M2 anti-inflammatory/regulatory macrophages. Cancer Res2009; 69: 9395–9403.
109.
FarkasRSiwowskaKAmetameySMet al. 64Cu- and 68Ga-based PET imaging of folate receptor-positive tumors: Development and evaluation of an albumin-binding NODAGA-folate. Mol Pharmaceut2016; 13: 1979–1987.
110.
ChenQMengXMcQuadePet al. Synthesis and preclinical evaluation of folate-NOTA-Al(18)F for PET imaging of folate-receptor-positive tumors. Mol Pharm2016; 13: 1520–1527.
111.
ChenQMengXMcQuadePet al. Folate-PEG-NOTA-Al(18)F: A new folate based radiotracer for PET imaging of folate receptor-positive tumors. Mol Pharm2017; 14: 4353–4361.
112.
GentYYWeijersKMolthoffCFet al. Evaluation of the novel folate receptor ligand [18F]fluoro-PEG-folate for macrophage targeting in a rat model of arthritis. Arthritis Res Ther2013; 15: R37.
113.
ChandrupatlaDJansenGVosRet al. In-vivo monitoring of anti-folate therapy in arthritic rats using [18F]fluoro-PEG-folate and positron emission tomography. Arthritis Res Ther2017; 19: 114.
114.
BrandCLongoVAGroaningMet al. Development of a new folate-derived Ga-68-based PET imaging agent. Mol Imaging Biol2017; 19: 754–761.
115.
KonneckeHBechmannI.The role of microglia and matrix metalloproteinases involvement in neuroinflammation and gliomas. Clin Dev Immunol2013; 2013: 914104.
116.
WagnerSBreyholzHJHoltkeCet al. A new 18F-labelled derivative of the MMP inhibitor CGS 27023A for PET: Radiosynthesis and initial small-animal PET studies. Appl Radiat Isot2009; 67: 606–610.
117.
ZinnhardtBVielTWachsmuthLet al. Multimodal imaging reveals temporal and spatial microglia and matrix metalloproteinase activity after experimental stroke. J Cereb Blood Flow Metab2015; 35: 1711–1721.
118.
ZinnhardtBPigeonHThezeBet al. Combined PET imaging of the inflammatory tumor microenvironment identifies margins of unique radiotracer uptake. Cancer Res2017; 77: 1831–1841.
119.
PalumboS.Pathogenesis and progression of multiple sclerosis: The role of arachidonic acid-mediated neuroinflammation. In: ZagonISMcLaughlinPJ (eds) Multiple sclerosis: Perspectives in treatment and pathogenesis. Brisbane, QLD, Australia: Codon Publications, 2017, pp. 111–123.
120.
JiBKumataKOnoeHet al. Assessment of radioligands for PET imaging of cyclooxygenase-2 in an ischemic neuronal injury model. Brain Res2013; 1533: 152–162.
121.
de VriesEFDoorduinJDierckxRAet al. Evaluation of [(11)C]rofecoxib as PET tracer for cyclooxygenase 2 overexpression in rat models of inflammation. Nucl Med Biol2008; 35: 35–42.
122.
KaunznerUWKangYMonohanEet al. Reduction of PK11195 uptake observed in multiple sclerosis lesions after natalizumab initiation. Mult Scler Relat Disord2017; 15: 27–33.
123.
SucksdorffMRissanenETuiskuJet al. Evaluation of the effect of fingolimod treatment on microglial activation using serial PET imaging in multiple sclerosis. J Nucl Med2017; 58: 1646–1651.
124.
RatchfordJNEndresCJHammoudDAet al. Decreased microglial activation in MS patients treated with glatiramer acetate. J Neurol2012; 259: 1199–1205.
