Epilepsy is a complex neurological disorder characterized by recurrent, unprovoked seizures. Emerging evidence indicates that the sphingosine-1-phosphate receptor (S1PR) family plays a significant and multifaceted role in the pathological processes underlying epileptogenesis and blood–brain barrier integrity. This review comprehensively explores the intricate role of S1PR signaling in epilepsy, with a particular focus on the integration of neuroimaging findings. In this review, we summarize recent advances in Positron Emission Tomography techniques that offer invaluable insights into S1PR-related pathophysiological changes in the epileptic brain. Furthermore, we discuss the substantial potential of S1PRs as novel therapeutic targets. By integrating these cutting-edge neuroimaging biomarkers with our evolving understanding of the underlying molecular pathways, this review aims to highlight promising new diagnostic tools and innovative treatment strategies for epilepsy.
ThijsRDSurgesRO'BrienTJ, et al.Epilepsy in adults. Lancet. 2019;393(10172):689-701. doi:10.1016/S0140-6736(18)32596-0
2.
LoscherWPotschkaHSisodiyaSM, et al.Drug resistance in epilepsy: Clinical impact, potential mechanisms, and new innovative treatment options. Pharmacol Rev. 2020;72(3):606-638. doi:10.1124/pr.120.019539
3.
WangLKongQLengX, et al.The sphingosine-1-phosphate signaling pathway (sphingosine-1-phosphate and its receptor, sphingosine kinase) and epilepsy. Epilepsia Open. 2025;10(1):55-73. doi:10.1002/epi4.13112
4.
McGinleyMPCohenJA. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions. Lancet. 2021;398(10306):1184-1194. doi:10.1016/S0140-6736(21)00244-0
5.
GrassiSMauriLPrioniS, et al.Sphingosine 1-phosphate receptors and metabolic enzymes as druggable targets for brain diseases. Front Pharmacol. 2019;10:807. doi:10.3389/fphar.2019.00807
6.
PonisioMRZempelJMDayBK, et al.The role of SPECT and PET in epilepsy. Am J Roentgenol. 2021;216(3):759-768. doi:10.2214/AJR.20.23336
7.
CollaboratorsGBDE. Global, regional, and national burden of epilepsy, 1990-2021: A systematic analysis for the Global Burden of Disease Study 2021. Lancet Public Health. 2025;10(3):e203-e227. doi:10.1016/S2468-2667(24)00302-5
8.
BeghiE. The epidemiology of epilepsy. Neuroepidemiology. 2020;54(2):185-191. doi:10.1159/000503831
9.
SinghGSanderJW. The global burden of epilepsy report: Implications for low- and middle-income countries. Epilepsy Behav. 2020;105:106949. doi:10.1016/j.yebeh.2020.106949
10.
KeezerMRSisodiyaSMSanderJW. Comorbidities of epilepsy: Current concepts and future perspectives. Lancet Neurol. 2016;15(1):106-115. doi:10.1016/S1474-4422(15)00225-2
11.
OpertoFFPastorinoGMGViggianoA, et al.Epilepsy and cognitive impairment in childhood and adolescence: A mini-review. Curr Neuropharmacol. 2023;21(8):1646-1665. doi:10.2174/1570159X20666220706102708
12.
MayorRGunnSReuberM, et al.Experiences of stigma in people with epilepsy: A meta-synthesis of qualitative evidence. Seizure. 2022;94:142-160. doi:10.1016/j.seizure.2021.11.021
13.
FriedmanD. Sudden unexpected death in epilepsy. Curr Opin Neurol. 2022;35(2):181-188. doi:10.1097/WCO.0000000000001034
14.
KalilaniLSunXPelgrimsB, et al.The epidemiology of drug-resistant epilepsy: A systematic review and meta-analysis. Epilepsia. 2018;59(12):2179-2193. doi:10.1111/epi.14596
15.
PeruccaEPeruccaPWhiteHS, et al.Drug resistance in epilepsy. Lancet Neurol. 2023;22(8):723-734. doi:10.1016/S1474-4422(23)00151-5
16.
SanzPRubioTGarcia-GimenoMA. Neuroinflammation and epilepsy: From pathophysiology to therapies based on repurposing drugs. Int J Mol Sci. 2024;25(8):20240409. doi:10.3390/ijms25084161
17.
Soltani KhaboushanAYazdanpanahNRezaeiN. Neuroinflammation and proinflammatory cytokines in epileptogenesis. Mol Neurobiol. 2022;59(3):1724-1743. doi:10.1007/s12035-022-02725-6
18.
Aguilar-CastilloMJCabezudo-GarciaPGarcia-MartinG, et al.A systematic review of the predictive and diagnostic uses of neuroinflammation biomarkers for epileptogenesis. Int J Mol Sci. 2024;25(12):20240612. doi:10.3390/ijms25126488
19.
LiWWuJZengY, et al.Neuroinflammation in epileptogenesis: From pathophysiology to therapeutic strategies. Front Immunol. 2023;14:1269241. doi:10.3389/fimmu.2023.1269241
20.
DevinskyOVezzaniANajjarS, et al.Glia and epilepsy: Excitability and inflammation. Trends Neurosci. 2013;36(3):174-184. doi:10.1016/j.tins.2012.11.008
21.
RavizzaTVezzaniA. Pharmacological targeting of brain inflammation in epilepsy: Therapeutic perspectives from experimental and clinical studies. Epilepsia Open. 2018;3(Suppl Suppl 2):133-142. doi:10.1002/epi4.12242
22.
MarosoMBalossoSRavizzaT, et al.Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med. 2010;16(4):413-419. doi:10.1038/nm.2127
23.
HuangNHuangYDengZ, et al.Blood-brain barrier dysfunction in epilepsy: Mechanisms, therapeutic strategies and future orientation (Review). Int J Mol Med. 2025;56(3):20250704. doi:10.3892/ijmm.2025.5577
24.
ShiJXieJLiZ, et al.The role of neuroinflammation and network anomalies in drug-resistant epilepsy. Neurosci Bull. 2025;41(5):881-905. doi:10.1007/s12264-025-01348-w
25.
PatelDCTewariBPChaunsaliL, et al.Neuron-glia interactions in the pathophysiology of epilepsy. Nat Rev Neurosci. 2019;20(5):282-297. doi:10.1038/s41583-019-0126-4
26.
TringaliCGiussaniP. Ceramide and sphingosine-1-phosphate in neurodegenerative disorders and their potential involvement in therapy. Int J Mol Sci. 2022;23(14):7806. doi:10.3390/ijms23147806
27.
Martinez-GardeazabalJPereira-CasteloGMoreno-RodriguezM, et al.Sphingosine 1-phosphate receptor subtype 1 (S1P(1)) activity in the course of Alzheimer's disease. Neurobiol Dis. 2024;202:106713. doi:10.1016/j.nbd.2024.106713
28.
SchwedhelmEEnglischCNiemannL, et al.Sphingosine-1-phosphate, motor severity, and progression in Parkinson's disease (MARK-PD). Mov Disord. 2021;36(9):2178-2182. doi:10.1002/mds.28652
29.
Di PardoAAmicoEBasitA, et al.Defective sphingosine-1-phosphate metabolism is a druggable target in Huntington's disease. Sci Rep. 2017;7(1):5280. doi:10.1038/s41598-017-05709-y
30.
van Echten-DeckertG. The role of sphingosine 1-phosphate metabolism in brain health and disease. Pharmacol Ther. 2023;244:108381. doi:10.1016/j.pharmthera.2023.108381
ChenHWangJZhangC, et al.Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases. Biomed Pharmacother. 2022;153:113341. doi:10.1016/j.biopha.2022.113341
35.
GhasemiRDargahiLAhmadianiA. Integrated sphingosine-1 phosphate signaling in the central nervous system: From physiological equilibrium to pathological damage. Pharmacol Res. 2016;104:156‐164. doi:10.1016/j.phrs.2015.11.006
36.
PitschJKuehnJCGnatkovskyV, et al.Anti-epileptogenic and anti-convulsive effects of fingolimod in experimental temporal lobe epilepsy. Mol Neurobiol. 2019;56(3):1825‐1840. doi:10.1007/s12035-018-1181-y
YangLXYaoYYYangJR, et al.Sphingosine 1-phosphate receptor 1 regulates blood-brain barrier permeability in epileptic mice. Neural Regen Res. 2023;18(8):1763‐1769. doi:10.4103/1673-5374.360263
39.
GolMGhorbanianDHassanzadehS, et al.Fingolimod enhances myelin repair of hippocampus in pentylenetetrazol-induced kindling model. Eur J Pharm Sci. 2017;96:72‐83. doi:10.1016/j.ejps.2016.09.016
40.
GaoFLiuYLiX, et al.Fingolimod (FTY720) inhibits neuroinflammation and attenuates spontaneous convulsions in lithium-pilocarpine induced status epilepticus in rat model. Pharmacol Biochem Behav. 2012;103(2):187‐196. doi:10.1016/j.pbb.2012.08.025
41.
LeoACitraroRAmodioN, et al.Fingolimod exerts only temporary antiepileptogenic effects but longer-lasting positive effects on behavior in the WAG/Rij rat absence epilepsy model. Neurotherapeutics. 2017;14(4):1134‐1147. doi:10.1007/s13311-017-0550-y
42.
JainARaltaABatraG, et al.SEW2871 Reduces seizures via the sphingosine 1-phosphate receptor-1 pathway in the pentylenetetrazol and phenobarbitone kindling model of drug-refractory epilepsy. Clin Exp Pharmacol Physiol. 2024;51(3):e13839. doi:10.1111/1440-1681.13839
43.
LeoACitraroRMarraR, et al.The sphingosine 1-phosphate signaling pathway in epilepsy: A possible role for the immunomodulator drug fingolimod in epilepsy treatment. CNS Neurol Disord Drug Targets. 2017;16(3):311‐325. doi:10.2174/1871527315666161104163031
44.
YounYSungIKLeeIG. The role of cytokines in seizures: Interleukin (IL)-1beta, IL-1Ra, IL-8, and IL-10. Korean J Pediatr. 2013;56(7):271‐274. doi:10.3345/kjp.2013.56.7.271
45.
VezzaniAFrenchJBartfaiT, et al.The role of inflammation in epilepsy. Nat Rev Neurol. 2011;7(1):31‐40. doi:10.1038/nrneurol.2010.178
LeeDHJeonBTJeongEA, et al.Altered expression of sphingosine kinase 1 and sphingosine-1-phosphate receptor 1 in mouse hippocampus after kainic acid treatment. Biochem Biophys Res Commun. 2010;393(3):476‐480. doi:10.1016/j.bbrc.2010.02.027
48.
WuDChenQChenX, et al.The blood-brain barrier: Structure, regulation, and drug delivery. Signal Transduct Target Ther. 2023;8(1):217. doi:10.1038/s41392-023-01481-w
49.
van VlietEAAronicaEGorterJA. Blood-brain barrier dysfunction, seizures and epilepsy. Semin Cell Dev Biol. 2015;38:26‐34. doi:10.1016/j.semcdb.2014.10.003
50.
ChengHMenYAnY, et al.Overexpression of endothelial S1pr2 promotes blood-brain barrier disruption via JNK/c-Jun/MMP-9 pathway after traumatic brain injury in both in vivo and in vitro models. Front Pharmacol. 2024;15:1448570. doi:10.3389/fphar.2024.1448570
51.
YanagidaKLiuCHFaracoG, et al.Size-selective opening of the blood-brain barrier by targeting endothelial sphingosine 1-phosphate receptor 1. Proc Natl Acad Sci U S A. 2017;114(17):4531‐4536. doi:10.1073/pnas.1618659114
52.
GaengelKNiaudetCHagikuraK, et al.The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev Cell. 2012;23(3):587‐599. doi:10.1016/j.devcel.2012.08.005
53.
PitkanenALukasiukKDudekFE, et al.Epileptogenesis. Cold Spring Harb Perspect Med. 2015;5(10):a022822. doi:10.1101/cshperspect.a022822
54.
SumadewiKTHarkitasariSTjandraDC. Biomolecular mechanisms of epileptic seizures and epilepsy: A review. Acta Epileptol. 2023;5(1):28. doi:10.1186/s42494-023-00137-0
55.
ReddySDYounusISridharV, et al.Neuroimaging biomarkers of experimental epileptogenesis and refractory epilepsy. Int J Mol Sci. 2019;20(1):220. doi:10.3390/ijms20010220
56.
SidhuMKDuncanJSSanderJW. Neuroimaging in epilepsy. Curr Opin Neurol. 2018;31(4):371‐378. doi:10.1097/WCO.0000000000000568
57.
Hernandez-MartinNPozo-CabanellIFernandez de la RosaR, et al.Preclinical PET imaging in epileptogenesis: Towards identification of biomarkers and therapeutic targets. EJNMMI Res. 2025;15(1):43. doi:10.1186/s13550-025-01237-3
58.
BullmoreESpornsO. Complex brain networks: Graph theoretical analysis of structural and functional systems. Nat Rev Neurosci. 2009;10(3):186‐198. doi:10.1038/nrn2575
59.
DuynJHKoretskyAP. Novel frontiers in ultra-structural and molecular MRI of the brain. Curr Opin Neurol. 2011;24(4):386‐393. doi:10.1097/WCO.0b013e328348972a
60.
RuberTElgerDBEC. MRI in epilepsy: Clinical standard and evolution. Curr Opin Neurol. 2018;31(2):223‐231. doi:10.1097/WCO.0000000000000539
61.
XiaoFCaciagliLWandschneiderB, et al.Identification of different MRI atrophy progression trajectories in epilepsy by subtype and stage inference. Brain. 2023;146(11):4702‐4716. doi:10.1093/brain/awad284
62.
BernhardtBCBernasconiALiuM, et al.The spectrum of structural and functional imaging abnormalities in temporal lobe epilepsy. Ann Neurol. 2016;80(1):142‐153. doi:10.1002/ana.24691
63.
BonilhaLNeslandTMartzGU, et al.Medial temporal lobe epilepsy is associated with neuronal fibre loss and paradoxical increase in structural connectivity of limbic structures. J Neurol Neurosurg Psychiatry. 2012;83(9):903‐909. doi:10.1136/jnnp-2012-302476
64.
TaschECendesFLiLM, et al.Neuroimaging evidence of progressive neuronal loss and dysfunction in temporal lobe epilepsy. Ann Neurol. 1999;45(5):568‐576. doi:10.1002/1531-8249(199905)45:5 < 568::aid-ana4 > 3.0.co;2-p
65.
HaufMJannKSchindlerK, et al.Localizing seizure-onset zones in presurgical evaluation of drug-resistant epilepsy by electroencephalography/fMRI: Effectiveness of alternative thresholding strategies. AJNR Am J Neuroradiol. 2012;33(9):1818‐1824. doi:10.3174/ajnr.A3052
66.
BergerACohenNFahoumF, et al.Preoperative localization of seizure onset zones by magnetic source imaging, EEG-correlated functional MRI, and their combination. J Neurosurg. 2021;134(3):1037‐1043. doi:10.3171/2020.3.JNS192794
67.
MatsuuraKMaedaMOkamotoK, et al.Usefulness of arterial spin-labeling images in periictal state diagnosis of epilepsy. J Neurol Sci. 2015;359(1-2):424‐429. doi:10.1016/j.jns.2015.10.009
68.
KojanMGajdosMRihaP, et al.Arterial spin labeling is a useful MRI method for presurgical evaluation in MRI-negative focal epilepsy. Brain Topogr. 2021;34(4):504‐510. doi:10.1007/s10548-021-00833-5
69.
WenJFGuoXWCaoXY, et al.A PET imaging study of the brain changes of glucose metabolism in patients with temporal lobe epilepsy and depressive disorder. BMC Med Imaging. 2021;21(1):33. doi:10.1186/s12880-021-00547-x
70.
TheodoreWHHaslerGGiovacchiniG, et al.Reduced hippocampal 5HT1A PET receptor binding and depression in temporal lobe epilepsy. Epilepsia. 2007;48(8):1526‐1530. doi:10.1111/j.1528-1167.2007.01089.x
71.
PonisioMRZempelJMDayBK, et al.The role of SPECT and PET in epilepsy. AJR Am J Roentgenol. 2021;216(3):759‐768. doi:10.2214/AJR.20.23336
72.
LiewCJLimYMBonwetschR, et al.18F-FCWAY and 18F-FDG PET in MRI-negative temporal lobe epilepsy. Epilepsia. 2009;50(2):234‐239. doi:10.1111/j.1528-1167.2008.01789.x
73.
Montaz-RossetMSSchollyJVoulleminotP, et al.Comparison of functional deficit zone defined by FDG PET to the epileptogenic zones described in stereo-electroencephalograph in drug-resistant epileptic patients treated by surgery. Clin Nucl Med. 2019;44(7):526‐531. doi:10.1097/RLU.0000000000002615
74.
KilmerJRodrigoSPetrescuAM, et al.TSPO-PET in pre-surgical evaluations: Correlation of neuroinflammation and SEEG epileptogenicity mapping in drug-resistant focal epilepsy. Epilepsia. 2025;66(2):430‐443. doi:10.1111/epi.18182
75.
HuJCuiBWangZ, et al.Transcriptomic and glucose metabolism of connectome dynamics variability in temporal lobe epilepsy revealed by simultaneous PET-fMRI. Neurobiol Dis. 2025;212:106967. doi:10.1016/j.nbd.2025.106967
GoodmanAMSzaflarskiJP. Recent advances in neuroimaging of epilepsy. Neurotherapeutics. 2021;18(2):811‐826. doi:10.1007/s13311-021-01049-y
78.
MeikleSRSossiVRoncaliE, et al.Quantitative PET in the 2020s: A roadmap. Phys Med Biol. 2021;66(6):06RM01.. doi:10.1088/1361-6560/abd4f7
79.
NerellaSGSinghPSanamT, et al.PET Molecular imaging in drug development: The imaging and chemistry perspective. Front Med (Lausanne). 2022;9:812270. doi:10.3389/fmed.2022.812270
80.
KoeppMJArstadEBankstahlJP, et al.Neuroinflammation imaging markers for epileptogenesis. Epilepsia. 2017;58(Suppl 3):11‐19. doi:10.1111/epi.13778
81.
ZhangLHuKShaoT, et al.Recent developments on PET radiotracers for TSPO and their applications in neuroimaging. Acta Pharm Sin B. 2021;11(2):373‐393. doi:10.1016/j.apsb.2020.08.006
82.
DicksteinLPLiowJSAustermuehleA, et al.Neuroinflammation in neocortical epilepsy measured by PET imaging of translocator protein. Epilepsia. 2019;60(6):1248‐1254. doi:10.1111/epi.15967
83.
GershenLDZanotti-FregonaraPDustinIH, et al.Neuroinflammation in temporal lobe epilepsy measured using positron emission tomographic imaging of translocator protein. JAMA Neurol. 2015;72(8):882‐888. doi:10.1001/jamaneurol.2015.0941
84.
BogdanovicRMSyvanenSMichlerC, et al.(R)-[11C]PK11195 brain uptake as a biomarker of inflammation and antiepileptic drug resistance: Evaluation in a rat epilepsy model. Neuropharmacology. 2014;85:104‐112. doi:10.1016/j.neuropharm.2014.05.002
85.
KanekoKIIrieSMawatariA, et al.[(18)F]DPA-714 PET imaging for the quantitative evaluation of early spatiotemporal changes of neuroinflammation in rat brain following status epilepticus. Eur J Nucl Med Mol Imaging. 2022;49(7):2265‐2275. doi:10.1007/s00259-022-05719-7
86.
Kagitani-ShimonoKKatoHKuwayamaR, et al.Clinical evaluation of neuroinflammation in child-onset focal epilepsy: A translocator protein PET study. J Neuroinflammation. 2021;18(1):8. doi:10.1186/s12974-020-02055-1
87.
NotterTCoughlinJMGschwindT, et al.Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia. Mol Psychiatry. 2018;23(2):323‐334. doi:10.1038/mp.2016.248
88.
OwenDRYeoAJGunnRN, 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):1‐5. doi:10.1038/jcbfm.2011.147
89.
WerryELBrightFMPiguetO, et al.Recent developments in TSPO PET imaging as a biomarker of neuroinflammation in neurodegenerative disorders. Int J Mol Sci. 2019;20(13):20190628. doi:10.3390/ijms20133161
90.
ChauveauFWinkelerAChalonS, et al.PET imaging of neuroinflammation: Any credible alternatives to TSPO yet?. Mol Psychiatry. 2025;30(1):213‐228. doi:10.1038/s41380-024-02656-9
91.
Jimenez-PachecoAMesuretGSanz-RodriguezA, et al.Increased neocortical expression of the P2X7 receptor after status epilepticus and anticonvulsant effect of P2X7 receptor antagonist A-438079. Epilepsia. 2013;54(9):1551‐1561. doi:10.1111/epi.12257
92.
MorganJMorenoOAlvesM, et al.Increased uptake of the P2X7 receptor radiotracer (18) F-JNJ-64413739 in the brain and peripheral organs according to the severity of status epilepticus in male mice. Epilepsia. 2023;64(2):511‐523. doi:10.1111/epi.17484
93.
BascunanaPGendronTSanderK, et al.Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers. Epilepsia. 2019;60(11):2325‐2333. doi:10.1111/epi.16353
94.
Takkinen JS, Lopez-Picon FR, Al Majidi R, et al. Brain energy metabolism and neuroinflammation in ageing APP/PS1-21 mice using longitudinal (18)F-FDG and (18)F-DPA-714 PET imaging. J Cereb Blood Flow Metab. 2017;37(8):2870‐2882. doi:10.1177/0271678X16677990
95.
BascunanaPBrackhanMLeiterI, et al.Divergent metabolic substrate utilization in brain during epileptogenesis precedes chronic hypometabolism. J Cereb Blood Flow Metab. 2020;40(1):204‐213. doi:10.1177/0271678X18809886
96.
KungBTSerajSMZadehMZ, et al.An update on the role of (18)F-FDG-PET/CT in major infectious and inflammatory diseases. Am J Nucl Med Mol Imaging. 2019;9(6):255‐273.
97.
Franco MachadoJSilvaRDMeloR, et al.Less exploited GPCRs in precision medicine: Targets for molecular imaging and theranostics. Molecules. 2018;24(1):49. doi:10.3390/molecules24010049
98.
RosenbergAJLiuHJinH, et al.Design, synthesis, and in vitro and in vivo evaluation of an (18)F-labeled sphingosine 1-phosphate receptor 1 (S1P1) PET tracer. J Med Chem. 2016;59(13):6201‐6220. doi:10.1021/acs.jmedchem.6b00390
99.
QiuLJiangHYuY, et al.Radiosynthesis and evaluation of a fluorine-18 radiotracer [(18)F]FS1P1 for imaging sphingosine-1-phosphate receptor 1. Org Biomol Chem. 2022;20(5):1041‐1052. doi:10.1039/d1ob02225c
100.
QiuLJiangHZhouC, et al.Design, synthesis, and biological evaluation of multiple F-18 S1PR1 radiotracers in rodent and nonhuman primate. Org Biomol Chem. 2024;22(26):5428‐5453. doi:10.1039/d4ob00712c
101.
QiuLJiangHZhouC, et al.Discovery of a promising fluorine-18 positron emission tomography radiotracer for imaging sphingosine-1-phosphate receptor 1 in the brain. J Med Chem. 2023;66(7):4671‐4688. doi:10.1021/acs.jmedchem.2c01752
102.
WangLBiLQiuY, et al.Effectiveness of electro-acupuncture for cognitive improvement on Alzheimer's disease quantified via PET imaging of sphingosine-1-phosphate receptor 1. Alzheimers Dement. 2024;20(12):8331‐8345. doi:10.1002/alz.14260
103.
LiuHLuoZGuJ, et al.In vivo characterization of four (18)F-labeled S1PR1 tracers for neuroinflammation. Mol Imaging Biol. 2020;22(5):1362‐1369. doi:10.1007/s11307-020-01514-8
104.
JiangHGuJZhaoH, et al.PET study of sphingosine-1-phosphate receptor 1 expression in response to S. aureus infection. Mol Imaging. 2021;2021:9982020. doi:10.1155/2021/9982020
105.
JinHYangHLiuH, et al.A promising carbon-11-labeled sphingosine-1-phosphate receptor 1-specific PET tracer for imaging vascular injury. J Nucl Cardiol. 2017;24(2):558‐570. doi:10.1007/s12350-015-0391-1
106.
LiuHJinHYueX, et al.PET imaging study of S1PR1 expression in a rat model of multiple sclerosis. Mol Imaging Biol. 2016;18(5):724‐732. doi:10.1007/s11307-016-0944-y
107.
LiuHJinHYueX, et al.PET Study of sphingosine-1-phosphate receptor 1 expression in response to vascular inflammation in a rat model of carotid injury. Mol Imaging. 2017;16:1536012116689770. doi:10.1177/1536012116689770
108.
JiangHJoshiSLiuH, et al.Invitro and in vivo investigation of S1PR1 expression in the central nervous system using [(3)H]CS1P1 and [(11)C]CS1P1. ACS Chem Neurosci. 2021;12(19):3733‐3744. doi:10.1021/acschemneuro.1c00492
109.
BrierMRHamdiMRajamanikamJ, et al.Phase 1 evaluation of (11)C-CS1P1 to assess safety and dosimetry in human participants. J Nucl Med. 2022;63(11):1775‐1782. doi:10.2967/jnumed.121.263189
110.
NaiYHQiuLJiangH, et al.Kinetic Modeling of a Novel Putative Sphingosine‐1‐Phosphate Receptor 1 (S 1 PR 1) Radiotracer [18 F] TZ 82112 in Nonhuman Primates. J Neurochem.. 2026;170:e70447.
111.
Colin ZhangYH. Developing novel ligands with enhanced binding affinity for the sphingosine 1-phosphate receptor 1 using machine learning, https://doi.org/10.48550/arXiv.2307.16037 (2023).
112.
DongYYXiaMWangL, et al.Spatiotemporal expression of SphK1 and S1PR2 in the hippocampus of pilocarpine rat model and the epileptic foci of temporal lobe epilepsy. Front Cell Dev Biol. 2020;8:800. doi:10.3389/fcell.2020.00800
113.
JiangHHuangTYuY, et al.Characterization of a S1PR2 specific (11)C-labeled radiotracer in streptozotocin-induced diabetic murine model. Nucl Med Biol. 2023;122-123:108370. doi:10.1016/j.nucmedbio.2023.108370
114.
PrasadVPWagnerSKeulP, et al.Synthesis, radiosynthesis and biochemical evaluation of fluorinated analogues of sphingosine-1-phosphate receptor 3 specific antagonists using PET. Bioorg Med Chem. 2024;104:117697. doi:10.1016/j.bmc.2024.117697
115.
O'SullivanCSchubartAMirAK, et al.The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures. J Neuroinflammation. 2016;13:31. doi:10.1186/s12974-016-0494-x
116.
HanTWuZZhuJ, et al.Analysis and construction of a molecular diagnosis model of drug-resistant epilepsy based on bioinformatics. Front Mol Biosci. 2021;8:683032. doi:10.3389/fmolb.2021.683032
117.
LangJZhouWHuangT, et al.Design and synthesis of novel PET radiotracers for imaging sphingosine-1-phosphate receptor 5 (S1PR5) in the brain. J Med Chem. 2025;68(12):12991‐13018. doi:10.1021/acs.jmedchem.5c00881
118.
MorganTEFGrantEKShawRC, et al.Synthesis and evaluation of 6-arylaminobenzamides as positron emission tomography imaging ligands for the sphingosine-1-phosphate-5 receptor. RSC Med Chem. 2025;16(3):1235‐1249. doi:10.1039/d4md00929k
119.
GuJZhengMQHoldenD, et al.PET imaging of sphingosine-1-phosphate receptor 1 with [18F]TZ4877 in nonhuman primates. Mol Imaging Biol. 2025;27(1):54‐63. doi:10.1007/s11307-024-01979-x
