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• Original Article •
Experimental study of magnetic resonance targeted myelin probe Gd-DTDAS in multiple sclerotic rat myelin injury model
LIU Caiyun  SHAO Cuijie  WENG Na  LI Guodong  HUANG Danqi  LIU Jia  BIN Li  WANG Xu 

Cite this article as: LIU C Y, SHAO C J, WENG N, et al. Experimental study of magnetic resonance targeted myelin probe Gd-DTDAS in multiple sclerotic rat myelin injury model[J]. Chin J Magn Reson Imaging, 2024, 15(2): 122-128. DOI:10.12015/issn.1674-8034.2024.02.018.


[Abstract] Objective To investigate the application value of MRI contrast agent Gd-DTDAS in multiple sclerosis (MS) rat myelin injury model.Materials and Methods In cell experiments, oligodendrocyte precursor cells (OLN-93) were randomly divided into control group 2 (n=3) and lysophosphatidylcholine (LPC) group (n=3), and the cells of LPC group were incubated with 1 mL of 800 μM LPC in a sterile confocal dish for 30 min. Cytotoxicity was evaluated by methyl thiazolyl tetrazolium (MTT), and the absorbance and survival rate of OLN-93 after incubation with Gd-DTDAS for 24 h were calculated. In the uptake experiment, the control group 2 and the LPC group were compared to quantify the uptake value of Gd-DTDAS and the corresponding fluorescence intensity of the two groups. In animal experiments, 6-8 week-old SD rats were randomly divided into control group (n=12) and experimental group (n=18), and the left corpus callosum of rats in the experimental group was injected with 1% LPC solution (1% LPC dissolved in PBS). After molding, behavioral observation was performed (1, 3, 7 d), and T1WI and T2WI sequence scanning were performed 7 d after injecting. Gd-DTDAS staining (n=6) and soaking (n=6) of rat brain tissue were performed according to the MRI abnormal signal site to evaluate the binding of Gd-DTDAS to the myelin site. Among them, the staining experiment was named as control group 3 and experimental group 3, while the soaking experiment group was named as control group 4 and experimental group 4. Gd-DTDAS was injected by tail vein, MRI assessed cerebral myelin sheath changes before and after Gd-DTDAS injection in the experiment group (n=6).Results In the cytotoxicity experiment, when the concentration of Gd-DTDAS increased to 400 μM, the survival rate of OLN-93 cells was about 95%, and there was no significant difference in cell survival between concentrations (t=4.20, P>0.05). In the cell uptake experiment, both groups of cells could uptake Gd-DTDAS, and the uptake of LPC group was significantly lower than that of the control group 2, and the difference was statistically significant (t=31.75, P<0.01). In vitro experiments, compared with the control group 3, the fluorescence intensity of brain tissue sections in the experiment 3 group stained with Gd-DTDAS decreased significantly, and the difference was statistically significant (U=9, P<0.01). After immersion of brain tissue slices in Gd-DTDAS, the MRI resolution significantly increased in both the control group 4 (n=3) and the experiment group 4 (n=6), with statistically significant differences (control group 4, t =8.76, P<0.01; experiment group 4, t =2.89, P<0.01). In vivo experiments, MRI T1maps relaxation in the medullary region was significantly reduced after injection compared with before tail vein injection (t =14.46, P<0.01).Conclusions The myelin probe Gd-DTDAS can better bind to myelin-rich regions, and the myelin sheath can be better targeted for MRI, and can specifically show the damage site of myelin sheath in multiple sclerosis.
[Keywords] autoimmune diseases；multiple sclerosis；myelin probe；molecular imaging；magnetic resonance imaging

LIU Caiyun1   SHAO Cuijie2   WENG Na1   LI Guodong1   HUANG Danqi1   LIU Jia1   BIN Li1   WANG Xu1*  

1 Department of Nuclear Medicine, Binzhou Medical University Hospital, Binzhou 256600, China

2 Department of Medical Research Center, Binzhou Medical University Hospital, Binzhou 256600, China

Corresponding author: WANG X, E-mail: wangxu1978@163.com

Conflicts of interest   None.

Received  2023-06-08
Accepted  2024-01-20
DOI: 10.12015/issn.1674-8034.2024.02.018
Cite this article as: LIU C Y, SHAO C J, WENG N, et al. Experimental study of magnetic resonance targeted myelin probe Gd-DTDAS in multiple sclerotic rat myelin injury model[J]. Chin J Magn Reson Imaging, 2024, 15(2): 122-128. DOI:10.12015/issn.1674-8034.2024.02.018.

[1]
ALSHEHRI A, AL-IEDANI O, ARM J, et al. Neural diffusion tensor imaging metrics correlate with clinical measures in people with relapsing-remitting MS[J]. Neuroradiol J, 2022, 35(5): 592-599. DOI: 10.1177/19714009211067400.
[2]
FILIPPI M, PREZIOSA P, BARKHOF F, et al. Diagnosis of progressive multiple sclerosis from the imaging perspective: a review[J]. JAMA Neurol, 2021, 78(3): 351-364. DOI: 10.1001/jamaneurol.2020.4689.
[3]
WALTON C, KING R, RECHTMAN L, et al. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition[J]. Mult Scler, 2020, 26(14): 1816-1821. DOI: 10.1177/1352458520970841.
[4]
TIAN D C, ZHANG C Y, YUAN M, et al. Incidence of multiple sclerosis in China: a nationwide hospital-based study[J/OL]. Lancet Reg Health West Pac, 2020, 1: 100010 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/34327341/. DOI: 10.1016/j.lanwpc.2020.100010.
[5]
OLEK M J. Multiple sclerosis[J/OL]. Ann Intern Med, 2021, 174(6): ITC81-ITC96 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/34097429/. DOI: 10.7326/aitc202106150.
[6]
FILIPPI M, BAR-OR A, PIEHL F, et al. Multiple sclerosis[J/OL]. Nat Rev Dis Primers, 2018, 4: 43 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/30410033/. DOI: 10.1038/s41572-018-0041-4.
[7]
HAIDER L, ZRZAVY T, HAMETNER S, et al. The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain[J]. Brain, 2016, 139(Pt 3): 807-815. DOI: 10.1093/brain/awv398.
[8]
LASSMANN H, BRÜCK W, LUCCHINETTI C F. The immunopathology of multiple sclerosis: an overview[J]. Brain Pathol, 2007, 17(2): 210-218. DOI: 10.1111/j.1750-3639.2007.00064.x.
[9]
ZHUO Z Z, LI Y M, DUAN Y Y, et al. Subtyping relapsing-remitting multiple sclerosis using structural MRI[J]. J Neurol, 2021, 268(5): 1808-1817. DOI: 10.1007/s00415-020-10376-7.
[10]
HEATH F, HURLEY S A, JOHANSEN-BERG H, et al. Advances in noninvasive myelin imaging[J]. Dev Neurobiol, 2018, 78(2): 136-151. DOI: 10.1002/dneu.22552.
[11]
PETIET A, ADANYEGUH I, AIGROT M S, et al. Ultrahigh field imaging of myelin disease models: toward specific markers of myelin integrity?[J]. J Comp Neurol, 2019, 527(13): 2179-2189. DOI: 10.1002/cne.24598.
[12]
WEI B, WENG N, FU L, et al. Synthesis and bioactivity evaluation of a myelin-specific contrast agent for magnetic resonance imaging of myelination in central nervous system[J/OL]. Bioorg Med Chem, 2023, 84: 117257 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/37001243/. DOI: 10.1016/j.bmc.2023.117257.
[13]
FRISCH M L, POLARZ S. Molecular fusion of surfactant and Lewis-acid properties for attacking dirt by catalytic bond cleavage[J/OL]. Sci Rep, 2021, 11: 5131 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/33664375/. DOI: 10.1038/s41598-021-84654-3.
[14]
DE PAULA FARIA D. Myelin positron emission tomography (PET) imaging in multiple sclerosis[J]. Neural Regen Res, 2020, 15(10): 1842-1843. DOI: 10.4103/1673-5374.280311.
[15]
WU C Y, WEI J J, TIAN D H, et al. Molecular probes for imaging myelinated white matter in CNS[J]. J Med Chem, 2008, 51(21): 6682-6688. DOI: 10.1021/jm8003637.
[16]
JOHNSON G A, CALABRESE E, BADEA A, et al. A multidimensional magnetic resonance histology atlas of the Wistar rat brain[J]. Neuroimage, 2012, 62(3): 1848-1856. DOI: 10.1016/j.neuroimage.2012.05.041.
[17]
BI S J, DONG X Y, WANG Z Y, et al. Salvianolic acid B alleviates neurological injury by upregulating stanniocalcin 1 expression[J/OL]. Ann Transl Med, 2022, 10(13): 739 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/35957712/. DOI: 10.21037/atm-21-4779.
[18]
WU C Y, WEI J J, TIAN D H, et al. Molecular probes for imaging myelinated white matter in CNS[J]. J Med Chem, 2008, 51(21): 6682-6688. DOI: 10.1021/jm8003637.
[19]
WALLIN M T, CULPEPPER W J, CAMPBELL J D, et al. The prevalence of MS in the United States: a population-based estimate using health claims data[J/OL]. Neurology, 2019, 92(10): e1029-e1040 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/30770430/. DOI: 10.1212/WNL.0000000000007035.
[20]
MAHAD D H, TRAPP B D, LASSMANN H. Pathological mechanisms in progressive multiple sclerosis[J]. Lancet Neurol, 2015, 14(2): 183-193. DOI: 10.1016/S1474-4422(14)70256-X.
[21]
FUJIYOSHI K, HIKISHIMA K, NAKAHARA J, et al. Application of q-space diffusion MRI for the visualization of white matter[J]. J Neurosci, 2016, 36(9): 2796-2808. DOI: 10.1523/JNEUROSCI.1770-15.2016.
[22]
SHETH V R, FAN S J, HE Q, et al. Inversion recovery ultrashort echo time magnetic resonance imaging: a method for simultaneous direct detection of myelin and high signal demonstration of iron deposition in the brain - A feasibility study[J/OL]. Magn Reson Imaging, 2017, 38: 87-94 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/28038965/. DOI: 10.1016/j.mri.2016.12.025.
[23]
DONADIEU M, LEE N J, GAITÁN M I, et al. In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis[J/OL]. Elife, 2023, 12: e73786 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/37083540/. DOI: 10.7554/eLife.73786.
[24]
XIN W, CHAN J R. Myelin plasticity: sculpting circuits in learning and memory[J]. Nat Rev Neurosci, 2020, 21(12): 682-694. DOI: 10.1038/s41583-020-00379-8.
[25]
DE FARIA O, PIVONKOVA H, VARGA B, et al. Periods of synchronized myelin changes shape brain function and plasticity[J]. Nat Neurosci, 2021, 24(11): 1508-1521. DOI: 10.1038/s41593-021-00917-2.
[26]
WU C Y, ZHU J Q, BAESLACK J, et al. Longitudinal positron emission tomography imaging for monitoring myelin repair in the spinal cord[J]. Ann Neurol, 2013, 74(5): 688-698. DOI: 10.1002/ana.23965.
[27]
VAN DER WEIJDEN C W J, MEILOF J F, VAN DER HOORN A, et al. Quantitative assessment of myelin density using[11C]MeDAS PET in patients with multiple sclerosis: a first-in-human study[J]. Eur J Nucl Med Mol Imaging, 2022, 49(10): 3492-3507. DOI: 10.1007/s00259-022-05770-4.
[28]
FRULLANO L, ZHU J Q, MILLER R H, et al. Synthesis and characterization of a novel gadolinium-based contrast agent for magnetic resonance imaging of myelination[J]. J Med Chem, 2013, 56(4): 1629-1640. DOI: 10.1021/jm301435z.
[29]
BUCKINX R, SMOLDERS I, SAHEBALI S, et al. Morphological changes do not reflect biochemical and functional differentiation in OLN-93 oligodendroglial cells[J]. J Neurosci Methods, 2009, 184(1): 1-9. DOI: 10.1016/j.jneumeth.2009.07.004.
[30]
XIE Y, ZHANG X H, XU P F, et al. Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia[J/OL]. J Clin Invest, 2021, 131(1): e128114 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/33141760/. DOI: 10.1172/JCI128114.
[31]
ZHOU Y, SU M, JIE J F, et al. Study on the optimal differentiation culture media for OLN-93 cell culture[J]. Chin J Histochem Cytochem, 2020, 29(2): 125-130. DOI: 10.16705/j.cnki.1004-1850.2020.02.004.
[32]
YU Q, GUAN T, GUO Y, et al. The initial myelination in the central nervous system[J/OL]. ASN Neuro, 2023, 15: 17590914231163039 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/36974372/. DOI: 10.1177/17590914231163039.
[33]
PLEMEL J R, MICHAELS N J, WEISHAUPT N, et al. Mechanisms of lysophosphatidylcholine-induced demyelination: a primary lipid disrupting myelinopathy[J]. Glia, 2018, 66(2): 327-347. DOI: 10.1002/glia.23245.
[34]
WALY B E, BUTTIGIEG E, KARAKUS C, et al. Longitudinal intravital microscopy reveals axon degeneration concomitant with inflammatory cell infiltration in an LPC model of demyelination[J/OL]. Front Cell Neurosci, 2020, 14: 165 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/32655371/. DOI: 10.3389/fncel.2020.00165.
[35]
PEZZANITE L, CHOW L, PIQUINI G, et al. Use of in vitro assays to identify antibiotics that are cytotoxic to normal equine chondrocytes and synovial cells[J]. Equine Vet J, 2021, 53(3): 579-589. DOI: 10.1111/evj.13314.
[36]
WANG J S, MA D, LI Y, et al. Targeted delivery of CYP2E1 recombinant adenovirus to malignant melanoma by bone marrow-derived mesenchymal stem cells as vehicles[J]. Anticancer Drugs, 2014, 25(3): 303-314. DOI: 10.1097/CAD.0000000000000046.
[37]
AZADPOUR M, FARAJOLLAHI M M, VARZI A M, et al. Extraction, chemical composition, antioxidant property, and In-vitro anticancer activity of silymarin from Silybum marianum on kb and A549 cell lines[J]. Curr Drug Discov Technol, 2021, 18(4): 511-517. DOI: 10.2174/1570163817666200827111127.
[38]
BIRGBAUER E, RAO T S, WEBB M. Lysolecithin induces demyelination in vitro in a cerebellar slice culture system[J]. J Neurosci Res, 2004, 78(2): 157-166. DOI: 10.1002/jnr.20248.
[39]
HOLLER J G, HENRIKSEN D P, MIKKELSEN S, et al. Erratum to: shock in the emergency department; a 12year population based cohort study[J/OL]. Scand J Trauma Resusc Emerg Med, 2017, 25(1): 103 [2023-06-07]. https://pubmed.ncbi.nlm.nih.gov/29070046/. DOI: 10.1186/s13049-017-0429-2.
[40]
WU C Y, ECK B, ZHANG S, et al. Discovery of 1, 2, 3-triazole derivatives for multimodality PET/CT/cryoimaging of myelination in the central nervous system[J]. J Med Chem, 2017, 60(3): 987-999. DOI: 10.1021/acs.jmedchem.6b01328.
[41]
FRULLANO L, WANG C N, MILLER R H, et al. A myelin-specific contrast agent for magnetic resonance imaging of myelination[J]. J Am Chem Soc, 2011, 133(6): 1611-1613. DOI: 10.1021/ja1040896.
[42]
FRULLANO L, ZHU J Q, WANG C N, et al. Myelin imaging compound (MIC) enhanced magnetic resonance imaging of myelination[J]. J Med Chem, 2012, 55(1): 94-105. DOI: 10.1021/jm201010e.

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