移植单核细胞对中枢系统不同病变趋化作用的PET/CT示踪观察
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摘要
目的通过PET/CT显像示踪,观察中枢系统病变的趋化作用对移植单核细胞走向和分布的影响,为细胞移植的临床应用提供依据。方法放射性核素氟-脱氧葡萄糖(18F-FDG)标记兔外周血单核细胞,经枕大池植入脑膜炎模型兔的蛛网膜下腔,PET/CT显像观察标记细胞在蛛网膜下腔的走向和分布情况;放射性核素18F-FDG标记鼠单核细胞植入阿尔兹海默症(AD)APP/PS1双转基因小鼠和作为对照组的C57BL/6小鼠侧脑室,PET/CT显像观察标记细胞在小鼠中枢系统的走向与分布情况。结果放射性核素在脑膜炎模型兔的蛛网膜下腔中分布范围比正常兔更广,向头端沿蛛网膜下腔到达整个脑部,且脑实质、肾、肝的放射性核素的摄取也较正常兔强,3h显像仍可见到脑实质有放射性核素的摄取。AD小鼠侧脑室移植的单核细胞,仅仅局限分布于脑室内和脑部的蛛网膜下腔,主要集中于注射部位和海马附近,而C57BL/6小鼠移植的细胞分布范围较更广,可达到脊髓蛛网膜下腔内;同时,AD小鼠在移植后15h时仍可以检测到18F-FDG标记的单核细胞。结论植入中枢系统的单核细胞会受病变趋化作用的影响,在制定细胞移植方案时应予考虑;侧脑室与蛛网膜下腔是中枢系统疾病如AD和脑膜炎可选的单核细胞移植部位;利用18F-FDG标记单核细胞中枢系统PET/CT示踪,是有效的植入细胞活体检测方法。
Objective To observe the chemotactic effect of transplanted monocytes in central nervous system lesions with PET/CT imaging tracer. Methods Rabbit peripheral blood mononuclear cells labeled with radionuclide18 F-FDG were implanted in the subarachnoid cavity through occipital pool in meningitis model rabbits, and the direction and distribution of labeled cells in subarachnoid cavity were observed by PET/CT imaging. Radionuclide18 F-FDG-labeled mouse monocytes were implanted in lateral ventricle of Alzheimer's disease(AD)APP/PS1 double transgenic mice, the direction and distribution of labeled cells were observed in central nervous system of AD mice with PET/CT imaging. Results The distribution of radionuclides in the subarachnoid cavity of meningitis model rabbits was more widely than normal rabbits, reaching the entire brain from the head end along the subarachnoid cavity; and the radionuclide intake in brain parenchyma,kidney and liver was stronger than normal rabbits. The intake of radionuclides was still shown in the brain parenchyma 3 h after injection. The APP/PS1 cells transplanted in the lateral ventricle of double transgenic mice were confined to the subarachnoid cavity in the brain, mainly in the injection site and near the hippocampus, while the cells transplanted in normal C57 BL/6 mice were more widely distributed and could reach the subarachnoid cavity of the spinal cord. The18 F-FDG labeled mononuclear cells were still shown at 15 h after transplantation. Conclusion The monocytes of the central system can be accurately affected by the chemotactic effect of the lesion, which should be considered in the development of the cell transplantation strategy. Lateral ventricle and subarachnoid cavity are optional transplantation sites for diseases of central nervous system, such as AD and meningitis. The PET/CT imaging tracer is an effective method for overall monitoring of implanted cells in vivo.
Objective To observe the chemotactic effect of transplanted monocytes in central nervous system lesions with PET/CT imaging tracer. Methods Rabbit peripheral blood mononuclear cells labeled with radionuclide18 F-FDG were implanted in the subarachnoid cavity through occipital pool in meningitis model rabbits, and the direction and distribution of labeled cells in subarachnoid cavity were observed by PET/CT imaging. Radionuclide18 F-FDG-labeled mouse monocytes were implanted in lateral ventricle of Alzheimer's disease(AD)APP/PS1 double transgenic mice, the direction and distribution of labeled cells were observed in central nervous system of AD mice with PET/CT imaging. Results The distribution of radionuclides in the subarachnoid cavity of meningitis model rabbits was more widely than normal rabbits, reaching the entire brain from the head end along the subarachnoid cavity; and the radionuclide intake in brain parenchyma,kidney and liver was stronger than normal rabbits. The intake of radionuclides was still shown in the brain parenchyma 3 h after injection. The APP/PS1 cells transplanted in the lateral ventricle of double transgenic mice were confined to the subarachnoid cavity in the brain, mainly in the injection site and near the hippocampus, while the cells transplanted in normal C57 BL/6 mice were more widely distributed and could reach the subarachnoid cavity of the spinal cord. The18 F-FDG labeled mononuclear cells were still shown at 15 h after transplantation. Conclusion The monocytes of the central system can be accurately affected by the chemotactic effect of the lesion, which should be considered in the development of the cell transplantation strategy. Lateral ventricle and subarachnoid cavity are optional transplantation sites for diseases of central nervous system, such as AD and meningitis. The PET/CT imaging tracer is an effective method for overall monitoring of implanted cells in vivo.
引文
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[13]Deichen J,Prante O,Gack M,et al.Uptake of[18 F]fluorodeoxyglucose in human monocyte-macrophages in vitro[J].Eur J Nucl Med Mol Imaging,2003,30(2):267-273.DOI:10.1007/s00259-002-1018-8.
[14]Courtois A,Nusgens BV,Hustinx R,et al.18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture[J].Journal of Nuclear Medicine,2013,54(10):1740-1747.DOI:10.2967/jnumed.112.115873.
[15]Kang WJ,Kang HJ,Kim HS,et al.Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction.[J].Journal of Nuclear Medicine,2006,47(8):1295-1301.PMID:16883008.
[16]沈锐,刘盛,钱海燕,等.核素标记自体骨髓单个核细胞监测心脏干细胞移植后存活情况[J].中华心血管病杂志,2010,38(6):545-548.DOI:10.3760/cma.j.issn.0253-3758.2010.06.014.
[2]Masayuki Hino,Tadanori Ogata,Tadao Morino,et al.Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats[J].Neurosci Res 2009,64(1):56-62.DOI:10.1016/j.neures.2009.01.011.
[3]Merres J,Ho Ss J,Albrecht LJ,et al.Role of the Cathelicidin-Related Antimicrobial Peptide in Inflammation and Mortality in a Mouse Model of Bacterial Meningitis[J].Journal of Innate Immunity,2014,6(2):205-218.DOI:10.1159/000353645.
[4]Varvel NH,Neher JJ,Bosch A,et al.Infiltrating monocytes promote brain inflammation and exacerbate neuronal damage after status epilepticus[J].Proceedings of the National Academy of Sciences,2016,113(38):E5665-5674.DOI:10.1073/pnas.1604263113.
[5]Ciernik IF,Dizendorf E,Baumert BG,et al.Radiation treatment planning with an integrated positron emission and computer tomography(PET/CT):a feasibility study[J].International Journal of Radiation Oncology Biology Physics,2003,57(3):853-863.
[6]李英华.正电子发射断层(PET)显像剂~(18)F-Fethypride化学合成、放射标记及生物学评价[D].吉林大学,2014.
[7]Sachpekidis C,Goldschmidt H,Hose D,et al.PET/CT studies of multiple myeloma using 18F-FDG and 18 F-Na F:comparison of distribution patterns and tracers'pharmacokinetics[J].European Journal of Nuclear Medicine and Molecular Imaging,2014,41(7):1343-1353.DOI:10.1007/s00259-014-2721-y.
[8]Liu Y,Huang HY.Treatment of spinal cord injury by transplantation of cells via cerebrospinal fluid[J].Neuroscience Bulletin,2008,24(5):323-328.DOI:10.1007/s12264-008-0618-0.
[9]陈云富,刘蕊,王文志.PET/CT常用示踪剂^18F-FDG的作用原理、特性及应用[J].中国医疗设备,2008,23(10):78-80.DOI:10.3969/j.issn.1674-1633.2008.10.031.
[10]Lauridsen TK,Iversen KK,Ihlemann N,et al.Clinical utility of 18F-FDG positron emission tomography/computed tomography scan vs.99m Tc-HMPAO white blood cell single-photon emission computed tomography in extra-cardiac work-up of infective endocarditis[J].International Journal of Cardiovascular Imaging,2017,67(13):1-10.
[11]Bax JJ,Patton JA,Poldermans D,et al.18-Fluorodeoxyglucose imaging with positron emission tomography and single photon emission computed tomography:cardiac applications[J].Seminars in Nuclear Medicine,2000,30(4):281-298.DOI:10.1053/snuc.2000.9543.
[12]Qian H,Yang Y,Huang J,et al.Intracoronary delivery of autologous bone marrow mononuclear cells radiolabeled by 18F-fluoro-deoxy-glucose:Tissue distribution and impact on postinfarct swine hearts[J].Journal of cellular biochemistry,2007,102(1):64-74.DOI:10.1002/jcb.21277.
[13]Deichen J,Prante O,Gack M,et al.Uptake of[18 F]fluorodeoxyglucose in human monocyte-macrophages in vitro[J].Eur J Nucl Med Mol Imaging,2003,30(2):267-273.DOI:10.1007/s00259-002-1018-8.
[14]Courtois A,Nusgens BV,Hustinx R,et al.18F-FDG Uptake Assessed by PET/CT in Abdominal Aortic Aneurysms is Associated with Cellular and Molecular Alterations Prefacing Wall Deterioration and Rupture[J].Journal of Nuclear Medicine,2013,54(10):1740-1747.DOI:10.2967/jnumed.112.115873.
[15]Kang WJ,Kang HJ,Kim HS,et al.Tissue distribution of 18F-FDG-labeled peripheral hematopoietic stem cells after intracoronary administration in patients with myocardial infarction.[J].Journal of Nuclear Medicine,2006,47(8):1295-1301.PMID:16883008.
[16]沈锐,刘盛,钱海燕,等.核素标记自体骨髓单个核细胞监测心脏干细胞移植后存活情况[J].中华心血管病杂志,2010,38(6):545-548.DOI:10.3760/cma.j.issn.0253-3758.2010.06.014.