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小鼠胶质母细胞瘤中募集的CD8 + T淋巴细胞的体内磁共振成像

In Vivo Magnetic Resonance Imaging of CD8+ T Lymphocytes Recruiting to Glioblastoma in Mice.

作者信息

Li Anning, Wu Yue, Tang Feng, Li Wei, Feng Xiaoyuan, Yao Zhenwei

机构信息

1 Department of Radiology, Qilu Hospital of Shandong University , Jinan, People's Republic of China .

2 Department of Radiology, Fudan University , Shanghai, People's Republic of China .

出版信息

Cancer Biother Radiopharm. 2016 Nov;31(9):317-323. doi: 10.1089/cbr.2016.2061.

Abstract

Noninvasive in vivo tracking of adopted immune cells would help improve immunotherapy on glioblastoma. In this study, the authors tried to track adoptive CD8+ T lymphocytes in an in situ GL261 glioblastoma mouse model with magnetic resonance imaging (MRI). CD8+ T lymphocytes from spleen of preimmunized GL261 glioblastoma mice were labeled with superparamagnetic iron oxide, with polylysine as transfection agent. From Prussian blue staining, the labeling efficiency was 0.77% ± 0.06%, without altering cell viability and function. From anti-CD8, and anti-dextran staining, superparamagnetic iron oxide could be seen in the cytoplasm. In vitro imaging of agar gel mixtures with different concentrations of labeled CD8+ T lymphocytes was done with a 3.0T MR T2*WI sequence. Higher cell concentrations showed lower signal values. Twenty-four hours after tail vein injection of labeled and unlabeled CD8+ T lymphocytes, imaging of GL261 mice brain showed black spots at the periphery of the tumor in the labeled group only. Brain tumor pathology further verified infiltration of labeled CD8+ T lymphocytes in the tumor. Thus, preimmunized CD8+ T lymphocytes could be efficiently labeled with superparamagnetic iron oxide and tracked both in vitro and in vivo with 3.0T MRI.

摘要

对移植免疫细胞进行无创体内追踪将有助于改善胶质母细胞瘤的免疫治疗。在本研究中,作者尝试在原位GL261胶质母细胞瘤小鼠模型中利用磁共振成像(MRI)追踪过继性CD8+ T淋巴细胞。用超顺磁性氧化铁标记预免疫的GL261胶质母细胞瘤小鼠脾脏中的CD8+ T淋巴细胞,以聚赖氨酸作为转染剂。普鲁士蓝染色显示标记效率为0.77%±0.06%,且未改变细胞活力和功能。抗CD8和抗葡聚糖染色显示,超顺磁性氧化铁可见于细胞质中。利用3.0T MR T2*WI序列对含有不同浓度标记CD8+ T淋巴细胞的琼脂凝胶混合物进行体外成像。细胞浓度越高,信号值越低。尾静脉注射标记和未标记的CD8+ T淋巴细胞24小时后,GL261小鼠脑部成像显示仅标记组肿瘤周边有黑点。脑肿瘤病理学进一步证实标记的CD8+ T淋巴细胞浸润到肿瘤中。因此,预免疫的CD8+ T淋巴细胞可用超顺磁性氧化铁有效标记,并通过3.0T MRI在体外和体内进行追踪。

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