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氟-19 细胞 MRI 检测免疫抑制小鼠模型中粒细胞巨噬细胞集落刺激因子激活的人外周血单个核细胞的定量和特征分析。

Quantification and characterization of granulocyte macrophage colony-stimulating factor activated human peripheral blood mononuclear cells by fluorine-19 cellular MRI in an immunocompromised mouse model.

机构信息

Biotherapeutics Research Laboratory, Robarts Research Institute, London, Ontario N6A 5B7, Canada; Department of Microbiology and Immunology, University of Western Ontario, London, Ontario N6A 5B7, Canada.

Imaging Research Laboratories, Robarts Research Institute, London, Ontario N6A 5B7, Canada; Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5B7, Canada.

出版信息

Diagn Interv Imaging. 2020 Sep;101(9):577-588. doi: 10.1016/j.diii.2020.02.004. Epub 2020 Feb 28.

DOI:10.1016/j.diii.2020.02.004
PMID:32122802
Abstract

PURPOSE

The purpose of this study was to test fluorine-19 (19F) cellular magnetic resonance (MRI) as a non-invasive imaging modality to track therapeutic cell migration as a surrogate marker of immunotherapeutic effectiveness.

MATERIALS AND METHODS

Human peripheral blood mononuclear cell- (PBMC)-derived antigen presenting cell (APC) were labeled with a 19F-perfluorocarbon (PFC) and/or activated with granulocyte macrophage colony-stimulating factor (GM-CSF). Viability, phenotype and cell lineage characterization preceded 19F cellular MRI of PFC PBMC under both pre-clinical 9.4 Tesla (T) and clinical 3T conditions in a mouse model.

RESULTS

A high proportion of PBMC incorporated PFC without affecting viability, phenotype or cell lineage composition. PFC PBMC were in vivo migration-competent to draining and downstream lymph nodes. GM-CSF addition to culture increased PBMC migration to, and persistence within, secondary lymphoid organs.

CONCLUSION

19F cellular MRI is a non-invasive imaging technique capable of detecting and quantifying in vivo cell migration in conjunction with an established APC-based immunotherapy model. 19F cellular MRI can function as a surrogate marker for assessing and improving upon the therapeutic benefit that this immunotherapy provides.

摘要

目的

本研究旨在测试氟-19(19F)细胞磁共振成像(MRI)作为一种非侵入性成像方式,以追踪治疗细胞迁移作为免疫治疗效果的替代标志物。

材料与方法

用 19F 全氟化碳(PFC)标记人外周血单核细胞衍生的抗原呈递细胞(APC),并用粒细胞巨噬细胞集落刺激因子(GM-CSF)激活。在临床 3T 和临床前 9.4T 条件下,对小鼠模型中 19F 细胞 MRI 进行了 PBMC APC 的细胞活力、表型和细胞谱系特征的预实验。

结果

相当大比例的 PBMC 可摄取 PFC,而不影响细胞活力、表型或细胞谱系组成。PFC PBMC 具有体内迁移能力,可迁移至引流和下游淋巴结。GM-CSF 培养物的添加增加了 PBMC 向二级淋巴器官的迁移和在其中的持久性。

结论

19F 细胞 MRI 是一种非侵入性成像技术,能够检测和定量体内细胞迁移,并与已建立的基于 APC 的免疫治疗模型相结合。19F 细胞 MRI 可以作为替代标志物,用于评估和提高这种免疫疗法的治疗效果。

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