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