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一种用于使用磁共振成像检测和定量人树突状细胞的新型 (19)F 探针。

A novel (19)F agent for detection and quantification of human dendritic cells using magnetic resonance imaging.

机构信息

Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.

出版信息

Int J Cancer. 2011 Jul 15;129(2):365-73. doi: 10.1002/ijc.25672. Epub 2010 Nov 3.

Abstract

Monitoring of cell therapeutics in vivo is of major importance to estimate its efficacy. Here, we present a novel intracellular label for (19)F magnetic resonance imaging (MRI)-based cell tracking, which allows for noninvasive, longitudinal cell tracking without the use of radioisotopes. A key advantage of (19)F MRI is that it allows for absolute quantification of cell numbers directly from the MRI data. The (19)F label was tested in primary human monocyte-derived dendritic cells. These cells took up label effectively, resulting in a labeling of 1.7 ± 0.1 × 10(13) (19)F atoms per cell, with a viability of 80 ± 6%, without the need for electroporation or transfection agents. This results in a minimum detection sensitivity of about 2,000 cells/voxel at 7 T, comparable with gadolinium-labeled cells. Comparison of the detection sensitivity of cells labeled with (19)F, iron oxide and gadolinium over typical tissue background showed that unambiguous detection of the (19)F-labeled cells was simpler than with the contrast agents. The effect of the (19)F agent on cell function was minimal in the context of cell-based vaccines. From these data, we calculate that detection of 30,000 cells in vivo at 3 T with a reasonable signal to noise ratio for (19)F images would require less than 30 min with a conventional fast spin echo sequence, given a coil similar to the one used in this study. This is well within acceptable limits for clinical studies, and thus, we conclude that (19)F MRI for quantitative cell tracking in a clinical setting has great potential.

摘要

监测细胞疗法在体内的情况对于评估其疗效至关重要。在这里,我们提出了一种用于基于 (19)F 磁共振成像(MRI)的细胞跟踪的新型细胞内标记物,它允许进行非侵入性、纵向细胞跟踪,而无需使用放射性同位素。(19)F MRI 的一个主要优点是它允许直接从 MRI 数据对细胞数量进行绝对定量。我们在原代人单核细胞衍生的树突状细胞中测试了 (19)F 标记物。这些细胞有效地摄取了标记物,导致每个细胞标记了 1.7 ± 0.1×10(13)个 (19)F 原子,细胞活力为 80 ± 6%,而无需电穿孔或转染试剂。这导致在 7 T 下最小检测灵敏度约为 2,000 个细胞/体素,与镧系元素标记的细胞相当。比较用 (19)F、氧化铁和镧系元素标记的细胞的检测灵敏度与典型组织背景表明,与对比剂相比,用 (19)F 标记的细胞的检测更加简单。在细胞疫苗的背景下,(19)F 试剂对细胞功能的影响最小。根据这些数据,我们计算出,在 3 T 下用合理的信噪比进行体内 30,000 个细胞的检测,对于 (19)F 图像,使用类似于本研究中使用的线圈的常规快速自旋回波序列,所需时间不到 30 分钟。这远远低于临床研究的可接受范围,因此,我们得出结论,(19)F MRI 具有在临床环境中进行定量细胞跟踪的巨大潜力。

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