Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
Int J Cancer. 2011 Jul 15;129(2):365-73. doi: 10.1002/ijc.25672. Epub 2010 Nov 3.
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.
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。