Immunotherapies, such as dendritic cell- (DC-)based therapies, are useful for treating cancer as an alternative to or in combination with traditional therapies. Cells must migrate to lymphoid organs to be effective and the magnitude of the ensuing T cell response is proportional to the number of lymph node-migrated DC. With less than 10% of cells expected to reach their destination, there is a need for an imaging modality capable of sensitively and quantitatively detecting cells. MRI has been used to track DC using iron and 19F methods, with limitations. Quantification of iron-induced signal loss is indirect and challenging; 19F signal is directly quantifiable but lacks sensitivity. Magnetic Particle Imaging (MPI) directly detects superparamagnetic iron oxide nanoparticles (SPIO) and enables quantitation of low numbers of SPIO-labeled cells. Here we describe the first study using MPI to track and quantify the migration of DC, injected into the footpads of C57BL/6 mice, to the popliteal lymph nodes (pLNs). As DC migrate from the site of injection to the lymph nodes, we measured a decrease in signal in the footpads and an increase in signal at the pLNs. The presence of SPIO-labeled DC in nodes was validated by ex vivo MPI and histology. By measuring the iron mass per cell in samples of labeled cells, we were able to provide an estimate of cell number for each source of signal and we report a sensitivity of approximately 4000 cells in vivo and 2000 cells ex vivo. For some mice, MPI was compared to cellular MRI. We also bring attention to the issue of resolving unequal signals within close proximity, a challenge for many pre-clinical studies using a highly concentrated tracer bolus that over shadows nearby lower signals. This study demonstrates the clear advantage of MPI to detect and quantify cells in vivo, bridging the gap left by cellular MRI, and all other in vivo imaging modalities, and opening the door for quantitative imaging of cellular immunotherapies.

中文翻译：

---

磁性粒子成像是一种灵敏的体内成像方式，用于量化树突细胞迁移

免疫疗法，例如基于树突细胞 (DC) 的疗法，可用于治疗癌症，作为传统疗法的替代方法或与传统疗法相结合。细胞必须迁移到淋巴器官才能发挥作用，随后 T 细胞反应的大小与迁移到淋巴结的 DC 的数量成正比。由于预计到达目的地的细胞不到 10%，因此需要一种能够灵敏和定量检测细胞的成像方式。MRI 已被用于使用铁和 19F 方法跟踪 DC，但有局限性。铁诱导信号损失的量化是间接且具有挑战性的；19F 信号可直接量化但缺乏灵敏度。磁性粒子成像 (MPI) 直接检测超顺磁性氧化铁纳米粒子 (SPIO)，并能够对少量 SPIO 标记的细胞进行定量。在这里，我们描述了第一项使用 MPI 跟踪和量化 DC 迁移的研究，注射到 C57BL/6 小鼠的脚垫中，到腘窝淋巴结 (pLN)。随着 DC 从注射部位迁移到淋巴结，我们测量了脚垫中信号的降低和 pLN 信号的增加。节点中 SPIO 标记的 DC 的存在通过以下方法验证离体MPI 和组织学。通过测量标记的细胞的样品每个细胞的铁块，我们能够提供的信号的每一个源细胞数的估计值，我们报告大约4000个细胞的灵敏度体内和2000个细胞先体外后体内。对于某些小鼠，将 MPI 与细胞 MRI 进行比较。我们还引起了对解决近距离内不等信号的问题的关注，这是许多使用高度集中的示踪剂团块覆盖附近较低信号的临床前研究的挑战。这项研究证明了 MPI在体内检测和量化细胞方面的明显优势，弥合了细胞 MRI 和所有其他体内细胞留下的差距。 成像方式，并为细胞免疫疗法的定量成像打开了大门。