MR signal changes in superparamagnetic iron oxide nanoparticle-labeled macrophages in response to X irradiation
MR signal changes in superparamagnetic iron oxide nanoparticle-labeled macrophages in response to X irradiation
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DOI：
10.1002/nbm.4132
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发表时间：
2019-07-15
影响因子：
2.9
通讯作者：
Fujii, Hirofumi
中科院分区：
文献类型：
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作者：
Yamaguchi, Masayuki;Ohnuki, Kazunobu;Fujii, Hirofumi
为了研究与超顺磁性氧化铁纳米颗粒（SPION）标记的巨噬细胞相关的MR信号是否随X射线照射而变化，我们对SPION标记的巨噬细胞样J774A.1细胞进行了体外MRI，随后进行了X射线照射。我们用浓度为10 μ g铁/mL的ferucarbotran在培养基中标记细胞16小时，随后使用低能X射线装置以0、2、10或20戈伊的剂量进行X射线照射。在第3天和第6天，我们将细胞以2 x 10（6）个细胞/mL的浓度悬浮在琼脂中，并使用3 T扫描仪获取细胞样本的多梯度回波和多自旋回波图像，以估计R-2* 和R-2。此外，我们还在显微镜下研究了MR信号变化、细胞内SPION和酸性细胞器之间的关系。我们的数据表明，X射线照射标记的细胞引起增加的SPION沉积在溶酶体相比，未照射的控制。在第3天，0至10戈伊辐照样品中的R-2* 和R-2值与未辐照对照中的17 +/- 2和13 +/- 1/s相比分别呈剂量依赖性增加5.4倍和1.5倍;这些值在超过10戈伊时达到稳定。尽管在第6天和第7天，在10和20戈伊样品中仍观察到R-2*、R-2和SPION沉积增加，但2戈伊样品显示这些参数随着细胞生长恢复而恢复。酸性细胞器暂时增加，在照射的细胞，这表明，在溶酶体酸度的减少是不是由于SPION沉积。结论：X射线照射巨噬细胞在一定剂量范围内可引起SPION沉积和R-2和R-2升高。SPION标记和随后的X射线照射的巨噬细胞的MRI可用作研究巨噬细胞对X射线照射的反应的新技术。
To investigate whether MR signals associated with macrophages labeled with superparamagnetic iron oxide nanoparticles (SPIONs) change in response to X irradiation, we performed in vitro MRI of SPION-labeled macrophage-like J774A.1 cells that were subsequently X irradiated. We labeled the cells with ferucarbotran at a concentration of 10 mu g iron/mL in culture medium for 16 h and subsequently performed X irradiation at doses of 0, 2, 10, or 20 Gy using a low-energy X-ray unit. On Days 3 and 6, we suspended the cells in agar at a concentration of 2 x 10(6) cells/mL and acquired multi-gradient echo and multi-spin echo images of the cell samples using a 3 T scanner to estimate R-2* and R-2. In addition, we microscopically investigated the relationship among the MR signal changes, intracellular SPIONs, and acidic organelles. Our data showed that X irradiation of labeled cells caused increased SPION deposition in lysosomes compared with the non-irradiated control. On Day 3, R-2* and R-2 values in the 0 to 10 Gy irradiated samples were dose-dependently increased 5.4- and 1.5-fold compared with 17 +/- 2 and 13 +/- 1/s, respectively, in the non-irradiated control; these values plateaued at more than 10 Gy. Although the increases in R-2*, R-2, and SPION deposition were still observed in the 10 and 20 Gy samples on Days 6 and 7, the 2 Gy samples showed recovery in these parameters as cell growth was restored. Acidic organelles were temporarily increased in the irradiated cells, which suggests that the reduction in lysosomal acidity was not attributable to SPION deposition. In conclusion, X irradiation of macrophages can cause SPION deposition and R-2* and R-2 elevation in a specific dose range. MRI of SPION-labeled and subsequently X-irradiated macrophages may be utilized as a novel technique for investigating macrophage responses to X irradiation.