Magnetic Resonance Imaging of Cells Overexpressing MagA, an Endogenous Contrast Agent for Live Cell Imaging
Magnetic Resonance Imaging of Cells Overexpressing MagA, an Endogenous Contrast Agent for Live Cell Imaging
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DOI：
10.2310/7290.2009.00006
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发表时间：
2009-05-01
影响因子：
2.8
通讯作者：
Prato, Frank S.
中科院分区：
文献类型：
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作者：
Goldhawk, Donna E.;Lemaire, Claude;Prato, Frank S.
磁共振成像（MRI）的分子成像可能受益于磁小体的亚铁磁性，膜封闭的铁生物矿物，其在趋磁细菌中的形成是由多个基因编码。一个这样的基因是MagA，一种假定的铁转运蛋白。我们研究了小鼠神经母细胞瘤N2A细胞中MagA的表达，并通过MRI表征了其对铁负荷和细胞成像的反应。在铁补充剂存在下生长的培养物中，MagA表达增强了普鲁士蓝染色和N2A细胞的元素铁含量，而不改变细胞增殖。尽管有证据表明MagA和变体MagA（E137V）中存在铁掺入，但只有MagA表达产生了在11特斯拉下通过MRI可检测到的细胞内对比度。我们使用这种稳定的表达系统来模拟一种新的序列，用于MRI细胞成像，使用梯度和自旋回波图像之间的差异来区分视野中的细胞和伪影。我们的研究结果表明，在哺乳动物细胞中的MagA活性响应于铁的补充和功能作为造影剂，可以通过一个单一的点突变失活。我们的结论是，MagA是一个候选的MRI报告基因，可以更充分地利用磁共振成像的上级分辨率在无创医学成像。
Molecular imaging with magnetic resonance imaging (MRI) may benefit from the ferrimagnetic properties of magnetosomes, membrane-enclosed iron biominerals whose formation in magnetotactic bacteria is encoded by multiple genes. One such gene is MagA, a putative iron transporter. We have examined expression of MagA in mouse neuroblastoma N2A cells and characterized their response to iron loading and cellular imaging by MRI. MagA expression augmented both Prussian blue staining and the elemental iron content of N2A cells, without altering cell proliferation, in cultures grown in the presence of iron supplements. Despite evidence for iron incorporation in both MagA and a variant, MagA(E137V), only MagA expression produced intracellular contrast detectable by MRI at 11 Tesla. We used this stable expression system to model a new sequence for cellular imaging with MRI, using the difference between gradient and spin echo images to distinguish cells from artifacts in the field of view. Our results show that MagA activity in mammalian cells responds to iron supplementation and functions as a contrast agent that can be deactivated by a single point mutation. We conclude that MagA is a candidate MRI reporter gene that can exploit more fully the superior resolution of MRI in noninvasive medical imaging.