Manganese-enhanced MRI of human choroidal melanoma xenografts
Manganese-enhanced MRI of human choroidal melanoma xenografts
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DOI：
10.1167/iovs.06-1156
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发表时间：
2007-03-01
影响因子：
4.4
通讯作者：
Berkowitz, Bruce A.
中科院分区：
文献类型：
--
作者：
Braun, Rod D.;Gradianu, Marius;Berkowitz, Bruce A.
目的。为了验证使用锰增强MRI （MEMRI）可以同时评估实验性人脉络膜黑色素瘤异种移植和邻近非肿瘤视网膜的结构和功能的假设。将人脉络膜黑色素瘤细胞系C918培养的球体植入11只WAG/Nij-rnu裸鼠的上脉络膜上间隙。两周后，在腹腔注射生理盐水或MnCl2 4小时后收集MRI数据。MnCl2是一种MRI造影剂，可以作为细胞对离子（如钙）需求的生物标志物。测量以下参数：(1)肿瘤信号强度；(2)无肿瘤的下视网膜内、外信号强度；(3)下视网膜整体及内视网膜厚度。在体外对球体进行MnCl2暴露和洗涤后，分别进行MEMRI实验。在体外，暴露于MnCl2的球体在MEMRI期间保留了足够的Mn2+以显示对比度增强。在体内，与生理盐水相比，注射MnCl2可使肿瘤信号强度增加30% （P < 0.05）。荷瘤眼下视网膜外信号强度较对照眼相似区域增加17% (P < 0.05)，而下视网膜内信号强度无变化。荷瘤眼下视网膜总厚度较非荷瘤眼增加8% （P < 0.05）。目前在脉络膜黑色素瘤中发现了Mn2+摄取增强的区域，在邻近的非肿瘤视网膜中发现了意想不到的水肿和视网膜外离子需求增加，这表明MEMRI是一种潜在的无创监测肿瘤进展、治疗反应和疗效的有力方法。
PURPOSE. To test the hypothesis that the structure and function of an experimental human choroidal melanoma xenograft and neighboring non-tumor-bearing retina can be simultaneously assessed by using manganese-enhanced MRI (MEMRI).METHODS. Spheroids grown from the human choroidal melanoma cell line C918 were implanted in the superior suprachoroidal space of 11 WAG/Nij-rnu nude rats. Two weeks later, MRI data were collected 4 hours after intraperitoneal injection of saline or MnCl2, an MRI contrast agent that can act as a biomarker of cellular demand for ions, such as calcium. The following parameters were measured: (1) tumor signal intensity, (2) inner and outer retinal signal intensity in non-tumor-bearing inferior retina, and (3) whole and irmer retinal thickness of inferior retina. Separate MEMRI experiments were performed on spheroids in vitro after MnCl2 exposure and washing.RESULTS. In Vitro, spheroids exposed to MnCl2 retained sufficient Mn2+ to demonstrate contrast enhancement during MEMRI. In vivo, injection of MnCl2 resulted in a 30% increase in tumor signal intensity compared with tumors in rats injected with saline (P < 0.05). In inferior retina of tumor-bearing eyes, outer retinal signal intensity increased by 17% relative to a similar region in control eyes (P < 0.05), but there was no change in the inferior inner retinal intensity. Total retinal thickness of the inferior retina in the tumor-bearing eyes increased by 8%, compared with that in the non-tumor-bearing eyes (P < 0.05).CONCLUSIONS. The present identification of regions of enhanced Mn2+ uptake in choroidal melanoma and a somewhat unexpected edema and increased outer retinal ion demand in neighboring non-tumor-bearing retina highlights MEMRI as a potentially powerful method for noninvasively monitoring tumor progression and treatment response and efficacy.