Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection.
Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection.
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DOI：
10.1186/s12967-017-1221-9
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发表时间：
2017-05-30
影响因子：
7.4
通讯作者：
Reddy R
中科院分区：
文献类型：
--
作者：
Bagga P;Haris M;D'Aquilla K;Wilson NE;Marincola FM;Schnall MD;Hariharan H;Reddy R
通过外源性造影剂增强的图像对比度在早期检测、表征和确定癌症的精确位置中起着至关重要的作用。在这里，我们研究了使用非营养甜味剂三氯蔗糖（商品名Splenda）作为癌症研究的磁共振成像（MRI）造影剂的可行性。采用高分辨核磁共振波谱（HNMR）和磁共振（MR）技术对三氯蔗糖溶液体模进行研究，以检测三氯蔗糖羟基质子与本体水的化学交换饱和转移（CEST）特性。对于动物实验，使用雌性Fisher大鼠（F344/NCR）来产生9 L-胶质肉瘤模型。在9.4T磁共振扫描仪上对麻醉大鼠进行了CEST MRI实验。基线CEST扫描后，在对照和荷瘤大鼠中静脉内施用三氯蔗糖溶液。在三氯蔗糖给药期间和给药后继续进行CEST收购。在sucCEST之后，注射钆-二亚乙基三胺五乙酸以进行Gd增强成像以使肿瘤可视化。发现体外sucCEST对比度与三氯蔗糖浓度呈正相关，与pH呈负相关，表明该技术在癌症成像中的潜力。在对照动物中，发现来自脑的CEST对比度在给予三氯蔗糖后不受影响，证明其血脑屏障不渗透性。在9 L神经胶质瘤模型中，检测到肿瘤区域中增强的局部sucCEST对比度，而未受影响的脑区域显示未改变的CEST效应，这意味着三氯蔗糖对肿瘤组织的特异性。在三氯蔗糖输注之前和之后从肿瘤区域获得的CEST不对称性图显示在1 ppm处不对称性升高，指向三氯蔗糖在增加对比度中的作用。我们展示了使用三氯蔗糖和sucCEST在癌症临床前模型研究中的可行性。这项研究为三氯蔗糖和其他蔗糖衍生物作为临床MRI应用的造影剂的潜在发展铺平了道路。本文的在线版本（doi：10.1186/s12967-017-1221-9）包含补充材料，可供授权用户使用。
Image contrast enhanced by exogenous contrast agents plays a crucial role in the early detection, characterization, and determination of the precise location of cancers. Here, we investigate the feasibility of using a non-nutritive sweetener, sucralose (commercial name, Splenda), as magnetic resonance imaging (MRI) contrast agent for cancer studies. High-resolution nuclear-magnetic-resonance spectroscopy and MR studies on sucralose solution phantom were performed to detect the chemical exchange saturation transfer (CEST) property of sucralose hydroxyl protons with bulk water (sucCEST). For the animal experiments, female Fisher rats (F344/NCR) were used to generate 9L-gliosarcoma model. MRI with CEST experiments were performed on anesthetized rats at 9.4 T MR scanner. Following the baseline CEST scans, sucralose solution was intravenously administered in control and tumor bearing rats. CEST acquisitions were continued during and following the administration of sucralose. Following the sucCEST, Gadolinium-diethylenetriamine pentaacetic acid was injected to perform Gd-enhanced imaging for visualizing the tumor. The sucCEST contrast in vitro was found to correlate positively with the sucralose concentration and negatively with the pH, indicating the potential of this technique in cancer imaging. In a control animal, the CEST contrast from the brain was found to be unaffected following the administration of sucralose, demonstrating its blood–brain barrier impermeability. In a 9L glioma model, enhanced localized sucCEST contrast in the tumor region was detected while the unaffected brain region showed unaltered CEST effect implying the specificity of sucralose toward the tumorous tissue. The CEST asymmetry plots acquired from the tumor region before and after the sucralose infusion showed elevation of asymmetry at 1 ppm, pointing towards the role of sucralose in increased contrast. We show the feasibility of using sucralose and sucCEST in study of preclinical models of cancer. This study paves the way for the potential development of sucralose and other sucrose derivatives as contrast agents for clinical MRI applications. The online version of this article (doi:10.1186/s12967-017-1221-9) contains supplementary material, which is available to authorized users.