Bagga Puneet, Haris Mohammad, D'Aquilla Kevin, Wilson Neil E, Marincola Francesco M, Schnall Mitchell D, Hariharan Hari, Reddy Ravinder
Department of Radiology, Center for Magnetic Resonance and Optical Imaging, Perelman School of Medicine, University of Pennsylvania, 422 Curie Blvd, B1-Stellar-Chance Laboratories, Philadelphia, PA, USA.
Research Branch, Sidra Medical and Research Center, Doha, Qatar.
J Transl Med. 2017 May 30;15(1):119. doi: 10.1186/s12967-017-1221-9.
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.
外源性造影剂增强的图像对比度在癌症的早期检测、特征描述及精确位置确定中起着关键作用。在此,我们研究将非营养性甜味剂三氯蔗糖(商品名,Splenda)用作磁共振成像(MRI)造影剂用于癌症研究的可行性。
对三氯蔗糖溶液模型进行高分辨率核磁共振波谱和MR研究,以检测三氯蔗糖羟基质子与大量水的化学交换饱和转移(CEST)特性(sucCEST)。在动物实验中,使用雌性Fisher大鼠(F344/NCR)建立9L胶质肉瘤模型。在9.4 T MR扫描仪上对麻醉的大鼠进行带有CEST实验的MRI。在进行基线CEST扫描后,对对照大鼠和荷瘤大鼠静脉注射三氯蔗糖溶液。在注射三氯蔗糖期间及之后持续进行CEST采集。在进行sucCEST之后,注射钆-二乙烯三胺五乙酸以进行钆增强成像以可视化肿瘤。
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,发现注射三氯蔗糖后大脑的CEST对比度未受影响,表明其不能透过血脑屏障。在9L胶质瘤模型中,检测到肿瘤区域局部sucCEST对比度增强,而未受影响的脑区CEST效应未改变,这意味着三氯蔗糖对肿瘤组织具有特异性。在注射三氯蔗糖前后从肿瘤区域获取的CEST不对称图显示在1 ppm处不对称性升高,表明三氯蔗糖在增加对比度方面的作用。
我们展示了使用三氯蔗糖和sucCEST研究癌症临床前模型的可行性。本研究为三氯蔗糖和其他蔗糖衍生物作为临床MRI应用造影剂的潜在开发铺平了道路。