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Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection

BACKGROUND: 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 magn...

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Autores principales: Bagga, Puneet, Haris, Mohammad, D’Aquilla, Kevin, Wilson, Neil E., Marincola, Francesco M., Schnall, Mitchell D., Hariharan, Hari, Reddy, Ravinder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450413/
https://www.ncbi.nlm.nih.gov/pubmed/28558795
http://dx.doi.org/10.1186/s12967-017-1221-9
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author Bagga, Puneet
Haris, Mohammad
D’Aquilla, Kevin
Wilson, Neil E.
Marincola, Francesco M.
Schnall, Mitchell D.
Hariharan, Hari
Reddy, Ravinder
author_facet Bagga, Puneet
Haris, Mohammad
D’Aquilla, Kevin
Wilson, Neil E.
Marincola, Francesco M.
Schnall, Mitchell D.
Hariharan, Hari
Reddy, Ravinder
author_sort Bagga, Puneet
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-017-1221-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-54504132017-06-01 Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection Bagga, Puneet Haris, Mohammad D’Aquilla, Kevin Wilson, Neil E. Marincola, Francesco M. Schnall, Mitchell D. Hariharan, Hari Reddy, Ravinder J Transl Med Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12967-017-1221-9) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-30 /pmc/articles/PMC5450413/ /pubmed/28558795 http://dx.doi.org/10.1186/s12967-017-1221-9 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bagga, Puneet
Haris, Mohammad
D’Aquilla, Kevin
Wilson, Neil E.
Marincola, Francesco M.
Schnall, Mitchell D.
Hariharan, Hari
Reddy, Ravinder
Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection
title Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection
title_full Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection
title_fullStr Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection
title_full_unstemmed Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection
title_short Non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection
title_sort non-caloric sweetener provides magnetic resonance imaging contrast for cancer detection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450413/
https://www.ncbi.nlm.nih.gov/pubmed/28558795
http://dx.doi.org/10.1186/s12967-017-1221-9
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