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CEST MRI monitoring of tumor response to vascular disrupting therapy using high molecular weight dextrans
Author(s) -
Chen Hanwei,
Liu Dexiang,
Li Yuguo,
Xu Xiang,
Xu Jiadi,
Yadav Nirbhay N.,
Zhou Shibin,
Zijl Peter C. M.,
Liu Guanshu
Publication year - 2019
Publication title -
magnetic resonance in medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.696
H-Index - 225
eISSN - 1522-2594
pISSN - 0740-3194
DOI - 10.1002/mrm.27818
Subject(s) - dextran , vascular permeability , magnetic resonance imaging , tumor necrosis factor alpha , magnetization transfer , medicine , chemistry , fluorescence lifetime imaging microscopy , pathology , nuclear magnetic resonance , cancer research , fluorescence , radiology , biochemistry , physics , quantum mechanics
Purpose Vascular disrupting therapy of cancer has become a promising approach not only to regress tumor growth directly but also to boost the delivery of chemotherapeutics in the tumor. An imaging approach to monitor the changes in tumor vascular permeability, therefore, has important applications for monitoring of vascular disrupting therapies. Methods Mice bearing CT26 subcutaneous colon tumors were injected intravenously with 150 kD dextran (Dex150, diameter, d~ 20 nm, 375 mg/kg), tumor necrosis factor‐alpha (TNF‐α; 1 µg per mouse), or both (n = 3 in each group). The Z‐spectra were acquired before and 2 h after the injection, and the chemical exchange saturation transfer (CEST) signals in the tumors as quantified by asymmetric magnetization transfer ratio (MTR asym ) at 1 ppm were compared. Results The results showed a significantly stronger CEST contrast enhancement at 1 ppm (∆MTR asym = 0.042 ± 0.002) in the TNF‐α‐treated tumors than those by Dex150 alone (∆MTR asym = 0.000 ± 0.005, P = 0.0229) or TNF‐α alone (∆MTR asym = 0.002 ± 0.004, P = 0.0264), indicating that the TNF‐α treatment strongly augmented the tumor uptake of 150 kD dextran. The MRI findings were verified by fluorescence imaging and immunofluorescence microscopy. Conclusions High molecular weight dextrans can be used as safe and sensitive CEST MRI contrast agents for monitoring tumor response to vascular disrupting therapy and, potentially, for developing dextran‐based theranostic drug delivery systems.