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CEST MRI monitoring of tumor response to vascular disrupting therapy using high molecular weight dextrans
Hanwei Chen1,2, Dexiang Liu1,2, Yuguo Li2,3
1Department of Radiology, Guangzhou Panyu Central Hospital, Guangzhou, Guangdong, China.
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 (MTRasym ) at 1 ppm were compared.
Results:
The results showed a significantly stronger CEST contrast enhancement at 1 ppm (∆MTRasym = 0.042 ± 0.002) in the TNF-α-treated tumors than those by Dex150 alone (∆MTRasym = 0.000 ± 0.005, P = 0.0229) or TNF-α alone (∆MTRasym = 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.
Insights
High molecular weight dextrans serve as effective contrast agents for monitoring cancer vascular disrupting therapies. Tumor necrosis factor-alpha significantly enhances dextran uptake, improving imaging sensitivity for treatment response.
Area of Science:
- Biomedical Imaging
- Cancer Therapy
- Pharmacology
Background:
- Vascular disrupting therapy (VDT) is a promising cancer treatment strategy.
- Monitoring tumor vascular permeability is crucial for assessing VDT efficacy.
- Chemical Exchange Saturation Transfer (CEST) MRI offers a potential imaging modality.
Purpose of the Study:
- To evaluate high molecular weight dextrans as CEST MRI contrast agents for monitoring VDT.
- To investigate the effect of tumor necrosis factor-alpha (TNF-α) on dextran uptake in tumors.
- To assess the feasibility of using dextran-based agents for theranostic applications.
Main Methods:
- CT26 colon tumors were established in mice.
- Mice received intravenous injections of 150 kD dextran (Dex150), TNF-α, or both.
- CEST MRI (Z-spectra) was performed before and after injections to quantify MTRasym at 1 ppm.
Main Results:
- TNF-α treatment significantly enhanced CEST contrast at 1 ppm compared to Dex150 or TNF-α alone.
- This enhancement indicated augmented tumor uptake of 150 kD dextran following TNF-α administration.
- MRI findings were corroborated by fluorescence imaging and immunofluorescence microscopy.
Conclusions:
- High molecular weight dextrans are safe and sensitive CEST MRI contrast agents for monitoring VDT response.
- TNF-α effectively augments tumor dextran uptake, improving imaging sensitivity.
- Dextran-based agents hold potential for developing theranostic drug delivery systems in cancer therapy.
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