Characterization of tumor vascular permeability using natural dextrans and CEST MRI

Yuguo Li, Yuan Qiao, Hanwei Chen, Renyuan Bai, Verena Staedtke, Zheng Han, Jiadi Xu, Kannie W.Y. Chan, Nirbhay Yadav, Jeff W Bulte, Shibin Zhou, Peter C Van Zijl, Guanshu Liu

Research output: Contribution to journalArticle

Abstract

Purpose: To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability. Methods: Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N=5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6nm) and 70 kD (D70, 12nm) dextran at a dose of 375mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40min after each injection using a dynamic CEST imaging scheme. Results: All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9ppm. The detectability and effects of pH and saturation conditions (B1 and Tsat) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant "dexCEST" enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry. Conclusions: As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems.

Original languageEnglish (US)
JournalMagnetic Resonance in Medicine
DOIs
StateAccepted/In press - Jan 1 2017

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Capillary Permeability
Dextrans
Neoplasms
Injections
Permeability
Molecular Weight
Optical Imaging
Drug Delivery Systems
Particle Size
Colon
Immunohistochemistry

Keywords

  • Cancer
  • CEST
  • Dextran
  • MRI
  • Permeability

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{b7d54c4fbb4b482789ed2c6157c20b93,
title = "Characterization of tumor vascular permeability using natural dextrans and CEST MRI",
abstract = "Purpose: To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability. Methods: Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N=5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6nm) and 70 kD (D70, 12nm) dextran at a dose of 375mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40min after each injection using a dynamic CEST imaging scheme. Results: All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9ppm. The detectability and effects of pH and saturation conditions (B1 and Tsat) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant {"}dexCEST{"} enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry. Conclusions: As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems.",
keywords = "Cancer, CEST, Dextran, MRI, Permeability",
author = "Yuguo Li and Yuan Qiao and Hanwei Chen and Renyuan Bai and Verena Staedtke and Zheng Han and Jiadi Xu and Chan, {Kannie W.Y.} and Nirbhay Yadav and Bulte, {Jeff W} and Shibin Zhou and {Van Zijl}, {Peter C} and Guanshu Liu",
year = "2017",
month = "1",
day = "1",
doi = "10.1002/mrm.27014",
language = "English (US)",
journal = "Magnetic Resonance in Medicine",
issn = "0740-3194",
publisher = "John Wiley and Sons Inc.",

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TY - JOUR

T1 - Characterization of tumor vascular permeability using natural dextrans and CEST MRI

AU - Li, Yuguo

AU - Qiao, Yuan

AU - Chen, Hanwei

AU - Bai, Renyuan

AU - Staedtke, Verena

AU - Han, Zheng

AU - Xu, Jiadi

AU - Chan, Kannie W.Y.

AU - Yadav, Nirbhay

AU - Bulte, Jeff W

AU - Zhou, Shibin

AU - Van Zijl, Peter C

AU - Liu, Guanshu

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Purpose: To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability. Methods: Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N=5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6nm) and 70 kD (D70, 12nm) dextran at a dose of 375mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40min after each injection using a dynamic CEST imaging scheme. Results: All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9ppm. The detectability and effects of pH and saturation conditions (B1 and Tsat) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant "dexCEST" enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry. Conclusions: As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems.

AB - Purpose: To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability. Methods: Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N=5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6nm) and 70 kD (D70, 12nm) dextran at a dose of 375mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40min after each injection using a dynamic CEST imaging scheme. Results: All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9ppm. The detectability and effects of pH and saturation conditions (B1 and Tsat) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant "dexCEST" enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry. Conclusions: As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems.

KW - Cancer

KW - CEST

KW - Dextran

KW - MRI

KW - Permeability

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U2 - 10.1002/mrm.27014

DO - 10.1002/mrm.27014

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SN - 0740-3194

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