Characterization of tumor vascular permeability using natural dextrans and CEST MRI

PurposeTo investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability. MethodsDextrans 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. ResultsAll 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 (B-1 and T-sat) 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. ConclusionsAs 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. Magn Reson Med 79:1001-1009, 2018. (c) 2017 International Society for Magnetic Resonance in Medicine.