Mapping Extracellular pH of Gliomas in Presence of Superparamagnetic Nanoparticles: Towards Imaging the Distribution of Drug-Containing Nanoparticles and Their Curative Effect on the Tumor Microenvironment

Figure 1

Transverse relaxation rate () maps of an RG2 glioma-bearing rat that underwent renal ligation for TmDOTP⁵⁻ infusion, (a) without any contrast agent, (b) after infusion of TmDOTP⁵⁻, and (c) after infusion of SPIO-NPs. The scale bar in (a–c) denotes values from 0 to 80 s⁻¹. Compared to the map before TmDOTP⁵⁻ infusion (a), the enhancement was observed throughout the brain after TmDOTP⁵⁻ infusion (b), but superior enhancement and tumor delineation were observed following infusion of SPIO-NPs which also had cumulative effects from infusion of TmDOTP⁵⁻ (c). The contrast enhancement from both TmDOTP⁵⁻ and TmDOTP⁵⁻ with SPIO-NPs was region-specific, with highest enhancement in the tumor core and limited enhancement outside the tumor (relative to the intrinsic contrast, (a)). The black outline in (a–c) denotes the tumor boundary, which is based on the superior MRI contrast after infusion of SPIO-NPs. The region of interest (ROI) mask based on 1 mm circular rings from the tumor center (d) was used to generate the radial distribution histogram of these ROIs (e). Scale bar in (d) denotes 0 to 10 mm diameter circular ROIs (portrayed on a representative rat brain slice). The gray dashed line in (e) denotes the demarcation between tumor and nontumor regions. The amount of SPIO-NPs in the tumor was 4.3 times greater than in the healthy tissue suggesting a preferential extravasation and accumulation of SPIO-NPs in the tumor. See Figure S1 for examples of Prussian blue staining for SPIO-NPs of an RG2 glioma-bearing rat that underwent renal ligation for TmDOTP⁵⁻ infusion. See Figure S2 for examples of maps of an RG2 glioma-bearing rat that underwent coinfusion of probenecid and TmDOTP⁵⁻.

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