Magnetic resonance imaging assays for dimethyl sulfoxide effect on cancer vasculature

Objectives: To evaluate the potential of quantitative assays of vascular characteristics based on dynamic contrast-enhanced magnetic resonance imaging (MRI) using a macromolecular contrast medium (MMCM) to search for and measure effects of dimethyl sulfoxide (DMSO) on cancer vasculature with microscopic correlations. Material and Methods: Saline-treated control (n = 8) and DMSO-treated (n = 7) human breast cancer xenografts (MDA-MB-435) in rats were imaged dynamicall y by MMCM-enhanced MRI using albumin-(Gd-DTPA)(27)-(biotin)(11) (molecular weight approximately 90 kDa), before and after a 1-week, 3-dose treatment course. After the posttreatment MRI examinations, tumors were perfused with lectin and fixative and subsequently stained with RECA-1 and streptavidin for quantitative fluorescent microscopy. Quantitative MRI estimates of cancer microvessel permeability (K-PS; mu L/min.100 cm(3)) and fractional plasma volume (fPV; %) were based on a 2-compartment kinetic model. Fluorescent microscopy yielded estimates of MMCM extravasation and vascular density that were compared to the MRI results. Results: DMSO decreased cancer vascular endothelial permeability significantly (P < 0.05) from tumor K(PS)day0 = 19.3 +/- 8.8 mu L/min.100 cm(3) to K(PS)day7 = 0 mu L/min.100 cm(3)). K-PS values in the saline-treated tumors did not change significantly. The amount of extravasated albumin-Gd-(DTPA)(27)-(biotin)(11), as assayed by a fluorescently labeled streptavidin stain that strongly binds to the biotin tag on the MMCM, was significantly (P < 0.05) lower in the DMSO-treated cancers than in the control cancers (57.7% +/- 5.5% vs. 34.2% +/- 4.9%). Tumor vascular richness as reflected by the MRI-assayed fPV and by the RECA-1 and lectin-stained microscopy did not change significantly with DMSO or saline treatment. Conclusion: Reductions in cancer microvascular leakiness induced by a 7-day course of DMSO could be detected and measured by dynamic MMCM-enhanced MRI and were confirmed by microscopic measurements of the leaked macromolecular agents in the same cancers. Results support the robustness of an MMCM-enhanced MRI approach to the characterization of cancers and providing first evidence for an in vivo effect of DMSO on cancer blood vessels.