Abstract 718: Novel characterization of tumor transport dynamics using Cross-Voxel eXchange Model and DCE-MRI.

Abstract Despite significant advances in oncology, tumor heterogeneity continues to drive inconsistent responses to emerging therapeutics. Biophysical features of the tumor microenvironment (TME) - particularly elevated interstitial fluid pressure (IFP) and reduced hydraulic conductivity (K) generate outward convective flow that limits drug and tracer transport, contributing to resistance. Improved characterization of these parameters is essential for understanding TME-mediated barriers across tumor sites. In this work, the diverse ME180 tumor microenvironments were evaluated to test the ability of the Cross-Voxel eXchange Model (CVXM) to quantify transport properties and elucidate dynamic interactions between the TME and pharmacokinetics.ME180 cervical carcinoma xenografts were established in orthotopic, intramuscular, and subcutaneous sites in immunodeficient NRG mice. CVXM applied to 7T DCE-MRI (Biospec, Bruker) yielded voxel-wise estimates of extravasation, convection (velocity), diffusion, and hydraulic conductivity. Direct IFP measured with a solid-state transducer and ex vivo hydraulic conductivity measurements were used to validate CVXM-derived K. A subset of orthotopic tumors received fractionated radiotherapy (RT): 5×5 Gy (SmART+, Precision), and DCE-MRI acquired five days post-RT was used to assess CVXM sensitivity to RT-induced TME changes.CVXM produced spatial maps of key transport parameters (extravasation, tracer velocity, diffusion, and hydraulic conductivity) across tumor models. Extravasation ranged from 0.002-0.084min-1, peripheral velocity from 0.91-6.8μm/s and mean diffusion from 168-250μm2/s, all within reported physiological ranges. CVXM-derived K strongly correlated with convection-derived velocity (R2 = 0.49-0.65, p 0.001), with mean values ranging from 9.96×10-8 to 3.88×10-7cm2/(mmHg·s), consistent with previously published ME180 measurements. Following RT, orthotopic tumors exhibited a 12% reduction in IFP, accompanied by a 49% decrease in tracer velocity and a 29% decrease in CVXM-derived K at five days post-RT. These data indicate that CVXM provides a non-invasive means to characterize transport behavior within tumors and to detect biophysical changes resulting from treatment.These findings demonstrate that CVXM provides a non-invasive, imaging-based platform for quantifying tumor transport properties and detecting treatment-induced shifts in TME biophysics. By linking radiologic transport metrics with underlying physiology, CVXM offers a translational tool for monitoring therapy response and identifying biophysical biomarkers relevant to drug delivery and radiation efficacy. Citation Format: Janny Kim, Noha Sinno, Michael Milosevic, Catherine Coolens. Novel characterization of tumor transport dynamics using Cross-Voxel eXchange Model and DCE-MRI abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 718.