S2550
Radiobiology - Microenvironment
ESTRO 2026
figure below. From the CVXM convection map, CVXM- derived K strongly correlated with velocity (R2 = 0.49– 0.65, p < 0.001) across tumour models, with mean values ranged from 9.96 × 10-8 to 3.88 × 10- 7cm ² /(mmHg·s), consistent with previously reported values for ME180 tumours5. Following RT, mice 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 results demonstrated that CVXM can non-invasively characterize tumour transport properties and detect treatment-induced changes in the biophysical properties of the tumour.
evasion. Nat Commun 2024 Keywords: microenvironment, angiogenesis, transcriptomics
Poster Discussion 2514
Quantitative and non-invasive assessment of tumour microenvironment dynamics with the Cross-Voxel Exchange Model and DCE-MRI Janny Kim 1,2 , Noha Sinno 2 , Michael Milosevic 3,4 , Catherine Coolens 1,2 1 Medical Biophysics, University of Toronto, Toronto, Canada. 2 Medical Physics, Princess Margaret Cancer Centre, Toronto, Canada. 3 Radiation Oncology, University of Toronto, Toronto, Canada. 4 Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada Purpose/Objective: Despite major advances in cancer treatment, tumour heterogeneity contributes to variable responses to novel therapies. Among the diverse components of the tumour microenvironment (TME), elevated interstitial fluid pressure (IFP) and low hydraulic conductivity (K) drive outward convective fluid flow, hindering therapeutic penetration and contributing to treatment resistance1,2. Characterizing these biophysical properties is essential for understanding the TME-mediated treatment resistance across tumour types. In this study, diverse TMEs were evaluated to assess the capability of the Cross-Voxel eXchange Model (CVXM) to quantify transport parameters and elucidate the dynamic relationship between the TME and pharmacokinetics. Material/Methods: ME180 human cervical carcinoma xenografts were implanted in NRG mice to establish orthotopic (n=26), intramuscular (n=18), and subcutaneous (n=12) tumours, demonstrating diverse TME. Extravasation, convection (velocity), and diffusion were quantified using CVXM and DCE-MRI (7T, Bruker). Direct IFP measurements using a solid-state pressure transducer (SPR-1000, Millar) and ex vivo K measurements were used to validate CVXM-derived K. A subset of orthotopic tumours received fractionated radiotherapy (RT) (5 x 5Gy; SmART+, Precision), followed by DCE-MRI five days post-RT to evaluate the model’s ability to capture RT-induced changes in the TME. Results: CVXM generated transport maps quantifying tumour extravasation, tracer velocity, diffusion, and hydraulic conductivity. Extravasation ranged from 0.002– 0.084min-1, peripheral velocity from 0.91-6.8 μ m/s and mean diffusion from 168–250 μ m2/s, all within physiologically reported ranges3,4, as shown in the
Conclusion: CVXM non-invasively quantified various tumour transport properties, including extravasation, convection, diffusion, and hydraulic conductivity, across diverse TME. CVXM also captured reductions in velocity and hydraulic conductivity following radiotherapy, illustrating its sensitivity to dynamic TME changes. By establishing the relationship between imaging-based biophysical metrics and underlying tumour physiology, this work advances translational radiobiology by providing a framework to monitor treatment-induced changes and identify predictive biomarkers for optimizing drug and radiation response. References: 1. Salavati, H. et al. Biochim. Biophys. Acta BBA - Rev. Cancer1877, 188792 (2022).2. Boucher, Y. et al.Br. J.
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