Purpose: Transport models, when paired with non-invasive imaging techniques, aim to predict drug accumulation in tumor tissue, greatly advantageous for tumor diagnosis and treatment outcome assessment. A Cross-Voxel Exchange Model (CVXM) describes the change in tracer concentration as the exchange of tracer between blood and tissue, in addition to the transport of tracer through the interstitium (diffusion and convection). At the level of a voxel, CVXM considers intra- and inter-voxel exchange of tracer. The goal is to derive kinetic properties of tumor tissue from DCE-MRI to predict drug perfusion and accumulation.
Methods: Twenty TS-415 human cervical carcinoma xenografts were established inside the gastrocnemius muscle of adult female BALB/c nu/nu mice. The mice were subjected to DCE-MRI for a period of 15 minutes using a 1.5-T whole body scanner (Signa, General Electric) at a spatial resolution of 0.23x0.23x2.0mm³ and a time resolution of 14 seconds. The tracer injected was Gd-DTPA. Regions of interests were selected radially from the tumor center outwards. CVXM was fitted to the data to generate spatial maps for fluid flow velocities v, diffusion coefficients D and extravasation parameters Kext and vₑ.
Results: The fitting results allowed distinguishing higher velocity measures at the periphery averaging to 14.37±3.65µm/s. The other resulting parameters are D (mean 253.98±85.37µm²/sec), Kext (mean 0.02±0.01min⁻¹) and vₑ (mean 0.09±0.02). These kinetic properties are in line with the observations in the MRI scans: strong contrast enhancements at the periphery (convection) and slower concentration uptakes towards the center of the tumor (slower acting diffusion).
Conclusion: CVXM fittings show a heterogeneous distribution of transport parameters suggesting an uneven accumulation of drug in the tumor microenvironment. The results support the need to investigate CVXM as a non-invasive technique to determine kinetic properties of the tumor tissue leading to better predictions of tumor aggressiveness and more informed treatment decisions.