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Updated: Jul 16, 2026
Spatial Measurements of Perfusion, Interstitial Fluid Pressure and Liposomes Accumulation in Solid Tumors
Published on: August 18, 2016
Effect of heterogeneous vasculature on interstitial transport within a solid tumor
Jianbing Zhao1, Howard Salmon, Malisa Sarntinoranont
1Department of Mechanical and Aerospace Engineering, 212 MAE-A, University of Florida, Gainesville, FL 32611, USA.
Abstract:
Novel strategies for cancer treatment involving macromolecular therapeutic agents have been recently developed and show promising results. Inadequate and heterogeneous uptake in tumor tissue has been shown to be a major obstacle for these compounds in clinical cancer therapy. Such distributions have been difficult to account for in predictive models. A three-dimensional computational model was developed to investigate the role of heterogeneous vasculature on interstitial transport within a murine sarcoma. The model accounts for extravasation and extracellular transport in a porous media. Spatial variation of fluid filtration rate per unit volume of tissue and vascular permeability were estimated from a dynamic contrast-enhanced (DCE)-MRI data set. Fluid filtration (L(p)S/V) and permeability (PS/V) maps were embedded in a model of tumor tissue and used to predict interstitial fluid pressure (IFP) and fluid flow. As in previous studies, pressure profiles were predicted to be elevated within the tumor. The model predicted boundary-dependent variation in outwardly directed interstitial velocity with lower velocities predicted near the skin boundary. Simulated tissue distribution of a macromolecular albumin tracer (MW approximately 60 kDa) was found to be heterogeneous with lower concentrations predicted in certain central regions. Simulated distributions of Gd-DTPA tracer (MW approximately 0.57 kDa) were less heterogeneous than albumin tracer. In sensitivity analysis, predicted tracer uptake was enhanced by increasing vascular leakiness. Increasing the interstitial hydraulic conductivity relative to the surrounding tissue reduced the overall drug uptake.
Insights
Heterogeneous tumor vasculature hinders macromolecular drug delivery. A computational model revealed that increased vascular leakiness enhances tracer uptake, while higher interstitial hydraulic conductivity reduces it, impacting cancer therapy strategies.
Area of Science:
- Biomedical Engineering
- Computational Biology
- Cancer Research
Background:
- Macromolecular therapeutic agents show promise for cancer treatment but face challenges with heterogeneous tumor uptake.
- Predictive models struggle to account for the complex distribution of these agents within tumor tissues.
Purpose of the Study:
- To develop and utilize a three-dimensional computational model to investigate the impact of heterogeneous tumor vasculature on interstitial transport of therapeutic agents.
- To predict interstitial fluid pressure (IFP) and tracer distribution within a murine sarcoma model.
Main Methods:
- A 3D computational model was developed incorporating extravasation and extracellular transport in a porous medium.
- Fluid filtration and vascular permeability maps were derived from dynamic contrast-enhanced (DCE)-MRI data.
- The model simulated the distribution of macromolecular (albumin) and small molecule (Gd-DTPA) tracers and predicted IFP and interstitial fluid flow.
Main Results:
- Elevated interstitial fluid pressure was predicted within the tumor.
- Simulated macromolecular tracer distribution was heterogeneous, with lower concentrations in central regions, unlike the less heterogeneous small molecule tracer distribution.
- Increased vascular leakiness enhanced tracer uptake, whereas increased interstitial hydraulic conductivity reduced it.
Conclusions:
- Tumor vasculature heterogeneity significantly influences macromolecular drug distribution.
- Computational modeling integrating DCE-MRI data provides valuable insights into interstitial transport dynamics for optimizing cancer therapeutics.
- Modulating vascular permeability and interstitial hydraulic conductivity presents potential strategies to improve drug delivery in solid tumors.
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