Purpose: The purpose of this study was to quantify and model the longitudinal intra-tumor physiological response to a single dose of a monoclonal antibody specific to the VEGFR2 using dynamic contrast-enhanced CT. Material and Methods: Dynamic contrast-enhanced CT imaging was performed on athymic nude mice bearing xenograft VEGF-transfected MCF-7 tumors (MCF7 VEGF) to quantify intra-tumor physiology pre- and post-injection (days 2, 7, and 14) of a nonspecific (IgG1, controls) and specific (DC101, treated) monoclonal antibody targeting VEGFR2. Parametrical maps of tumor physiology-perfusion (F), permeability surface area (PS), fractional plasma (f p), and interstitial space (f is)-were obtained at four time points over a 2-week period. Results: A temporal multistage recovery process whereby a decoupling of the fractional change in physiological parameters (f p, F) was observed when comparing treated to control tumors: f p and perfusion decreased by a combined 27% (P<0.01) and 65% (P<0.01) on day 2, while only perfusion remained reduced by 46% (P<0.01) on day 7. Intra-tumor heterogeneity defined by the change in variance of perfusion decreased on days 2 and 7; no change in the variance of f p was observed. Analysis based on a mathematical model linking perfusion and vascular morphology indicates that a decrease in f p and perfusion was consistent with a reduction in blood vessel radius, followed by an increase in the vascular radius and tortuosity resulting in the decoupling of f p and perfusion before returning to control levels. Conclusion: Inhibiting VEGFR2 activity results in a temporal decoupling of physiological parameters, which can be explained by a combination of morphological changes influencing perfusion. Such a decoupling has the potential to significantly impact the delivery of pharmaceuticals and oxygen within solid tumors, critical factors in combined anti-angiogenic and radio- and chemotherapies.
- Fractional plasma volume
ASJC Scopus subject areas
- Cancer Research
- Radiology Nuclear Medicine and imaging