Monitoring the longitudinal intra-tumor physiological impulse response to VEGFR2 blockade in breast tumors using DCE-CT

Keith M. Stantz, Minsong Cao, Ning Cao, Yun Liang, Kathy D. Miller

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1183-1195
Number of pages13
JournalMolecular Imaging and Biology
Volume13
Issue number6
DOIs
StatePublished - Dec 1 2011

Keywords

  • DC101
  • DCE-CT
  • Fractional plasma volume
  • Heterogeneity
  • Perfusion

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging

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