Noninvasive imaging of the functional effects of anti-VEGF therapy on tumor cell extravasation and regional blood volume in an experimental brain metastasis model

Juan Juanyin, Kirsten Tracy, Luhua Zhang, Jeeva Munasinghe, Erik Shapiro, Alan Koretsky, Kathleen Kelly

Research output: Contribution to journalArticle

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Abstract

Brain metastasis has become an increasing cause of morbidity and mortality in cancer patients as the treatment of systemic disease has improved. Brain metastases frequently are highly vascularized, a process driven primarily by VEGF. VEGF mediates numerous changes within the vasculature including endothelial cell retraction and increased permeability, vasodilation, and new vessel formation. Here we describe a xenograft brain metastasis model that mimics the critical steps of metastasis including tumor cell dissemination and vascular adhesion, tumor growth and tumor associated angiogenesis. Magnetic resonance (MR) imaging was used to evaluate two aspects of the functional response of brain metastasis to the anti-VEGF receptor therapeutic, AZD2171 (Cediranib, RECENTIN™). MR tracking of individual cells demonstrated that cediranib did not impede tumor cell extravasation into the brain parenchyma despite evidence that anti-VEGF treatment decreases the permeability of the blood brain barrier. In a second assay, blood volume imaging using ultrasmall superparamagnetic iron oxide revealed that treatment of well-developed brain metastasis with cediranib for 7 days led to a heterogeneous response with respect to individual tumors. Overall, there was a significant average decrease in the tumor vascular bed volume. The majority of large tumors demonstrated substantially reduced central blood volumes relative to normal brain while retaining a rim of elevated blood volume at the tumor brain interface. Small tumors or occasional large tumors displayed a static response. Models and assays such as those described here will be important for designing mechanism-based approaches to the use of anti-angiogenesis therapies for the treatment of brain metastasis.

Original languageEnglish (US)
Pages (from-to)403-414
Number of pages12
JournalClinical and Experimental Metastasis
Volume26
Issue number5
DOIs
StatePublished - Jun 2009
Externally publishedYes

Profile

Blood Volume
Vascular Endothelial Growth Factor A
Neoplasm Metastasis
Brain
Neoplasms
Blood Vessels
Permeability
Cell Tracking
Vascular Endothelial Growth Factor Receptor
Blood-Brain Barrier
Heterografts
Vasodilation
Brain Neoplasms
Oxides
Magnetic Resonance Spectroscopy
Iron
Endothelial Cells
Magnetic Resonance Imaging
Morbidity
Mortality

Keywords

  • Animal model
  • AZD2171/Cediranib
  • Blood volume
  • Brain metastasis
  • MPIO
  • MRI
  • Prostate cancer
  • USPIO

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Noninvasive imaging of the functional effects of anti-VEGF therapy on tumor cell extravasation and regional blood volume in an experimental brain metastasis model. / Juanyin, Juan; Tracy, Kirsten; Zhang, Luhua; Munasinghe, Jeeva; Shapiro, Erik; Koretsky, Alan; Kelly, Kathleen.

In: Clinical and Experimental Metastasis, Vol. 26, No. 5, 06.2009, p. 403-414.

Research output: Contribution to journalArticle

Juanyin, Juan; Tracy, Kirsten; Zhang, Luhua; Munasinghe, Jeeva; Shapiro, Erik; Koretsky, Alan; Kelly, Kathleen / Noninvasive imaging of the functional effects of anti-VEGF therapy on tumor cell extravasation and regional blood volume in an experimental brain metastasis model.

In: Clinical and Experimental Metastasis, Vol. 26, No. 5, 06.2009, p. 403-414.

Research output: Contribution to journalArticle

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