Premium
Evaluation of novel combined carbogen USPIO (CUSPIO) imaging biomarkers in assessing the antiangiogenic effects of cediranib (AZD2171) in rat C6 gliomas
Author(s) -
Burrell Jake S.,
WalkerSamuel Simon,
Baker Lauren C.J.,
Boult Jessica K.R.,
Jamin Yann,
Ryan Anderson J.,
Waterton John C.,
Halliday Jane,
Robinson Simon P.
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27460
Subject(s) - carbogen , medicine , hypoxia (environmental) , perfusion , magnetic resonance imaging , tumor hypoxia , vascular endothelial growth factor , pathology , vegf receptors , chemistry , radiology , radiation therapy , organic chemistry , oxygen
The recently described combined carbogen USPIO (CUSPIO) magnetic resonance imaging (MRI) method uses spatial correlations in independent imaging biomarkers to assess specific components of tumor vascular structure and function. Our study aimed to evaluate CUSPIO biomarkers for the assessment of tumor response to antiangiogenic therapy. CUSPIO imaging was performed in subcutaneous rat C6 gliomas before and 2 days after treatment with the potent VEGF‐signaling inhibitor cediranib ( n = 12), or vehicle ( n = 12). Histological validation of Hoechst 33342 uptake (perfusion), smooth muscle actin staining (maturation), pimonidazole adduct formation (hypoxia) and necrosis were sought. Following treatment, there was a significant decrease in fractional blood volume (−43%, p < 0.01) and a significant increase in hemodynamic vascular functionality (treatment altered Δ R 2 * carbogen from 1.2 to −0.2 s −1 , p < 0.05). CUSPIO imaging revealed an overall significant decrease in plasma perfusion (−27%, p < 0.05) following cediranib treatment, that was associated with selective effects on immature blood vessels. The CUSPIO responses were associated with a significant 15% reduction in Hoechst 33342 uptake ( p < 0.05), but no significant difference in vascular maturation or necrosis. Additionally, treatment with cediranib resulted in a significant 40% increase in tumor hypoxia ( p < 0.05). The CUSPIO imaging method provides novel and more specific biomarkers of tumor vessel maturity and vascular hemodynamics, and their response to VEGF‐signaling inhibition, compared to current MR imaging biomarkers utilized in the clinic. Such biomarkers may prove effective in longitudinally monitoring tumor vascular remodeling and/or evasive resistance in response to antiangiogenic therapy.