Data from Magnetic Resonance Imaging Defines Cervicovaginal Anatomy, Cancer, and VEGF Trap Antiangiogenic Efficacy in Estrogen-Treated K14-HPV16 Transgenic Mice

Abstract

<div>Abstract<p>Noninvasive detection of dysplasia provides a potential platform for monitoring the efficacy of chemopreventive therapy of premalignancy, imaging the tissue compartments comprising dysplasia: epithelium, microvasculature, and stromal inflammatory cells. Here, using respiratory-gated magnetic resonance imaging (MRI), the anatomy of premalignant and malignant stages of cervical carcinogenesis in estrogen-treated K14-HPV16 transgenic mice was noninvasively defined. Dynamic contrast enhanced (DCE)-MRI was used to quantify leakage across premalignant dysplastic microvasculature. Vascular permeability as measured by DCE-MRI, <i>K</i><sup>trans</sup>, was similar in transgenic (0.053 ± 0.020 min<sup>−1</sup>; <i>n</i> = 32 mice) and nontransgenic (0.056 ± 0.029 min<sup>−1</sup>; <i>n</i> = 17 mice) animals despite a 2-fold increase in microvascular area in the former compared with the latter. DCE-MRI did detect a significant decrease in vascular permeability accompanying diminution of dysplastic microvasculature by the antiangiogenic agent, vascular endothelial growth factor Trap (<i>K</i><sup>trans</sup> = 0.052 ± 0.013 min<sup>−1</sup> pretreatment; <i>n</i> = 6 mice versus <i>K</i><sup>trans</sup> = 0.019 ± 0.008 min<sup>−1</sup> post-treatment; <i>n</i> = 5 mice). Thus, we determined that the threshold of microvessel leakage associated with cervical dysplasia was <17 kDa and highlighted the potential of DCE-MRI to noninvasively monitor the efficacy of antiangiogenic drugs or chemoprevention regimens targeting the vasculature in premalignant cervical dysplasia. [Cancer Res 2009;69(20):7945–52]</p></div>