Magnetic resonance imaging defines cervico-vaginal anatomy cancer and VEGF Trap antiangiogenic efficacy in estrogen-treated K14-HPV16 transgenic mice

摘要

Non-invasive 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, K^trans, was similar in transgenic (0.053 ± 0.020 min⁻¹, n=32 mice) and nontransgenic (0.056 ± 0.029 min⁻¹, n=17 mice) animals, despite a two-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 anti-angiogenic agent, VEGF Trap (K^trans =0.052 ± 0.013 min⁻¹ pre-treatment; n=6 mice, vs. 0.019 +/− 0.008 min⁻¹ post-treatment; n = 5 mice). Thus, we determined that the threshold of microvessel leakage associated with cervical dysplasia was below 17 kDa, and highlighted the potential of DCE-MRI to non-invasively monitor the efficacy of anti-angiogenic drugs or chemoprevention regimens targeting the vasculature, in premalignant cervical dysplasia.