Abstract
BackgroundAbnormalities in the tumor microenvironment are associated with resistance to treatment, aggressive growth, and poor clinical outcome in patients with advanced cervical cancer. The potential of dynamic contrast-enhanced (DCE) MRI to assess the microvascular density (MVD), interstitial fluid pressure (IFP), and hypoxic fraction of patient-derived cervical cancer xenografts was investigated in the present study.MethodsFour patient-derived xenograft (PDX) models of squamous cell carcinoma of the uterine cervix (BK-12, ED-15, HL-16, and LA-19) were subjected to Gd-DOTA-based DCE-MRI using a 7.05 T preclinical scanner. Parametric images of the volume transfer constant (Ktrans) and the fractional distribution volume (ve) of the contrast agent were produced by pharmacokinetic analyses utilizing the standard Tofts model. Whole tumor median values of the DCE-MRI parameters were compared with MVD and the fraction of hypoxic tumor tissue, as determined histologically, and IFP, as measured with a Millar catheter.ResultsBoth on the PDX model level and the single tumor level, a significant inverse correlation was found between Ktrans and hypoxic fraction. The extent of hypoxia was also associated with the fraction of voxels with unphysiological ve values (ve > 1.0). None of the DCE-MRI parameters were related to MVD or IFP.ConclusionsDCE-MRI may provide valuable information on the hypoxic fraction of squamous cell carcinoma of the uterine cervix, and thereby facilitate individualized patient management.
Highlights
Abnormalities in the tumor microenvironment are associated with resistance to treatment, aggressive growth, and poor clinical outcome in patients with advanced cervical cancer
And late generation tumors of the same patient-derived xenograft (PDX) model were qualitatively similar in terms of histological features and hypoxia staining
Considering the relatively high microvascular permeability in many cancerous tissues, as well as the low molecular weight of gadolinium-tetraazacyclododecane‐ tetraacetic acid (Gd-DOTA), Ktrans is thought to be largely dependent on blood perfusion in our dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations of cervical cancer. Both on the PDX model level and the single tumor level, we found significant correlations between Ktrans and hypoxic fraction
Summary
Abnormalities in the tumor microenvironment are associated with resistance to treatment, aggressive growth, and poor clinical outcome in patients with advanced cervical cancer. The potential of dynamic contrastenhanced (DCE) MRI to assess the microvascular density (MVD), interstitial fluid pressure (IFP), and hypoxic fraction of patient-derived cervical cancer xenografts was investigated in the present study. Hypoxia has been associated with invasive growth, treatment resistance, and poor survival rates in many cancers, including cervical cancer [4,5,6]. Both microvascular density (MVD) and IFP are thought. Hauge et al J Transl Med (2017) 15:225 to influence the metastatic propensity of solid tumors [2, 7, 8] Accurate assessment of these critical parameters would be of great prognostic value and facilitate clinical decision-making on an individual patient basis. Promising observations have been made in clinical settings [13,14,15], but further investigations are required to explore the true benefits of DCE-MRI for other purposes than anatomical characterization of the tumor tissue
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