DCE-MRI of Patient-derived Xenograft Models of Uterine Cervix Carcinoma: Associations with Parameters of the Tumor Microenvironment

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2017 Nov 5

PMID 29100521

Citations 12

Authors

Anette Hauge

Catherine S Wegner

Jon-Vidar Gaustad

Trude G Simonsen

Lise Mari K Andersen

Einar K Rofstad

Affiliations

Soon will be listed here.

Abstract

Background: 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 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.

Methods: Four 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 (K ) and the fractional distribution volume (v ) 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.

Results: Both on the PDX model level and the single tumor level, a significant inverse correlation was found between K and hypoxic fraction. The extent of hypoxia was also associated with the fraction of voxels with unphysiological v values (v > 1.0). None of the DCE-MRI parameters were related to MVD or IFP.

Conclusions: DCE-MRI may provide valuable information on the hypoxic fraction of squamous cell carcinoma of the uterine cervix, and thereby facilitate individualized patient management.

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