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DCE-MRI of patient-derived xenograft models of uterine cervix carcinoma: associations with parameters of the tumor microenvironment.

DCE-MRI of patient-derived xenograft models of uterine cervix carcinoma: associations with parameters of the tumor microenvironment.
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Hauge A, Wegner CS, Gaustad JV, Simonsen TG, Andersen LMK, Rofstad EK,


Hauge A, Wegner CS, Gaustad JV, Simonsen TG, Andersen LMK, Rofstad EK, (click to view)

Hauge A, Wegner CS, Gaustad JV, Simonsen TG, Andersen LMK, Rofstad EK,

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Journal of translational medicine 2017 11 0315(1) 225 doi 10.1186/s12967-017-1331-4
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 (trans)) and the fractional distribution volume (v e) 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 (trans) and hypoxic fraction. The extent of hypoxia was also associated with the fraction of voxels with unphysiological v e values (v e > 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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