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

• Published in: Journal of translational medicine Vol. 15; no. 1; p. 225
• Main Authors: Hauge, Anette, Wegner, Catherine S, Gaustad, Jon-Vidar, Simonsen, Trude G, Andersen, Lise Mari K, Rofstad, Einar K
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.11.2017; BioMed Central; BMC
• Subjects: Animals; Automation; Biomarkers; Cancer therapies; Care and treatment; Cervical cancer; Cervical carcinoma; Cervix; Contrast agents; Contrast Media - chemistry; DCE-MRI; Diagnosis; Echo surveys; Female; Heterocyclic Compounds - chemistry; Humans; Hypoxia; Magnetic Resonance Imaging; Mice, Inbred BALB C; Mice, Nude; Microvessels - diagnostic imaging; Microvessels - pathology; NMR; Nuclear magnetic resonance; Organometallic Compounds - chemistry; Patients; PDX models; Respiration; Squamous cell carcinoma; Tumor Microenvironment; Tumors; Uterine Cervical Neoplasms - blood supply; Uterine Cervical Neoplasms - diagnostic imaging; Uterine Cervical Neoplasms - pathology; Uterus; Xenografts; Hypoxia; DCE-MRI; Cervical carcinoma; Tumor microenvironment; PDX models
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-017-1331-4

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