Restricted Water Diffusion in Diffusion-Weighted Magnetic Resonance Imaging in Pancreatic Cancer is Associated with Tumor Hypoxia

Hypoxia is a hallmark of pancreatic cancer (PDAC) due to its compact and extensive fibrotic tumor stroma. Hypoxia contributes to high lethality of this disease, by inducing a more malignant phenotype and resistance to radiation and chemotherapy. Thus, non-invasive methods to quantify hypoxia could b...

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Bibliographic Details
Published in:	Cancers 2020-12, Vol.13 (1), p.89
Main Authors:	Mayer, Philipp, Kraft, Anne, Witzel, Hagen R, Marnet, Nicole, Hörner, Nina, Roth, Wilfried, Heinrich, Stefan, Hackert, Thilo, Bergmann, Frank, Kauczor, Hans-Ulrich, Klauss, Miriam, Gaida, Matthias M
Format:	Article
Language:	eng
Subjects:	Abdomen Cancer therapies Chemotherapy diffusion-weighted imaging Functional magnetic resonance imaging Hypoxia Invasiveness Lethality Lymphocytes B Magnetic resonance imaging Medical prognosis Metastasis Pancreatic cancer pancreatic ductal adenocarcinoma Patients Phenotypes Stroma Tumors Vascular endothelial growth factor
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Summary:	Hypoxia is a hallmark of pancreatic cancer (PDAC) due to its compact and extensive fibrotic tumor stroma. Hypoxia contributes to high lethality of this disease, by inducing a more malignant phenotype and resistance to radiation and chemotherapy. Thus, non-invasive methods to quantify hypoxia could be helpful for treatment decisions, for monitoring, especially in non-resectable tumors, or to optimize personalized therapy. In the present study, we investigated whether tumor hypoxia in PDAC is reflected by diffusion-weighted magnetic resonance imaging (DW-MRI), a functional imaging technique, frequently used in clinical practice for identification and characterization of pancreatic lesions. DW-MRI assesses the tissue microarchitecture by measuring the diffusion of water molecules, which is more restricted in highly compact tissues. As reliable surrogate markers for hypoxia, we determined Blimp-1 (B-lymphocyte induced maturation protein), a transcription factor, as well as vascular endothelial growth factor (VEGF), which are up-regulated in response to hypoxia. In 42 PDAC patients, we observed a close association between restricted water diffusion in DW-MRI and tumor hypoxia in matched samples, as expressed by high levels of Blimp-1 and VEGF in tissue samples of the respective patients. In summary, our data show that DW-MRI is well suited for the evaluation of tumor hypoxia in PDAC and could potentially be used for the identification of lesions with a high hypoxic fraction, which are at high risk for failure of radiochemotherapy.
ISSN:	2072-6694 2072-6694