Abstract
Tumor hypoxia is associated with resistance to treatment, aggressive growth, metastatic dissemination, and poor clinical outcome in many cancer types. The potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess the extent of hypoxia in tumors has been investigated in several studies in our laboratory. Cervical carcinoma, melanoma, and pancreatic ductal adenocarcinoma (PDAC) xenografts have been used as models of human cancer, and the transfer rate constant (Ktrans) and the extravascular extracellular volume fraction (ve) have been derived from DCE-MRI data by using Tofts standard pharmacokinetic model and a population-based arterial input function. Ktrans was found to reflect naturally occurring and treatment-induced hypoxia when hypoxia was caused by low blood perfusion, radiation responsiveness when radiation resistance was due to hypoxia, and metastatic potential when metastasis was hypoxia-induced. Ktrans was also associated with outcome for patients with locally-advanced cervical carcinoma treated with cisplatin-based chemoradiotherapy. Together, the studies imply that DCE-MRI can provide valuable information on the hypoxic status of cervical carcinoma, melanoma, and PDAC. In this communication, we review and discuss the studies and provide some recommendations as to how DCE-MRI data can be analyzed and interpreted to assess tumor hypoxia.
Highlights
Regions with hypoxic tissue are a characteristic feature of most experimental and human tumors [1]
We demonstrated that excluding voxels with ve > 1.0 is sufficient to exclude the majority of unphysiological voxel values in cervical carcinoma and pancreatic ductal adenocarcinoma (PDAC) xenograft models [24,25]
We have demonstrated that Ktrans derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-Magnetic resonance imaging (MRI)) data by using Tofts standard pharmacokinetic model and a population-based AIF is associated with tumor hypoxia in xenograft models of cervical carcinoma, melanoma, and PDAC
Summary
Regions with hypoxic tissue (pO2 < 10 mmHg) are a characteristic feature of most experimental and human tumors [1]. Preclinical studies have demonstrated that tumors with extensive hypoxia are resistant to several types of therapy and that tumor hypoxia can promote malignant progression and metastatic spread [1,2,3]. MRI can be performed with substantially higher spatial resolution than PET imaging, and DCE-MRI is highly attractive because the technique is associated with a high signal to noise ratio and is routinely used to detect and characterize various types of cancer in the clinic. Correlations have been found between DCE-MRI derived parameters and oxygen tension or the outcome of radiation therapy in some cancer types [13,14,15,16,17]. We investigated whether DCE-MRI derived parameters can be used to predict outcome for patients with locally-advanced cervical carcinoma In this communication, we review and discuss this work and provide recommendations as to how DCE-MRI can be used to detect tumor hypoxia
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