Limitations of dynamic contrast‐enhanced MRI in monitoring radiation‐induced changes in the fraction of radiobiologically hypoxic cells in human melanoma xenografts

Benjaminsen, Ilana C.; Melås, Elin A.; Mathiesen, Berit; Rofstad, Einar K.

doi:10.1002/jmri.21602

Cited by 5 publications

(2 citation statements)

References 33 publications

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“…The hypoxic tumor fraction may increase shortly after radiation exposure because aerobic cancer cells are inactivated, whereas the hypoxic cancer cells survive. To investigate whether K trans and/or v e are sensitive to radiation-induced hypoxia, we subjected melanoma xenografts to DCE-MRI before (day 0) and after (day 1) radiation exposure [40]. Although the hypoxic fraction increased after irradiation, no changes in K trans nor v e were observed ( Figure 5).…”

Section: K Trans Is Insensitive To Radiation-induced Hypoxiamentioning

confidence: 99%

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness

Gaustad

Hauge

Wegner

et al. 2020

Cancers

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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.

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Section: K Trans Is Insensitive To Radiation-induced Hypoxiamentioning

confidence: 99%

DCE-MRI of Tumor Hypoxia and Hypoxia-Associated Aggressiveness

Gaustad

Hauge

Wegner

et al. 2020

Cancers

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“…It was also shown that hypoxia estimated by 18 F-FMISO-PET correlated negatively with Ktrans from DCE-MRI in animal models, in head and neck cancers and in breast tumors, supporting the use of DCE-MRI to measure perfusion-driven hypoxia (Cho et al, 2009;Simoncic et al, 2017;Carmona-Bozo et al, 2021). However, several important limitations were also noted (Benjaminsen et al, 2008;Gulliksrud et al, 2010;Jordan and Gallez, 2010;Borren et al, 2013), including the absence of correlation of DCE-MRI parameters with the expression of HIF-1α and HIF-2α (Øvrebø et al, 2012). It should be emphasized that DCE-MRI takes only into account the perfusion without consideration to the oxygen consumption that plays also an important role in the establishment of tumor hypoxia.…”

Section: Magnetic Resonance Imaging With Exogenous Contrastmentioning

confidence: 83%

The Role of Imaging Biomarkers to Guide Pharmacological Interventions Targeting Tumor Hypoxia

Gallez

2022

Front. Pharmacol.

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Hypoxia is a common feature of solid tumors that contributes to angiogenesis, invasiveness, metastasis, altered metabolism and genomic instability. As hypoxia is a major actor in tumor progression and resistance to radiotherapy, chemotherapy and immunotherapy, multiple approaches have emerged to target tumor hypoxia. It includes among others pharmacological interventions designed to alleviate tumor hypoxia at the time of radiation therapy, prodrugs that are selectively activated in hypoxic cells or inhibitors of molecular targets involved in hypoxic cell survival (i.e., hypoxia inducible factors HIFs, PI3K/AKT/mTOR pathway, unfolded protein response). While numerous strategies were successful in pre-clinical models, their translation in the clinical practice has been disappointing so far. This therapeutic failure often results from the absence of appropriate stratification of patients that could benefit from targeted interventions. Companion diagnostics may help at different levels of the research and development, and in matching a patient to a specific intervention targeting hypoxia. In this review, we discuss the relative merits of the existing hypoxia biomarkers, their current status and the challenges for their future validation as companion diagnostics adapted to the nature of the intervention.

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