ArticleCancer research communications2024
Combined Oxygen-Enhanced MRI and Perfusion Imaging Detect Hypoxia Modification from Banoxantrone and Atovaquone and Track Their Differential Mechanisms of Action.
Article in Cancer research communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The iron-sulfur cluster assembly factor FDX2 is required for tumor initiation but not for growth of established tumors in transplantation models.The Journal of biological chemistry · 2026Article
- Targeting tumor transition windows.Exploration of targeted anti-tumor therapy · 2026Review
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12 authors.
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Abstract
Oxygen-enhanced MRI (OE-MRI) has shown promise for quantifying and spatially mapping tumor hypoxia, either alone or in combination with perfusion imaging. Previous studies have validated the technique in mouse models and in patients with cancer. Here, we report the first evidence that OE-MRI can track change in tumor oxygenation induced by two drugs designed to modify hypoxia. Mechanism of action of banoxantrone and atovaquone were confirmed using in vitro experiments. Next, in vivo OE-MRI studies were performed in Calu6 and U87 xenograft tumor models, alongside fluorine-18-fluoroazomycin arabinoside PET and immunohistochemistry assays of hypoxia. Neither drug altered tumor size. Banoxantrone reduced OE-MRI hypoxic fraction in Calu6 tumors by 52.5% ± 12.0% (P = 0.008) and in U87 tumors by 29.0% ± 15.8% (P = 0.004) after 3 days treatment. Atovaquone reduced OE-MRI hypoxic fraction in Calu6 tumors by 53.4% ± 15.3% (P = 0.002) after 7 days therapy. PET and immunohistochemistry provided independent validation of the MRI findings. Finally, combined OE-MRI and perfusion imaging showed that hypoxic tissue was converted into necrotic tissue when treated by the hypoxia-activated cytotoxic prodrug banoxantrone, whereas hypoxic tissue became normoxic when treated by atovaquone, an inhibitor of mitochondrial complex III of the electron transport chain. OE-MRI detected and quantified hypoxia reduction induced by two hypoxia-modifying therapies and could distinguish between their differential mechanisms of action. These data support clinical translation of OE-MRI biomarkers in clinical trials of hypoxia-modifying agents to identify patients demonstrating biological response and to optimize treatment timing and scheduling. Significance: For the first time, we show that hypoxic fraction measured by oxygen-enhanced MRI (OE-MRI) detected changes in tumor oxygenation induced by two drugs designed specifically to modify hypoxia. Furthermore, when combined with perfusion imaging, OE-MRI hypoxic volume distinguished the two drug mechanisms of action. This imaging technology has potential to facilitate drug development, enrich clinical trial design, and accelerate clinical translation of novel therapeutics into clinical use.
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