Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.
Disselhorst, Jonathan A
American Association for Cancer Research
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Tomaszewski, M., Gehrung, M., Gehrung, M., Joseph, J., Joseph, J., Quiros-Gonzalez, I., Disselhorst, J. A., & et al. (2018). Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.. Cancer research, 78 (20), 5980-5991. https://doi.org/10.1158/0008-5472.can-18-1033
Measuring the functional status of the tumour vasculature, including blood flow fluctuations and changes in oxygenation is important in cancer staging and therapy monitoring. Current clinically approved imaging modalities suffer long procedure times and limited spatio-temporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that overcomes these challenges; by acquiring data at multiple wavelengths, OT can interrogate haemoglobin concentration and oxygenation directly, and resolve contributions from injected contrast agents. To establish the potential for OT to be used for rapid, multi-parametric, non-invasive assessment of the tumour vasculature, we tested whether two dynamic OT techniques, oxygen enhanced (OE) and dynamic contrast enhanced (DCE)-OT, could provide surrogate biomarkers of tumour vascular function, hypoxia and necrosis. We found that vascular maturity leads to changes in vascular function that affect tumour perfusion, modulating the DCE-OT signal. Perfusion in turn regulates oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumour and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumour hypoxia quantified ex vivo. Our findings suggest that OT may in the future offer significant advantage for localised imaging of tumour response to vascular targeted therapies when compared to existing clinical DCE methods.
Cell Line, Tumor, Animals, Mice, Inbred BALB C, Humans, Mice, Mice, Nude, Neoplasms, Necrosis, Oxygen, Contrast Media, Perfusion, Cell Hypoxia, Algorithms, Software, Photoacoustic Techniques, Biomarkers, Tumor, Tumor Hypoxia
Cancer Research UK (16465)
Cancer Research UK (C14303/A17197)
Cancer Research UK (C14303_do not transfer)
External DOI: https://doi.org/10.1158/0008-5472.can-18-1033
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282952