Oxygen-enhanced and dynamic contrast- enhanced optoacoustic tomography provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis

TY - JOUR

T1 - Oxygen-enhanced and dynamic contrast- enhanced optoacoustic tomography provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis

AU - Tomaszewski, Michal R.

AU - Gehrung, Marcel

AU - Joseph, James

AU - Quiros-Gonzalez, Isabel

AU - Disselhorst, Jonathan A.

AU - Bohndiek, Sarah E.

PY - 2018/10/15

Y1 - 2018/10/15

N2 - Measuring the functional status of tumor 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 spatiotemporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that may overcome these challenges. By acquiring data at multiple wavelengths,OTcan interrogate hemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found that vascular maturity led to changes in vascular function that affected tumor perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumor and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumor hypoxia quantified ex vivo. Our findings indicate that OT may offer a significant advantage for localized imaging of tumor response to vascular-targeted therapies when compared with existing clinical DCE methods.

AB - Measuring the functional status of tumor 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 spatiotemporal resolution. Optoacoustic tomography (OT) is an emerging clinical imaging modality that may overcome these challenges. By acquiring data at multiple wavelengths,OTcan interrogate hemoglobin concentration and oxygenation directly and resolve contributions from injected contrast agents. In this study, we tested whether two dynamic OT techniques, oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found that vascular maturity led to changes in vascular function that affected tumor perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen availability, driving the OE-OT signal. In particular, we demonstrate for the first time a strong per-tumor and spatial correlation between imaging biomarkers derived from these in vivo techniques and tumor hypoxia quantified ex vivo. Our findings indicate that OT may offer a significant advantage for localized imaging of tumor response to vascular-targeted therapies when compared with existing clinical DCE methods.

UR - https://www.scopus.com/pages/publications/85054889696

U2 - 10.1158/0008-5472.CAN-18-1033

DO - 10.1158/0008-5472.CAN-18-1033

M3 - Article

C2 - 30115696

AN - SCOPUS:85054889696

SN - 0008-5472

VL - 78

SP - 5980

EP - 5991

JO - Cancer Research

JF - Cancer Research

IS - 20

ER -