Optoacoustics delineates murine breast cancer models displaying angiogenesis and vascular mimicry

Quiros-Gonzalez, Isabel; Tomaszewski, Michal R.; Aitken, Sarah J.; Ansel-Bollepalli, Laura; McDuffus, Leigh-Ann; Gill, Michael B.; Hacker, Lina; Brunker, Joanna; Bohndiek, Sarah E.

doi:10.1038/s41416-018-0033-x

Cited by 46 publications

(52 citation statements)

References 41 publications

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“…S5A). Furthermore, we found evidence of hypoxia in the core of 4T1 tumors, a finding also reported in the MDA-MB-231 tumor xenograft model (39). We conclude that the presence of hypoxia in the core of tumors cannot explain the observed decrease in FDG uptake in that region of the tumor.…”

Section: Discussionsupporting

confidence: 80%

Lactic Acid Accumulation in the Tumor Microenvironment Suppresses 18F-FDG Uptake

et al. 2019

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The process by which tumor cells take up 2-[ 18 F]fluoro-2deoxy-D-glucose (FDG) is heterogeneous and influenced by a multitude of factors. In mouse tumor grafts, the core of the tumor often presents lower FDG uptake than the periphery. Whether this pattern is caused by the intrinsic avidity of individual cells for FDG, the density of viable cells in the tumor, or the perfusion of the radiotracer remains unknown. In this study, we used radioluminescence microscopy to measure FDG uptake in single cells isolated from the core and periphery of the tumor and found that differences in FDG uptake persist on the level of single cells. Single cells from the core of 4T1 and MDA-MB-231 tumors grafts took up 26% to 84% less FDG than those from the periphery. These differences were observed in mice with large tumors (>8 mm diameter) but not in those with smaller tumors. To explain the origin of these differences, we examined the influence of three microenvironmental factors on FDG uptake. Hypoxia was ruled out as a possible explanation because its presence in the core would increase and not decrease FDG uptake. Higher cell proliferation in the periphery was consistent with higher FDG uptake, but there was no evidence of a causal relationship. Finally, lactate was higher in the core of the tumor, and it suppressed FDG uptake in a dose-dependent fashion. We therefore conclude that lactic acidosis-the combination of lactate ion buildup and acidic pH-can increase the heterogeneity of FDG uptake in MDA-MB-231 and 4T1 tumor grafts.Significance: Analysis of single cells from heterogeneous tumors reveals the role played by the tumor microenvironment, lactic acidosis in particular, on the uptake by tumor cells of 18 F-FDG, a PET imaging agent.

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Section: Discussionsupporting

confidence: 80%

Lactic Acid Accumulation in the Tumor Microenvironment Suppresses 18F-FDG Uptake

et al. 2019

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“…Photoacoustic tomography (PAT) exploits optically generated ultrasound to provide images that combine the high contrast and spectral specificity of optical imaging with the high spatial resolution of ultrasound. In particular, PAT has been widely used to image blood hemoglobin concentration and oxygenation, which have the potential to inform on a range of pathophysiologies, from tumour aggressiveness 1 and treatment response 2,3…”

Section: Introductionmentioning

confidence: 99%

Development of a blood oxygenation phantom for photoacoustic tomography combined with online pO2 detection and flow spectrometry

2019

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Photoacoustic tomography (PAT) is intrinsically sensitive to blood oxygen saturation (sO 2 ) in vivo. However, making accurate sO 2 measurements without knowledge of tissue-and instrumentation-related correction factors is extremely challenging. We have developed a low-cost flow phantom system to facilitate validation of photoacoustic tomography systems. The phantom is composed of a flow circuit, which is partially embedded within a tissue mimicking phantom, with independent sensors providing online monitoring of the optical absorption spectrum and partial pressure of oxygen in the tube. We first establish the flow phantom using two small molecule dyes that are frequently used for photoacoustic imaging: methylene blue (MB) and indocyanine green (ICG). We then demonstrate the potential of the phantom for evaluating sO 2 using chemical oxygenation and deoxygenation of blood in the phantom. Using this dynamic assessment of the photoacoustic sO 2 measurement in phantoms in relation to a ground truth, we explore the influence of multispectral processing and spectral coloring on accurate assessment of sO 2 . Future studies could exploit this low-cost dynamic flow phantom to validate fluence correction algorithms and explore additional blood parameters such as pH, and also absorptive and other properties of different fluids.

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“…These imaging biomarkers provide complementary hemodynamic information to those measured clinically with DCE-based techniques and also the label-free MRI-based techniques introduced above. OT has been shown to monitor the evolution of tumor vasculature during disease development (27,28) and to detect response to vascular-targeted therapies (29,30). OT has also been combined with DCE ultrasound (31,32), showing relationships between hemoglobin parameters and perfusion metrics.…”

Section: Introductionmentioning

confidence: 99%

Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis

et al. 2018

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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, OT can 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 techniques and tumor hypoxia quantified 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. Imaging biomarkers derived from optoacoustic tomography can be used as surrogate measures of tumor perfusion and hypoxia, potentially yielding rapid, multiparametric, and noninvasive cancer staging and therapeutic response monitoring in the clinic. http://cancerres.aacrjournals.org/content/canres/78/20/5980/F1.large.jpg .

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Optoacoustics delineates murine breast cancer models displaying angiogenesis and vascular mimicry

Cited by 46 publications

References 41 publications

Lactic Acid Accumulation in the Tumor Microenvironment Suppresses 18F-FDG Uptake

Lactic Acid Accumulation in the Tumor Microenvironment Suppresses 18F-FDG Uptake

Development of a blood oxygenation phantom for photoacoustic tomography combined with online pO2 detection and flow spectrometry

Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis

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