Oxygen Enhanced Optoacoustic Tomography (OE-OT) Reveals Vascular Dynamics in Murine Models of Prostate Cancer
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Authors
Gonzalez, IQ
O'Connor, JPB
Abeyakoon, Oshaani
Parker, GJM
Williams, KJ
Publication Date
2017-09-01Journal Title
Theranostics
ISSN
1838-7640
Publisher
Ivyspring International Publisher
Volume
7
Issue
11
Pages
2900-2913
Language
English
Type
Article
This Version
VoR
Metadata
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Tomaszewski, M., Gonzalez, I., O'Connor, J., Abeyakoon, O., Parker, G., Williams, K., Gilbert, F., & et al. (2017). Oxygen Enhanced Optoacoustic Tomography (OE-OT) Reveals Vascular Dynamics in Murine Models of Prostate Cancer. Theranostics, 7 (11), 2900-2913. https://doi.org/10.7150/thno.19841
Abstract
Poor oxygenation of solid tumours has been linked with resistance to chemo- and radio-therapy and poor patient outcomes, hence non-invasive imaging of oxygen supply and demand in tumours could improve disease staging and therapeutic monitoring. Optoacoustic tomography (OT) is an emerging clinical imaging modality that provides static images of endogenous haemoglobin concentration and oxygenation. Here, we demonstrate oxygen enhanced (OE)-OT, exploiting an oxygen gas challenge to visualise the spatiotemporal heterogeneity of tumour vascular function. We show that tracking oxygenation dynamics using OE-OT reveals significant differences between two prostate cancer models in nude mice with markedly different vascular function (PC3 & LNCaP), which appear identical in static OT. LNCaP tumours showed a spatially heterogeneous response within and between tumours, with a substantial but slow response to the gas challenge, aligned with ex vivo analysis, which revealed a generally perfused and viable tumour with marked areas of haemorrhage. PC3 tumours had a lower fraction of responding pixels compared to LNCaP with a high disparity between rim and core response. While the PC3 core showed little or no dynamic response, the rim showed a rapid change, consistent with our ex vivo findings of hypoxic and necrotic core tissue surrounded by a rim of mature and perfused vasculature. OE-OT metrics are shown to be highly repeatable and correlate directly on a per-tumour basis to tumour vessel function assessed ex vivo. OE-OT provides a non-invasive approach to reveal the complex dynamics of tumour vessel perfusion, permeability and vasoactivity in real time. Our findings indicate that OE-OT holds potential for application in prostate cancer patients, to improve delineation of aggressive and indolent disease as well as in patient stratification for chemo- and radio-therapy.
Keywords
optoacoustic, imaging, oxygenation, angiogenesis, hypoxia
Sponsorship
We would also like to thank the CRUK Cambridge Institute Core Facilities for their support, including the BRU, Histopathology, Light Microscopy, Biorepository, and Preclinical Imaging. We are grateful for advice from Dr Simon Richardson (Institute of Cancer Research, Sutton, UK) on optimal use of the Oxylite pO2 probe. This work was supported by the EPSRC-CRUK Cancer Imaging Centre in Cambridge and Manchester (C197/A16465), Cancer Research UK (C14303/A17197, C47594/A16267) and the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° FP7-PEOPLE-2013-CIG-630729.
Funder references
Cancer Research UK (16465)
Cancer Research UK (C14303_do not transfer)
European Commission (630729)
Identifiers
External DOI: https://doi.org/10.7150/thno.19841
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266784
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
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