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Theranostics 2017; 7(11):2900-2913. doi:10.7150/thno.19841 This issue Cite

Research Paper

Oxygen Enhanced Optoacoustic Tomography (OE-OT) Reveals Vascular Dynamics in Murine Models of Prostate Cancer

Michal R Tomaszewski^{1, 2}, Isabel Quiros Gonzalez^{1, 2}, James PB O'Connor^{3, 4}, Oshaani Abeyakoon⁵, Geoff JM Parker^{6, 7}, Kaye J Williams⁸, Fiona J Gilbert⁵, Sarah E Bohndiek^{1, 2✉}

1. Department of Physics, University of Cambridge, U.K.;
2. Cancer Research UK Cambridge Institute, University of Cambridge, U.K.;
3. Institute of Cancer Sciences, University of Manchester, U.K.;
4. Department of Radiology, The Christie NHS Foundation Trust, U.K.;
5. Department of Radiology, University of Cambridge, U.K.;
6. Centre for Imaging Sciences, University of Manchester, U.K.;
7. Bioxydyn Limited, Manchester, U.K.;
8. Manchester Pharmacy School, University of Manchester, U.K.

✉ Corresponding author: Address: Department of Physics, Cavendish Laboratory, JJ Thomson Avenue, Cambridge, CB3 0HE, U.K. and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Robinson Way, Cambridge, CB2 0RE, U.K. Phone: +44 1223 337267; Fax: +44 1223 337000; Email: seb53ac.uk. More

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.

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