In vivo noninvasive preclinical tumor hypoxia imaging methods: a review

Abstract

Tumors exhibit areas of decreased oxygenation due to malformed blood vessels. This low oxygen concentration decreases the effectiveness of radiation therapy, and the resulting poor perfusion can prevent drugs from reaching areas of the tumor. Tumor hypoxia is associated with poorer prognosis and disease progression, and is therefore of interest to preclinical researchers. Although there are multiple different ways to measure tumor hypoxia and related factors, there is no standard for quantifying spatial and temporal tumor hypoxia distributions in preclinical research or in the clinic. This review compares imaging methods utilized for the purpose of assessing spatio-temporal patterns of hypoxia in the preclinical setting. Imaging methods provide varying levels of spatial and temporal resolution regarding different aspects of hypoxia, and with varying advantages and disadvantages. The choice of modality requires consideration of the specific experimental model, the nature of the required characterization and the availability of complementary modalities as well as immunohistochemistry.

Keywords:

• Cancer
• tumor
• hypoxia
• microenvironment
• imaging
• preclinical

Disclosure statement

No potential conflict of interest was reported by the author(s). The contents of this manuscript are solely the responsibility of the University of Western Australia and other participating institutions or individual authors and do not reflect the views of Cancer Australia.

Additional information

Funding

This study was supported by grant 1163065 from the Cancer Australia Priority-driven Collaborative Cancer Research Scheme. The contents of this manuscript are solely the responsibility of the individual authors and do not reflect the views of Cancer Australia.

Notes on contributors

Rebecca A. D’Alonzo

Rebecca A. D’Alonzo, MSc (Medical Physics) is a PhD candidate in Medical Physics at the University of Western Australia, Perth Australia. She has a background in physics and pathology, with a focus on preclinical research.

Suki Gill

Suki Gill, MBBS, FRCR, MRCP, FRANZCR, is a Radiation Oncologist at Sir Charles Gairdner hospital. His research interests are in stereotactic radiotherapy, physics, nuclear medicine, and immuno-oncology.

Pejman Rowshanfarzad

Pejman Rowshanfarzad, PhD, is the UWA Medical Physics Program Chair. His research interests are in radiotherapy physics, nuclear medicine, image processing, and machine learning. He has been awarded multiple faculty teaching and education awards.

Synat Keam

Synat Keam, MSc (Infectious Diseases) is a PhD candidate in Tumour Immunology at The University of Western Australia, Perth Australia.

Kelly M. MacKinnon

Kelly M. MacKinnon, MSc (Medical Physics), is a PhD candidate in Medical Physics at the University of Western Australia, Perth, Australia. Her research interests include radiobiology and computational approaches to cancer research.

Alistair M. Cook

Alistair M. Cook, PhD, is a Senior Postdoctoral Researcher at the University of Western Australia. His research aims to identify prognostic and predictive biomarkers for cancer immunotherapy, particularly malignant mesothelioma, and to investigate whether combination radiotherapy can improve response rates to immunotherapy drugs in patients with mesothelioma.

Martin A. Ebert

Martin A. Ebert, PhD, is Director of Physics Research in Radiation Oncology at the Sir Charles Gairdner Hospital, where he coordinates programs of research spanning clinical trials, basic radiobiology and radiobiological modelling, and the applications of quantitative imaging to oncology.