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Hypoxia and perfusion in breast cancer: simultaneous assessment using PET/MR imaging.

Accepted version
Peer-reviewed

Type

Article

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Authors

Carmona-Bozo, Julia C 
Manavaki, Roido 
Woitek, Ramona 
Torheim, Turid 
Baxter, Gabrielle C 

Abstract

OBJECTIVES: Hypoxia is associated with poor prognosis and treatment resistance in breast cancer. However, the temporally variant nature of hypoxia can complicate interpretation of imaging findings. We explored the relationship between hypoxia and vascular function in breast tumours through combined 18F-fluoromisonidazole (18 F-FMISO) PET/MRI, with simultaneous assessment circumventing the effect of temporal variation in hypoxia and perfusion. METHODS: Women with histologically confirmed, primary breast cancer underwent a simultaneous 18F-FMISO-PET/MR examination. Tumour hypoxia was assessed using influx rate constant Ki and hypoxic fractions (%HF), while parameters of vascular function (Ktrans, kep, ve, vp) and cellularity (ADC) were derived from dynamic contrast-enhanced (DCE) and diffusion-weighted (DW)-MRI, respectively. Additional correlates included histological subtype, grade and size. Relationships between imaging variables were assessed using Pearson correlation (r). RESULTS: Twenty-nine women with 32 lesions were assessed. Hypoxic fractions > 1% were observed in 6/32 (19%) cancers, while 18/32 (56%) tumours showed a %HF of zero. The presence of hypoxia in lesions was independent of histological subtype or grade. Mean tumour Ktrans correlated negatively with Ki (r = - 0.38, p = 0.04) and %HF (r = - 0.33, p = 0.04), though parametric maps exhibited intratumoural heterogeneity with hypoxic regions colocalising with both hypo- and hyperperfused areas. No correlation was observed between ADC and DCE-MRI or PET parameters. %HF correlated positively with lesion size (r = 0.63, p = 0.001). CONCLUSION: Hypoxia measured by 18F-FMISO-PET correlated negatively with Ktrans from DCE-MRI, supporting the hypothesis of perfusion-driven hypoxia in breast cancer. Intratumoural hypoxia-perfusion relationships were heterogeneous, suggesting that combined assessment may be needed for disease characterisation, which could be achieved using simultaneous multimodality imaging. KEY POINTS: • At the tumour level, hypoxia measured by 18F-FMISO-PET was negatively correlated with perfusion measured by DCE-MRI, which supports the hypothesis of perfusion-driven hypoxia in breast cancer. • No associations were observed between 18F-FMISO-PET parameters and tumour histology or grade, but tumour hypoxic fractions increased with lesion size. • Intratumoural hypoxia-perfusion relationships were heterogeneous, suggesting that the combined hypoxia-perfusion status of tumours may need to be considered for disease characterisation, which can be achieved via simultaneous multimodality imaging as reported here.

Description

Keywords

Breast cancer, Hypoxia, PET/MRI, Perfusion, Breast Neoplasms, Female, Humans, Hypoxia, Magnetic Resonance Imaging, Perfusion, Positron-Emission Tomography

Journal Title

Eur Radiol

Conference Name

Journal ISSN

0938-7994
1432-1084

Volume Title

31

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cancer Research Uk (None)
Medical Research Council (MR/M009041/1)
Department of Health (via National Institute for Health Research (NIHR)) (NF-SI-0515-10067)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
This study was co-funded by Cancer Research UK (CRUK) – Cambridge Institute (CCCIT02) and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (BRC). J C Carmona-Bozo is supported by the Vargas Scholarship, Darwin College, University of Cambridge. R Manavaki, M J Graves and A J Patterson are supported by NIHR Cambridge BRC. F J Gilbert is a Senior Investigator at NIHR Cambridge BRC. The University of Cambridge PET/MR facility was funded by the Medical Research Council (MRC), UK. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care, UK.