Investigation of atovaquone-induced spatial changes in tumour hypoxia assessed by hypoxia PET/CT in non-small cell lung cancer patients

Background Tumour hypoxia promotes an aggressive tumour phenotype and enhances resistance to anticancer treatments. Following the recent observation that the mitochondrial inhibitor atovaquone increases tumour oxygenation in NSCLC, we sought to assess whether atovaquone affects tumour subregions dif...

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Published in:EJNMMI research Vol. 11; no. 1; pp. 130 - 10
Main Authors: Bourigault, Pauline, Skwarski, Michael, Macpherson, Ruth E., Higgins, Geoff S., McGowan, Daniel R.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 29.12.2021
Springer Nature B.V
SpringerOpen
Subjects:
Atovaquone
Cancer therapies
Cardiac Imaging
Coronary vessels
FMISO
Gene expression
Hypoxia
Imaging
Lung cancer
Medical imaging
Medicine
Medicine & Public Health
Metabolism
Monte Carlo simulation
Non-small cell lung cancer
Nuclear Medicine
Oncology
Original Research
Orthopedics
Oxygenation
Patients
PET
Positron emission
Radiation therapy
Radiology
Tomography
Tumors
Tumour hypoxia
FMISO
Atovaquone
Tumour hypoxia
PET
Non-small cell lung cancer
ISSN:2191-219X, 2191-219X
Online Access:Get full text
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Summary:Background Tumour hypoxia promotes an aggressive tumour phenotype and enhances resistance to anticancer treatments. Following the recent observation that the mitochondrial inhibitor atovaquone increases tumour oxygenation in NSCLC, we sought to assess whether atovaquone affects tumour subregions differently depending on their level of hypoxia. Methods Patients with resectable NSCLC participated in the ATOM trial (NCT02628080). Cohort 1 ( n  = 15) received atovaquone treatment, whilst cohort 2 ( n  = 15) did not. Hypoxia-related metrics, including change in mean tumour-to-blood ratio, tumour hypoxic volume, and fraction of hypoxic voxels, were assessed using hypoxia PET imaging. Tumours were divided into four subregions or distance categories: edge, outer, inner, and centre, using MATLAB. Results Atovaquone-induced reduction in tumour hypoxia mostly occurred in the inner and outer tumour subregions, and to a lesser extent in the centre subregion. Atovaquone did not seem to act in the edge subregion, which was the only tumour subregion that was non-hypoxic at baseline. Notably, the most intensely hypoxic tumour voxels, and therefore the most radiobiologically resistant areas, were subject to the most pronounced decrease in hypoxia in the different subregions. Conclusions This study provides insights into the action of atovaquone in tumour subregions that help to better understand its role as a novel tumour radiosensitiser. Trial registration : ClinicalTrials.gov, NCT0262808. Registered 11th December 2015, https://clinicaltrials.gov/ct2/show/NCT02628080
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ISSN:2191-219X
2191-219X
DOI:10.1186/s13550-021-00871-x