In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer
Open accessAbstract
Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP 1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts 2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18 F]fluorobenzyl-triphenylphosphonium (18 F-BnTP)4. By using PET imaging of 18 F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18 F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.
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A new PET probe, 18F-BnTP, accumulates in tumors in proportion to their reliance on OXPHOS, and in mouse models of lung cancer 18F-BnTP imaging predicts sensitivity to OXPHOS inhibition regardless of whether the tumors take up 18FDG.
“A new probe, 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP), accumulates in tumors in proportion to their reliance on OXPHOS (123). In mouse models of lung cancer, 18F-BnTP imaging predicts sensitivity to OXPHOS inhibition, regardless of whether or not the tumors take up 18FDG.”
From Metabolic reprogramming and cancer progression (2020) · cites this paper as [123]
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References 30 · Cited by 214
- Authors
- Momcilovic, M., Jones, A., Bailey, S. T., Waldmann, C. M., Li, R., Lee, J. T., Abdelhady, G., Gomez, A., Holloway, T., Schmid, E., Stout, D., Fishbein, M. C., Stiles, L., Dabir, D. V., Dubinett, S. M., Christofk, H., Shirihai, O., Koehler, C. M., Sadeghi, S., & Shackelford, D. B.
- Affiliations
- University of California, Los Angeles (US)
- University of North Carolina at Chapel Hill (US)
- Regis College (US)
- Loyola Marymount University (US)
- Corresponding author
- Shackelford, David B.
- ORCID
- Venue
- Nature
- Published
- 2019-10-30
- Volume
- 575
- Issue
- 7782
- Pages
- 380-384
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC7328016
- OpenAlex
- W2982664504
- Cited by
- 214
- References
- 30
- Citations by year
- 2026: 20 · 2025: 28 · 2024: 27 · 2023: 35 · 2022: 30 · 2021: 35 · 2020: 38 · 2019: 1
- FWCI
- 8.20
- Type
- journal article
- Language
- en
- Update notices
- correction (2020-01-03)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (KL2TR000122, KL2TR001882, UL1TR001881)
- National Heart, Lung, and Blood Institute (T32HL072752)
- National Cancer Institute (R01CA208642, P30CA016042, R01CA215185, R01CA267721, T32CA009056)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR070245)
- National Center for Advancing Translational Sciences
- Congressionally Directed Medical Research Programs
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Keywords
- mitochondrial membrane potential, non-small cell lung cancer, PET radiotracer, mitochondrial bioenergetics, oxidative phosphorylation, tumor heterogeneity, autochthonous mouse model, in vivo imaging, mitochondrial function
- MeSH terms
- A549 Cells, Animals, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Mice, Transgenic, Organophosphorus Compounds, Positron-Emission Tomography, Mice, Membrane Potential, Mitochondrial
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