In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer

Milica Momcilovic, Anthony Jones, Sean T. Bailey, Christopher M. Waldmann, Rui Li, Jason T. Lee, Gihad Abdelhady, Adrian Gomez, Travis Holloway, Ernst Schmid, David Stout, Michael C. Fishbein, Linsey Stiles, Deepa V. Dabir, Steven M. Dubinett, Heather Christofk, Orian Shirihai, Carla M. Koehler, Saman Sadeghi and David B. Shackelford ()
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Milica Momcilovic: David Geffen School of Medicine at the University of California
Anthony Jones: David Geffen School of Medicine at the University of California
Sean T. Bailey: The Mouse Phase I Unit, Lineberger School of Medicine at the University of North Carolina Chapel Hill
Christopher M. Waldmann: David Geffen School of Medicine at the University of California
Rui Li: David Geffen School of Medicine at the University of California
Jason T. Lee: David Geffen School of Medicine at the University of California
Gihad Abdelhady: David Geffen School of Medicine at the University of California
Adrian Gomez: David Geffen School of Medicine at the University of California
Travis Holloway: David Geffen School of Medicine at the University of California
Ernst Schmid: David Geffen School of Medicine at the University of California
David Stout: Regis College
Michael C. Fishbein: David Geffen School of Medicine at the University of California
Linsey Stiles: David Geffen School of Medicine at the University of California
Deepa V. Dabir: Loyola Marymount University
Steven M. Dubinett: David Geffen School of Medicine at the University of California
Heather Christofk: David Geffen School of Medicine at the University of California
Orian Shirihai: David Geffen School of Medicine at the University of California
Carla M. Koehler: David Geffen School of Medicine at the University of California
Saman Sadeghi: David Geffen School of Medicine at the University of California
David B. Shackelford: David Geffen School of Medicine at the University of California

Nature, 2019, vol. 575, issue 7782, 380-384

Abstract: Abstract 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 ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. 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-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-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 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.

Date: 2019
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DOI: 10.1038/s41586-019-1715-0

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