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, David B. Shackelford

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

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.

Original languageEnglish
Pages (from-to)380-384
Number of pages5
JournalNature
Volume575
Issue number7782
DOIs
StatePublished - 14 Nov 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

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