In vivo imaging of mitochondrial membrane potential in non-small-cell lung cancer
| Autor: | Anthony E. Jones, Adrian M. Gomez, Milica Momcilovic, Carla M. Koehler, Jason T. Lee, Saman Sadeghi, Travis Holloway, Heather R. Christofk, Rui Li, Orian S. Shirihai, Sean T. Bailey, Linsey Stiles, Michael C. Fishbein, David Stout, Steven M. Dubinett, Christopher M. Waldmann, Deepa V. Dabir, David B. Shackelford, Gihad Abdelhady, Ernst W. Schmid |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lung Neoplasms General Science & Technology 1.1 Normal biological development and functioning Oxidative phosphorylation Mitochondrion Membrane Potential Transgenic Mice 03 medical and health sciences Organophosphorus Compounds 0302 clinical medicine Underpinning research In vivo medicine Animals Humans Non-Small-Cell Lung Lung Cancer Membrane potential screening and diagnosis Multidisciplinary Chemistry Cell growth Carcinoma Lung Cancer medicine.disease Mitochondrial 4.1 Discovery and preclinical testing of markers and technologies Cell biology Detection 030104 developmental biology A549 Cells Positron-Emission Tomography 030220 oncology & carcinogenesis Cancer cell Biomedical Imaging Generic health relevance Preclinical imaging |
| Zdroj: | Nature, vol 575, iss 7782 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. A positron emission tomography imaging tracer is developed to image mitochondrial function in vivo, and application of this tracer to a mouse model of lung cancer identifies distinct functional mitochondrial heterogeneity between tumour cells. |
| Databáze: | OpenAIRE |
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