Abstract 2818: In vivo imaging of mitochondrial bioenergetics in lung cancer
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AbstractNon-small cell lung cancer (NSCLC) is a histologically, genetically and metabolically heterogeneous disease. The mitochondria are essential regulators of cellular energy and metabolism and they play a critical role in sustaining growth and survival of lung tumor cells. However, our understanding of mitochondrial metabolism in cancer at an in vivo level has been limited thus leaving a large gap in our knowledge of how mitochondrial bioenergetics support tumor growth. To better study mitochondrial bioenergetics in lung tumors, we recently developed and validated a voltage sensitive, positron emission tomography (PET) tracer known as 4-[18F]fluorobenzyl triphenylphosphonium (18FBnTP) that we used to profile mitochondrial bioenergetics in autochthonous K-Ras driven mouse models of lung cancer (Momcilovic et al., (2019) Nature). The use of 18FBnTP PET imaging enabled us to functionally profile mitochondrial bioenergetics in live tumors and discover distinct functional mitochondrial heterogeneity conserved across different NSCLC tumor subtypes. In order to study mitochondria at the level of ultrastructure we coupled 18FBnTP PET with 3D serial block-face scanning electron microscopy (3D SBEM). By coupling these two techniques we are able to image and quantify mitochondria heterogeneity from whole tumors down to the ultrastructures of individual mitochondria within tumor cells. Our study reveals distinct organization of mitochondrial structure and function as lung tumors adapt during tumorigenesis. We anticipate that coupling 18FBnTP PET imaging with 3D SBEM will have dynamic applications beyond that of lung cancer and enrich our understanding how mitochondria impact human disease.Citation Format: Mingqi Han, Milica Momcilovic, Eric Bushong, Linsey Stiles, Orian Shirihai, Carla Koehler, Saman Sadeghi, Mark Ellisman, David B. Shackelford. In vivo imaging of mitochondrial bioenergetics in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2818.
