Non-invasive visualization of mast cell recruitment and its effects in lung cancer by optical reporter gene imaging and glucose metabolism monitoring

Seul-Gi Oh; Xian Li; Ho Won Lee; Thoudam Debraj Singh; Sang Bong Lee; Hyun Dong Ji; GhilSuk Yoon; Sung Jin Cho; In-Kyu Lee; Shin Young Jeong; Byeong-Cheol Ahn; Jaetae Lee; Hyeun Wook Chang; Sang-Woo Lee; Yong Hyun Jeon

doi:10.1016/j.biomaterials.2016.10.023

Non-invasive visualization of mast cell recruitment and its effects in lung cancer by optical reporter gene imaging and glucose metabolism monitoring

Biomaterials. 2017 Jan:112:192-203. doi: 10.1016/j.biomaterials.2016.10.023. Epub 2016 Oct 13.

Authors

Affiliations

¹ Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
² College of Pharmacy, Yeungnam University, Gyeongsan, South Korea.
³ Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea.
⁴ Department of Pathology, School of Medicine, Kyungpook National University, Daegu, South Korea.
⁵ Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 41061, South Korea.
⁶ Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, 41944, South Korea.
⁷ Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
⁸ College of Pharmacy, Yeungnam University, Gyeongsan, South Korea. Electronic address: [email protected].
⁹ Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea. Electronic address: [email protected].
¹⁰ Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea. Electronic address: [email protected].

PMID: 27768973
DOI: 10.1016/j.biomaterials.2016.10.023

Abstract

The inability to monitor the in vivo dynamics of mast cells (MCs) limits the better understanding of its role in cancer progression. Here, we report on noninvasive imaging of MC migration to tumor lesions in mice and evaluation of the effects of migrated MCs on tumor progression through reporter gene-based in vivo optical imaging and glucose metabolism monitoring in cancer with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in vitro and in vivo. Murine MCs (MC-9) and Lewis lung cancer cells (LLC) expressing an enhanced firefly luciferase (effluc) gene were established, termed MC-9/effluc and LLC/effluc, respectively. MC-9/effluc cell migration to LLC tumor lesions was initially detected within 1 h post-transfer and distinct bioluminescence imaging signals emitted from MC-9/effluc cells were observed at tumor sites until 96 h. In vivo optical imaging as well as a biodistribution study with ¹⁸F-FDG demonstrated more rapid tumor growth and upregulated glucose uptake potentially associated with MC migration to tumor lesions. These results suggest that the combination of a reporter gene-based optical imaging approach and glucose metabolism status monitoring with ¹⁸F-FDG represents a promising tool to better understand the biological role of MCs in tumor microenvironments and to develop new therapeutic drugs to regulate their involvement in enhanced tumor growth.

Keywords: (18)F-fluorodeoxyglucose; Glucose metabolism; Lung tumor lesion; Mast cells; Optical reporter gene imaging; Recruitment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Line, Tumor
Cell Tracking / methods*
Female
Genes, Reporter / genetics
Glucose / metabolism*
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology*
Mast Cells / metabolism*
Mast Cells / pathology*
Mice
Mice, Inbred C57BL
Microscopy, Fluorescence / methods*
Molecular Imaging / methods
Neoplasm Invasiveness

Substances

Glucose