title: Non-invasive visualization of mast cell recruitment and its effects in lung cancer by optical reporter gene imaging and glucose metabolism monitoring.
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 with18F-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 with18F-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 with18F-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.
authors: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors: Seul-Gi
authors: SG
authors: Oh
authors: College of Pharmacy, Yeungnam University, Gyeongsan, South Korea.
authors: Xian
authors: X
authors: Li
authors: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors: Ho Won
authors: HW
authors: Lee
authors: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors: Thoudam Debraj
authors: TD
authors: Singh
authors: 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.
authors: Sang Bong
authors: SB
authors: Lee
authors: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors: Hyun Dong
authors: HD
authors: Ji
authors: Department of Pathology, School of Medicine, Kyungpook National University, Daegu, South Korea.
authors: GhilSuk
authors: G
authors: Yoon
authors: 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.
authors: Sung Jin
authors: SJ
authors: Cho
authors: 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.
authors: In-Kyu
authors: IK
authors: Lee
authors: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors: Shin Young
authors: SY
authors: Jeong
authors: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.
authors: Byeong-Cheol
authors: BC
authors: Ahn
authors: Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.
authors: Jaetae
authors: J
authors: Lee
authors: College of Pharmacy, Yeungnam University, Gyeongsan, South Korea. Electronic address: hwchang@ynu.ac.kr.
authors: Hyeun Wook
authors: HW
authors: Chang
authors: 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: swleenm@knu.ac.kr.
authors: Sang-Woo
authors: SW
authors: Lee
authors: 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: jeon9014@gmail.com.
authors: Yong Hyun
authors: YH
authors: Jeon
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D058948:Cell Tracking / Q000379:methods*; D005260:Female; D017930:Genes, Reporter / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008407:Mast Cells / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods*; D057054:Molecular Imaging / Q000379:methods; D009361:Neoplasm Invasiveness
chemical_list: D005947:Glucose
keywords: (18)F-fluorodeoxyglucose; Glucose metabolism; Lung tumor lesion; Mast cells; Optical reporter gene imaging; Recruitment