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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. 

Author information

Oh SG1, Li X2, Lee HW1, Singh TD1, Lee SB3, Ji HD1, Yoon G4, Cho SJ5, Lee IK6, Jeong SY1, Ahn BC1, Lee J7, Chang HW8, Lee SW9, Jeon YH10.

1Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.

2College of Pharmacy, Yeungnam University, Gyeongsan, South Korea.

3Department 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.

4Department of Pathology, School of Medicine, Kyungpook National University, Daegu, South Korea.

5Leading-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.

6Leading-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.

7Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.

8College of Pharmacy, Yeungnam University, Gyeongsan, South Korea. Electronic address: hwchang@ynu.ac.kr.

9Department 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.

10Department 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.