바로가기  >

Abstract
Purpose: Owing to the close relationship between mast cells and cancer progression, an imaging technique that can be applied in a clinical setting to explore the biological behavior of mast cells in the tumor microenvironment is needed. In this study, we visualized mast cell migration to lung tumor lesions in live mice using sodium iodide symporter (NIS) as a nuclear medicine reporter gene.

Experimental design: The murine mast cell line MC-9 was infected with retrovirus including NIS, luciferase (as a surrogate marker for NIS), and Thy1.1 to generate MC-9/NFT cells. Radioiodine uptake was measured in MC-9/NFT cells, and an inhibition assay of radioiodine uptake using KCLO4 was also performed. Cell proliferation and FcεRI expression was examined in MC-9 and MC-9/NFT cells. The effect of mast cell-conditioned media (CM) on the proliferation of Lewis lung cancer (LLC) cells was examined. The migration level of MC-9/NFT cells was confirmed in the presence of serum-free media (SFM) and CM of cancer cells. After intravenous injection of MC-9/NFT cells into mice with an LLC tumor, I-124 PET/CT and biodistribution analysis was performed.

Results: MC-9/NFT cells exhibited higher radioiodine avidity compared to parental MC-9 cells; this increased radioiodine avidity in MC-9/NFT cells was reduced to basal level by KCLO4. Levels of FcεRI expression and cell proliferation were not different in parental MC-9 cell and MC-9/ NFT cells. The CM of MC-9/NFT cells increased cancer cell proliferation relative to that of the SFM. The migration level of MC-9/NFT cells was higher in the CM than the SFM of LLC cells. PET/CT imaging with I-124 clearly showed infiltration of reporter mast cells in lung tumor at 24 h after transfer, which was consistent with the findings of the biodistribution examination.

Conclusion: These findings suggest that the sodium iodide symporter can serve as a reliable nuclear medicine reporter gene for non-invasively imaging the biological activity of mast cells in mice with lung tumors. Visualizing mast cells in the tumor microenvironment via a nuclear medicine reporter gene would provide valuable insights into their biological functions.

Affiliations

Seul-Gi Oh 1, Jun Young Choi 2, Jae-Eon Lee 2, SoYeon Jeon 3, Bo-Ra Lee 3, Kwang Hee Son 3, Sang Bong Lee 4, Beum-Soo An 5, Dae Youn Hwang 5, Seong-Jang Kim 6, Ki-Tae Ha 7, Jaetae Lee 4, Yong Hyun Jeon 8
1Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea; Institute of Breast Cancer Precision Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
2Preclincial Research Center (PRC), Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of Korea; Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea.
3Preclincial Research Center (PRC), Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of Korea.
4Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.
5Department of Biomaterials Science (BK21 FOUR Program), Life and Industry Convergence Research Institute, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea.
6Pusan National University College of Medicine, Pusan National University School of Medicine, Busan, Republic of Korea.
7Department of Korean Medicine, School of Korean Medicine, Pusan National University, Yangsan 50612, Gyeongsangnam-do, Republic of Korea.
8Preclincial Research Center (PRC), Daegu-Gyeongbuk Medical Innovation Foundation (K-MEDI hub), Daegu, Republic of Korea. Electronic address: jeon9014@kmedihub.re.kr.