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Dual Reporter Gene Imaging for Tracking Macrophage Migration Using the Human Sodium Iodide Symporter and an Enhanced Firefly Luciferase in a Murine Inflammation Model

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Abstract

Purpose

The purpose of this study is to visualize the migration of reporter macrophages expressing both the human sodium iodide symporter (hNIS) and enhanced firefly luciferase (effluc) gene in mice with chemically induced inflammation.

Procedures

A macrophage cell line expressing both hNIS and effluc genes (Raw264.7/hNIS–effluc, herein referred to as a Raw264.7/NF) was established by cotransduction of two genes into a murine macrophage cell line (Raw264.7), and cell proliferation and phagocytic activity were compared between parental Raw264.7 and Raw264.7/NF cells. Both serial bioluminescence imaging (BLI) and small animal positron emission tomography (PET) imaging with I-124 were performed in inflammation-induced mice at various time points after intravenous injection of either Raw264.7 or Raw264.7/NF cells.

Results

There was no significant difference in cellular proliferation and phagocytic activity between parental Raw264.7 and Raw264.7/NF cells. Early distribution of Raw264.7/NF cells was successfully visualized in the lung and spleen by BLI, but not by I-124 PET imaging. BLI signals, but not PET signals, were observed from the inflammation site at day 4 after the injection of Raw264.7/NF cells, and the signal intensity gradually increased until day 8. In contrast, focal uptake of I-124 was first detected at the site of inflammation at postinjection day 8, and signal intensity from the inflamed lesion was highest at that time point. While visualization of the inflamed lesion was possible by both BLI and PET imaging until day 14, it was only possible by BLI until day 21 after injection.

Conclusions

Tracking of macrophage migration toward inflammation foci was successfully achieved in vivo from early time points by dual reporter gene imaging with a combination of nuclear and optical reporters. Multimodal reporter imaging of macrophages might successfully overcome the limitations of single reporter gene imaging in preclinical models of inflammation.

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Abbreviations

effluc:

Enhanced firefly luciferase

hNIS:

Human sodium iodide symporter

BLI:

Bioluminescence imaging

Raw264.7/NF:

Raw264.7/hNIS–effluc

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Acknowledgments

This work was supported by the Nuclear Research and Development Program (BAERI) of the National Research Foundation of Korea (NRF), the Ministry of Education, Science and Technology (MEST), the Brain Korea 21 Project in 2012, and a grant from the Korea Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A111345).

Conflict of Interest

All authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, School of Medicine, Kyungpook National University, 50 Samduk 2-ga, Daegu, 700-721, Republic of Korea

    Ho Won Lee, Yong Hyun Jeon, Mi-Hye Hwang, Jung-Eun Kim, Sang-Woo Lee, Byeong-Cheol Ahn & Jaetae Lee

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

    Tae-in Park

  3. Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu, South Korea

    Jeoung-Hee Ha

  4. Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, 807 Hogukro, Bukgu, Daegu, 702-210, South Korea

    Yong Hyun Jeon

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  1. Ho Won Lee
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Corresponding author

Correspondence to Jaetae Lee.

Additional information

H.W. Lee and Y.H. Jeon contributed equally to this study.

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Lee, H.W., Jeon, Y.H., Hwang, MH. et al. Dual Reporter Gene Imaging for Tracking Macrophage Migration Using the Human Sodium Iodide Symporter and an Enhanced Firefly Luciferase in a Murine Inflammation Model. Mol Imaging Biol 15, 703–712 (2013). https://doi.org/10.1007/s11307-013-0645-8

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  • DOI: https://doi.org/10.1007/s11307-013-0645-8

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