방사선의학 웹진

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Abstract
There has been considerable interest in the clinical use of exosomes as delivery vehicles for treatments as well as for promising diagnostic biomarkers, but the physiological distribution of exosomes must be further elucidated to validate their efficacy and safety. Here, we aimed to develop novel methods to monitor exosome biodistribution in vivo using positron emission tomography (PET) and optical imaging. Exosomes were isolated from cultured mouse breast cancer cells and labeled for PET and optical imaging. In mice, radiolabeled and fluorescently labeled exosomes were injected both via lymphatic and hematogenous metastatic routes. PET and fluorescence images were obtained and quantified. Radioactivity and fluorescence intensity of ex vivo organs were measured. PET signals from exosomes in the lymphatic metastatic route were observed in the draining sentinel lymph nodes. Immunohistochemistry revealed greater exosome uptake in brachial and axillary versus inguinal lymph nodes. Following administration through the hematogenous metastasis pathway, accumulation of exosomes was clearly observed in the lungs, liver, and spleen. Exosomes from tumor cells were successfully labeled with 64Cu (or 68Ga) and fluorescence and were visualized via PET and optical imaging, suggesting that this simultaneous and rapid labeling method could provide valuable information for further exosome translational research and clinical applications.

Affiliations

Kyung Oh Jung  1   2 , Young-Hwa Kim  1   3   4   5 , Seock-Jin Chung  1 , Chul-Hee Lee  1   3 , Siyeon Rhee  6 , Guillem Pratx  2 , June-Key Chung  1 , Hyewon Youn  1   3   4   5   7
1 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
2 Department of Radiation Oncology, Division of Medical Physics, Stanford University School of Medicine, Stanford University, Stanford, CA 94305, USA.
3 Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
4 Medical Research Center, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
5 Tumor Microenvironment Global Core Research Center, Seoul National University, Seoul 08826, Korea.
6 Department of Biology, Stanford University, Stanford, CA 94305, USA.
7 Cancer Imaging Center, Seoul National University Hospital, Seoul 03080, Korea.