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Mol Imaging Biol. 2019 Aug 5. doi: 10.1007/s11307-019-01410-w. [Epub ahead of print]

Noninvasive Photoacoustic Imaging of Dendritic Cell Stimulated with Tumor Cell-Derived Exosome.

Author information

1
Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
2
Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
3
Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. hoeskim@snu.ac.kr.
4
Department of Radiology, Seoul National University Hospital and Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. moonwk@snu.ac.kr.
5
Department of Biomedical Sciences, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea. moonwk@snu.ac.kr.

Abstract

PURPOSE:

The tools to trigger dendritic cell (DC) activation and to verify DC migration in vivo are important for directing DC immunotherapy toward successful treatment. We evaluated whether tumor cell-derived exosome (TEX)-stimulated DC migration into lymph node (LN) in mouse could be tracked using gold nanoparticle (GN)-labeling and ultrasound (US)-guided photoacoustic imaging (PAI).

PROCEDURES:

GFP-transduced DC2.4 cells were used. RFP-tagged TEXs were purified from a stable 4T1 cell line overexpressing the exosomal CD63-RFP fusion protein. The TEX uptake by DCs was visualized using confocal laser scanning microscopy. GNs with surface plasmon resonance at 808 nm were used for DC-labeling. DCs that migrated into axillary LN were longitudinally monitored by US-guided PAI and analyzed by silver staining and immunohistochemistry.

RESULTS:

TEXs were easily internalized in DCs, increased proliferation and migration capacities, and upregulated co-stimulatory molecules, CCR7 and TNF-α without cytotoxicity. The GN-labeling exerted no adverse effects on the biological functions of DCs. US-guided PAI and DC-labeling allowed for sensitive and longitudinal monitoring of TEX-stimulated DC migration toaxillary LN.

CONCLUSIONS:

TEXs efficiently activated DCs and GN-labeled DC migration into LN was successfully monitored using US-guided PAI, suggesting that TEXs are a good source for DC activation and US-guided PAI is a cost-effective and easy-to-use imaging modality for noninvasive tracking of DCs.

KEYWORDS:

Dendritic cell; Exosomes; Gold nanoparticle; Photoacoustic imaging

PMID:
31385127
DOI:
10.1007/s11307-019-01410-w

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