Open AccessMR and optical imaging of early micrometastases in lymph nodes: triple labeling with nano‐sized agents yielding distinct signals
Author(s) -
Kosaka Nobuyuki,
Bernardo Marcelino,
Mitsunaga Makoto,
Choyke Peter L.,
Kobayashi Hisataka
Publication year - 2012
Publication title -
contrast media & molecular imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.714
H-Index - 50
eISSN - 1555-4317
pISSN - 1555-4309
DOI - 10.1002/cmmi.489
Subject(s) - lymphatic system , in vivo , lymph node , lymph , preclinical imaging , sentinel lymph node , cancer cell , medicine , pathology , breast cancer , magnetic resonance imaging , cancer , biomedical engineering , radiology , biology , microbiology and biotechnology
Few imaging methods are available for depicting in vivo cancer cell migration within the lymphatic system. Detection of such early micrometastases requires extremely high target to background. In this study, we dual‐labeled human breast cancer cells (MDA‐MB468) with a small particle of iron oxide (SPIO) and a quantum dot (QD), and tracked these cells in the lymphatic system in mice using in vivo MRI and optical imaging. A generation‐6 gadolinium‐dendrimer‐based MRI contrast agent (Gd‐G6) was employed for visualizing regional lymphatic channels and nodes. Since Gd‐G6 shortened T 1 leading to high signal, whereas SPIO‐labeled cancer cells greatly lowered signal, a small number of cells were simultaneously visualized within the draining lymphatic basins. One million dual‐labeled cancer cells were subcutaneously injected into the paws of mice 24 h prior to imaging. Then whole body images were acquired pre‐ and post‐intracutaneous injection of Gd‐G6 with 3D‐ T 1 w‐FFE and balanced‐FFE sequences for cancer cell tracking and MR lymphangiography. In vivo MRI clearly visualized labeled cancer cells migrating from the paw to the axillary lymph nodes using draining lymphatics. In vivo optical imaging using a fluorescence surgical microscope demonstrated tiny cancer cell clusters in the axillary lymph node with high spatial resolution. Thus, using a combination of MRI and optical imaging, it is possible to depict macro‐ and early micrometastases within the lymphatic system. This platform offers a versatile research tool for investigating and treating lymphatic metastases in animal models. Copyright © 2011 John Wiley & Sons, Ltd.