Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 1, Pages 208-213Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1414821112
Keywords
PET; lymph node; optical imaging; albumin; Evans blue
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Funding
- Intramural Research Program of the National Institute of Biomedical Imaging and Bioengineering, NIH
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The ability to accurately and easily locate sentinel lymph nodes (LNs) with noninvasive imaging methods would assist in tumor staging and patient management. For this purpose, we developed a lymphatic imaging agent by mixing fluorine-18 aluminum fluoride-labeled NOTA (1,4,7-triazacyclononane-N, N',N''-triaceticacid)-conjugated truncated Evans blue (F-18-AlF-NEB) and Evans blue (EB) dye. After local injection, both 18F-AlF-NEB and EB form complexes with endogenous albumin in the interstitial fluid and allow for visualizing the lymphatic system. Positron emission tomography (PET) and/or optical imaging of LNs was performed in three different animal models including a hind limb inflammation model, an orthotropic breast cancer model, and a metastatic breast cancer model. In all three models, the LNs can be distinguished clearly by the apparent blue color and strong fluorescence signal from EB as well as a high-intensity PET signal from F-18-AlF-NEB. The lymphatic vessels between the LNs can also be optically visualized. The easy preparation, excellent PET and optical imaging quality, and biosafety suggest that this combination of F-18-AlF-NEB and EB has great potential for clinical application to map sentinel LNs and provide intraoperative guidance.
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