In vivo imaging of inflammation- and tumor-induced lymph node lymphangiogenesis by immuno-positron emission tomography.

Metastasis to regional lymph nodes is a prognostic indicator for cancer progression. There is a great demand for sensitive and non-invasive methods to detect metastasis to the lymph nodes. While conventional in vivo imaging approaches have focused on the detection of cancer cells, lymphangiogenesis within tumor draining lymph nodes might be the earliest sign of metastasis. In mouse models of lymph node lymphangiogenesis, we found that systemically injected antibodies to lymphatic epitopes accumulated in the lymphatic vasculature in tissues and lymph nodes. Using a 124I-labeled antibody against the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), we imaged, for the first time, inflammation-and tumor-draining lymph nodes with expanded lymphatic networks in vivo by positron emission tomography (PET). Anti-LYVE-1 immuno-PET enabled visualization of lymphatic vessel expansion in lymph nodes bearing metastases that were not detected by 18F-fluorodeoxyglucose-PET, which is clinically applied to detect cancer metastases. Immuno-PET with lymphatic specific antibodies may open up new avenues for the early detection of metastasis and the images obtained might be used as biomarkers for the progression of diseases associated with lymphangiogenesis.