In vivo imaging of inflammation- and tumor-induced lymph node lymphangiogenesis by immuno-positron emission tomography.
Metastasis to regional lymph nodes (LN) is a prognostic indicator for cancer progression. There is a great demand for sensitive and noninvasive methods to detect metastasis to LNs. Whereas conventional in vivo imaging approaches have focused on the detection of cancer cells, lymphangiogenesis within tumor-draining LNs might be the earliest sign of metastasis. In mouse models of LN lymphangiogenesis, we found that systemically injected antibodies to lymphatic epitopes accumulated in the lymphatic vasculature in tissues and LNs. Using a (124)I-labeled antibody against the lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), we imaged, for the first time, inflammation- and tumor-draining LNs with expanded lymphatic networks in vivo by positron emission tomography (PET). Anti-LYVE-1 immuno-PET enabled visualization of lymphatic vessel expansion in LNs bearing metastases that were not detected by [(18)F]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.
Institute of Pharmaceutical Sciences and Philochem AG, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.
Viviane
V
Mumprecht
Michael
M
Honer
Benjamin
B
Vigl
Steven T
ST
Proulx
Eveline
E
Trachsel
Manuela
M
Kaspar
Nadja E
NE
Banziger-Tobler
Roger
R
Schibli
Dario
D
Neri
Michael
M
Detmar
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003952:Diagnostic Imaging; D005260:Female; D019788:Fluorodeoxyglucose F18; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology / Q000473:pathology; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008163:Luminescent Measurements; D008198:Lymph Nodes / Q000000981:diagnostic imaging* / Q000276:immunology / Q000473:pathology; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008546:Melanoma, Experimental / Q000150:complications* / Q000276:immunology / Q000473:pathology; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography; D011379:Prognosis; D019275:Radiopharmaceuticals; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000276:immunology
D000911:Antibodies, Monoclonal; D019788:Fluorodeoxyglucose F18; D006023:Glycoproteins; D007457:Iodine Radioisotopes; D026901:Membrane Transport Proteins; D019275:Radiopharmaceuticals; D042582:Vascular Endothelial Growth Factor C; D040321:Vascular Endothelial Growth Factor Receptor-3; C492273:LYVE1 protein, mouse; C467483:vascular endothelial growth factor C, mouse