title: Quantitative imaging of lymphatic function with liposomal indocyanine green.
abstract: Lymphatic vessels play a major role in cancer progression and in postsurgical lymphedema, and several new therapeutic approaches targeting lymphatics are currently being developed. Thus, there is a critical need for quantitative imaging methods to measure lymphatic flow. Indocyanine green (ICG) has been used for optical imaging of the lymphatic system, but it is unstable in solution and may rapidly enter venous capillaries after local injection. We developed a novel liposomal formulation of ICG (LP-ICG), resulting in vastly improved stability in solution and an increased fluorescence signal with a shift toward longer wavelength absorption and emission. When injected intradermally to mice, LP-ICG was specifically taken up by lymphatic vessels and allowed improved visualization of deep lymph nodes. In a genetic mouse model of lymphatic dysfunction, injection of LP-ICG showed no enhancement of draining lymph nodes and slower clearance from the injection site. In mice bearing B16 luciferase-expressing melanomas expressing vascular endothelial growth factor-C (VEGF-C), sequential near-IR imaging of intradermally injected LP-ICG enabled quantification of lymphatic flow. Increased flow through draining lymph nodes was observed in mice bearing VEGF-C-expressing tumors without metastases, whereas a decreased flow pattern was seen in mice with a higher lymph node tumor burden. This new method will likely facilitate quantitative studies of lymphatic function in preclinical investigations and may also have potential for imaging of lymphedema or improved sentinel lymph detection in cancer.
authors.affiliation: Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.
authors.forename: Steven T
authors.initials: ST
authors.lastname: Proulx
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Stefanie
authors.initials: S
authors.lastname: Derzsi
authors.forename: Matthias
authors.initials: M
authors.lastname: Rinderknecht
authors.forename: Viviane
authors.initials: V
authors.lastname: Mumprecht
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Leroux
authors.forename: Michael
authors.initials: M
authors.lastname: Detmar
mesh_terms: D000818:Animals; D004396:Coloring Agents / Q000008:administration & dosage; D007208:Indocyanine Green / Q000008:administration & dosage; D007271:Injections, Intradermal; D008081:Liposomes / Q000008:administration & dosage; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008546:Melanoma, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis
chemical_list: D004396:Coloring Agents; D008081:Liposomes; D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse; D007208:Indocyanine Green
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