title: The effect of mannosylation of liposome-encapsulated indocyanine green on imaging of sentinel lymph node.
abstract: The imaging of sentinel lymph nodes (SLN) has been researched for its role in assessing cancer progression and postsurgical lymphedema. Indocyanine green (ICG) is a near-infrared (NIR) optical dye that has been approved by the Food and Drug Administration. It is known that liposome-encapsulated ICG (LP-ICG) has improved stability and fluorescence signal compared with ICG. We designed mannosylated liposome-encapsulated ICG (M-LP-ICG) as an optical contrast agent for SLN. M-LP-ICG has a higher UV absorbance spectrum and fluorescence intensity than LP-ICG. The stability of M-LP-ICG measured in 50% fetal bovine serum solution by a dialysis method was better than that of LP-ICG. M-LP-ICG demonstrated a high uptake in RAW 264.7 macrophage cell because the density of mannose is high. There were differences between M-LP-ICG and glucosylated liposome-encapsulated ICG (G-LP-ICG), which are geometrical isomers. The result of an inhibition study of M-LP-ICG showed a statistically significant decrease in uptake in RAW 264.7 cells after either co-treatment or pre-treatment with D-(+)-mannose as an inhibitor. Results from an in vitro experiment demonstrated that M-LP-ICG was specifically taken up by macrophage cells through the mannose receptor on its surface. The time-series images acquired from a normal mouse model after subcutaneous injection showed that the signal from M-LP-ICG in SLN and other organs appeared early and disappeared quickly in comparison with signals from LP-ICG. Not only the sentinel but also the draining lymph nodes were observed partly in M-LP-ICG. M-LP-ICG appears to increase the specificity of uptake and retention in macrophages, making it a good candidate contrast agent for an optic imaging system for SLN and the lymphatic system.
authors.affiliation: Department of Nuclear Medicine .
authors.forename: Hwan-Seok
authors.initials: HS
authors.lastname: Jeong
authors.forename: Chang-Moon
authors.initials: CM
authors.lastname: Lee
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Cheong
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: Hyosook
authors.initials: H
authors.lastname: Hwang
authors.forename: Kyung Sook
authors.initials: KS
authors.lastname: Na
authors.forename: Seok Tae
authors.initials: ST
authors.lastname: Lim
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D007208:Indocyanine Green / Q000008:administration & dosage*; D008081:Liposomes; D008198:Lymph Nodes / Q000473:pathology*; D008358:Mannose / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence
chemical_list: D008081:Liposomes; D007208:Indocyanine Green; D008358:Mannose