title: Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors.
abstract: Macrophages mediate atheroma expansion and disruption, and denote high-risk arterial plaques. Therefore, they are substantially gaining importance as a diagnostic imaging target for the detection of rupture-prone plaques. Here, we developed an injectable near-infrared fluorescence (NIRF) probe by chemically conjugating thiolated glycol chitosan with cholesteryl chloroformate, NIRF dye (cyanine 5.5 or 7), and maleimide-polyethylene glycol-mannose as mannose receptor binding ligands to specifically target a subset of macrophages abundant in high-risk plaques. This probe showed high affinity to mannose receptors, low toxicity, and allowed the direct visualization of plaque macrophages in murine carotid atheroma. After the scale-up of the MMR-NIRF probe, the administration of the probe facilitated in vivo intravascular imaging of plaque inflammation in coronary-sized vessels of atheromatous rabbits using a custom-built dual-modal optical coherence tomography (OCT)-NIRF catheter-based imaging system. This novel imaging approach represents a potential imaging strategy enabling the identification of high-risk plaques in vivo and holds promise for future clinical implications.
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea.
authors.forename: Ji Bak
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Division of Bio-imaging, Chuncheon Center, Korea Basic Science Institute, Republic of Korea.
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Jiheun
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea.
authors.forename: Jae Joong
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Min Woo
authors.initials: MW
authors.lastname: Lee
authors.affiliation: Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Han Saem
authors.initials: HS
authors.lastname: Cho
authors.affiliation: Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Hyeong Soo
authors.initials: HS
authors.lastname: Nam
authors.affiliation: Division of Bio-imaging, Chuncheon Center, Korea Basic Science Institute, Republic of Korea.
authors.forename: Ok Kyu
authors.initials: OK
authors.lastname: Park
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea.
authors.forename: Joon Woo
authors.initials: JW
authors.lastname: Song
authors.affiliation: Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Tae Shik
authors.initials: TS
authors.lastname: Kim
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea.
authors.forename: Dong Joo
authors.initials: DJ
authors.lastname: Oh
authors.affiliation: Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: DaeGab
authors.initials: D
authors.lastname: Gweon
authors.affiliation: Department of Mechanical Engineering, KAIST, Daejeon, Republic of Korea.
authors.forename: Wang-Yuhl
authors.initials: WY
authors.lastname: Oh
authors.affiliation: Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea.
authors.forename: Hongki
authors.initials: H
authors.lastname: Yoo
authors.affiliation: Multimodal Imaging and Theranostic Lab, Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea.
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Kim
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging*; D037181:Lectins, C-Type / Q000032:analysis*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000032:analysis*; D008810:Mice, Inbred C57BL; D061848:Optical Imaging / Q000379:methods*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000032:analysis*
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface