Intravascular optical imaging of high-risk plaques in vivo by targeting macrophage mannose receptors

• Published in: Scientific reports Vol. 6; no. 1; p. 22608
• Main Authors: Kim, Ji Bak, Park, Kyeongsoon, Ryu, Jiheun, Lee, Jae Joong, Lee, Min Woo, Cho, Han Saem, Nam, Hyeong Soo, Park, Ok Kyu, Song, Joon Woo, Kim, Tae Shik, Oh, Dong Joo, Gweon, DaeGab, Oh, Wang-Yuhl, Yoo, Hongki, Kim, Jin Won
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.03.2016; Nature Publishing Group
• Subjects: 639/624/1107/510; 692/4019/592/75/593/2100; Animals; Atherosclerosis - diagnostic imaging; Chitosan; Humanities and Social Sciences; I.R. radiation; Lectins, C-Type - analysis; Macrophages; Macrophages - metabolism; Male; Mannose; Mannose receptors; Mannose-Binding Lectins - analysis; Medical imaging; Mice, Inbred C57BL; multidisciplinary; Optical Imaging - methods; Plaques; Polyethylene glycol; Rabbits; Receptors, Cell Surface - analysis; Rupture; Science; Science (multidisciplinary); Toxicity
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep22608

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.