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

• DOI: 10.1038/srep22608
• Publication Date: 2016-03-07T11:22:19Z
• Authors: Ji Bak Kim; Kyeongsoon Park; Jiheun Ryu; Jae Joong Lee; Min Woo Lee; Han Saem Cho; Hyeong Soo Nam; Ok Kyu Park; Joon Woo Song; Tae Shik Kim; Dong Joo Oh; DaeGab Gweon; Wang-Yuhl Oh; Hongki Yoo; Jin Won Kim
• Keywords: Male; 0301 basic medicine; Macrophages; Optical Imaging; Receptors, Cell Surface; Atherosclerosis; Article; 3. Good health; Mice, Inbred C57BL; 03 medical and health sciences; Mannose-Binding Lectins; Animals; Lectins, C-Type; Rabbits; Mannose Receptor

AbstractMacrophages 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.