Abstract 19605: Identification of M1 Macrophages in Vulnerable Plaques With Folate Receptor Beta Targeted Liposomal Indocyanine Green J-Aggregates
In the US alone, approximately 500,000 deaths per year result from the rupture of plaques considered “insignificant” upon angiographic evaluation. These “vulnerable plaques” are characterized by a lipid-rich necrotic core, thin fibrous cap, and macrophage dense inflammation, where a high ratio of M1 versus M2 activated macrophages is indicative of high plaque vulnerability. We tested the hypothesis that the M1 to M2 ratio can be assessed by utilizing a molecularly-targeted dye-loaded liposome as a contrast agent and sensor for intravascular photoacoustic (IVPA) imaging. This was accomplished via synthesis of a liposomal system containing indocyanine green (ICG) J-aggregates with high absorption at 890 nm. This “Lipo-ICG” was targeted to a biomarker of M1 activated macrophages in vulnerable plaques: folate receptor beta (FRβ). The targeted liposomes can accumulate in plaques through areas of endothelial dysfunction and specifically interact with M1 activated macrophages, causing a spectral shift and change in the 890/780 nm photoacoustic intensity ratio upon breakdown of J-aggregates. In in vitro testing, Lipo-ICG showed a 5-fold preferential uptake in M1 vs. M2 macrophages, with no statistically significant cytotoxicity. In a pilot in vivo study utilizing ApoE deficient mouse models of atherosclerosis, diseased mice showed increased uptake of FRβ targeted Lipo-ICG in the heart and arteries vs. normal mice. Likewise, targeted Lipo-ICG showed increased uptake vs. two non-targeted controls (PEG, RG16 - see Figure). In conclusion, we successfully synthesized a contrast agent to detect M1 activated macrophages in high risk atherosclerotic plaques and exhibited targeting both in vitro and in vivo. This biocompatible agent could enable M1 macrophage detection in many light-based intravascular imaging techniques, allowing better clinical decision making in treatment of atherosclerosis through identification of vulnerable plaques.
Author Disclosures: J.T. Harris: None. D.S. Dumani: None. J.R. Cook: None. K.V. Sokolov: None. S.Y. Emelianov: None. K.A. Homan: None.
- © 2016 by American Heart Association, Inc.