Intravascular detection of inflamed atherosclerotic plaques using a fluorescent photosensitizer targeted to the scavenger receptor
Inflammation plays an important role in the pathophysiology of atherosclerotic disease. We have previously shown that the targeted photosensitizer chlorin (e(6)) conjugated with maleylated albumin (MA-ce6) is taken up by macrophages via the scavenger receptor with high selectivity. In a rabbit model of inflamed plaque in New Zealand white rabbits via balloon injury of the aorto-iliac arteries and high cholesterol diet we showed that the targeted conjugate showed specificity towards plaques compared to free ce6. We now show that an intravascular fiber-based spectrofluorimeter advanced along the -iliac vessel through blood detects 24-fold higher fluorescence in atherosclerotic vessels compared to control rabbits (p < 0.001 ANOVA). Within the same animals, signal derived from the injured iliac artery was 16-fold higher than the contralateral uninjured iliac (p < 0.001). Arteries were removed and selective accumulation of MA-ce6 in plaques was confirmed using: (1) surface spectrofluorimetry, (2) fluorescence extraction of ce6 from aortic segments, and (3) confocal microscopy. Immunohistochemical analysis of the specimens showed a significant correlation between MA-ce6 uptake and RAM-11 macrophage staining (R = 0.83, p < 0.001) and an inverse correlation between MA-ce6 uptake and smooth muscle cell staining (R = -0.74, p < 0.001). MA-ce6 may function as a molecular imaging agent to detect and/or photodynamically treat inflamed plaques.