Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

Michael R. Hamblin; Ahmed Tawakol; Ana P Castano; Faten Gad; Touqir Zahra; Atosa Ahmadi; Jeremy Stern; Bernhard Ortel; Stephanie Chirico; Azadeh Shirazi; Sakeena Syed; James E. Muller

doi:10.1117/12.476218

12 September 2003 Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

Michael R. Hamblin, Ahmed Tawakol, Ana P Castano, Faten Gad, Touqir Zahra, Atosa Ahmadi, Jeremy Stern, Bernhard Ortel, Stephanie Chirico, Azadeh Shirazi, Sakeena Syed, James E. Muller

Author Affiliations +

Proceedings Volume 4949, Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems XIII; (2003) https://doi.org/10.1117/12.476218
Event: Biomedical Optics, 2003, San Jose, CA, United States

Abstract

Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular spectrofluorimetry. It may also be possible to use macrophage-targeted PDT to therapeutically modify inflammatory cell-laden VPs leading to plaque stabilization and reduction of sudden cardiovascular death.

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Michael R. Hamblin, Ahmed Tawakol, Ana P Castano, Faten Gad, Touqir Zahra, Atosa Ahmadi, Jeremy Stern, Bernhard Ortel, Stephanie Chirico, Azadeh Shirazi, Sakeena Syed, and James E. Muller "Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque", Proc. SPIE 4949, Lasers in Surgery: Advanced Characterization, Therapeutics, and Systems XIII, (12 September 2003); https://doi.org/10.1117/12.476218

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