It is now accepted that the non-stenotic highly inflamed atherosclerotic plaque with a thin collagen cap in the coronary arteries is vulnerable to rupture, frequently causing a massive coronary thrombosis and sudden death. Since most patients with vulnerable plaque have no prior symptoms of heart disease, there is increasing interest in technologies to both detect and treat vulnerable plaque (VP).
It is clear that the most important cellular component and causative agent within VP is the activated macrophage, which is responsible for collagen cap degradation by secreting matrix metalloproteinases, thus increasing likelihood of rupture. Since the scavenger-targeted conjugates (modified serum albumin, see above) show a high degree of selectivity for macrophages, they are an attractive targeting vehicle for delivering fluorescent dyes to VP allowing intravascular fluorescence diagnosis, and delivering photoactive dyes allowing photodynamic stabilization of VP by increasing the fibrous cap and reducing the inflammatory macrophages.
We are actively studying the use of targeted fluorescence probes to allow intravascular detection of macrophage-rich plaques in rabbit models, and the effects that intravascular PDT has on metrics of plaque vulnerability as judged by histology and immunohistochemistry.
Hamblin MR, Tawakol A. Castano AP, Gad F, Zahra T, Ahmadi A, Stern J, Ortel B, Chirico S, Shirazi A, Syed S Muller JE. Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque. Proc SPIE; 2003, Vol 4949: p 466-476.
Tawakol A, Castano AP, Anatelli F, Bashian G, Stern J, Zahra T, Gad F, Chirico S, Ahmadi A, Fischman AJ, Muller JE, Hamblin MR. Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorin(e6). J Biomed Optics, 2006, 11: 210-218.
Tawakol, A., Castano AP, Gad F, Zahra T, Bashian G, Migrino RQ, Ahmadi A, Stern J, Anatelli F, Chirico S, Shirazi A, Syed S, Fischman AJ, Muller JE, and Hamblin, MR. Intravascular detection of inflamed atherosclerotic plaques with a scavenger receptor-targeted fluorescent photosensitizer. Photochem Photobiol Sci, 2008, 7, 33-39