Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorine(e6)
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Tawakol-2006-Photosensitizer deli.pdf
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Author(s)
Tawakol, Ahmed
Castano, Ana P.
Anatelli, Florencia
Bashian, Gregory
Stern, Jeremy
Zahra, Touqir
Gad, Faten
Chirico, Stephanie
Ahmadi, Atosa
Fischman, Alan J.
Date Issued
April 2006
Journal
Journal of Biomedical Optics
Publisher
SPIE
Citation
Tawakol, Ahmed, Ana P. Castano, Florencia Anatelli, Gregory Bashian, Jeremy Stern, Touqir Zahra, Faten Gad, et al. “Photosensitizer Delivery to Vulnerable Atherosclerotic Plaque: Comparison of Macrophage-Targeted Conjugate Versus Free Chlorine(e6).” Journal of Biomedical Optics 11, no. 2 (2006): 021008. © 2006 Society of Photo-Optical Instrumentation Engineers
Version
Final published version
Abstract
We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits. Rabbits are sacrificed at 6 and 24 h after injection and intravascular fluorescence spectroscopy is carried out by fiber-based fluorimetry in intact blood-filled arteries. Surface spectrofluorimetry of numbered excised aortic segments together with injured and normal iliac arteries is carried out, and quantified ce6 content by subsequent extraction and quantitative fluorescence determination of the arterial segments and also of nontarget organs. There is good agreement between the various techniques for quantifying ce6 localization, and high contrast between arteries from atherosclerotic and normal rabbits is obtained. Fluorescence correlates with the highest burden of plaque in the aorta and the injured iliac artery. The highest accumulation in plaques is obtained using MA-ce6 at 24 h. Free ce6 gives better accumulation at 6 h compared to 24 h. The liver, spleen, lung, and gall bladder have the highest uptake in nontarget organs. Macrophage-targeted photosensitizer conjugates may have applications in both detecting and treating inflamed vulnerable plaque.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1117/1.2186039
