title: Intravascular detection of inflamed atherosclerotic plaques using a fluorescent photosensitizer targeted to the scavenger receptor.
abstract: 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.
authors.affiliation: Department of Medicine (Cardiac Unit), Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.forename: Ana P
authors.initials: AP
authors.lastname: Castano
authors.forename: Faten
authors.initials: F
authors.lastname: Gad
authors.forename: Touqir
authors.initials: T
authors.lastname: Zahra
authors.forename: Gregory
authors.initials: G
authors.lastname: Bashian
authors.forename: Raymond Q
authors.initials: RQ
authors.lastname: Migrino
authors.forename: Atosa
authors.initials: A
authors.lastname: Ahmadi
authors.forename: Jeremy
authors.initials: J
authors.lastname: Stern
authors.forename: Florencia
authors.initials: F
authors.lastname: Anatelli
authors.forename: Stephanie
authors.initials: S
authors.lastname: Chirico
authors.forename: Azadeh
authors.initials: A
authors.lastname: Shirazi
authors.forename: Sakeenah
authors.initials: S
authors.lastname: Syed
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Fischman
authors.forename: James E
authors.initials: JE
authors.lastname: Muller
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D017319:Photosensitizing Agents; D011817:Rabbits; D051116:Receptors, Scavenger / Q000378:metabolism*
chemical_list: D017319:Photosensitizing Agents; D051116:Receptors, Scavenger