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Cardiovascular Research 2001 49(2):449-455; doi:10.1016/S0008-6363(00)00278-9
© 2001 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

Photoangioplasty with local motexafin lutetium delivery reduces macrophages in a rabbit post-balloon injury model

Motoya Hayasea,b, Kathryn W Woodbumc, Joshua Perlrotha, Richard A Millerc, Wendy Baumgardnera, Paul G Yocka and Alan Yeunga,*

aDivision of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA
bToyohashi Heart Center, Toyohashi, Japan
cPharmacyclics Inc., Sunnyvale, CA, USA

* Corresponding author. Tel.: +1-650-723-0180; fax: +1-650-725-6766 alan_yeung{at}cvmed.stanford.edu

Objective: Motexafin lutetium (Lu-Tex, Antrin® Injection) is a photosensitizer that selectively accumulates in atheromatous plaque where it can be activated by far-red light. The localization and retention of intra-arterially administered Lu-Tex and its efficacy following activation by endovascularly delivered light (photoangioplasty) was evaluated. Methods: Bilateral iliac artery lesions were induced in 17 rabbits by balloon denudation, followed by a high cholesterol diet. Lu-Tex distribution within the atheroma was examined (n = 8) following local injection. Fluorescence spectral imaging and chemical extraction techniques were used to measure Lu-Tex levels within the atheroma and adjacent normal tissue. Photoactivation was performed 15 min following Lu-Tex administration (180 J/cm fiber at 200 mW/cm fiber). Two weeks post photoangioplasty, vessels were harvested and hematoxylin and eosin (H&E) and RAM11 (macrophages) staining was performed. Results: Local delivery of Lu-Tex achieved immediate high concentrations within plaque (mean 40x control iliac atheroma). Mean percent plaque area in the treated segments was significantly lower than in the non-treated contralateral lesions (73 vs. 82%, P<0.01). No medial damage was observed. Quantitative analysis using RAM11 positive cells revealed significant reduction of macrophages in treated lesions in both the intima (5 vs. 22%, P<0.01) and in media (8 vs. 23%, P<0.01) compared to untreated contralateral segments. Conclusions: Local delivery provides high levels of Lu-Tex selectively within atheroma. Photoactivation results in a significant decrease in macrophage and a small decrease in atheroma burden without damage to the normal vessel wall.

KEYWORDS Angioplasty; Arteries; Atherosclerosis; Macrophages; Restenosis


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