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

Objective: Motexafin lutetium (Lu-Tex, Antrin(R) Injection) is a photosensi tizer that selectively accumulates in atheromatous plaque where it can be a ctivated by far-red light. The localization and retention of intra-arterial ly administered Lu-Tex and its efficacy following activation by endovascula rly delivered Light (photoangioplasty) was evaluated. Methods: Bilateral il iac artery lesions were induced in 17 rabbits by balloon denudation, follow ed 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 t he atheroma and adjacent normal tissue. Photoactivation was performed 15 mi n following Lu-Tex administration (180 J/cm fiber at 200 mW/cm fiber). Two weeks post photoangioplasty, vessels were harvested and hematoxylin and eos in (H&E) and RAM11 (macrophages) staining was performed. Results: Local del ivery of Lu-Tex achieved immediate high concentrations within plaque (mean 40X control iliac atheroma). Mean percent plaque area in the treated segmen ts was significantly lower than in the non-treated contralateral lesions (7 3 vs. 82%, P<0.01). No medial damage was observed. Quantitative analysis us ing RAM11 positive cells revealed significant reduction of macrophages in t reated lesions in both the intima (5 vs. 22%, P<0.01) and in media (8 vs. 2 3%, P<0.01) compared to untreated contralateral segments. Conclusions: Loca l delivery provides high levels of Lu-Tex selectively within atheroma. Phot oactivation results in a significant decrease in macrophage and a small dec rease in atheroma burden without damage to the normal vessel wall. (C) 2001 Elsevier Science B.V. All rights reserved.