Photoangioplasty with local motexafin lutetium delivery reduces macrophages in a rabbit post-balloon injury model.
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.
Hayase
M
M
Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Woodbum
K W
KW
Perlroth
J
J
Miller
R A
RA
Baumgardner
W
W
Yock
P G
PG
Yeung
A
A
D000800:Angioplasty, Balloon / Q000009:adverse effects; D016342:Angioplasty, Laser / Q000379:methods*; D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000473:pathology / Q000601:surgery*; D007083:Iliac Artery / Q000473:pathology; D007261:Infusions, Intra-Arterial; D008264:Macrophages / Q000473:pathology; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000032:analysis; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000032:analysis; D011184:Postoperative Period; D011817:Rabbits; D012815:Signal Processing, Computer-Assisted
D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C102825:motexafin lutetium; C437683:motexafin gadolinium