Endovascular photodynamic therapy using mono-L-aspartyl-chlorin e6 to inhibit Intimal hyperplasia in balloon-injured rabbit arteries.
OBJECTIVE
Intimal hyperplasia (IH) leading to restenosis is a major complication of arterial revascularization. The purpose of this study was to investigate the effect of photodynamic therapy (PDT) using mono-L-aspartyl chlorin e6 (NPe6) as a photosensitizer and intraluminal radial irradiation for inhibition of IH experimentally.


METHODS
Study of laser transmission through the blood indicated that exclusion of blood is a prerequisite for intraluminal PDT. For homogeneous radial laser irradiation to the vessel wall, we used a newly developed cylindrical diffusing balloon laser fiber. Injuries were induced by pulling a balloon catheter through the right iliac artery of rabbits. One and 6 hours after the NPe6 injection (5mg/kg i.v.), drug distribution was examined by fluorescence microscopy. Nineteen rabbits received NPe6 at the time of injuries and PDT was performed with 664-nm laser at 30 and 10 J/cm(2) (20, 30, 40 mW/cm(2)) 1 hour after the injuries. The arteries were harvested at 2 days. In a second group of rabbits, PDT was given at 30 mW/cm(2) (30 J/cm(2)). Two weeks after treatment, the arteries were removed and examined histologically.


RESULTS
NPe6 was found to be distributed selectively in the injured media. Endovascular NPe6-PDT showed complete depletion of smooth muscle cells even with 10 J/cm(2) at 2 days. IH was significantly inhibited at 14 days after PDT.


CONCLUSIONS
Endovascular PDT of injured artery using NPe6 can prevent IH in this model of arterial wall injury and may become clinically useful for the prophylaxis of IH.
Nagae
T
T
Department of Surgery, Tokyo Medical University, Tokyo, Japan. tnagae@tokyo-med.ac.jp
Aizawa
K
K
Uchimura
N
N
Tani
D
D
Abe
M
M
Fujishima
K
K
Wilson
S E
SE
Ishimaru
S
S
D000800:Angioplasty, Balloon; D000818:Animals; D002404:Catheterization / Q000009:adverse effects*; D006965:Hyperplasia; D007083:Iliac Artery / Q000293:injuries*; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology
D017319:Photosensitizing Agents; D011166:Porphyrins; C053434:Talaporfin