Photodynamic therapy with motexafin lutetium (Lu-Tex) reduces experimental graft coronary artery disease.
BACKGROUND
Motexafin lutetium (Lu-Tex) is a photodynamic therapy (PDT) agent that localizes in atheromatous plaque in which it can be activated by far-red light. Lu-Tex biolocalization was examined in graft coronary artery disease (GCAD) with a rodent allograft model. After photoactivation, the effect on intimal proliferation was assessed.


METHODS
A PVG to ACI rat heterotopic heart transplantation model was used. Lu-Tex (10 mg/kg) was intravenously administered 90 days after transplantation. Photoactivation was performed 24 hr after Lu-Tex administration. A light-emitting diode, central wavelength of 742 nm, was used to illuminate the intraperitoneally placed allografts via a laparotomy (light fluence of 75 J/cm2 at a power density of 75 mW/cm2). Animals were divided into four groups according to postoperative treatments: PDT with Lu-Tex injection and light illumination (n=21), Lu-Tex injection and laparotomy (n=14), laparotomy with light only (n=14), and laparotomy only (n=16). GCAD was quantitatively assessed 14 days after treatments.


RESULTS
Lu-Tex localized in atherosclerotic plaque in vessels with GCAD. PDT significantly reduced both the percent of affected vessels and intimal proliferation compared to all other control study groups. alpha-Smooth muscle cell actin and anti-rat macrophage antibody-positive areas were significantly reduced within the neointima in allografts treated with PDT compared to all other study groups.


CONCLUSIONS
PDT significantly reduced atherosclerotic lesions of GCAD. Lu-Tex-mediated PDT may, therefore, be a potential method for treating accelerated atherosclerosis associated with transplantation.
Yamaguchi
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A
Department of Cardiothoracic Surgery, Stanford University School of Medicine, Falk Cardiovascular Research Center, Stanford, CA 94305, USA. robbins@leland.stanford.edu
Woodburn
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KW
Hayase
M
M
Hoyt
G
G
Robbins
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RC
D000199:Actins / Q000378:metabolism; D000818:Animals; D003324:Coronary Artery Disease / Q000473:pathology / Q000517:prevention & control*; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D016027:Heart Transplantation / Q000009:adverse effects*; D008297:Male; D008665:Metalloporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D011912:Rats, Inbred ACI; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
D000199:Actins; D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C102825:motexafin lutetium; C437683:motexafin gadolinium