Photodynamic therapy with motexafin lutetium (Lu-Tex) reduces experimental graft coronary artery disease.

Abstract

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.

• Authors: A Yamaguchi, K W Woodburn, M Hayase, G Hoyt, R C Robbins
• Journal: Transplantation (Transplantation) Vol. 71 Issue 11 Pg. 1526-32 (Jun 15 2001) ISSN: 0041-1337 [Print] United States
• PMID: 11435960 (Publication Type: Journal Article)

Chemical References

• Actins
• Metalloporphyrins
• Photosensitizing Agents
• motexafin lutetium
• motexafin gadolinium

Topics

• Actins (metabolism)
• Animals
• Coronary Artery Disease (pathology, prevention & control)
• Coronary Vessels (metabolism, pathology)
• Heart Transplantation (adverse effects)
• Male
• Metalloporphyrins (pharmacokinetics, therapeutic use)
• Myocardium (metabolism)
• Photochemotherapy
• Photosensitizing Agents (pharmacokinetics, therapeutic use)
• Rats
• Rats, Inbred ACI
• Rats, Inbred Strains
• Tissue Distribution
• Tunica Intima (metabolism, pathology)