Photodynamic therapy: applications in atherosclerotic vascular disease with motexafin lutetium

Abstract

Photodynamic therapy (PDT) has been approved as a tissue-specific light-activated cytotoxic therapy for many diseases. The ability of PDT to destroy target tissues selectively is especially appealing for atherosclerotic plaque. Biotechnology has developed a new generation of selective photosensitizers and catheter-based technological advances in light delivery have allowed the introduction of PDT into the vasculature. The largest experience to date is with motexafin lutetium (MLu, Antrin), an expanded porphyrin (texaphyrin) that accumulates in plaque. The combination of the motexafin lutetium and endovascular illumination, or Antrin phototherapy, has been shown to reduce plaque in animal models. Antrin phototherapy generates cytotoxic singlet oxygen that has been shown to induce apoptosis in macrophages and smooth muscle cells. The safety, tolerability, and preliminary efficacy of Antrin phototherapy has been assessed in a phase 1 dose-ranging clinical trial in subjects with peripheral artery disease and is currently being examined in a phase 1 study in subjects with lesions of the native coronary arteries undergoing stent implantation. The preliminary results suggest that Antrin phototherapy is safe, well tolerated, and nontraumatic.