Intracoronary photodynamic therapy reduces neointimal growth without suppressing re-endothelialisation in a porcine model

Abstract

Objective: To examine the effects of intracoronary PhotoPoint photodynamic therapy (PDT) with a new photosensitiser, MV0611, in the overstretch balloon and stent porcine models of restenosis. Methods: 28 pigs were injected with 3 mg/kg of MV0611 systemically 4 h before the procedure. Animals were divided into either the balloon overstretch injury (BI) group (n = 19) or the stented group (n = 9). After BI, a centred delivery catheter was positioned in the artery to cover the injured area, and light (532 nm, 125 J/cm2 ) was applied to activate the drug (n = 10). Control arteries (n = 9) were not activated by light. In the stented group, the drug was light activated before stent deployment. Serial sections of vessels were processed 14 days after treatment in the BI group and 30 days after treatment in the stented group for histomorphometric or immunohistochemical analysis.

Nonthermal Cardiac Catheter Ablation Using Photodynamic Therapy

“…18 Even for sites with high impedance, which often leads to unsuccessful treatment with radiofrequency catheter ablation, PDT ablation might be more easily applied to the target area and thus produce the best treatment outcome. The real clinical limitation of radiofrequency ablation may be the maximum lesion size.…”

PhotoPoint Photodynamic Therapy Promotes Stabilization of Atherosclerotic Plaques and Inhibits Plaque Progression

“…In an uninjured rat carotid artery model we characterized the photosensitizer (MV0611), optimal dose of the MV0611 (3 mg/kg), the wave length (542 nm) of the light for an adequate activation of the MV0611, and the dose of the light to detect optimal denucleation of the medial cells (17). We also tested the efficacy of MV0611 in stented and nonstented native porcine coronary arteries (18). We then tested the hypothesis that MV0611-PDT could significantly eliminate atherogenic cells in New Zealand White (NZW) rabbits with established lesions.…”

“…Recently endovascular PDT has emerged as a promising therapy for the treatment of restenosis after injury (14) and in short-term studies has shown efficacy in limiting atherosclerotic plaque inflammation in animal models (15)(16)(17)(18).…”

“…PhotoPoint PDT is a combination endovascular therapy designed to systemically deliver a photosensitizer drug (gallium chloride mesoporphyrin dimethyl ester that belongs to the metallotetrapyrrollic group [MV0611]; Miravant Medical Technologies, Santa Barbara, California) (18) that is capable of being taken up by macrophages and other plaque inflammatory cells. A light delivery catheter connected to a laser light source is then guided to areas of plaque formation to provide localized activation of the photosensitizer, which in turn creates the formation of singlet oxygen that induces localized cell apoptosis.…”

Platelets, photosensitizers, and PDT

“…This effect persisted for up to 30 days [124]. Supporting information was obtained with a porcine restenosis model [125]. A study using collagen type I matrix gels and human fibroblasts showed that the fibroblast proliferation can be significantly impaired via methylene blue PDT.…”