Combined verteporfin- mediated photodynamic therapy and catheter- based 192Ir- mediated brachytherapy for neoatherosclerosis inhibition after laser angioplasty

Abstract Background and aims The laser atherectomy methods that are currently in use, cause to inflammation and subsequent restenosis. The aim of this study was to evaluate the effect of combined verteporfin photodynamic therapy and catheter-based 192Ir-mediated β-brachytherapy on inflammation and neoatherosclerosis reduction after laser angioplasty of the animal occluded femoral artery, wherein diagnostic ultrasound is adjuncted with laser angioplasty system and combination therapy system, with a goal of increased safety. Methods Briefly, New Zealand white rabbits were submitted to femoral artery advanced atherosclerotic occlusion by primary perivascular severe cold injury followed by a 2% cholesterol- rich diet for fourteen weeks. Histopathology results showed the formation of stable advanced atherosclerosis with lipid and neovessel-rich plaque, resulted in occlusion in all of the rabbits' arteries. Then treatment group underwent B- mode ultrasound-guided argon laser (488 nm) angioplasty followed by catheter- based β-brachytherapy (192Ir, 15 Gy) in combination with verteporfin (10mg/kg)-mediated low level red laser (λ=635 nm, E=130 J/cm2) photodynamic therapy. Results Results from ultrasonography and histopathology showed a significant reduction in the mean value for immune cells and smooth muscle hyperplasia cells density after angioplasty in the treatment group compared with the other groups (p<0.05). Conclusions Apoptotic effect of catheter-based 192Ir-mediated β-brachytherapy in combination with toxicity effect of verteporfin, can cause to reduce the density of macrophage cells and smooth muscle hyperplasia cells in the intimal layer. These findings provide the basis for developing of combined β-brachytherapy and verteporfin- mediated photodynamic therapy for a successful clinical application in the treatment of neoatherosclerosis after laser angioplasty. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab