Radiofrequency thermal balloon angioplasty of vulnerable atherosclerotic plaque accompanied by delta-aminolevulinic acid photodynamic therapy and catheter-based samarium-153 brachytherapy

Abstract

Abstract Background The balloon angioplasty methods that are currently in use, cause to inflammation and subsequent neoatherosclerosis. Purpose The aim of this study was to evaluate the effect of combined photodynamic therapy and brachytherapy on inflammation and intimal hyperplasia reduction after radiofrequency thermal balloon angioplasty of carotid artery in an animal model of thin fibrous cap atheromatous plaque, wherein a high resolution diagnostic ultrasound is adjuncted with angioplasty and combination therapy system, with a goal of increased safety. Methods Briefly, New Zealand white rabbits were submitted to carotid artery vulnerable atherosclerotic plaque by primary intravascular balloon injury followed by a 1.5% cholesterol-rich diet for eight weeks. Histopathology results showed the formation of advanced atherosclerosis with a foam cell-rich atheromatous plaque, resulted in severe stenosis (>70%) in all of the rabbits' arteries. Then treatment group underwent B-mode ultrasound-guided radiofrequency thermal balloon angioplasty followed by catheter-based samarium-153 brachytherapy (153Sm, 18 Gy, β particles) and photosensitizer delta-aminolevulinic acid (delta-ALA)-mediated fiber optic catheter-based polarized light-emitting diodes (LEDs) violet light (λ±Δλ = 405±5 nm, E/A = 120 J/cm2) photodynamic therapy. Results Results from ultrasonography and histopathology showed a significant reduction in the mean value for macrophages, lymphocytes, mast cells, foam cells and hyperplastic vascular smooth muscle cells density after angioplasty in the treatment group compared with the other groups (p<0.05). Conclusion Apoptotic effect of brachytherapy in combination with cytotoxic and anti-inflammatory effect of delta-ALA photodynamic therapy on immune cells and hyperplastic vascular smooth muscle cells, can cause to reduce the neoatherosclerosis in the intimal layer. These findings provide the basis for developing of combined brachytherapy and photodynamic therapy for a successful clinical application in the inhibition of neoatherosclerosis after radiofrequency thermal balloon angioplasty. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab