Neointimal hyperplasia regression using combined paclitaxel- mediated confocal dual pulse shock wave sonoporation therapy and catheter- based 90Y- mediated brachytherapy

Background and aims Intimal hyperplasia refers to proliferation and migration of vascular smooth muscle cells primarily in the tunica intima, resulting in arterial wall thickening and decreased arterial lumen size. Neointimal hyperplasia is the major cause of restenosis after percutaneous carotid interventions such as stenting or angioplasty. The aim of this study was to investigate the effect of combined shock wave enhanced sonoporation therapy and catheter-based 90Y-mediated β-brachytherapy on neointimal hyperplasia regression in an animal model, wherein diagnostic B-mode ultrasound is combined with therapy system, with a goal of increased safety. Methods Endothelial balloon catheter denudation of the abdominal aorta of golden Syrian hamsters was performed. Histopathologic evaluation confirmed neointimal hyperplasia formation in all of the hamsters' arteries. The treatment group underwent intravenous lipid-based encapsulated paclitaxel nanoparticles (10mg/kg)-mediated extracorporeal confocal dual pulse low-level focused electrohydraulic shock wave (V=15 kV, F=2 Hz, Impulses = 50 and V=10 kV, F=0.2 Hz, Impulses = 150) enhanced sonoporation therapy accompanied by catheter-based 90Y-mediated β-brachytherapy (90Y, 15 Gy), guided by simultaneous B-mode ultrasound imaging. Results B-mode ultrasound guided combined shock wave enhanced sonoporation therapy and β-brachytherapy was feasible and appeared safe for the targeting of stenosis in the aorta artery. Furthermore, pathological results showed a significant reduction in the mean value for smooth muscle hyperplasia cells density, lumen wall thickness and percentage of luminal cross- sectional area of stenosis in the treatment group compared with the other groups (p<0.05). Conclusions Enhanced toxicity effect of paclitaxel, induced by enhanced sonoporation effect of shock wave therapy, due to inertial cavitation effect of collapsed capsules and dual pulse system application accompanied by apoptotic effect of brachytherapy, can cause to neointimal hyperplasia regression. Combined shock wave enhanced sonoporation therapy and β-brachytherapy is significantly associated with reduced aorta artery stenosis in hamsters. The mechanism may relate to reduced smooth muscle hyperplasia cells and inflammation in the tunica intima. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Mehrad Research Lab