PB0016 - Sonodynamic therapy in combination with Auger electron therapy for inhibition of arterial restenosis after radiofrequency ablation: monitored by ultrasonography and optical coherence tomography

Background: When an artery that has been opened with a stent or angioplasty narrows once more, it is said to have undergone restenosis. Restenosis result in neoatherosclerosis and plaque formation and plaque rupture leads to arterial thromboembolism.

Aims: In this study, we developed an experimental sonodynamic- Auger electron combination therapy system and investigated its effectiveness on restenosis inhibition.

Methods: In brief, after receiving primary perivascular Co2 laser- based far-infrared injury to the right common carotid artery, New Zealand white rabbits were administered 2% cholesterol-rich diet for six weeks. According to the results of the histopathology, all of the rabbits' arteries were blocked as a result of the development of a fibroatheromatic plaque. Following an ultrasound-guided radiofrequency ablation, the treatment group received sonosensitizer methylene blue-laden PESDA (Perfluorocarbon Exposed Sonicated Dextrose Albumin) microbubbles (100ml/kg, 2-5 × 105 bubbles/ml)- mediated focused shock wave (V= 20 Kv, F= 2 Hz, Impulses= 120) sonodynamic therapy accompanied by X-rays-based Auger electron therapy using lipid-based, encapsulated gold nanoparticles (AuNPs). Both histology and optical coherence tomography (OCT) were used to evaluate the restenosis after procedure.

Results: The treated group's mean values for the smooth muscle hyperplasia cells density and the lumen wall mean thickness and the percentage of luminal cross-sectional area of stenosis, were significantly lower than the other groups' values (p < 0.05).

Conclusion(s): Reduced smooth muscle hyperplasia cells in the intimal layer can result from the enhanced anti-proliferative effect of methylene blue- mediated sonodynamic therapy, caused by the enhanced sonoporation effect of shock wave, induced by the inertial cavitation effect of collapsed capsules and microbubbles, along with the anti-proliferative effect of gold nanoparticles- based- Auger electron therapy.