Sonodynamic Therapy Decreased Neointimal Hyperplasia After Stenting in the Rabbit Iliac Artery

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Abstract
In-stent restenosis remains a pivotal problem after coronary and peripheral stenting. Sonodynamic therapy inhibits tumor growth by means of cytotoxicity after the activation of sonochemical sensitizers by ultrasound. PAD-S31 is known to be a water-soluble, chlorin-derivative sonochemical sensitizer. We assessed the efficacy of sonodynamic therapy using this sensitizer on neointimal hyperplasia in a rabbit stent model. Stents were implanted in the iliac arteries of 16 rabbits. A total of 32 stented arteries were randomized to sonodynamic therapy, control, ultrasound exposure, and PAD-S31 groups. One hour after the intravenous administration of PAD-S31 (25 mg/kg body weight), ultrasound energy (1 MHz, 0.3 W/cm(2)) was delivered transdermally to the sonodynamic therapy group. At 28 days, all stent sites were analyzed morphometrically. The size of the intimal cross-sectional area was smaller in the sonodynamic therapy group than in the control, ultrasound, and PAD-S31 groups (0.31+/-0.07 versus 1.38+/-0.47, 1.66+/-0.71, and 1.61+/-0.42 mm(2), respectively; P<0.05). The ratio of the intimal and medial cross-sectional area was smaller in the sonodynamic therapy group than in the control, ultrasound, and PAD-S31 groups (0.71+/-0.22 versus 2.53+/-1.39, 2.48+/-0.60, and 3.45+/-1.42 mm(2); P<0.05). Sonodynamic therapy with PAD-S31 is considered to be a feasible treatment modality for noninvasively inhibiting neointimal hyperplasia in a rabbit iliac stent model.

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