Objective: In this study, C118P, a novel vascular disrupting agent (VDA), was evaluated for its ability in improving the ablative effect of high-intensity focused ultrasound (HIFU) on uterine fibroids by reducing blood perfusion.
Methods: Eighteen female rabbits were infused with isotonic sodium chloride solution (ISCS), C118P or oxytocin for 30 min, and an HIFU ablation of the leg muscles was performed within the last 2 min. Blood pressure, heart rate and laser speckle flow imaging (LSFI) of the auricular blood vessels were recorded during perfusion. Ears with vessels, uterus and muscle ablation sites were collected and sliced for hematoxylin-eosin (HE) staining to compare vascular size, as well as nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR) staining to observe necrosis after ablation.
Results: Analyses revealed that the perfusion of C118P or oxytocin steadily reduced blood perfusion in the ears to approximately half by the end of the perfusion, constricted the blood vessels of the ears and uterus, and improved HIFU ablation in the muscle tissues. C118P increased blood pressure and decreased heart rate. The degree of contraction of the auricular and uterine blood vessels was positively correlated.
Conclusion: This study confirmed that C118P could reduce blood perfusion in various tissues and had a better synergistic effect with HIFU ablation of muscle (the same tissue type as fibroids) than did oxytocin. C118P could therefore possibly replace oxytocin in facilitating HIFU ablation of uterine fibroids; however, electrocardiographic monitoring is required.
Keywords: Vascular disrupting agent; blood perfusion; high-intensity focused ultrasound; laser speckle flow imaging; vasoconstriction.