Feasibility of the novel vascular disrupting agent C118P for facilitating high-intensity focused ultrasound ablation of uterine fibroids

Abstract

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
• high-intensity focused ultrasound
• blood perfusion
• vasoconstriction
• laser speckle flow imaging

Acknowledgements

The authors thank Nanjing Sanhome Pharmaceutical Co. Ltd. for the kind gift of C118P.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data used and analyzed during the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

The authors would like to acknowledge the support from the National Natural Science Foundation of China, Grant Numbers [81603142 and 82127807]; the National Key Research and Development Program of China [2020YFA0909000]; Shanghai Key Laboratory of Molecular Imaging [18DZ2260400]; and CZC Technology Co., Ltd. Nanjing.