Ultrasound Molecular Imaging With VEGFR2-Targeted Microbubbles to Evaluate Intrauterine Adhesion After Endometrial Injury and Monitor the Therapeutic Effects.

Abstract

Objectives: To assess the severity of intrauterine adhesion (IUA) after endometrial injury via ultrasound molecular imaging (USMI) of vascular endothelial growth factor receptor 2 (VEGFR2) expression on the uterine endothelium.

Methods: MB_VEGFR2 was constructed via "biotin-avidin-biotin" bridging technology. A rat IUA animal model was constructed via chemical injury. Fourteen days after the model was constructed, MB_Con and MB_VEGFR2 contrast agents were injected into the standard group and the model group of rats, and simultaneous ultrasound molecular imaging was carried out and ultrasound molecular imaging was performed and the changes in ultrasound signals in vivo were normalized to differential targeted enhancement (dTE). In addition, immunohistochemistry was used to detect the expression levels of VEGFR2 and α-SMA in the uterine tissues of the rats in both groups.

Results: Targeted-VEGFR2 microbubble (MB_VEGFR2) was successfully constructed, the average particle size of the targeted VEGFR2 microbubble contrast agent was 2309.6 ± 234.3 nm, with the average zeta potential -16.9 ± 0.15 mV and the dispersity coefficient less than 0.4. In addition, its essential performance and biosafety were examined, which revealed that the MB_VEGFR2 contrast agent had an appropriate size, stable imaging performance, good target adhesion, and good biocompatibility. In vivo, ultrasound imaging results revealed that after the injection of the targeted MB_VEGFR2, the contrast ultrasound signal intensity of uterine tissues in the model group (62.5 ± 17.9 dB) was higher than in the normal group (33.5 ± 12.5 dB), and the difference was statistically significant (P < .05). The immunohistochemistry results revealed that the expression of VEGFR2 and α-SMA in the uterine tissue of the model group was greater than that in the standard group (P < .05), further indicating that the signal intensity of the MB_VEGFR2 contrast agent can reflect the expression level of VEGFR2 molecules.

Conclusions: Ultrasound molecular imaging based on MB_VEGFR2 can be used to evaluate the expression level of VEGFR2 in uterine vascular endothelial cells. This provides a potential approach for the early diagnosis and treatment monitoring of intrauterine adhesions after endometrial injury.