VEGFR2 targeted microbubble-based ultrasound molecular imaging improving the diagnostic sensitivity of microinvasive cervical cancer

Background: The current diagnostic methods of microinvasive cervical Cancer lesions are imaging diagnosis and pathological evaluation. Pathological evaluation is invasive and imaging approaches are of extremely low diagnostic performance. There is a paucity of effective and noninvasive imaging approaches for these extremely early cervical Cancer during clinical practice. In recent years, ultrasound molecular imaging (USMI) with vascular endothelial growth factor receptor type 2 (VEGFR2/KDR/Flk-1) targeted microbubble (MB_{VEGFR2/KDR/Flk-1}) has been reported to improve the early diagnosis rates of breast Cancer (including ductal carcinoma in situ), pancreatic Cancer and hepatic micrometastases. Herein, we aimed to assess the feasibility of MB_{VEGFR2/KDR/Flk-1}-based USMI in extremely early cervical Cancer detection to provide an accurate imaging modality for microinvasive cervical Cancer (International Federation of Gynecology and Obstetrics (FIGO) Stage IA1 and IA2).

Results: We found MB_{VEGFR2/KDR/Flk-1}-based USMI could successfully distinguish extremely early lesions in diameter < 3 mm from surrounding normal tissues (all P < 0.05), and the sensitivity gradually decreased along with increasing tumor diameter. Moreover, normalized intensity difference (NID) values showed a good linear correlation with microvessel density (MVD) (R² = 0.75). In addition, all tumors could not be identified from surrounding muscles in subtracted ultrasound images when mice were administered MB_Con.

Conclusions: Overall, MB_{VEGFR2/KDR/Flk-1}-based USMI has huge potential for clinical application for the early detection of microinvasive cervical Cancer (FIGO Stage IA1 and IA2), providing the foothold for future studies on the imaging screening of this patient population.

Microinvasive cervical cancer; Molecular ultrasound imaging; Noninvasive diagnosis; VEGFR2.