Dual-Targeted Microbubbles Specific to Integrin αVß3 and Vascular Endothelial Growth Factor Receptor 2 for Ultrasonography Evaluation of Tumor Angiogenesis.

Aggressive tumors are characterized by angiogenesis that promotes the migration and dissemination of tumor cells. Our aim was to develop a dual-targeted microbubble system for non-invasive evaluation of tumor angiogenesis in ultrasound. Avidinylated microbubbles were conjugated with biotinylated arginylglycylaspartic acid and vascular endothelial growth factor receptor 2 (VEGFR2) antibodies. Subcutaneous MHCC-97H liver carcinoma models were established. Non-targeted, αvß3-targeted, VEGFR2-targeted and dual-targeted microbubbles was intravenously injected in series while acquiring ultrasound images of the tumor. The microbubbles were destroyed by a high-mechanical-index pulse 4 min after the injection. Peak intensity (PI) before and after the destructive pulse was recorded to compare contrast enhancement by different microbubbles. The targeting rates of the integrin-targeted, VEGFR2-targeted and dual-targeted groups were 95.02%, 96.04% and 94.23%, respectively, with no significant differences. Tumors in all groups were significantly enhanced. The time-intensity curve indicated no significant differences in arrival time, PI, area under the curve, amplitude and mean transit time. The difference in ultrasound signal intensity before and after the destructive pulse (⊿PI) for all targeted microbubble groups was significantly greater than that for the non-targeted microbubble group (all p values < 0.05), and the difference for the dual-targeted microbubble group was significantly greater than those of both mono-targeted groups (p <0.05).

Contrast-enhanced ultrasonography in differential diagnosis of focal gallbladder adenomyomatosis and gallbladder cancer.

BACKGROUND: Focal gallbladder adenomyomatosis (ADM) is a common disease that mimics gallbladder cancer (GBC) on ultrasonography. OBJECTIVE: Here we aim to assess the value of contrast-enhanced ultrasound (CEUS) in differentiating ADM from GBC. METHODS: Forty-one histopathologically proven focal ADMs and 34 GBCs (≤T2 stage) were enrolled in the study. Lesion location, blood flow signals, contrast pattern and appearance on contrast-enhanced ultrasound (CEUS) were compared respectively. RESULTS: Lesions were detected in fundus, body, neck at the rates of 61.0% (25/41), 26.8% (11/41) and 12.2% (5/41), respectively, in ADM patients, in comparison to 29.4% (10/34), 32.4% (11/34) and 38.2% (13/34), respectively, in GBC patients (p = 0.009). Blood flow signals were detected in 19.5% (8/41) of cases in ADMs, compared to 58.8% (20/34) in GBCs (p = 0.001). On CEUS, iso-enhancement, hypo-enhancement, intramural anechoic space and intactness of GB wall were detected in 41.5% (17/41), 39.0% (16/41), 56.1% (23/41) and 80.5% (33/41) cases of ADMs, in contrast to 17.6% (6/34), 20.6% (7/34), 20.6% (7/34) and 17.6% (6/34) of GBCs (p = 0.001, p = 0.001, p = 0.002, p < 0.001, respectively). The prior Youden's index were 0.81 based on intactness of GB wall on CEUS. CONCLUSION: Combined with CEUS helps improve the differential diagnosis accuracy of focal gallbladder ADMs.