Functional and molecular ultrasound as a tool for therapy monitoring in a mouse tumor model under anti-angiogenic treatment

With regard to personalized tumor therapy, functional and molecular factors are becoming increasingly important in therapy monitoring. Histological methods can reliably visualize changes in vessel growth up to molecular alterations. However, follow-up of the same tissue in-vivo is not possible. In the present study, functional and molecular ultrasound methods are evaluated as therapy monitoring using the example of antiangiogenic tumor therapy with ASA (acetylsalicylic acid). Antiangiogenic therapy with ASA for 11 days was performed in a 4T1 mouse model selected for its strong vascularization. In therapy and control groups, ultrasound examinations with nonspecific- as well as VEGF-2-specific microbubbles and measurements of tumor volume with ultrasound-based 3D reconstruction were performed on day 1, 7 and 11. In the measurement with non-specific microbubbles, intratumoral blood flow decreased from day 1 to 11 in both groups, from 1.1 to 0.75 in the therapy group, from 0.61 to 1.19 in the control group (p=0.42). VEGFR-2 microbubbles assay showed a significant decrease in VEGFR-2 expression from day 7 to 11 compared to the control group (2.24 vs. 0.54; p=0.0015). Volume measurement with 3D reconstruction was able to account for peritumoral edema compared to conventional measurement, with a significant difference in measurement at day 11 in the control group (p=0.04). Experimental molecular ultrasound is a valuable tool for monitoring therapy over time in animal studies. Future application in clinical routine opens up new possibilities for more individualized tumor therapy.

Publikationsverlauf

Artikel online veröffentlicht:
12. Mai 2023