CEUS with VEGFR2-targeted microbubbles for monitoring of early immunotherapy effects in a colorectal cancer model.

To evaluate contrast-enhanced ultrasound (CEUS) with VEGFR2-targeted microbubbles for longitudinal monitoring of early treatment effects during combined anti-PD-L1/anti-CTLA-4 immunotherapy in a murine colorectal cancer model. Murine colorectal cancer allografts (CT26) were established subcutaneously in 29 female Balb/c mice (therapy n = 15; control n = 14). Baseline CEUS with VEGFR2-targeted microbubbles was performed on day 7. The therapy group received intraperitoneal anti-PD-L1 and anti-CTLA-4 antibodies between days 7-15; controls received sham treatment.

Follow-up CEUS was performed on days 14 and 21. Tumor perfusion (WiAUC) and VEGFR2 binding (SI8min, SI10min) were quantified, and immunohistochemistry assessed CD8, Ki-67, TUNEL, CD31, and VEGFR2. At FU1, WiAUC was significantly lower in the therapy group compared with controls (4,029 ± 61 vs. 6,391 ± 412; p