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

Authors

Felix L Herr, Jonathan K Stock, Verena Gräfin Zu Solms-Baruth, Larissa V Blume, Sandra Kloiber-Langhorst, Heidrun Hirner-Eppeneder, Jennifer Stueckl, Barbara Akla, Jens Ricke, Thomas Geyer, Wolfgang Kunz, Maurice M Heimer, Dirk-Andre Clevert, Melissa J Antons, Clemens C Cyran

Published in

Cancer imaging : the official publication of the International Cancer Imaging Society. Volume 26. Issue 1. Jul 31, 2026. Epub Jul 31, 2026.

Abstract

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 (SI_8min, SI_10min) 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 < 0.001), and remained significantly lower at FU2 (1,028 ± 27 vs. 2,049 ± 39; p < 0.001). VEGFR2-targeted microbubble binding was consistently lower under therapy. At FU1, SI_8min was 407 ± 11 vs. 626 ± 13 and SI_10min was 409 ± 10 vs. 634 ± 28 (both p < 0.001). At FU2, SI_8min was 106 ± 6 vs. 207 ± 4 and SI_10min was 107 ± 5 vs. 207 ± 4 (both p < 0.001). Immunohistochemistry confirmed higher apoptosis and tumor-infiltrating lymphocytes, and lower proliferation, microvascular density, and VEGFR2 expression in treated tumors (all p < 0.05).
VEGFR2-targeted CEUS enabled longitudinal monitoring of early response to dual anti-PD-L1/anti-CTLA-4 immunotherapy in colorectal cancer. Treated tumors showed lower perfusion and VEGFR2-targeted binding, paralleled by reduced vessel density and VEGFR2 expression as well as increased CD8 infiltration and apoptosis. These findings support VEGFR2-targeted CEUS as a promising noninvasive imaging biomarker for monitoring early immunotherapy-associated vascular changes.

PMID:
42538573
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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