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Congress: ECR25
Poster Number: C-10265
Type: Poster: EPOS Radiologist (scientific)
Authorblock: F. Herr, M. J. Antons, L. Blume, J. Stueckl, H. Hirner-Eppeneder, J. Ricke, M. Heimer, D-A. Clevert, C. C. Cyran; München/DE
Disclosures:
Felix Herr: Nothing to disclose
Melissa J. Antons: Nothing to disclose
Larissa Blume: Nothing to disclose
Jennifer Stueckl: Nothing to disclose
Heidrun Hirner-Eppeneder: Nothing to disclose
Jens Ricke: Nothing to disclose
Maurice Heimer: Nothing to disclose
Dirk-André Clevert: Nothing to disclose
Clemens C. Cyran: Nothing to disclose
Keywords: Molecular imaging, Oncology, Ultrasound physics, MR-Functional imaging, PET-CT, Ultrasound, Experimental investigations, Molecular imaging, Radionuclide therapy, Cancer, Image guided radiotherapy, Molecular, genomics and proteomics
Purpose In a number of preclinical studies, multiparametric CEUS with VEGFR2-targeted microbubbles (MB) has been demonstrated to be a highly sensitive tool for monitoring the effects of therapy in a range of tumour entities (1-3). Consequently, VEGFR2-targeted CEUS may also be capable of providing combined functional and molecular imaging biomarkers for the non-invasive in vivo assessment of tumour angiogenesis and early therapy response in murine melanoma allografts under combined anti-PD-L1/anti-CTLA-4 immunotherapy.Therefore, we hypothesised that CEUS with VEGFR2-targeted MB enables the functional...
Read more Methods and materials Murine melanoma allografts (B16-F10) were implanted subcutaneously in n = 10 therapy and n = 10 control female C57BL/6 mice. Baseline CEUS with VEGFR2-targeted MB (BR55) was performed on day 7 and follow-up on day 12. The therapy group received 3 intraperitoneal injections on days 7, 9 and 11, the control group received a placebo. CEUS assessed tumour perfusion during an early vascular phase (wash-in area under the curve = WiAUC) and VEGFR2-specific binding during a late molecular phase (signal...
Read more Results At follow-up, the CEUS perfusion parameter WiAUC demonstrated a significantly higher decrease in the therapy than in the control group (p = 0.008, fig. 1 and fig. 2). At follow-up, the number of VEGFR2-targeted MB in the late phase was significantly lower in the therapy than in the control group (SI8min p = 0.003; SI10min p = 0.002, fig. 1 and fig. 3). Immunohistochemistry revealed significantly more apoptotic tumour cells (TUNEL, p = 0.001), more tumour infiltrating lymphocytes (CD8, p...
Read more Conclusion CEUS with VEGFR2-targeted microbubbles allowed for monitoring early treatment effects of a combined anti-PD-L1/anti-CTLA-4 immunotherapy on melanoma allografts with a significantly lower tumour perfusion and a significantly lower binding of VEGFR2-targeted microbubbles in the therapy than in the control group. The formation of an immunosuppressive tumour microenvironment, induced by VEGFR2, results in decreased apoptosis and enhanced proliferation of melanoma cells. This immunosuppressive effect of VEGFR2 can be inhibited by immunotherapy. Our results underscore the potential of a combined anti-PD-L1/anti-CTLA-4 immunotherapy...
Read more References 1. Baetke SC, Rix A, Tranquart F, Schneider R, Lammers T, Kiessling F, et al. Squamous Cell Carcinoma Xenografts: Use of VEGFR2-targeted Microbubbles for Combined Functional and Molecular US to Monitor Antiangiogenic Therapy Effects. Radiology. 2016;278:430–40.2. Baron Toaldo M, Salvatore V, Marinelli S, Palamà C, Milazzo M, Croci L, et al. Use of VEGFR-2 targeted ultrasound contrast agent for the early evaluation of response to sorafenib in a mouse model of hepatocellular carcinoma. Mol Imaging Biol. 2015;17:29–37.3. Eschbach RS, Clevert...
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