Clinical Research Directory

Clinical Study on Noninvasive Evaluation of Ivonescimab Antibody Distribution and Expression in Esophageal Cancer Patients by 89Zr-AK112 PET Imaging

Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Summary

As a humanized bispecific antibody targeting PD-1 and VEGF-A, everolizumab exhibits high specificity for binding PD-1 and VEGF-A in vivo. This critical property was systematically validated in a recent molecular imaging study based on positron emission tomography (PET). The study utilized radiolabeled everolizumab to construct an everolizumab PET probe, enabling non-invasive and dynamic monitoring of drug distribution and targeting behavior in living organisms. The results demonstrated that the PET probe exhibited excellent target tissue enrichment in the HCT-116 colorectal cancer xenograft model. In vivo PET imaging revealed a sustained increase in tumor uptake over time, peaking at 48 hours post-administration at 13.73 ± 0.95% ID/g, indicating strong tumor retention. Blocking experiments (pre-injection of excess everolizumab) significantly reduced tumor uptake to 5.20 ± 0.10% ID/g (P=0.00011), strongly supporting that its in vivo targeting is mediated by PD-1/VEGF-A-specific interactions rather than nonspecific accumulation. At 48 hours, the tumor-to-muscle signal-to-noise ratio (T/M ratio) reached 15.62, with an outstanding target-to-background ratio explaining the superior efficacy and safety of everolizumab. Furthermore, in vitro distribution studies confirmed that the retention levels of this antibody in non-target organs such as the liver and blood were significantly lower than those in tumor tissues, suggesting favorable pharmacokinetic properties that may reduce associated potential toxicity risks. Histopathological analysis (H\&E staining) demonstrated no signs of inflammation, necrosis, or other pathological damage in major organs (including the heart, liver, spleen, and kidneys), indicating that evolocimab exhibits good biocompatibility and tolerable safety characteristics.

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