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

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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* 1\) Patients aged over 18 years with no gender restriction;
* 2\) Patients diagnosed with esophageal cancer;
* 3\) Patients eligible for 89Zr-AK112 PET examination;
* 4\) Written informed consent signed by the subject or their legal guardian.

Exclusion Criteria:

* 1\) Patients who have received antitumor therapy prior to PET/CT scanning;
* 2\) Patients with severe diseases that cannot tolerate PET/CT scanning;
* 3\) Alternative subjects with contraindications to PET/CT scanning;
* 4\) Radiation exposure exceeding 50 mSv dose in the past year;
* 5\) Alternative subjects who underwent major surgery within the past 3 months; those who received experimental drugs or devices (with unclear efficacy or safety) within the past 1 month;
* 6\) Alternative subjects with any clinical conditions that the principal investigator of this study considers may cause or pose potential hazards from the investigational product.