Claudin18.2-Targeted SPECT/CT Imaging for Gastric Cancer: Preclinical Evaluation and Clinical Translation of the 99m Tc-Labeled Nanobody (PHG102) Radiotracer.

Claudin18.2 (CLDN18.2) has emerged as a significant target in the treatment of advanced gastric cancer. The screening of patients positive for CLDN18.2 is crucial for the effective application of targeted therapies specific to CLND18.2. In this study, we developed a novel nanobody-based probe, [ 99m Tc]Tc-PHG102, for use in nuclear medicine. We analyzed its radiochemical yield and stability to ensure accurate probe characterization. Additionally, we assessed the probe's affinity and specificity toward the CLDN18.2 target and evaluated its efficacy in the BGC823 18.2 xenograft model for SPECT/CT imaging of gastric cancer. The binding of [ 99m Tc]Tc-PHG102 to HEK-293T 18.2 and BGC823 18.2 cells was notably higher than its binding to HEK-293T 18.1 , HEK-293T, and BGC823 cells, with bound values of 12.87 ± 1.46%, 6.16 ± 0.34%, 1.25 ± 0.22%, 1.14 ± 0.26%, and 1.32 ± 0.07% AD, respectively. The binding ability of [ 99m Tc]Tc-PHG102 was significantly different between CLDN18.2-positive and negative cells ( P < 0.001). Imaging results demonstrated a time-dependent tumor accumulation of the radiotracer. Notably, at 0.5 h postinjection, rapid accumulation was observed with an average tumor uptake of 4.63 ± 0.81% ID/cc ( n = 3), resulting in clear tumor visualization. By 1 h postinjection, as [ 99m Tc]Tc-PHG102 was rapidly metabolized, a decrease in uptake by other organs was noted. Preliminary clinical imaging trials further confirmed the safety and effectiveness of the probe, indicating specificity for lesions expressing CLDN18.2 in gastric cancer and favorable in vivo metabolic properties. In conclusion, the nanobody-based probe [ 99m Tc]Tc-PHG102 proves to be a safe and effective tool for detecting CLDN18.2 expression levels in gastric cancer tumors and for screening CLDN18.2-positive patients.