Abstract

Given that claudin 18.2 (CLDN18.2) is a cell surface protein specifically expressed by gastric cancer cells, anti-CLDN18.2 antibodies have demonstrated significant antitumor effects in patients with advanced gastric adenocarcinoma. The correlation of [18F]FDG PET/CT with CLDN18.2 expression remains unexplored. This study aimed to investigate whether CLDN18.2 expression was associated with [18F]FDG uptake and whether [18F]FDG PET/CT can be used to predict the CLDN18.2 status of gastric cancer. A retrospective analysis of [18F]FDG PET/CT images from 163 patients diagnosed with metastatic gastric cancer was conducted, and the expression of CLDN18.2 was assessed immunohistochemically. SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated in 3D mode using vendor-provided software. The relationship between PET metabolic parameters and CLDN18.2 status was analyzed. CLDN18.2-negative tumors showed a higher median SUVmax of 13.2 (1.8-46.7) compared to CLDN18.2-positive tumors at 7.55 (2.3-34.8), with a significant difference (p < 0.001). The median TLG was significantly higher in CLDN18.2-negative tumors (231.6) than in CLDN18.2-positive ones (81.14), indicating greater metabolic activity (p = 0.001). Multivariate analysis suggested that SUVmax remained significantly correlated with the status of CLDN18.2 (p = 0.01). CLDN18.2 expression was predicted with an accuracy of 69.9% when the SUVmax value of 10.9 was used as a cutoff point for analysis. Relatively reduced [18F]FDG uptake in metastatic gastric cancers correlates with positive CLDN18.2 expression compared to those with negative CLDN18.2 expression. [18F]FDG PET/CT may be useful for predicting the CLDN18.2 status of gastric cancer and thus aid in optimal treatment decisions. Question The study resolves the clinical issue of determining the correlation between [18F]FDG PET/CT imaging and claudin 18.2 expression in metastatic gastric cancer. Findings Claudin 18.2-positive metastatic gastric cancers exhibit relatively lower [18F]FDG uptake than negative ones. The SUVmax of 10.9 moderately predicts claudin 18.2 expression. Clinical relevance [18F]FDG PET/CT imaging could be a noninvasive way to predict claudin 18.2 status in metastatic gastric cancer, helping to improve personalized treatment plans.

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