Relationship between [¹⁸F]FDG PET/CT findings and claudin 18.2 expression in metastatic gastric cancer

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. SUV_max, 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 SUV_max 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 SUV_max 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 SUV_max 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 SUV_max 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.