[68Ga]Ga-FAPI-04 PET/MR imaging strategy in management of Krukenberg tumors (KTs) from gastric signet-ring-cell carcinoma: to overcome limitation of [68Ga]Ga-FAPI-04 PET imaging in KTs

Purpose To compare performance of whole-body [Ga-68]Ga-FAPI-04 and [F-18]FDG PET imaging in the detection of Krukenberg tumors (KTs), primary site and extra-ovarian metastases of gastric signet-ring-cell carcinoma (GSRCC), and evaluate the value of [Ga-68]Ga-FAPI-04 PET/MR imaging strategy and its potential impact on the management of KTs from GSRCC. Methods Twelve patients with twenty-three KTs from GSRCC, who underwent both [Ga-68]Ga-FAPI-04 pelvic PET/MR and whole-body [Ga-68]Ga-FAPI-04 and [F-18]FDG PET imaging were retrospectively analyzed. [Ga-68]Ga-FAPI-04 and [F-18]FDG uptakes were compared by using Wilcoxon signed-rank test or paired t test. McNemar's test was used to compare lesion detectability between two modalities. Two-tailed P<0.05 was considered statistically significant. Immunohistochemistry staining was utilized to analyze the fibroblast activation protein (FAP) expression in KTs. Results A total of 12 patients with 23 KTs from GSRCC (8 synchronous and 4 metachronous) were evaluated. [Ga-68]Ga-FAPI-04 was superior to [F-18]FDG PET in detecting primary sites of GSRCC (100% [11/11] vs. 18.2% [2/11], p = 0.002), involved lymph nodes (90.9% [10/11] vs. 54.5% [6/11], p = 0.046) and peritoneal metastases (100% [12/12] vs. 41.7% [5/12], p = 0.008), with higher SUVmax and TBR (all p < 0.005). Both tracers had limited value in identifying KTs, with 100% false negative rate on [Ga-68]Ga-FAPI-04 PET and a low detection rate of 8.7% on [F-18]FDG PET. Fap immunohistochemistry showed negative or slight FAP expression in neoplastic signet ring cells and ovarian stroma. [Ga-68]Ga-FAPI-04 PET/MR imaging strategy greatly improved the detection rate of Krukenberg tumors (87%, 20/23). After adding diffusion-weighted imaging (DWI), the detection rate was further improved (87.5% vs. 100%, p = 0.083). [Ga-68]Ga-FAPI-04 PET/MR imaging strategy either upgraded TNM staging or changed treatment management in twelve patients. Conclusions [Ga-68]Ga-FAPI-04 PET outperformed [F-18]FDG PET in detecting primary site and most extra-ovarian metastases of GSRCC, but both tracers had limited value in identifying Krukenberg tumors. Pelvis MRI should be applied to compensate the limitation of [Ga-68]Ga-FAPI-04 PET imaging to identify Krukenberg tumours. The [Ga-68]Ga-FAPI-04 PET/MR imaging strategy has the potential to impact treatment decisions for GSRCC patients with KTs.