68Ga-FAPI-04

This study aimed to compare the diagnostic capabilities of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT imaging in staging gastric carcinoma, exploring the impact of 68Ga-FAPI-04 PET/CT on treatment planning and its prognostic significance.

The research included 31 patients undergoing staging for gastric cancer, who received both 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT scans. We compared the SUVmax and SUVmean of the primary tumor and lymph nodes, the count of organ metastases, tumor-to-background ratios, and overall staging accuracy. Additionally, the study evaluated radiological progression-free survival and overall survival rates.

The 68Ga-FAPI-04 PET/CT demonstrated superior efficacy in identifying the primary tumor compared with 18F-FDG PET/CT, particularly in cases of poorly cohesive, signet-ring cell, and mucinous subtypes, with detection rates of 96.7% versus 77.4% (P = 0.006 and P = 0.008, respectively). Analysis of lymph nodes showed a significantly higher detection of positive nodes with 68Ga-FAPI-04 (P = 0.026), although no significant differences were observed in SUVmax and tumor-to-background ratio on a patient basis (P > 0.05). SUVmax and tumor-to-background ratios for peritoneal involvement were notably higher with 68Ga-FAPI-04 PET/CT compared with 18F-FDG PET/CT (P = 0.04 for both). No significant differences were found in the detection of organ metastases and disease stage between the 2 imaging modalities (P > 0.05). Primary tumor uptake did not significantly impact radiological progression-free survival or overall survival in either modality.

68Ga-FAPI-04 PET/CT imaging surpasses 18F-FDG PET/CT in detecting the primary tumor, especially in poorly cohesive and signet-ring cell gastric cancer types, and offers improved accuracy in disease staging. This indicates its potential to enhance treatment management and prognostic assessment in gastric cancer patients.

Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) can interact with tumor parenchymal cells to promote tumor growth and migration. Fibroblast activation protein (FAP) expressed by CAFs can be targeted with positron emission tomography (PET) tracers, but studies on FAP expression patterns in intracranial tumors remain scarce. We aimed to evaluate FAP expression patterns in intracranial tumors with gallium-68 FAP inhibitor-04 (⁶⁸Ga-FAPi-04) and immunohistochemical staining and to observe the interactions between CAFs and tumor cells with a head-to-head comparison of ⁶⁸Ga-FAPi-04 and fluoride-18 fluoroethyl-L-tyrosine (¹⁸F-FET) for PET quantification analysis.

We prospectively enrolled 22 adult patients with intracranial mass lesions. ⁶⁸Ga-FAPi-04 and ¹⁸F-FET PET-computed tomography (PET/CT) brain imaging were applied before surgery. Maximal tumor-to-brain ratio (TBRmax), metabolic tumor volume (MTV), and total lesion tracer uptake (TLU) was obtained, and different thresholds were used for ⁶⁸Ga-FAPi-04-positive lesion delineation owing to the lack of relevant guidelines. The MTV and TLU ratios of both tracers were calculated. Linear regression was applied to observe the differential efficacy of semiquantitative PET parameters.

A total of 22 patients with a mean age of 50±13 years (range, 27-69 years) were enrolled. Heterogeneous patterns of ⁶⁸Ga-FAPi-04 uptake [median of maximal standardized uptake value (SUVmax) =3.8; range, 0.1-19.1] were found. More malignant tumors, including brain metastasis, glioblastoma, and medulloblastoma, generally exhibited more significant ⁶⁸Ga-FAPi-04 uptake than did the less malignant tumors, while the SUVmax and TBRmax exhibited nonsignificant differences across three intracranial lesion groups of primary brain tumor, brain metastasis, and noncancerous disease (SUVmax: P=0.092; TBRmax: P=0.189). Immunohistochemistry staining showed different stromal FAP expression status in various intracranial lesions. In 15 patients with positive ⁶⁸Ga-FAPi-04 intracranial tumor uptake, the MTV_FAPi:MTV_FET ratio had differential efficacy in various types of intracranial tumors [95% confidence interval (CI): 0.572-7.712; P=0.027], and further quantification analyses confirmed the differential ability of the MTV_FAPi:MTV_FET ratio (95% CI: -0.045 to 11.013, P=0.052; 95% CI: 0.044-17.903, P=0.049; 95% CI: -1.131 to 30.596, P=0.065) with different isocontour volumetric thresholds.

This head-to-head study demonstrated heterogeneous FAP expression in intracranial tumors. The FAP expression volume percentage in tumor parenchyma may therefore offer benefit with respect to differentiating between intracranial tumor types.