FAPI PET/CT shows favorable potential for the evaluation of gallbladder cancer: a prospective study comparing [68Ga]Ga-FAPI-04 and [18F]FDG.

BACKGROUND: Accurate staging of gallbladder cancer (GBC) is crucial for treatment planning. [18F]FDG PET/CT is limited in evaluating GBC due to high liver background signal and difficulty distinguishing inflammatory from malignant lesions. [68Ga]Ga-FAPI-04 PET/CT offers high tumor uptake and tumor-background contrast, demonstrating significant value in assessing multiple tumor types. This study aimed to investigate the value and the impact on clinical staging management of [68Ga]Ga-FAPI-04 comparing with [18F]FDG PET/CT in patients with gallbladder cancer. METHODS: This prospective study included patients diagnosed with primary or recurrent gallbladder cancer based on ultrasound, MRI, and PET/CT evaluations. All patients underwent two scans with [68Ga]Ga-FAPI-04 and [18F]FDG PET/CT within one week. The study compared the detection capabilities and uptake (SUVmax and TBR) differences of both tracers in primary tumors, distant metastases, lymph nodes, and peritoneal metastases. RESULTS: This study included 22 patients (age: 60.18 ± 9.53; 11 male, 11 female). [68Ga]Ga-FAPI-04 and [18F]FDG demonstrated comparable detection rates and maximum standardized uptake values (SUVmax) for primary gallbladder cancer lesions. However, [68Ga]Ga-FAPI-04 demonstrated significantly higher tumor-to-background ratios (TBR) in primary tumors (15.97 ± 9.70 vs. 5.96 ± 3.14, 95%CI [4.78,15.23], p=0.001). Higher detection rates (100% vs. 80%; 99% vs. 94%, respectively) and maximum standardized uptake values were observed for [68Ga]Ga-FAPI-04 in distant metastases and lymph node metastases (distant metastases: 8.88[5.53, 11.83] vs. 5.34[3.35, 9.80], 95%CI [1.93,4.25], p<0.001; lymph node metastasis: 8.85 [6.58, 11.20] vs. 6.00 [4.24, 8.03], 95%CI [2.44,3.43], p<0.001) and TBR values (distant metastasis: 11.18 [5.64, 14.97] vs. 6.11 [3.48, 12.75], 95%CI [7.46,11.15], p<0.001; Lymph node metastasis: 15.90 [10.31, 20.41] vs. 9.96 [6.09, 14.37], 95%CI [6.19,8.43], p<0.001). Additionally, [68Ga]Ga-FAPI-04 detected lesions in peritoneal involvement with higher SUVmax values. Ultimately, two patients had their staging upgraded based on [68Ga]Ga-FAPI-04 results, while two others had their staging downgraded. CONCLUSIONS: [68Ga]Ga-FAPI-04 outperformed [¹⁸F]FDG in detecting primary gallbladder cancer tumors, distant metastases, lymph node metastases, and peritoneal metastases, demonstrating higher SUVmax values and TBR ratios. Additionally, [68Ga]Ga-FAPI-04 shows promise in staging gallbladder cancer and selecting patients for radionuclide-targeted therapy.