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

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. 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. 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. [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.