[18F] AlF‑NOTA‑FAPI‑04 PET/CT as a promising tool for imaging fibroblast activation protein in gastrointestinal system cancers: a prospective investigation of comparative analysis with 18F-FDG

Abstract

Purpose: The radiopharmaceutical [¹⁸F]AlF-NOTA-FAPI-04 presents a promising alternative to ⁶⁸ Ga-FAPI owing to its relatively longer half-life. This study aimed to evaluate the clinical usefulness of [¹⁸F]AlF-NOTA-FAPI-04 PET/CT for the diagnosis of primary and metastatic lesions in various types of gastrointestinal system cancers, compared with ¹⁸F-FDG PET/CT.

Methods: Patients diagnosed with gastrointestinal system malignancies were prospectively enrolled. All patients underwent both ¹⁸F-FDG and ¹⁸F-FAPI-04 PET/CT scans within one week, with 44 (73.3%) for cancer staging and 16 (26.7%) for tumor restaging. Diagnostic efficacy of the primary tumor, as well as the presence and number of lymph nodes and distant metastases, were assessed. Tumor uptake was quantified by the maximum standard uptake value (SUVmax).

Results: For detection of primary tumor, the diagnostic sensitivity of ¹⁸F-FDG PET/CT was 72.7%, while it was 97.7% for ¹⁸F-FAPI-04 PET/CT. Based on per-lymph node analysis, the sensitivity, specificity, and accuracy of ¹⁸F-FAPI-04 PET/CT in diagnosing metastatic lymph nodes were 91.89%, 92.00%, and 91.96%, respectively. These values were notably higher than those ¹⁸F-FDG PET/CT (79.72%, 81.33% and 80.80%, respectively). The ¹⁸F-FAPI-04 PET/CT surpassed ¹⁸F-FDG PET/CT in detecting suspected metastases in the brain (7 vs. 3), liver (39 vs. 20), bone (79 vs. 51), lung (11 vs. 4), and peritoneal carcinoma (48 vs. 22). Based on per-patient analysis, differential diagnostic accuracies (¹⁸F-FAPI-04 vs. ¹⁸F-FDG PET/CT) were observed in all patients (91.7% vs. 76.7%), the initial staging group (90.9% vs. 79.5%), and the re-staging group (93.8% vs. 68.7%). Additionally, ¹⁸F-FAPI-04 PET/CT revised final diagnosis in 31.7% of patients, contrasting with ¹⁸F-FDG PET/CT, and prompted changes in clinical management for 21.7% of the patients.

Conclusion: ¹⁸F-FAPI-04 PET/CT outperforms ¹⁸F-FDG PET/CT in delineating the primary gastrointestinal tumors and detecting suspected metastatic lesions due to a higher target-to-background ratio (TBR). Moreover, ¹⁸F-FAPI-04 PET/CT could provide valuable guidance for tumor staging, thereby having a potential impact on patient management.

Keywords: Cancer-associated fibroblast; Clinical management; FAPI PET/CT; FDG PET/CT; Gastrointestinal system cancers.