The analysis of biodistribution and tumor uptake of [18F]AlF-FAPI-74 in patients with soft tissue sarcoma and gastro-intestinal tumors compared with [18F]FDG in a prospective, exploratory study

Abstract Background The roll-out of FAP (fibroblast-activation-protein) imaging with small-molecule PET tracers marks one of the major breakthroughs in nuclear medicine. The majority of current evidence, however, has been generated by 68Ga-labelled FAPI tracers, a reliance that presents serious economical and logistic challenges to the oncological community. Hence, current research focuses on development of 18F-labelled FAPI tracers to overcome the limitations of 68Ga-labelling. [18F]AlF-FAPI-74, a recently introduced radiotracer, emerges as a promising candidate to fulfill those unmet clinical needs. This single-center, exploratory study sought to investigate the biodistribution and tumor uptake of [18F]AlF-FAPI-74 across various tumor entities in a head-to-head comparison with [18F]FDG imaging. Material and method A total of 19 patients (15 males and 4 females) were enrolled in this prospective study with a head-to-head analysis of [18F]FAPI-74 and [18F]FDG PET/CT imaging between May 2021 and January 2024. According to inclusion criteria, patients underwent PET/CT scans, when they had either a biopsy-proven or highly suspected malignancy with a prior FDG imaging, or highly suspected or proven recurrence by clinical or other imaging findings or therapy monitoring after neoadjuvant or also palliative radiochemotherapy. All patients had histologically proven malignancies of pancreatic adenocarcinoma (PDAC) in 8 patients, soft tissue sarcoma (STS) in 6 patients, colorectal carcinoma (CRC) in 4 patients and gastric carcinoma in 1 patient. The mean injected activity for [18F]FAPI-74 and [18F]FDG PET/CT was 239 MBq (± 57) and 209 MBq (± 74) and the mean uptake time was 72 min (± 10) and 73 min (± 17), respectively. Results [18F]AlF-FAPI-74 demonstrated superior imaging characteristics compared to [18F]FDG, identifying a greater number of both primary and metastatic lesions across all tumor entities. Our SUV-metrics analysis revealed more favorable results for the detection of primary lesions with [18F]FAPI-74 imaging (e.g. SUVmax ± SD, 9.79 ± 4.2 vs. 6.41 ± 2.8, [18F]FAPI-74 vs. [18F]FDG, respectively), whereas only the TBR in relation to blood pool appeared to be statistically significant (5.08 vs. 3.15 (p: 0.03); [18F]FAPI-74 vs. [18F]FDG, respectively). We observed a similar tendency in the analysis of SUV-metrics (e.g. SUVmax ± SD, 7.42 ± 2.8 vs. 6.18 ± 2.7, [18F]FAPI-74 vs. [18F]FDG, respectively) in metastatic lesions as well. Conclusions In this prospective, exploratory study cohort, [18F]FAPI-74 appeared to display more favorable imaging characteristics such as lesion contrast and delineation compared with [18F]FDG. Given the advantages of 18F-labeling, [18F]FAPI-74 warrants further investigation with larger cohorts to determine its diagnostic potential and clinical impact.