Novruzov_2023_Cancers.(Basel)_15_

BACKGROUND: Radiolabeled fibroblast activation protein (FAP) ligands, a novel class of tracers for PET/CT imaging, have demonstrated very promising results in various oncological, as well as in some benign, diseases with long-term potential to supplant the current pan-cancer agent [(18)F]FDG in some cancer types. Pancreatic ductal carcinoma (PDAC) belongs to the group of epithelial malignancies with a strong so-called "desmoplastic reaction", leading to a prominent tumor stroma with cancer-associated fibroblasts that exhibit a marked overexpression of fibroblast activation protein (FAP). The first clinical experiences in PDAC with (68)Ga-labeled FAP ligands suggested superior sensitivity to [(18)F]FDG. However, there is limited data with (18)F-labeled FAP derivatives, i.e. [(18)F]FAPI-74, yet prospective single- and multicenter trials are already ongoing. In this proof-of-concept study, we sought to evaluate the biodistribution, tumor uptake, and lesion detectability in patients with PDAC using [(18)F]FAPI-74 PET/CT as compared to [(18)F]FDG PET/CT scans for staging. METHODS: This study includes 7 patients (median age 69) who underwent both [(18)F]FDG PET/CT with contrast-enhancement and [(18)F]FAPI-74 PET with low-dose CT for primary staging (n = 3) and therapy response control after neoadjuvant (n = 1) or re-staging after palliative therapy (n = 3). The mean interval between PET scans was 11 +/- 4 days (range 1-15 days). The [(18)F]FDG and [(18)F]FAPI-74 PET/CT scans were acquired at 64 +/- 4.1 min (range 61-91 min) and 66.4 +/- 6.3 min (range 60-76 min), respectively, after administration of 200 +/- 94 MBq (range 79-318 MBq) and 235 +/- 88 MBq (range 90-321 MBq), respectively. Quantification of tracer uptake was determined with SUV(max) and SUV(mean). Furthermore, the tumor-to-background ratio (TBR) was derived by dividing the SUV(max) of tumor lesions by the SUV(max) of adipose tissue, skeletal muscle, and blood pool. RESULTS: Overall, 32 lesions were detected in 7 patients including primary (n = 7), lung (n = 7), bone (n = 3), lymph node (n = 13), and peritoneal metastases (n = 2). [(18)F]FAPI-74 detected 22% more lesions compared with [(18)F]FDG with a better TBR and visual lesion delineation. In one patient the primary lesion could be detected unequivocally with [(18)F]FAPI-74 but was missed by [(18)F]FDG imaging. Altogether, most of the lesions demonstrated markedly elevated uptake of [(18)F]FAPI-74 with a simultaneous lower uptake in the background, providing a very high visual contrast. CONCLUSION: To the best of our knowledge, this is the first, prospective, intra-individual investigation comparing [(18)F]FAPI-74 with [(18)F]FDG imaging in PDAC with encouraging results. These pivotalresults supporta larger, multicentric, prospective study to determine the value of [(18)F]FAPI-74 in detecting and staging PDAC in comparison with current standard of care imaging.