Head-to-Head Intra-Individual Comparison of Biodistribution and Tumor Uptake of [¹⁸F]FAPI-74 with [¹⁸F]FDG in...

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 [¹⁸F]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 ⁶⁸Ga-labeled FAP ligands suggested superior sensitivity to [¹⁸F]FDG. However, there is limited data with ¹⁸F-labeled FAP derivatives, i.e. [¹⁸F]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 [¹⁸F]FAPI-74 PET/CT as compared to [¹⁸F]FDG PET/CT scans for staging.

This study includes 7 patients (median age 69) who underwent both [¹⁸F]FDG PET/CT with contrast-enhancement and [¹⁸F]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 [¹⁸F]FDG and [¹⁸F]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.

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). [¹⁸F]FAPI-74 detected 22% more lesions compared with [¹⁸F]FDG with a better TBR and visual lesion delineation. In one patient the primary lesion could be detected unequivocally with [¹⁸F]FAPI-74 but was missed by [¹⁸F]FDG imaging. Altogether, most of the lesions demonstrated markedly elevated uptake of [¹⁸F]FAPI-74 with a simultaneous lower uptake in the background, providing a very high visual contrast.

To the best of our knowledge, this is the first, prospective, intra-individual investigation comparing [¹⁸F]FAPI-74 with [¹⁸F]FDG imaging in PDAC with encouraging results. These pivotalresults supporta larger, multicentric, prospective study to determine the value of [¹⁸F]FAPI-74 in detecting and staging PDAC in comparison with current standard of care imaging.