Head-to-head Intra-individual Comparison of [18F]FAPI-74 and [18F]FDG-PET/CT in Patients with PDAC; Interim Analysis of an ongoing, prospective study

Introduction: Fibroblast activation protein-(FAP)-ligands, a novel class of tracers for PET/CT imaging, demonstrated very promising results in various oncological, especially epithelial malignancies, and also in some benign diseases with long-term potential, to surpass the current pan-cancer agent [¹⁸F]FDG PET/CT. 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 a marked overexpression of fibroblast activation protein (FAP). The first clinical experiences with ⁶⁸Ga-labeled FAP ligands opened a new avenue for the utility of PET/CT modality in PDAC management. However, due to well-known limitations regarding the use of Ga-labeling of radiopharmaceuticals, great efforts have been made to employ ¹⁸F labeled FAP derivatives, i.e. [¹⁸F]FAPI-74. With this analysis of interim data from our ongoing prospective, proof-of-concept study, we sought to evaluate the biodistribution, tumor uptake, and lesion detectability in patients with PDAC using [¹⁸F]FAPI-74 compared to contrast-enhanced [¹⁸F]FDG PET/CT for PDAC staging on an intra-individual basis.

Methods: This interim analysis includes 5 patients (median age 66) who underwent both [¹⁸F]FDG with contrast-enhanced CT and [¹⁸F]FAPI-74 PET/CT whole-body imaging for primary staging (n=4) or re-staging (n=1) with a mean scan time interval of 11.6 ± 4.2 days (range 1 - 15 days) and without any change of treatment during the interval. [¹⁸F]FDG and [¹⁸F]FAPI-74 PET/CT scans were acquired at 64 ± 3.6 min (range 61 - 69 min) and 66 ± 4.8 min (range 60 - 76 min) after administration of 200 ± 78 MBq (range 79 - 307 MBq) and 235 ± 59 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, 20 lesions were detected in five patients including primary (n=5), lung (n= 7), bone (n=2), and lymph node (n=6) metastases. [¹⁸F]FAPI-74 detected 33 % more lesions compared to [¹⁸F]FDG with a better TBR and sharp image contrast. Concerning patient-based comparison, in one patient the primary lesion could be detected unequivocally with [¹⁸F]FAPI-74 that 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.

Conclusions: To our best knowledge, this is the first intra-individual investigation comparing [¹⁸F]FAPI-74 with [¹⁸F]FDG in PDAC with very promising results. These promising results support further investigation with larger, prospective-designed studies.

• Download figure
• Open in new tab
• Download powerpoint