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Prognostic impact of discordant lesions on [18F]FDG and [68Ga]Ga-FAPI-04 PET/CT compared to histological FAP
Tim Jedamzik1, Aleksander Kosmala1, Stefan Kircher2
1Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany.
Objective:
On dual-tracer positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) and fibroblast activation protein inhibitor ([⁶⁸Ga]Ga-FAPI-04), discordant lesions (FDG+/FAPI-) in aggressive neuroendocrine neoplasms (NENs) are linked to shorter progression-free survival (PFS). This study evaluated the prognostic value of such lesions in comparison to histological fibroblast activation protein (FAP) expression from a clinically obtained biopsy and their impact on PFS.
Methods:
23 patients with aggressive NENs underwent both [¹⁸F]FDG and [⁶⁸Ga]Ga-FAPI-04 PET/CT as well as biopsy within a short period of time. PET parameters [standardized uptake values (SUV): SUVmax, SUVmean, SUVpeak] were measured, as were tumor volume (TV), and total lesion uptake (TLU = TV × SUVmean). FDG+/FAPI- lesions were identified. FAP expression was assessed immunohistochemically using the immunoreactive score (IRS-FAP). Correlations between PET metrics, IRS-FAP, and FDG+/FAPI- lesions were analyzed. Cox regression and log-rank test were used to evaluate associations with PFS.
Results:
IRS-FAP correlated significantly with TV ([¹⁸F]FDG: p=0.0165; [⁶⁸Ga]Ga-FAPI-04: p = 0.0181) and TLU ([¹⁸F]FDG: p = 0.0170; [⁶⁸Ga]Ga-FAPI-04: p = 0.0253). There was no significant correlation for IRS-FAP with SUV parameters. FDG+/FAPI- lesions were found in 9/23 patients and associated with significantly shorter PFS (4 vs. 10 months, HR: 3.383, p = 0.0015). [¹⁸F]FDG-TV and [¹⁸F]FDG-TLU correlated with PFS, but IRS-FAP showed no significant association with either PFS or FDG+/FAPI- lesions.
Conclusions:
FAP expression on immunohistochemistry obtained from a single biopsy site does not predict discordant PET/CT findings. In contrast, the presence of FDG+/FAPI- lesions is a strong prognostic factor for reduced PFS. Thus, dual-tracer PET/CT may offer superior risk stratification compared to single-lesion histological FAP assessment in aggressive NENs.
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