[F]FDG and [Ga]Ga-FAPI-04 Imaging for Outcome Prediction in Patients with High-Grade Neuroendocrine Neoplasms.

We aimed to quantitatively investigate the prognostic value of PET-based biomarkers on [F]FDG and [Ga]Ga-fibroblast activation protein inhibitor (FAPI)-04 PET/CT in patients with highly aggressive neuroendocrine neoplasms (NENs) and to compare the visually assessed differences in uptake on both examinations with progression-free survival (PFS). In this single-center retrospective analysis, 20 patients with high-grade NENs had undergone [F]FDG and [Ga]Ga-FAPI-04 PET. Both PET scans were visually compared, and the presence of [F]FDG-positive, [Ga]Ga-FAPI-04-negative (FDG+/FAPI-) lesions was noted. In addition, we assessed maximum, peak, and mean SUV; tumor volume (TV); and total lesion uptake (TLU = TV × SUV) for both radiotracers using a 40% lesion-based threshold. The results of quantitative and visual analysis were correlated with PFS using log-rank analysis or univariate Cox regression. PFS was defined radiographically using RECIST 1.1., clinically using signs of disease progression, or as death. Most primary tumors were located in the gastrointestinal tract (13/20 patients, 65%) or were cancer of unknown primary (5/20 patients, 25%). FDG+/FAPI- lesions were found in 9 of 20 patients (45%). Patients with FDG+/FAPI- lesions had a significantly decreased PFS of 4 mo, compared with 9 mo for patients without FDG+/FAPI- metastases ( = 0.0063 [log-rank test]; hazard ratio [HR], 5.637; 95% CI 1.619-26.16; = 0.0110 [univariate Cox regression]). On univariate analysis, a significant correlation was also found between PFS and TV for both radiotracers ([F]FDG: mean TV, 258 ± 588 cm; HR, 1.024 [per 10 cm]; 95% CI, 1.007-1.046; = 0.0204) ([Ga]Ga-FAPI-04: mean TV, 130 ± 192 cm; HR, 1.032 [per 10 cm]; 95% CI, 1.001-1.062; = 0.0277) and TLU on [F]FDG PET (mean TLU, 1,931 ± 4,248 cm; HR, 1.004 [per 10 cm]; 95% CI, 1.001-1.007; = 0.0135). The presence of discordant FDG+/FAPI- lesions is associated with a significantly shorter PFS, which might indicate more aggressive disease prone to early progression. Dual-tracer PET/CT of patients with highly aggressive NENs could help guide treatment decisions or identify high-risk lesions for additional local therapeutic approaches.