RT Journal Article SR Electronic T1 [18F]FDG and [68Ga]Ga-FAPI-04–Directed Imaging for Outcome Prediction in Patients with High-Grade Neuroendocrine Neoplasms JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.124.268288 DO 10.2967/jnumed.124.268288 A1 Michalski, Kerstin A1 Kosmala, Aleksander A1 Hartrampf, Philipp E. A1 Heinrich, Marieke A1 Serfling, Sebastian E. A1 Schlötelburg, Wiebke A1 Buck, Andreas K. A1 Meining, Alexander A1 Werner, Rudolf A. A1 Weich, Alexander YR 2024 UL http://jnm.snmjournals.org/content/early/2024/10/30/jnumed.124.268288.abstract AB We aimed to quantitatively investigate the prognostic value of PET-based biomarkers on [18F]FDG and [68Ga]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). Methods: In this single-center retrospective analysis, 20 patients with high-grade NENs had undergone [18F]FDG and [68Ga]Ga-FAPI-04 PET. Both PET scans were visually compared, and the presence of [18F]FDG-positive, [68Ga]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 × SUVmean) 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. Results: 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 (P = 0.0063 [log-rank test]; hazard ratio [HR], 5.637; 95% CI 1.619–26.16; P = 0.0110 [univariate Cox regression]). On univariate analysis, a significant correlation was also found between PFS and TV for both radiotracers ([18F]FDG: mean TV, 258 ± 588 cm3; HR, 1.024 [per 10 cm3]; 95% CI, 1.007–1.046; P = 0.0204) ([68Ga]Ga-FAPI-04: mean TV, 130 ± 192 cm3; HR, 1.032 [per 10 cm3]; 95% CI, 1.001–1.062; P = 0.0277) and TLU on [18F]FDG PET (mean TLU, 1,931 ± 4,248 cm3; HR, 1.004 [per 10 cm3]; 95% CI, 1.001–1.007; P = 0.0135). Conclusion: 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.