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 x SUV_mean) 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.

我们旨在定量研究基于 PET 的生物标志物对 [¹⁸F]FDG 和 [⁶⁸Ga]Ga-成纤维细胞活化蛋白抑制剂 （FAPI）-04 PET/CT 在高度侵袭性神经内分泌肿瘤 （NEN） 患者中的预后价值，并比较视觉评估的两种检查摄取差异与无进展生存期 （PFS）。方法：在这项单中心回顾性分析中，20 例高级别 NEN 患者接受了 [¹⁸F]FDG 和 [⁶⁸Ga]Ga-FAPI-04 PET。目视比较了两种 PET 扫描，并注意到存在 [¹⁸F]FDG 阳性、[⁶⁸Ga]Ga-FAPI-04 阴性 （FDG+/FAPI–） 病变。此外，我们评估了最大、峰值和平均 SUV;肿瘤体积 （TV）;和两种放射性示踪剂的总病灶摄取 （TLU = TV x SUV_mean） 使用基于 40% 病灶的阈值。使用对数秩分析或单变量 Cox 回归将定量和可视化分析的结果与 PFS 相关。PFS 使用 RECIST 1.1. 在放射学上定义，临床上使用疾病进展的迹象或死亡。结果：大多数原发性肿瘤位于胃肠道 （13/20 例患者，65%） 或未知原发性癌症 （5/20 例患者，25%）。20 例患者中有 9 例 （45%） 发现 FDG+/FAPI– 病变。FDG+/FAPI– 病变患者的 PFS 显著降低 4 个月，而无 FDG+/FAPI– 转移的患者为 9 个月 （P = 0.0063 [对数秩检验];风险比 [HR]，5.637;95% CI 1.619-26.16;P = 0.0110 [单变量 Cox 回归]）。在单变量分析中，还发现两种放射性示踪剂的 PFS 和 TV 之间存在显著相关性 （[¹⁸F]FDG：平均 TV，258 ± 588 cm³;人力资源，1.024 [每 10 cm³];95% CI，1.007–1.046;P = 0.0204） （[⁶⁸Ga]Ga-FAPI-04：平均电视，130 ± 192 cm³;心率，1.032 [每 10 厘米³];95% CI，1.001–1.062;P = 0.0277）和 [¹⁸F]FDG PET 上的 TLU（平均 TLU，1,931 ± 4,248 cm³;心率，1.004 [每 10 厘米³];95% CI，1.001–1.007;P = 0.0135）。结论：不一致的 FDG+/FAPI– 病变的存在与显着缩短的 PFS 相关，这可能表明更易出现早期进展的侵袭性疾病。对高度侵袭性 NENs 患者进行双重示踪 PET/CT 有助于指导治疗决策或识别高危病变，以寻求额外的局部治疗方法。