Yu Haonan, Bao Xiangyuan, Gu Yian, Pan Meijie, He Qing, Li Dong, Chen Qiusong, Yao Shaobo
Department of PET/CT Diagnostic, Tianjin Medical University General Hospital, Tianjin, 300052, China.
The Clinical Research and Translational Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian Province, China.
Eur J Nucl Med Mol Imaging. 2025 Apr 22. doi: 10.1007/s00259-025-07288-x.
Accurate preoperative localization is particularly important for surgical treatment of insulinomas. Current imaging methods, including F-FDG (FDG) PET/CT, Ga-DOTATATE (TATE) PET/CT, CE-CT, and CE-MRI, have limitations. This prospective study provides a direct comparison of Ga-NOTA-Exendin-4 (Ex4) PET/CT with other imaging techniques.
47 patients with biochemically proven endogenous hyperinsulinemic hypoglycemia underwent Ex4 PET/CT and other imaging methods. Sensitivity and accuracy of all imaging procedures for localizing insulinoma were calculated at the patient level and lesion level. Both clinical (>10 years experience) and junior (< 2 years experience) nuclear medicine physician readings were used to assess the diagnostic efficacy. We compared the SUV and tumor-to-background ratio (TBR) of three tracers and analyzed the values with Ki-67, maximum tumor diameter, and glucose metabolism indicators.
In patient level, the sensitivity and accuracy of Ex4 PET/CT (94.11% and 95.74%) were higher than TATE PET/CT (70.59%, p = 0.026; 78.72%, p = 0.030), FDG PET/CT (50.00%, p < 0.001; 63.83%, p < 0.001), CE-CT (77.77%, p = 0.135; 72.22%, p = 0.007), and CE-MRI (63.64%, p = 0.135; 43.75%, p < 0.001), respectively. Interobserver agreement was higher for Ex4 PET/CT than TATE PET/CT and FDG PET/CT (Cohen κ, 0.839 vs. 0.707 and 0.784, respectively). SUV and TBR of Ex4 and TATE PET/CT were significantly higher than FDG PET/CT (p < 0.01). Negative correlations of tumor Ki-67 with TATE PET/CT were observed with SUV (r = -0.637, p < 0.001). SUV and TBR of three molecular imaging methods had positive correlations with the maximum tumor diameter (p < 0.05), except TBR of FDG PET/CT. Semi-quantitative values of the three tracers showed no correlation with the lowest blood glucose level, corresponding insulin, and C-peptide level. TBR of TATE PET/CT showed a positive correlation with C-peptide (r = 0.393, p = 0.043).
Ex4 PET/CT showed superior characteristics in localization compared to routine imaging modalities in benign insulinomas. Ex4 PET/CT demonstrates better imaging quality and interpretability than FDG PET/CT and TATE PET/CT. Combined Ex4 and TATE PET/CT could provide a comprehensive evaluation/localization of insulinoma.
The trial was retrospectively registered at ClinitalTrial.gov (NCT06690957 and NCT06725693) on November 14, 2024 and December 5, 2024.
准确的术前定位对于胰岛素瘤的手术治疗尤为重要。目前的成像方法，包括F-FDG（FDG）PET/CT、Ga-DOTATATE（TATE）PET/CT、增强CT（CE-CT）和增强MRI（CE-MRI）都存在局限性。这项前瞻性研究对Ga-NOTA-艾塞那肽-4（Ex4）PET/CT与其他成像技术进行了直接比较。
47例经生化证实为内源性高胰岛素血症性低血糖症的患者接受了Ex4 PET/CT及其他成像检查。在患者层面和病灶层面计算所有成像检查对胰岛素瘤定位的敏感性和准确性。由临床经验丰富（>10年经验）和初级（<2年经验）的核医学医师阅片来评估诊断效能。我们比较了三种示踪剂的SUV（标准摄取值）和肿瘤与本底比值（TBR），并分析了其与Ki-67、最大肿瘤直径及葡萄糖代谢指标的关系。
在患者层面，Ex4 PET/CT的敏感性和准确性（分别为94.11%和95.74%）高于TATE PET/CT（分别为70.59%，p = 0.026；78.72%，p = 0.030）、FDG PET/CT（分别为50.00%，p < 0.001；63.83%，p < 0.001）、CE-CT（分别为77.77%，p = 0.135；72.22%，p = 0.007）和CE-MRI（分别为63.64%，p = 0.135；43.75%，p < 0.001）。Ex4 PET/CT的观察者间一致性高于TATE PET/CT和FDG PET/CT（Cohen κ值分别为0.839、0.707和0.784）。Ex4和TATE PET/CT的SUV和TBR显著高于FDG PET/CT（p < 0.01）。观察到肿瘤Ki-67与TATE PET/CT的SUV呈负相关（r = -0.637，p < 0.001）。三种分子成像方法的SUV和TBR与最大肿瘤直径呈正相关（p < 0.05），FDG PET/CT的TBR除外。三种示踪剂的半定量值与最低血糖水平、相应胰岛素及C肽水平均无相关性。TATE PET/CT的TBR与C肽呈正相关（r = 0.393；p = 0.043）。
与良性胰岛素瘤的常规成像方式相比，Ex4 PET/CT在定位方面表现出更优越的特性。Ex4 PET/CT的成像质量和可解读性优于FDG PET/CT和TATE PET/CT。联合Ex4和TATE PET/CT可对胰岛素瘤进行全面评估/定位。
该试验于2024年11月14日和2024年12月5日在ClinicalTrial.gov上进行回顾性注册（NCT06690957和NCT06725693）。
