Liu Huanhuan, Ma Guangyu, Wen Hui, Xu Xiaodan, Wu Shina, Wang Yuan, Pan Yue, Zhang Cong, Zhang Jingfeng, Liu Yachao, Dong Yanliang, Dong Zhouhuan, Zhang Xiaojun, Wang Ruimin, Zhang Jinming
Department of Nuclear Medicine, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Haidian District, Beijing, 100853, China.
Medical School of Chinese PLA, Beijing, 100853, China.
Eur J Nucl Med Mol Imaging. 2025 Sep 12. doi: 10.1007/s00259-025-07532-4.
A prospective comparison was conducted between [¹⁸F]AlF-NOTA-TATE and the routinely used clinical imaging agent [⁶⁸Ga]Ga-DOTA-TATE in patients with neuroendocrine tumors (NETs) to evaluate diagnostic performance, pharmacokinetic characteristics, and safety. Additionally, the clinical potential of [¹⁸F]AlF-NOTA-TATE as an alternative imaging agent was explored.
[¹⁸F]AlF-NOTA-TATE was synthesized automatically using a self-developed direct purification technology based on column chromatography, with strict adherence to quality control standards. A clinical comparative study enrolled 20 patients with suspected or confirmed neuroendocrine tumors (NETs) (median age: 52 years). All patients underwent PET/CT imaging with both [¹⁸F]AlF-NOTA-TATE (7.8 ± 1.8 mCi) and [⁶⁸Ga]Ga-DOTA-TATE (3.9 ± 0.6 mCi) within a 3-day interval. Image analysis included evaluation of parameters such as lesion detection rate, maximum standardized uptake value (SUVmax), and tumor-to-background ratio (TBR). In parallel, radiation dosimetry and biodistribution characteristics were also assessed.
Among the 20 patients, 13 were diagnosed with NETs, 4 exhibited negative imaging findings, and 3 had non-NET lesions. Biodistribution analysis revealed that [¹⁸F]AlF-NOTA-TATE showed higher physiological uptake in normal organs such as the pituitary gland and spleen compared to [⁶⁸Ga]Ga-DOTA-TATE, but lower uptake in the brain and blood pool. The overall lesion detection rates of [¹⁸F]AlF-NOTA-TATE and [Ga]Ga-DOTA-TATE in pancreas, liver, lymph nodes and bone metastases were consistent; however, [¹⁸F]AlF-NOTA-TATE demonstrated significantly higher uptake in liver metastases (SUVmax: 63.9 ± 24.9 vs. 37.2 ± 6.2, P = 0.009), lymph node metastases (median SUVmax: 33.8 vs. 22.4, P = 0.021), and bone metastases (SUVmax: 112.9 ± 20.7 vs. 66.1 ± 6.7, P < 0.001). In terms of tumor-to-background ratio (TBR), [¹⁸F]AlF-NOTA-TATE also outperformed [⁶⁸Ga]Ga-DOTA-TATE for liver lesions (77.8 ± 32.4 vs. 57.3 ± 17.6, P = 0.040) and bone metastases (135.2 ± 28.6 vs. 89.3 ± 18.9, P = 0.001). Dosimetry analysis indicated an effective dose of 0.021 ± 0.007 mSv/MBq, with the spleen receiving the highest absorbed dose (0.109 ± 0.059 mGy/MBq), and confirmed good safety.
[¹⁸F]AlF-NOTA-TATE demonstrated a comparable lesion detection rate to [⁶⁸Ga]Ga-DOTA-TATE for the diagnosis of neuroendocrine tumors (NETs), while exhibiting higher tumor uptake and superior tumor-to-background ratios (TBR). These results suggest that [¹⁸F]AlF-NOTA-TATE may serve as a promising alternative for the diagnosis of NETs.
Chinese Clinical Trial Registry (ChiCTR2300072266), registered on 8 June 2023.
对神经内分泌肿瘤（NETs）患者进行了前瞻性比较，比较了[¹⁸F]AlF-NOTA-TATE与常规使用的临床显像剂[⁶⁸Ga]Ga-DOTA-TATE，以评估诊断性能、药代动力学特征和安全性。此外，还探索了[¹⁸F]AlF-NOTA-TATE作为替代显像剂的临床潜力。
采用基于柱色谱的自行研发的直接纯化技术自动合成[¹⁸F]AlF-NOTA-TATE，并严格遵守质量控制标准。一项临床对照研究纳入了20例疑似或确诊为神经内分泌肿瘤（NETs）的患者（中位年龄：52岁）。所有患者在3天内间隔接受了[¹⁸F]AlF-NOTA-TATE（7.8±1.8mCi）和[⁶⁸Ga]Ga-DOTA-TATE（3.9±0.6mCi）的PET/CT显像。图像分析包括评估病变检出率、最大标准化摄取值（SUVmax）和肿瘤与本底比值（TBR）等参数。同时，还评估了辐射剂量学和生物分布特征。
20例患者中，13例诊断为NETs，4例显像结果为阴性，3例为非NET病变。生物分布分析显示，与[⁶⁸Ga]Ga-DOTA-TATE相比，[¹⁸F]AlF-NOTA-TATE在垂体和脾脏等正常器官中的生理性摄取较高，但在脑和血池中的摄取较低。[¹⁸F]AlF-NOTA-TATE和[⁶⁸Ga]Ga-DOTA-TATE在胰腺、肝脏、淋巴结和骨转移灶中的总体病变检出率一致；然而，[¹⁸F]AlF-NOTA-TATE在肝转移灶中的摄取显著更高（SUVmax：63.9±24.9 vs. 37.2±6.2，P = 0.009）、淋巴结转移灶（中位SUVmax：33.8 vs. 22.4，P = 0.021）和骨转移灶（SUVmax：112.9±20.7 vs. 66.1±6.7，P < 0.001）。在肿瘤与本底比值（TBR）方面，[¹⁸F]AlF-NOTA-TATE在肝病变（77.8±32.4 vs. 57.3±17.6，P = 0.040）和骨转移灶（135.2±28.6 vs. 89.3±18.9，P = 0.001）方面也优于[⁶⁸Ga]Ga-DOTA-TATE。剂量学分析表明有效剂量为0.021±0.007mSv/MBq，脾脏接受的吸收剂量最高（0.109±0.059mGy/MBq），并证实安全性良好。
[¹⁸F]AlF-NOTA-TATE在诊断神经内分泌肿瘤（NETs）方面的病变检出率与[⁶⁸Ga]Ga-DOTA-TATE相当，同时显示出更高的肿瘤摄取和更好的肿瘤与本底比值（TBR）。这些结果表明，[¹⁸F]AlF-NOTA-TATE可能是诊断NETs的一种有前景的替代方法。
中国临床试验注册中心（ChiCTR2300072266），于2023年6月8日注册。
