[18F]AlF-NOTA-MAL-Cys39-艾塞那肽-4在胰岛素瘤中的PET初步评估。
Preliminary evaluation of [18F]AlF-NOTA-MAL-Cys39-exendin-4 in insulinoma with PET.
作者信息
Xu Qing, Zhu Chen, Xu Yuping, Pan Donghui, Liu Ping, Yang Runlin, Wang Lizhen, Chen Fei, Sun Xinchen, Luo Shineng, Yang Min
机构信息
a Department of Radiation Oncology , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China .
b Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine , Jiangsu Institute of Nuclear Medicine , Wuxi , China , and.
出版信息
J Drug Target. 2015;23(9):813-20. doi: 10.3109/1061186X.2015.1020808. Epub 2015 Mar 11.
BACKGROUND
High expression of glucagon-like peptide-1 receptor (GLP-1R) in insulinoma supplies a potential drug target for tumor imaging. Exendin-4 can specifically bind to GLP-1R as an agonist and its analogs are extensively used in receptor imaging studies.
PURPOSE
A new GLP-1R imaging agent, [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4, was designed and prepared for insulinoma imaging.
METHODS
Cys(39)-exendin-4 was conjugated with NOTA-MAL, then the compound was radiolabeled with [(18)F]AlF complex to obtained [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4. The tumor-targeting characters of the tracer were evaluated in INS-1 cells and BALB/c nude mice models.
RESULTS
[(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 can be efficiently produced with a yield of 17.5 ± 3.2% (non-decay corrected) and radiochemical purity of >95%. The IC50 value of displacement [(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 with Cys(39)-exendin-4 was 13.52 ± 1.36 nM. PET images showed excellent tumor visualization with high uptake (9.15 ± 1.6%ID/g at 30 min and 7.74 ± 0.87%ID/g at 60 min). The tumor to muscle, pancreas and liver ratios were 63.25, 3.85 and 7.29 at 60 min after injection. GLP-1R binding specificity was demonstrated by co-injection with an excess of unlabeled Cys(39)-exendin-4 and the tumor uptake was found to be reduced significantly.
CONCLUSION
[(18)F]AlF-NOTA-MAL-Cys(39)-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.
背景
胰岛素瘤中胰高血糖素样肽-1受体（GLP-1R）的高表达为肿瘤成像提供了一个潜在的药物靶点。艾塞那肽-4作为一种激动剂可特异性结合GLP-1R，其类似物广泛应用于受体成像研究。
目的
设计并制备一种新型GLP-1R成像剂[(18)F]AlF-NOTA-MAL-Cys(39)-艾塞那肽-4用于胰岛素瘤成像。
方法
将Cys(39)-艾塞那肽-4与NOTA-MAL偶联，然后用[(18)F]AlF络合物对该化合物进行放射性标记，得到[(18)F]AlF-NOTA-MAL-Cys(39)-艾塞那肽-4。在INS-1细胞和BALB/c裸鼠模型中评估该示踪剂的肿瘤靶向特性。
结果
[(18)F]AlF-NOTA-MAL-Cys(39)-艾塞那肽-4能够高效制备，产率为17.5±3.2%（未进行衰变校正），放射化学纯度>95%。用Cys(39)-艾塞那肽-4置换[(18)F]AlF-NOTA-MAL-Cys(39)-艾塞那肽-4的IC50值为13.52±1.36 nM。PET图像显示肿瘤可视化效果极佳，摄取率高（30分钟时为9.15±1.6%ID/g，60分钟时为7.74±0.87%ID/g）。注射后60分钟时，肿瘤与肌肉、胰腺和肝脏的比值分别为63.25、3.85和7.29。与过量未标记的Cys(39)-艾塞那肽-4共同注射证明了GLP-1R结合特异性，发现肿瘤摄取显著降低。
结论
[(18)F]AlF-NOTA-MAL-Cys(39)-艾塞那肽-4在胰岛素瘤成像方面显示出良好的特性，可能会转化为临床研究。
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