Preliminary evaluation of [18F]AIF-NOTA-MAL-Cys39-exendin-4 in insulinoma with PET
Preliminary evaluation of [18F]AIF-NOTA-MAL-Cys39-exendin-4 in insulinoma with PET
复制标题
PET 初步评价 [F-18]AIF-NOTA-MAL-Cys(39)-exendin-4 在胰岛素瘤中的作用
DOI：
10.3109/1061186x.2015.1020808
复制
发表时间：
2015-10-21
影响因子：
4.5
通讯作者：
Yang, Min
中科院分区：
文献类型：
--
作者：
Xu, Qing;Zhu, Chen;Yang, Min
背景：胰高血糖素样肽-1受体（GLP-1 R）在胰岛素瘤中的高表达为肿瘤显像提供了潜在的药物靶点。Exendin-4是一种与GLP-1 R特异性结合的激动剂，其类似物广泛应用于受体显像研究。目的：设计并制备一种新型GLP-1 R显像剂[F-18]AlF-NOTA-MAL-Cys（39）-exendin-4，用于胰岛素瘤显像。将Cys（39）-exendin-4与NOTA-MAL偶联，然后用[F-18]AlF复合物放射性标记化合物，得到[F-18]AlF-NOTA-MAL-Cys（39）-exendin-4。结果：[F-18]AlF-NOTA-MAL-Cys（39）-exendin-4的产率为17.53.2%（非衰变校正），放化纯度> 95%。用Cys（39）-毒蜥外泌肽-4置换[F-18]AlF-NOTA-MAL-Cys（39）-毒蜥外泌肽-4的IC 50值为13.52 +/-1.36 nM。PET图像显示了良好的肿瘤可视化，具有高摄取（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，肿瘤与肌肉、胰腺和肝脏的比值分别为63.25、3.85和7.29。结论：[F-18]AlF-NOTA-MAL-Cys（39）-exendin-4具有良好的胰岛素瘤显像特性，可用于临床研究。
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, [F-18]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 [F-18]AlF complex to obtained [F-18]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: [F-18]AlF-NOTA-MAL-Cys(39)-exendin-4 can be efficiently produced with a yield of 17.53.2% (non-decay corrected) and radiochemical purity of >95%. The IC50 value of displacement [F-18]AlF-NOTA-MAL-Cys(39)-exendin-4 with Cys(39)-exendin-4 was 13.52 +/- 1.36nM. PET images showed excellent tumor visualization with high uptake (9.15 +/- 1.6%ID/g at 30min and 7.74 +/- 0.87%ID/g at 60min). The tumor to muscle, pancreas and liver ratios were 63.25, 3.85 and 7.29 at 60min 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: [F-18]AlF-NOTA-MAL-Cys(39)-exendin-4 shows favorable characteristics for insulinoma imaging and may be translated to clinical studies.