Imaging the expression of glypican-3 in hepatocellular carcinoma by PET
Imaging the expression of glypican-3 in hepatocellular carcinoma by PET
复制标题
肝细胞癌中磷脂酰肌醇蛋白聚糖3表达的PET成像
DOI：
10.1007/s00726-017-2517-z
复制
发表时间：
2018-02-01
期刊：
影响因子：
3.5
通讯作者：
Wu, Hu-Bing
中科院分区：
文献类型：
--
作者：
Wang, Zhen;Han, Yan-Jiang;Wu, Hu-Bing
glypican-3 （GPC3）受体在肝细胞癌（HCC）中过表达，是一种潜在的诊断和治疗靶点。gpc3靶向分子显像有助于鉴别诊断和指导治疗。在本研究中，我们将开发一种新的PET探针来成像GPC-3的表达。L5（序列：RLNVGGTYFLTTRQ）是GPC3靶向肽，用5-羧基荧光素（FAM）和f -18氟化物标记。通过细胞结合试验鉴定FAM-L5和F-18放射性标记肽的结合特异性。使用MicroPET/CT成像来确定一种新型PET示踪剂对高表达GPC3的HCC肿瘤的可视化潜力。体外结合实验显示，高表达GPC3的HepG2细胞对FAM-L5的摄取明显高于GPC3阴性表达的HL-7702细胞（平均荧光强度：14,094 +/- 797 vs. 2765 +/- 314事件，t = 32.363, P = 0.000）。共聚焦荧光成像发现FAM-L5聚集在GPC3受体所在的位置。一种新型PET示踪剂（F-18-AlF-NODA-MP-6-Aoc-L5）通过螯合化学标记成功。体外细胞摄取研究表明，F-18-AlF-NODA-MP-6-Aoc-L5可与HepG2肿瘤细胞结合，并在PBS和小鼠血清稳定性试验中稳定。MicroPET/CT显示HepG2肿瘤清晰可见，肿瘤/肌比为2.46 +/- 0.53。然而，由于肝脏的高生理摄取，肿瘤/肝脏比例较低（0.93 +/- 0.16）。本研究表明，FAM和f -18标记的L5肽在体外和体内均可选择性靶向GPC3高表达的HCC。F-18-AlF-NODA-MP-C6-L5具有成为GPC3靶标示踪剂的潜力，但需要进行一些化学修饰才能达到足够高的肿瘤/肝脏比例，以检测肝脏中的肿瘤。
The glypican-3 (GPC3) receptor is overexpressed in hepatocellular carcinoma (HCC) and is a potential diagnostic and therapeutic target. GPC3-targeted molecular imaging will be helpful to differentiate diagnosis and guide therapy. In the present study, we will develop a novel PET probe for imaging the expression of GPC-3. L5 (sequence: RLNVGGTYFLTTRQ), a GPC3 targeting peptide, was labeled with 5-carboxyfluorescein (FAM) and F-18-fluoride. Cell binding tests were performed to identify the binding specificity of FAM-L5 and F-18 radiolabeled peptide. MicroPET/CT imaging was used to determine the potential of a novel PET tracer for visualizing HCC tumors with a high expression of GPC3. In vitro binding tests showed that the uptake of FAM-L5 in HepG2 cells (high expression of GPC3) was significantly higher than that of HL-7702 cells (negative expression of GPC3) (mean fluorescent intensity: 14,094 +/- 797 vs. 2765 +/- 314 events, t = 32.363, P = 0.000). Confocal fluorescent imaging identified that FAM-L5 accumulated where the GPC3 receptor was located. A novel PET tracer (F-18-AlF-NODA-MP-6-Aoc-L5) was successfully labeled by chelation chemistry. In vitro cell uptake studies showed that F-18-AlF-NODA-MP-6-Aoc-L5 can bind to HepG2 tumor cells and was stable in PBS and mouse serum stability tests. MicroPET/CT showed that HepG2 tumors could be clearly visualized with a tumor/muscle ratio of 2.46 +/- 0.53. However, the tumor/liver ratio was low (0.93 +/- 0.16) due to the high physiological uptake in the liver. This study demonstrates that FAM and the F-18-labeled L5 peptide can selectively target HCC with a high expression of GPC3 in vitro and in vivo. F-18-AlF-NODA-MP-C6-L5 has the potential to be a GPC3 target tracer but requires some chemical modifications to achieve a high enough tumor/liver ratio for detection of the tumor in the liver.