Use of Labelled tLyP-1 as a Novel Ligand Targeting the NRP Receptor to Image Glioma.
Use of Labelled tLyP-1 as a Novel Ligand Targeting the NRP Receptor to Image Glioma.
复制标题
使用标记的 tLyP-1 作为靶向 NRP 受体的新型配体对胶质瘤进行成像
DOI：
10.1371/journal.pone.0137676
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Li HS
中科院分区：
文献类型：
--
作者：
Wu HB;Wang Z;Wang QS;Han YJ;Wang M;Zhou WL;Li HS
神经纤毛蛋白（NRP）受体在神经胶质瘤组织中过表达，因此可能是一个潜在的成像标记物的靶点。我们研究了标记的tLyP-1（一种NRP靶向肽）是否可用作开发神经胶质瘤成像试剂的靶向配体。方法用5-羧基荧光素（FAM）或18F-氟化物标记tLyP-1肽（CGNKRTR）。对照肽（MAQKTSH）也用FAM标记。测定FAM-tLyP-1和U87 MG细胞之间的体外结合以及FAM-tLyP-1在U87 MG胶质母细胞瘤异种移植模型（裸鼠）中的体内生物分布。还通过microPET/CT测定了18F-tLyP-1的体内生物分布。结果在体外，FAM-tLyP-1在极低浓度（1μM）下即被U87 MG细胞摄取。在体内，FAM-tLyP-1积累在胶质瘤（U87 MG）肿瘤，但摄取是最小的正常脑组织给药后1小时。FAM-tLyP-1在肿瘤组织中的分布与NRP 1的表达一致。在施用后1小时，用FAM-tLyP-1处理的小鼠中的肿瘤/脑荧光强度比显著高于对照FAM标记肽（3.44 ± 0.83对1.32 ± 0.15; t = 5.547，P = 0.001）。神经胶质瘤肿瘤中FAM-tLyP-1的摄取可以通过施用过量的非缀合tLyP-1肽来阻断。用18F标记[Lys 4] tLyP-1以合成PET（18F-tLyP-1）。MicroPET/CT成像显示肿瘤清晰可见，60 min（2.69 ± 0.52）和120 min（3.11±0.25）肿瘤/脑放射性标记比值较高。结论tLyP-1可作为一种新型的胶质瘤荧光或放射性示踪剂。
Background Neuropilin (NRP) receptors are overexpressed in glioma tumor tissue, and therefore may be a potential target for imaging markers. We investigated whether labelled tLyP-1, an NRP targeting peptide, could be used as the targeting ligand for developing reagents for imaging glioma tumors. Methods The tLyP-1 peptide (CGNKRTR) was labeled with 5-carboxyfluorescein (FAM) or 18F-fluoride. A control peptide (MAQKTSH) was also labeled with FAM. The in vitro binding between FAM-tLyP-1 and U87MG cells and in vivo biodistribution of FAM-tLyP-1 in a U87MG glioblastoma xenograft model (nude mouse) were determined. The in vivo biodistribution of 18F-tLyP-1 was also determined by microPET/CT. Results In vitro, FAM-tLyP-1 was strongly taken up by U87MG cells at very low concentrations (1μM). In vivo, FAM-tLyP-1 accumulated in glioma (U87MG) tumors, but uptake was minimal in the normal brain tissue 1 h after administration. The distribution of FAM-tLyP-1 in the tumor tissue was consistent with expression of NRP1. The tumor/brain fluorescence intensity ratio in mice treated with FAM-tLyP-1 was significantly higher than the control FAM-labeled peptide 1 h after administration (3.44 ± 0.83 vs. 1.32 ± 0.15; t = 5.547, P = 0.001). Uptake of FAM-tLyP-1 in glioma tumors could be blocked by administering an excess of non-conjugated tLyP-1 peptide. [Lys4] tLyP-1 was labeled with 18F to synthesis a PET (18F-tLyP-1). MicroPET/CT imaging showed the tumor was visualized clearly with a high tumor/brain radiolabel ratio at 60 min (2.69 ± 0.52) and 120 min (3.11±0.25). Conclusion Taken together, our results suggest that tLyP-1 could be developed as a novel fluorescent or radio labelled tracer for imaging glioma.