Synthesis and Evaluation of 18F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging
Synthesis and Evaluation of 18F-Labeled Peptide for Gonadotropin-Releasing Hormone Receptor Imaging
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用于促性腺激素释放激素受体成像的 F-18 标记肽的合成和评价
DOI：
10.1155/2019/5635269
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Hu, Kongzhen
中科院分区：
文献类型：
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作者：
Huang, Shun;Li, Hongsheng;Hu, Kongzhen
促性腺激素释放激素（GnRH）受体在大多数人类生殖系统肿瘤中过表达。本研究的目的是开发一种用于肿瘤GnRH受体显像的F-18标记肽。本研究设计并合成了GnRH（pGlu（1）-His（2）-Trp（3）-Ser（4）-Tyr（5）-Gly（6）-Leu（7）-Arg（8）-Pro（9）-Gly（10）-NH 2）肽类似物FP-d-Lys（6）-GnRH（FP=2-氟丙酰基）和NOTA-P-d-Lys（6）-GnRH（P=乙二醇）。FP-d-Lys（6）-GnRH和NOTA-P-d-Lys（6）-GnRH的IC 50值分别为2.0 nM和56.2 nM。将4-硝基苯基-2-[F-18]氟丙酸酯与d-Lys（6）-GnRH的d-赖氨酸侧链的ε-氨基偶联，得到新的示踪剂[F-18]FP-d-Lys（6）-GnRH，衰变校正产率为8 ± 3%，比活度为20- 100 GBq/μ mol（n=6）。[F-18]FP-d-Lys（6）-GnRH在GnRH受体阳性PC-3细胞和GnRH受体阴性CHO-K1细胞中的细胞摄取研究表明受体特异性蓄积。在携带PC-3异种移植瘤的裸鼠中的生物分布和PET研究表明，[F-18]FP-d-Lys（6）-GnRH定位于肿瘤中，其摄取高于周围肌肉和心脏组织。此外，在示踪剂注射后1小时，测定了[F-18]FP-d-Lys（6）-GnRH在小鼠血液和PC-3肿瘤匀浆中的代谢稳定性。结果表明，[F-18]FP-d-Lys（6）-GnRH可用于肿瘤GnRH受体显像。
The gonadotropin-releasing hormone (GnRH) receptor is overexpressed in the majority of tumors of the human reproductive system. The purpose of this study was to develop an F-18-labeled peptide for tumor GnRH receptor imaging. In this study, the GnRH (pGlu(1)-His(2)-Trp(3)-Ser(4)-Tyr(5)-Gly(6)-Leu(7)-Arg(8)-Pro(9)-Gly(10)-NH2) peptide analogues FP-d-Lys(6)-GnRH (FP=2-fluoropropanoyl) and NOTA-P-d-Lys(6)-GnRH (P=ethylene glycol) were designed and synthesized. The IC50 values of FP-d-Lys(6)-GnRH and NOTA-P-d-Lys(6)-GnRH were 2.0nM and 56.2nM, respectively. 4-Nitrophenyl-2-[F-18]fluoropropionate was conjugated to the epsilon-amino group of the d-lysine side chain of d-Lys(6)-GnRH to yield the new tracer [F-18]FP-d-Lys(6)-GnRH with a decay-corrected yield of 8 +/- 3% and a specific activity of 20-100GBq/mu mol (n=6). Cell uptake studies of [F-18]FP-d-Lys(6)-GnRH in GnRH receptor-positive PC-3cells and GnRH receptor-negative CHO-K1 cells indicated receptor-specific accumulation. Biodistribution and PET studies in nude mice bearing PC-3 xenografted tumors showed that [F-18]FP-d-Lys(6)-GnRH was localized in tumors with a higher uptake than in surrounding muscle and heart tissues. Furthermore, the metabolic stability of [F-18]FP-d-Lys(6)-GnRH was determined in mouse blood and PC-3 tumor homogenates at 1h after tracer injection. The presented results indicated a potential of the novel tracer [F-18]FP-d-Lys(6)-GnRH for tumor GnRH receptor imaging.