合成及评价 [F]FP-Lys-GE11 作为一种新型表皮生长因子受体（EGFR）放射性肽探针。

Synthesis and evaluation of [F]FP-Lys-GE11 as a new radiolabeled peptide probe for epidermal growth factor receptor (EGFR) imaging.

机构信息

Medical Imaging Profession, Nanfang Hospital, Southern Medical University, Guangdong 510515, China.

Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangdong 510515, China.

出版信息

Nucl Med Biol. 2020 Nov-Dec;90-91:84-92. doi: 10.1016/j.nucmedbio.2020.10.004. Epub 2020 Oct 29.

DOI:10.1016/j.nucmedbio.2020.10.004

PMID:33189948

Abstract

INTRODUCTION

The epidermal growth factor receptor (EGFR) has emerged as an attractive target in the treatment of various cancers. Radiolabeled small molecules, antibodies, and peptides that specifically target EGFR are promising probes for tumor imaging to guide personalized treatment with EGFR-targeted drugs. This study aimed to radiolabel GE11 (an EGFR-specific targeting peptide) with 18-fluorine to develop a new EGFR-targeting positron emission tomography (PET) probe, [F]FP-Lys-GE11, for imaging tumors overexpressing EGFR.

METHODS

[F]FP-Lys-GE11 was produced by radiolabeling a GE11 peptide with the prosthetic group 4-nitrophenyl-2-[F]fluoropropionate ([F]NFP). Stability in PBS and mice serum, affinity for A431 cell line, U87 and PC-3 cells uptake and blocking studies, and biodistribution of [F]FP-Lys-GE11 were determined. 2 h dynamic and static PET scans of probe for tumor-bearing mice normal and inhibition uptake were performed.

RESULTS

[F]FP-Lys-GE11 was stable in PBS and mice serum. The Kd and Bmax values of probe for A431 were 42.43 ± 3.75 nM and 3383 ± 81.73 CPM, respectively. In cell uptake and blocking experiments, a significant reduction in radioactivity accumulation (over 4-fold) was observed by blocking U87 and PC-3 cells with unlabeled peptide. PET imaging of U87 and PC-3 tumor-bearing mice revealed clear tumor imaging (tumor radioactivity accumulation was 3.48 ± 0.44 and 3.68 ± 0.76%ID/g respectively, tumor-to-muscle ratio was 3.45 ± 0.43 and 3.64 ± 0.76 respectively). Blocking imaging revealed that the U87 tumor uptake was significantly inhibited (2.21 ± 0.41%ID/g). The biodistribution and dynamic PET imaging showed that [F]FP-Lys-GE11 was mainly excreted by the kidneys and the rest was excreted through the bile and intestines.

CONCLUSION

The current results showed that [F]FP-Lys-GE11was a good radiolabeled peptide probe for EGFR overexpression tumor's imaging.

摘要

简介

表皮生长因子受体（EGFR）已成为治疗各种癌症的有吸引力的靶点。专门针对 EGFR 的放射性标记小分子、抗体和肽是肿瘤成像的有前途的探针，可指导使用 EGFR 靶向药物进行个性化治疗。本研究旨在用 18-氟标记 GE11（一种 EGFR 特异性靶向肽），开发一种新的 EGFR 靶向正电子发射断层扫描（PET）探针[F]FP-Lys-GE11，用于成像过表达 EGFR 的肿瘤。

方法

通过用 4-硝基苯基-2-[F]氟丙酸酯（[F]NFP）标记 GE11 肽来制备[F]FP-Lys-GE11。在 PBS 和小鼠血清中的稳定性、对 A431 细胞系的亲和力、U87 和 PC-3 细胞的摄取和阻断研究以及[F]FP-Lys-GE11 的生物分布均进行了测定。对荷瘤小鼠进行了 2 h 动态和静态 PET 扫描，以观察探针的摄取和抑制情况。

结果

[F]FP-Lys-GE11 在 PBS 和小鼠血清中稳定。探针对 A431 的 Kd 和 Bmax 值分别为 42.43±3.75 nM 和 3383±81.73 CPM。在细胞摄取和阻断实验中，用未标记的肽阻断 U87 和 PC-3 细胞可观察到放射性摄取的显著减少（超过 4 倍）。对 U87 和 PC-3 荷瘤小鼠的 PET 成像显示出清晰的肿瘤成像（肿瘤放射性摄取分别为 3.48±0.44 和 3.68±0.76%ID/g，肿瘤与肌肉的比值分别为 3.45±0.43 和 3.64±0.76）。阻断成像显示 U87 肿瘤摄取明显受到抑制（2.21±0.41%ID/g）。生物分布和动态 PET 成像表明，[F]FP-Lys-GE11 主要通过肾脏排泄，其余通过胆汁和肠道排泄。