Department of Nuclear Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Int J Radiat Biol. 2020 Nov;96(11):1443-1451. doi: 10.1080/09553002.2020.1811419. Epub 2020 Sep 1.
This study investigated a novel SPECT agent for the noninvasive imaging of EGFR-overexpressing tumors.
The EGFR-targeting peptide GE11 was synthesized with the introduction of four amino acids (GGGC) to its C-terminal to act as a strong chelator and radiolabeled using Tc. The radiochemical yield of the Tc-peptide-GE11 were evaluated using RP-HPLC. Cellular assays of the probe were performed on two NSCLC cell lines: A549 (high expression) and H23 (low expression). Biodistribution and SPECT imaging were performed in BALB/c nude mice bearing A549 and H23 NSCLC xenografts.
The Tc-peptide-GE11 was prepared at high efficiency with radiochemical yield of 98.40 ± 1.00 % and it showed favorable stability. The cellular uptake was significantly higher in A549 than in H23 at all time points (especially at 1 h, which was 10.34 ± 0.72 and 2.04 ± 0.18, respectively). A nearly 56% reduction in probe uptake was observed after pretreatment with excess unlabeled peptides. The performance of SPECT imaging and biodistribution demonstrated higher uptake of the Tc-peptide-GE11 in A549 xenograft than in H23 xenografts.
The new SPECT tracer c-peptide-GE11 showed EGFR specificity, favorable pharmacokinetics and great potential for EGFR-targeted imaging.
本研究旨在探索一种新型 SPECT 探针，用于非侵入性成像 EGFR 过表达肿瘤。
合成了靶向 EGFR 的肽 GE11，在其 C 端引入四个氨基酸（GGGC）作为强螯合剂，并使用 Tc 进行放射性标记。使用 RP-HPLC 评估 Tc-肽-GE11 的放射化学产率。在两种 NSCLC 细胞系（A549[高表达]和 H23[低表达]）上进行了探针的细胞测定。在荷有 A549 和 H23 NSCLC 异种移植瘤的 BALB/c 裸鼠中进行了生物分布和 SPECT 成像。
Tc-肽-GE11 以高效率制备，放射化学产率为 98.40±1.00%，且表现出良好的稳定性。在所有时间点，A549 中的细胞摄取均明显高于 H23（尤其是在 1 小时时，分别为 10.34±0.72 和 2.04±0.18）。用过量未标记的肽预处理后，探针摄取减少近 56%。SPECT 成像和生物分布的性能表明，Tc-肽-GE11 在 A549 异种移植瘤中的摄取高于 H23 异种移植瘤。
新型 SPECT 示踪剂 c-肽-GE11 表现出 EGFR 特异性、良好的药代动力学特性和用于 EGFR 靶向成像的巨大潜力。
