Abstract

Purpose

This study investigated a novel SPECT agent for the noninvasive imaging of EGFR-overexpressing tumors.

Methods

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 ^99mTc. The radiochemical yield of the ^99mTc-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.

Results

The ^99mTc-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 ^99mTc-peptide-GE11 in A549 xenograft than in H23 xenografts.

Conclusion

The new SPECT tracer ^99mTc-peptide-GE11 showed EGFR specificity, favorable pharmacokinetics and great potential for EGFR-targeted imaging.

中文翻译：

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用于EGFR SPECT成像的新型99mTc标记的GE11肽的合成。

摘要

目的

这项研究调查了一种新型SPECT剂，用于EGFR过表达的肿瘤的非侵入性成像。

方法

EGFR靶向肽GE11通过在其C端引入四个氨基酸（GGGC）来合成，作为强螯合剂，并使用^99m Tc进行了放射性标记。使用RP-HPLC评估^99m Tc-肽-GE11的放射化学产率。探针的细胞分析是在两种NSCLC细胞系上进行的：A549（高表达）和H23（低表达）。在具有A549和H23 NSCLC异种移植物的BALB / c裸鼠中进行生物分布和SPECT成像。

结果

所述^99米锝肽GE11在与98.40±1.00％的放射化学产高效率制备，并且它显示出良好的稳定性。在所有时间点（特别是在1小时，分别为10.34±0.72和2.04±0.18），A549中的细胞摄取均显着高于H23。用过量的未标记肽进行预处理后，观察到探针吸收减少了近56％。SPECT成像和生物分布的性能表明，与H23异种移植相比，A549异种移植对^99m Tc-肽-GE11的摄取更高。

结论

新的SPECT示踪剂^99mT c-肽^-GE11具有EGFR特异性，良好的药代动力学和巨大的EGFR靶向成像潜力。