Human epidermal growth factor receptor-2 (HER2)-enriched breast cancer is characterized by strong invasiveness, high recurrence rate, and poor prognosis. HER2-specific imaging can help screening right patients for appropriate HER2-targeted therapies. Previously, we have developed a ^99mTc-labeled HER2-targeted H6 peptide for SPECT imaging of breast cancer. However, the poor metabolic stability and high gallbladder uptake hamper its clinical application. In this study, a retro-inverso D-peptide of H6 (RDH6) was designed to increase the metabolic stability. PEGylation was used to improve its water solubility and in vivo pharmacokinetics. The results showed that the D-amino acids in ^99mTc-PEG₄-RDH6 brought better metabolic stability than ^99mTc-PEG₄-H6, thus achieving higher tumor uptake. As the length of the PEG chain increases, the hydrophilicity of the probes gradually increased, which may also be the main cause for the decreased liver uptake. Compared with radiotracers modified by PEG₄ and PEG₁₂, ^99mTc-PEG₂₄-RDH6 had a comparable tumor uptake and the lowest liver radioactivity. The SPECT imaging demonstrated that ^99mTc-PEG₂₄-RDH6 could specifically distinguish HER2-positive tumors from HER2-negative tumors with better imaging contrast, which thus has the potential for clinical screening of HER2-positive breast patients.

中文翻译：

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发展PEG化的反向D肽作为乳腺癌检测的新型HER2靶向SPECT成像探针。

富含人类表皮生长因子受体2（HER2）的乳腺癌的特点是侵袭性强，复发率高，预后差。HER2特异性成像可以帮助筛查合适的患者以进行HER2靶向治疗。以前，我们已经开发了^99m Tc标记的HER2靶向H6肽用于乳腺癌的SPECT成像。然而，不良的代谢稳定性和高的胆囊摄取阻碍了其临床应用。在这项研究中，H6的逆反D肽（RDH6）被设计为增加代谢稳定性。聚乙二醇化用于改善其水溶性和体内药代动力学。结果表明，^99m Tc-PEG ₄ -RDH6中的D-氨基酸比^99m具有更好的代谢稳定性。Tc-PEG ₄ -H6，从而实现更高的肿瘤吸收。随着PEG链长度的增加，探针的亲水性逐渐增加，这也可能是肝脏摄取减少的主要原因。与由PEG ₄和PEG ₁₂修饰的放射性示踪剂相比，^99m Tc-PEG ₂₄ -RDH6具有相当的肿瘤吸收和最低的肝放射性。SPECT成像显示^99m Tc-PEG ₂₄ -RDH6可以特异性地将HER2阳性肿瘤与HER2阴性肿瘤区分开，具有更好的成像对比度，因此具有临床筛查HER2阳性乳腺癌患者的潜力。