The erythropoietin-producing hepatoma A2 receptor (EphA2) is a tyrosine kinase, which is overexpressed in tumors while having lower expression in normal tissues, making it an excellent target for tumor diagnosis and treatment. Peptide radiotracers offer unique advantages in tumor diagnosis and therapy and have been approved for clinical use. In this study, a high-affinity EPHA2-targeted radiotracer, ^99mTc-HYNIC-PEG4-EPH-3, was developed and designed based on linear peptides. ^99mTc-HYNIC-PEG4-EPH-3 exhibited superior water solubility and stability. And ^99mTc-HYNIC-PEG4-EPH-3 could specifically target EphA2-expressing tumors, particularly with a tumor-to-non-target (T/NT) ratio >4.7 excluding kidneys. As a result of excellent biodistribution and tumor targeting capability of ^99mTc-HYNIC-PEG4-EPH-3, it might be a promising candidate drug for clinical diagnosis of EphA2-overexpressing tumors.

促红细胞生成素肝癌A2受体（EphA2）是一种酪氨酸激酶，在肿瘤中过度表达，而在正常组织中表达较低，使其成为肿瘤诊断和治疗的绝佳靶点。肽类放射性示踪剂在肿瘤诊断和治疗方面具有独特的优势，已被批准用于临床。本研究基于线性肽开发设计了一种高亲和力的EPHA2靶向放射性示踪剂^99m Tc-HYNIC-PEG4-EPH-3。 ^99m Tc-HYNIC-PEG4-EPH-3 表现出优异的水溶性和稳定性。 ^99m Tc-HYNIC-PEG4-EPH-3 可以特异性靶向表达 EphA2 的肿瘤，特别是肿瘤与非靶点 (T/NT) 的比率为 >4.​​7（不包括肾脏）。由于^99m Tc-HYNIC-PEG4-EPH-3具有优异的生物分布和肿瘤靶向能力，它可能成为临床诊断EphA2过表达肿瘤的有前途的候选药物。