Development of a novel EphA2-targeting radioligand for SPECT imaging in different tumor models

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.