Evaluation of a novel EphA2 targeting peptide for triple negative breast cancer based on radionuclide molecular imaging

A new strategy for the early diagnosis of triple-negative breast cancer (TNBC) is urgently needed however specific targets are lacking. EphA2 has been reported to be over-expressed in a variety of tumors, including TNBC, and is closely related to tumor progression. In this study, we designed a novel peptide, SD01, and tested its potential in the diagnosis of TNBC. FITC-SD01 and FITC-YSA were prepared and found to bind to the 4T1 TNBC cell line, the former showing greater affinity. ¹²⁵I-SD01 and ¹²⁵I-YSA were obtained with high radiochemical yield and radiochemical purity, and both showed a high binding affinity to 4T1 cells, with a higher B_max in ¹²⁵I-SD01. Whole-body phosphoautoradiography showed clearer imaging of tumors in the group of ¹²⁵I-SD01 than in ¹²⁵I-YSA. Biodistribution demonstrated higher tumor accumulation in the ¹²⁵I-SD01 group. In group of ¹²⁵I-SD01, the tumor to the opposite muscle tissue (T/NT) ratio was 5.998 ± 0.37, in contrast to 4.69 ± 0.18 in ¹²⁵I-YSA group. Our results indicated that ¹²⁵I-SD01 could selectively and specifically target 4T1 cells in vitro and in vivo, and showed higher binding affinity and better imaging compared to ¹²⁵I-YSA. Therefore, SD01 was deemed to be a novel peptide with more favorable properties in terms of targeting EphA2.