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 Bmax 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.(c) 2022 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Automated summary

A novel peptide, SD01, was designed and tested for its potential in the diagnosis of TNBC. Compared to another peptide YSA, SD01 showed higher affinity, better imaging, and higher tumor accumulation, making it a promising targeting agent for EphA2.