A Novel CXCR4-Targeted Peptide for SPECT/CT Imaging in Tumor

As the most commonly expressed chemokine receptor in tumor cells, CXCR4 is associated with the development and metastasis of a variety of tumors, which has always been an important target for tumor diagnosis and treatment. We present a series of peptides designed to target CXCR4 and determine their affinity values (Kd) for human CXCR4 proteins using surface ion resonance technology. Despite the significant variations in their affinities, our results demonstrate the feasibility of our peptide engineering strategy. Among them, YQ-X-9 (Gly-Gly-Pro-D-Tyr-Arg-D-Val-Gly-Arg-D-2Nal-Pro-NH2) had the highest affinity (Kd=530nM) compared to the positive control AMD3100 (Kd=240nM). Furthermore, YQ-X-9 was selected as the target and 99mTc was functionalized by HYNIC to form a specific targeting probe (99mTc-HYNIC-YQ-X-9). Additionally, we established a xenograft mouse model of B16 melanoma cells for in vivo SPECT/CT imaging, resulting in evident tumor uptake, excellent imaging efficacy, and high contrast. And in vivo distribution experiments confirmed that in B16 tumor-bearing mice, tumors had significant uptake, reaching 2.4% ID/g. Therefore, 99mTc-HYNIC-YQ-X-9 may serve as a promising peptide-based probe for clinical imaging of CXCR4 overexpressed tumors.’