Design of a New ^99mTc-radiolabeled Cyclo-peptide as Promising Molecular Imaging Agent of CXCR₄ Receptor: Molecular Docking, Synthesis, Radiolabeling, and Biological Evaluation

aims: Synthesis and biological evaluation of a new CXCR4 radiolabeled antagonist for imaging of malignant tumors using SPECT imaging technique background: C-X-C Chemokine receptor type 4 (CXCR4) is often overexpressed or overactivated in different types and stages of cancer disease and therefore is considered a promising target for imaging and early detection of primary tumors and metastasis. objective: In the present research, a new cyclo-peptide radiolabelled with 99mTc, 99mTc-Cyclo [D-Phe-D-Tyr-Lys (HYNIC)-D-Arg-2-Nal-Gly- Lys(iPr)], was designed based on the parental LY251029 peptide, as a potential in vivo imaging agent of CXCR4-expressing tumors. method: High stability (95%, n=3) in human serum and favorable affinity (Kd = 28.70 ± 13.56 nM and Bmax = 1.896 ± 0.123 fmol/mg protein) in the B16-F10 cell line, resulted. Biodistribution evaluation findings and planar image interpretation of mice both showed high affinity and selectivity of the radiotracer to the CXCR4 receptors. result: RTLC and HPLC analysis of radiolabeled peptide indicated more than 95% (n=3) radiochemical purity. Incubated 99mTc-HYNIC-peptide in human serum for 24 hr at 37 °C showed high stability more than 95% (n=3). The biodistribution study showed 1.84 ± 0.13 %ID and 3.49 ± 0.27 %ID in tumor tissue at 30 min post-injection with and without plerixafor as a receptor antagonist, respectively which shows high affinity and selectivity of the radioligand for the CXCR4 receptors. conclusion: Therefore, the findings indicate this designed radioligand could be used as a potential SPECT imaging agent in highly proliferated CXCR4 receptors tumors. other: .