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

Leila Hassanzadeh; Mostafa Erfani; Safura Jokar; Marjan Shariatpanahi

doi:10.2174/0118744710249305231017073022

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

Curr Radiopharm. 2023 Oct 25. doi: 10.2174/0118744710249305231017073022. Online ahead of print.

Authors

Leila Hassanzadeh^{1

2}, Mostafa Erfani³, Safura Jokar⁴, Marjan Shariatpanahi⁵

Affiliations

¹ Department of Nuclear Medicine, School of Medicine, Rajaie Cardiovascular, Medical & Research Center, Iran University of Medical Sciences, Tehran, Iran.
² Department of Medical Imaging Technology, Molecular Imaging, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
³ Radiation Application Research School, Nuclear Science and Technology Research Institute, (NSTRI), Tehran, Iran.
⁴ Department of Nuclear Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Department of Pharmacology and Toxicology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.

PMID: 37921191
DOI: 10.2174/0118744710249305231017073022

Abstract

Introduction: C-X-C Chemokine receptor type 4 (CXCR4) is often overexpressed or overactivated in different types and stages of cancer disease. Therefore, it is considered a promising target for imaging and early detection of primary tumors and metastasis. 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.

Methods: The radioligand was successfully prepared using the method of Fmoc solid-phase peptide synthesis and was evaluated in biological assessment. Molecular docking findings revealed high affinity (binding energy of -9.7 kcal/mol) and effective interaction of Cyclo [D-Phe- D-Tyr-Lys (HYNIC)-D-Arg-2-Nal-Gly-Lys(iPr)] in the binding pocket of CXCR4 receptor (PDB code: 3OE0) as well.

Result: The synthesized peptide and its purity were assessed by both reversed-phase high-performance liquid chromatography (RP-HPLC) and mass spectroscopy. 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.

Conclusion: Therefore, the findings indicate this designed radioligand could be used as a potential SPECT imaging agent in highly proliferated CXCR4 receptor tumors.

Keywords: AMD3100.; C-X-C chemokine; HYNIC; SPECT imaging; Technetium 99m; cancer.