Synthesis, Radiolabeling, and Biological Evaluation of Peptide LIKKPF Functionalized with HYNIC as Apoptosis Imaging Agent

Document Type: Research article

Authors

1 Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran,

2 Research center for nuclear medicine, Tehran University of Medical Sciences, Tehran, Iran.

3 Department of Pharmaceutical Chemistry, School of Pharmacy, Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,

4 Department of Toxicology & Pharmacology, Faculty of Pharmacy, and Toxicology and poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran,

5 Department of Medicinal Chemistry, and Drug Design and Development Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran,

6 Department of Life Science Engineering, Faculty of new Sciences & Technologies, University of Tehran, Tehran, Iran,

7 Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences

Abstract

Introduction: A noninvasive method of detecting exposure of phosphatidylserine (PS) on the external surface of the plasma membrane such as nuclear imaging could assist the diagnosis and therapy of apoptosis related pathologies. The most studied imaging agent for apoptosis is Annexin V so far. Because of limitations of Annexin V other agents have been introduced such as small peptides and molecules. Radiopeptides that have affinity and bind to PS are good candidates for noninvasive imaging of apoptosis. The LIKKPF, introduced by Burtea et al, with nanomolar affinity for PS, was used as templete.
Methods: The biological properties of LIKKPF radiolabeled with Tc-99m was assessed in vitro using apoptotic Jurkat cells and in vivo using mouse model of liver apoptosis.
Results: The radiolabeled LIKKPF with 99mTc was stable in human serum at 37C for at least 2 hr. Results showed that the radiolabeled LIKKPF has less affinity to PS compare to original phage peptide, but high enough for specific binding to apoptotic cells in vitro and in vivo. Conclusion: It is concluded that the less affinity of radiolabeled LIKKPF might be attributed to hydrophobicity of peptide. The future peptides should be more hydrophobic compare to LIKKPF.

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