title: Synthesis and evaluation of novel Tc-99m labeled NGR-containing hexapeptides as tumor imaging agents.
abstract: Asparagine-glycine-arginine (NGR)-containing peptides targeting aminopeptidase N (APN)/CD13 can be an excellent candidate for targeting ligands in molecular tumor imaging. In this study, we developed two NGR-containing hexapeptides, and evaluated the diagnostic performance of Tc-99m labeled hexapeptides as molecular imaging agents in an HT-1080 fibrosarcoma-bearing murine model. Peptides were synthesized using Fmoc solid-phase peptide synthesis. Radiochemical purity of Tc-99m was evaluated using instant thin-layer chromatography. The uptake of two NGR-containing hexapeptides within HT-1080 cells was evaluated in vitro. In HT-1080 fibrosarcoma tumor-bearing mice, gamma images were acquired. A biodistribution study was performed to calculate percentage of the injected dose per gram of tissue (%ID/g). Two hexapeptides, glutamic acid-cysteine-glycine (ECG)-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complexes Tc-99m hexapeptides were prepared in high yield. The uptake of Tc-99m ECG-NGR within the tumor cells had been assured by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-NGR was accumulated substantially in the subcutaneously engrafted tumor. However, Tc-99m NGR-ECG was accumulated minimally in the tumor. Two NGR-containing hexapeptides, ECG-NGR and NGR-ECG were developed as molecular imaging agents to target APN/CD13 in HT-1080 fibrosarcoma. Tc-99m ECG-NGR showed a significant uptake in the tumor, and it is a good candidate for tumor imaging.
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, Iksan, Jeollabuk-do, South Korea; Research Unit of Molecular Imaging Agent (RUMIA), Wonkwang University School of Medicine, Iksan, Jeollabuk-do, South Korea.
authors.forename: Dae-Weung
authors.initials: DW
authors.lastname: Kim
authors.forename: Woo Hyoung
authors.initials: WH
authors.lastname: Kim
authors.forename: Myoung Hyoun
authors.initials: MH
authors.lastname: Kim
authors.forename: Chang Guhn
authors.initials: CG
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005354:Fibrosarcoma / Q000000981:diagnostic imaging*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013667:Technetium / Q000737:chemistry*
chemical_list: C526428:NGR peptide; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D013667:Technetium
keywords: CD13; NGR; Tc-99 m; aminopeptidase N; asparagine-glycine-arginine; radiopharmaceutical