Novel Tc-99m labeled NGR-containing 6-mer peptides for tumor imaging

1005 Objectives NGR-containing peptides targeting APN/CD13 could be the excellent candidate for targeting ligand of molecular tumor imaging [1-3]. In this study, we had developed two NGR-containing 6-mer peptides and evaluated the diagnostic performance of Tc-99m labeled 6-mer peptides as a molecular imaging agent in murine models bearing HT-1080 fibrosarcoma. Methods Peptides were synthesized using Fmoc solid phase peptide synthesis. Radiolabeling efficiency with Tc-99m was evaluated using instant thin layer chromatography. In HT-1080 fibrosarcoma cancer-bearing mice, gamma images had acquired acquired after intravenous injection of Tc-99m NGR peptides, and tumor-to-muscle uptake ratio was calculated. In cancer models, Tc-99m ECG-NGR and free NGR (15 mg/kg) were co-injected to simulate the competitive effects of free NGR. Biodistribution study had performed to calculate %ID/g. Results Two 6-mer peptides, ECG-NGR and NGR-ECG were successfully synthesized. After radiolabeling procedures with Tc-99m, the complex Tc-99m ECG-NGR and NGR-ECG were prepared in high yield. In the gamma-camera imaging of murine model, Tc-99m ECG-NGR was substantially accumulated in the subcutaneously engrafted tumor (tumor/muscle uptake ratio = 5.7 ± 0.4 at 4 h), and tumoral uptake was blocked by the co-injection of excess free NGR. However, Tc-99m NGR-ECG was minimally accumulated in the tumor (2.9 ± 0.5 at 4 h). Conclusions Two NGR-containing 6-mer peptides, ECG-NGR and NGR-ECG were developed as a molecular imaging agents to target APN/CD13 of HT-1080 fibrosarcoma. Tc-99m ECG-NGR had showed significant uptake in tumor and it was good candidate for a tumor imaging. Research Support This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2013R1A1A2059262).