Dae-Weung Kim1,2, Woo Hyoung Kim2, Myoung Hyoun Kim1, Chang Guhn Kim3. 1. Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, 344-2 Shinyong-Dong, Iksan, Jeollabuk-do, 570-711, Republic of Korea. 2. Research Unit of Molecular Imaging Agent (RUMIA), Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Republic of Korea. 3. Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, 344-2 Shinyong-Dong, Iksan, Jeollabuk-do, 570-711, Republic of Korea. akaxan@naver.com.
Abstract
OBJECTIVE: Arginine-arginine-leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model. METHODS: The hexapeptide, glutamic acid-cysteine-glycine (ECG)-RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99m ECG-RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammation mouse model. A biodistribution study was performed to calculate %ID/g. RESULTS: A high yield of Tc-99m ECG-RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99m ECG-RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99m ECG-RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99m ECG-RRL accumulated minimally in inflammatory lesions. CONCLUSIONS: We successfully developed Tc-99m ECG-RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99m ECG-RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99m ECG-RRL effectively distinguished between cancerous tissue and inflammatory lesions.
OBJECTIVE:Arginine-arginine-leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model. METHODS: The hexapeptide, glutamic acid-cysteine-glycine (ECG)-RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99mECG-RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammationmouse model. A biodistribution study was performed to calculate %ID/g. RESULTS: A high yield of Tc-99mECG-RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99mECG-RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99mECG-RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99mECG-RRL accumulated minimally in inflammatory lesions. CONCLUSIONS: We successfully developed Tc-99mECG-RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99mECG-RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99mECG-RRL effectively distinguished between cancerous tissue and inflammatory lesions.