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.
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Acknowledgments
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (No. 2013R1A1A2059262).
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Kim, DW., Kim, W.H., Kim, M.H. et al. Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model. Ann Nucl Med 29, 779–785 (2015). https://doi.org/10.1007/s12149-015-1002-6
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DOI: https://doi.org/10.1007/s12149-015-1002-6