Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model.

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.

• Authors: Dae-Weung Kim, Woo Hyoung Kim, Myoung Hyoun Kim, Chang Guhn Kim
• Journal: Annals of nuclear medicine (Ann Nucl Med) Vol. 29 Issue 9 Pg. 779-85 (Nov 2015) ISSN: 1864-6433 [Electronic] Japan
• PMID: 26179963 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oligopeptides
• Organotechnetium Compounds
• Radiopharmaceuticals
• technetium 99m Glu-Cys-Gly-Arg-Arg-Leu

Topics

• Animals
• Cell Line, Tumor
• Disease Models, Animal
• Female
• Fibrosarcoma (diagnostic imaging, metabolism, pathology)
• Gamma Cameras
• Humans
• Mice, Inbred BALB C
• Mice, Nude
• Microscopy, Confocal
• Molecular Structure
• Muscles (diagnostic imaging, metabolism)
• Neoplasm Transplantation
• Oligopeptides (chemical synthesis, chemistry, pharmacokinetics)
• Organotechnetium Compounds (chemical synthesis, chemistry, pharmacokinetics)
• Radionuclide Imaging
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)
• Whole Body Imaging