Preparation and preclinical evaluation of a Gd(ΙΙΙ)-RGD peptide for MR molecular imaging in non-small cell lung carcinoma (NSCLC)

Document Type : Original Article


1 Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran

3 Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

4 Nuclear Medicine and Molecular Imaging Department, Imam Reza International University, Razavi Hospital, Mashhad, Iran

5 Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran


Introduction: Excessive expression of the αvβ3 integrin receptors is seen in rapidly multiplying endothelial cells, including cancerous growth of various tumors. αvβ3 integrin receptors’ specific targeting by peptides containing the RGD motif makes these short sequences a suitable nominee for diagnostic imaging and lung cancer follow-up. A high-affinity RGD-containing peptide is designed. The di-RGD peptide has a greater affinity along with tumor-selective targeting properties. Peptide labeling with gadolinium for magnetic resonance imaging was accomplished, permitting efficient cancer molecular imaging accompanied by high spatial resolution. This peptide will have better sensitivity for the early identification of tumors and is appropriate for follow-up routines.
Methods: DOTA-E(cRGDfK)2 was labeled with Gd(ΙΙΙ) effectively. The cytotoxicity to cells was measured. The biodistribution was evaluated in a mouse model for lung cancer. The very early diagnostic capacity of the Gd-RGD peptide was studied using MR molecular imaging.
Results: MR imaging shows high binding specificity of Gd(ΙΙΙ)-DOTA-E(cRGDfK)2 to A549 lung tumor in mice. Gd-DOTA-E(cRGDfK)2 did not show cytotoxicity at high concentrations and on different cell lines. Biodistribution studies confirm tumor uptake up to 24h after the injection. The peptide-based contrast agent leaded to an improved tumor contrast enhancement at a dose of 0.1 mmol Gd/kg. The tumor uptake peaks were after 30 min of injection. A clear picture of the tumor was seen in all images.
Conclusion: Gd(ΙΙΙ)-DOTA-E(cRGDfK)2 can be used as a peptidic MR imaging contrast agent enabling initial detection of different cancers overexpressing the αvβ3 integrin receptors and can be a prospective candidate in clinical studies of non-small cell lung carcinoma.


Main Subjects

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