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

Introduction: Excessive expression of the αvβ۳ integrin receptors is seen in rapidly multiplying endothelial cells, including cancerous growth of various tumors. αvβ۳ 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)۲ 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)۲ to A۵۴۹ lung tumor in mice. Gd-DOTA-E(cRGDfK)۲ did not show cytotoxicity at high concentrations and on different cell lines. Biodistribution studies confirm tumor uptake up to ۲۴h after the injection. The peptide-based contrast agent leaded to an improved tumor contrast enhancement at a dose of ۰.۱ mmol Gd/kg. The tumor uptake peaks were after ۳۰ min of injection. A clear picture of the tumor was seen in all images.Conclusion: Gd(ΙΙΙ)-DOTA-E(cRGDfK)۲ can be used as a peptidic MR imaging contrast agent enabling initial detection of different cancers overexpressing the αvβ۳ integrin receptors and can be a prospective candidate in clinical studies of non-small cell lung carcinoma.

Keywords:

RGD peptide , Gadolinium , MR imaging , Non-small cell lung carcinoma