Research Progress of Radiolabeled Asn-Gly-Arg (NGR) Peptides for Imaging and Therapy

Abstract

Asn-Gly-Arg (NGR) motifs have vasculature-homing properties via interactions with the aminopeptidase N (CD13) expressed on tumor neovasculature. Numerous NGR peptides with different molecular scaffolds have been exploited for targeted delivery of different compounds for imaging and therapy. When conjugated with NGR, complexes recognize the CD13 receptor expressed on the tumor vasculature, which improves the specificity to tumor and avoids systematic toxic reactions. Both preclinical and clinical studies performed with these products suggest that NGR-mediated vascular targeting is an effective strategy for delivering bioactive amounts of cytokines to tumor endothelial cells. For molecular imaging, radiolabeled peptides have been the most successful approach and have been translated into clinic. This review describes current data on radiolabeled tumor vasculature-homing NGR peptides for imaging and therapy.

Keywords: NGR; imaging; radiolabeled; therapy; tumor.

Figure 1.

Structure of common NGR peptides.

Figure 2.

Representative micro positron emission tomography images of mice bearing HT-1080 or HT-29 tumors. Right front flank images shown 4 hours after intravenous (IV) administration of 64Cu-DOTA-NGR1 or 64Cu-DOTA-NGR2. The blocking study was performed by IV injection of 64Cu-DOTA-NGR1 or 64Cu-DOTA-NGR2 with coinjection of NGR peptide [c(CNGRC)] in HT-1080 tumor xenografts. It suggested a nearly 2-fold higher CD13 avidity of 64Cu-DOTA-NGR2 than the corresponding monomeric 64Cu-DOTA-NGR1 in HT-1080 cells. Adapted with permission from Kai Chen et al.⁴⁴ Copyright (2019) America Chemical Society.

Figure 3.

Representative image of mice bearing HT-1080 or HT-29 tumors after intravenous administration of 68Ga-NOTA-G3-NGR2 or 68Ga-NOTA-G3-RGD2 at 1 hour postinjection, and the coinjection of nonlabeled NOTA-G3-NGR2 or NOTA-G3-RGD2 as blocking agents. Tumors are indicated using circles. There is no significant difference between the 2 probes in terms of tumor uptake based on micro positron emission tomography imaging. Adapted with permission from Yahui Shao et al.⁴⁶ Copyright (2019) America Chemical Society.