Iodine 125-labeled mesenchymal-epithelial transition factor binding peptide-click-cRGDyk heterodimer for glioma imaging

In our previous study, mesenchymal-epithelial transition factor (c-Met)-binding peptides (cMBP) had been readily radiolabeled with radioactive iodide for glioma imaging because of five histidine amino acids. However, iodinated cMBP showed relatively unfavorable in vivo kinetics. For this reason, we tried to design dual peptide ligands that would be advantageous in recognizing both c-Met receptor and integrin α_vβ₃. A cMBP-click-cRGDyk (cyclic Arg-Gly-Asp-Tyr-Lys) heterodimer was synthesized from mini polyethylene glycol-conjugated cMBP-3 glycine (GGG)-a single name of amino acids (SC) (Ser-Cys) and cRGDyk through a click (1+3 cycloaddition), and then labeled with iodine 125 (I-125) via histidine in the cMBP and tyrosine in the cRGDyk. The receptor-binding characteristics and tumor-targeting efficacy of cMBP-click-cRGDyk were tested in vitro and in vivo. A cMBP-click-cRGDyk had comparable integrin α_vβ₃-binding affinity with cRGDyk. The results of the biodistribution of ¹²⁵I-cMBP-click-cRGDyk at 4h showed higher tumor-to-blood, tumor-to-liver, and tumor-to-muscle ratios: 10.07, 6.76, and 11.12, compared to 2.34, 1.99, and 5.18 of ¹²⁵I-cMBP-GGG-SC, respectively. U87MG tumor xenografts could be visualized by single photon emission computed tomography (SPECT)/CT using ¹²⁵I-cMBP-click-cRGDyk and also image contrast and overall quality were improved compared to ¹²⁵I-cMBP-GGG-SC. As the results of in vivo inhibition using free cRGDyk or cMBP-GGG-SC indicated, the tumoral uptake of ¹²⁵I-cMBP-click-cRGDyk decreased. This finding means that ¹²⁵I-cMBP-click-cRGDyk was specifically uptaken by integrin α_vβ₃ and the c-Met receptor. Although imaging quality was improved, additional experiments are needed to acquire significant image-quality improvement.