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(v) β(3) . 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(v) β(3) -binding affinity with cRGDyk. The results of the biodistribution of (125) I-cMBP-click-cRGDyk at 4 h 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 (125) I-cMBP-GGG-SC, respectively. U87MG
tumor xenografts could be visualized by single photon emission computed tomography (SPECT)/CT using (125) I-cMBP-click-cRGDyk and also image contrast and overall quality were improved compared to (125) I-cMBP-GGG-SC. As the results of in vivo inhibition using free cRGDyk or cMBP-GGG-SC indicated, the tumoral uptake of (125) I-cMBP-click-cRGDyk decreased. This finding means that (125) I-cMBP-click-cRGDyk was specifically uptaken by
integrin α(v) β(3) and the c-Met receptor. Although imaging quality was improved, additional experiments are needed to acquire significant image-quality improvement.