title: Iodine 125-labeled mesenchymal-epithelial transition factor binding peptide-click-cRGDyk heterodimer for glioma imaging.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine, Research Institute of Clinical Medicine, Cyclotron Research Center, Chonbuk National University Medical School and Hospital, Jeonbuk, South Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Kim
authors.forename: Min-Hee
authors.initials: MH
authors.lastname: Jeong
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Hwan-Jeong
authors.initials: HJ
authors.lastname: Jeong
authors.forename: Seok Tae
authors.initials: ST
authors.lastname: Lim
authors.forename: Myung-Hee
authors.initials: MH
authors.lastname: Sohn
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D002352:Carrier Proteins / Q000378:metabolism*; D057930:Click Chemistry; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging*; D007457:Iodine Radioisotopes; D051379:Mice; D010456:Peptides, Cyclic / Q000378:metabolism*; D055503:Protein Multimerization; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D014057:Tomography, X-Ray Computed
chemical_list: D002352:Carrier Proteins; D007457:Iodine Radioisotopes; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; D019859:Proto-Oncogene Proteins c-met