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- W198885435 abstract "1529 Objectives In our previous study, c-Met binding peptides (cMBPs) has been readily radiolabeled with radioactive iodide for glioma imaging because of five histidine amino acids. However, iodinated cMBPs showed relatively unfavorable in vivo kinetics. For this reason, we tried dual peptide ligands that would be advantageous recognizing both c-Met receptor and integrin αvβ3. Methods A cMBP-click-cRGDyk heterodimer was synthesized from mini-PEG conjugated cMBP-GGG-SC and cRGDyk through a click [1+3 cycloaddition] and then labeled with I-125 via histidine in the cMBP and thyrosin in the cRGDyk. The receptor-binding characteristics and tumor-targeting efficacy of cMBP-click-cRGDyk were tested in vitro and in vivo. Results A cMBP-click-cRGDyk had comparable integrin αvβ3-binding affinity with cRGDyk and comparable c-Met receptor binding affinity with cMBP-GGG-SC. The biodistribution and SPECT/CT studies with a dedicated small-animal imaging system were performed in U87MG-bearing athymic mice. The results of biodistribution of 125I-cMBP-click-cRGDyk at 4 h showed higher tumor-to-blood, tumor-to-liver and tumor-to-muscle ratio as 10.07, 6.76 and 11.12 than 2.34, 1.99 and 5.18 of 125I-cMBP-GGG-SC, respectively. U87MG tumor xenografts could be visualized by SPECT/CT using 125I-cMBP-click-cRGDyk, image contrast and overall quality were improve than 125I-cMBP-GGG-SC. As results of in vivo inhibition using free cRGDyk or cMBP-GGG-SC, the tumoral uptake of 125I-cMBP-click-cRGDyk significantly decreased. This finding means that 125I-cMBP-click-cRGDyk was specifically uptaked by integrin αvβ3 and c-Met receptor. Conclusions Although imaging quality was more improved, additional experiments are needed to acquire significant improving pharmacokinetics" @default.
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- W198885435 date "2011-05-01" @default.
- W198885435 modified "2023-09-27" @default.
- W198885435 title "I-125 labeled c-Met binding peptide-click-cRGDyk heterodimer as potential radiopharmaceuticals for specific targeting of c-MET receptors expressed on glioma" @default.
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