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• W2005490647 abstract "Epidermal growth factor receptor-2 (EGFR-2) has been implicated in the pathogenesis of breast and other carcinomas. In this report, we tested the ability of a bacteriophage selected peptide KCCYSL, radiolabeled with 64Cu, to image EGFR-2 expressing breast tumors in vivo by positron emission tomography (PET). We evaluated and compared the in vivo tissue distribution and imaging properties of 64Cu-X-(Gly-Ser-Gly)-KCCYSL peptide (X = 1,4,7,10, tetraazacyclododecane-N,N’,N’’,N’’’-tetracetic acid, [DOTA] 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane-4,11-diacetic acid [CB-TE2A], and 1,4,7-triazacyclononane-1,4,7-triacetic acid [NOTA] chelators) in a human breast cancer xenograft mouse model using dual modality PET and computed tomography (CT). The synthesized peptides DO3A-GSG-KCCYSL, CB-TE2A-GSG-KCCYSL, and NO2A-GSG-KCCYSL were purified, radiolabeled with 64Cu, and evaluated for human breast cancer cell (MDA-MB-435) binding, 50% inhibitory concentration, and serum stability. In vivo pharmacokinetic and small animal PET/CT imaging studies were performed using SCID mice bearing MDA-MB-435 xenografts. The radiolabeled peptides bound with an 50% inhibitory concentration of 42.0 ± 10.2 nM (DO3A), 31 ± 7.9 nM (CB-TE2A), and 44.2 ± 6.6 nM (NO2A) to cultured MDA-MB-435 cells. All of the radiolabeled peptides were stable in vitro. The tumor uptake of DO3A, CB-TE2A, and NO2A peptides were 0.73 ± 0.15 percent injected dose per gram (%ID/g), 0.64 ± 0.08%ID/g, and 0.52 ± 0.04%ID/g, respectively at 1 hour. Liver uptake for the 64Cu-DO3A-peptide (1.68 ± 0.42%ID/g) was more than that of the 64Cu-CB-TE2A-peptide (0.52 ± 0.02% ID/g) and 64Cu-NO2A-peptide (0.48 ± 0.05%ID/g) at 2 hours. PET/CT studies revealed successful tumor uptake of 64Cu-peptides at 2 hours postinjection. In vivo kidney retention was observed with all of the radiolabeled peptides. The optimization of bifunctional chelators improves the pharmacokinetic properties of the 64Cu-labeled GSG-KCCYSL peptide, which enables the selection of a suitable peptide homolog as a PET imaging agent for EGFR-2 expressing breast carcinomas." @default.
• W2005490647 created "2016-06-24" @default.
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• W2005490647 date "2010-12-01" @default.
• W2005490647 modified "2023-10-01" @default.
• W2005490647 title "<i>In Vitro</i>and<i>In Vivo</i>Evaluation of⁶⁴Cu-Radiolabeled KCCYSL Peptides for Targeting Epidermal Growth Factor Receptor-2 in Breast Carcinomas" @default.
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• W2005490647 doi "https://doi.org/10.1089/cbr.2010.0820" @default.
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