Facile preparation of a novel Ga-67-labeled NODAGA-conjugated lactam-cyclized alpha-MSH peptide at room temperature for melanoma targeting

在室温下简便制备新型Ga-67标记的NODAGA偶联内酰胺环化α-MSH肽,用于黑色素瘤靶向治疗

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Abstract

In this study, the melanoma targeting property of (67)Ga-NODAGA-GGNle-CycMSH(hex) {1,4,7-triazacyclononane,1-gluteric acid-4,7-acetic acid-GlyGlyNle-c[Asp-His-D-Phe-Arg-Trp-Lys]-CONH(2)} was determined on B16/F10 melanoma-bearing C57 mice to demonstrate the feasibility of NODAGA as a radiometal chelator for facile room temperature radiolabeling of NODAGA-GGNle-CycMSH(hex). The IC(50) value of NODAGA-GGNle-CycMSH(hex) was 0.87 ± 0.12 nM on B16/F10 melanoma cells. (67)Ga-NODAGA-GGNle-CycMSH(hex) was readily prepared at room temperature with greater than 98% radiolabeling yield and displayed MC1R-specific binding on B16/F10 melanoma cells. The B16/F10 melanoma uptake of (67)Ga-NODAGA-GGNle-CycMSH(hex) was 10.31 ± 0.78, 14.96 ± 1.34, 13.7 ± 3.33 and 10.4 ± 2.2% ID/g at 0.5, 2, 4 and 24 h post-injection, respectively. Approximately 85% of the injected dose was cleared out the body via urinary system at 2 h post-injection. (67)Ga-NODAGA-GGNle-CycMSH(hex) showed high tumor/blood, tumor/muscle and tumor/skin uptake ratios after 2 h post-injection. Overall, (67)Ga-NODAGA-GGNle-CycMSH(hex) could be easily prepared at room temperature and exhibited favorable melanoma targeting property, suggesting the potential use of NODAGA as a radiometal chelator for facile room temperature radiolabeling of α-MSH peptides.

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