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• W2103676890 abstract "The purpose of this study was to examine the profound effect of the ring size of the radiolabeled lactam bridge-cyclized alpha-melanocyte-stimulating hormone (alpha-MSH) peptide on its melanoma-targeting properties.A novel cyclic alpha-MSH peptide, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-CONH(2) (DOTA-Nle-CycMSH(hex)), was synthesized and radiolabeled with (111)In. The melanocortin-1 receptor-binding affinity of DOTA-Nle-CycMSH(hex) was determined in B16/F1 melanoma cells. The internalization and efflux of (111)In-DOTA-Nle-CycMSH(hex) were examined in B16/F1 cells. The melanoma-targeting properties and SPECT/CT characteristics of (111)In-DOTA-Nle-CycMSH(hex) were determined in B16/F1 melanoma-bearing C57 mice.DOTA-Nle-CycMSH(hex) displayed 1.77 nM receptor-binding affinity. (111)In-DOTA-Nle-CycMSH(hex) exhibited rapid internalization and extended retention in B16/F1 cells. The tumor uptake of (111)In-DOTA-Nle-CycMSH(hex) was 24.94% +/- 4.58% and 10.53% +/- 1.11% injected dose per gram at 0.5 and 24 h after injection, respectively. Greater than 82% of the injected radioactivity was cleared through the urinary system by 2 h after injection. The tumor-to-kidney uptake ratios reached 2.04 and 1.70 at 2 and 4 h after injection, respectively. Flank melanoma tumors were clearly visualized by SPECT/CT using (111)In-DOTA-Nle-CycMSH(hex) as an imaging probe at 2 and 24 h after injection. The radioactivity accumulation in normal organs, except for the kidneys, was low at 2, 4, and 24 h after injection.The reduction of the peptide ring size dramatically increased the melanoma uptake and decreased the renal uptake of (111)In-DOTA-Nle-CycMSH(hex), providing a new insight into the design of a novel radiolabeled lactam bridge-cyclized alpha-MSH peptide for melanoma imaging and treatment." @default.
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• W2103676890 date "2010-02-11" @default.
• W2103676890 modified "2023-10-13" @default.
• W2103676890 title "Reduction of the Ring Size of Radiolabeled Lactam Bridge–Cyclized α-MSH Peptide, Resulting in Enhanced Melanoma Uptake" @default.
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• W2103676890 doi "https://doi.org/10.2967/jnumed.109.071787" @default.
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