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Introduction of an 8-Aminooctanoic Acid Linker Enhances Uptake of 99m Tc-Labeled Lactam Bridge–Cyclized α-MSH Peptide in Melanoma

2014; Society of Nuclear Medicine and Molecular Imaging; Volume: 55; Issue: 12 Linguagem: Inglês

10.2967/jnumed.114.145896

1535-5667

Haixun Guo, Yubin Miao,

Cell Adhesion Molecules Research

The purpose of this study was to examine the effects of amino acid, hydrocarbon, and polyethylene glycol (PEG) linkers on the melanoma targeting and imaging properties of 99m Tc-labeled lactam bridge–cyclized HYNIC-linker-Nle-CycMSH hex (hydrazinonicotinamide-linker-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH 2 ) peptides. Methods: Four novel peptides (HYNIC-GGGNle-CycMSH hex , HYNIC-GSGNle-CycMSH hex , HYNIC-PEG 2 Nle-CycMSH hex , and HYNIC-AocNle-CycMSH hex ) were designed and synthesized. The melanocortin-1 receptor binding affinities of the peptides were determined in B16/F1 melanoma cells. The biodistribution of 99m Tc(ethylenediaminediacetic acid [EDDA])-HYNIC-GGGNle-CycMSH hex , 99m Tc(EDDA)-HYNIC-GSGNle-CycMSH hex , 99m Tc(EDDA)-HYNIC-PEG 2 Nle-CycMSH hex , and 99m Tc(EDDA)-HYNIC-AocNle-CycMSH hex were determined in B16/F1 melanoma–bearing C57 mice at 2 h after injection to select a lead peptide for further evaluation. The melanoma targeting and imaging properties of 99m Tc(EDDA)-HYNIC-AocNle-CycMSH hex were further examined because of its high melanoma uptake. Results: The inhibitory concentrations of 50% (IC 50 ) for HYNIC-GGGNle-CycMSH hex , HYNIC-GSGNle-CycMSH hex , HYNIC-PEG 2 Nle-CycMSH hex , and HYNIC-AocNle-CycMSH hex were 0.7 ± 0.1, 0.8 ± 0.09, 0.4 ± 0.08, and 0.3 ± 0.06 nM, respectively, in B16/F1 melanoma cells. Among these four 99m Tc-labeled peptides, 99m Tc(EDDA)-HYNIC-AocNle-CycMSH hex displayed the highest melanoma uptake (22.3 ± 1.72 percentage injected dose/g) at 2 h after injection. 99m Tc(EDDA)-HYNIC-AocNle-CycMSH hex exhibited high tumor–to–normal-organ uptake ratios except for the kidneys. The tumor-to-kidney uptake ratios of 99m Tc(EDDA)-HYNIC-AocNle-CycMSH hex were 3.29, 3.63, and 6.78 at 2, 4, and 24 h, respectively, after injection. The melanoma lesions were clearly visualized by SPECT/CT using 99m Tc(EDDA)-HYNIC-AocNle-CycMSH hex as an imaging probe at 2 h after injection. Conclusion: High melanoma uptake and fast urinary clearance of 99m Tc(EDDA)-HYNIC-AocNle-CycMSH hex highlighted its potential for metastatic melanoma detection in the future.