111In-Labeled Lactam Bridge-Cyclized α-Melanocyte Stimulating Hormone Peptide Analogues for Melanoma Imaging

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Abstract
The purpose of this study was to examine the influence of the lactam bridge cyclization on melanoma targeting and biodistribution properties of the radiolabeled conjugates. Two novel lactam bridge-cyclized α-MSH peptide analogues, DOTA-CycMSH (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]) and DOTA-GlyGlu-CycMSH (DOTA-Gly-Glu-c[Lys-Nle-Glu-His-DPhe-Arg-Trp-Gly-Arg-Pro-Val-Asp]), were synthesized and radiolabeled with 111In. The internalization and efflux of 111In-labeled CycMSH peptides were examined in B16/F1 melanoma cells. The melanoma targeting properties, pharmacokinetics, and SPECT/CT imaging of 111In-labeled CycMSH peptides were determined in B16/F1 melanoma-bearing C57 mice. Both 111In-DOTA-CycMSH and 111In-DOTA-GlyGlu-CycMSH exhibited fast internalization and extended retention in B16/F1 cells. The tumor uptake values of 111In-DOTA-CycMSH and 111In-DOTA-GlyGlu-CycMSH were 9.53 ± 1.41% injected dose/gram (% ID/g) and 10.40 ± 1.40% ID/g at 2 h postinjection, respectively. Flank melanoma tumors were clearly visualized with 111In-DOTA-CycMSH and 111In-DOTA-GlyGlu-CycMSH by SPECT/CT images at 2 h postinjection. Whole-body clearance of the peptides was fast, with greater than 90% of the radioactivities cleared through urinary system by 2 h postinjection. There was low radioactivity (111In-labeled lactam bridge-cyclized α-MSH peptide analogues as a novel class of imaging probes for receptor-targeting melanoma imaging.