Imaging human melanoma using a novel Tc-99m-labeled lactam bridge-cyclized alpha-MSH peptide

In this study, the human melanoma targeting property of^99mTc(EDDA)-HYNIC-AocNle-CycMSH_hex{hydrazinonicotinamide-8-aminooctanoic acid-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-CONH₂} was determined in M21 human melanoma-xenografts to demonstrate its potential for human melanoma imaging. The IC₅₀value of HYNIC-AocNle-CycMSH_hexwas 0.48 ± 0.01 nM in M21 human melanoma cells (1281 receptors/cell). The M21 human melanoma uptake of^99mTc(EDDA)-HYNIC-AocNle-CycMSH_hexwas 4.03 ± 1.25, 3.26 ± 1.23 and 3.36 ± 1.48% ID/g at 0.5, 2 and 4 h post-injection, respectively. Approximately 92% of injected dose cleared out the body via urinary system at 2 h post-injection.^99mTc(EDDA)-HYNIC-AocNle-CycMSH_hexshowed high tumor/blood, tumor/muscle and tumor/skin uptake ratios after 2 h post-injection. The M21 human melanoma-xenografted tumor lesions were clearly visualized by SPECT/CT using^99mTc(EDDA)-HYNIC-AocNle-CycMSH_hexas an imaging probe at 2 h post-injection. Overall,^99mTc(EDDA)-HYNIC-AocNle-CycMSH_hexexhibited favorable human melanoma imaging property, highlighting its potential as an imaging probe for human metastatic melanoma detection.