Reduction of the ring size of radiolabeled lactam bridge-cyclized alpha-MSH peptide resulting in enhanced melanoma uptake

The purpose of this study was to examine the profound effect of the ring size of the radiolabeled lactam bridge–cyclized a-melanocyte–stimulating hormone (a-MSH) peptide on its mel-anoma-targeting properties. Methods: A novel cyclic a-MSH peptide, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Nle-c[Asp-His-D-Phe-Arg-Trp-Lys]-CONH2 (DOTA-Nle-CycMSHhex), was synthesized and radiolabeled with 111In. The melanocortin-1 receptor–binding affinity of DOTA-Nle-CycMSHhex was determined in B16/F1 melanoma cells. The internalization and efflux of 111In-DOTA-Nle-CycMSHhex were examined in B16/F1 cells. The melanoma-targeting properties and SPECT/ CT characteristics of 111In-DOTA-Nle-CycMSHhex were deter-mined in B16/F1 melanoma–bearing C57 mice. Results: DOTA-Nle-CycMSHhex displayed 1.77 nM receptor-binding affinity. 111In-DOTA-Nle-CycMSHhex exhibited rapid internaliza