Reduction of the Ring Size of Radiolabeled Lactam Bridge–Cyclized α-MSH Peptide, Resulting in Enhanced Melanoma Uptake

Journal of Nuclear Medicine

Yubin Miao¹  Haixun Guo¹  Jianquan Yang¹  Fabio Gallazzi¹ 

关键词: melanoma imaging;    radiolabeled cyclic peptide;    α-melanocyte–stimulating hormone;    small-animal imaging;   

DOI  :  10.2967/jnumed.109.071787

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

The purpose of this study was to examine the profound effect of the ring size of the radiolabeled lactam bridge–cyclized α-melanocyte–stimulating hormone (α-MSH) peptide on its melanoma-targeting properties. Methods: A novel cyclic α-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 determined in B16/F1 melanoma–bearing C57 mice. Results: DOTA-Nle-CycMSHhex displayed 1.77 nM receptor-binding affinity. 111In-DOTA-Nle-CycMSHhex exhibited rapid internalization and extended retention in B16/F1 cells. The tumor uptake of 111In-DOTA-Nle-CycMSHhex 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 111In-DOTA-Nle-CycMSHhex 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. Conclusion: The reduction of the peptide ring size dramatically increased the melanoma uptake and decreased the renal uptake of 111In-DOTA-Nle-CycMSHhex, providing a new insight into the design of a novel radiolabeled lactam bridge–cyclized α-MSH peptide for melanoma imaging and treatment.

【 授权许可】

Unknown