Development of a Tc-99m-labeled lactam bridge-cyclized alpha-MSH derivative peptide as a possible single photon imaging agent for melanoma tumors

作者：Shamshirian Danial; Erfani Mostafa^*; Beiki Davood; Fallahi Babak; Shafiei Mohammad

来源：Annals of Nuclear Medicine, 2015, 29(8): 709-720.

DOI：10.1007/s12149-015-0998-y

• alpha-MSH
• Tc-99m
• B16/F10 cells
• Tumor imaging

Melanocortin-1 (MC1) receptor is an attractive melanoma-specific target which has been used for melanoma imaging and therapy. In this work, a new lactam bridge alpha-MSH analog was labeled with Tc-99m via HYNIC and EDDA/tricine as coligands including gamma aminobutyric acid (GABA) as a three carbon chain spacer between HYNIC and the N-terminus of the cyclic peptide. Also, stability in human serum, receptor bound internalization, in vivo tumor uptake, and tissue biodistribution were thoroughly investigated.
HYNIC-GABA-Nle-CycMSH(hept) was synthesized using a standard Fmoc strategy. Labeling was performed at 95 A degrees C and analysis involved instant thin layer chromatography and high performance liquid chromatography methods. The receptor bound internalization rate was studied in MC1 receptor expressing B16/F10 cells. Biodistribution of radiopeptide was studied in nude mice bearing B16/F10 tumor.
Labeling yield of > 98 % (n = 3) was obtained corresponding to a specific activity of 81 MBq/nmol. Peptide conjugate showed efficient stability in the presence of human serum. The radioligand showed specific internalization into B16/F10 cells (12.45 +/- A 1.1 % at 4 h). In biodistribution studies, a receptor-specific uptake was observed in MC1 receptor-positive organs so that after 2 h the uptake in mouse tumor was 5.10 +/- A 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 +/- A 0.68 % ID/g at 2 h after injection).
The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors.

• 出版日期2015-10