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

Abstract

OBJECTIVE:

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 α-MSH analog was labeled with (99m)Tc 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.

METHODS:

HYNIC-GABA-Nle-CycMSHhept was synthesized using a standard Fmoc strategy. Labeling was performed at 95 °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.

RESULTS:

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 ± 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 ± 0.08 % ID/g, while low accumulation in the kidney uptake was observed (4.58 ± 0.68 % ID/g at 2 h after injection).

CONCLUSIONS:

The obtained results show that the presented new designed labeled peptide conjugate may be a suitable candidate for diagnosis of malignant tumors.

• Authors: Danial Shamshirian, Mostafa Erfani, Davood Beiki, Babak Fallahi, Mohammad Shafiei
• Journal: Annals of nuclear medicine (Ann Nucl Med) Vol. 29 Issue 8 Pg. 709-20 (Oct 2015) ISSN: 1864-6433 [Electronic] Japan
• PMID: 26152564 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6-hydrazinopyridine-3-carboxylic acid
• Hydrazines
• Lactams
• Nicotinic Acids
• Peptides, Cyclic
• gamma-Aminobutyric Acid
• alpha-MSH
• Technetium

Topics

• Amino Acid Sequence
• Animals
• Biological Transport
• Cell Line, Tumor
• Drug Stability
• Hydrazines (chemistry)
• Hydrophobic and Hydrophilic Interactions
• Lactams (chemistry)
• Melanoma (diagnostic imaging)
• Mice
• Nicotinic Acids (chemistry)
• Peptides, Cyclic (chemistry, metabolism, pharmacokinetics)
• Photons
• Radionuclide Imaging (methods)
• Technetium
• Tissue Distribution
• alpha-MSH (chemistry)
• gamma-Aminobutyric Acid (chemistry)