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Radiopharmacological characterization of 64Cu-labeled α-MSH analogs for potential use in imaging of malignant melanoma
- Source :
- Amino Acids 48(2016)3, 833-847, Amino acids (Wien, Print) 48 (2016): 833–847. doi:10.1007/s00726-015-2131-x, info:cnr-pdr/source/autori:Gao F.; Sihver W.; Jurischka C.; Bergmann R.; Haase-Kohn C.; Mosch B.; Steinbach J.; Carta D.; Bolzati C.; Calderan A.; Pietzsch J.; Pietzsch H.-J./titolo:Radiopharmacological characterization of 64Cu-labeled alfa-MSH analogs for potential use in imaging of malignant melanoma/doi:10.1007%2Fs00726-015-2131-x/rivista:Amino acids (Wien, Print)/anno:2016/pagina_da:833/pagina_a:847/intervallo_pagine:833–847/volume:48
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- The melanocortin-1 receptor (MC1R) plays an important role in melanoma growth, angiogenesis and metastasis, and is overexpressed in melanoma cells. α-Melanocyte stimulating hormone (α-MSH) and derivatives are known to bind with high affinity at this receptor that provides the potential for selective targeting of melanoma. In this study, one linear α-MSH-derived peptide Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) without linker and with eAhx-β-Ala linker, and a cyclic α-MSH derivative, [Lys-Glu-His-D-Phe-Arg-Trp-Glu]-Arg-Pro-Val-NH2 (NAP-NS2) with eAhx-β-Ala linker were conjugated with p-SCN-Bn-NOTA and labeled with (64)Cu. Radiochemical and radiopharmacological investigations were performed with regard to transchelation, stability, lipophilicity and in vitro binding assays as well as biodistribution in healthy rats. No transchelation reactions, but high metabolic stability and water solubility were demonstrated. The linear derivatives showed higher affinity than the cyclic one. [(64)Cu]Cu-NOTA-eAhx-β-Ala-NAP-NS1 ([(64)Cu]Cu-2) displayed rapid cellular association and dissociation in murine B16F10 cell homogenate. All [(64)Cu]Cu-labeled conjugates exhibited affinities in the low nanomolar range in B16F10. [(64)Cu]Cu-2 showed also high affinity in human MeWo and TXM13 cell homogenate. In vivo studies suggested that [(64)Cu]Cu-2 was stable, with about 85 % of intact peptide in rat plasma at 2 h p.i. Biodistribution confirmed the renal pathway as the major elimination route. The uptake of [(64)Cu]Cu-2 in the kidney was 5.9 % ID/g at 5 min p.i. and decreased to 2.0 % ID/g at 60 min p.i. Due to the prospective radiochemical and radiopharmacological properties of the linear α-MSH derivative [(64)Cu]Cu-2, this conjugate is a promising candidate for tracer development in human melanoma imaging.
- Subjects :
- 0301 basic medicine
Biodistribution
alfa-MSH analogs
Clinical Biochemistry
malignant melanoma
Peptide
Biochemistry
03 medical and health sciences
Melanocortin-1 receptor
In vivo
Receptor
α-MSH analogs
chemistry.chemical_classification
Malignant melanoma
Organic Chemistry
Array
64Cu labeling
Molecular biology
030104 developmental biology
chemistry
Lipophilicity
Linker
Melanocortin 1 receptor
Conjugate
Subjects
Details
- ISSN :
- 14382199 and 09394451
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Amino Acids
- Accession number :
- edsair.doi.dedup.....969f9b7d3bf0ce3719a628d914d52116