Melanoma targeting with [99mTc(N)(PNP3)]-labeled α-melanocyte stimulating hormone peptide analogs: Effects of cyclization on the radiopharmaceutical properties
| Autor: | H.-J. Pietzsch, Barbara Biondi, Antonio Rosato, Wiebke Sihver, Feng Gao, Nicola Salvarese, Cristina Bolzati, Davide Carta, Nicolò Morellato, Fiorenzo Refosco, Paolo Ruzza, Debora Carpanese |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Melanocyte-stimulating hormone Stereochemistry Peptide 99mTc Imaging Melanoma Peptides SPECT α-MSH Molecular Medicine Radiology Nuclear Medicine and Imaging ?-MSH 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Nuclear Medicine and Imaging MC1R medicine melanoma Radiology Nuclear Medicine and imaging Receptor chemistry.chemical_classification Peptide analog medicine.disease In vitro Tc-99m 030104 developmental biology chemistry alpha-MSH 030220 oncology & carcinogenesis Lactam peptides 99m Tc Radiology |
| Zdroj: | Nuclear Medicine and Biology 43(2016)12, 788-801 Nuclear medicine and biology 43 (2016): 788–801. doi:10.1016/j.nucmedbio.2016.08.014 info:cnr-pdr/source/autori:Carta D.; Salvarese N.; Morellato N.; Gao F.; Sihver W.; Pietzsch H.J.; Biondi B.; Ruzza P.; Refosco F.; Carpanese D.; Rosato A.; Bolzati C./titolo:Melanoma targeting with [Tc-99m(N)(PNP3)]-labeled alpha-melanocyte stimulating hormone peptide analogs: Effects of cyclization on the radiopharmaceutical properties/doi:10.1016%2Fj.nucmedbio.2016.08.014/rivista:Nuclear medicine and biology/anno:2016/pagina_da:788/pagina_a:801/intervallo_pagine:788–801/volume:43 |
| DOI: | 10.1016/j.nucmedbio.2016.08.014 |
| Popis: | The purpose of this study was to evaluate the effect of cyclization on the biological profile of a [ 99m Tc(N)(PNP3)]-labeled α-melanocyte stimulating hormone peptide analog. A lactam bridge-cyclized H-Cys-Ahx-βAla 3 -c[Lys 4 -Glu-His-D-Phe-Arg-Trp-Glu 10 ]-Arg 11 -Pro-Val-NH 2 (NAP―NS2) and the corresponding linear H-Cys-Ahx-βAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH 2 (NAP―NS1) peptide were synthetized, characterized by ESI-MS spectroscopy and their melanocortin-1 receptor (MC1R) binding affinity was determined in B16/F10 melanoma cells. The consistent [ 99m Tc(N)(PNP3)]-labeled compounds were readily obtained in high specific activity and their stability and biological properties were assessed. As an example, the chemical identity of [ 99m Tc(N)(NAP–NS1)(PNP3)] + was confirmed by carrier added experiments supported by radio/UV HPLC analysis combined with ESI(+)-MS. Compared with the linear peptide, cyclization negatively affected the biological properties of NAP–NS2 peptide by reducing its binding affinity for MC1R and by decreasing the overall excretion rate of the corresponding [ 99m Tc(N)(PNP3)]-labeled peptide from the body as well as its in vivo stability. [ 99m Tc(N)(NAP–NS1)(PNP3)] + was evaluated for its potential as melanoma imaging probe in murine melanoma model. Data from in vitro and in vivo studies on B16/F10 melanoma model of [ 99m Tc(N)(NAP–NS1)(PNP3)] + clearly evidenced that the radiolabeled linear peptide keeps its biological properties up on the conjugation to the [ 99m Tc(N)(PNP3)]-building block. The progressive increase of the tumor-to-nontarget ratios over the time indicates a quite stable interaction between the radio-complex and the MC1R. |
| Databáze: | OpenAIRE |
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