Synthesis,Characterization, and Initial Biological Evaluation of [99mTc]Tc‐Tricarbonyl‐labeled DPA‐α‐MSH Peptide Derivatives for Potential Melanoma Imaging |
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Authors: | Dr Feng Gao Dr Wiebke Sihver Dr Ralf Bergmann Dr Birgit Belter Dr Cristina Bolzati Dr Nicola Salvarese Prof?Dr Jörg Steinbach Prof?Dr Jens Pietzsch Dr Hans‐Jürgen Pietzsch |
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Affiliation: | 1. Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany;2. Institute of Condensed Matter Chemistry and Technologies for Energy-ICMATE-CNR, Padova, Italy;3. Department of Chemistry and Food Chemistry, School of Science, Technische Universit?t Dresden, Dresden, Germany |
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Abstract: | α‐Melanocyte stimulating hormone (α‐MSH) derivatives target the melanocortin‐1 receptor (MC1R) specifically and selectively. In this study, the α‐MSH‐derived peptide NAP‐NS1 (Nle‐Asp‐His‐d ‐Phe‐Arg‐Trp‐Gly‐NH2) with and without linkers was conjugated with 5‐(bis(pyridin‐2‐ylmethyl)amino)pentanoic acid (DPA‐COOH) and labeled with 99mTc]Tc‐tricarbonyl by two methods. With the one‐pot method the labeling was faster than with the two‐pot method, while obtaining similarly high yields. Negligible trans‐chelation and high stability in physiological solutions was determined for the 99mTc]Tc‐tricarbonyl–peptide conjugates. Coupling an ethylene glycol (EG)‐based linker increased the hydrophilicity. The peptide derivatives displayed high binding affinity in murine B16F10 melanoma cells as well as in human MeWo and TXM13 melanoma cell homogenates. Preliminary in vivo studies with one of the 99mTc]Tc‐tricarbonyl–peptide conjugates showed good stability in blood and both renal and hepatobiliary excretion. Biodistribution was performed on healthy rats to gain initial insight into the potential relevance of the 99mTc‐labeled peptides for in vivo imaging. |
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Keywords: | [99mTc]Tc-tricarbonyl labeling melanocortin-1 receptor peptides radiopharmaceuticals α -MSH analogues |
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