Abstract | INTRODUCTION: METHODS:
Ghrelin peptide labeled with mono- and trivalent technetium-99m complexes, (99m)Tc-Lys-GHR, has been prepared on the n.c.a. scale. The physicochemical (stability, charge, shape, lipophilicity) and biological (receptor affinity, biodistribution) properties of the conjugates have been studied relevant to use the conjugates as receptor-based diagnostic radiopharmaceuticals. RESULTS: The obtained conjugates [(99m)Tc(CO)3LN,O(CN-Lys-GHR)](+), (99m)Tc(CO)3LS,O(CN-Lys-GHR) and (99m)Tc(NS3)(CN-Lys-GHR) show different shape, charge, lipophilicity and two of them, (99m)Tc(CO)3LS,O(CN-Lys-GHR) and (99m)Tc(NS3)(CN-Lys-GHR), high stability in neutral aqueous solutions, even in the presence of excess concentration of histidine/ cysteine competitive standard ligands or human serum. The in vitro binding affinity of (99m)Tc-Lys-GHR conjugates with respect to growth hormone secretagogue receptor (GHS-R1a) present on DU-145 cells was in the range of IC50 from 45 to 54 nM. The conjugate (99m)Tc(CO)3LS,O(CN-Lys-GHR) exhibited excretion route by the liver and kidney in comparable degree, while the more lipophilic conjugate (99m)Tc(NS3)(CN-Lys-GHR)-mainly by the liver. CONCLUSIONS: Basing on the results concerning physicochemical and biochemical properties, the conjugates (99m)Tc(CO)3LS,O(CN-Lys-GHR) and (99m)Tc(NS3)(CN-Lys-GHR) might be considered to be promising models for diagnostic radiopharmaceutical.
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Authors | Przemysław Koźmiński, Ewa Gniazdowska |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 42
Issue 1
Pg. 28-37
(Jan 2015)
ISSN: 1872-9614 [Electronic] United States |
PMID | 25218025
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 Elsevier Inc. All rights reserved. |
Chemical References |
- Cyanides
- Ghrelin
- Radiopharmaceuticals
- Receptors, Ghrelin
- Technetium
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Topics |
- Animals
- Cell Line, Tumor
- Chemistry Techniques, Synthetic
- Cyanides
(chemistry, metabolism)
- Ghrelin
(chemistry, metabolism, pharmacokinetics)
- Humans
- Hydrophobic and Hydrophilic Interactions
- Isotope Labeling
- Male
- Mice
- Radiopharmaceuticals
(chemistry, metabolism, pharmacokinetics)
- Receptors, Ghrelin
(metabolism)
- Technetium
(chemistry)
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