Abstract
Lactoperoxidase (LPO) inhibitors are very selective for solid tumor due to their high binding affinity to the LPO enzyme. A computational study was used to select top-ranked LPO inhibitor (alone and in complex with (99m)Tc) with high in silico affinity. The novel prepared (99m)Tc-amitrole complex demonstrated both in silico and in vivo high affinity toward solid tumors.(99m)Tc-amitrole was radio-synthesized with a high radiochemical yield (89.7±3.25). It showed in vitro stability for up to 6h. Its preclinical evaluation in solid tumor-bearing mice showed high retention and biological accumulation in solid tumor cells with a high Target/Non-Target (T/NT) ratio equal to 4.9 at 60min post-injection. The data described previously could recommend (99m)Tc-amitrole as potential targeting scintigraphic probe for solid tumor imaging.
Keywords:
Amitrole; Hypoxia; Imaging; In silico; Lactoperoxidase enzyme; Technetium-99m; Tumor.
Copyright © 2015 Elsevier B.V. All rights reserved.
MeSH terms
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Amitrole / administration & dosage
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Amitrole / chemistry
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Amitrole / pharmacokinetics*
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacokinetics*
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Carcinoma, Ehrlich Tumor / diagnostic imaging*
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Carcinoma, Ehrlich Tumor / drug therapy
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Carcinoma, Ehrlich Tumor / enzymology
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Computer-Aided Design*
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Drug Design*
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Drug Stability
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacokinetics*
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Female
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Hydrogen-Ion Concentration
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Lactoperoxidase / antagonists & inhibitors*
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Lactoperoxidase / metabolism
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Mice
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Molecular Docking Simulation
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Molecular Structure
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Radionuclide Imaging
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Radiopharmaceuticals / administration & dosage
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Radiopharmaceuticals / chemistry
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Radiopharmaceuticals / pharmacokinetics*
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Structure-Activity Relationship
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Technetium / administration & dosage
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Technetium / chemistry
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Technetium / pharmacokinetics*
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Tissue Distribution
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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Radiopharmaceuticals
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Technetium
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Lactoperoxidase
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Amitrole