title: (99m)Tc-amitrole as a novel selective imaging probe for solid tumor: In silico and preclinical pharmacological study.
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.
authors.affiliation: Radioactive Isotopes and Generator Department, Hot Laboratories Center, Atomic Energy Authority (EAEA), P.O. Box 13759, Cairo, Egypt.
authors.forename: B M
authors.initials: BM
authors.lastname: Essa
authors.affiliation: Radioactive Isotopes and Generator Department, Hot Laboratories Center, Atomic Energy Authority (EAEA), P.O. Box 13759, Cairo, Egypt. Electronic address: Tamer_sakr78@yahoo.com.
authors.forename: T M
authors.initials: TM
authors.lastname: Sakr
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Ein Helwan, Cairo 11795, Egypt.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Khedr
authors.affiliation: Faculty of Science, Department of Chemistry, Menoufia University, Shebin El-Koam, Egypt.
authors.forename: F A
authors.initials: FA
authors.lastname: El-Essawy
authors.affiliation: Radioactive Isotopes and Generator Department, Hot Laboratories Center, Atomic Energy Authority (EAEA), P.O. Box 13759, Cairo, Egypt.
authors.forename: A A
authors.initials: AA
authors.lastname: El-Mohty
mesh_terms: D000640:Amitrole / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D002286:Carcinoma, Ehrlich Tumor / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000201:enzymology; D017076:Computer-Aided Design; D015195:Drug Design; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D006863:Hydrogen-Ion Concentration; D007784:Lactoperoxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship; D013667:Technetium / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019275:Radiopharmaceuticals; D013667:Technetium; D007784:Lactoperoxidase; D000640:Amitrole
keywords: Amitrole; Hypoxia; Imaging; In silico; Lactoperoxidase enzyme; Technetium-99m; Tumor