title: Bis(methylpyridine)-EDTA derivative as a potential ligand for PET imaging: synthesis, complexation, and biological evaluation.
abstract: A novel transitional metal ligand derivatized from EDTA-conjugated 2-amino-4-methyl pyridine, an acyclic vehicle (EDTA-Mepy2 ) was designed, synthesized, and characterized for PET imaging with ⁶⁸Ga. The drug likeliness and appropriate lipophilicity were first analyzed by molecular docking studies which shows interactive property of ligand with serum albumin protein (HSA: PDB 1E78), at Lys199, Arg257, and His242 residues, which make it more appropriate in transportation as a specific ligand for PET imaging. As a confirmation, binding constant of the ligand with human serum albumin was calculated at λex = 350 nm which was found to be 4.9 × 10³ m⁻¹. The pharmacokinetics of (68) Ga-EDTA-Mepy2 was analyzed by blood kinetics (t(1/2) slow: 3 h 56 min and t(1/2) fast: 32 min) and biodistribution (maximum % ID/g was found in kidney at 1 h). Further the capability of this ligand was analyzed as optical marker also, by recording λex = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed λem = 280 nm. Additionally, in physiological conditions where its stability was calculated, suggests 15-20 times selectivity over the endogenously present metal ions (KG aL /KZ nL = 14.3, KG aL /KC uL = 18.1).
authors.affiliation: Division of Cyclotron and Radiopharmaceutical Sciences, Institute of Nuclear Medicine and Allied Sciences, Brig. S.K. Mazumdar Road, Delhi, 110054, India; Department of Chemistry, University of Delhi, Delhi, 110007, India.
authors.forename: Pooja
authors.initials: P
authors.lastname: Singh
authors.forename: Swati
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Anjani K
authors.initials: AK
authors.lastname: Tiwari
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.forename: Ramendra
authors.initials: R
authors.lastname: Pratap
authors.forename: Krishna
authors.initials: K
authors.lastname: Chuttani
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004492:Edetic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D005708:Gallium / Q000737:chemistry; D006801:Humans; D006860:Hydrogen Bonding; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011725:Pyridines / Q000737:chemistry*; D011817:Rabbits; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D056831:Coordination Complexes; D008024:Ligands; D011725:Pyridines; D012709:Serum Albumin; D004492:Edetic Acid; D005708:Gallium; C023666:pyridine
keywords: 68Ga-EDTA-Mepy2; EDTA-Mepy2; Ga kinetics; human serum albumin interaction; stability constant