Bis(methylpyridine)-EDTA derivative as a potential ligand for PET imaging: synthesis, complexation, and biological evaluation.
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).
['Singh|Pooja|P|', 'Aggarwal|Swati|S|', 'Tiwari|Anjani K|AK|', 'Kumar|Vikas|V|', 'Pratap|Ramendra|R|', 'Chuttani|Krishna|K|', 'Mishra|Anil K|AK|']
D000818:Animals D003287:Contrast Media D056831:Coordination Complexes D004492:Edetic Acid D005708:Gallium 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 D011817:Rabbits D012709:Serum Albumin D014018:Tissue Distribution
EDTA-Mepy2 68Ga-EDTA-Mepy2 Ga kinetics human serum albumin interaction stability constant