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 λ_ex = 350 nm which was found to be 4.9 × 10³ m ^?1. The pharmacokinetics of ⁶⁸Ga‐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 λ_ex = 380 nm, RFU = 8000; 710 nm, RFU = 1000 units at fixed λ_em = 280 nm. Additionally, in physiological conditions where its stability was calculated, suggests 15–20 times selectivity over the endogenously present metal ions (K_GaL/K_ZnL = 14.3, K_GaL/K_CuL = 18.1).