Phosphine-Containing Ligands and the Search for a Tc-99m Based Myocardial Imaging Agent

A strategy used to develop several potential 99m Tc-based myocardial imaging agents is described. Ether-substituted 1,2- and 1,3-diphosphine ligands were prepared and used to produce a range of cationic Tc-99m complexes for subsequent screening. Ligand/core combinations were optimised in several cases to produce agents showing good heart uptake and retention in both animals and humans. A range of phosphine-containing polydentate ligands has also been prepared and their potential for use in myocardial imaging agents assessed. A tridentate phosphine/amine/thiolate chelate system has been developed which gives a [ 99m Tc(PNS) 2 ] + complex showing good heart uptake in the rat. Synthetic routes to ether-substituted derivatives of this PNS ligand system have also been developed.