Phosphine-containing ligands and the search for a Tc-99m based myocardial imaging agent

A strategy used to develop several potential Tc-99m-based myocardial imagin g agents is described. Ether-substituted 1,2- and 1,3-diphosphine ligands w ere prepared and used to produce a range of cationic Tc-99m complexes for s ubsequent screening. Ligand/core combinations were optimised in several cas es to produce agents showing good heart uptake and retention in both animal s and humans. A range of phosphine-containing polydentate ligands has also been prepared and their potential for use in myocardial imaging agents asse ssed. A tridentate phosphine/amine/thiolate chelate system has been develop ed which gives a [Tc-99m(PNS)(2)](+) complex showing good heart uptake in t he rat. Synthetic routes to ether-substituted derivatives of this PNS ligan d system have also been developed.