Synthesis and characterisation of functionalised diamino-dithiol ligands for radionuclide complexation

Full text: Tc-99m is the most widely used diagnostic agent in nuclear medicine. Re-188 (t1/2 17 h, 155 keV γ 15%, β- Emax 2.1 MeV), with its similar chemistry, has been postulated as a suitable therapeutic analogue for the diagnostic radionuclide. The development of the 188W/188Re generator which produces carrier-free and salt-free 188Re has created considerable impetus for the production of a matched-pair of radiopharmaceuticals for diagnosis and treatment of disease. The organic ligands used to complex these agents frequently determine physiological half-life, stability and mode of excretion. Nitrogen and sulfur containing ligands, specifically diamino-dithiol ligands have been explored by us and others for this purpose. We have been interested in selective monofunctionalisation of the diamino-dithiol backbone, to allow for linkage onto other carrier molecules such as peptides or antibody fragments. Ligands with the generic structures illustrated have been synthesised from the readily available bicyclic precursor. The ligands have been characterised by the usual methods. Preliminary labelling methods with perrhenate have been attempted