Radiopharmaceuticals for targeted radiotherapy

This work intends to find specific radiopharmaceuticals for cancer therapy based on beta (153Sm and 166Ho) or Auger (99Tcm) emitter radionuclides, using cyclic and acyclic polyamines as bifunctional chelators. These chelators are designed to allow the binding of a tumour seeking biomolecule and/or a DNA intercalator. The cyclic amines, such as 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid and 1,4,7,10-tetraazacyclotridecane-1,4,7,10-tetraacetic acid, were radiolabelled with 153Sm and 166Ho. The radiochemical and biological behaviour of the resulting complexes were evaluated in order to assess their potential as building blocks for the attachment of selected biomolecules, with the aim of further applying them for the development of specific therapeutic radiopharmaceuticals. Novel pyrazolyldiamines, bearing a DNA intercalating anthracenyl fragment, were also explored to synthesize radioactive complexes with the fac-[99Tcm(CO)]3]+ moiety. The identity of these 99Tcm tricarbonyl complexes was confirmed by high-performance liquid chromatography comparison with rhenium congeners fully characterized. By including a DNA intercalator into the chelator framework, we expect to induce more efficient and selective damage to the DNA of cancer cells by the action of the short-range Auger electrons emitted by 99Tcm.