Potential of unconventional phosphorus-nitrogen backbone ligands for use in formulating new radiopharmaceuticals

The development of new ligand systems for chelation of various early and late transition-metal radioisotopes continues to be an essential aspect in the design of new radiopharmaceuticals for diagnostic and therapeutic applications. A multitude of conventional, carbon backboned ligands have dominated in radiochemical studies of different transition metal radionuclides. However, the use of other main group elements (e.g., P) to link chelating functional groups have not been used for radiopharmaceutical applications. These types of ligands may hold enormous potential for achieving subtle beneficial structure activity relationships because of their unusual steric and electronic characteristics. Several different phosphorous-nitrogen hydrazido ligands have been developed in this laboratory and have been shown to hold the potential for preparing stable, small complexes with a variety of radionuclides (incl. Tc-99m, Re-188, Re-186 and Pd-109). These chelates have been characterized at both tracer and open-quotes carrierclose quotes level chemistry (e.g., X-ray crystallography). Preparation of derivatives is quite feasible by modification of the R-group(s) attached to the P or N atoms. The results of studies summarized in this paper demonstrate the potential utility of using a wide spectrum of P-N based ligands to produce a new genre of complexes for the development of future radiopharmaceuticals