While a number of chelates and strategies have been developed for the organometallic precursor fac-[M(OH2)3(CO)3]+ (M= Re, 99mTc), a unique challenge remains to improve the overall function and performance of these complexes formed for in vitro and in vivo applications. Since its discovery, the fac-[MI(CO)3]+ core has served as an essential scaffold for the development of new targeted 99mTc based radiopharmaceuticals due to its labile aquo ligands. However, the overall stability and lipophilic nature of the CO ligands inherently impacts the pharmacodynamic behavior and in vivo clearance properties of fac-]MI(CO)3]+ complexes. In an effort to improve this behavior, mono-substituted pyridine ligands were used to assess the impact of donor nitrogen basicity on the binding strength and stability of fac-[MI(CO)3]+ complexes. Using a 2 + 1 labeling strategy, a series of monodentate 4-substituted pyridine ligand complexes were synthesized with picolinic acid as a bidentate ligand. These complexes investigated the effect of pKa of the monodentate ligand on the stability, complexation and crystallographic properties both at the macro scale and radiochemical concentrations. Data from these experiments were used in the design of new multidentate ligands with enhanced binding capabilities.

Development of new ligands for [MI(CO)3]+ (M= Re, 99mTc) complexes with enhanced chemical properties and stability

249th National Meeting (2015)

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