Technetium-99m complexes with 2-pyrrolylthiones a new class of radiopharmaceuticals for medical imaging

Abstract

Technetium-99m ([superscript 99m]Tc) is the most useful radioisotope in medical imaging due to its favourable nuclear characteristics, wide availability and low cost. Since [superscript 99m]Tc is a metal, it must be chelated using appropriate ligands to impart affinity for target tissues. A series of new 2-pyrrolylthiones were synthesised as potential ligands for transition metals, particularly [superscript 99m]Tc, and were fully characterised. Both lipophilic and water-soluble compounds were obtained. Chemical reactions of the 2-pyrrolylthiones were studied. It was found that physical and chemical properties of these ligands are highly dependent on the substituents in the outer periphery of the molecule. Transition metals such as Ni, Cu, Co, Cd, and Zn react smoothly with synthesised 2-pyrrolylthiones. A general complexation procedure was developed for technetium and rhenium. [superscript 99m]Tc and non-radioactive Re complexes were used to establish the chemical structure of the new [supescript 99m]Tc compounds and to study their properties. Labelling of the 2-pyrrolylthiones with [superscript99m]Tc was performed. The biodistribution and pharmacokinetics of the selected complexes were studied. The biodistribution pattern of the new [superscript 99m]Tc-complexes greatly depends on their lipophilicity. Chemical changes in the ligand periphery, from highly lipophilic through amphiphilic to water-soluble, allow for fine turning of the biological properties of the corresponding technetium complexes. Novel 2-pyrrolylthiones would provide a new class of radiopharmaceuticals for medical imaging, where the periphery of the radiopharmaceutical can be modified according to desirable properties, while the central technetium core remains the same.