Bis-Arene Complexes: A New Direction in Tc-99m Radiopharmaceuticals

Abstract

Technetium-99m (99mTc) is one of the most promising radionuclides for SPECT imaging. Multidentate chelators are commonly used to label Tc-99m. The use of a chelator requires derivatization of a targeting molecule with a chelating group followed by the addition of the Tc-99m radionuclide. Tc-99m radiolabeling without using traditional multidentate chelators was shown about 30 years ago with the synthesis of 99mTc bis-arenes, following Fischer-Hafner reaction conditions. However, the preparation of 99mTc bis-arenes by this method requires a lengthy and complicated process and was incompatible with functional groups containing oxygen or nitrogen. In recent years, new reaction conditions have been found to successfully prepare 99mTc bis-arene complexes in a convenient and relatively simple procedure that can be utilized with highly functionalized arenes. In the first part of the thesis, a new method for Tc-99m radiolabeling of L-Dopa was proposed. This new method was called Sandwich Technetium and involved single-step labeling without the need for any chelators. In addition to radiolabeling experiments, in vitro and in vivo assays were also performed. Due to the highly hydrophilic character of [99mTc(η6-Dopa)2]+, new L-DOPA derivatives were synthesized to increase the hydrophobicity of ligands and subsequently, the hydrophobicity of the Tc-99m radiolabeled compounds. In the future, hydrophobic L-DOPA derivatives Tc-99m labeling can be prepared in one step. The second part of the thesis focuses on preparation of 99mTc bis-arenes using [99mTc(η6-naphth)2]+ as a synthon. This two-step reaction procedure is proposed for more complex bis-arene compounds that cannot be achieved in one step. In this part, [99mTc(η6-naphth)2]+, and [Re(η6-naphth)2]+ were synthesized with the aim to substitute naphthalene in [99mTc(η6-naphth)2]+ with a ligand of interest. This new method may be a new way for Tc-99m compounds, which could not be synthesized in a single step before.