Technetium-99m radiopharmaceuticals—Radiochemistry and radiolabeling

Since the mid of the 60s of last century technetium-99m radiopharmaceuticals have been and still are the most used tracer agents for planar scintigraphy and single photon emission computed tomography. Factors at the basis of this are the favorable radiation and chemical properties of the radionuclide, its continuous availability in hospitals from easy to handle 99Mo/99mTc generators and the availability of numerous labeling kits that allow simple and efficient in house preparation of numerous 99mTc-radiopharmaceuticals shortly before use for diagnosis and follow-up of a variety of diseases. Hundreds of 99mTc labeled compounds with diverging biodistribution characteristics have been developed in intensive and innovative research and biologically tested during the last 50 years. Today about 30 of these agents are in routine clinical use as licensed diagnostic drugs. Only a few of the 99mTc radiopharmaceuticals are inorganic compounds whereas the majority consists of metallo-organic complexes in which the transition metal technetium is present in oxidation states 1, 3, 4 or 5. The 99mTc complexing ligands have a widely diverging structure and range from simple organic complexing agents to well designed Tc-chelating ligands and conjugates in which a bifunctional chelating agent is bound to a receptor targeting chemical, peptide or protein, including antibodies and their fragments. This article discusses the chemistry and radiolabeling of the 99mTc radiopharmaceuticals in clinical use and briefly their clinical applications. 99mTc labeled compounds that are not, no longer or not yet in clinical use are not discussed but reference is made to an extensive literature on their development and biological evaluation.