The Radiopharmaceutical Chemistry of Technetium-99m

Technetium-99m (99mTc) is a radiometal that has nearly ideal nuclear properties for diagnostic nuclear medicine imaging, which has helped make it high impact and extensively utilized radionuclide in medicine. 99mTc-based imaging—which can be done using a simple gamma camera or a more advanced 3-D method known as single photon emission computed tomography (SPECT)—has been a mainstay of diagnostic nuclear medicine for decades. In this chapter, we provide an introduction to the nuclear and coordination chemistry of 99mTc, emphasizing areas that relate to its use to create radiopharmaceuticals. The ease of access to the radionuclide is described along with how one can take advantage of the many oxidation states of technetium and unique ligand environments to create a diverse array of radiopharmaceuticals. Several established clinical agents are presented as examples along with details of their structures, methods of preparation, and diagnostic utility. This discussion is followed by detailed descriptions of the procedures used to prepare and characterize selected 99mTc-labeled compounds that can be used to create the next generation of targeted radiopharmaceuticals, along with commentary on the influence of chelators on the pharmacokinetics of 99mTc-based radiotracers. Additional information concerning the characterization and evaluation of novel constructs is provided as well, including ligand challenge, stability, and other useful assays as well as how to prepare for biodistribution studies. It is important to note that this chapter was written as an introductory guide for those who are new to the field and is not a comprehensive examination of the chemistry and nuclear medicine applications of 99mTc. A more comprehensive treatment of this material can be obtained from a number of excellent review articles.