Radiometal complexes: characterization and relevant in vitro studies

Radiometals are, and will continue to be, very important to diagnostic and therapeutic nuclear medicine applications as they predominantly possess the most suitable nuclear properties for these types of applications. This article attempts to give the reader an overview of key aspects that need to be considered in the design and synthesis of a radiopharmaceutical using the commonly known and employed radionuclides, such as technetium, rhenium, the lanthanides and copper. While it is important to understand each radiometal ion has its own specific coordination chemistry requirements, there are several issues that are critical to all radiometal ions for their incorporation into a radiopharmaceutical. 1) The route of production and the presence of long lived contaminating radionuclides and or of naturally occurring metal ions that will interfere with the efficient and optimum radiolabelling of their ligand of choice as well as the final specific activity of the product; 2) the significant differences between the chemistry at the macroscopic (mM and higher concentrations) and radiotracer levels (uM and lower concentrations for the high specific activity radionuclides); 3) the rate of complexation and of dissociation of the radiometal ion vs the competing reaction of radiometal hydrolysis; 4) natural biological pathway of the radio-metal ion and therefore the design of the appropriate and relevant in vitro tests to assess the stability of the radiometal complex. These are a selection of critical factors that need to be considered in the design of a successful radiopharmaceutical, whether it is used for imaging or therapy. However, one should consider tailoring their investigations to suit the radiometal under investigation, and to be mindful where the technology is to be applied (e.g. imaging organs or disease).