Advanced Chelator Design for Metal Complexes in Imaging Applications

Chelating ligands can be designed to control the interactions of metal complexes with biological systems with specific relevance to molecular imaging techniques. Properties of interest include the stability of the complex under physiological conditions and how the complex will interact with biological macromolecules including proteins, genetic material, and polysaccharides. In medical imaging applications, targeting specific organs or disease sites, the metal complex will most commonly have the requirement of it being delivered to the site of interest, cleared from the other organs (followed by imaging), and then ultimately excreted remaining intact throughout. Design features such as rigidity, donor atom type and arrangement, and cavity size can be tuned to optimize the specificity, stability, and kinetics of binding. Examples are presented on chelator design for radiopharmaceuticals, how targeting for imaging can be achieved utilizing metal complexes that bind to specific proteins and how chelators can be modified for attachment (bioconjugation) to antibodies and peptides as bifunctional chelators.