A brief overview of metal complexes as nuclear imaging agents

Metallic radionuclides have been instrumental in the field of nuclear imaging for over half a century. While recent years have played witness to a dramatic rise in the use of radiometals as labels for chelator-bearing biomolecules, imaging agents based solely on coordination compounds of radiometals have long played a critical role in the discipline as well. In this work, we seek to provide a brief overview of metal complex-based radiopharmaceuticals for positron emission tomography (PET) and single photon emission computed tomography (SPECT). More specifically, we have focused on imaging agents in which the metal complex itself rather than a pendant biomolecule or targeting moiety is responsible for the in vivo behavior of the tracer. This family of compounds contains metal complexes based on an array of different nuclides as well as probes that have been used for the imaging of a variety of pathologies, including infection, inflammation, cancer, and heart disease. Indeed, two of the defining traits of transition metal complexes-modularity and redox chemistry-have both been creatively leveraged in the development of imaging agents. In light of our audience, particular attention is paid to structure and mechanism, though clinical data is addressed as well. Ultimately, it is our hope that this review will not only educate readers about some of the seminal work performed in this space over the last 30 years but also spur renewed interest in the creation of radiopharmaceuticals based on small metal complexes.