EAPSI: Synthesis and Characterization of Metal-Based Imaging and Therapeutic Agents

Lemon Christopher M, Cambridge MA

Investigators

Abstract

Metal ions, particularly iron and platinum, have an important role as both diagnostic and therapeutic agents in the field of medicine. The majority of magnetic resonance imaging (MRI) agents feature a metal ion. Some radioactive metals are used for diagnostic imaging, while others can be used for chemotherapy, delivering localized radiation to a tumor and minimizing damage to healthy tissue. In order to exploit these metals for medical applications, a molecule with flexible arms capable of wrapping around a metal ion will be prepared. These experiments will be carried out at the University of Auckland in New Zealand in collaboration with Dr. Penelope Brothers, an expert in the field of metal-based medicine. The potential of these compounds as photosensitizers for photodynamic therapy (PDT) and contrast agents for MRI will be studied at the University of Auckland Photon Factory laser laboratory and the Centre for Advanced MRI, respectively. With the development of new compounds, therapeutics with greater efficacy, or imaging agents with better sensitivity, will improve patient outcomes across the globe. This project will exploit novel picket-fence corrole ligands that are amenable to the coordination of biologically relevant metal ions for a variety of applications: PDT, alpha-radiotherapy, Beta-radiotherapy, and MRI. In this motif, the corrole macrocycle will be appended with flexible arms that can rapidly and tightly coordinate a metal center. The coordination chemistry of these compounds will be studied with a variety of metals for which corrole complexes are rare or nonexistent, including bismuth, rhenium, gadolinium, and other lanthanides. Finally, the stability of the metal complexes will be evaluated when exposed to conditions, such as reducing thiols, which mimic a biological environment. This NSF EAPSI award is funded in collaboration with the Royal Society of New Zealand.