CAREER: Exploring Cherenkov Radiation for the In Situ Excitation of Discrete Luminescent Lanthanide Complexes

Developing more sensitive and accurate diagnostic agents is an important step towards the faster and more accurate diagnosis of cancer. Agents that can be introduced to the body to produce a visual readout of the tissues of interest are called imaging probes. Certain imaging probes can specifically bind to tumor cells and emit light at specific wavelengths that can be detected by specialized imaging equipment. These probes are called targeted optical imaging probes. An ideal optical imaging probe can detect even a small population of cancer cells with high accuracy, deep under the surface of the skin. Currently, most current imaging probes require the presence of large amounts of superficially located tumor cells and therefore are not ideal optical imaging probes. Recently, Dr. Eszter Boros from Stony Brook University has developed a new approach to sensitive optical imaging probes that is based on the use of rare earth elements. In this project, Dr. Boros is working to optimize the properties of these radioactive imaging probes. The long-term goal of this research is to use these new optical imaging probes to visualize small amounts of tumor tissue deep under the skin. As an expert in work with radioactive agents, Dr. Boros is dedicated to educating the public about radioactivity and is actively engaged in developing outreach activities that educate high school students in a one-day laboratory course with the Institute for STEM Education about the significance of radioactivity in safety, energy, and medicine applications. With funding from the Chemical Structure, Dynamics and Mechanisms-B Program of the Chemistry Division, Dr. Eszter Boros from Stony Brook University is developing new discrete luminescent lanthanide complexes that can be efficiently excited with Cherenkov radiation emitted by radioactive isotopes utilized in nuclear medicine. This in situ excitation method paves the way for lanthanide-based optical imaging probes with enhanced depth penetration and improved biocompatibility. To maximize the excitation efficiency of the lanthanide-sensitizing antenna, density functional theory (DFT)-supported molecular designs of discrete terbium and europium complexes are synthesized that enable the incorporation of intramolecular, Cherenkov-emissive radiolabels. In addition to improving the excitation efficiency of terbium(III) complexes, the synthesis of new bifunctional chelators is pursued to incorporate sensitizing antennas with a more ideal energy match for europium(III) excited states. The ability of these optimized probes to visualize specific cell surface-receptors in vitro is used as a proof-of-concept for the feasibility of Cherenkov-radiation mediated excitation of lanthanide based optical probes. As a radiochemist dedicated to educating the public about radioactivity, Dr. Boros is developing an outreach activity in the form of a full day, hands-on Nuclear and Radiochemistry science module for high school students with the Institute for STEM Education at Stony Brook University. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.