MURPHY RESEARCH GROUP
UNIVERSITY OF CALIFORNIA LOS ANGELES
Our lab seeks to discover chemical reactivity that can lead to interdisciplinary solutions for the advancement of human health. Research in our group focuses on developing new methodologies for the preparation of high-affinity imaging probes that are useful for studying biochemical processes using the molecular imaging technique of positron emission tomography (PET).
Molecular imaging is an essential part of biomedical research and clinical care particularly by providing tools for better understanding the biology of disease and its therapeutic modulation. We aim to identify and overcome significant roadblocks in fluorine-18 chemistry that hinder the critically important molecular imaging technique of PET from practical, routine clinical use. Towards this goal we have developed the first automated synthesis of 16β-[18F]-Fluoro-5α-dihydrotestosterone ([18F]-FDHT), a fluorinated analog of the native androgen receptor binding ligand dihydrotestosterone, for routine clinical production and in vivo evaluation of patients with metastatic prostate cancer. In collaboration with Tobias Ritter and colleagues, we optimized the synthesis of [18F]5-fluorouracil ([18F]5-FU) from [18F]-fluoride via a nickel-mediated oxidative fluorination. Likewise, this report is the first clinical translation of transition metal-mediated fluorination chemistry for use in human PET imaging studies.
Studies in my group have focused on developing robust, bioorthogonal chemical methods for labeling proteins and peptides towards targeted molecular imaging in oncology. Towards this goal, we have recently designed an optical/PET tracer and have employed it for dual-modality imaging of PSCA-expressing prostate cancer with colleagues in the Crump Institute. This approach ultimately could be used in the clinic for presurgical PET detection and staging followed by intraoperative visualization of tumors. In addition, we are utilizing a novel bioorthogonal ligation developed in our lab to prepare 18F-labeled peptides and proteins that may become valuable tools for imaging CD4/CD8 immune cell subsets. Imaging immune cell subsets noninvasively by PET will be an informative and valuable tool for studying the immune system including development of diseases with an immune/inflammatory component, for developing and evaluating immunotherapuetic strategies, and to detect responses to the therapeutic modulation of disease.
The aim is to simplify and facilitate general access to promising PET imaging probes for examining the biology of disease, enhancing molecular diagnostic tools and advancing therapeutic developments. Overall, our ultimate goal is to impact molecular imaging and therefore overall disease management by advances in chemical methods.