Radioactive Mice! How We Use the Mouse Model to Study Radiotherapeutics and Decontamination at LBNL

Alexia Cosby, Ph.D.

The mouse model is an essential component for validating preclinical research. Here at LBNL, we use the mouse model to investigate two distinct challenges: 1) designing and evaluating radiotheranostics, and 2) understanding radiocontamination in the event of a nuclear disaster.Radiotheranostics for cancer diagnosis is a dynamic approach to dually diagnose and treat malignancies with a pair of tandem radioisotopes. An alternative approach to a targeting system is herein explored through the development of siderocalin-Trastuzumab fusion proteins, where the Scn protein is fused with HER2+ targeting antibody trastuzumab. We demonstrate the efficacy of the tetravalent theranostic metal pair 227 Th (therapy, α, t 1/2 =10 d) and 89 Zr (imaging, β +, t 1/2 = 78 hr). In addition to radiotheranostics, we investigate the decontamination of radiometals after inhalation. The hydroxypyridinone chelator HOPO demonstrates prophylactic efficacy in mice contaminated with Am-241.

Bio: Alexia Cosby graduated with a B.S. in Chemistry in 2017 from the University of Oregon after conducting research under Darren Johnson and Jim Hutchison. She then pursued a Chemistry Ph.D. at Stony Brook University under Eszter Boros. Her dissertation focused on utilizing luminescent lanthanides toward designing bimodal cancer imaging agents, using the phenomenon of Cherenkov radiation. Following graduation in November 2021, Cosby started her postdoctoral research in actinide chemistry with Rebecca Abergel at Lawrence Berkeley National Lab. Her postdoc research has focused on working with actinides in the context of in vivo decorporation and developing theranostic models with 89 Zr and 227 Th. Cosby intends to find a faculty position to continue studying the imaging and treatment of cancers using fundamental coordination chemistry.