Investigating Actinium-225 Radiochemistry: A Step Towards Next-Generation Radiotherapy

The U.S. Department of Energy (DoE) highlighted potential applications of Actinium-225 (225Ac) in treating prostate cancer in 2018, opening a new era of alpha emitter-based targeted therapy. Alpha particle emitter, 225Ac has high linear energy transfer that leads to lethal double stranded DNA breaks that can effectively kill tumor cells. Additionally, 225Ac has a short path length (< 100 µm) in tissues, which confines the off-target toxicity. Therefore, developing targeted radiotherapy with 225Ac and exploring its applications in hard-to-treat cancers is timely and innovative, and brings strong impact to patients suffering from untreatable tumors that cannot be completely removed by surgical resection and are resistant to frontline chemo- and immuno-therapies.
We propose to investigate the feasibility of targeted 225Ac radiotherapy in immune-evasive metastatic ovarian cancer via a highly collaborative multidisciplinary study that will design and systematically characterize novel 225Ac-labeled antibody-based probes and evaluate their anti-tumor efficacy in vitro and in vivo. This project aligns with University’s four strategic goals: 1) the proposed work will set important guidelines for future research on targeted alpha radiotherapy at the University of Utah as well as the scientific community; 2) students involved in this study will gain unique experience and skillset by conducting interdisciplinary research and publishing high-profile papers; 3) this work engages multidisciplinary research community including radiology, biotechnology, chemistry, and cancer therapy to build an inclusive team to eventually benefit clinical management of refractory cancers; 4) this work will contribute to the University’s long-term visibility. To achieve these goals, we have established a new cross-campus collaboration between the School of Medicine (Dr Sixiang Shi), College of Engineering (Dr Tara Mastren) and College of Pharmacy (Dr Shreya Goel).