TAT-11: Pretargeted Ac-225 Radioimmunotherapy Strategies

Ottawa, ON, Canada (UroToday.com) In more traditional targeted therapy, the radioisotope is bound to a chelating agent that is then linked to an antibody expressed by the tumor of interest. The antibody piece attaches to the tumor receptor to deliver the dose. In contrast, Dr. Lewis described the process of "click-pair" chemistry. Here the chelate and antibody are chosen such the link can be formed in vivo without catalysts. The labeled molecule "clicks" into the antibody piece while it is attached to the tumor. The whole point of what seems like a more complicated method is that it allows for "pre-targeting."

In pre-targeting, the antibody is first injected to sufficient quantities to nearly saturate the receptors. After any excess antibodies have been rapidly cleared, the radiolabeled molecules are injected to click into the antibody at the site of the tumor. This technique was tried first with Lu177 conjugates, then Ac225 in mice. They observed comparable uptake compared with traditionally labeled injection.

Human trials will be starting soon.

Presented by: Jason S. Lewis, MD, Vice Chair for Research, Chief of the Radiochemistry and Imaging Sciences Service, and Director of the Radiochemistry and Molecular Imaging Probe Core Facility, Memorial Sloan Kettering Cancer Center

Written by: William Carithers, Lawrence Berkeley National Laboratory at the 11th International Symposium on Targeted Alpha Therapy (TAT-10)  April 1 - April 4, 2019 - Ottawa, ON, Canada