D-Amino Acid Oxidase Occupancy and Pharmacodynamic Effects of Luvadaxistat (TAK-831) in the Human Brain: A Combined PET and Functional MRI Study

Using multimodal PET/MRI to quantify DAAO target engagement and pharmacodynamic effects in healthy volunteers.

Authors: Eugenii A. Rabiner, Peter E. Cole, Frans van den Berg, Yvonne Lewis, Carlos Coello, Matthew B. Wall, Leonie Demetriou, Robert D. Newbould, James McGonigle, Marc Huiban, Cyril Plisson, Katharina Schaefer, Thomas Brown, Adam J. Schwarz, Jan Passchier, Roger N. Gunn and Johannes Tauscher.

Target engagement is a critical milestone in CNS drug development, providing evidence that a therapeutic reaches and modulates its intended biological target. In this study, researchers combined PET imaging with functional MRI to characterize brain distribution of the novel D-amino acid oxidase (DAAO) PET radioligand [¹⁸F]PGM299 and evaluate target occupancy following administration of the DAAO inhibitor luvadaxistat (TAK-831).

The study demonstrated dose-dependent DAAO occupancy in the human brain and showed corresponding modulation of brain activity during executive function tasks. These findings highlight the value of integrated molecular and functional imaging for confirming pharmacological target engagement and informing dose selection in early-phase CNS clinical development.

Download this poster to learn:

• How a first-in-human DAAO PET radioligand was used to quantify enzyme occupancy in vivo.
• How combined PET and functional MRI can assess both target engagement and downstream pharmacodynamic effects.
• How multimodal neuroimaging can support dose selection and de-risk early clinical CNS drug development.

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