Synthesis and Evaluation of ¹⁸F-PGM028299: A Novel PET Ligand for In Vivo Delineation of D-Amino Acid Oxidase (DAAO)

Preclinical evaluation of a novel DAAO PET radiotracer supporting CNS drug development and therapeutic enzyme occupancy assessment.

Authors: Mayca Onega¹, Charlotte Fieldhouse², Sarah Almond², William Farnaby², Catrina Kerr², Rosa Fradley², Toshal Patel², Nicholas Keat¹, Christopher Coello¹, Sharon Ashworth¹, Sac-Pham Tang¹, Lisa A Wells¹, Jan Passchier¹, Giulia Boscutti¹, Eugenii Rabiner¹, Johannes Tauscher², David J Miller², Christophe Plisson¹

¹Perceptive Discovery

²Takeda Cambridge Ltd

Abnormal NMDA receptor signaling has been implicated in a range of CNS disorders, including schizophrenia, driving growing interest in therapeutic strategies targeting D-amino acid oxidase (DAAO). This poster highlights the synthesis and preclinical evaluation of ¹⁸F-PGM028299, a novel PET radiotracer developed for in vivo imaging of DAAO in the central nervous system.

The study demonstrates successful radiolabeling, favorable brain uptake, reversible pharmacokinetics, and strong target-specific binding in rodent models. Enzyme occupancy studies further showed dose-dependent displacement with luvadaxistat, supporting the tracer’s utility for evaluating therapeutic engagement and advancing translational CNS imaging research.

These findings support the continued clinical translation of ¹⁸F-PGM028299 as a promising tool for quantitative DAAO imaging and CNS drug development.

Download the poster to explore:

• Development and radiolabeling strategies for the novel DAAO PET tracer ¹⁸F-PGM028299
• Preclinical PET imaging, pharmacokinetic modeling, and target engagement findings
• Enzyme occupancy and displacement data supporting translational CNS imaging applications