Preclinical Evaluation of [¹⁸F]JNJ-1: A Novel PET Ligand Targeting AMPAR/TARP γ8

A new preclinical PET tracer demonstrates high specificity, robust target engagement, and translational potential for advancing CNS drug development.

Authors: Chunfang A. Xia, Wei Zhang, Tamara Berdyyeva, Chaofeng Huang, Michael K. Ameriks, Terry P. Lebold, Michael P. Maher, Cristian C. Constantinescu, Leslie Nguyen, Nyantsz Wu, Gang Chen, Hartmuth C. Kolb, Anna Katrin Szardenings

AMPA receptors play a critical role in excitatory neurotransmission, synaptic plasticity, learning, and memory. Dysregulation of AMPAR signaling has been implicated in numerous neurological and psychiatric disorders, making the AMPAR/TARP γ8 complex an attractive therapeutic target. However, the development of selective imaging biomarkers capable of measuring target engagement has remained a significant challenge.

This publication presents the development and preclinical evaluation of [¹⁸F]JNJ-1, a novel PET radiotracer designed to selectively image AMPAR/TARP γ8. Through in vitro characterization, autoradiography, biodistribution studies, rodent PET imaging, and non-human primate imaging, the study demonstrates strong binding affinity, high regional specificity, and dose-dependent receptor occupancy. These findings support the potential of [¹⁸F]JNJ-1 as a valuable translational imaging biomarker for CNS drug development and clinical dose optimization.

Perceptive Discovery collaborated on this research by providing advanced preclinical PET imaging expertise, including quantitative imaging and analysis in non-human primates. This work highlights our experience supporting the development and translational evaluation of novel CNS imaging biomarkers, helping sponsors generate the data needed to assess target engagement, receptor occupancy, and clinical translatability.

Read this publication to learn:

• How a novel PET tracer selectively targets AMPAR/TARP γ8 with high binding affinity and minimal off-target activity across multiple preclinical species.
• How quantitative PET imaging can measure receptor occupancy and target engagement, supporting dose selection and translational decision-making during CNS drug development.
• How integrated preclinical imaging approaches—including immunohistochemistry, autoradiography, biodistribution, rodent PET, and non-human primate imaging—provide comprehensive validation of novel neuroimaging biomarkers.