Summary: Researchers have developed a new PET radiotracer, ¹⁸F-PDE-1905, that produces high-resolution images of neuroinflammation by binding directly to phosphodiesterase 4B (PDE4B), an enzyme inside microglia—the brain’s resident immune cells. Unlike conventional tracers that target broad downstream markers, this tracer focuses on a specific intracellular regulator of inflammatory signaling, offering a more targeted view of microglial activation.
In preclinical mouse models of Parkinson’s disease and multiple sclerosis, ¹⁸F-PDE-1905 produced clearer images and showed wider brain distribution compared with a standard TSPO-targeting tracer. These results suggest the tracer could improve early detection and monitoring of neuroinflammatory processes in conditions such as Alzheimer’s disease, ALS, Parkinson’s disease, and multiple sclerosis, and support the development of more personalized therapeutic strategies.
Key Facts:
- New Target: ¹⁸F-PDE-1905 selectively targets PDE4B, a key enzyme involved in microglial inflammatory signaling.
- Superior Imaging: In animal studies, the tracer delivered higher image clarity and broader brain coverage than conventional TSPO tracers.
- Clinical Potential: The tracer may enable earlier diagnosis, more precise monitoring of treatment response, and individualized care for neurodegenerative and neuroinflammatory disorders.
Source: SNMMI
Overview: A newly developed PET radiotracer, ¹⁸F-PDE-1905, has demonstrated the ability to visualize active neuroinflammation with improved specificity and image quality, according to research presented at the Society of Nuclear Medicine and Molecular Imaging (SNMMI) 2025 Annual Meeting. The tracer targets PDE4B, an intracellular enzyme that modulates inflammatory responses in microglia, providing an upstream marker of immune activation in the central nervous system.
Neuroinflammation—immune activation within the brain and spinal cord triggered by infection, toxic buildup, injury, or chronic disease—is a major contributor to the progression of many neurological and psychiatric disorders. Accurate imaging of neuroinflammation is critical for early diagnosis, for tracking disease progression, and for evaluating therapeutic responses in clinical and research settings.
“Current clinical PET imaging for neuroinflammation primarily uses tracers that bind to TSPO, a downstream marker that is expressed in multiple cell types,” said Jiahui Chen, PhD, associate scientist in the Department of Radiology and Imaging Sciences at Emory University School of Medicine in Atlanta, Georgia. “Our study introduces ¹⁸F-PDE-1905, a tracer designed to directly target PDE4B, which sits upstream within microglial inflammatory signaling pathways and offers a more specific window into microglial activation.”
The research team first used bioinformatics to analyze genomics databases and assess PDE4B expression across neuroinflammatory diseases. These analyses identified elevated PDE4B expression in both Parkinson’s disease and multiple sclerosis patient samples as well as in corresponding mouse models, supporting PDE4B as a meaningful imaging target.
Next, investigators developed mouse models of neuroinflammation and performed dynamic PET imaging with ¹⁸F-PDE-1905 alongside the TSPO-specific tracer ¹⁸F-D2-LW223. Follow-up biochemical and histological analyses confirmed that increased PDE4B protein expression correlated with the PET signal, strengthening the link between tracer uptake and microglial inflammatory activity.
PET scans in diseased mice revealed significantly higher uptake of ¹⁸F-PDE-1905 compared with healthy controls, consistent with increased neuroinflammatory activity. When directly compared to the TSPO tracer ¹⁸F-D2-LW223, ¹⁸F-PDE-1905 produced images with greater clarity and a broader distribution across affected brain regions, highlighting its potential to detect inflammation earlier and with improved spatial resolution.
“By directly targeting PDE4B, ¹⁸F-PDE-1905 provides a more specific and upstream measure of microglial activation—an early and critical feature in the pathophysiology of many neurodegenerative diseases,” Chen said. “For patients, this could translate to earlier and more accurate diagnoses, more reliable monitoring of treatment effects, and the ability to tailor therapies based on direct measures of neuroinflammation.”
The investigators emphasize that these findings are preclinical and were presented as part of the SNMMI 2025 Annual Meeting. Further studies, including additional preclinical validation and eventual clinical translation, will be necessary to determine how ¹⁸F-PDE-1905 performs in humans and whether it can be integrated into diagnostic and therapeutic workflows for disorders characterized by neuroinflammation.
About this neuroinflammation and neuroimaging research news
Author: Rebecca Maxey
Source: SNMMI
Contact: Rebecca Maxey – SNMMI
Image: The image is credited to Neuroscience News
Original Research: The findings were presented at the Society of Nuclear Medicine and Molecular Imaging 2025 Annual Meeting