Targeted PET imaging of neuroinflammation in neuropsychiatric disorders using ergothioneine-based radioligand
A novel PET radioligand based on the antioxidant ergothioneine (ERGO) enables non-invasive imaging of neuroinflammation linked to neuropsychiatric disorders. The probe crosses the blood-brain barrier via the OCTN1 receptor and scavenges reactive oxygen species and transition metals implicated in amyloid aggregation.
Overview
This solution offers a novel PET imaging approach for visualizing neuroinflammation associated with neuropsychiatric disorders such as Alzheimer's disease. The technology centers on a carbon-11 labeled ergothioneine radioligand that targets oxidative stress pathways in the brain. Ergothioneine is a naturally occurring antioxidant with a unique dual capability: it scavenges both reactive oxygen species and transition metals, and it is actively transported into the brain via the OCTN1 receptor, bypassing the blood-brain barrier.
The value proposition for industry partners lies in obtaining a non-invasive imaging biomarker that can track disease progression and therapeutic response in neurodegenerative and psychiatric conditions. Preclinical studies in 5XFAD mouse models demonstrated that long-term ergothioneine treatment improved memory and cognition while significantly reducing amyloid plaque burden, suggesting the probe may also inform treatment monitoring strategies.
Technical specifications
- Novel radioligand: [11C]ERGO PET probe developed and characterized by the research team
- Dual-action mechanism: Scavenges reactive oxygen species and chelates transition metals associated with amyloid aggregation
- Brain delivery: Crosses the blood-brain barrier through receptor-mediated transport via the OCTN1 transporter, enabling effective brain uptake
- Tissue retention: Acts as an adaptive antioxidant, accumulating in tissues prone to inflammation for sustained signal
- Validated specificity: Tested in LPS-induced neuroinflammation models and 5XFAD Alzheimer's mouse models using [11C]ERGO alongside [11C]PIB and 18F-FDG probes for multimodal comparison
- Imaging modalities: Compatible with quantitative PET imaging workflows for small animal and translational studies
Technology readiness level
The technology has been validated at a preclinical level through multiple animal studies. Specificity testing was completed using an LPS neuroinflammation model, and a three-year treatment study in 5XFAD mice demonstrated both therapeutic effects of ergothioneine and the probe's ability to differentiate treated from untreated cohorts. The research team is seeking collaborations to advance quantitative PET imaging and analysis, particularly to enhance resolution for mouse brain imaging through AI-based approaches. The probe is ready for further co-development and translational validation partnerships.
About Vanderbilt University Medical Center
Vanderbilt University Medical Center is a large, independent academic medical center and health system in Nashville, uniting patient care, research, and training at scale. Co-located hospitals and research facilities give partners access to core labs, biobanking, advanced imaging, and secure, de‑identified EHR data resources. A centralized trials office, experienced contracting, and proximity to Nashville’s healthcare management cluster streamline multi-site studies and real‑world evidence work. Research is backed by competitive federal funding, led by NIH and complemented by DoD and CDC. A dedicated technology transfer office supports IP, licensing, and startup formation to accelerate clinical translation.
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