UCSF tests first PET tracer aimed at astrocytes, not amyloid or tau, in dementia

A first-in-human trial at the University of California, San Francisco is imaging a glutamate transporter found mainly on astrocytes, the brain's support cells, to see whether it can flag changes in Alzheimer's disease and frontotemporal dementia before other markers shift. Published results so far cover safety alone.

The University of California, San Francisco is recruiting people ages 40 to 75, including healthy volunteers, for a first-in-human trial of [18F]RP-115, a PET imaging agent designed to bind EAAT2, the glutamate transporter found mainly on astrocytes rather than neurons. The study, registered on ClinicalTrials.gov as NCT05374278 and led by David Wilson of UCSF's Department of Radiology and Biomedical Imaging, is comparing tracer binding in people with Alzheimer's disease and frontotemporal dementia against age-matched cognitively normal controls. Its status was last verified as recruiting in April 2025, with an estimated total enrollment of 102 people and completion expected by May 2027.

EAAT2 clears more than 80 percent of the glutamate released at brain synapses and sits overwhelmingly on astrocytes, the star-shaped support cells that maintain the chemical environment around neurons. Researchers on the project have reported that EAAT2 is reduced in Alzheimer's disease and other neurodegenerative conditions, which is the rationale for testing whether a tracer that binds this transporter could reveal astrocyte changes earlier or differently than the amyloid, tau, and alpha-synuclein PET tracers already used in dementia research. No tracer targeting this transporter had previously been tested in people.

The only results published so far come from the trial's initial safety phase, not from the ongoing comparison in people with dementia. In a paper published online January 28, 2025 in Nuclear Medicine and Biology, UCSF researchers led by Chih-Kai Chao reported that eight healthy volunteers, aged 56 to 75, received an intravenous injection of [18F]RP-115 and underwent PET-MRI scanning over roughly 94 minutes across three sessions. The injections were well tolerated, with no adverse events reported within 48 hours, and the team used the radiation dose data to recommend an injected activity below 211 megabecquerels for future scans, in line with doses used for established tracers such as FDG.

Whether [18F]RP-115 can actually distinguish Alzheimer's disease or frontotemporal dementia from normal aging, or detect either condition before other biomarkers change, has not yet been reported. Those comparisons are the subject of the trial's ongoing diagnostic cohorts, which UCSF continues to recruit for as of this month.

Families should note this is an imaging research study, not a diagnostic test: it does not produce a result a clinician can use today to confirm or rule out any dementia. People interested in eligibility can find the trial's contact information through ClinicalTrials.gov or UCSF's clinical trials listing.