NIH Brain-Scan Study Tests a New Tracer for a Suspected Inflammation Enzyme

Arecruiting study sponsored by the National Institute of Mental Health is testing whether a new imaging tracer can measure a protein tied to inflammation in the brains of people with Alzheimer disease or mild cognitive impairment. The goal is a measurement tool, not a cure.

That distinction matters. Before anyone can treat brain inflammation in Alzheimer's, researchers need a reliable way to see it in living people.

Our research desk flagged a Phase 1 study, enrollment 90, seeking people aged 50 and older with Alzheimer disease or mild cognitive impairment plus healthy volunteers. It uses PET imaging with an experimental tracer, 18F-PF974, alongside the amyloid tracer 18F-florbetaben. The stated aim is to determine whether the new tracer can measure PDE4B in the brain.

We confirmed the trial against its ClinicalTrials.gov record (NCT07169630): the National Institute of Mental Health as sponsor, Phase 1, 90 participants, ages 50 and older, and the two tracers named. The tracer's full name is [18F]PF-06445974, which earlier work from the same NIH group showed preferentially labels PDE4B.

That earlier work is real. Wakabayashi and colleagues reported the first-in-human evaluation of the tracer in 2022, imaging it successfully in five healthy volunteers. One limitation matters here: total distribution volume rose about 10 percent late in scans because a radiometabolite entered the brain, which bears on whether the tracer can measure PDE4B reliably. Separately, a 2024 conference abstract (SNMMI meeting, J Nucl Med vol 65, supplement 2) reported that in rats, tracer binding rose about 50 percent in a brain region after an inflammatory stimulus. The study is not peer-reviewed, so this is preliminary support for use as an inflammation marker. PDE4B itself breaks down cAMP, and drugs that block PDE4 enzymes, including PDE4B, are used against inflammation in psoriasis and COPD.

On dates, the registry lists an estimated primary completion of April 11, 2029 and an estimated study completion of April 11, 2030. Both are estimates and study milestones, not a promised date for published results.

Inflammation is a leading suspect in Alzheimer's, but studying it as a treatment target requires measuring the right biology in people. A validated PDE4B tracer could let researchers test whether this specific pathway is active in patients and whether anti-inflammatory drugs touch it.

This is a measurement study, not a trial showing that an anti-inflammatory treatment improves memory. Success would support further research into the suspected inflammatory process. It would not, by itself, establish that targeting the enzyme helps patients, and no results have been posted. The weakest link is the evidence for the tracer itself: the human data come from five healthy volunteers, and the inflammation signal comes from a non-peer-reviewed rat abstract.

• Whether the tracer reliably measures PDE4B in Alzheimer patients, not just healthy volunteers. • Posted results and any update to the estimated completion dates on the trial registry. • Any follow-on trial testing an anti-inflammatory therapy guided by this imaging.

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