PET tracer detects alpha-synuclein buildup in Parkinson’s brains
Imaging of protein may serve as a biomarker of the disease
A new positron emission tomography (PET) developed by Merck can enter the brains of people with Parkinson’s and highlight the toxic alpha-synuclein fibrils responsible for nerve cell loss, a small first-in-human study shows.
Working with the Michael J. Fox Foundation for Parkinson’s Research (MJFF), researchers recruited eight patients with mild to moderate Parkinson’s and four healthy older adults to have PET scans using [11C]MK-7337, a tracer that was able to detect a buildup of alpha-synuclein in regions of the brain affected by the disease.
Robert E. Drolet, PhD, senior principal scientist at Merck, presented the results, “First In Human Clinical Imaging with [11C]MK-7337, a Novel Alpha-Synuclein PET Ligand, in Idiopathic Parkinson’s Disease Patients,” at the International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders (AD/PD) 2025 in Vienna.
“Thanks to support from the Michael J. Fox Foundation for Parkinson’s Research, the headline from the research we presented at AD/PD 2025 is that we have succeeded in demonstrating proof-of-concept for imaging alpha-synuclein pathology in living Parkinson’s disease patients, potentially enabling a biomarker for Parkinson’s disease,” Jason Uslaner, PhD, vice president and head of neuroscience at Merck, wrote in an email to Parkinson’s News Today.
Diagnosing Parkinson’s can be challenging as no single test can accurately confirm the disease. Biomarkers could help detect the disease earlier, monitor its progression, and assess treatment effectiveness. They could also enhance the design of clinical trials, leading to better research outcomes.
“This is a critical unmet need and as the research progresses, we hope that we can improve our understanding of Parkinson’s disease biology, the selection of therapeutic targets, and our ability to execute in clinical trials,” Uslaner said.
A possible biomarker of Parkinson’s
[11C]MK-7337, is a radioactively labeled tracer that binds to toxic fibrils of alpha-synuclein, but not to normal monomers of the protein. In Parkinson’s, single units of alpha-synuclein, or monomers, begin to clump together into clusters that can spread to form long, thread-like fibers (fibrils).
To be used as a PET tracer, a small amount of [11C]MK-7337 is injected into the bloodstream and a scanner takes pictures of the body to show which tissues are taking up the tracer. Those where alpha-synuclein has built up as fibrils will take up the tracer and appear brighter than surrounding tissues.
Preclinical studies in mouse models of Parkinson’s show [11C]MK-7337 emits a robust signal in regions of the midbrain and brainstem, where fibrils of alpha-synuclein had formed. In studies with monkeys, the tracer entered the brain well and was cleared effectively by the body.
The first-in-human study included six men and two women, ages 63-84, diagnosed with idiopathic Parkinson’s, that is, of unknown cause, for at least three years. All tested positive for alpha-synuclein aggregates in the cerebrospinal fluid, which flows around the brain and spinal cord. Six had either no sense of smell, called anosmia, or a reduced ability to smell (severe miscrosmia), a common nonmotor symptom of Parkinson’s.
[11C]MK-7337 accumulated in the midbrain’s substantia nigra of six patients with reduced sense of smell and the brainstem of seven patients, including one with normal sense of smell. Parkinson’s occurs when nerve cells in the substantia nigra degenerate, leading to symptoms associated with the disease.
In patients with a reduced sense of smell, [11C]MK-7337 accumulated in the olfactory epithelium, which houses the nerve cells that sense smell. These patterns weren’t observed in the healthy older adults, ages 61-76.
While the studies with monkeys showed some off-target binding of [11C]MK-7337 in some regions of the brain (the cortex, thalamus, and cerebellum), background binding in the midbrain and brainstem was low, suggesting the tracer could be a useful biomarker to detect disease-causing accumulation of alpha-synuclein in Parkinson’s.
The study was funded in part by an award from MJFF’s Ken Griffin Alpha-synuclein Imaging Competition.
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