Ultra-high-resolution PET imaging of aging, neurodegeneration, and psychotic disorders

Ultra-High Resolution PET of the Human Brain and Spinal Cord in Healthy Aging, Dementia, Movement Disorders, ALS and Psychotic Disorders

We will test whether ultra-high-resolution PET and 3T MRI scans can reveal early brain and spinal cord changes in healthy adults and people with Alzheimer's, Parkinson's disease, ALS, PSP, REM sleep behavior disorder, or psychotic disorders.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 18 Years to 90 Years
• Sex: All
• Sponsor: Universitaire Ziekenhuizen KU Leuven (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Leuven, Vlaams-Brabant)
• Trial ID: NCT07509125 on ClinicalTrials.gov

What this trial studies

This single-center interventional imaging protocol uses the NeuroExplorer ultra-high-resolution PET/CT system together with 3T MRI to visualize very small brain and spinal cord structures in healthy volunteers and patients with neurodegenerative or psychotic conditions. Participants undergo multiple PET scans with tracers for metabolism (18F-FDG), synaptic density (18F-SynVesT-1), dopamine transporters (18F-PE2I), and tau (18F-MK6240), plus structural MRI. The study focuses on changes in small but important regions such as the locus coeruleus, substantia nigra, and thalamic nuclei across aging and disease. Imaging results will be compared across groups to identify patterns that could support earlier diagnosis and better characterization of disease processes.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–90 who are either healthy controls or have a diagnosis of Alzheimer dementia, Parkinson's disease, ALS, PSP, REM sleep behavior disorder, or a psychotic disorder and who can undergo multiple PET scans, MRI, and blood draws.

Not a fit: Participants should not expect direct therapeutic benefit from imaging-only procedures, and people who cannot tolerate PET/MRI, are pregnant, or have uncontrolled medical or psychiatric conditions are unlikely to benefit or to be eligible.

Why it matters

Potential benefit: If successful, this approach could allow earlier and more precise detection of neurodegenerative and psychiatric-related brain changes, which may help guide diagnosis and future treatments.

How similar studies have performed: Prior PET research using tracers such as 18F-FDG, 18F-SynVesT-1, 18F-PE2I, and 18F-MK6240 has shown informative disease-related signals, but using the NeuroExplorer ultra-high-resolution scanner to target tiny brainstem and thalamic nuclei is a relatively new approach.

Eligibility criteria

Inclusion Criteria:

* WP1: Healthy controls
* Age between 18 and 90 years old (15 aged 18-50 years and 25 aged 50 90 years);
* Subject is judged to be in good health by the investigator on the basis of medical history, physical examination including vital signs and clinical laboratory tests;
* No history or evidence of current major neurological, internal or psychiatric disorder, based on the medical assessment as described hereabove and neuropsychological assessment;
* No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline;
* In subjects \< 60 years of age, a normal structural MRI scan as assessed by expert radiologist.
* In subjects \>= 60 years of age white matter hyperintensities corresponding to a WML (white matter lesion) score \<= 2 (of 3) on the Age-Related White Matter changes scale are acceptable;
* When older than 50 years of age, the volunteer is willing to undergo a p- tau217 blood sample.
* WP2: Dementia
* Patient has a clinical diagnosis of biomarker-proven prodromal AD
* WP3: ALS spectrum
* Subject must meet El Escorial Criteria (30) and Awaji-Shima criteria (31) for at least possible ALS;
* WP4: Movement disorders
* (all): Patient (or legal representative, when applicable) is able to understand the patient information form and give written informed consent.
* Parkinson´s disease (PD):
* Patient has clinically established PD based on the Movement Disorder Society (MDS) diagnostic criteria (32);
* Patient has an abnormal 18F-PE2I PET;
* No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline.
* Multiple system atrophy (MSA)
* Patient has clinically established or clinically probable MSA-P based on the
* Movement Disorder Society (MDS) diagnostic criteria (33);
* Patient has an abnormal 18F-PE2I PET.
* Progressive supranuclear palsy (PSP)
* Patient has an abnormal 18F-PE2I PET;
* Patient has clinically established probable PSP according to the latest MDS criteria
* Dementia with Lewy bodies (DLB)
* Patient has probable DLB by consensus criteria (cognitive impairment MoCA \< 26 + visual hallucinations and/or fluctuating alertness);
* Patient has an abnormal 18F-PE2I PET.
* Idiopathic REM sleep behavior disorder (iRBD)
* Patient has Polysomnography-confirmed iRBD;
* No evidence of cognitive impairment as assessed by a Montreal Cognitive Assessment (MoCA) score of 26 or higher at baseline;
* No clinical evidence of parkinsonism at baseline.
* WP5: Psychosis
* DSM 5 criteria for a non-affective schizophrenia spectrum psychotic disorder;
* Age between 18 and 55 years old for adult-onset psychosis, onset of psychosis (and age) above 60 years old for very late onset psychosis.

Exclusion Criteria:

* Subject has a history of any major (other) internal, psychiatric or neurological disease that may interfere with the investigations (especially liver and kidney disease, uncontrolled diabetes, cancer, severe depression, stroke, severe TBI);
* Subject is currently a user (including recreational use) of any illicit drugs, including cannabis, or has a history of drug or alcohol abuse;
* Subject chronically uses medication that has central nervous system effects (e.g. strong painkillers such as opioids, neuroleptics,..; ) (other than prescribed for the illness in case of patients);
* Subject has had exposure to ionizing radiation (\> 1 mSv) in other research studies within the last 12 months;
* Subject has a contra-indication for MRI scanning;
* Subject suffers from claustrophobia or cannot tolerate confinement during PET-MRI scanning procedures; subject cannot lie still for (at least) 60 minutes inside the scanner;
* (For subjects with arterial sampling): The subject is hypersensitive to lidocaine (used for local anaesthesia during the placement of the arterial catheter), has an abnormal Allen test (a test to check blood flow in the arteries of the forearm) or is on anti-coagulant therapy;
* Subject (or his/her legal representative) does not understand the study procedures;
* Subject is unwilling or unable to perform all of the study procedures, or is considered unsuitable in any way by the principal investigator;
* Subject is potentially pregnant (hCG test can be done if doubt exists).

Where this trial is running

Leuven, Vlaams-Brabant

• UZ Leuven — Leuven, Vlaams-Brabant, Belgium (Recruiting)

Study contacts

• Study coordinator: Koen Van Laere, Prof. Dr.

Conditions Alzheimer Dementia; ALS - Amyotrophic Lateral Sclerosis; Parkinson s Disease; REM Sleep Behavior Disorder; PSP - Progressive Supranuclear Palsy; MSA - Multiple System Atrophy; Dementia With Lewy Bodies; ALS With Frontotemporal Dementia