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NCT Number: NCT07509125

Ultra-High Resolution PET in Aging, Neurodegeneration and Psychotic Disorders

The goal of this study is to use ultra-high-resolution (UHR) PET imaging to better understand how the brain and spinal cord change in healthy aging and in neurological and psychiatric disorders such as Alzheimer's disease (AD), Parkinson's disease and related movement disorders, amyotrophic lateral sclerosis (ALS), and psychotic disorders. Researchers will use the NeuroExplorer PET/CT system, a new scanner that can show very small structures in the brain and spinal cord in much more detail than regular PET.

The main questions this study aims to answer are:

* How do small but important brain regions (like the locus coeruleus, substantia nigra, and thalamic nuclei) change in healthy aging? * What early brain changes occur in neurodegenerative and psychotic disorders, and can they help improve early diagnosis?

Participants will:

* Undergo PET and MRI brain scans using different tracers that measure brain metabolism (18F-FDG), synaptic density (¹⁸F-SynVesT-1), dopamine transporters (¹⁸F-PE2I), and tau protein buildup (¹⁸F-MK6240). * Complete cognitive and clinical assessments related to memory, mood, and motor or psychiatric symptoms, depending on their group.

This study will include healthy volunteers and patients with mild cognitive impairment due to Alzheimer´s disease, ALS, Parkinson's disease and related disorders, or psychotic disorders.

The results will help create detailed brain imaging maps for healthy aging and identify early biomarkers for different diseases to support better diagnosis and treatment in the future.

Recruiting

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Key information

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

UHR PET/CT scan of the brain with ¹⁸F-FDG

Other

Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-FDG radiotracer to assess glucose metabolism

UHR PET/CT scan of the brain with ¹⁸F-PE2I

Other

Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-PE2I radiotracer to assess dopaminergic activity

UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1

Other

Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-SynVesT-1 radiotracer to assess synaptic density

UHR PET/CT scan of the brain with ¹⁸F-MK6240

Other

Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-MK6240 radiotracer to assess neurofibrillary tangles

3T MRI imaging of the brain

Other

All participants will undergo 3T MRI, including T1- and FLAIR-weighted sequences for anatomical reference and white matter pathology, neuromelanin-sensitive imaging to assess SN and LC integrity, and multi-shell diffusion-weighted imaging (DWI) for white matter tractography.

Primary outcomes

  1. Volume distribution (mL/cm³) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240

    Time frame: Through study completion, an average of 4 year

    To evaluate the regional binding patterns in small brain nuclei using four PET tracers (18F-FDG, 18F-PE2I, 18F-SynVest-1, 18F-MK6240) in different subject groups (healthy controls and disease cohorts). Quantitative outcome metrics will include distribution volumes with and without partial volume correction (PVC).

  2. Standardized uptake value ratios (SUVR) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240

    Time frame: Through study completion, an average of 4 year

    To evaluate the regional binding patterns in small brain nuclei using four PET tracers (18F-FDG, 18F-PE2I, 18F-SynVest-1, 18F-MK6240) in different subject groups (healthy controls and disease cohorts). Quantitative outcome metrics will include standardized uptake value ratios (SUVR) with and without partial volume correction (PVC).

Secondary outcomes

  1. Correlation between regional PET tracer uptake and cognitive performance

    Time frame: Through study completion, an average of 4 year

    Quantitative PET measures (SUVR from ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVest-1, and ¹⁸F-MK6240) will be correlated with cognitive performance across disease cohorts.

    Cognitive outcomes will be assessed using standardized neuropsychological tests covering global cognition, memory, language, executive function, and attention.

    Examples include the Montreal Cognitive Assessment (MoCA) (0-30, a higher score indicating a better outcome), Boston Naming Test (BNT) (0-60, a higher score indicating a better outcome) and Raven's Coloured Progressive Matrices (RCPM) (0-24, a higher score indicating a better outcome)

  2. Correlation between regional PET tracer uptake and motor and functional impairment

    Time frame: Through study completion, an average of 4 year

    Quantitative PET measures (SUVR from ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVest-1, and ¹⁸F-MK6240) will be correlated with motor and functional outcome measures, including performance across disease cohorts. Cognitive outcomes will be assessed using standardized clinical rating scales such as the MDS-UPDRS (all items scored between 0-4, with a higher score indicative of a higher symptom severity)

Study contacts

Contact information is provided by the study sponsor or research team.

Francine Reniers

CONTACT

[email protected]

+32 16 34 37 15

Koen Van Laere, Prof. Dr.

CONTACT

[email protected]

+32 16 34 37 11

Sponsors and collaborators

Lead sponsor

Universitaire Ziekenhuizen KU Leuven

Other

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Apr 3, 2026
Registry last updated
Apr 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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