Ultra-High Resolution PET in 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

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.

Study Overview

• Status: Recruiting
• Conditions: MSA - Multiple System Atrophy; Dementia With Lewy Bodies (DLB); Alzheimer Dementia (AD); PSP - Progressive Supranuclear Palsy; ALS With Frontotemporal Dementia (ALS/FTD); Parkinson s Disease; REM Sleep Behavior Disorder (iRBD); ALS - Amyotrophic Lateral Sclerosis; Adult Onset Psychotic Disorder; Very Late Onset Psychotic Disorder
• Intervention / Treatment: Other: UHR PET/CT scan of the brain with ¹⁸F-FDG; Other: UHR PET/CT scan of the brain with ¹⁸F-PE2I; Other: UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1; Other: UHR PET/CT scan of the brain with ¹⁸F-MK6240; Other: 3T MRI imaging of the brain

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Koen Van Laere, Prof. Dr.; Phone Number: +32 16 34 37 11; Email: koen.vanlaere@uzleuven.be
• Study Contact Backup: Name: Francine Reniers; Phone Number: +32 16 34 37 15; Email: francine.reniers@uzleuven.be

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • Recruiting
      • UZ Leuven
      • Contact: Koen Van Laere, Prof. Dr.; Phone Number: +32 16 34 37 11; Email: koen.vanlaere@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healthy controls; Participants in this arm are healthy controls undergoing ultra-high-resolution (UHR) PET imaging on the NeuroEXPLORER system using multiple radiotracers (¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240), in combination with 3T MRI. No therapeutic intervention is administered.	Other: UHR PET/CT scan of the brain with ¹⁸F-FDG; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-FDG radiotracer to assess glucose metabolism; Other: UHR PET/CT scan of the brain with ¹⁸F-PE2I; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-PE2I radiotracer to assess dopaminergic activity; Other: UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-SynVesT-1 radiotracer to assess synaptic density; Other: UHR PET/CT scan of the brain with ¹⁸F-MK6240; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-MK6240 radiotracer to assess neurofibrillary tangles; Other: 3T MRI imaging of the brain; 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.
Other: Patient with aMCI; Participants in this arm are patients with biomarker-confirmed amnestic mild cognitive impairment due to Alzheimer's disease undergoing UHR PET imaging using ¹⁸F-FDG and ¹⁸F-MK6240, in combination with 3T MRI. No therapeutic intervention is administered.	Other: UHR PET/CT scan of the brain with ¹⁸F-FDG; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-FDG radiotracer to assess glucose metabolism; Other: UHR PET/CT scan of the brain with ¹⁸F-MK6240; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-MK6240 radiotracer to assess neurofibrillary tangles; Other: 3T MRI imaging of the brain; 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.
Other: Patients with ALS/ALS-FTD; Participants in this arm are patients within the ALS and ALS-FTD spectrum undergoing UHR PET imaging using ¹⁸F-FDG, with a subgroup additionally undergoing ¹⁸F-SynVesT-1 PET, in combination with 3T MRI. No therapeutic intervention is administered.	Other: UHR PET/CT scan of the brain with ¹⁸F-FDG; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-FDG radiotracer to assess glucose metabolism; Other: UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-SynVesT-1 radiotracer to assess synaptic density; Other: 3T MRI imaging of the brain; 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.
Other: Patients with movement disorders; Participants in this arm include patients with Parkinson's disease, atypical parkinsonism, dementia with Lewy bodies or idiopathic REM sleep behavior disorder undergoing UHR PET imaging using ¹⁸F-FDG, ¹⁸F-PE2I and ¹⁸F-SynVesT-1, in combination with 3T MRI. No therapeutic intervention is administered.	Other: UHR PET/CT scan of the brain with ¹⁸F-FDG; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-FDG radiotracer to assess glucose metabolism; Other: UHR PET/CT scan of the brain with ¹⁸F-SynVesT-1; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-SynVesT-1 radiotracer to assess synaptic density; Other: 3T MRI imaging of the brain; 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.
Other: Patients with psychotic disorders; Participants in this arm are patients with adult-onset or very late-onset psychotic disorders undergoing UHR PET imaging using ¹⁸F-FDG, in combination with 3T MRI. No therapeutic intervention is administered.	Other: UHR PET/CT scan of the brain with ¹⁸F-FDG; Ultra-high-resolution PET/CT imaging of the brain on the NeuroEXPLORER system using ¹⁸F-FDG radiotracer to assess glucose metabolism; Other: 3T MRI imaging of the brain; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volume distribution (mL/cm³) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240	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).	Through study completion, an average of 4 year
Standardized uptake value ratios (SUVR) in small brain nuclei of tracers ¹⁸F-FDG, ¹⁸F-PE2I, ¹⁸F-SynVesT-1 and ¹⁸F-MK6240	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).	Through study completion, an average of 4 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between regional PET tracer uptake and cognitive performance	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)	Through study completion, an average of 4 year
Correlation between regional PET tracer uptake and motor and functional impairment	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)	Through study completion, an average of 4 year

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• Li H, Badawi RD, Cherry SR, Fontaine K, He L, Henry S, Hillmer AT, Hu L, Khattar N, Leung EK, Li T, Li Y, Liu C, Liu P, Lu Z, Majewski S, Matuskey D, Morris ED, Mulnix T, Omidvari N, Samanta S, Selfridge A, Sun X, Toyonaga T, Volpi T, Zeng T, Jones T, Qi J, Carson RE. Performance Characteristics of the NeuroEXPLORER, a Next-Generation Human Brain PET/CT Imager. J Nucl Med. 2024 Aug 1;65(8):1320-1326. doi: 10.2967/jnumed.124.267767.
• Omidvari N, Shanina E, Leung EK, Sun X, Li Y, Mulnix T, Gravel P, Henry S, Matuskey D, Volpi T, Jones T, Badawi RD, Li H, Carson RE, Qi J, Cherry SR. Quantitative Accuracy Assessment of the NeuroEXPLORER for Diverse Imaging Applications: Moving Beyond Standard Evaluations. J Nucl Med. 2025 Jan 3;66(1):150-157. doi: 10.2967/jnumed.124.268309.

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: January 16, 2026
• First Submitted That Met QC Criteria: March 27, 2026
• First Posted (Actual): April 3, 2026

Study Record Updates

• Last Update Posted (Actual): April 3, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Schizophrenia; Amyotrophic Lateral Sclerosis; Dementia; Multiple System Atrophy; Psychotic disorders; Dementia with Lewy Bodies; Alzheimer´s disease; PET/CT scan; Progressive supranuclear palsy; Locus coeruleus; Parkinson´s disease; Papez circuit; REM sleep behavior disorders; ALS with frontotemporal dementia; UHR PET; Thalamic subnuclei
• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neuromuscular Diseases; Metabolic Diseases; Neurocognitive Disorders; Eye Diseases; Tauopathies; Neurodegenerative Diseases; Sleep Wake Disorders; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Cranial Nerve Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Primary Dysautonomias; Autonomic Nervous System Diseases; Motor Neuron Disease; Ophthalmoplegia; Ocular Motility Disorders; Paralysis; Parasomnias; Hypotension; REM Sleep Parasomnias; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Schizophrenia; Psychotic Disorders; Alzheimer Disease; Parkinson Disease; Amyotrophic Lateral Sclerosis; Multiple System Atrophy; Shy-Drager Syndrome; Dementia; Supranuclear Palsy, Progressive; Lewy Body Disease; REM Sleep Behavior Disorder
• Other Study ID Numbers: S71328

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No