[18F]-MFBG Versus [123I]-MIBG and [18F]-PE2I in PD vs. MSA and DLB vs. AD

NCT06120049 | Recruiting Phase 2

• 1 other identifier: S67620
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 2

Brief Summary

Study goal: The goal of this prospective head to head comparison is to evaluate the effectiveness of \[18F\]-MFBG PET in assessing cardiac innervation, comparing it with \[123I\]-MIBG SPECT The study's primary focus is on distinguishing between Parkinson's disease (PD) and multiple system atrophy (MSA), as well as between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Main questions:

• Feasibility: How well can \[18F\]-MFBG PET detect changes in myocardial uptake in PD and DLB compared to the expected normal values in healthy individuals and AD and MSA-P patients? How well can it differentiate between these groups based on the detected changes?
• Non-inferiority: Is \[18F\]-MFBG PET as accurate as \[123I\]-MIBG SPECT in distinguishing between PD and MSA-P, and between DLB and AD? Participant requirements: For the main study, participants will be required to visit the hospital for 3 or 4 appointments. During these visits, they will undergo a screening visit, MRI brain scan, a comprehensive neurological assessment, \[18F\]-PE2I PET, \[123I\]-MIBG SPECT, and \[18F\]-MFBG PET scans. Additionally, a separate dosimetry study will be conducted, involving healthy subjects who will visit the hospital for a screening visit and undergo \[18F\]-MFBG PET scans.

Conditions

Parkinson Disease; Dementia With Lewy Bodies; MSA - Multiple System Atrophy; Alzheimer Disease

Keywords

Parkinson Disease; Dementia with Lewy Bodies; MSA - Multiple System Atrophy; Alzheimer Disease; [18F]-MFBG; [18F]-PE2I; [123I]-MIBG; Positron emission tomography; PET; Single photon emission tomography; SPECT; Autonomic dysfunction; Cardiac innervation; Brain DAT; Dosimetry; Kinetic modelling; Differential diagnosis; Dementia; Parkinsonism; Nuclear imaging; Neurology; Movement disorders; Prospective

Outcome Measures

Primary Outcomes (1)

• Difference in diagnostic accuracy between [18F]-MFBG and [I123]-MIBG

  Diffirence in diagnostic accuracy ((sensitivity) (prevalence) + (specificity) (1 - prevalence)) of \[18F\]-MFBG versus \[I123\]-MIBG in differentiating PD versus MSA-P and LBD versus AD. The index test is semi-quantitative analysis or visual inspection of the change in myocardial uptake of the tracer. Semi-quantitative analysis will be based on \[18F\]-MFBG myocardial volume of distribution (VT) in L/kg, early and late standardized uptake volume (SUV) in g/ml , heart-to-mediastinum ratio (HRM), and washout ratio (WR) as a percentage. The reference test is the previously established clinical diagnosis.

  Diagnostic accuracy will be calculated when the scans of the PD and MSA panels have been completed and again when scanning of DLB and AD panels has been completed (estimated 3 years after study start).

Secondary Outcomes (4)

• Effect size

  Effect size will be calculated when all scans have been completed (estimated 3 years after study start).

• Relation to brain DAT

  The relation to brain DAT will be calculated when the scans of PD, DLB and HC groups have been completed (estimated 3 years).

• Correlation of myocardial uptake of [18F]-MFBG to autonomic dysfunction

  The relation to autonomic dysfunction will be calculated when the scans of PD and DLB patients have been completed (estimated 2 years after study start)..

• Utility of regional myocardial parameter variation

  The regional myocardial parameter variation will be calculated when the scans of patient groups have been completed (estimated 3 years after study start).

Study Arms (4)

Healthy controls (part 2)

EXPERIMENTAL

25 healthy subjects (5 young 20-40y and 20 between 50-85y) will be enrolled for the head-to-head comparison with \[18F\]-MFBG, \[123I\]-MIBG and \[18F\]-FE-PE2I (Part 2). In 5 healthy controls, arterial sampling will be carried out for kinetic modelling.

Diagnostic Test: [18F]-MFBG PET CT; Diagnostic Test: [18F]-FE-PE2I PET CT or PET MRI; Diagnostic Test: [123I]-MIBG SPECT CT

PD vs MSA cohort (part 3a)

EXPERIMENTAL

In total, 40 PD patients will be included. In order to determine relationships with disease progression, two subgroups will be included with disease duration up to 5 years and 5 years or more respectively. In total, 15 MSA-P patients will be enrolled. For both groups, abnormal previous \[18F\]-FE-PE2I or \[123I\]-FP-CIT SPECT scan is required. Head-to-head comparison with \[18F\]-MFBG, \[123I\]-MIBG and \[18F\]-FE-PE2I (Part 3).

Diagnostic Test: [18F]-MFBG PET CT; Diagnostic Test: [18F]-FE-PE2I PET CT or PET MRI; Diagnostic Test: [123I]-MIBG SPECT CT

AD vs DLB cohort (part 3b)

EXPERIMENTAL

In total 15 patients with probable DLB (including biomarker selection through abnormal previous \[18F\]-FE-PE2I or \[123I\]-FP-CIT SPECT scan) and 15 patients with probable AD (including biomarker proven amyloid-beta positivity either by cerebrospinal fluid biomarker analysis or by \[18F\]-NAV4694 imaging as standard of care). Head-to-head comparison with \[18F\]-MFBG, \[123I\]-MIBG and \[18F\]-FE-PE2I (Part 3).

Diagnostic Test: [18F]-MFBG PET CT; Diagnostic Test: [18F]-FE-PE2I PET CT or PET MRI; Diagnostic Test: [123I]-MIBG SPECT CT

Dosimetry in healthy controls (Part 1)

EXPERIMENTAL

For dosimetry of \[18F\]-MFBG only, 3 subjects (18-80 y) will be enrolled (Part 1).

Diagnostic Test: [18F]-MFBG PET dosimetry scans

Interventions

[18F]-MFBG PET CT DIAGNOSTIC_TEST

\[18F\]-MFBG will be acquired at the Leuven University hospital on a GE MI4 PET/CT camera, with low dose CT and 120 MBq injected activity. Dynamic imaging between 0-60 minutes and 100-120 minutes (patients) and 0-70 minutes and 90-120 minutes (healthy volunteers). Venous sampling between 5-120 minutes will be obtained through a second catheter, 6 venous samples will be taken. In healthy up to 5 control subjects, full arterial sampling (0-120 minutes,) will also be done. If patient comfort allows, after the dynamic cardiac scan 2 hours post-injection field dynamic scan, a fast late timepoint whole body PET/CT will be taken (2 min/bed position, 11 mAs low dose CT; estimated 10-12 minutes).

AD vs DLB cohort (part 3b); Healthy controls (part 2); PD vs MSA cohort (part 3a)

[18F]-FE-PE2I PET CT or PET MRI DIAGNOSTIC_TEST

\[18F\]-FE-PE2I will be performed at the University Hospital Leuven with the GE Signa simultaneous PET/MR with acquisition at 50-70 minutes postinjection or at the University Hospital in Gent using a Siemens PET/CT, GE MI4 PET/CT. Injected activity: 120 MBq

AD vs DLB cohort (part 3b); Healthy controls (part 2); PD vs MSA cohort (part 3a)

[123I]-MIBG SPECT CT DIAGNOSTIC_TEST

\[123I\]-MIBG SPECT/CT (low dose CT) will be performed at the local nuclear medicine department of each participating center. Injected activity: 111 MBq

AD vs DLB cohort (part 3b); Healthy controls (part 2); PD vs MSA cohort (part 3a)

[18F]-MFBG PET dosimetry scans DIAGNOSTIC_TEST

\[18F\]-MFBG will be acquired at the Leuven University hospital on a Siemens Truepoint or GE MI4 PET/CT camera or equivalent newer camera, with low dose CT and 120 MBq injected activity. Three segments of consecutive whole-body scanning with increasing bed position duration will be carried out up to 3 half-lives (physical half-life T1/2 for 18F = 110 minutes): from 0-90 minutes (scan 1-8), 120-150 (scan 9) and 300-330 (scan 10) minutes post injection. In total 10 whole body biodistribution scans will be taken. Urine will be collected and its total activity measured to measure bladder excretion for correction of integrated bladder organ residence. Before each segment, a low dose whole body CT scan (11 mAs) will be acquired for attenuation correction and organ delineation.

Dosimetry in healthy controls (Part 1)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Controls:
• Voluntary written informed consent.
• Use of highly effective methods of birth control.
• Age between 18 and 85 years.
• Good health based on medical history, physical examination, clinical laboratory tests, and urinalysis.
• No history or evidence of major neurological, internal, or psychiatric disorders.
• Normal structural MRI scan for subjects \< 60 years or minor lesions for subjects \>= 60 years.
• Parkinson's Disease:
• Age 45-85 years.
• Clinically established PD based on Movements Disorder Society diagnostic criteria.
• Disease duration since onset of motor symptoms: 5 years or longer for one group and less than 5 years for another.
• Previous abnormal \[18F\]-FE-PE2I PET or \[123I\]-FP-CIT SPECT scan.
• Ability to understand the patient information brochure and provide written informed consent.
• Multiple System Atrophy - Parkinsonian Variant:
• Age 45-85 years.

You may not qualify if:

• Healthy controls:
• Major diseases that may interfere with the investigations.
• Evidence of cognitive impairment.
• History or evidence of psychiatric disease.
• Use of illicit drugs or history of drug or alcohol abuse.
• Chronic medication interfering with cardiac neuronal norepinephrine transporter (NET) or \[18F\]-FE-PE2I imaging.
• Exposure to ionizing radiation \> 1 mSv in other research studies within the last 12 months.
• Contraindication for MRI scanning.
• Claustrophobia or inability to tolerate confinement during PET-MRI scanning.
• Unwillingness to avoid strenuous physical activity.
• Lack of understanding of the study procedures.
• Pregnancy or breastfeeding.
• Lack of agreement to communicate incidental findings to the general practitioner.
• Abnormal Allen test or lidocaine hypersensitivity/allergy for subjects willing to undergo arterial sampling.
• Parkinson's Disease:

Sponsors & Collaborators

• prof. dr. Koen Van Laere: lead
• University Hospital, Ghent: collaborator
• Fund for Scientific Research, Flanders, Belgium: collaborator
• KU Leuven: collaborator
• Universitaire Ziekenhuizen KU Leuven: collaborator

Study Sites (2)

UZ Ghent

Ghent, Gent, 9000, Belgium

RECRUITING

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

RECRUITING

Related Publications (1)

• Versweyveld L, Delva A, Cohilis M, Deroose CM, Van Weehaeghe D, Koole M, Vandenberghe W, Van Laere K. [18F]MFBG PET/CT imaging of myocardial sympathetic innervation in healthy controls and patients with parkinson's disease: dosimetry and pharmacokinetics. Eur J Nucl Med Mol Imaging. 2026 Jan;53(2):1103-1112. doi: 10.1007/s00259-025-07517-3. Epub 2025 Sep 9.

  PMID: 40924149 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Lewy Body Disease; Shy-Drager Syndrome; Alzheimer Disease; Primary Dysautonomias; Dementia; Parkinsonian Disorders; Movement Disorders

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Synucleinopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Multiple System Atrophy; Autonomic Nervous System Diseases; Hypotension; Vascular Diseases; Cardiovascular Diseases; Tauopathies

Study Officials

• Koen Van Laere

  Professor at KULeuven, department head of nuclear medicine at UZ Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Koen Van Laere, Prof. dr.

CONTACT

+3216343715; koen.vanlaere@UZLeuven.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Nuclear Medicine, professor, Principal Investigator

Model Details: Prospective head-to-head comparison with 5 subject panels (healthy controls, Parkinson's disease, Multiple System Atrophy, Dementia with Lewy Bodies and Alzheimer's disease). The main study is a prospective diagnostic study in three cohorts (1/ CON, 2/ PD vs. MSA-P, 3/ DLB vs AD). The study in healthy controls is designated part 2. The study in patients is designated part 3. There is a seperate dosimetry study, designated as part 1.

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: November 7, 2023
• Study Start: January 19, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

BE (2)