NCT06120049

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

Prospective Head-to-head Comparison of Cardiac [18F]-MFBG PET Versus [123I]-MIBG SPECT in the Differentiation Between Parkinson's Disease and Multiple System Atrophy and Between Dementia With Lewy Bodies and Alzheimer's Disease

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 113 (estimated)
• Sponsor: prof. dr. Koen Van Laere · Academic / Other
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Accepted

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.

Detailed description

Study Rationale: This prospective study, to be conducted in two centers (UZ Leuven and UZ Gent), aims to validate cardiac \[18F\]-MFBG PET in distinguishing Parkinson's disease (PD) from multiple system atrophy (MSA-P) and differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Both PD and DLB, caused by alpha-synuclein deposits (Lewy bodies), exhibit not only nigrostriatal dopaminergic deficits but also early peripheral changes in myocardial norepinephrine (NE) innervation. These defects can be visualized and quantified using NE transporter tracers. \[18F\]-MFBG was developed several years ago with high-yield production and has already been employed in multiple centers worldwide, mainly in the context of imaging neuroendocrine tumors. \[18F\]-MFBG offers logistical, technical, and pharmacological advantages, including faster scanning, high spatial resolution, and improved quantification compared to the existing method using \[123I\]-MIBG SPECT. Participant Population: The study will include 28 healthy volunteers (CON), of which 3 will participate in \[18F\]-MFBG PET dosimetry (part 1) and 25 in the main study for optimization/age-dependence of cardiac \[18F\]-MFBG parameters (part 2). In part 3, 40 PD, 15 MSA-P, 15 DLB, and 15 AD patients with biomarker-confirmed diagnoses will be included. Total: 113 subjects. Intervention: All subjects will undergo three examinations in the main work packages (parts 2 and 3) dynamic cardiac \[18F\]-MFBG PET, with dynamic \[123I\]-MIBG SPECT as a comparator, as well as cerebral \[18F\]-PE2I PET. Endpoints: Primary: Non-inferiority in discriminating populations using \[18F\]-MFBG; Secondary: effect size, relationship between myocardial uptake and cerebral dopamine active transporter (DAT) changes, autonomic dysfunction, regional myocardial variation. Secondary: 1. Determine the effect size (ES) of the reduction in myocardial uptake of \[18F\]-MFBG in PD and DLB compared to \[123I\]-MIBG SPECT and \[123I\]-MIBG planar scintigraphy. 2. Identify any significant correlation between the reduction in myocardial uptake of \[18F\]-MFBG in PD and DLB and the reduction in \[18F\]-PE2I binding in early to moderate disease stages. 3. Assess the relationship between the reduction in myocardial uptake of \[18F\]-MFBG in PD and DLB and measures of autonomic dysfunction. 4. Examine the regional pattern of reduced \[18F\]-MFBG uptake in PD/DLB compared to controls, with an endpoint considered met if different regional segment scores are evident between PD/MSA-P or DLB/AD or subtypes of PD.

Conditions

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

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	[18F]-MFBG PET CT	\[18F\]-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).
DIAGNOSTIC_TEST	[18F]-FE-PE2I PET CT or PET MRI	\[18F\]-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
DIAGNOSTIC_TEST	[123I]-MIBG SPECT CT	\[123I\]-MIBG SPECT/CT (low dose CT) will be performed at the local nuclear medicine department of each participating center. Injected activity: 111 MBq
DIAGNOSTIC_TEST	[18F]-MFBG PET dosimetry scans	\[18F\]-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.

Timeline

• Start date: 2024-01-19
• Primary completion: 2026-07-01
• Completion: 2026-07-01
• First posted: 2023-11-07
• Last updated: 2025-02-06

Locations

2 sites across 1 country: Belgium