[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
prof. dr. Koen Van Laere
113 participants
Jan 19, 2024
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria27
- 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.
- Clinically established or clinically probable MSA-P based on MDS diagnostic criteria.
- Previous abnormal \[18F\]-FE-PE2I PET or \[123I\]-FP-CIT SPECT scan.
- Ability to understand the patient information brochure and provide written informed consent.
- Dementia Due to Alzheimer's Disease:
- Age 50-85 years.
- Diagnosis of probable AD with evidence of the AD pathophysiological process.
- Ability to understand the patient information brochure and provide written informed consent.
- Dementia with Lewy Bodies:
- Age 50-85 years.
- Diagnosis of probable DLB.
- Previous abnormal \[18F\]-FE-PE2I PET or \[123I\]-FP-CIT SPECT scan.
- Ability to understand the patient information brochure and provide written informed consent.
Exclusion Criteria33
- 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:
- Neuropsychiatric diseases other than PD.
- Major internal medical comorbidity, especially diabetes or heart disease.
- White matter lesion load on FLAIR Fazekas score 2 or higher or other relevant MRI abnormalities.
- History of alcohol or drug abuse.
- Previous participation in research studies involving ionizing radiation.
- Contraindications for MR.
- Claustrophobia or inability to tolerate confinement during PET 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.
- Anticoagulant therapy.
- Multiple System Atrophy - Parkinsonian Variant:
- Same as for Parkinson's disease.
- Dementia Due to Alzheimer's Disease:
- Same as for Parkinson's disease.
- Dementia with Lewy Bodies:
- Same as for Parkinson's disease.
Interventions
\[18F\]-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).
\[18F\]-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
\[123I\]-MIBG SPECT/CT (low dose CT) will be performed at the local nuclear medicine department of each participating center. Injected activity: 111 MBq
\[18F\]-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.
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT06120049