[18F]MC225-PET in Neurodegenerative Disease

Study Overview
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Brief Summary
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P-glycoprotein, an efflux transporter at the blood-brain barrier plays an important role in de development of neurodegenerative disease. A novel PET tracer ([18F]MC225) was developed to measure the function of P-glycoprotein and was tested with succes in healthy volunteers. This study aims to evaluate [18F]MC225 in neurodegenerative disease.

Detailed Description
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A decrease in P-glycoprotein (P-gp) function is associated with the onset of neurodegenerative disease. New treatment strategies in neurodegenerative disease, including Parkinson's disease and Alzheimer's disease, aim to restore the P-gp function. To evaluate the effect of these potential therapies, measurement of the P-gp function is necessary. Up until now [11C]verapamil is considered to be the gold standard to measure P-gp function. However tracer uptake in the brain of [11C]verapamil is too low for adequate measurement of treatment effect, especially of restoring P-gp function. A novel PET tracer to measure P-gp function, [18F]MC225, has the potential advantage of higher brain uptake values at baseline and might therefore able to measure both up- and down regulation P-gp function. [18F]MC225 was recently studied in healthy volunteers and a method to quantify P-gp function was developed. This study aims to evaluate [18F]MC225 to measure P-gp function in neurodegenerative disease. To this aim 10 MCI patients, 10 patients with Alzheimer's disease and 10 Parkinson's disease patients will be included and undergo one 60 min dynamic [18F]MC225 PET scan, combined with a 10 min [15O]H2O PET. Tracer uptake values (Vt) and influx (K1) in several brain regions of interest, representing local P-gp function will be compared with the [18F]MC225 uptake values in the brain of healthy volunteers obtained in a previous study.

Official Title
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Evaluation of [18F]MC225-PET to Measure P-glycoprotein Function in Neurodegenerative Disease

Conditions
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Neurodegenerative Diseases, Alzheimer Disease, Parkinson Disease, Mild Cognitive Impairment

Intervention / Treatment
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* Drug: [18F]MC225


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is diagnosed with Alzheimer's disease, Parkinson's disease or Mild Cognitive Impairment Exclusion Criteria: Use of any medication influencing the P-glycoprotein function History of neuropsychiatric disorders Contra-indications MRI Allergy contrast agent

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: [18F]MC225 is administrated to patients in three groups to evaluate the P-glycoprotein function in these groups and compare the results with the P-gp function of healthy volunteers obtained in a previous study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Alzheimer's disease<br>Patients diagnosed with Alzheimer's disease | Drug: [18F]MC225<br>* All participants will undergo a PET scan with [18F]MC225. No pharmaceutical effects are expected and the study will exclusively have a diagnostic purpose. However, since [18F]MC225 is a new PET tracer, it is included in pharmaceutical studies and any study performed with [18F]MC225 will be automatically be registered as intervention study.<br>|
| Active Comparator: Mild Cognitive Impairment<br>Patients diagnosed with Mild Cognitive Impairment | Drug: [18F]MC225<br>* All participants will undergo a PET scan with [18F]MC225. No pharmaceutical effects are expected and the study will exclusively have a diagnostic purpose. However, since [18F]MC225 is a new PET tracer, it is included in pharmaceutical studies and any study performed with [18F]MC225 will be automatically be registered as intervention study.<br>|
| Active Comparator: Parkinson's disease<br>Patients diagnosed with Parkinson's disease | Drug: [18F]MC225<br>* All participants will undergo a PET scan with [18F]MC225. No pharmaceutical effects are expected and the study will exclusively have a diagnostic purpose. However, since [18F]MC225 is a new PET tracer, it is included in pharmaceutical studies and any study performed with [18F]MC225 will be automatically be registered as intervention study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| P-glycoprotein function | The function of P-glycoprotein at the blood-brain barrier measured by PET tracer-uptake (volume of distribution) in the brain | 60 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET, pharmacokinetic modeling, [18F]MC225