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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Alzheimer's disease | Active Comparator | Patients diagnosed with Alzheimer's disease |
|
| Mild Cognitive Impairment | Active Comparator | Patients diagnosed with Mild Cognitive Impairment |
|
| Parkinson's disease | Active Comparator | Patients diagnosed with Parkinson's disease |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [18F]MC225 | Drug | 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pascalle Mossel, Msc | Contact | +31503616161 | p.mossel@umcg.nl |
| Name | Affiliation | Role |
|---|---|---|
| Gert Luurtsema, Phd | University Medical Center Groningen | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Medical Center Groningen | Recruiting | Groningen | 9713GZ | Netherlands |
No IPD will be shared with other researchers
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| ID | Term |
|---|---|
| D019636 | Neurodegenerative Diseases |
| D000544 | Alzheimer Disease |
| D010300 | Parkinson Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D009422 | Nervous System Diseases |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C000621385 | MC225 compound |
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[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
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|
| D024801 |
| Tauopathies |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D003072 | Cognition Disorders |