[18F]MC225-PET in Neurodegenerative Disease

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

PET, pharmacokinetic modeling, [18F]MC225

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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