Abstract
P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1 or ABCB1), is a transporter protein located at the blood-brain barrier. This transporter appears to play a significant role in the development of various neurodegenerative disorders, such as Alzheimer’s disease and Parkinson’s disease. Additionally, the transporter is involved in the uptake of various pharmaceuticals into the brain, and alterations in its function can lead to drug resistance or unwanted side effects. To evaluate the function of P-glycoprotein in vivo, Positron Emission Tomography (PET) imaging can be used. This imaging modality uses radioactively labeled substances to visualize processes within the human body. The novel PET tracer [18F]MC225 was developed to monitor P-gp function at the blood-brain barrier. This dissertation tested the [18F]MC225 in preclinical studies and clinical studies involving healthy volunteers and patients with Alzheimer’s disease (AD). Initially, methodological research was conducted to identify the appropriate model for quantifying tracer uptake in the brain. Subsequently, the selected model was used to investigate whether differences in P-gp function could be demonstrated with the new PET tracer. The outcomes of these studies are promising, with the key finding being the difference in brain uptake of [18F]MC225 between healthy volunteers and Alzheimer’s disease patients in a proof-of-concept study. Future research projects with [18F]MC225 can, based on the pharmacokinetic studies conducted in this dissertation, adequately quantify P-gp function at the human blood-brain barrier.
Original language | English |
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Qualification | Doctor of Philosophy |
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Award date | 14-Oct-2024 |
Place of Publication | [Groningen] |
DOIs | |
Publication status | Published - 2024 |