The glymphatic system plays a critical role in waste clearance from the brain, and its dysfunction has been implicated in neurodegenerative diseases such as Alzheimer’s. This thesis investigated the synthesis of 18F-Fluorodeoxysorbitol (18F-FDS) as a positron emission tomography (PET) tracer for assessing glymphatic clearance and compared different administration routes to identify the most effective and clinically translatable method.The synthesis of 18F-FDS from widely available 18F-FDG was achieved through a simple reduction reaction and confirmed by high-performance liquid chromatography (HPLC). The product exhibited high stability and purity, making it a viable candidate for glymphatic imaging. PET imaging was employed to assess glymphatic clearance in both young and aged rat models following intrathecal (IT) and intranasal (IN) administration of 18F-FDS. Results from IT administration in young animals showed significant clearance of the tracer, indicating rapid glymphatic activity, whereas aged animals exhibited severely diminished clearance, highlighting the age-related decline in this system. The study also explored the potential of IN administration as a non-invasive alternative to IT injections. IN delivery through the nose-to-brain (N2B) pathway was compared to intravenous (IV) and IT administration, with IN showing the highest levels in the brain. Despite variability in early IN experiments, this method holds promise for clinical translation due to its non-invasive nature and desirable brain delivery. 18F-FDS demonstrated significant potential as a PET tracer for glymphatic clearance studies, particularly in identifying age-related changes in brain function. Future research should focus on refining IN administration techniques and exploring its application in clinical settings for the early detection and monitoring of neurodegenerative diseases.
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