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dc.contributor.authorFisher, Emily Mary
dc.date.accessioned2018-07-23T08:52:35Z
dc.date.available2018-07-23T08:52:35Z
dc.date.issued2019-01-25
dc.date.submitted2017-09-22
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/278393
dc.description.abstractPositron emission tomography (PET) is a non-invasive medical imaging technique that allows visualisation and quantification of biochemical, physiological and pharmacological processes in living subjects. This is achieved through application of radiotracers – compounds labelled with positron emitting radionuclides. Neurodegeneration is the progressive loss of neurons resulting in impairment of brain function leading to cognitive decline and can affect movement. The underlying pathology of many neurodegenerative diseases is misfolding of proteins such as α-synuclein, the key pathological hallmark of Parkinson’s disease. Also implicated in the processes of neurodegeneration is neuroinflammation, which is observed by the activation of microglia – the immune cells of the brain. Activation of microglia is associated with the upregulation of the 18 kDa mitochondrial translocator protein (TSPO). This work has involved the synthesis and characterisation of novel compounds that have the potential for being applied as radiotracers for imaging α-synuclein fibrils (project 1), or TSPO (project 2) via PET. Over the course of project 1 a library of compounds was synthesised based upon structural modifications of a lead structure identified from the literature. These compounds then underwent screening via biophysical methodologies in order to determine their affinity to α-synuclein fibrils. This stage of the work involved the development of a novel biophysical technique – microscale thermophoresis (MST). A general automated radiosynthetic method to afford the [18F]fluoro-derivatives of these compounds has also been developed, and preliminary in vitro autoradiography studies and an in vivo microPET scan has been performed. For project 2, an automated radiosynthetic method was developed to produce [18F]GE387, a lead compound identified through collaboration with GE Healthcare. This radiotracer has then been applied to preliminary in vitro autoradiography and an in vivo microPET study using rats with induced neuroinflammation alongside control rats.
dc.description.sponsorshipThe funding for this PhD project came from the MRC
dc.language.isoen
dc.rightsAll rights reserved
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectPositron emission tomography
dc.subjectPET
dc.subjectalpha-synuclein
dc.subjectsynuclein
dc.subjectα-synuclein
dc.subjectTSPO
dc.subjectradiolabelling
dc.subjectneurodegeneration
dc.titleDevelopment of PET Radiotracers for Imaging Neurodegeneration: Targeting alpha-Synuclein Fibrils and TSPO
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentDepartment of Clinical Neurosciences
dc.date.updated2018-07-22T11:19:54Z
dc.identifier.doi10.17863/CAM.25739
dc.publisher.collegeNewnham
dc.type.qualificationtitlePhD in Chemistry
cam.supervisorAigbirhio, Franklin
cam.thesis.fundingfalse
rioxxterms.freetoread.startdate2018-07-22


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