Synthesis and biological evaluation of carbon-11 and fluorine-18 labelled P2X7-receptor ligands for diagnosis of neurological diseases using positron emission tomography
Neurodegenerative brain diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis are associated with progressive neuronal cell loss and neuroinflammation. Neuroinflammatory processes can be described as a release of neurotoxic substances which accelerate disease progression. As the incidence of neurodegenerative disorders increases and treatment is in most cases only effective in the early stage, these diseases need to be diagnosed as early as possible. Targets that are specifically expressed during early neuroinflammation are of special interest for (early) disease diagnosis and follow-up of treatment.
Positron emission tomography (PET) is a molecular imaging technique that detects radiation emitted by radiolabelled molecules (PET tracers) and enables detection of functional disturbances which appear in a much earlier stage than do structural abnormalities. An interesting target for early diagnosis of neuroinflammation is the P2X7 receptor (P2X7R), which plays an important role in cerebral inflammation associated with neurodegeneration and is upregulated in several animal models of neurodegenerative disease.
The aim of this project is the development and biological evaluation of carbon-11 and fluorine-18 labelled PET tracers which would allow visualization of the P2X7R and thus early detection of neuroinflammation and evaluation of novel treatments that target neuroinflammation.