Molecular imaging of α7 nAChR in cancer and brain diseases: design and evaluation of novel 18F-labelled 1,4-diazabicyclo-[3.2.2]nonane based PET radiotracers
The ubiquitous expression and the particular intracellular signalling triggered by activation of the homomeric nicotinic acetylcholine receptor α7 nAChR in mammalian cells make this protein an interesting target for diagnostic and therapeutic approaches. α7 nAChR regulates not only the neurotransmitter release in brain regions related to learning, memory, and information processing but is also involved in cancer development and progression. Because density and functionality of α7 nAChR is closely connected with various neurological disorders and most types of cancer, non-invasive visualisation and quantification of α7 nAChR by positron emission tomography (PET) as well as receptor occupancy studies supporting novel pharmacological approaches has the potential to improve clinical diagnostics and drug development. The primary objective of this project is to design and evaluate 18F-labelled α7 nAChR PET radiotracers based on the 1,4-diazabicyclo-[3.2.2]nonane skeleton.
|Sagittal tomographic image of a porcine brain after injection of the radiotracer [18F]NS10743. The heterogeneous pattern of the intensity of radioactivity in the brain with a high accumulation in cortex (C) and thalamus (Th) and low accumulation in cerebellum (Cb) indicates specific binding of the radiotracer.|
DanPET, Malmö, Sweden
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