Diabetes is characterized by hyperglycemia associated with beta cell dysfunction in type 2 diabetes (T2D) or loss in type 1 diabetes (T1D). Positron emission tomography (PET) could provide a possibility for the in vivo imaging of beta cells. This could be used for pathogenetic studies and to monitor therapeutic interventions. Currently, such a radiotracer is not clinically available. 

In this thesis, the vesicular monoamine transporter 2 (VMAT2) and glucagon-like peptide-1 receptor (GLP-1R) were investigated as targets for beta cell imaging using [11C]DTBZ, [68Ga]NODAGA-exendin-4, [64Cu]NODAGA-exendin-4, [64Cu]NODAGA-MAL-exendin-4 and [18F]exendin-4. The biodistribution and kinetics of the radiotracers in healthy and T1D animals was investigated by in vivo PET/CT imaging and ex vivo radioactivity measurements. The spatial distribution of radioactivity in pancreatic tissue sections of experimental animals and humans was analyzed by autoradiography. 

The results showed that [11C]DTBZ accumulation in pancreas is mainly nonspecific and does not represent specific binding to beta cells. [18F]exendin-4, on the other hand, is a promising candidate for beta cell imaging. [18F]exendin-4, produced at high specific activity, specifically labeled the islets in both human and rat pancreas, while exhibiting low binding in the exocrine pancreas. Unlike the metal-labeled exendin tracers investigated, excretion of [18F]exendin-4 via the kidneys was rapid, resulting in a relatively low estimated absorbed radiation dose. 

In conclusion, [18F]exendin-4 is a promising radiotracer for beta cell imaging due to its specific labeling of the islets and concomitant low kidney retention. These properties make it suitable for further clinical development. For preclinical research, [64Cu]NODAGA-exendin-4, with its long radioactive half-life, is also a useful tool.