Production of radiopharmaceuticals
Production of radiopharmaceuticals for preclinical and clinical research
Examples for the production of radiopharmaceuticals
[18F]FDG is a glucose analogue well suited to measure glucose metabolism non-invasively in the human body. Many tumors show an increased activity of hexokinase and an increased glucose transporter level. This results in a high accumulation of [18F]FDG in tumor tissue. After cell uptake, FDG is phosphorylated by hexokinase to form FDG-6-phosphate. No further glycolysis of this metabolite takes place leading to tracer retention in the tumor, which can be visualized with very high sensitivity using positron emission tomography (PET).
The [18F]FDG-synthesis scheme is shown below:
Using a cryptofix-mediated nucleophilic reaction, the cyclotron-produced [18F]fluoride is substituted for the triflate leaving-group of the protected precursor. Next, the protecting groups are cleaved using sodium hydroxide and the radiolabelled glucose analogue is purified by solid phase extraction. Finally, [18F]FDG is filled into multi-injection vials and sterilized.
Figure on the right:
[18F]FDG synthesis: The diagram shows vessels for precursor and other reactants, main reaction vessel and the solid phase extraction column for final product purification
Microglia, a particular cell type in the brain, play an important role in the brain’s immune defence. Once activated, these macrophages destroy dead cells and thus help tissue regeneration. However, they are also thought to be involved in inflammatory processes often observed after brain lesions caused by stroke, Alzheimer’s disease, Multiple Sclerosis or other types of neurodegeneration.
The marker substance [11C]PK11195 can be used for to detect such neuroinflammatory processes. It addresses the peripheral benzodiazepine receptor which is expressed by activated microglia. Using [11C]PK11195-PET, binding of the radiotracer indicates regions of activated microglia and inflammatory processes. In this way, estimation of both size and location of an inflammatory process is possible.
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The research and development group Radiochemistry/Cyclotron produces and develops radiopharmaceuticals.