Synthesis of fluorine-18-labelled TSPO ligands for imaging neuroinflammation with Positron Emission Tomography

Fluorine-18 radiochemistry is an essential tool in Positron Emission Tomography, providing the bridge between the cyclotron-produced raw radioisotope and the biomedical image of an in vivo radioactivity distribution. From the fluorine-18 labelled radioligands for the translocator protein 18 kDa that are produced in our laboratory, namely [18F]FEDAA1106, 6-[18F]F-PBR28, [18F]PBR111 and [18F]DPA-714, we address various aspects of fluorine-18 radiochemistry, such as rationales of radiotracer design, radioisotope production and [18F]fluoride activation, and procedures of radiofluorination, purification and formulation. Automation of the radiochemistry process has become indispensable in order to assure a constant radiopharmaceutical quality and reproducible radiochemical yields as well as to meet the required radiation protection aspects.

[18F]FEDAA1106, 6-[18F]F-PBR28, [18F]PBR111 and [18F]DPA-714 are four selected fluorine-18 labelled radioligands produced in our laboratory for imaging the translocator protein 18 kDa with Positron Emission Tomography. Various aspects of fluorine-18-radiochemistry, such as radiotracer design rationales, radioisotope production and [18F]fluoride activation, radiofluorination procedures, purification and formulation are addressed based on these structures.Figure optionsDownload as PowerPoint slideHighlights
► Design of novel TSPO 18 kDa radioligands for imaging neuroinflammation with PET.
► Radiofluorination of FEDAA1106, PBR111 and DPA-714 via standardized aliphatic SN.
► Heteroaromatic radiofluorination of the pyridinyl derivative 6-F-PBR28.
► Nonafluorobutane-1-sulfonyl [18F]fluoride for no-carrier-added OH-for-18F exchange.
► Automated production including HPLC purification of fluorine-18 radiopharmaceuticals.