The potential of carbon-11 and fluorine-18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa.

摘要: The TSPO (translocator protein), also known as the peripheral benzodiazepine receptor, is upregulated in brain of subjects suffering from neurodegenerative disorders such Alzheimer's, Parkinson's and Huntington's disease. Moreover, this overexpression has been proved to be linked microglia activation making thus a marker choice neuroinflammatory processes therefore potential target for development radioligands positron emission tomography imaging. discovery selective ligands their labelling with short-lived positron-emitter isotopes carbon-11 fluorine-18 emerged mid-1980s preparation 3-isoquinolinecarboxamide [11C]PK11195. To date, an impressive number promising compounds—[11C]PK11195-challengers—have developed; some radioligands—for example, [11C]PBR28, [11C]DPA-713, [18F]FEDAA1106 [18F]DPA-714—are currently used clinical trials. As illustrated review, methodologies applied these compounds remain mainly [11C]methylations using [11C]MeI or [11C]MeOTf SN2-type nucleophilic aliphatic [18F]fluorinations—two illustrating state-of-the-art arsenal reactions that involves two radioisotopes—but alternative processes, [11C]carbonylations [11C]CO [11C]COCl2 well SNAr-type [18F]fluorinations, have reported such, reviewed herein.