Optimisation of synthesis, purification and reformulation of (R)-[N-Methyl-11C]PK11195 for in vivo PET imaging studies

Neurodegenerative, inflammatory and neoplastic disorders involve neuroinflammatory reactions in the central nervous system that isolate the damaged tissue and promote im-mune responses by the activation of resident cells of the mono-cytes lineage (microglia). This process involves an overexpression of the 18 kDa translocator protein receptor (TSPO). PK11195 is an isoquinoline carboxamide which binds selectively to this re-ceptor. The (R)-enantiomer radiolabelled with carbon-11 is the most widely used radiotracer for in vivo TSPO imaging with Posi-tron Emission Tomography (PET). We report the optimisation of synthesis, purification and reformulation of (R)-[N-MethyJ-¹¹C]PK11195 by the captive solvent method suitable for use in human PET imaging studies. (R)-[NMethyJ-¹¹C]PK11195 was prepared from [N-Desmethyl]PK11195 by alkylation with [llC]methyl iodide reacting at room temperature in an high-performance liquid chromatography loop, purified and reformulated by solid phase extraction. Synthesis process is carried out in about 35 minutes, and quality control tests were performed to ensure the good quality of product. The specific activity of (R)-[N-MethyJ-¹¹C]PK11195 was 25±10 GBq/μmol, and radiochemical purity was better than 95%.