An optimized radiosynthesis of 18F-THK-5351 for routine production on TRACERlab™ FXFN

Abstract

18F−THK−5351 18F−THK−5351 is a PET radiotracer to image the hyperphosphorylated tau fibrillar aggregates in human brain. This protocol describes the optimized radiosynthesis of 18F−THK−5351 18F−THK−5351 using a commercial GE TRACERlabTM TRACERlabTM FXFN FXFN radiosynthesis module. 18F−THK−5351 18F−THK−5351 was prepared by nucleophilic [18F 18F ]fluorination from its protected tosylate precursors, (S)-(2-(2-methylaminopyrid-5-yl)-6-[[2-(tetrahydro-2H-pyran-2-yloxy)-3-tosyloxy]propoxy] quinolone(THK-5352), at 110∘C 110∘C for 10 min in dimethyl sulfoxide, followed by deprotection with 1 N HCl. The average radiochemical yield of 18F−THK−5351 18F−THK−5351 was 31.9±6.7 31.9±6.7 (decay-corrected, n = 10), with molar activity of 198.1±33.9GBq/μmol 198.1±33.9GBq/μmol (5.4±0.9Ci/μmol 5.4±0.9Ci/μmol , n = 10). The radiochemical purity was determined to be above 98%. The overall production time including HPLC purification is approximately 70 min. This fully-automated protocol is validated for clinical use.