[18F]DAA1106: Automated radiosynthesis using spirocyclic iodonium ylide and preclinical evaluation for positron emission tomography imaging of translocator protein (18 kDa)

Abstract DAA1106 ( N -(2,5-dimethoxybenzyl)- N -(5-fluoro-2-phenoxyphenyl)acetamide), is a potent and selective ligand for the translocator protein (18 kDa, TSPO) in brain mitochondrial fractions of rats and monkey (K i  = 0.043 and 0.188 nM, respectively). In this study, to translate [ 18 F]DAA1106 for clinical studies, we performed automated syntheses of [ 18 F]DAA1106 using the spirocyclic iodonium ylide ( 1 ) as a radiolabelling precursor and conducted preclinical studies including positron emission tomography (PET) imaging of TSPO in ischemic rat brains. Radiofluorination of the ylide precursor 1 with [ 18 F]F − , followed by HPLC separation and formulation, produced the [ 18 F]DAA1106 solution for injection in 6% average ( n  = 10) radiochemical yield (based on [ 18 F]F − ) with >98% radiochemical purity and molar activity of 60–100 GBq/μmol at the end of synthesis. The synthesis time was 87 min from the end of bombardment. The automated synthesis achieved [ 18 F]DAA1106 with sufficient radioactivity available for preclinical and clinical use. Biodistribution study of [ 18 F]DAA1106 showed a low uptake of radioactivity in the mouse bones. Metabolite analysis showed that >96% of total radioactivity in the mouse brain at 60 min after the radiotracer injection was unmetabolized [ 18 F]DAA1106. PET study of ischemic rat brains visualized ischemic areas with a high uptake ratio (1.9 ± 0.3) compared with the contralateral side. We have provided evidence that [ 18 F]DAA1106 could be routinely produced for clinical studies.