[18F]DAA1106: Automated radiosynthesis using spirocyclic iodonium ylide and preclinical evaluation for positron emission tomography imaging of translocator protein (18 kDa). Issue 17 (15th September 2018)

• Record Type: Journal Article
• Authors: Kumata, Katsushi; Zhang, Yiding; Fujinaga, Masayuki; Ohkubo, Takayuki; Mori, Wakana; Yamasaki, Tomoteru; Hanyu, Masayuki; Xie, Lin; Hatori, Akiko; Zhang, Ming-Rong
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 17(2018)
• Page Start: 4817
• Page End: 4822
• Publication Date: 2018-09-15
• Subjects: [18F]DAA1106 -- Spirocyclic iodonium ylide -- [18F]Fluorination -- TSPO -- Ischemia; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.08.017
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 (Ki = 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.