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

Bioorganic & Medicinal Chemistry
Katsushi KumataMing-Rong Zhang

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 [18F]DAA1106 for clinical studies, we performed automated syntheses of [18F]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 [18F]F-, followed by HPLC separation and formulation, produced the [18F]DAA1106 solution for injection in 6% average (n = 10) radiochemical yield (based on [18F]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 [18F]DAA1106 with sufficient radioactivity available for preclinical and clinical use. Biodistribution study of [18F]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 ...Continue Reading

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Citations

Mar 2, 2021·Acta Pharmaceutica Sinica. B·Lingling ZhangSteven H Liang
Jul 11, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Nadja Van CampHervé Boutin
Aug 17, 2021·Radiologic Clinics of North America·Christian MasonJason S Lewis

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