1. High‐yielding, automated radiosynthesis of [11C]martinostat using [11C]methyl triflate.
- Author
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Hopewell, Robert, Jolly, Dean, Li, Qian Ying, Ross, Karen, Tsai, I‐Huang, Lacatus‐Samoila, Monica, Soucy, Jean‐Paul, Kobayashi, Eliane, Rosa‐Neto, Pedro, and Massarweh, Gassan
- Subjects
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METHYL triflate , *SOLID phase extraction , *HIGH performance liquid chromatography , *METHYL iodide , *CENTRAL nervous system , *NEUROBEHAVIORAL disorders , *MARINE toxins , *ETHANOL - Abstract
Histone deacetylases (HDACs) mediate epigenetic mechanisms implicated in a broad range of central nervous system dysfunction, including neurodegenerative diseases and neuropsychiatric disorders. [11C]Martinostat allows in vivo quantification of class I/IIb HDACs and may be useful for the quantification of drug–occupancy relationship, facilitating drug development for disease modifying therapies. The present study reports a radiosynthesis of [11C]martinostat using [11C]methyl triflate in ethanol, as opposed to the originally described synthesis using [11C]methyl iodide and DMSO. [11C]Methyl triflate is trapped in a solution of 2 mg of precursor 1 dissolved in anhydrous ethanol (400 μl), reacted at ambient temperature for 5 min and purified by high‐performance liquid chromatography; 1.5–1.8 GBq (41–48 mCi; n = 3) of formulated [11C]martinostat was obtained from solid‐phase extraction using a hydrophilic–lipophilic cartridge in a radiochemical yield of 11.4% ± 1.1% (nondecay corrected to trapped [11C]MeI), with a molar activity of 369 ± 53 GBq/μmol (9.97 ± 1.3 Ci/μmol) at the end of synthesis (40 min) and validated for human use. This methodology was used at our production site to produce [11C]martinostat in sufficient quantities of activity to scan humans, including losses incurred from decay during pre‐release quality control testing. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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