High ‐yielding, automated radiosynthesis of [11C]martinostat using [11C]methyl triflate

An efficient, automated radiosynthesis of [11C]martinostat using [11C]methyl triflate as the alkylating agent in anhydrous ethanol is presented. 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 precursor1 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 dec...
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: SHORT NOTE Source Type: research