Synthesis of 18F-labelled 2-fluoro-1,4-quinones using acetylhypofluorite

The fluorination of 1,4-benzo- and naphthoquinones using [18F]acetylhypofluorite is described. For compounds with electron-donating substituents fair to good radiochemical yields have been reached

One-pot synthesis of [11C]ureas via triphenylphosphinimines

A series of 11C-labeled ureas was prepared using a rapid and efficient one-pot procedure. First, the intermediate [11C] phenylisocyanate was formed with phenyltriphenylphosphinimine and [ 11C]CO2. A range of amines was then reacted with the [11C]phenylisocyanate yielding the [11C]urea derivatives in short synthesis times. This easy-to-handle method circumvents disadvantages of known procedures and generates the possibility to prepare other kinds of 11C-labeled compounds using a variety of phenylphosphinimines in combination with different nucleophiles. The presented approach is an alternative to the use of established methods in 11C-labeling chemistry

Fully automated high yield synthesis of (R)- and (S)-[11C]verapamil for measuring P-glycoprotein function with positron emission tomography

Racemic (±) verapamil is a well characterized substrate for P-glycoprotein (P-gp). However, the in vivo pharmacokinetics and pharmacodynamics of both enantiomers are reported to be different. In the preparation of evaluation studies of both enantiomers in animals and humans, the purpose of the present study was to optimize and automate the synthesis of (R)- and (S)- [11C]verapamil. (R)- and (S)-[11C]verapamil were prepared from (R)- and (S)-desmethyl-verapamil, respectively, by methylation with no-carrier added [11C]methyliodide or [11C]methyltriflate. Different conditions of the methylation reaction were studied: reaction time, temperature, base and solvent, and chemical form of the precursor using either the hydrochloric acid salt or the free base of the starting material. After optimization, the synthesis was fully automated using home-made modules and performed according to GMP guidelines. Optimal yields of 60-70% for the methylation reaction were obtained using 1.5 mg of the free base of (R)- or (S)-desmethyl-verapamil in 0.5ml of acetonitrile at 50°C for 5min with [11C]methyltriflate as methylating agent. Under the same reaction conditions, but with a reaction temperature of 100°C, the radiochemical yield starting with [11C]methyliodide as methylation reagent was 40%. The specific activity of (R)- and (S)-[11C]verapamil was > 20 GBq/μmol and the radiochemical purity was > 99% for both methods. The total synthesis time was 45 min. The automated high yield synthesis of (R)- and (S)-[11C]verapamil provides the means for evaluating both enantiomers as in vivo tracers of P-gp function