Efficient in-loop synthesis of high specific radioactivity [11C]carfentanil

• Published in: Journal of labelled compounds & radiopharmaceuticals Vol. 46; no. 9; pp. 837 - 842
• Main Authors: Studenov, Andrei R., Jivan, Salma, Buckley, Kenneth R., Adam, Michael J.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.08.2003; Wiley
• Subjects: [11C]carfentanil; Biochemical Research Methods; Biochemistry & Molecular Biology; Biological and medical sciences; Chemistry; Chemistry, Analytical; Chemistry, Medicinal; Contrast media. Radiopharmaceuticals; in-loop synthesis; Life Sciences & Biomedicine; Medical sciences; opioid receptor; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Science & Technology; opioid receptor; [C-11]carfentanil; in-loop synthesis; AUTOMATED PREPARATION; RADIOSYNTHESIS; NITRILES; RADIOTRACER; Agonist; Analgesic; Carfentanil; Radiolabelling; μ Opioid receptor; Carbon 11; Carbon Isotopes; Iodomethane; Chemical synthesis
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.722

The synthesis of the precursor for [11C]carfentanil and the precursor labelling with 11C have both been improved. The problem ‘bottleneck’ step in the carfentanil precursor synthesis, due to low chemical yield (14%) of intermediates nitrile into amide conversion, has been solved. Application of a H2O2/K2CO3/DMSO reaction method significantly increased the yield of this chemical transformation (up to 84%). A simple and straight‐forward synthesis of [11C]carfentanil was achieved by combining in‐loop methylation of the ammonia salt of the precursor by [11C]CH3I, using tetrabutylammonium hydroxide as a base, with a previously developed product purification procedure using a C2 extraction disc. A decay corrected yield with respect to [11C]CH3I of [11C]carfentanil was 64±12% (n=6) with the synthesis time of 21 min. The radiochemical purity was >98%. Comparatively high specific radioactivity of [11C]carfentanil [11.2±4.8 Ci/μmol (EOS, n=5)] was partially attributed to the use of [11C]methane target gas for production of carbon‐11 methyl iodide. Copyright © 2003 John Wiley & Sons, Ltd.