title: Automated radiochemical synthesis and biodistribution of [¹¹C]l-α-acetylmethadol ([¹¹C]LAAM).
abstract: Long-acting opioid agonists methadone and l-α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [(11)C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharmacologic similarities, we aimed to develop [(11)C]LAAM as a PET ligand to probe the brain exposure of long-lasting opioids in humans. This manuscript describes [(11)C]LAAM synthesis and its biodistribution in mice. The radiochemical synthetic strategy afforded high radiochemical yield, purity and specific activity, thereby making the synthesis adaptable to automated modules.
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Radiology, Wake Forest School of Medicine, 1 Medical Center Blvd, Winston Salem, NC 27157, USA.
authors.forename: Kiran Kumar Solingapuram
authors.initials: KK
authors.lastname: Sai
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Radiology, University of Alabama School of Medicine, 720 2nd Ave S, Birmingham, AL 35294, USA.
authors.forename: Jinda
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Zhude
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Zerkel
authors.affiliation: Department of Radiology, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Radiology, Perelman School of Medicine, University of Pennsylvania, 231 S. 34th Street, Philadelphia, PA 19104, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Mach
authors.affiliation: Department of Anesthesiology, and Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, 660 S. Euclid Ave., Campus Box 8054, St. Louis, MO 63110, USA. Electronic address: kharasch@wustl.edu.
authors.forename: Evan D
authors.initials: ED
authors.lastname: Kharasch
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000737:chemistry*; D008297:Male; D008692:Methadyl Acetate / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051379:Mice; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D008692:Methadyl Acetate
keywords: Biodistribution; LAAM; Methadone; PET; Positron emission tomography; l-α-Acetylmethadol