Automated radiochemical synthesis and biodistribution of [11C]l-α-acetylmethadol ([11C]LAAM)

•Radiochemical synthesis of opioid [11C]l-α-acetylmethadol (LAAM) described for the first time.•High radiochemical yield, purity and specific activity.•Easily reproducible and adaptable synthesis to any C-11 automated modules.•[11C]LAAM utility as a PET radiopharmaceutical for assessing brain penetration.

Long-acting opioid agonists methadone and l-α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [11C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharmacologic similarities, we aimed to develop [11C]LAAM as a PET ligand to probe the brain exposure of long-lasting opioids in humans. This manuscript describes [11C]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.