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

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. - Highlights: • 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