A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey

• Published in: Nuclear medicine and biology Vol. 32; no. 4; pp. 353 - 360
• Main Authors: Finnema, Sjoerd J, Seneca, Nicholas, Farde, Lars, Shchukin, Evgeny, Sóvágó, Judit, Gulyás, Balázs, Wikström, Håkan V, Innis, Robert B, Neumeyer, John L, Halldin, Christer
• Format: Journal Article
• Language: English
• Published: United States 01.05.2005
• Subjects: Animals; Apomorphine - analogs & derivatives; Apomorphine - chemistry; Apomorphine - pharmacokinetics; Brain - diagnostic imaging; Brain - metabolism; Feasibility Studies; Macaca fascicularis; Medicin och hälsovetenskap; Pilot Projects; Positron-Emission Tomography - methods; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - pharmacokinetics; Receptors, Dopamine D2 - agonists; Receptors, Dopamine D2 - metabolism; Tissue Distribution
• ISSN: 0969-8051
• DOI: 10.1016/j.nucmedbio.2005.01.007

This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D(2)-like receptor agonist, (R)-2-(11)CH(3)O-N-n-propylnorapomorphine ([(11)C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D(2) receptor (D(2)R). MNPA is a selective D(2)-like receptor agonist with a high affinity (K(i)=0.17 nM). [(11)C]MNPA was successfully synthesized by direct O-methylation of (R)-2-hydroxy-NPA using [(11)C]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D(2)R, with a maximum striatum-to-cerebellum ratio of 2.23+/-0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37+/-0.06 at 72 min. The pretreatment study demonstrated high specific binding to D(2)R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [(11)C]MNPA has potential as an agonist radioligand for the D(2)-like receptor and has potential for examination of the high-affinity state of the D(2)R in human subjects and patients with neuropsychiatric disorders.