A preliminary PET evaluation of the new dopamine D 2 receptor agonist [ 11C]MNPA in cynomolgus monkey

• Published in: Nuclear medicine and biology 2005, Vol.32 (4), p.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: Article
• Language: English
• Subjects: [ 11C]MNPA; D 2 receptor; Dopamine agonist; High-affinity state; Monkey; PET
• ISSN: 0969-8051; 1872-9614
• 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- 11CH 3O- N- n-propylnorapomorphine ([ 11C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D 2 receptor (D 2R). MNPA is a selective D 2-like receptor agonist with a high affinity ( K i=0.17 nM). [ 11C]MNPA was successfully synthesized by direct O-methylation of ( R)-2-hydroxy-NPA using [ 11C]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 2R, 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 2R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [ 11C]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 2R in human subjects and patients with neuropsychiatric disorders.