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

This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D-2-like receptor agonist, (R)-2(11)-CH3O-N-n-propylnorapomorphine ([C-11]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D-2 receptor (D2R). MNPA is a selective D2-like receptor agonist with a high affinity (K-i=0.17 nM). [C-11]MNPA was successfully synthesized by direct O-methylation of(R)-2-hydroxy-NPA using [C-11]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 D2R, 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 D2R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [C-11]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 D2R in human subjects and patients with neuropsychiatric disorders. (c) 2005 Elsevier Inc. All rights reserved.