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Brain uptake and distribution of the dopamine D3/D2 receptor partial agonist [11C]cariprazine: An in vivo positron emission tomography study in nonhuman primates


Correspondence to: Miklós Tóth, Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institute, S-171 76 Stockholm, Sweden. E-mail:


Cariprazine is a dopamine D3/D2 receptor partial agonist antipsychotic candidate, which binds with high affinity to dopamine D3 and D2 receptors (with ∼10-fold higher in vitro affinity to D3 vs. D2 receptors) and with moderate affinity to 5-HT1A receptors. The main objective of the present molecular imaging investigation was to evaluate the uptake and reversible binding of 11-C labeled cariprazine in the nonhuman primate brain, in relation to the known distributions of dopamine D2 and D3 receptors. We examined the brains of two cynomolgus monkeys at baseline condition as well as during a pharmacological blocking condition, using unlabeled cariprazine or raclopride as blockers before injection of [11C]cariprazine. Of the total injected radioactivity, ∼7% entered the brain and ∼3–4% remained in the brain after 90 min, indicating good blood brain barrier penetration and slow washout. It was possible to block cariprazine binding with unlabeled cariprazine and raclopride indicating that [11C]cariprazine binds to dopamine D3/D2 receptors. Nondisplaceable binding potential (BPND) measurements, using a simplified reference tissue model and cerebellum as the reference region, yielded values of ∼1.5 and 0.3 in the striatum and thalamus, respectively. Striatum BPND values were reduced by 80 and 85% following pretreatment with 0.1 mg/kg IV injection of unlabeled cariprazine and 1 mg/kg IV injection of unlabeled raclopride, respectively. The data confirm that cariprazine, a novel antipsychotic drug candidate, enters the nonhuman primate brain readily and binds to dopamine D3/D2 receptors. Furthermore, in PET imaging [11C]cariprazine can effectively visualize dopamine D3/D2 receptors in the nonhuman primate brain. Synapse 67:258–264, 2013. © 2013 Wiley Periodicals, Inc.