PT - JOURNAL ARTICLE AU - Ragy Girgis AU - Balu Easwaramoorthy AU - John Castrillon AU - Roger Gunn AU - Eugenii Rabiner AU - Anissa Abi-Dargham AU - Mark Slifstein TI - In vivo binding of antipsychotics to D3 and D2 receptors: A PET study in baboons with [<sup>11</sup>C] PHNO DP - 2010 May 01 TA - Journal of Nuclear Medicine PG - 1752--1752 VI - 51 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/51/supplement_2/1752.short 4100 - http://jnm.snmjournals.org/content/51/supplement_2/1752.full SO - J Nucl Med2010 May 01; 51 AB - 1752 Objectives Measuring the occupancy of antipsychotic drugs (APD) at dopamine D2 and D3 receptors separately has been difficult due to lack of selectivity of available tracers. The recently developed [11C] PHNO is D3 preferring, allowing estimates of the relative D2 and D3 binding of APD. We used PET imaging in baboons with [11C] PHNO to examine the binding to D2 and D3 by clozapine (CLOZ) and haloperidol (HAL). Methods 3 animals (A,B,C) were scanned. Baseline and post-APD scans (2-scan studies) were acquired in one session for HAL (A, B, 0.0109 mg/kg) and CLOZ (A,C, 0.5534 mg/kg). Post-APD -only-scans (1-scan studies) were acquired in 2 animals for CLOZ (A, C) and HAL (A,B) and compared to mean baseline. Metabolite-corrected arterial plasma inputs were collected and data analyzed by 2 tissue-compartment modeling. All scans were 120 min. APD were given as a 5 min bolus 15 min prior to the scan. We measured ΔBPND, the % decrease in BPND following APD. A regression model based on literature values of D2 and D3 fractions of [11C] PHNO BPND in putamen (PUT), caudate (CAU) substantia nigra (SN) globus pallidus (PDM) ventral striatum (VST) and thalamus (THA) was used to infer occupancy at D2 and D3. Results ΔBPND was similar in PUT and CAU for 1 and 2 scan studies but larger in D3-rich regions for 2-scan studies than 1-scan studies, suggesting a mass carryover effect due to the high affinity of [11C] PHNO for D3. Subsequent analysis was done with 1-scan studies only (Table). The regression model estimated D2:D3 selectivity as 9.4 for CLOZ and 2.4 for HAL. Conclusions The selectivity ratio for HAL was very similar to published in vitro values (2.5 for CLOZ and HAL) but larger for CLOZ. This may be due to different behavior in vivo, or due to a kinetic artifact from the fast off rate of CLOZ and the slow washout of [11C] PHNO in D3-rich regions. Research Support Lieber Ctr for Schiz. Res., GS