***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Abstract Positron emission tomography ( PET ) is increasingly being used to study dopamine receptor occupancy and the clinical effects of antipsychotic medication . Dopamine D2 receptor occupancy has been shown to predict several clinical effects of antipsychotic medication including therapeutic response , motor and endocrine side-effects . Plasma levels may be used as a surrogate marker for central occupancy if the relationship between these two measures may be accurately described . This study was design ed to test the capacity of a previously derived relationship equation ( % D2 occupancy = plasma level/ED50+plasma level , where ED50= 0.40 ng/ml ) to predict striatal D2 occupancy from plasma level . Twenty-one patients receiving treatment with low dose haloperidol  underwent a 11C-raclopride PET scan to measure D2 occupancy . The D2 occupancy levels were accurately predicted by use of the previously generated equation with only a small degree of error ( 3.89 % CI 0.45–7.33 ) . Predicted and measured D2 occupancy values correlated closely ( Pearson ’s r=0.864 , P=0.003 ) . The study indicates that reliable prediction of D2 occupancy from plasma levels is possible . This provides a potentially useful surrogate measure of D2 occupancy for research and possibly clinical practice , as the routine use of PET to measure occupancy levels is not feasible Antipsychotic-induced D2 receptor occupancy values tend to be lower when measured with [(123)I]IBZM SPECT than with [(11)C]Raclopride PET . To clarify this issue , D2 receptor occupancy was measured in the same subjects using both techniques . Twenty patients with schizophrenia on monotherapy with risperidone ( n=7 ; 3 - 9 mg/d ) , olanzapine ( n=5 ; 5 - 20 mg/d ) or clozapine ( n=8 ; 150 - 450 mg/d ) at stable doses , and ten healthy volunteers ( HV ) underwent both a [(123)I]IBZM SPECT and a [(11)C]Raclopride PET examinations in r and om order on different days within a week . Patients with schizophrenia were scanned at a fixed interval after last dose administration . Quantification of receptor availability was performed using the most conventional methods from the literature : the tissue ratio derived specific uptake ratios ( SUR ) were used for SPECT , and simplified reference tissue model ( SRTM ) derived binding potentials ( BP(ND ) ) for PET . Analysis was performed using both occipital cortex and cerebellum as reference regions for both modalities . Striatal D2 receptor occupancy was measured as the percentage reduction of [(123)I]IBZM SUR or [(11)C]Raclopride BP(ND ) compared to the population average measured in HV using the same modality . Occupancy values measured by SPECT were lower than those measured with PET , by 12.4 % and 13.8 % when occipital cortex and cerebellum were used as reference regions . This difference should be taken in consideration when interpreting reported antipsychotic striatal D2 receptor occupancy values from the literature CONTEXT Most antipsychotics are thought to have an effect on D(2 ) and D(3 ) receptors . The development of carbon 11-labeled (+)-4-propyl-9-hydroxynaphthoxazine ( [(11)C]-(+)-PHNO ) , the first agonist radiolig and with higher affinity for D(3 ) than D(2 ) receptors , allows one to differentiate the effects of antipsychotics on high-affinity vs low-affinity sites of the D(2 ) receptor and on D(3 ) vs D(2 ) receptor subtypes . OBJECTIVES To examine the effects of antipsychotics ( clozapine , risperidone , or olanzapine ) on the high- vs high- + low-affinity sites of the D(2 ) and D(3 ) receptors by comparing the [(11)C]-(+)-PHNO and [(11)C]raclopride binding in the D(3 ) receptor-rich ( globus pallidus and ventral striatum ) and D(2 ) receptor-rich ( cau date and putamen ) regions . DESIGN Two sequential studies with different participants and appropriate controls were performed . The first compared the occupancy produced by 3 antipsychotics as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride . The second was a double-blind , placebo-controlled experiment to compare the effect of pramipexole ( a D(3 ) receptor-preferring agonist ) vs placebo on the increased [(11)C]-(+)-PHNO signal observed in the globus pallidus of patients . SETTING Positron Emission Tomography Centre , Centre for Addiction and Mental Health , Toronto , Ontario , Canada . PARTICIPANTS Twenty-three patients with schizophrenia and 23 healthy controls . MAIN OUTCOME MEASURES Antipsychotic occupancies as measured with [(11)C]-(+)-PHNO and [(11)C]raclopride .  RESULTS The antipsychotic-treated patients showed high occupancies with both [(11)C]-(+)-PHNO and [(11)C]raclopride in the dorsal striatum , with [(11)C]raclopride occupancies about 20 % higher . Most strikingly , patients did not show any occupancy with [(11)C]-(+)-PHNO in the globus pallidus as compared with normal controls or with their own scans using [(11)C]raclopride . This unblocked [(11)C]-(+)-PHNO signal was displaced by a single dose of pramipexole . CONCLUSIONS Antipsychotics block both the high- and low-affinity states of the D(2 ) receptors across the brain , but antipsychotic treatment does not block the [(11)C]-(+)-PHNO signal in the D(3 ) receptor-rich regions , despite the ongoing D(2 ) receptor blockade . This [(11)C]-(+)-PHNO signal in regions such as the globus pallidus seems increased despite antipsychotic treatment and is displaceable by a D(3 ) receptor-preferring agonist . The radiotracer [(11)C]-(+)-PHNO and the data open up new avenues for exploring the potential therapeutic significance of the D(3 ) receptor in schizophrenia Abstract We recently developed [11C]FLB 457 a substituted benzamide with the very high affinity of 20 pM for D2-dopamine receptors in vitro . The aim of the present exploratory study was to examine the anatomical distribution of [11C]FLB 457 binding in the human brain and to determine extrastriatal D2-receptor occupancy in antipsychotic drug-treated patients .  [11C]raclopride was used to obtain reference values for D2-dopamine receptor occupancy in the putamen . After IV injection of [11C]FLB 457 there was a high concentration of radioactivity , not only in the cau date putamen but also in the thalamus and the temporal cortex . The concentration of radioactivity in the frontal cortex , the substantia nigra and the colliculi was slightly higher than in the cerebellum . Pretreatment with haloperidol and fluphenazine indicated that [11C]FLB 457 binding in extrastriatal regions to a high degree represents specific binding to D2-dopamine receptors . The D2-occupancy in antipsychotic drug-treated patients was on the same level in the thalamus and the temporal cortex as that determined with [11C]raclopride in the putamen . The study shows that [11C]FLB 457 has potential for quantitative PET-examination of D2-dopamine receptors in man OBJECTIVE Aripiprazole has a unique pharmacological profile that includes partial agonism at D(2 ) receptors , antagonism at 5-HT(2 ) receptors , and partial agonism at 5-HT(1A ) receptors . The authors conducted a positron emission tomography ( PET ) study to characterize the simultaneous effects of aripiprazole at the D(2 ) , 5-HT(2 ) , and 5-HT(1A ) receptors in patients with schizophrenia or schizoaffective disorder . METHOD Twelve patients who had previously received antipsychotic treatment were r and omly assigned to receive 10 mg , 15 mg , 20 mg , or 30 mg of aripiprazole . After at least 14 days of treatment , participants underwent high-resolution PET scans using [(11)C]raclopride , [(18)F]setoperone , and [(11)C]WAY100635 . RESULTS Very high occupancy was observed at striatal D(2 ) receptors ( average putamen , 87 % ; cau date , 93 % ; and ventral striatum , 91 % ) , lower occupancy at 5-HT(2 ) receptors ( 54%-60 % ) , and even lower occupancy at 5-HT(1A ) receptors ( 16 % ) . D(2 ) occupancy levels were significantly correlated with plasma drug concentrations , and even the lowest dose ( 10 mg ) led to 85 % D(2 ) occupancy . Extrapyramidal side effects were seen only in two of the four participants with occupancies exceeding 90 % . CONCLUSIONS Aripiprazole exhibits a unique occupancy profile as compared with other conventional and atypical antipsychotics . The threshold for response appears to be higher than 60 % , extrapyramidal side effects appear to be uncommon even at occupancies that exceed the conventional extrapyramidal side effects threshold of 80 % , and 5-HT(2 ) occupancy is lower than D(2 ) occupancy . Implication s for aripiprazole 's mechanism of action are discussed A long-acting depot formulation of olanzapine that sustains plasma olanzapine concentrations for over a month after a single injection is currently under development . This multicenter , open-label study explored D2 receptor occupancy of a fixed dose of olanzapine pamoate ( OP ) depot given every 4 weeks . Patients ( nine male , five female ) with schizophrenia or schizoaffective disorder previously stabilized on oral olanzapine  were switched to OP depot 300 mg by intramuscular injection every 4 weeks for 6 months . No visitwise within-group significant changes were found in Brief Psychiatric Rating Scale Total or Clinical Global Impressions-Severity of Illness scores , although seven patients received oral olanzapine supplementation during the first four injection cycles . To minimize impact on D2 occupancy , positron emission tomography ( PET ) scans were not completed during injection cycles that required supplemental oral olanzapine . Two patients reported transient injection site adverse events , which did not result in discontinuation . The most frequently reported treatment-emergent adverse events were insomnia , aggravated psychosis , and anxiety . Mean striatal D2 receptor occupancy , as measured by [11C]-raclopride PET , was 69 % on oral olanzapine ( 5–20 mg/day ) and 50 % ( trough ) on OP depot at steady state . Following an initial decline , occupancy returned to 84 % of baseline oral olanzapine occupancy after six injections . Over the study period , D2 receptor occupancy and plasma olanzapine concentrations were significantly correlated ( r=0.76 , P⩽0.001 ) . OP depot result ed in mean D2 receptor occupancy of approximately 60 % or higher at the end of the 6-month study period , a level consistent with antipsychotic efficacy and found during treatment with oral olanzapine . However , supplemental oral olanzapine or another dosing strategy may be necessary to maintain adequate therapeutic response during the first few injection cycles To eluci date the " atypicality " of ziprasidone , its striatal and extrastriatal D2/D3-receptor binding was characterized in patients with schizophrenia under steady-state conditions . These data were compared with striatal receptor occupancy values after single-dose ziprasidone ingestion in healthy controls .  [18F]fallypride positron emission tomography ( PET ) recordings were obtained in 15 patients under steady-state ziprasidone treatment at varying time points after the last dose . Binding potentials were calculated for striatal and extrastriatal regions . D2/D3-receptor occupancies were expressed relative to binding potentials in 8 unmedicated patients . In a parallel [11C]raclopride-PET study , striatal D2/D3-receptor occupancy was measured in healthy subjects after single oral doses of 40 mg ziprasidone or 7.5 mg haloperidol . Ziprasidone plasma concentrations correlated significantly with D2/D3-receptor occupancies in all volumes of interests . Occupancy in extrastriatal regions was approximately 10 % higher than in striatal regions . Half maximal effective concentration values were consistently higher in striatal than in extrastriatal regions ( temporal cortex : 39 ng/mL ; putamen : 64 ng/mL ) , irrespective of the time between last dosing and scan . Single ziprasidone doses result ed in higher occupancies exceeding the 95 % prediction limits of the occupancy versus plasma concentrations for chronic dosing . Ziprasidone shares moderate preferential extrastriatal D2/D3-receptor binding with some other atypicals . D2/D3-receptor occupancy is rapidly attuning to the daily course of ziprasidone plasma levels , suggesting relatively high intraday variations of D2 
    Output:
    
These findings suggest that D₂ occupancy of antipsychotics could be estimated with a high degree of accuracy using widely available plasma levels