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Yuan-Hwa Chou

Publications and source records attributed to Yuan-Hwa Chou.

18 recordsLinked to original sources
PubMed2006

Dopamine transporters and cognitive function in methamphetamine abuser after a short abstinence: A SPECT study.

The purpose of this study was to examine the change of dopamine transporters (DAT) binding in methamphetamine (METH) abusers in a two-week period of abstinence and its association with cognitive function. Seven healthy subjects and seven METH abusers were recruited. At baseline conditions, the values of specific uptake ratio (SUR) of DAT binding measured by single photon emission computed tomography were lower in METH abusers than in controls. After a two-week period of abstinence, DAT binding was partially recovered and there were no statistic differences in SUR between METH abusers and controls. There was a borderline correlation between the changes of DAT binding in the right, but not the left, striatum and the %Error of Wisconsin Card Sorting Test. These findings indicate that DAT binding in METH abusers can be reversed in a short period of abstinence. The recovery of DAT binding was asymmetric and possibly parallel with the improvement of cognitive function.

Adult↗
PubMed2006

Ziprasidone-associated pedal edema in the treatment of schizophrenia.

It has been reported that second generation of antipsychotic drugs may induce pedal edema. The purpose of this case report is to demonstrate that the recently marketed antipsychotic drug, ziprasidone induced pedal edema with an increased plasma immunoglobulin E (IgE) level. A 51-year-old female schizophrenic patient who developed severe pedal edema was treated with ziprasidone for 6 weeks. Admission routine data that included biochemical, blood and urine analysis were normal except for the plasma IgE level, which was significantly elevated. Although the pedal edema subsided after discontinuation of ziprasidone and administration of diuretics, the plasma IgE level remained high. This is the first case report attempting to demonstrate the existence of ziprasidone-induced pedal edema in the treatment of schizophrenia. In this case, the pedal edema was associated with an IgE-related allergic reaction.

Antipsychotic Agents↗
PubMed2006

Clozapine binds preferentially to cortical D1-like dopamine receptors in the primate brain: a PET study.

RATIONALE: The D1-like dopamine receptors have been suggested to play a role in the pathophysiology and treatment of schizophrenia. Previous positron emission tomography studies have demonstrated that the atypical antipsychotic clozapine occupies D1-like dopamine receptors in the striatum in clozapine-treated patients. OBJECTIVES: The aim of the present study was to compare striatal and cortical D1-like dopamine receptor occupancy by clozapine in the primate brain. METHODS: Three monkeys were each examined three times at the same day with the radioligand (+)-[11C]NNC 112. The first measurement was at baseline conditions, the second after 1.5 mg/kg and the third after 6 mg/kg clozapine IV. To compare regional levels of nonspecific binding in brain regions, an additional monkey was examined using the inactive enantiomer (-)-[11C]NNC 112. Receptor occupancy was calculated using both the equilibrium-ratio analysis and the simplified reference tissue model. RESULTS: After 1.5 mg/kg the D1-like dopamine receptor occupancy ranged from 30 to 38% in the striatum, whereas the range was 51 to 57% in the frontal cortex. After 6.0 mg/kg the occupancy was 53 to 64% in the striatum and 63 to 83% in the frontal cortex. The differences between striatal and cortical D(1)-like receptors occupancy were between 12 and 25%. The study with (-)-[11C]NNC 112 did not show regional differences in nonspecific binding that might explain the regional differences in occupancy. CONCLUSIONS: The higher D1-like dopamine receptor occupancy in the frontal cortex may reflect a different distribution of the D1 and D5 dopamine receptor subtypes among brain regions and different affinity of clozapine for the two subtypes. The finding supports the suggestion that binding to D1-like dopamine receptors may explain clozapine's atypical drug actions.

Animals↗
PubMed2006

Evaluating dopamine transporter activity with 99mTc-TRODAT-1 SPECT in drug-naive Tourette's adults.

OBJECTIVES: Findings on imaging of dopamine transporter (DAT) activity in patients with Tourette's syndrome remain inconclusive. The present study was carried out to observe DAT activity in patients with well-controlled Tourette's syndrome by using (99m)Tc-TRODAT-1 single photon emission computerized tomography (SPECT). METHODS: Six drug-naive patients with Tourette's syndrome (mean age+/-SD, 21.2+/-1.5 years) were recruited. All met the criteria for Tourette's syndrome established in the DSM-IV. Seventeen age-matched and sex-matched healthy subjects served as the controls. Brain SPECT were acquired 165-195 min after administrating 740 MBq of (99m)Tc-TRODAT-1, using a double-headed camera equipped with ultra-high-resolution fan-beam collimators. The specific uptake ratio was calculated by subtracting the mean counts per pixel in the occipital cortex from the mean counts per pixel in the striatum, putamen or caudate nucleus and by dividing the result by the mean counts per pixel in the occipital cortex. Tic-severity scores were also measured and correlated with the specific uptake ratios. RESULTS: No significant difference in DAT activity between patients with Tourette's syndrome and control subjects was found in the striatum and its sub-regions. Tic-severity scores were also not correlated with specific uptake ratios measured from the striatum and its sub-regions. CONCLUSIONS: In conjunction with previous findings, our results suggested that functional abnormality of the dopamine system in patients with Tourette's syndrome might be evident only in its early stage. Adaptation to tic symptoms might play a role in regulating the neural system.

Adult↗
PubMed2005

Combined treatment of olanzapine and mirtazapine in anorexia nervosa associated with major depression.

Several studies have shown that olanzapine is effective in weight restoration and maintenance for patients with anorexia nervosa (AN). However, major depression is a very common comorbid psychiatric disorder associated with AN. Additional antidepressant therapy may be required for treating anorexic patients with major depression. The authors present a case of AN associated with major depression, who responded well to the combination treatment of olanzapine and mirtazapine. A 27-year-old Taiwanese woman was admitted because of severe weight loss, poor nutrition, amenorrhea, major depression, and starvation complications including hematological dyscrasis, electrolytes and endocrine imbalance, and sinus bradycardia. In additional to nutritional and medical treatments, the patient was given olanzapine 10 mg/day and mirtazapine 30 mg/day. She took the combined medications for six months. Meanwhile she received cognitive behavior therapy and family therapy. With these treatments, the patient's depression was in remission, her body weight was increased from 24 to 38 kg, and her body mass index was increased from 9.8 to 15.5. Our case suggests that the combined treatment of olanzapine and mirtazapine can be used in the treatment of AN associated with major depression.

Adult↗
PubMed2005

N-oxide analogs of WAY-100635: new high affinity 5-HT(1A) receptor antagonists.

WAY-100635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl)ethyl))-N-(2-pyridinyl)cyclohexanecarboxamide] 1 and its O-desmethyl derivative DWAY 2 are well-known high affinity 5-HT(1A) receptor antagonists, which when labeled with carbon-11 (beta+; t(1/2) = 20.4 min) in the carbonyl group are effective radioligands for imaging brain 5-HT(1A) receptors with positron emission tomography (PET). In a search for new 5-HT(1A) antagonists with different pharmacokinetic and metabolic properties, the pyridinyl N-oxide moiety was incorporated into analogs of 1 and 2. NOWAY 3, in which the pyridinyl ring of 1 was oxidized to the pyridinyl N-oxide, was prepared via nucleophilic substitution of 2-[4-(2-methoxyphenyl)piperazin-1-yl]ethylamine on 2-chloropyridine-N-oxide followed by acylation with cyclohexanecarbonyl chloride. 6Cl-NOWAY 4, a more lipophilic (pyridinyl-6)-chloro derivative of 3, was prepared by treating 1-(2-methoxyphenyl)-4-(2-(2-(6-bromo)aminopyridinyl-N-oxide)ethyl)piperazine with cyclohexanecarbonyl chloride for acylation and concomitant chloro for bromo substitution. NEWWAY 5, in which the 2-hydroxy-phenyl group of 2 is replaced with a 2-pyridinyl N-oxide group with the intention of mimicking the topology of 2, was prepared in five steps from 2-(chloroacetylamino)pyridine. N-Oxides 3-5 were found to be high affinity antagonists at 5-HT(1A) receptors, with 3 having the highest affinity and a Ki value (0.22 nM) comparable to that of 1 (0.17 nM). By calculation the lipophilicity of 3 (LogP = 1.87) is lower than that of 1 by 1.25 LogP units while TLC and reverse phase HPLC indicate that 3 has slightly lower lipophilicity than 1. On the basis of these encouraging findings, the N-oxide 3 was selected for labeling with carbon-11 in its carbonyl group and for evaluation as a radioligand with PET. After intravenous injection of [carbonyl-11C]3 into cynomolgus monkey there was very low uptake of radioactivity into brain and no PET image of brain 5-HT(1A) receptors was obtained. Either 3 inadequately penetrates the blood-brain barrier or it is excluded from brain by an active efflux mechanism. Rapid deacylation of 3 was not apparent in vivo; in cynomolgus monkey plasma radioactive metabolites of [carbonyl-11C]3 appeared less rapidly than from the radioligands [carbonyl-11C]1 and [carbonyl-11C]2, which are known to be primarily metabolized by deacylation. Ligand 3 may have value as a new pharmacological tool, but not as a radioligand for brain imaging.

Animals↗
PubMed2005

No alcoholism-protection effects of ADH1B*2 allele in antisocial alcoholics among Han Chinese in Taiwan.

BACKGROUND: suggested that the genetic variation at ADH1B and ALDH2 influences the risk of alcoholism. The ADH1B*2 and ALDH2*2 alleles had been thought to be protective against alcoholism. Recent studies have suggested that either physiological tolerance of blood acetaldehyde, or innate insensitivity to it, or both may play a crucial role in keeping alcoholism from developing by protecting against adverse reactions. ALDH inactive form resulting from ALDH2*2, which slows the elimination of acetaldehyde and the more active isozymes produced by ADH1B*2, could generate higher acetaldehyde levels and thus deter heavy drinking (). The genotype frequency of ADH1B*2/*2 and ALDH2*(1/*2 or 2/*2), which are regarded protective against drinking behavior, is about 70% and 50%, respectively, among the Han Chinese population in Taiwan (Chen et al., 1999a). Most previous studies, however, have failed to separate the effects of antisocial personality disorder from those of alcoholism because of their high comorbidity. To understand the relationship among alcoholism, antisocial personality disorder, and the protective effects of ADH and ALDH, it is necessary to recruit individuals with antisocial personality disorder but without alcoholism. This study was designed to stratify subjects by various ADH1B and ALDH2 genotypes for a more effective association study. The strata were: antisocial alcoholics, antisocial non-alcoholics, community alcoholics, and normal controls. METHODS: We recruited 579 Han Chinese individuals in Taiwan, intending to examine the alcoholism-protection effects of different ADH1B and ALDH2 genotypes with or without antisocial personality disorder. RESULTS: We found no difference of ADH1B*2 allele frequency between the subjects of antisocial alcoholism and subjects of antisocial non-alcoholism, but we found significant difference of ALDH2*2 allele between these two groups. CONCLUSIONS: We concluded that there is no alcoholism-protection effect of ADH1B*2 allele in antisocial alcoholics among Han Chinese in Taiwan.

Adult↗
PubMed2005

Pharmacoeconomic evaluation of schizophrenia in Taiwan: model comparison of long-acting risperidone versus olanzapine versus depot haloperidol based on estimated costs.

Antipsychotics are the keystone in schizophrenia treatment. Although the benefits of the new generation of antipsychotics has been demonstrated over the last decade, the issues of patient compliance and higher purchasing price of atypical antipsychotics remain unresolved. Risperidone is the only atypical antipsychotic agent with long-acting formulation. Long-acting risperidone is a water-based injection and it has been associated with a low level of pain. The aim of the present study was to test whether an improvement in compliance with the use of a long-acting risperidone, compared with olanzapine and depot haloperidol, can increase the effectiveness and the cost-effectiveness indexes. An economic comparison model with decision tree, rather than a prospective design with real clinical drug trial, was applied. The unit cost for each medical procedure was obtained from the claimed-database of the Bureau of National Health Insurance in Taiwan. An executive committee simulated the incidence of extrapyramidal side-effects and proposed a therapeutic model for each strategy based on a literature review. The probabilities of treatment response of different agents and those of different mental health states were estimated by the executive committee and 10 senior psychiatrists who were randomly selected. Sensitivity analysis was performed for drug cost-effectiveness and compliance improvement for using long-acting risperidone. The results showed that long-acting risperidone is more cost-effective than either olanzapine or depot haloperidol for treating schizophrenia patients whose conditions are stable and whose illness duration ranges from 1 to 5 years. The comparison model with the Kaplan-Meier decision tree may serve as an alternative to prospectively designed studies for cost-effectiveness of atypical antipsychotics.

Adult↗
PubMed2004

Imaging serotonin transporters with 123I-ADAM brain SPECT in healthy non-human primates.

BACKGROUND: Serotonin transporters (SERTs) play a major role in modulating serotonergic neuronal function and are the target of many antidepressant drugs used in neuro-psychiatric disorders. To gain more information on the temporal distribution of SERTs, 2-([2-([dimethylamino]methyl)phenoxyl]thio)-5-[I]iodophenylamine (I-ADAM) single photon emission computed tomography (SPECT) was utilized in an in vivo imaging study using non-human primates. METHODS: Two female monkeys (Macaca cyclopis) were studied. Eight brain SPECT imaging examinations, each 30 min in duration, were obtained after injection of 185 MBq of I-ADAM. Images were obtained using a dual-head gamma camera equipped with ultra-high resolution fan-beam collimators. In addition to visual inspection, the radio-uptake and specific uptake ratios (SURs) of midbrain (MB), thalamus (TH), striatum (ST), temporal and frontal cortices and the whole brain in reference to the corresponding magnetic resonance image at the eight time points were measured. The SUR of MB, using cerebellum (CB) as the reference tissue, was calculated as (MB - CB)/CB, in mean counts/pixel. The SURs of the other brain regions were similarly measured. RESULTS: There was relatively high uptake of I-ADAM in the MB and TH, moderate uptake in ST, lower uptake in the cerebral cortex, and almost no uptake in the CB. The image of MB could be easily identified at the first 30 min time point. It appeared that the SURs of MB, TH and ST reached equilibrium around 210 min after injection. No adverse reactions of the primates were found during and after imaging. Brain distribution of I-ADAM in the primate appeared consistent with the known distribution of SERTs. CONCLUSION: In conjunction with a high SUR in MB, TH and ST, we speculate that I-ADAM may be a potential radioligand for SPECT studies of serotonin transporters in humans.

Animals↗
PubMed2004

Possible interaction of alcohol dehydrogenase and aldehyde dehydrogenase genes with the dopamine D2 receptor gene in anxiety-depressive alcohol dependence.

BACKGROUND: The role of the dopamine D2 receptor (DRD2) gene in the development of alcohol abuse or dependence is controversial. The controversy is due in part to the disparate definitions pertaining to the control groups used and to the definitions of subtypes in alcohol dependence. In the Han Chinese population, the alcohol dehydrogenase 1B*2/*2 (ADH1B*2/*2) genotype and the aldehyde dehydrogenase 2*2 (ALDH2*2) allele have been considered as protective factors against alcohol abuse or dependence. Moreover, the ADH1B and ALDH2 genes might be involved in dopamine metabolism. We hypothesized that the ADH1B and ALDH2 genes might interact with the DRD2 gene and that the association between the DRD2 gene and alcohol dependence might be affected by different ADH1B and ALDH2 genotypes. This study examined whether the DRD2 gene is associated with specific subtypes of alcohol dependence and evaluated the relationship between the DRD2 gene and alcohol-metabolizing genes in a specific subtype of alcohol dependence. METHODS: Of the 465 Han Chinese subjects who were recruited for the study, 71 were classified with pure alcohol dependence, 113 with both alcohol dependence and anxiety-depression (ANX/DEP ALC), and 129 with anxiety-depression but without alcohol dependence (ANX/DEP). The remaining 152 subjects were supernormal controls. All subjects were interviewed with the Chinese version of the modified Schedule of Affective Disorders and Schizophrenia-Lifetime; all alcohol dependence, anxiety, and major depressive diagnoses were made according to DSM-IV criteria. RESULTS: The DRD2 gene was not found to be associated with pure alcohol dependence or ANX/DEP, but was found to be associated with ANX/DEP ALC. Furthermore, the association between the DRD2 gene and ANX/DEP ALC was shown to be under the control of the ALDH2*1/*1 and ADH1B*1/*2 genotypes. CONCLUSIONS: ANX/DEP ALC is a specific subtype of alcohol dependence. Because ANX/DEP ALC was associated with the DRD2 gene only under the stratification of ADH1B*1/*2 or ALDH2*1/*1, the DRD2 gene might interact with the ADH1B gene and the ALDH2 gene, respectively, in the development of ANX/DEP ALC in the Taiwan Han Chinese population.

Adult↗
PubMed2003

[(11)C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain.

The aim of this study was to explore the potential of a new selective dopamine transporter (DAT) compound as a radioligand for positron emission tomography (PET) examination of DAT in the human brain. The high affinity DAT compound N-(3-iodoprop-2 E-enyl)-2beta-carbomethoxy-3beta-(4-methylphenyl)nortropane (PE2I) was radiolabelled by the O-methylation approach and the binding was characterised by PET in cynomolgus monkeys and a healthy man. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography. O-methylation of the corresponding free acid precursor with [(11)C]methyl triflate gave high radiochemical yield (80%) and specific radioactivity (55 GBq/ microM). [(11)C]PE2I binding in cynomolgus monkeys was nine times higher in the striatum than in the cerebellum at peak equilibrium, which appeared 55-65 min after injection. Displacement and pretreatment measurements using unlabelled beta-CIT, GBR 12909, cocaine, citalopram and maprotiline confirmed that [(11)C]PE2I binds selectively to DAT. In a preliminary study in one human subject the radioactivity ratios of the striatum and substantia nigra to the cerebellum were 10 and 1.8, respectively, at peak equilibrium, which appeared at 40-50 min and 20 min, respectively, after injection. The fraction of the total radioactivity in monkey and human plasma representing unchanged [(11)C]PE2I was 15-20% at 40 min after injection. The present characterisation of binding in monkey and man suggests that [(11)C]PE2I is a suitable PET radioligand for quantitative regional examination of DAT in man.

Adult↗
PubMed2003

Occupancy of 5-HT1A receptors by clozapine in the primate brain: a PET study.

RATIONALE: The pharmacological mechanism underlying the atypical properties of the antipsychotic drug clozapine remains to be identified. The serotonin 5-hydroxytryptamine-1A (5-HT(1A)) receptor subtype has been suggested to play a role in the pathophysiology of schizophrenia and is one among several central neuroreceptors for which clozapine has moderate affinity in vitro. OBJECTIVE: The aim of this positron emission tomography (PET) study was to determine 5-HT(1A) receptor occupancy in the monkey brain after IV injection of clozapine in doses that previously have been shown to give plasma concentrations representative of the 200 to 800 mg oral dose range recommended for clinical management of patients. METHODS: Each of four cynomolgus monkeys was examined three times on the same day with PET and the radioligand [carbonyl-(11)C]WAY-100635. The first measurement was performed at baseline conditions, the second after clozapine 1.5 mg/kg and the third after 6 mg/kg. Two additional monkeys were examined at baseline and after 15 mg/kg IV. Central 5-HT(1A) receptor occupancy was calculated using an equilibrium-ratio analysis. RESULTS: The occupancy ranged from 23 to 34% after 1.5 mg/kg clozapine and from 36 to 49% after 6 mg/kg in different brain regions of the four monkeys. The regional receptor occupancy values after 15 mg/kg were between 39 and 51% in the two monkeys. There was no evident difference between the frontal cortex, the temporal cortex and the raphe nucleus. CONCLUSION: The study shows that clozapine occupies 5-HT(1A) receptors in the primate brain at clinically representative plasma concentrations. The results support that the 5-HT(1A) receptor is a candidate target for the atypical drug actions of clozapine.

Animals↗
PubMed2003

Crossover study of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET in Parkinson's disease patients.

UNLABELLED: 99mTc-TRODAT-1 ([2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3,2,1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N2',S2,S2']oxo-[1R-(exo-exo)]) is a potential agent for dopamine transporter (DAT) SPECT, whereas 6-(18)F-fluoro-L-dopa ((18)F-FDOPA) PET has been used for the quantitative assessment of presynaptic nigrostriatal dopaminergic function. The current study investigated the relationship between the 2 imaging modalities in evaluating patients with Parkinson's disease (PD). METHODS: Twenty patients in whom PD was diagnosed by generally accepted criteria were recruited. In addition to visual inspection, specific uptake ratios (SURs) of (99m)Tc-TRODAT-1 in the striatum and putamen were measured bilaterally. For PET, all patients received 100 mg of carbidopa 90 min before (18)F-FDOPA (300 MBq) injection. Images were acquired between 120 and 150 min after injection, using a whole-body PET scanner with settings identical to those for the SPECT studies. The SURs for PET were calculated similarly to those for SPECT. Individual SURs of the striatum or putamen from SPECT were correlated with the corresponding PET values using linear regression. RESULTS: A consistent image pattern between SPECT and PET was achieved by visual inspection except for 3 cases. In 1 case (a patient with Hoehn and Yahr Scale I PD), the SPECT images were more compatible with the patient's clinical findings whereas PET showed nearly normal uptake. In the other 2 cases (both patients with Hoehn and Yahr Scale II PD), PET correlated better with the clinical findings. The caudate and putamen nuclei were more discernable on PET. An acceptable correlation of SUR, however, was found between SPECT and PET in both the striatum and the putamen (P < 0.01 for both). CONCLUSION: The comparability of (99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET suggests that (99m)Tc-TRODAT-1 SPECT may provide a reliable alternative to (18)F-FDOPA PET in the evaluation of clinical PD patients.

Aged↗
PubMed2002

PET-examination and metabolite evaluation in monkey of [(11)C]NAD-299, a radioligand for visualisation of the 5-HT(1A) receptor.

NAD-299 is a selective 5-HT(1A) receptor antagonist that is currently developed as a putative antidepressant drug. [(11)C]NAD-299 was examined in the cynomolgus monkey brain with positron emission tomography (PET). After radioligand injection high accumulation of radioactivity was observed in the frontal and temporal cortex and the raphe nuclei, regions known to contain a high density of 5-HT(1A) receptors. Peak equilibrium appeared already at about 10 min after i.v. injection. Pre-treatment with a high dose of the antagonist WAY-100635 reduced the amount of radioactivity in the cortex and the raphe to the level of the cerebellum. A strong pre-treatment effect could also be achieved using pindolol, a partial agonist at the 5-HT(1A)-receptors. The appearance of labeled metabolites in monkey plasma was measured with HPLC. At 45 minutes after injection 49% (range 27-55%, n = 5) of radioactivity in monkey plasma represented unchanged radioligand. [(11)C]NAD-299 was metabolized to more polar labeled metabolites of which one has the same chromatographic mobility as the descyclobutyl analogue of NAD-299 (NAD-272). The results indicate that [(11)C]NAD-299 has potential as a PET radioligand for studies of 5-HT(1A) receptors in the primate brain.

Animals↗
PubMed2002

PET examination of [(11)C]5-methyl-6-nitroquipazine, a radioligand for visualization of the serotonin transporter.

Radiohalogenated 5-halo-6-nitroquipazine analogues have been shown to be potential radioligands for visualization of the serotonin transporter (5-HTT) with PET and SPECT. In the present study a methylated analogue, 5-methyl-6-nitroquipazine (MNQP), was radiolabeled with carbon-11 in a two step reaction via a palladium catalyzed cross coupling reaction between N-t-BOC-protected 5-tributylstannyl-6-nitroquipazine and [(11)C]methyl iodide as key step. [(11)C]MNQP was examined in the cynomolgus monkey brain with positron emission tomography (PET) and the appearance of labeled metabolites in monkey plasma was measured with gradient HPLC. Radioactivity increased continuously in all brain regions during the 90 minutes acquisition time. Highest accumulation of radioactivity was observed in the thalamus and brainstem, regions with a known high density of 5-HTT. The calculated ratios between the thalamus and brainstem to the 5-HTT poor cerebellum were 1.5 and 1.3-1.4, respectively, 80 minutes after radioligand injection. Pretreatment with citalopram prior to the PET measurement markedly reduced the binding in the thalamus and the brainstem. At 15 and 30 minutes after injection of [(11)C]MNQP approximately 90% and 60%, respectively, of radioactivity in plasma represented unchanged radioligand. The slow kinetics and moderate ratios recorded however, may limit its use as a PET radioligand for quantitative studies of the serotonin transporter with PET.

Animals↗
PubMed2002

Saturation of striatal D(2) dopamine receptors by clozapine.

Positron emission tomography (PET) studies have demonstrated low striatal D2 dopamine receptor occupancy in clozapine-treated schizophrenic patients. The aim of this pilot study was to explore if this low receptor occupancy indeed represents partial saturability of striatal D2 dopamine receptors by clozapine. Three anaesthetized Cynomolgus monkeys were examined during one day with PET and [11C]raclopride at baseline and after intravenous injections of clozapine 1.5 mg/kg followed by 18.5 mg/kg. The estimated corresponding human oral doses were approx. 210 mg/d and 2800 mg/d. D2 dopamine receptor occupancy was calculated using an equilibrium-ratio analysis and ranged from 54 to 58% after 1.5 mg/kg and 87 to 89% after the total dose 20 mg/kg. The calculated maximal occupancy was 93%. We conclude that PET-measured D2 dopamine receptor occupancy by clozapine can be described using a model based on the law of mass action, previously validated for conventional antipsychotics. Therefore, sufficiently high doses of clozapine are expected to produce complete striatal D2 dopamine receptor occupancy. The findings further support our previous findings of low D2 dopamine receptor occupancy in patients treated with standard doses of clozapine.

Algorithms↗
PubMed2000

A PET study of

Several radiolabelled cocaine analogues have been proposed for brain imaging of the dopamine transporter in research on neuropsychiatric disorders and drug abuse. In a recent positron emission tomography (PET) study we labelled the cocaine analogue ß-CIT-FE with carbon-11 and demonstrated high specific binding in the monkey striatum. In the present study, the selectivity of [11C]ß-CIT-FE binding in the primate brain was examined by pretreatment experiments with reference ligands for the dopamine, serotonin and norepinephrine transporter. In three healthy human subjects the regional binding of [11C]ß-CIT-FE was analysed using equilibrium and kinetic analyses. A Scatchard analysis showed that [11C]ß-CIT-FE bound in a saturable manner yielded a density value of the same order as that reported in vitro. The pharmacological characterization indicated that a high degree of [11C]-CIT-FE binding in the primate striatum represents the dopamine transporter. In human subjects the radioligand provided high brain uptake and reached peak equilibrium within 1 hour after i.v. injection. Different quantitative approaches gave similar values for the binding potential. The results support the view that [11C]ß-CIT-FE is a suitable radioligand for clinical studies of the dopamine transporter. In particular for studies requiring short data acquisition or repeated PET measurements on the same day.

Journal Article↗