Biomedical subjects

J S Fowler

Publications and source records attributed to J S Fowler.

At least 127 records · Page 7Linked to original sources

PubMed1996

Reproducibility of regional brain metabolic responses to lorazepam.

UNLABELLED: Changes in regional brain glucose metabolism in response to benzodiazepine agonists have been used as indicators of benzodiazepine-GABA receptor function. The purpose of this study was to assess the reproducibility of these responses. METHODS: Sixteen healthy right-handed men underwent scanning with PET and [18F]fluorodeoxyglucose (FDG) twice: before placebo and before lorazepam (30 micrograms/kg). The same double FDG procedure was repeated 6-8 wk later on the men to assess test-retest reproducibility. RESULTS: The regional absolute brain metabolic values obtained during the second evaluation were significantly lower than those obtained from the first evaluation regardless of condition (p < or = 0.001). Lorazepam significantly and consistently decreased both whole-brain metabolism and the magnitude. The regional pattern of the changes were comparable for both studies (12.3% +/- 6.9% and 13.7% +/- 7.4%). Lorazepam effects were the largest in the thalamus (22.2% +/- 8.6% and 22.4% +/- 6.9%) and occipital cortex (19% +/- 8.9% and 21.8% +/- 8.9%). Relative metabolic measures were highly reproducible both for pharmacologic and replication condition. CONCLUSION: This study measured the test-retest reproducibility in regional brain metabolic responses, and although the global and regional metabolic values were significantly lower for the repeated evaluation, the response to lorazepam was highly reproducible.

Adult↗

PubMed1996

PET evaluation of the dopamine system of the human brain.

Dopamine plays a pivotal role in the regulation and control of movement, motivation and cognition. It also is closely linked to reward, reinforcement and addiction. Abnormalities in brain dopamine are associated with many neurological and psychiatric disorders including Parkinson's disease, schizophrenia and substance abuse. This close association between dopamine and neurological and psychiatric diseases and with substance abuse make it an important topic in research in the neurosciences and an important molecular target in drug development. PET enables the direct measurement of components of the dopamine system in the living human brain. It relies on radiotracers which label dopamine receptors, dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine. Additionally, by using tracers that provide information on regional brain metabolism or blood flow as well as neurochemically specific pharmacological interventions, PET can be used to assess the functional consequences of changes in brain dopamine activity. PET dopamine measurements have been used to investigate the normal human brain and its involvement in psychiatric and neurological diseases. It has also been used in psychopharmacological research to investigate dopamine drugs used in the treatment of Parkinson's disease and of schizophrenia as well as to investigate the effects of drugs of abuse on the dopamine system. Since various functional and neurological parameters can be studied in the same subject, PET enables investigation of the functional integrity of the dopamine system in the human brain and investigation of the interactions of dopamine with other neurotransmitters. Through the parallel development of new radiotracers, kinetic models and better instruments, PET technology is enabling investigation of increasingly more complex aspects of the human brain dopamine system. This paper summarizes the different tracers and experimental strategies developed to evaluate the various elements of the dopamine system in the human brain with PET and their applications to clinical research.

Brain↗

PubMed1995

Binding of d-threo-[11C]methylphenidate to the dopamine transporter in vivo: insensitivity to synaptic dopamine.

The regional distribution of [11C]d-threo-methylphenidate in mouse brain was very similar to that of [3H]WIN 35,428 ((-)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane), and the two radioligands were displaced from striatum similarly after administration of the potent cocaine analog RTI-55 ((-)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane). However, while striatal [3H]WIN 35,428 increased between 5 and 30 min, striatal [11C]d-threo-methylphenidate halved. Thus [11C]d-threo-methylphenidate binds similarly to but more reversibly than [3H]WIN 35,428. The methyl ester of L-DOPA (L-3,4-dihydroxyphenylalanine; 200 mg/kg) plus benserazide plus clorgyline, which markedly elevates rat striatal extracellular dopamine (Wachtel and Abercrombie, 1994, J. Neurochem. 63, 108), decreased the mouse striatum-to-cerebellum ratio for [11C]d-threo-methylphenidate at 30 min by 13% (P < 0.05). In positron emission tomographic (PET) baboon studies [11C]d-threo-methylphenidate binding was insensitive to drugs expected to lower endogenous dopamine. These experiments suggest that normal synaptic dopamine does not compete for binding with [11C]d-threo-methylphenidate, and will not affect PET measures of dopamine transporter availability.

Animals↗

PubMed1995

Serotonin 5-HT2 receptor availability in chronic cocaine abusers.

Serotonin 5-HT2 receptor availability was evaluated in chronic cocaine abusers (n = 19) using positron emission tomography and F-18 N-methylspiperone and was compared to control subjects (n =19). 5-HT2 Receptor availability was measured in frontal, occipital, cingulate and orbitofrontal cortices using the ratio of the distribution volume in the region of interest to that in the cerebellum which is a function of Bmax/Kd. 5-HT2 Receptor availability was significantly higher in cingulate and orbitofrontal cortices than in other frontal regions or occipital cortex. The values were not different in normal subjects and cocaine abusers. These results did not show any changes in 5-HT2 receptor availability in cocaine abusers as compared to the control subjects.

Adolescent↗

PubMed1995

Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain.

BACKGROUND: The purposes of this study were to investigate the pharmacokinetics of methylphenidate hydrochloride (Ritalin) in the human brain, to compare them with those of cocaine, and to evaluate whether cocaine and methylphenidate compete for the same binding sites. METHODS: We used positron emission tomography to measure the temporal and spatial distribution of carbon 11 (11C)-labeled methylphenidate. These results were compared with those obtained previously for [11C]cocaine. Eight healthy male subjects, 20 to 51 years of age, were scanned with [11C]methylphenidate. Three were tested twice to assess test-retest variability, four were tested at baseline and after administration of methylphenidate, and one was tested with [11C]methylphenidate and [11C]cocaine. Two baboons were scanned to evaluate whether there was competition between cocaine and methylphenidate for the same binding sites in the brain. RESULTS: The uptake of [11C]methylphenidate in the brain was high (mean +/- SD, 7.5% +/- 1.5%), and the maximal concentration occurred in striatum. Pretreatment with methylphenidate decreased binding only in striatum (40%). Although the regional distribution of [11C]methylphenidate, was identical to that of [11C]cocaine and they competed with each other for the same binding sites, these two drugs differed markedly in their pharmacokinetics. Clearance of [11C]methylphenidate from striatum (90 minutes) was significantly slower than that of [11C]cocaine (20 minutes). For both drugs, their fast uptake in striatum paralleled the experience of the "high." For methylphenidate, the high decreased very rapidly despite significant binding of the drug in the brain. In contrast, for cocaine, the decline in the high paralleled its fast rate of clearance from the brain. CONCLUSION: We speculate that because the experience of the high is associated with the fast uptake of cocaine and methylphenidate in the brain, the slow clearance of methylphenidate from the brain may serve as a limiting factor in promoting its frequent self-administration.

Adult↗

PubMed1995

Haloperidol blocks the uptake of [18F]N-methylspiroperidol by extrastriatal dopamine receptors in schizophrenic patients.

We had previously demonstrated extrastriatal uptake of [18F]N-methylspiroperidol (18F-NMS) in the human brain. This study evaluates the effect of haloperidol on 18F-NMS binding in extrastriatal brain regions. Six schizophrenic patients on haloperidol underwent two PET scans with 18F-NMS at 12 h and at 6 days after haloperidol withdrawal. There was a significant increase in 18F-NMS uptake in striatal, thalamic, and temporal regions but not in frontal, occipital, or cerebellar regions, following drug withdrawal. Haloperidol's ability to block the uptake of 18F-NMS is an indication of the specificity of the radioligand's binding in these regions and supports the postmortem data demonstrating the presence of dopamine D2 receptors in the thalamus and temporal cortex of the human brain.

Adult↗

PubMed1995

Long-lasting inhibition of in vivo cocaine binding to dopamine transporters by 3 beta-(4-iodophenyl)tropane-2-carboxylic acid methyl ester: RTI-55 or beta CIT.

Cocaine analogs such as 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) with a higher affinity for the dopamine transporter (DAT) may be potentially useful in interfering with cocaine's actions in brain. This study evaluates the time course of the effects of RTI-55 on cocaine binding in baboon brain using PET and [11C]cocaine. [11C]Cocaine binding was measured prior to, and 90 minutes, 24 hours, 4-5 days and 11-13 days after RTI-55 (0.3 mg/kg i.v.). Parallel studies with [3H]cocaine and RTI-55 (0.5 mg/kg i.v. or 2 mg/kg i.p.) were performed in the mouse. RTI-55 significantly inhibited [11C]cocaine binding at 90 minutes and 24 hours after administration. The half-life for the clearance of RTI-55 from the DAT was estimated to be 2 to 3 days in the baboon brain. In the mouse brain, RTI-55 significantly inhibited [3H]cocaine binding at 60 and 180 minutes after administration and recovery was observed at 12 hours. These results document long-lasting inhibition of cocaine binding by RTI-55 and corroborate that binding kinetics of RTI-55 in striatum observed in imaging studies with [123I]RTI-55 represents binding to DATs.

Animals↗

PubMed1995

Sensitivity of striatal [11C]cocaine binding to decreases in synaptic dopamine.

We have previously shown that tracer concentrations of [11C]cocaine binding to the dopamine transporter (DAT) in human and baboon striatum can be visualized using positron emission tomography (PET). To determine whether the concentration of dopamine normally present in the synaptic cleft can compete with [11C]cocaine for transporter binding sites, we conducted baboon PET studies with drugs (sodium 4-hydroxybutyrate, four studies, 200 mg/kg; gamma-vinylGABA, three studies, 300 mg/kg; and citalopram, three studies, 2 mg/kg) expected to decrease synaptic dopamine. Each study involved two [11C]cocaine injections and PET scans separated by 2-4 h, with drug administration after the first injection, and without movement of the subject between scans. Time-activity data from striatum and from cerebellum were used with the arterial plasma input function to determine graphically by Logan plotting [11C]cocaine distribution volumes for the brain regions. Specific binding of [11C]cocaine to DAT in striatum was calculated as the distribution volume ratio (DVR) for striatum and cerebellum. In nine of the ten studies drug treatment produced a small increase in DVR (range, 1-11%), and in seven of these studies the increase was > or = 7%. The mean increase was 6.2 +/- 4.1%. The reproducibility of the DVR measure was assessed by comparing [11C]cocaine studies conducted without pharmacological treatments using individual baboons on separate days, and thus involving possible repositioning errors, as well as long-term changes in the state of the striatal dopamine system.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Evaluation of age-related changes in serotonin 5-HT2 and dopamine D2 receptor availability in healthy human subjects.

We assessed the relation between serotonin 5-HT2 receptor availability and aging and compared it with that for dopamine D2 receptors on 19 healthy male volunteers (age range, 21-49 years) using positron emission tomography (PET) and F-18 N-methylspiperone (NMS). 5-HT2 Receptor availability was obtained using the ratio of the distribution volume in the region of interest to that in the cerebellum (Bmax'/Kd' + 1). 5-HT2 Receptor measures were obtained in frontal and occipital cortices. D2 receptor availability in striatum was measured using the "ratio index". 5-HT2 Receptor availability decreased significantly with age. This effect was significantly more accentuated for 5-HT2 receptor availability in the frontal (r = 0.92, p < or = 0.0001) than in the occipital (r = 0.67, p < or = 0.0016) cortex (df = 1, p < 0.025). Dopamine D2 receptors were also found to decrease significantly with age (r = 0.63, p < or = 0.007). In a given subject, striatal D2 receptor availability significantly correlated with 5-HT2 receptor availability in the frontal (r = 0.51, p < or = 0.035) but not in the occipital cortex. These results document a decline in 5-HT2 and D2 receptor availability with age and showed an association between frontal 5-HT2 and striatal D2 receptors.

Adult↗

PubMed1995

Comparison of two pet radioligands for imaging extrastriatal dopamine transporters in human brain.

We compared the sensitivity of two dopamine transporter (DAT) ligands ([C-11]cocaine and [C-11]d-threo-methylphenidate) for measurement of extrastriatal DAT availability using positron emission tomography (PET) on separated groups of 10 age matched male volunteers (age range, 21-49 years). DAT availability was obtained using the ratio of the distribution volume in the region of interest to that in the cerebellum (Bmax'/Kd'+ 1). DAT availability measured with [C-11]d-threo-methylphenidate was highest in basal ganglia, followed by thalamus > temporal insula, cingulate > orbitofrontal, frontal and occipital cortices. A similar ranking order for DAT availability was obtained with [C-11]cocaine. Specific binding (Bmax'/Kd') of [C-11]cocaine in thalamus was 25-33% that of basal ganglia and [C-11]d-threo-methylphenidate in thalamus was 11-13% that of basal ganglia. The regional measures with [C-11]cocaine were significantly correlated with those of [C-11]d-threo-methylphenidate (p < or = 0.0001). These results document extrastriatal binding in human brain with two different DAT ligands.

Adult↗

PubMed1995

Depression of thalamic metabolism by lorazepam is associated with sleepiness.

Though it is well recognized that the pharmacological actions of benzodiazepines are mediated by facilitation of GABAergic neurotransmission, the consequences of these changes in regional brain function are not well understood. This study measured regional brain glucose metabolism using Positron Emission Tomography and 2-deoxy-2[18F]fluoro-D-glucose in normal controls (n = 21) investigated with and without lorazepam (30 micrograms/kg IV) and with flumazenil given after lorazepam (n = 9). Lorazepam markedly decreased metabolism in thalamus (23 +/- 8%) and occipital cortex (19 +/- 8%), and flumazenil partially reversed these changes. Changes in metabolic activity in thalamus were significantly correlated with lorazepam-induced sleepiness (r = .69, df 20, p < .0005) and there was a trend of an association between the reversal by flumazenil of lorazepam-induced change in thalamus and in sleepiness (r = .63, df 8, p = .07). Benzodiazepine-induced changes in thalamic activity may account for their sedative properties.

Adult↗

PubMed1995

Plasma input function determination for PET using a commercial laboratory robot.

A commercial laboratory robot system (Zymate PyTechnology II Laboratory Automation System) was interfaced to standard and custom laboratory equipment and programmed to perform rapid radiochemical assays necessary for plasma input function determination in quantitative PET studies in humans and baboons. A Zymark XP robot arm was used to carry out two assays: (1) the determination of total plasma radioactivity concentrations in a series of small-volume whole blood samples and (2) the determination of unchanged (parent) radiotracer in plasma using only solid phase extraction methods. Steady state robotic throughput for determination of total plasma radioactivity in whole blood samples (0.350 mL) is 14.3 samples/h, which includes automated centrifugation, pipetting, weighing and radioactivity counting. Robotic throughput for the assay of parent radiotracer in plasma is 4-6 samples/h depending on the radiotracer. Percents of total radioactivities present as parent radiotracers at 60 min, postinjection of 25 +/- 5.0 (N = 25), 26 +/- 6.8 (N = 68), 13 +/- 4.4 (N = 30), 32 +/- 7.2 (N = 18), 16 +/- 4.9 (N = 20), were obtained for carbon-11 labeled benztropine, raclopride, methylphenidate, SR 46349B (trans, 4-[(3Z)3-(2-dimethylamino-ethyl) oxyimino-3 (2-fluorophenyl)propen-1-yl]phenol), and cocaine respectively in baboon plasma and 84 +/- 6.4 (N = 9), 18 +/- 11 (N = 10), 74 +/- 5.7 (N = 118) and 16 +/- 3.7 (N = 18) for carbon-11 labeled benztropine, deprenyl, raclopride, and methylphenidate respectively in human plasma. The automated system has been used for more than 4 years for all plasma analyses for 7 different C-11 labeled compounds used routinely in our laboratory. The robotic radiotracer assay runs unattended and includes automated cleanup procedures that eliminates all human contact with plasma-contaminated containers.

Animals↗

PubMed1995

Mechanistic positron emission tomography studies of 6-[18F]fluorodopamine in living baboon heart: selective imaging and control of radiotracer metabolism using the deuterium isotope effect.

Mechanistic positron emission tomography (PET) studies using the deuterium isotope effect and specific pharmacological intervention were undertaken to examine the behavior of 6-[18F]fluorodopamine (6-[18F]-FDA; 1) and (-)-6-[18F]fluoronorepinephrine [(-)-6-[18F]FNE; 2] in the baboon heart. Two regiospecifically deuterated derivatives of 6-[18F]FDA [alpha,alpha-D2 (3) and beta,beta-D2 (4)] were used to assess the contributions of monoamine oxidase (MAO) and dopamine beta-hydroxylase, respectively, to the clearance kinetics of 6-[18F]FDA. Compound 3 showed a reduced rate of clearance, consistent with MAO-catalyzed cleavage of the alpha C-D bond, whereas compound 4 showed no change, indicating that cleavage of the beta C-D bond is not a rate-limiting step. Pretreatment with pargyline, an MAO inhibitor, also decreased the rate of clearance. Desipramine and tomoxetine [norepinephrine (NE) uptake inhibitors], but not GBR-12909 (a dopamine uptake inhibitor), blocked the uptake of both (-)-6-[18F]FNE and 6-[18F]FDA, with (-)-6-[18F]FNE showing a higher degree of blockade. Chiral HPLC demonstrated that 6-[18F]FDA is stereoselectively converted to (-)-6-[18F]FNE in vivo in the rat heart. These studies demonstrate that (a) the more rapid clearance of 6-[18F]FDA relative to (-)-6-[18F]FNE can be largely accounted for by metabolism by MAO; (b) selective deuterium substitution can be used to protect a radiotracer from metabolism in vivo and to favor a particular pathway; (c) 6-[18F]FDA and (-)-6-[18F]FNE share the NE transporter; (d) 6-[18F]FDA is stereoselectively converted to (-)-6-[18F]FNE in vivo; and (e) the profile of radioactivity in the heart for 6-[18F]FDA is complex, probably including labeled metabolites as well as neuronal and nonneuronal uptake.

Animals↗

PubMed1995

Regional brain metabolic response to lorazepam in subjects at risk for alcoholism.

The mechanisms underlying the blunted response to alcohol administration observed in subjects at risk for alcoholism are poorly understood and may involve GABA-benzodiazepine receptors. The purpose of this study was to investigate if subjects at risk for alcoholism had abnormalities in brain GABA-benzodiazepine receptor function. This study measured the effects of 30 micrograms/kg (i.v.) of lorazepam, on regional brain glucose metabolism using positron emission tomography and 2-deoxy-2[18F]fluoro-D-glucose in subjects with a positive family history for alcoholism (FP) (n = 12) and compared their response with that of subjects with a negative family history for alcoholism (FN) (n = 21). At baseline, FP subjects showed lower cerebellar metabolism than FN. Lorazepam decreased whole-brain glucose metabolism, and FP subjects showed a similar response to FN in cortical and subcortical regions, but FP showed a blunted response in cerebellum. Lorazepam-induced changes in cerebellar metabolism correlated with its motor effects. The decreased cerebellar baseline metabolism in FP as well as the blunted cerebellar response to lorazepam challenge may reflect disrupted activity of benzodiazepine-GABA receptors in cerebellum. These changes could account for the decreased sensitivity to the motor effects of alcohol and benzodiazepines in FP subjects.

Adult↗

PubMed1995

Positron emission tomography. Biomedical research and clinical application.

Positron emission tomography (PET) is described as a tool in basic and clinical research in the neurosciences, especially in brain and heart. The physics and chemistry of the technique are reviewed. Numerous applications include measuring metabolism, blood flow and neurotransmitter properties quantitatively in vivo. Applications in facilitating drug research are outlined. PET is a unique tool for assessing in vivo biochemistry in humans.

Brain↗

PubMed1995

Selective reduction of radiotracer trapping by deuterium substitution: comparison of carbon-11-L-deprenyl and carbon-11-deprenyl-D2 for MAO B mapping.

UNLABELLED: Recent human PET studies with the monoamine oxidase B (MAO B) tracer [11C]L-deprenyl show that the rapid rate of radiotracer trapping relative to transport reduces the sensitivity of the tracer in regions of high MAO B concentration. This study investigates the use of deuterium substituted L-deprenyl ([11C]L-deprenyl-D2) to reduce the rate of trapping in tissue and to improve sensitivity. METHODS: Five normal subjects (43-64 yr) were studied with [11C]L-deprenyl and [11C]L-deprenyl-D2 on the same day. Time-activity data from different brain regions and the arterial plasma were analyzed using a three-compartment model as well as graphical analysis for irreversible systems. RESULTS: For both tracers, maximum radioactivity accumulation occurred at about 5 min. For [11C]L-deprenyl, 11C concentration peaked at 5 min and remained constant throughout the study. With [11C]L-deprenyl-D2, peak 11C concentration also occurred at about 5 min but was followed by an initial washout. Carbon-11 concentration generally plateaued from 30 to 60 min. The plateau for [11C]L-deprenyl was higher than the plateau for [11C]L-deprenyl-D2. Data analysis by a three-compartment model and by graphical analysis showed that deuterium substitution: (a) does not affect plasma to tissue transport (K1); (b) reduces the rate of trapping of 11C in all brain regions; (c) facilitates the separation of model terms related to radiotracer delivery from radiotracer trapping in tissue; and (d) improves tracer sensitivity. CONCLUSION: This study demonstrates that deuterium substitution causes a significant reduction in the rate of trapping of labeled deprenyl, providing a direct link between radiotracer uptake and MAO B in the human brain and enhancing tracer sensitivity to changes in MAO B concentration.

Adult↗

PubMed1995

Carbon-11-cocaine binding compared at subpharmacological and pharmacological doses: a PET study.

UNLABELLED: We have characterized cocaine binding in the brain to a high-affinity site on the dopamine transporter using PET and tracer doses of [11C]cocaine in the baboon in vivo. The binding pattern, however, of cocaine at tracer (subpharmacological) doses may differ from that observed when the drug is taken in behaviorally active doses particularly since in vitro studies have shown that cocaine also binds to low affinity binding sites. METHODS: PET was used to compare and characterize [11C]cocaine binding in the baboon brain at low subpharmacological (18 micrograms average dose) and at pharmacological (8000 micrograms) doses. Serial studies on the same day in the same baboon were used to assess the reproducibility of repeated measures and to assess the effects of drugs which inhibit the dopamine, norepinephrine and serotonin transporters. Time-activity curves from brain and the arterial plasma input function were used to calculate the steady-state distribution volume (DV). RESULTS: At subpharmacological doses, [11C]cocaine had a higher binding and slower clearance in striatum than in other brain regions. At pharmacological doses, [11C]cocaine had a more homogeneous distribution. Bmax/Kd for sub-pharmacological [11C]cocaine corresponded to 0.5-0.6 and for pharmacological [11C]cocaine it corresponded to 0.1-0.2. Two-point Scatchard analysis gave Bmax = 2300 pmole/g and Kd' = 3600 nM. Bmax/Kd for sub-pharmacological doses of [11C]cocaine was decreased by cocaine and drugs that inhibit the dopamine transporter, to 0.1-0.2, but not by drugs that inhibit the serotonin or the norepinephrine transporter. None of these drugs changed Bmax/Kd for a pharmacological dose of [11C]cocaine. CONCLUSION: At subpharmacological doses, [11C]cocaine binds predominantly to a high-affinity site on the dopamine transporter.

Animals↗

PubMed1995

A new PET ligand for the dopamine transporter: studies in the human brain.

UNLABELLED: Carbon-11-d-threo-methylphenidate, the active enantiomer of methylphenidate (ritalin), has been shown to bind uniquely to the dopamine transporter in the baboon brain. This study characterizes its binding in the human brain and measures its test-retest reproducibility. METHODS: Studies were done in seven normal controls, each of whom was scanned with [11C]d-threomethylphenidate on two different occasions. Six subjects were scanned twice 3-5 wk apart without intervention to assess reproducibility. One subject was scanned sequentially before and after treatment with methylphenidate to assess binding saturability. Graphical analysis was used to obtain tissue distribution volumes (DV). The ratio of the DV in the basal ganglia (BG) to that in cerebellum (CB) (DVBG/DVCB), which corresponds to (Bmax/Kd) + 1 was used to estimate dopamine transporter availability. RESULTS: Highest tracer uptake occurred in the basal ganglia, where activity peaked 7-11 min postinjection. The half-clearance time for the tracer in brain regions other than the basal ganglia was 74 min. In the basal ganglia, only 10%-15% of the activity had cleared at 74 min. Time-activity curves for [11C]d-threo-methylphenidate in the basal ganglia and cerebellum were highly reproducible. The average percent change for the absolute value for DVBG/DVCB was 6.5% +/- 4% (range 0-12%). Methylphenidate pretreatment decreased basal ganglia uptake but not cortical or cerebellar binding and reduced DVBG/DVCB by 62% and Bmax/Kd by 91%. CONCLUSION: These studies demonstrate that [11C]d-threo-methylphenidate binding in the human brain is reversible, highly reproducible and saturable. Thus, it is an appropriate PET ligand to measure dopamine transporter availability.

Adult↗