P Karlsson

Karolinska University Hospital, Tukholma, Stockholm, Sweden

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Publications (87)308.91 Total impact

  • NeuroImage. 01/2012; 59:3582-3593.
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    ABSTRACT: The dopamine transporter (DAT) is of central interest in research on the pathophysiology and treatment of neuro-psychiatric disorders. [(11)C]PE2I is an established radioligand that provides high-contrast delineation of brain regions that are rich in DAT. The aim of the present PET study in eight patients with juvenile myoclonic epilepsy (JME) was to evaluate the kinetics of [(11)C]PE2I in the brain and to compare binding parameters with those of age-matched control subjects (n = 6). Each patient participated in 90-minute PET measurements with [(11)C]PE2I. Data were analyzed using kinetic compartment analyses with metabolite-corrected arterial plasma input and reference tissue models using the cerebellum as a reference region. The time-activity curves were well described by the two-tissue compartment model (2TCM) for the DAT-rich regions. The 2TCM with fixed K(1)/k(2) ratio derived from the cerebellum provided robust and reliable estimates of binding potential (BP(ND)) and total distribution volume (V(T)). The reference tissue models also provided robust estimates of BP(ND), although they gave lower BP(ND) values than the kinetic analysis. Compared with those of control subjects, we found that BP(ND) values obtained by all approaches were reduced in the midbrain of the patients with JME. The finding indicates impaired dopamine uptake in the midbrain of JME patients. The three-tissue compartment model could best describe uptake in the cerebellum, indicating that two kinetically distinguishable compartments exist in cerebellar tissue, which may correspond to nonspecific binding and the blood-brain barrier passing metabolite. The reference tissue models should be applied with better understanding of the biochemical nature of the radioligand and the reliability of these approaches.
    NeuroImage 10/2011; 59(4):3582-93. · 6.25 Impact Factor
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    ABSTRACT: Dopamine (DA) availability in both striatal and extrastriatal brain regions has been implicated in cognitive performance. Given that different brain regions are neuroanatomically and functionally different, DA receptor binding in different brain regions may be selectively important to specific cognitive functions. Using PET and the radioligand SCH23390, we measured D1 receptor binding potential (BP(ND)) in dorsolateral prefrontal cortex (DLPFC), hippocampus (HC), as well as in sensorimotor (SMST), associative (AST), and limbic (LST) striatum in 20 healthy younger persons. Subjects completed tasks assessing executive functioning, episodic memory, speed, and general knowledge. Unlike previous reports, we found no linear or curvilinear relationships between D1 receptor binding in DLPFC and performance in any cognitive task. However, BP(ND) in HC was positively linked to executive performance as well as to speed and knowledge. With regard to the striatal subregions, D1 BP(ND) in SMST was more strongly related to speed compared to the other striatal subregions, whereas D1 BP(ND) in AST was more strongly linked to general knowledge. These findings provide support for the notion that D1 receptors in separate brain regions are differentially related to performance in tasks tapping various cognitive domains.
    NeuroImage 07/2011; 57(2):346-51. · 6.25 Impact Factor
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    ABSTRACT: [(18)F]FEDAA1106 is a recently developed positron emission tomography (PET) radioligand for in vivo quantification of the 18 kDa translocator protein [TSPO or, as earlier called, the peripheral benzodiazepine receptor (PBR)]. TSPO imaging is expected to be useful for the clinical evaluation of neuroinflammatory diseases. The aim of this study was to provide dosimetry estimates for [(18)F]FEDAA1106 based on human whole-body PET measurements. PET scans were performed for a total of 6.6 h after the injection of 183.8 ± 9.1 MBq of [(18)F]FEDAA1106 in six healthy subjects. Regions of interest were drawn on coronal images. Estimates of the absorbed doses of radiation were calculated using the OLINDA software. Peak uptake was largest in lungs, followed by liver, small intestine, kidney, spleen and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lungs (27.1%ID at 0.2 h), liver (21.1%ID at 0.6 h), small intestine (10.4%ID at 6.3 h), kidney (4.9%ID at 1.8 h) and spleen (4.6%ID at 0.6 h). The largest absorbed dose was found in the spleen (0.12 mSv/MBq), followed by kidneys (0.094 mSv/MBq). The calculated mean effective dose was 0.036 mSv/MBq. Based on the distribution and dose estimates, the estimated radiation burden of [(18)F]FEDAA1106 is moderately higher than that of [(18)F]fluorodeoxyglucose (FDG). In clinical studies, the administered activity of this radioligand ought to be adjusted in line with regional regulations. This result would be helpful for further clinical TSPO imaging studies.
    European Journal of Nuclear Medicine 07/2011; 38(11):2058-65. · 4.53 Impact Factor
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    ABSTRACT: The serotonin 5-HT(1B) receptor is a potential target for the pharmacologic treatment of depression. Positron emission tomography (PET) determination of 5-HT(1B) receptor occupancy with drug candidates targeting this receptor in non-human primate and human subjects may facilitate translation of research from animal models and guide dose selection for clinical studies. AZD3783 is a recently developed, orally bioavailable 5-HT(1B) receptor antagonist with potential antidepressant properties. To determine the relationship between plasma concentration of AZD3783 and occupancy at primate brain 5-HT(1B) receptors using PET and the radioligand [(11)C]AZ10419369. PET studies with [(11)C]AZ10419369 were performed in three non-human primates at baseline and after intravenous injection of AZD3783. Subsequently, PET measurements were undertaken in six human subjects at baseline and after administration of different single oral doses of AZD3783 (1-40 mg). After administration in non-human primates and human subjects, AZD3783 reduced regional [(11)C]AZ10419369 binding in a dose-dependent and saturable manner. The AZD3783 plasma concentration required for 50% receptor occupancy (K (i,plasma)) for monkeys was 25 and 27 nmol/L in occipital cortex and striatum, respectively. Corresponding estimates for human occipital cortex and ventral striatum were 24 and 18 nmol/L, respectively. The potential antidepressant AZD3783 binds in a saturable manner to brain 5-HT(1B) receptors with a similar in vivo affinity for human and monkey receptors. [(11)C]AZ10419369 can be successfully used to determine occupancy at brain 5-HT(1B) receptors in vivo and constitutes a useful tool for dose selection in clinical studies with 5-HT(1B) receptor compounds.
    Psychopharmacology 02/2011; 213(2-3):533-45. · 4.06 Impact Factor
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    ABSTRACT: A novel radioligand for positron emission tomography (PET) imaging of serotonin 5-HT(1B) receptors, [(11)C]AZ10419369, has been recently described. In this study, the potential for quantitative analysis of [(11)C]AZ10419369 binding to central 5-HT(1B) receptors was evaluated in human subjects. PET measurements were performed after injection of [(11)C]AZ10419369 in 10 subjects. Data were analyzed with kinetic modeling and linear graphical analysis using the arterial plasma as input function, and with reference tissue models using cerebellar cortex as the reference region. Binding of [(11)C]AZ10419369 was highest in pallidum, ventral striatum, and occipital cortex and lowest in cerebellum. The percentage of unchanged radioligand in plasma was 97% to 99%, indicating that no significant amounts of radioactive metabolites were formed during the time of analysis. Time-activity curves of [(11)C]AZ10419369 could be described with both one-tissue compartment (1-TC) and two-tissue compartment (2-TC) models in the majority of subjects. The 2-TC model failed to deliver reasonable estimates of the kinetic parameters. However, stable estimates of binding potential (BP(ND)) were obtained by constraining K(1)/k(2) to the distribution volume obtained with the 1-TC model in the cerebellar cortex. BP(ND) values estimated with reference tissue models were correlated with the corresponding values obtained with kinetic modeling. The findings support the use of reference tissue models in applied clinical studies with [(11)C]AZ10419369.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 01/2011; 31(1):113-23. · 5.46 Impact Factor
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    ABSTRACT: Age-related dopamine (DA) losses have been extensively demonstrated for the D2 receptor subtype. Comparatively little is known about adult age changes regarding D1 receptors. In this study, we demonstrate marked age-related D1 receptor losses in striatal, limbic, and cortical areas using positron emission tomography and the radioligand [(11)C]SCH23390 in humans. Interregional correlations of binding potential (BP) values were high for areas within DA pathways in younger and elderly adults alike. Furthermore, interregional correlations in D1 BP between DA pathways were uniformly high in younger adults, indicating that D1 receptor densities in striatal, limbic, and cortical areas are not regulated independently, despite dopaminergic innervation from different midbrain areas. For elderly adults, between-pathway correlations of D1 receptor densities were preserved only between mesolimbic and mesocortical areas, whereas striatal BPs were weakly related to those in limbic and neocortical regions. Importantly, weak between-pathway correlations in elderly adults were found only for the slower half of the sample when BP was estimated during a cognitive interference task. These results suggest that D1 receptor densities in different pathways are not regulated independently in younger adults, but segregate in older age, and that this segregation of D1 receptor systems may be related to age-related cognitive slowing.
    Cerebral Cortex 01/2011; 21(9):2023-32. · 8.31 Impact Factor
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    ABSTRACT: Huntington's disease (HD) is a neurodegenerative disorder, primarily affecting medium spiny neurones in the striatum. The density of striatal dopamine D(2) receptors is reduced in HD but there is little known about this biomarker in brain regions outside the striatum. The primary objective of this study was to compare extrastriatal dopamine D(2) receptor binding, in age-matched control subjects and patients with HD. All subjects were examined using a high-resolution positron emission tomography system and the high-affinity dopamine D(2) receptor radioligand [(11) C]FLB 457. A ROI based analysis was used with an atrophy correction method. Dopamine D(2) receptor binding potential was reduced in the striatum of patients with HD. Unlike the striatum, dopamine D(2) receptor binding in thalamic and cortical subregions was not significantly different from that in control subjects. A partial least square regression analysis which included binding potential values from all investigated cortical and subcortical regions revealed a significant model separating patients from controls, conclusively dependent on differences in striatal binding of the radioligand. Some clinical assessments correlated with striatal dopamine D(2) receptor binding, including severity of chorea and cognitive test performance. Hence, the present study demonstrates that dopamine D(2) receptors extrinsic to the striatum are well preserved in early to mid stage patients with HD. This observation may have implication for the development of therapy for HD.
    Human Brain Mapping 09/2010; 32(10):1626-36. · 6.88 Impact Factor
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    ABSTRACT: Age-dependent decrease in dopamine receptor density throughout adulthood is well described, meanwhile less is known about development of dopamine system in humans and in vivo it has not been investigated. We examined dopamine D1 receptor (D1DR) binding in the cerebral cortex and striatum of 12 adolescents (mean age 13.5+/-1.8 years) and 18 young adults (25+/-2.3 years) using positron emission tomography (PET) and radioligand [(11)C]SCH23390. Over the age span of 10-30 years [(11)C]SCH23390 binding (binding potential, BP) declined in all brain regions. The rate of BP decline was age-segment and brain region dependent. Most pronounced decline in BP was observed in the cortical regions during adolescence (mean BP in adults lower by 14-26% as compared to adolescents, P<0.0001). Significantly slower rate of decline in BP was observed in two cortical regions (orbitofrontal and posterior cingulate cortices) and striatal regions. The present PET-study provides new evidence on the development of D1DR in humans in vivo which is of critical importance for understanding of the biology of neurodevelopmental disorders.
    Neuroscience 04/2010; 167(1):104-10. · 3.12 Impact Factor
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    ABSTRACT: Previous correlational studies have indirectly linked dysfunctional dopaminergic neurotransmission to age-related cognitive deficits and associated reductions in task-induced functional brain activity. We used an experimental-pharmacological functional magnetic resonance imaging (fMRI) approach to more directly examine the role of dopamine in neurocognitive aging. Twenty younger and 20 healthy older adults were included. During fMRI scanning, a spatial working memory (SWM) task was administered under two conditions, varying in cognitive load. Positron emission tomography measurements with the D1 receptor antagonist [(11)C]SCH23390 confirmed that a given experimental dose of unlabeled solution occupied 50% of D1 receptors in younger adults. An age-related reduction in SWM performance was observed, and fMRI data revealed that, relative to younger adults under placebo conditions, elderly persons under-recruited load-sensitive fronto-parietal regions during SWM. Critically, in younger adults, the D1 antagonist resulted in a similar reduction in SWM performance and fMRI response. These results suggest that depletion of dopamine, whether ontogenetically or pharmacologically, results in decreased SWM performance as well as reduced load-dependent modulation of the blood oxygen level dependent signal in fronto-parietal regions, possibly by decreasing the signal-to-noise ratio in relevant neural networks.
    Biological psychiatry 02/2010; 67(6):575-80. · 8.93 Impact Factor
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    ABSTRACT: There is strong evidence that dopamine (DA) is implicated in higher-order cognitive functioning, but it remains controversial whether D1 receptor binding can be modified by cognitive activity. We examined striatal D1 binding potential (BP) in 20 younger (22–30 years) and 20 older (65–75 years) persons who underwent two [11C] SCH 23390 PET measurements, one while resting and one while performing a cognitive task taxing inhibitory functioning. The younger persons showed significant task-related BP reductions in sensorimotor, limbic, and associative striatum during cognitive activity compared to rest. Older persons showed no reliable BP reductions in any striatal subregion. These findings demonstrate that D1 receptor binding can be modified by cognitive activity in younger persons, but also provide novel evidence for the notion that human aging is associated not only with lower DA receptor density but also with altered modifiability of the DA system.
    NeuroImage 12/2009; 48(2):398-404. · 6.25 Impact Factor
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    ABSTRACT: In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.
    Neurobiology of aging 12/2009; 32(10):1849-56. · 5.94 Impact Factor
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    ABSTRACT: [(11)C]flumazenil is the reference radioligand for Positron Emission Tomography (PET) studies of central benzodiazepine (BZ) receptors. Fluorine is available in the flumazenil molecule and [(18)F]flumazenil has recently been prepared. The aim of the present PET-study in 8 male subjects was to examine the binding of [(18)F]flumazenil in the human brain by direct comparison with [(11)C]flumazenil. Each subject participated in two 93-minute PET-measurements with [(11)C]flumazenil and [(18)F]flumazenil, respectively. Data were analyzed using compartment models with metabolite-corrected arterial plasma input and reference tissue models using the pons as reference region. There was no evident difference between the kinetic behaviors of the two ligands. Overall, the noise in the time activity curves for [(18)F]flumazenil was lower at late time points, and the variance of the kinetic parameters was lower than for [(11)C]flumazenil. In BZ receptor rich regions, such as the neocortex, the 3-compartment model was statistically favored, whereas the 2-compartment model was favored in the pons. Binding potential values obtained by the reference tissue models were in good agreement with those obtained by the kinetic analysis. There was no support for the presence of specific binding in the pons. In conclusion, the binding and the kinetic behavior of [(11)C]flumazenil and [(18)F]flumazenil were similar. The present analysis supports the use of pons as reference region in simplified protocols without arterial blood sampling. [(18)F]flumazenil should thus be an excellent choice for applied studies at centers not having a cyclotron.
    NeuroImage 01/2009; 45(3):891-902. · 6.25 Impact Factor
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    ABSTRACT: The aim of the present study was to explore the effects of the menstrual cycle phases on 5-HT(1A) receptor and 5-HTT binding potentials (BPs) in healthy women by using positron emission tomography (PET). Women were investigated in the follicular and luteal phase of the menstrual cycle with radioligands [(11)C]WAY10035 (n=13) and [(11)C]MADAM (n=8) to study 5-HT(1A) and 5-HTT BPs. The BPs values were quantified using the simplified reference tissue model. The phases of the menstrual cycle were characterized by transvaginal ultrasound (TSV) and plasma levels of hormones estradiol (E(2)), progesterone (P(4)), follicle stimulating hormone (FSH) and luteinizing hormone (LH).The 5-HT(1A) receptor and 5-HTT BPs did not significantly differ between follicular and luteal phases in any of the investigated regions. There were no significant correlations between the change in E(2) or P(4) values with the change in 5-HT(1A) receptor or 5-HTT BPs. The results provide principally a new in vivo finding in human female biology, suggesting the absence of influence of menstrual cycle phase on 5-HT(1A) receptors or 5-HTT. The finding however does not preclude that gonadal hormones differentially influence central serotonin system inwomen and men, which might contribute to gender differences in serotonin-associated disorders.
    Psychiatry Research 01/2009; 172(1):31-7. · 2.68 Impact Factor
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    ABSTRACT: The 5-HT1B receptor has been implicated in several psychiatric disorders and is a potential pharmacological target in the treatment of depression. Here we report the synthesis of a novel PET radioligand, [11C]AZ10419369 (5-methyl-8-(4-methyl-piperazin-1-yl)-4-oxo-4H-chromene-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide), for in vivo visualization of 5-HT1B receptors in the brains of macaques and humans subjects. [11C]AZ10419369 was prepared by N-methylation of (8-(1-piperazinyl)-5-methylchrom-2-en-4-one-2-(4-morpholinophenyl) carboxamide, using carbon-11 methyl triflate. Regional brain uptake patterns of [11C]AZ10419369 were characterized by PET measurements in two macaques and a preliminary study in two human subjects. In addition, AZ10419369 was prepared in tritium labeled form for in vitro autoradiography studies in macaque brain tissue sections. The radiochemical purity of [11C]AZ10419369 was >99% and specific radioactivity was >3600 Ci/mmol. After iv injection of [11C]AZ10419369, 3-4% was in brain after 7.5 min. The regional brain distribution of radioactivity was similar in humans and macaques showing the highest uptake of radioactivity in the occipital cortex and the basal ganglia, in accord with autoradiographic studies performed using [3H]AZ10419369. Uptake was moderate in the temporal and frontal cortical regions, lower in the thalamus and lowest in the cerebellum. In macaques pre-treated with the selective 5-HT1B receptor antagonist, AR-A000002, binding was reduced in a dose-dependent manner, consistent with specific binding to 5-HT1B receptors. These data support [11C]AZ10419369 as a suitable radioligand for labeling 5-HT1B receptors in the primate brain. This radioligand may be useful in future studies evaluating drug-induced receptor occupancy and measurement of brain 5-HT1B receptor levels in patients with psychiatric disorders.
    NeuroImage 08/2008; 41(3):1075-85. · 6.25 Impact Factor
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    ABSTRACT: We have evaluated the detailed mapping of the norepinephrine transporter (NET) in the human brain with (S,S)-[(18)F]FMeNER-D(2) using a template method and the generation of functional ROIs based on the PET information. Brain PET measurements were performed from 90 to 210 min after the injection of (S,S)-[(18)F]FMeNER-D(2) in 20 healthy male subjects. Binding potential (BP(ND)) was calculated as late time ratio of the target region to the reference region (caudate) minus one. BP(ND) template images were generated from mean parametric images obtained in a group of 10 subjects using SPM2. On the BP(ND)/MRI template images, functional ROIs based on several different BP(ND) thresholds for the thalamus and brainstem were generated automatically using PMOD 2.8 software in addition to anatomical ROIs. PET/MRI data of another group of 10 subjects were used to evaluate the validity of the template method and the functional ROIs. NET BP(ND) template images demonstrated higher binding in the medial thalamus whereas the anterior and the pulvinar divisions had lower binding. In the brainstem, high binding was detected around the cerebral aqueduct of the midbrain and within the dorsal pons, in a volume comprising locus coeruleus. Functional ROIs with higher BP(ND) thresholds naturally yielded higher BP(ND) and lower coefficients of variance than did anatomical ROIs. This study indicated that (S,S)-[(18)F]FMeNER-D(2) combined with a template method provides detailed information on the distribution of NET in vivo and that functional ROIs on the template would be useful in further clinical studies.
    NeuroImage 08/2008; 42(2):474-82. · 6.25 Impact Factor
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    ABSTRACT: The mechanisms underlying the clinical properties of atypical antipsychotics have been postulated to be mediated, in part, by interactions with the 5-HT2A receptor. Recently, it has been recognized that clinically effective antipsychotic drugs are 5-HT2A receptor inverse agonists rather than neutral antagonists. In the present study, which is part of the clinical development of the novel, selective 5-HT2A receptor inverse agonist ACP-103, we applied positron emission tomography (PET) with the radioligand [11C]N-methylspiperone ([11C]NMSP) to study the relationship between oral dose, plasma level, and uptake of ACP-103 in living human brain. The safety of drug administration was also assessed. Four healthy volunteers were examined by PET at baseline, and after the oral administration of various single doses of ACP-103. Two subjects each received 1, 5, and 20 mg doses, and two subjects each received 2, 10, and 100 mg doses, respectively. ACP-103 was well tolerated. Detectable receptor binding was observed at very low ACP-103 serum levels. Cortical [11C]NMSP binding was found to be dose-dependent and fitted well to the law of mass action. A reduction in binding was detectable after an oral dose of ACP-103 as low as 1 mg, and reached near maximal displacement following the 10-20 mg dose. In conclusion, administration of ACP-103 to healthy volunteers was found to be safe and well tolerated, and single oral doses as low as 10 mg were found to fully saturate 5-HT2A receptors in human brain as determined by PET.
    The International Journal of Neuropsychopharmacology 04/2008; 11(2):163-71. · 5.64 Impact Factor
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    ABSTRACT: (S,S)-[(18)F]FMeNER-D(2) is a recently developed positron-emission tomography (PET) radioligand for in vivo quantification of the norepinephrine transporter system. The aim of this study was to provide dosimetry estimates for (S,S)-[(18)F]FMeNER-D(2) based on human whole-body PET measurements. PET scans were performed for a total of 6.4 h after the injection of 168.9 +/- 31.5 MBq of (S,S)-[(18)F]FMeNER-D(2) in four healthy male subjects. Volumes of interest were drawn on the coronal images. Estimates of the absorbed dose of radiation were calculated using the OLINDA software. Uptake was largest in lungs, followed by liver, bladder, brain and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lung (21.6%ID at 0.3 h), liver (5.1%ID at 0.3 h), bladder (12.2%ID at 6 h) and brain (2.3%ID at 0.3 h). The largest absorbed dose was found in the urinary bladder wall (0.039 mGy/MBq). The calculated effective dose was 0.017 mSv/MBq. Based on the distribution and dose estimates, the estimated radiation burden of (S,S)-[(18)F]FMeNER-D(2) is lower than that of [(18)F]FDG. The radioligand would allow multiple PET examinations in the same research subject per year.
    European journal of nuclear medicine and molecular imaging 04/2008; 35(3):630-6. · 5.11 Impact Factor
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    ABSTRACT: Women and men differ in serotonin associated psychiatric conditions, such as depression, anxiety and suicide. Despite this, very few studies focus on sex differences in the serotonin system. Of the biomarkers in the serotonin system, serotonin(1A) (5-HT(1A)) receptor is implicated in depression, and anxiety and serotonin transporter (5-HTT) is a target for selective serotonin reuptake inhibitors, psychotropic drugs used in the treatment of these disorders. The objective of the present study was to study sex related differences in the 5-HT(1A) receptor and 5-HTT binding potentials (BP(ND)s) in healthy humans, in vivo. Positron emission tomography and selective radioligands [(11)C]WAY100635 and [(11)C]MADAM were used to evaluate binding potentials for 5-HT(1A) receptors (14 women and 14 men) and 5-HTT (8 women and 10 men). The binding potentials were estimated both on the level of anatomical regions and voxel wise, derived by the simplified reference tissue model and wavelet/Logan plot parametric image techniques respectively. Compared to men, women had significantly higher 5-HT(1A) receptor and lower 5-HTT binding potentials in a wide array of cortical and subcortical brain regions. In women, there was a positive correlation between 5-HT(1A) receptor and 5-HTT binding potentials for the region of hippocampus. Sex differences in 5-HT(1A) receptor and 5-HTT BP(ND) may reflect biological distinctions in the serotonin system contributing to sex differences in the prevalence of psychiatric disorders such as depression and anxiety. The result of the present study may help in understanding sex differences in drug treatment responses to drugs affecting the serotonin system.
    NeuroImage 03/2008; 39(3):1408-19. · 6.25 Impact Factor
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    ABSTRACT: (S,S)-[(18)F]FMeNER-D(2) is a recently developed positron emission tomography (PET) ligand for in vivo quantification of norepinephrine transporter. A monkey occupancy study with the radioligand indicated that (S,S)-[(18)F]FMeNER-D(2) can be useful for quantitative PET analysis. In this preliminary study, regional distributions in the living human brain were evaluated. Brain PET measurements were performed for a total of 255 min after the injection of 188.3 +/- 5.7 MBq of (S,S)-[(18)F]FMeNER-D(2) in four healthy male subjects. Regions of interests were drawn on the thalamus and the caudate in the coregistered MRI/PET images. (S,S)-[(18)F]FMeNER-D(2) displayed good brain penetration and selective retention in regions rich in norepinephrine reuptake sites. The transient peak equilibrium was reached during the PET measurements. The ratios of radioactivity uptake in the thalamus to that in the caudate were 1.50 +/- 0.06 for the time period of 90-255 min. The present preliminary investigation indicates that (S,S)-[(18)F]FMeNER-D(2) has suitable characteristics for probing the norepinephrine reuptake system with PET in the human brain.
    European Journal of Nuclear Medicine 02/2008; 35(1):153-7. · 4.53 Impact Factor

Publication Stats

2k Citations
308.91 Total Impact Points

Institutions

  • 1994–2011
    • Karolinska University Hospital
      Tukholma, Stockholm, Sweden
    • Karolinska Institutet
      • Institutionen för klinisk neurovetenskap
      Solna, Stockholm, Sweden
  • 2008
    • AstraZeneca
      Tukholma, Stockholm, Sweden
  • 2003
    • Norra Stockholms Psykiatri
      Tukholma, Stockholm, Sweden
    • National Institutes of Health
      Maryland, United States
  • 1996
    • Novo Nordisk
      København, Capital Region, Denmark