Detection of alpha-2 adrenergic receptors in brain of living pig with [11C]yohimbine

Jakobsen, Steen; Pedersen, Kasper; Smith, Donald F.; Jensen, Svend Borup; Olsen, Annemarie; Cumming, Paul

doi:10.1016/j.neuroimage.2006.04.109

Cited by 30 publications

(56 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conclusions: Group differences in retention of the amyloid imaging agent for the amyloid( + ) vs. amyloid(-) subjects were highly concordant in amyloid-bearing areas of cortex for short and long-term intervals between PiB and Florbetapir scanning, despite brain changes that may arise during the interval (e.g., atrophy, amyloid accumulation), that likely contribute to discordance. Background: Yohimbine is a selective alpha-2 adrenoceptor antagonist, which can be labeled with carbon-11 and used as a positron emission tomography tracer (Jakobsen et al 2006). Amphetamine is an inhibitor of dopamine and norepinephrine reuptake sites in mammalian brain.…”

Section: P052 Preliminary Analysis Of the Difference Of Amyloid Betamentioning

confidence: 99%

Applications of Radiotracer Imaging Poster Abstracts

Stokes¹,

Myers²,

Benecke

et al. 2012

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Background: Alzheimer's disease (AD) with early onset often presents with a distinct cognitive profile, potentially reflecting a different distribution of underlying neuropathology. The purpose of this study was to examine the relationships between age and both in vivo fibrillary amyloid deposition and glucose metabolism in AD. Methods: Dynamic [11 C]Pittsburgh compound-B (PIB) (90 minutes) and static [18 F]fluorodeoxyglucose (FDG) (15 minutes) scans were obtained in 100 AD patients and 20 healthy controls. Parametric nondisplaceable binding potential images of [ 11 C]PIB and standardized uptake value ratio images of [ 18 F]FDG were generated using cerebellar grey matter as reference tissue. Nine [ 11 C]PIB negative patients were excluded. The remaining patients were categorized into younger (n = 45, age: 56±4) and older (n = 46, age: 69 ± 5) groups, based on the median age (62) at time-of-diagnosis. Results: Younger patients showed more severe impairment on visuo-spatial function, attention and executive function composite scores (p < 0.05), while we found a trend towards poorer memory performance for older patients (p = 0.11 18 F]FDG uptake in the parietal cortex of younger patients (both p < 0.05). Linear regression analyses showed negative associations between visuo-spatial functioning and parietal www.jcbfm.com entiation in downstream processes, but may originate from distinctive distributions of early upstream events. As such, increased amyloid burden, together with metabolic dysfunction, in the parietal lobe of younger AD patients may contribute to the distinct cognitive profile in these patients.P002. Differential impact of apolipoprotein E genotype on distributions of amyloid load and glucose metabolism in Alzheimer's disease Rik Ossenkoppele, Wiesje van der Flier, Sofie Adriaanse, Marissa Zwan, Ronald Boellaard, Albert Windhorst, Frederik Barkhof, Philip Scheltens, Adriaan Lammertsma and Bart van Berckel VU University Medical Center, Amsterdam, The Netherlands Background: Apolipoprotein E (APOE) e4 is the major genetic risk factor for sporadic Alzheimer's disease (AD), but its impact on pathophysiological processes and neuronal function is not completely understood. The purpose of this study was to examine the relationships between APOE e4-dose and in vivo distributions of both fibrillary amyloid burden and glucose metabolism in the same AD patients. 18 F]FDG were generated using cerebellar grey matter as reference tissue. Regions-of-interest are the frontal, parietal, temporal, posterior cingulate, and occipital cortices. AD patients were categorized into APOE e4 negative (n = 22), heterozygous (n = 40), and homozygous (n = 22) groups. Results: Multivariate ANOVAs with adjustment for age, gender, and MMSE, showed main effects for APOE e4-dose for distributions of both [11 C]PIB (p < 0.05) and [18 F]FDG (p < 0.01). More specifically, ANOVAs of individual regions showed increased [ 11 C]PIB BP ND in the frontal cortex of APOE e4 noncarriers compared with APOE e4 carriers (p < 0.05). By contrast, APOE e4...

show abstract

Section: P052 Preliminary Analysis Of the Difference Of Amyloid Betamentioning

confidence: 99%

Applications of Radiotracer Imaging Poster Abstracts

Stokes¹,

Myers²,

Benecke

et al. 2012

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

show abstract

“…We recently developed 11 C-yohimbine for use with PET. Yohimbine binds to all a 2 -adrenoceptor subtypes and has moderate affinity for the 5HT 1A receptors as well (11).…”

mentioning

confidence: 99%

“…Yohimbine binds to all a 2 -adrenoceptor subtypes and has moderate affinity for the 5HT 1A receptors as well (11). In porcine brain, 11 C-yohimbine enters brain tissue readily and binds specifically in brain areas with known high densities of a 2 adrenoceptors. In rat brain, 11 C-yohimbine is excluded from entry into brain tissue by the action of permeability glycoprotein (12).…”

mentioning

confidence: 99%

“…In porcine brain, 11 C-yohimbine enters brain tissue readily and binds specifically in brain areas with known high densities of a 2 adrenoceptors. In rat brain, 11 C-yohimbine is excluded from entry into brain tissue by the action of permeability glycoprotein (12). In porcine brain, both unlabeled yohimbine and RX821002 (2-(2-methoxy-1,4-benzodioxan-2yl)-2-imidazoline), a highly selective a 2 -adrenoceptor antagonist, displace 11 C-yohimbine binding (11).…”

mentioning

confidence: 99%

“…In rat brain, 11 C-yohimbine is excluded from entry into brain tissue by the action of permeability glycoprotein (12). In porcine brain, both unlabeled yohimbine and RX821002 (2-(2-methoxy-1,4-benzodioxan-2yl)-2-imidazoline), a highly selective a 2 -adrenoceptor antagonist, displace 11 C-yohimbine binding (11). These results prompted us to test 11 C-yohimbine as a radioligand for use in humans, particularly with respect to the ability of the tracer to readily cross the blood-brain barrier.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mapping α₂ Adrenoceptors of the Human Brain with ¹¹C-Yohimbine

et al. 2015

Self Cite

View full text Add to dashboard Cite

A previous study from this laboratory suggested that 11 C-yohimbine, a selective α 2 -adrenoceptor antagonist, is an appropriate ligand for PET of α 2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood-brain clearances, volumes of distribution, and receptor availability by means of PET with 11 C-yohimbine in healthy male adults. Methods: We recorded the distribution of 11 C-yohimbine with 90-min dynamic PET and sampled arterial blood to measure intact 11 C-yohimbine in plasma. For analysis, we coregistered PET images to individual MR images and automatically identified 27 volumes of interest. We used 1-tissue-compartment graphical analysis with 6 linearized solutions of the fundamental binding equation, with the metabolite-corrected arterial plasma curves as input function, to estimate the kinetic parameters of 11 C-yohimbine. With the lowest steady-state distribution volume (V T ), determined in the corpus callosum, we calculated the binding potential (receptor availability) of the radioligand in other regions. Results: The linear regressions yielded similar estimates of the kinetic parameters. The cortical values of V T ranged from 0.82 mL cm −3 in the right frontal cortex to 0.46 mL cm −3 in the corpus callosum, with intermediate V T values in subcortical structures. Binding potentials averaged 0.6-0.8 in the cortex and 0.2-0.5 in subcortical regions. Conclusion: The maps of 11 Cyohimbine binding to α 2 adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer 11 C-yohimbine for mapping α 2 adrenoceptors in human brain in vivo.

show abstract

Validation of [¹¹C]ORM‐13070 as a PET tracer for alpha_2c‐adrenoceptors in the human brain

Lehto

Hirvonen²,

Johansson

et al. 2015

Synapse

View full text Add to dashboard Cite

This study explored the use of the α2C -adrenoceptor PET tracer [(11) C]ORM-13070 to monitor α2C -AR occupancy in the human brain. The subtype-nonselective α2 -AR antagonist atipamezole was administered to eight healthy volunteer subjects to determine its efficacy and potency (Emax and EC50 ) at inhibiting tracer uptake. We also explored whether the tracer could reveal changes in the synaptic concentrations of endogenous noradrenaline in the brain, in response to several pharmacological and sensory challenge conditions. We assessed occupancy from the bound-to-free ratio measured during 5-30 min post injection. Based on extrapolation of one-site binding, the maximal extent of inhibition of striatal [(11) C]ORM-13070 uptake (Emax ) achievable by atipamezole was 78% (95% CI 69-87%) in the caudate nucleus and 65% (53-77%) in the putamen. The EC50 estimates of atipamezole (1.6 and 2.5 ng/ml, respectively) were in agreement with the drug's affinity to α2C -ARs. These findings represent clear support for the use of [(11) C]ORM-13070 for monitoring drug occupancy of α2C -ARs in the living human brain. Three of the employed noradrenaline challenges were associated with small, approximately 10-16% average reductions in tracer uptake in the dorsal striatum (atomoxetine, ketamine, and the cold pressor test; P < 0.05 for all), but insulin-induced hypoglycemia did not affect tracer uptake. The tracer is suitable for studying central nervous system receptor occupancy by α2C -AR ligands in human subjects. [(11) C]ORM-13070 also holds potential as a tool for in vivo monitoring of synaptic concentrations of noradrenaline, but this remains to be further evaluated in future studies.

show abstract

Detection of alpha-2 adrenergic receptors in brain of living pig with [11C]yohimbine

Cited by 30 publications

References 0 publications

Applications of Radiotracer Imaging Poster Abstracts

Applications of Radiotracer Imaging Poster Abstracts

Mapping α₂ Adrenoceptors of the Human Brain with ¹¹C-Yohimbine

Validation of [¹¹C]ORM‐13070 as a PET tracer for alpha_2c‐adrenoceptors in the human brain

Contact Info

Product

Resources

About

Detection of alpha-2 adrenergic receptors in brain of living pig with [11C]yohimbine

Cited by 30 publications

References 0 publications

Applications of Radiotracer Imaging Poster Abstracts

Applications of Radiotracer Imaging Poster Abstracts

Mapping α2 Adrenoceptors of the Human Brain with 11C-Yohimbine

Validation of [11C]ORM‐13070 as a PET tracer for alpha2c‐adrenoceptors in the human brain

Contact Info

Product

Resources

About

Mapping α₂ Adrenoceptors of the Human Brain with ¹¹C-Yohimbine

Validation of [¹¹C]ORM‐13070 as a PET tracer for alpha_2c‐adrenoceptors in the human brain