scholarly journals [11C]Befloxatone Distribution is well Correlated to Monoamine Oxidase a Protein Levels in the Human Brain

2014 ◽  
Vol 34 (12) ◽  
pp. 1951-1952 ◽  
Author(s):  
Paolo Zanotti-Fregonara ◽  
Michel Bottlaender
Keyword(s):  
Monoamine Oxidase ◽  
Human Brain ◽  
Volume Of Distribution ◽  
Monoamine Oxidase A ◽  
Binding Potential ◽  
Poor Correlation ◽  
Mrna Levels ◽  
Protein Levels ◽  
Positron Emission ◽  
Mao A

[11C]befloxatone is a positron emission tomography radioligand to image monoamine oxidase A (MAO-A) in the brain, which has been used in preclinical studies and in clinical protocols. However, a recent study found that [11C]befloxatone binding potential (k3/k4) has a poor correlation with MAO-A protein levels measured in the human brain. We here show that this poor correlation only depends on the choice of the parameter when performing kinetic modeling. In particular, the total volume of distribution of [11C]befloxatone shows a tight correlation with both protein and mRNA levels of MAO-A in the human brain.

scholarly journals Positron Emission Tomography Quantification of [11C]-Harmine Binding to Monoamine Oxidase-A in the Human Brain

2005 ◽  
Vol 26 (3) ◽  
pp. 330-344 ◽  
Author(s):  
Nathalie Ginovart ◽  
Jeffrey H Meyer ◽  
Anahita Boovariwala ◽  
Doug Hussey ◽  
Eugenii A Rabiner ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Monoamine Oxidase ◽  
Human Brain ◽  
Monoamine Oxidase A ◽  
Emission Tomography ◽  
Positron Emission

scholarly journals Distribution of Monoamine Oxidase Proteins in Human Brain: Implications for Brain Imaging Studies

2013 ◽  
Vol 33 (6) ◽  
pp. 863-871 ◽  
Author(s):  
Junchao Tong ◽  
Jeffrey H Meyer ◽  
Yoshiaki Furukawa ◽  
Isabelle Boileau ◽  
Li-Jan Chang ◽  
...  
Keyword(s):  
Human Brain ◽  
Outcome Measures ◽  
Regional Distribution ◽  
Clinical Importance ◽  
Binding Potential ◽  
Mao B ◽  
Protein Levels ◽  
Mao A

Positron emission tomography (PET) imaging of monoamine oxidases (MAO-A: [11C]harmine, [11C]clorgyline, and [11C]befloxatone; MAO-B: [11C]deprenyl-D2) has been actively pursued given clinical importance of MAOs in human neuropsychiatric disorders. However, it is unknown how well PET outcome measures for the different radiotracers are quantitatively related to actual MAO protein levels. We measured regional distribution ( n = 38) and developmental/aging changes (21 hours to 99 years) of both MAOs by quantitative immunoblotting in autopsied normal human brain. MAO-A was more abundant than MAO-B in infants, which was reversed as MAO-B levels increased faster before 1 year and, unlike MAO-A, kept increasing steadily to senescence. In adults, regional protein levels of both MAOs were positively and proportionally correlated with literature postmortem data of MAO activities and binding densities. With the exception of [11C]befloxatone (binding potential (BP), r = 0.61, P = 0.15), correlations between regional PET outcome measures of binding in the literature and MAO protein levels were good ( P < 0.01) for [11C]harmine (distribution volume, r = 0.86), [11C]clorgyline (λk3, r = 0.82), and [11C]deprenyl-D2 (λk3 or modified Patlak slope, r = 0.78 to 0.87), supporting validity of the latter imaging measures. However, compared with in vitro data, the latter PET measures underestimated regional contrast by ~2-fold. Further studies are needed to address cause of the in vivo vs. in vitro nonproportionality.

scholarly journals Reversible Inhibitors of Monoamine Oxidase-A (RIMAs): Robust, Reversible Inhibition of Human Brain MAO-A by CX157

2009 ◽  
Vol 35 (3) ◽  
pp. 623-631 ◽  
Author(s):  
Joanna S Fowler ◽  
Jean Logan ◽  
Albert J Azzaro ◽  
Robert M Fielding ◽  
Wei Zhu ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Human Brain ◽  
Monoamine Oxidase A ◽  
Reversible Inhibitors ◽  
Reversible Inhibition ◽  
Mao A

scholarly journals Dynamic, Adaptive Changes in MAO-A Binding after Alterations in Substrate Availability: An in vivo [11C]-Harmine Positron Emission Tomography Study

2011 ◽  
Vol 32 (3) ◽  
pp. 443-446 ◽  
Author(s):  
Julia Sacher ◽  
Eugenii A Rabiner ◽  
Michael Clark ◽  
Pablo Rusjan ◽  
Alexandra Soliman ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Monoamine Oxidase ◽  
Monoamine Oxidase A ◽  
Emission Tomography ◽  
Tryptophan Depletion ◽  
Major Depressive ◽  
Positron Emission ◽  
Mao A ◽  
Adaptive Role

Monoamine oxidase A (MAO-A) is an important target in the pathophysiology and therapeutics of major depressive disorder, aggression, and neurodegenerative conditions. We measured the effect of changes in MAO-A substrate on MAO-A binding in regions implicated in affective and neurodegenerative disease with [11C]-harmine positron emission tomography in healthy volunteers. Monoamine oxidase A VT, an index of MAO-A density, was decreased (mean: 14%±9%) following tryptophan depletion in prefrontal cortex ( P<0.031), and elevated (mean: 17%±11%) in striatum following carbidopa—levodopa administration ( P<0.007). These findings suggest an adaptive role for MAO-A in maintaining monoamine neurotransmitter homeostasis by rapidly compensating fluctuating monoamine levels.

scholarly journals High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain: a preliminary report

2021 ◽  
pp. 105381
Author(s):  
Georg S. Kranz ◽  
Marie Spies ◽  
Chrysoula Vraka ◽  
Ulrike Kaufmann ◽  
Eva-Maria Klebermass ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Human Brain ◽  
Preliminary Report ◽  
Monoamine Oxidase A ◽  
High Dose ◽  
Testosterone Treatment

scholarly journals Quantification of Ligand PET Studies using a Reference Region with a Displaceable Fraction: Application to Occupancy Studies with [11C]-DASB as an Example

2011 ◽  
Vol 32 (1) ◽  
pp. 70-80 ◽  
Author(s):  
Federico E Turkheimer ◽  
Sudhakar Selvaraj ◽  
Rainer Hinz ◽  
Venkatesha Murthy ◽  
Zubin Bhagwagar ◽  
...  
Keyword(s):  
Specific Binding ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Accurate Estimation ◽  
Data Sets ◽  
Reference Region ◽  
Reference Tissue ◽  
Positron Emission ◽  
Definition Of

This paper aims to build novel methodology for the use of a reference region with specific binding for the quantification of brain studies with radioligands and positron emission tomography (PET). In particular: (1) we introduce a definition of binding potential BPD = DVR–1 where DVR is the volume of distribution relative to a reference tissue that contains ligand in specifically bound form, (2) we validate a numerical methodology, rank-shaping regularization of exponential spectral analysis (RS-ESA), for the calculation of BPD that can cope with a reference region with specific bound ligand, (3) we demonstrate the use of RS-ESA for the accurate estimation of drug occupancies with the use of correction factors to account for the specific binding in the reference. [11C]-DASB with cerebellum as a reference was chosen as an example to validate the methodology. Two data sets were used; four normal subjects scanned after infusion of citalopram or placebo and further six test—retest data sets. In the drug occupancy study, the use of RS-ESA with cerebellar input plus corrections produced estimates of occupancy very close the ones obtained with plasma input. Test-retest results demonstrated a tight linear relationship between BPD calculated either with plasma or with a reference input and high reproducibility.

scholarly journals No Evidence for Additional Blood–Brain Barrier P-Glycoprotein Dysfunction in Alzheimer's Disease Patients with Microbleeds

2012 ◽  
Vol 32 (8) ◽  
pp. 1468-1471 ◽  
Author(s):  
Daniëlle ME van Assema ◽  
Jeroen DC Goos ◽  
Wiesje M van der Flier ◽  
Mark Lubberink ◽  
Ronald Boellaard ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Blood Brain Barrier ◽  
Volume Of Distribution ◽  
Brain Barrier ◽  
Binding Potential ◽  
Amyloid Angiopathy ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Positron Emission

Decreased blood–brain barrier P-glycoprotein (Pgp) function has been shown in Alzheimer's disease (AD) patients using positron emission tomography (PET) with the radiotracer ( R)-[11C]verapamil. Decreased Pgp function has also been hypothesized to promote cerebral amyloid angiopathy (CAA) development. Here, we used PET and ( R)-[11C]verapamil to assess Pgp function in eighteen AD patients, of which six had microbleeds (MBs), presumably reflecting underlying CAA. No differences were found in binding potential and nonspecific volume of distribution of ( R)-[11C]verapamil between patient groups. These results provide no evidence for additional Pgp dysfunction in AD patients with MBs.

scholarly journals Quantitation of Translocator Protein Binding in Human Brain with the Novel Radioligand [18F]-FEPPA and Positron Emission Tomography

2011 ◽  
Vol 31 (8) ◽  
pp. 1807-1816 ◽  
Author(s):  
Pablo M Rusjan ◽  
Alan A Wilson ◽  
Peter M Bloomfield ◽  
Irina Vitcu ◽  
Jeffrey H Meyer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Human Brain ◽  
Specific Binding ◽  
Compartment Model ◽  
Distribution Volume ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Specific Distribution ◽  
Positron Emission

This article describes the kinetic modeling of [18F]-FEPPA binding to translocator protein 18 kDa in the human brain using high-resolution research tomograph (HRRT) positron emission tomography. Positron emission tomography scans were performed in 12 healthy volunteers for 180 minutes. A two-tissue compartment model (2-CM) provided, with no exception, better fits to the data than a one-tissue model. Estimates of total distribution volume ( VT), specific distribution volume ( VS), and binding potential ( BPND) demonstrated very good identifiability (based on coefficient of variation ( COV)) for all the regions of interest (ROIs) in the gray matter ( COV VT < 7%, COV VS < 8%, COV BPND < 11%). Reduction of the length of the scan to 2 hours is feasible as VS and VT showed only a small bias (6% and 7.5%, respectively). Monte Carlo simulations showed that, even under conditions of a 500% increase in specific binding, the identifiability of VT and VS was still very good with COV<10%, across high-uptake ROIs. The excellent identifiability of VT values obtained from an unconstrained 2-CM with data from a 2-hour scan support the use of VT as an appropriate and feasible outcome measure for [18F]-FEPPA.

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