scholarly journals Molecular Imaging of Neuroinflammation in Neurodegenerative Dementias: The Role of In Vivo PET Imaging

2017 ◽  
Vol 18 (5) ◽  
pp. 993 ◽  
Author(s):  
Chiara Cerami ◽  
Leonardo Iaccarino ◽  
Daniela Perani
Keyword(s):  
Molecular Imaging ◽  
Pet Imaging ◽  
Neurodegenerative Dementias

scholarly journals Validation and noninvasive kinetic modeling of [11C]UCB-J PET imaging in mice

2019 ◽  
Vol 40 (6) ◽  
pp. 1351-1362 ◽  
Author(s):  
Daniele Bertoglio ◽  
Jeroen Verhaeghe ◽  
Alan Miranda ◽  
Istvan Kertesz ◽  
Klaudia Cybulska ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Neurodegenerative Disorder ◽  
Input Function ◽  
Dependent Manner ◽  
In Vivo Metabolism ◽  
Promising Tool ◽  
Positron Emission ◽  
Synaptic Pathology

Synaptic pathology is associated with several brain disorders, thus positron emission tomography (PET) imaging of synaptic vesicle glycoprotein 2A (SV2A) using the radioligand [11C]UCB-J may provide a tool to measure synaptic alterations. Given the pivotal role of mouse models in understanding neuropsychiatric and neurodegenerative disorders, this study aims to validate and characterize [11C]UCB-J in mice. We performed a blocking study to verify the specificity of the radiotracer to SV2A, examined kinetic models using an image-derived input function (IDIF) for quantification of the radiotracer, and investigated the in vivo metabolism. Regional TACs during baseline showed rapid uptake of [11C]UCB-J into the brain. Pretreatment with levetiracetam confirmed target engagement in a dose-dependent manner. VT (IDIF) values estimated with one- and two-tissue compartmental models (1TCM and 2TCM) were highly comparable (r=0.999, p < 0.0001), with 1TCM performing better than 2TCM for K1 (IDIF). A scan duration of 60 min was sufficient for reliable VT (IDIF) and K1 (IDIF) estimations. In vivo metabolism of [11C]UCB-J was relatively rapid, with a parent fraction of 22.5 ± 4.2% at 15 min p.i. In conclusion, our findings show that [11C]UCB-J selectively binds to SV2A with optimal kinetics in the mouse representing a promising tool to noninvasively quantify synaptic density in comparative or therapeutic studies in neuropsychiatric and neurodegenerative disorder models.

scholarly journals Non-invasive imaging of high-risk coronary plaque: the role of computed tomography and positron emission tomography

2020 ◽  
Vol 93 (1113) ◽  
pp. 20190740 ◽  
Author(s):  
Rong Bing ◽  
Krithika Loganath ◽  
Philip Adamson ◽  
David Newby ◽  
Alastair Moss
Keyword(s):  
Positron Emission Tomography ◽  
Molecular Imaging ◽  
Coronary Plaque ◽  
Emission Tomography ◽  
Plaque Morphology ◽  
Biological Processes ◽  
Non Invasive ◽  
Positron Emission

Despite recent advances, cardiovascular disease remains the leading cause of death globally. As such, there is a need to optimise our current diagnostic and risk stratification pathways in order to better deliver individualised preventative therapies. Non-invasive imaging of coronary artery plaque can interrogate multiple aspects of coronary atherosclerotic disease, including plaque morphology, anatomy and flow. More recently, disease activity is being assessed to provide mechanistic insights into in vivo atherosclerosis biology. Molecular imaging using positron emission tomography is unique in this field, with the potential to identify specific biological processes using either bespoke or re-purposed radiotracers. This review provides an overview of non-invasive vulnerable plaque detection and molecular imaging of coronary atherosclerosis.

scholarly journals Advances in Radiopharmaceutical Sciences for Vascular Inflammation Imaging: Focus on Clinical Applications

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7111
Author(s):  
Kevin Prigent ◽  
Jonathan Vigne
Keyword(s):  
Molecular Imaging ◽  
Pet Imaging ◽  
Fdg Pet ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Vascular Inflammation ◽  
Future Research ◽  
Molecular Features ◽  
18F Fdg

Biomedical imaging technologies offer identification of several anatomic and molecular features of disease pathogenesis. Molecular imaging techniques to assess cellular processes in vivo have been useful in advancing our understanding of several vascular inflammatory diseases. For the non-invasive molecular imaging of vascular inflammation, nuclear medicine constitutes one of the best imaging modalities, thanks to its high sensitivity for the detection of probes in tissues. 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) is currently the most widely used radiopharmaceutical for molecular imaging of vascular inflammatory diseases such as atherosclerosis and large-vessel vasculitis. The combination of [18F]FDG and positron emission tomography (PET) imaging has become a powerful tool to identify and monitor non-invasively inflammatory activities over time but suffers from several limitations including a lack of specificity and avid background in different localizations. The use of novel radiotracers may help to better understand the underlying pathophysiological processes and overcome some limitations of [18F]FDG PET for the imaging of vascular inflammation. This review examines how [18F]FDG PET has given us deeper insight into the role of inflammation in different vascular pathologies progression and discusses perspectives for alternative radiopharmaceuticals that could provide a more specific and simple identification of pathologies where vascular inflammation is implicated. Use of these novel PET tracers could lead to a better understanding of underlying disease mechanisms and help inform the identification and stratification of patients for newly emerging immune-modulatory therapies. Future research is needed to realize the true clinical translational value of PET imaging in vascular inflammatory diseases.

scholarly journals The Role of Molecular Imaging as a Marker of Remyelination and Repair in Multiple Sclerosis

2021 ◽  
Vol 23 (1) ◽  
pp. 474
Author(s):  
Ido Ben-Shalom ◽  
Arnon Karni ◽  
Hadar Kolb
Keyword(s):  
Multiple Sclerosis ◽  
Molecular Imaging ◽  
Disease Progression ◽  
Acute Inflammation ◽  
Imaging Biomarkers ◽  
Underlying Mechanisms

The appearance of new disease-modifying therapies in multiple sclerosis (MS) has revolutionized our ability to fight inflammatory relapses and has immensely improved patients’ quality of life. Although remarkable, this achievement has not carried over into reducing long-term disability. In MS, clinical disability progression can continue relentlessly irrespective of acute inflammation. This “silent” disease progression is the main contributor to long-term clinical disability in MS and results from chronic inflammation, neurodegeneration, and repair failure. Investigating silent disease progression and its underlying mechanisms is a challenge. Standard MRI excels in depicting acute inflammation but lacks the pathophysiological lens required for a more targeted exploration of molecular-based processes. Novel modalities that utilize nuclear magnetic resonance’s ability to display in vivo information on imaging look to bridge this gap. Displaying the CNS through a molecular prism is becoming an undeniable reality. This review will focus on “molecular imaging biomarkers” of disease progression, modalities that can harmoniously depict anatomy and pathophysiology, making them attractive candidates to become the first valid biomarkers of neuroprotection and remyelination.

scholarly journals Integrating nanomedicine and imaging

2017 ◽  
Vol 375 (2107) ◽  
pp. 20170110 ◽  
Author(s):  
Carlos Pérez-Medina ◽  
Sjoerd Hak ◽  
Thomas Reiner ◽  
Zahi A. Fayad ◽  
Matthias Nahrendorf ◽  
...  
Keyword(s):  
Immune System ◽  
Molecular Imaging ◽  
Biomedical Engineering ◽  
Multimodality Imaging ◽  
Clinical Implementation ◽  
New Era ◽  
Multicentre Trials ◽  
Recent Developments

Biomedical engineering and its associated disciplines play a pivotal role in improving our understanding and management of disease. Motivated by past accomplishments, such as the clinical implementation of coronary stents, pacemakers or recent developments in antibody therapies, disease management now enters a new era in which precision imaging and nanotechnology-enabled therapeutics are maturing to clinical translation. Preclinical molecular imaging increasingly focuses on specific components of the immune system that drive disease progression and complications, allowing the in vivo study of potential therapeutic targets. The first multicentre trials highlight the potential of clinical multimodality imaging for more efficient drug development. In this perspective, the role of integrating engineering, nanotechnology, molecular imaging and immunology to yield precision medicine is discussed. This article is part of the themed issue ‘Challenges for chemistry in molecular imaging’.

scholarly journals PET Imaging of Epigenetic Influences on Alzheimer’s Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Paul J. Couto ◽  
Richard M. Millis
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Pet Imaging ◽  
Pittsburgh Compound B ◽  
Pet Radiotracers ◽  
Precise Role ◽  
Neuroimaging Techniques

The precise role of environment-gene interactions (epigenetics) in the development and progression of Alzheimer’s disease (AD) is unclear. This review focuses on the premise that radiotracer-specific PET imaging allows clinicians to visualize epigenetically influenced events and that such imaging may provide new, valuable insights for preventing, diagnosing, and treating AD. Current understanding of the role of epigenetics in AD and the principles underlying the use of PET radiotracers forin vivodiagnosis are reviewed. The relative efficacies of various PET radiotracers for visualizing the epigenetic influences on AD and their use for diagnosis are discussed. For example, [18F]FAHA demonstrates sites of differential HDAC activity, [18F]FDG indirectly illuminates sites of neuronal hypomethylation, and the carbon-11 isotope-containing Pittsburgh compound B ([11C]PiB) images amyloid-beta plaque deposits. A definitive AD diagnosis is currently achievable only by postmortem histological observation of amyloid-beta plaques and tau neurofibrillary tangles. Therefore, reliablein vivoneuroimaging techniques could provide opportunities for early diagnosis and treatment of AD.

scholarly journals Preliminary Evaluations of [11C]Verubulin: Implications for Microtubule Imaging With PET

2021 ◽  
Vol 15 ◽  
Author(s):  
Anton Lindberg ◽  
Andrew V. Mossine ◽  
Arturo Aliaga ◽  
Robert Hopewell ◽  
Gassan Massarweh ◽  
...  
Keyword(s):  
Rat Brain ◽  
Pet Imaging ◽  
Imaging Study ◽  
Positron Emission ◽  
Human Use ◽  
Pretreatment Conditions ◽  
Human Primate

[11C]Verubulin (a.k.a.[11C]MCP-6827), [11C]HD-800 and [11C]colchicine have been developed for imaging microtubules (MTs) with positron emission tomography (PET). The objective of this work was to conduct an in vivo comparison of [11C]verubulin for MT imaging in mouse and rat brain, as well as an in vitro study with this radiotracer in rodent and human Alzheimer’s Disease tissue. Our preliminary PET imaging studies of [11C]verubulin in rodents revealed contradictory results between mouse and rat brain uptake under pretreatment conditions. In vitro autoradiography with [11C]verubulin showed an unexpected higher uptake in AD patient tissue compared with healthy controls. We also conducted the first comparative in vivo PET imaging study with [11C]verubulin, [11C]HD-800 and [11C]colchicine in a non-human primate. [11C]Verubulin and [11C]HD-800 require pharmacokinetic modeling and quantification studies to understand the role of how these radiotracers bind to MTs before translation to human use.

Mitochondrial matrix calcium ions regulate energy production in myocardium: A cytochemical study

1990 ◽  
Vol 48 (2) ◽  
pp. 166-167
Author(s):  
W.A. Jacob ◽  
R. Hertsens ◽  
A. Van Bogaert ◽  
M. De Smet
Keyword(s):  
Energy Metabolism ◽  
Calcium Ions ◽  
Energy Production ◽  
Regulation Of Respiration ◽  
Free Calcium ◽  
Mitochondrial Matrix ◽  
Cytochemical Study ◽  
Nmr Techniques

In the past most studies of the control of energy metabolism focus on the role of the phosphorylation potential ATP/ADP.Pi on the regulation of respiration. Studies using NMR techniques have demonstrated that the concentrations of these compounds for oxidation phosphorylation do not change appreciably throughout the cardiac cycle and during increases in cardiac work. Hence regulation of energy production by calcium ions, present in the mitochondrial matrix, has been the object of a number of recent studies.Three exclusively intramitochondnal dehydrogenases are key enzymes for the regulation of oxidative metabolism. They are activated by calcium ions in the low micromolar range. Since, however, earlier estimates of the intramitochondnal calcium, based on equilibrium thermodynamic considerations, were in the millimolar range, a physiological correlation was not evident. The introduction of calcium-sensitive probes fura-2 and indo-1 made monitoring of free calcium during changing energy metabolism possible. These studies were performed on isolated mitochondria and extrapolation to the in vivo situation is more or less speculative.

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