scholarly journals Novel PET Biomarkers to Disentangle Molecular Pathways across Age-Related Neurodegenerative Diseases

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2581
Author(s):  
Heather Wilson ◽  
Marios Politis ◽  
Eugenii A. Rabiner ◽  
Lefkos T. Middleton
Keyword(s):  
Neurodegenerative Diseases ◽  
Protein Misfolding ◽  
Imaging Technique ◽  
Emission Tomography ◽  
Imaging Biomarkers ◽  
Synaptic Dysfunction ◽  
Molecular Pathways ◽  
Age Related ◽  
Positron Emission

There is a need to disentangle the etiological puzzle of age-related neurodegenerative diseases, whose clinical phenotypes arise from known, and as yet unknown, pathways that can act distinctly or in concert. Enhanced sub-phenotyping and the identification of in vivo biomarker-driven signature profiles could improve the stratification of patients into clinical trials and, potentially, help to drive the treatment landscape towards the precision medicine paradigm. The rapidly growing field of neuroimaging offers valuable tools to investigate disease pathophysiology and molecular pathways in humans, with the potential to capture the whole disease course starting from preclinical stages. Positron emission tomography (PET) combines the advantages of a versatile imaging technique with the ability to quantify, to nanomolar sensitivity, molecular targets in vivo. This review will discuss current research and available imaging biomarkers evaluating dysregulation of the main molecular pathways across age-related neurodegenerative diseases. The molecular pathways focused on in this review involve mitochondrial dysfunction and energy dysregulation; neuroinflammation; protein misfolding; aggregation and the concepts of pathobiology, synaptic dysfunction, neurotransmitter dysregulation and dysfunction of the glymphatic system. The use of PET imaging to dissect these molecular pathways and the potential to aid sub-phenotyping will be discussed, with a focus on novel PET biomarkers.

scholarly journals News about the Role of Fluid and Imaging Biomarkers in Neurodegenerative Diseases

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 252
Author(s):  
Jacopo Meldolesi
Keyword(s):  
Neurodegenerative Diseases ◽  
Imaging Techniques ◽  
Imaging Biomarkers ◽  
Positron Emission ◽  
Specific Proteins ◽  
Great Relevance ◽  
The Brain ◽  
Positive Point

Biomarkers are molecules that are variable in their origin, nature, and mechanism of action; they are of great relevance in biology and also in medicine because of their specific connection with a single or several diseases. Biomarkers are of two types, which in some cases are operative with each other. Fluid biomarkers, started around 2000, are generated in fluid from specific proteins/peptides and miRNAs accumulated within two extracellular fluids, either the central spinal fluid or blood plasma. The switch of these proteins/peptides and miRNAs, from free to segregated within extracellular vesicles, has induced certain advantages including higher levels within fluids and lower operative expenses. Imaging biomarkers, started around 2004, are identified in vivo upon their binding by radiolabeled molecules subsequently revealed in the brain by positron emission tomography and/or other imaging techniques. A positive point for the latter approach is the quantitation of results, but expenses are much higher. At present, both types of biomarker are being extensively employed to study Alzheimer’s and other neurodegenerative diseases, investigated from the presymptomatic to mature stages. In conclusion, biomarkers have revolutionized scientific and medical research and practice. Diagnosis, which is often inadequate when based on medical criteria only, has been recently improved by the multiplicity and specificity of biomarkers. Analogous results have been obtained for prognosis. In contrast, improvement of therapy has been limited or fully absent, especially for Alzheimer’s in which progress has been inadequate. An urgent need at hand is therefore the progress of a new drug trial design together with patient management in clinical practice.

Positron Emission Tomography: Clinical Applications and Pharmaceutical Care

1994 ◽  
Vol 7 (3) ◽  
pp. 124-139 ◽  
Author(s):  
Richard J. Hammes ◽  
John W. Babich
Keyword(s):  
Positron Emission Tomography ◽  
Imaging Technique ◽  
Three Dimensional ◽  
Building Blocks ◽  
Emission Tomography ◽  
Pharmacokinetic Parameters ◽  
Nuclear Medicine Imaging ◽  
Receptor Ligands ◽  
Positron Emission

Positron emission tomography {PET) is a nuclear medicine imaging technique which exploits the unique physical characteristics of radionuclides that decay by positron emission. These characteristics allow for in vivo quantitative measurement of three-dimensional distributions of radioactivity with a spatial resolution of 5 mm using current detector technology. In addition to these physical advantages, PET is the only imaging technique that can use the short-lived positron emitting radionuclides of the so-called “organic” elements: carbon (C-11), nitrogen (N-13), and oxygen (0–15). These elements are the building blocks of physiological compounds and can be used to study most enzymes, receptors, and other metabolically important compounds and their associated reactions. PET allows for the study of a variety of physiological and biochemical processes through the application of particular radiopharmaceuticals. PET has also been used to study the interaction of receptor-specific ligands in several receptor systems including dopaminergic, adrenergic, serotinergic, and opiod. C-11 and F-18 labeled receptor ligands have been used to study receptor selectivity and receptor concentrations in vivo. Recently, PET has been used to measure the pharmacokinetics of several novel antibiotics in humans allowing the direct measurement of tissue concentrations and correlation with classical pharmacokinetic parameters. This review discusses some of the current applications of PET in more detail.

scholarly journals PET and the multitracer concept in the study of neurodegenerative diseases

2015 ◽  
Vol 9 (4) ◽  
pp. 343-349 ◽  
Author(s):  
Henry Engler ◽  
Andres Damian ◽  
Cecilia Bentancourt
Keyword(s):  
Positron Emission Tomography ◽  
Molecular Imaging ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Neurodegenerative Disorders ◽  
Clinical Symptoms ◽  
Emission Tomography ◽  
Positron Emission ◽  
The Brain

ABSTRACT The complexity of the pathological reactions of the brain to an aggression caused by an internal or external noxa represents a challenge for molecular imaging. Positron emission tomography (PET) can indicate in vivo,anatomopathological changes involved in the development of different clinical symptoms in patients with neurodegenerative disorders. PET and the multitracer concept can provide information from different systems in the brain tissue building an image of the whole disease. We present here the combination of 18F-flourodeoxyglucose (FDG) and N-[11C-methyl]-L-deuterodeprenyl (DED), FDG and N-[11C-methyl] 2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (PIB), PIB and L-[11C]-3'4-Dihydrophenylalanine (DOPA) and finally PIB and [15O]H2O.

scholarly journals Deep-Learning Based Positron Range Correction of PET Images

2020 ◽  
Vol 11 (1) ◽  
pp. 266
Author(s):  
Joaquín L. Herraiz ◽  
Adrián Bembibre ◽  
Alejandro López-Montes
Keyword(s):  
Imaging Technique ◽  
High Energy ◽  
The Body ◽  
Emission Tomography ◽  
Small Animals ◽  
Positron Energy ◽  
Positron Range ◽  
Positron Emission ◽  
Range Correction

Positron emission tomography (PET) is a molecular imaging technique that provides a 3D image of functional processes in the body in vivo. Some of the radionuclides proposed for PET imaging emit high-energy positrons, which travel some distance before they annihilate (positron range), creating significant blurring in the reconstructed images. Their large positron range compromises the achievable spatial resolution of the system, which is more significant when using high-resolution scanners designed for the imaging of small animals. In this work, we trained a deep neural network named Deep-PRC to correct PET images for positron range effects. Deep-PRC was trained with modeled cases using a realistic Monte Carlo simulation tool that considers the positron energy distribution and the materials and tissues it propagates into. Quantification of the reconstructed PET images corrected with Deep-PRC showed that it was able to restore the images by up to 95% without any significant noise increase. The proposed method, which is accessible via Github, can provide an accurate positron range correction in a few seconds for a typical PET acquisition.

scholarly journals Development of a blood sample detector for multi-tracer positron emission tomography using gamma spectroscopy

2019 ◽  
Vol 6 (1) ◽  
Author(s):  
Carlos Velasco ◽  
Adriana Mota-Cobián ◽  
Jesús Mateo ◽  
Samuel España
Keyword(s):  
Positron Emission Tomography ◽  
Blood Sample ◽  
Pet Imaging ◽  
Spectroscopic Analysis ◽  
Gamma Spectroscopy ◽  
Emission Tomography ◽  
Blood Samples ◽  
Positron Emission

Abstract Background Multi-tracer positron emission tomography (PET) imaging can be accomplished by applying multi-tracer compartment modeling. Recently, a method has been proposed in which the arterial input functions (AIFs) of the multi-tracer PET scan are explicitly derived. For that purpose, a gamma spectroscopic analysis is performed on blood samples manually withdrawn from the patient when at least one of the co-injected tracers is based on a non-pure positron emitter. Alternatively, these blood samples required for the spectroscopic analysis may be obtained and analyzed on site by an automated detection device, thus minimizing analysis time and radiation exposure of the operating personnel. In this work, a new automated blood sample detector based on silicon photomultipliers (SiPMs) for single- and multi-tracer PET imaging is presented, characterized, and tested in vitro and in vivo. Results The detector presented in this work stores and analyzes on-the-fly single and coincidence detected events. A sensitivity of 22.6 cps/(kBq/mL) and 1.7 cps/(kBq/mL) was obtained for single and coincidence events respectively. An energy resolution of 35% full-width-half-maximum (FWHM) at 511 keV and a minimum detectable activity of 0.30 ± 0.08 kBq/mL in single mode were obtained. The in vivo AIFs obtained with the detector show an excellent Pearson’s correlation (r = 0.996, p < 0.0001) with the ones obtained from well counter analysis of discrete blood samples. Moreover, in vitro experiments demonstrate the capability of the detector to apply the gamma spectroscopic analysis on a mixture of 68Ga and 18F and separate the individual signal emitted from each one. Conclusions Characterization and in vivo evaluation under realistic experimental conditions showed that the detector proposed in this work offers excellent sensibility and stability. The device also showed to successfully separate individual signals emitted from a mixture of radioisotopes. Therefore, the blood sample detector presented in this study allows fully automatic AIFs measurements during single- and multi-tracer PET studies.

scholarly journals Correction to: In vivo imaging of early stages of rheumatoid arthritis by α5β1-integrin-targeted positron emission tomography

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Johannes Notni ◽  
Florian T. Gassert ◽  
Katja Steiger ◽  
Peter Sommer ◽  
Wilko Weichert ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Positron Emission Tomography ◽  
In Vivo Imaging ◽  
Emission Tomography ◽  
Early Stages ◽  
Positron Emission ◽  
Α5β1 Integrin

Following publication of the original article [1], the authors have reported an error in the ‘Histopathology’ (under ‘Materials and methods’) section of the article that compromises the reproducibility of the paper.

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