Positronium as a biomarker of hypoxia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Paweł Moskal ◽  
Ewa Ł. Stępień
Keyword(s):  
Partial Pressure ◽  
High Sensitivity ◽  
Partial Pressure Of Oxygen ◽  
Physiological Processes ◽  
Positron Emission ◽  
Positronium Lifetime ◽  
Total Body ◽  
Living Organisms ◽  
Cancer Tissues

Abstract In this review article, we present arguments demonstrating that the advent of high sensitivity total-body PET systems and the invention of the method of positronium imaging, open realistic perspectives for the application of positronium as a biomarker for in-vivo assessment of the degree of hypoxia. Hypoxia is a state or condition, in which the availability of oxygen is not sufficient to support physiological processes in tissue and organs. Positronium is a metastable atom formed from electron and positron which is copiously produced in the intramolecular spaces in the living organisms undergoing positron emission tomography (PET). Properties of positronium, such as e.g., lifetime, depend on the size of intramolecular spaces and the concentration in them of oxygen molecules. Therefore, information on the partial pressure of oxygen (pO2) in the tissue may be derived from the positronium lifetime measurement. The partial pressure of oxygen differs between healthy and cancer tissues in the range from 10 to 50 mmHg. Such differences of pO2 result in the change of ortho-positronium lifetime e.g., in water by about 2–7 ps. Thus, the application of positronium as a biomarker of hypoxia requires the determination of the mean positronium lifetime with the resolution in the order of 2 ps. We argue that such resolution is in principle achievable for organ-wise positronium imaging with the total-body PET systems.

Pharmacokinetic Challenges against Brain Diseases with PET

2014 ◽  
pp. 997-1007
Author(s):  
Hiroshi Watabe ◽  
Keisuke Matsubara ◽  
Yoko Ikoma
Keyword(s):  
High Sensitivity ◽  
Brain Diseases ◽  
Positron Emission ◽  
Functional Images ◽  
Dopamine And Serotonin Receptors ◽  
Anatomical Image ◽  
Time Courses ◽  
Living Organisms ◽  
Types Of Information

Positron emission tomography (PET) is an imaging technology used to visualize distribution of particular ligands inside living organisms. The ligand is labeled by a positron-emitting isotope, such as 11C, 15O, 13N and 18F, and injected into subjects. By detecting ?-rays emitted from the ligand, in vivo biodistribution and kinetics of the ligand can be depicted with high sensitivity. By altering the target ligand for PET, one can see different distributions and time courses of the target. PET provides several biological and functional images inside the body, rather than simply an anatomical image. Therefore, PET can potentially detect biological changes that occur long before anatomical changes begin. PET has been widely used for neuroreceptor and neurotransmitter studies by tracing radioligands, which have selective affinity for a particular site. For example, the dopamine and serotonin receptors are highly related to brain disorders. By analyzing the pharmacokinetics of these ligands using PET, it is possible to noninvasively detect abnormalities in the brain. However, signals from PET contain many different types of information, and it is important to interpret the signals appropriately and choose the proper technique to analyze PET data. This chapter discusses several analytical methods for PET data.

Pharmacokinetic Challenges against Brain Diseases with PET

2011 ◽  
pp. 145-155
Author(s):  
Hiroshi Watabe ◽  
Keisuke Matsubara ◽  
Yoko Ikoma
Keyword(s):  
High Sensitivity ◽  
Brain Diseases ◽  
Positron Emission ◽  
Functional Images ◽  
Dopamine And Serotonin Receptors ◽  
Anatomical Image ◽  
Time Courses ◽  
Living Organisms ◽  
Types Of Information

Positron emission tomography (PET) is an imaging technology used to visualize distribution of particular ligands inside living organisms. The ligand is labeled by a positron-emitting isotope, such as 11C, 15O, 13N and 18F, and injected into subjects. By detecting ?-rays emitted from the ligand, in vivo biodistribution and kinetics of the ligand can be depicted with high sensitivity. By altering the target ligand for PET, one can see different distributions and time courses of the target. PET provides several biological and functional images inside the body, rather than simply an anatomical image. Therefore, PET can potentially detect biological changes that occur long before anatomical changes begin. PET has been widely used for neuroreceptor and neurotransmitter studies by tracing radioligands, which have selective affinity for a particular site. For example, the dopamine and serotonin receptors are highly related to brain disorders. By analyzing the pharmacokinetics of these ligands using PET, it is possible to noninvasively detect abnormalities in the brain. However, signals from PET contain many different types of information, and it is important to interpret the signals appropriately and choose the proper technique to analyze PET data. This chapter discusses several analytical methods for PET data.

Using inverse Laplace transform in positronium lifetime imaging

2022 ◽  
Author(s):  
Kengo Shibuya ◽  
Haruo Saito ◽  
Hideaki Tashima ◽  
Taiga Yamaya
Keyword(s):  
Laplace Transform ◽  
Inverse Laplace Transform ◽  
Emission Tomography ◽  
Statistical Accuracy ◽  
Lifetime Imaging ◽  
Positron Emission ◽  
Positronium Lifetime ◽  
Physical And Chemical ◽  
Limited Sensitivity

Abstract Positronium (Ps) lifetime imaging is gaining attention to bring out additional biomedical information from positron emission tomography (PET). The lifetime of Ps in vivo can change depending on the physical and chemical environments related to some diseases. Due to the limited sensitivity, Ps lifetime imaging may require merging some voxels for statistical accuracy. This paper presents a method for separating the lifetime components in the voxel to avoid information loss due to averaging. The mathematics for this separation is the inverse Laplace transform (ILT), and the authors examined an iterative numerical ILT algorithm using Tikhonov regularization, namely CONTIN, to discriminate a small lifetime difference due to oxygen saturation. The separability makes it possible to merge voxels without missing critical information on whether they contain abnormally long or short lifetime components. The authors conclude that ILT can compensate for the weaknesses of Ps lifetime imaging and extract the maximum amount of information.

scholarly journals FT-4202, an oral PKR activator, has potent antisickling effects and improves RBC survival and Hb levels in SCA mice

2021 ◽  
Vol 5 (9) ◽  
pp. 2385-2390
Author(s):  
Archana Shrestha ◽  
Mengna Chi ◽  
Kimberly Wagner ◽  
Astha Malik ◽  
Jennifer Korpik ◽  
...  
Keyword(s):  
Shear Stress ◽  
Blood Cell ◽  
Partial Pressure ◽  
Sickle Cell Anemia ◽  
Biological Effects ◽  
Membrane Damage ◽  
Partial Pressure Of Oxygen ◽  
Sickle Hemoglobin ◽  
Investigational Agent

Abstract Sickle cell anemia (SCA) results from an abnormal sickle hemoglobin (HbS). HbS polymerizes upon deoxygenation, resulting in red blood cell (RBC) sickling and membrane damage that cause vaso-occlusions and hemolysis. Sickle RBCs contain less adenosine triphosphate and more 2,3-diphosphoglycerate than normal RBCs, which allosterically reduces hemoglobin (Hb) oxygen (O2) affinity (ie, increases the partial pressure of oxygen at which hemoglobin is 50% saturated with oxygen [P50]), potentiating HbS polymerization. Herein, we tested the effect of investigational agent FT-4202, an RBC pyruvate kinase (PKR) activator, on RBC sickling and membrane damage by administering it to Berkeley SCA mice. Two-week oral FT-4202 administration was well tolerated, decreasing HbS P50 to levels similar to HbA and demonstrating beneficial biological effects. In FT-4202–treated animals, there was reduced sickling in vivo, demonstrated by fewer irreversibly sickled cells, and improved RBC deformability, assessed at varying shear stress. Controlled deoxygenation followed by reoxygenation of RBCs obtained from the blood of FT-4202–treated mice showed a shift in the point of sickling to a lower partial pressure of oxygen (pO2). This led to a nearly 30% increase in RBC survival and a 1.7g/dL increase in Hb level in the FT-4202–treated SCA mice. Overall, our results in SCA mice suggest that FT-4202 might be a potentially useful oral antisickling agent that warrants investigation in patients with SCA.

scholarly journals Preclinical Molecular Imaging for Precision Medicine in Breast Cancer Mouse Models

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
M. F. Fiordelisi ◽  
L. Auletta ◽  
L. Meomartino ◽  
L. Basso ◽  
G. Fatone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Imaging ◽  
Animal Models ◽  
Early Detection ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Clinical Medicine ◽  
High Sensitivity ◽  
Positron Emission

Precision and personalized medicine is gaining importance in modern clinical medicine, as it aims to improve diagnostic precision and to reduce consequent therapeutic failures. In this regard, prior to use in human trials, animal models can help evaluate novel imaging approaches and therapeutic strategies and can help discover new biomarkers. Breast cancer is the most common malignancy in women worldwide, accounting for 25% of cases of all cancers and is responsible for approximately 500,000 deaths per year. Thus, it is important to identify accurate biomarkers for precise stratification of affected patients and for early detection of responsiveness to the selected therapeutic protocol. This review aims to summarize the latest advancements in preclinical molecular imaging in breast cancer mouse models. Positron emission tomography (PET) imaging remains one of the most common preclinical techniques used to evaluate biomarker expression in vivo, whereas magnetic resonance imaging (MRI), particularly diffusion-weighted (DW) sequences, has been demonstrated as capable of distinguishing responders from nonresponders for both conventional and innovative chemo- and immune-therapies with high sensitivity and in a noninvasive manner. The ability to customize therapies is desirable, as this will enable early detection of diseases and tailoring of treatments to individual patient profiles. Animal models remain irreplaceable in the effort to understand the molecular mechanisms and patterns of oncologic diseases.

scholarly journals In vivo functional imaging with SPECT and PET

2001 ◽  
Vol 89 (4-5) ◽  
Author(s):  
H. Herzog
Keyword(s):  
Spatial Information ◽  
Single Photon ◽  
Photon Emission ◽  
The Body ◽  
Emission Computed Tomography ◽  
Physiological Processes ◽  
Positron Emission ◽  
In Vivo Functional Imaging ◽  
Photon Emission Computed Tomography

Nuclear medicine methods permit the visualisation of a variety of metabolic and physiological processes all over the body. Although planar scintigraphy has been found useful for many questions, detailed spatial information about the diseased organ can only be obtained with tomographic methods. Dependent on the radionuclide involved, two different tomographic procedures are available: single photon emission computed tomography (SPECT) and positron emission tomography (PET). The first part of this paper describes shortly the historical development of these methods as well as their technical and methodological basics. To elucidate the large variety of possible applications, an overview of SPECT and PET procedures utilised in research as well as in clinical practice are presented. Furthermore, both methods are compared and their individual advantages are pointed out.

Combined BNCT and PET for theranostics

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Michał Silarski ◽  
Katarzyna Dziedzic-Kocurek ◽  
Monika Szczepanek
Keyword(s):  
State Of The Art ◽  
Short Review ◽  
Monitoring Methods ◽  
Boron Uptake ◽  
Oncological Treatment ◽  
Boron Neutron Capture ◽  
Positron Emission ◽  
Total Body ◽  
Pet Scanners

Abstract This short review summarizes the issue of boron distribution monitoring in boron neutron capture therapy (BNCT), which remains a serious drawback of this powerful oncological treatment. Here we present the monitoring methods that are presently used with particular emphasis on the positron emission tomography (PET) which has the highest potential to be used for the real-time monitoring of boron biodistribution. We discuss the possibility of using present PET scanners to determine the boron uptake in vivo before the BNCT treatment with the use of p-boronphenylalanine (BPA) labeled with 18F isotope. Several examples of preclinical studies and clinical trials performed with the use of [18F]FBPA are shown. We also discuss shortly the perspectives of using other radiotracers and boron carriers which may significantly improve the boron imaging with the use of the state-of-the-art Total-Body PET scanners providing a theranostic approach in the BNCT.

scholarly journals In vivo oxygen measurement in cerebrospinal fluid of pigs to determine physiologic and pathophysiologic oxygen values during CNS infections

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nicole de Buhr ◽  
Alexander Martens ◽  
Marita Meurer ◽  
Marta C. Bonilla ◽  
Franz Söbbeler ◽  
...  
Keyword(s):  
Partial Pressure ◽  
Ph Value ◽  
Cell Number ◽  
Bacterial Number ◽  
Oxygen Level ◽  
Partial Pressure Of Oxygen ◽  
Oxygen Levels ◽  
In Vivo Measurement ◽  
Cns Infections

AbstractDuring infection and inflammation, a reduced oxygen level clearly affects cellular functions. Oxygen levels during CNS infections are unknown. Here we established and evaluated an in vivo measurement system to characterize the oxygen level in parallel with bacterial numbers (CFU/mL), the cell number and pH level inside the CSF of healthy compared to Streptococcus suis-infected pigs. The animals were anesthetized over a seven-hour period with isoflurane in air/oxygen at physiologic arterial partial pressure of oxygen. Oxygen levels in CSF of anesthetized pigs were compared to euthanized pigs. The detected partial pressure of oxygen in the CSF remained constant in a range of 47–63 mmHg, independent of the infection status (bacterial or cell number). In contrast, the pH value showed a slight drop during infection, which correlated with cell and bacterial number in CSF. We present physiologic oxygen and pH values in CSF during the onset of bacterial meningitis.

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