scholarly journals PET imaging of reactive astrocytes in neurological disorders

2021 ◽  
Author(s):  
Yu Liu ◽  
Han Jiang ◽  
Xiyi Qin ◽  
Mei Tian ◽  
Hong Zhang
Keyword(s):  
Pet Imaging ◽  
Biological Activities ◽  
Neurological Diseases ◽  
Critical Role ◽  
Reactive Astrocytes ◽  
Future Studies ◽  
Positron Emission ◽  
Pathological Mechanism ◽  
Functional Remodeling

AbstractThe reactive astrocytes manifest molecular, structural, and functional remodeling in injury, infection, or diseases of the CNS, which play a critical role in the pathological mechanism of neurological diseases. A growing need exists for dependable approach to better characterize the activation of astrocyte in vivo. As an advanced molecular imaging technology, positron emission tomography (PET) has the potential for visualizing biological activities at the cellular levels. In the review, we summarized the PET visualization strategies for reactive astrocytes and discussed the applications of astrocyte PET imaging in neurological diseases. Future studies are needed to pay more attention to the development of specific imaging agents for astrocytes and further improve our exploration of reactive astrocytes in various diseases.

scholarly journals PET imaging of cannabinoid type 2 receptors with [11C]A-836339 did not evidence changes following neuroinflammation in rats

2017 ◽  
Vol 37 (3) ◽  
pp. 1163-1178 ◽  
Author(s):  
Geraldine Pottier ◽  
Vanessa Gómez-Vallejo ◽  
Daniel Padro ◽  
Raphaël Boisgard ◽  
Frédéric Dollé ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Pet Imaging ◽  
Receptor Expression ◽  
Brain Inflammation ◽  
Cb2 Receptor ◽  
Future Studies ◽  
Positron Emission

Cannabinoid type 2 receptors (CB2R) have emerged as promising targets for the diagnosis and therapy of brain pathologies. However, no suitable radiotracers for accurate CB2R mapping have been found to date, limiting the investigation of the CB2 receptor expression using positron emission tomography (PET) imaging. In this work, we report the evaluation of the in vivo expression of CB2R with [11C]A-836339 PET after cerebral ischemia and in two rat models of neuroinflammation, first by intrastriatal LPS and then by AMPA injection. PET images and in vitro autoradiography showed a lack of specific [11C]A-836339 uptake in these animal models demonstrating the limitation of this radiotracer to image CB2 receptor under neuroinflammatory conditions. Further, using immunohistochemistry, the CB2 receptor displayed a modest expression increase after cerebral ischemia, LPS and AMPA models. Finally, [18F]DPA-714-PET and immunohistochemistry demonstrated decreased neuroinflammation by a selective CB2R agonist, JWH133. Taken together, these findings suggest that [11C]A-836339 is not a suitable radiotracer to monitor in vivo CB2R expression by using PET imaging. Future studies will have to investigate alternative radiotracers that could provide an accurate binding to CB2 receptors following brain inflammation.

scholarly journals In VivoPET Imaging of Adenosine 2A Receptors in Neuroinflammatory and Neurodegenerative Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Anna Vuorimaa ◽  
Eero Rissanen ◽  
Laura Airas
Keyword(s):  
Immune System ◽  
Pet Imaging ◽  
Neurological Diseases ◽  
Suppressive Effect ◽  
Receptor Targeting ◽  
Additional Tool ◽  
Positron Emission ◽  
The Central Nervous System ◽  
G Protein Coupled

Adenosine receptors are G-protein coupled P1 purinergic receptors that are broadly expressed in the peripheral immune system, vasculature, and the central nervous system (CNS). Within the immune system, adenosine 2A (A2A) receptor-mediated signaling exerts a suppressive effect on ongoing inflammation. In healthy CNS,A2Areceptors are expressed mainly within the neurons of the basal ganglia. Alterations inA2Areceptor function and expression have been noted in movement disorders, and in Parkinson’s disease pharmacologicalA2Areceptor antagonism leads to diminished motor symptoms. AlthoughA2Areceptors are expressed only at a low level in the healthy CNS outside striatum, pathological challenge or inflammation has been shown to lead to upregulation ofA2Areceptors in extrastriatal CNS tissue, and this has been successfully quantitated usingin vivopositron emission tomography (PET) imaging andA2Areceptor-binding radioligands. Several radioligands for PET imaging ofA2Areceptors have been developed in recent years, andA2Areceptor-targeting PET imaging may thus provide a potential additional tool to evaluate various aspects of neuroinflammationin vivo. This review article provides a brief overview ofA2Areceptors in healthy brain and in a selection of most important neurological diseases and describes the recent advances inA2Areceptor-targeting PET imaging studies.

PET Imaging of Adenosine Receptors in Diseases

2019 ◽  
Vol 19 (16) ◽  
pp. 1445-1463 ◽  
Author(s):  
Jindian Li ◽  
Xingfang Hong ◽  
Guoquan Li ◽  
Peter S. Conti ◽  
Xianzhong Zhang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Adenosine Receptors ◽  
Neurological Diseases ◽  
G Protein Coupled Receptors ◽  
Extracellular Adenosine ◽  
Positron Emission ◽  
Imaging Probes ◽  
Pet Probes ◽  
Cancer And Inflammation ◽  
G Protein Coupled

Adenosine receptors (ARs) are a class of purinergic G-protein-coupled receptors (GPCRs). Extracellular adenosine is a pivotal regulation molecule that adjusts physiological function through the interaction with four ARs: A1R, A2AR, A2BR, and A3R. Alterations of ARs function and expression have been studied in neurological diseases (epilepsy, Alzheimer’s disease, and Parkinson’s disease), cardiovascular diseases, cancer, and inflammation and autoimmune diseases. A series of Positron Emission Tomography (PET) probes for imaging ARs have been developed. The PET imaging probes have provided valuable information for diagnosis and therapy of diseases related to alterations of ARs expression. This review presents a concise overview of various ARs-targeted radioligands for PET imaging in diseases. The most recent advances in PET imaging studies by using ARs-targeted probes are briefly summarized.

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 11C- and 18F-Radiotracers for In Vivo Imaging of the Dopamine System: Past, Present and Future

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 108
Author(s):  
Michael R. Kilbourn
Keyword(s):  
Pet Imaging ◽  
In Vivo Imaging ◽  
Dopamine Synthesis ◽  
Dopamine System ◽  
Synaptic Release ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Pet Radiotracers ◽  
Selection Of

The applications of positron emission tomography (PET) imaging to study brain biochemistry, and in particular the aspects of dopamine neurotransmission, have grown significantly over the 40 years since the first successful in vivo imaging studies in humans. In vivo PET imaging of dopaminergic functions of the central nervous system (CNS) including dopamine synthesis, vesicular storage, synaptic release and receptor binding, and reuptake processes, are now routinely used for studies in neurology, psychiatry, drug abuse and addiction, and drug development. Underlying these advances in PET imaging has been the development of the unique radiotracers labeled with positron-emitting radionuclides such as carbon-11 and fluorine-18. This review focuses on a selection of the more accepted and utilized PET radiotracers currently available, with a look at their past, present and future.

STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [18F]FLT PET imaging

2021 ◽  
Vol 118 (36) ◽  
pp. e2105390118 ◽  
Author(s):  
Keke Liang ◽  
Evan R. Abt ◽  
Thuc M. Le ◽  
Arthur Cho ◽  
Amanda M. Dann ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Cell Metabolism ◽  
Nucleotide Metabolism ◽  
Type I Interferons ◽  
Ductal Adenocarcinoma ◽  
Type I ◽  
Flt Pet ◽  
Positron Emission ◽  
Pharmacodynamic Biomarkers

Type I interferons (IFNs) are critical effectors of emerging cancer immunotherapies designed to activate pattern recognition receptors (PRRs). A challenge in the clinical translation of these agents is the lack of noninvasive pharmacodynamic biomarkers that indicate increased intratumoral IFN signaling following PRR activation. Positron emission tomography (PET) imaging enables the visualization of tissue metabolic activity, but whether IFN signaling–induced alterations in tumor cell metabolism can be detected using PET has not been investigated. We found that IFN signaling augments pancreatic ductal adenocarcinoma (PDAC) cell nucleotide metabolism via transcriptional induction of metabolism-associated genes including thymidine phosphorylase (TYMP). TYMP catalyzes the first step in the catabolism of thymidine, which competitively inhibits intratumoral accumulation of the nucleoside analog PET probe 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT). Accordingly, IFN treatment up-regulates cancer cell [18F]FLT uptake in the presence of thymidine, and this effect is dependent upon TYMP expression. In vivo, genetic activation of stimulator of interferon genes (STING), a PRR highly expressed in PDAC, enhances the [18F]FLT avidity of xenograft tumors. Additionally, small molecule STING agonists trigger IFN signaling–dependent TYMP expression in PDAC cells and increase tumor [18F]FLT uptake in vivo following systemic treatment. These findings indicate that [18F]FLT accumulation in tumors is sensitive to IFN signaling and that [18F]FLT PET may serve as a pharmacodynamic biomarker for STING agonist–based therapies in PDAC and possibly other malignancies characterized by elevated STING expression.

scholarly journals Imaging Cardiovascular and Lung Macrophages With the Positron Emission Tomography Sensor 64 Cu-Macrin in Mice, Rabbits, and Pigs

2020 ◽  
Vol 13 (10) ◽  
Author(s):  
Matthias Nahrendorf ◽  
Friedrich Felix Hoyer ◽  
Anu E. Meerwaldt ◽  
Mandy M.T. van Leent ◽  
Max L. Senders ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Flow Cytometry ◽  
Confocal Microscopy ◽  
Pet Imaging ◽  
Near Infrared ◽  
Emission Tomography ◽  
Imaging Biomarker ◽  
Positron Emission ◽  
Pulmonary Macrophages

Background: Macrophages, innate immune cells that reside in all organs, defend the host against infection and injury. In the heart and vasculature, inflammatory macrophages also enhance tissue damage and propel cardiovascular diseases. Methods: We here use in vivo positron emission tomography (PET) imaging, flow cytometry, and confocal microscopy to evaluate quantitative noninvasive assessment of cardiac, arterial, and pulmonary macrophages using the nanotracer 64 Cu-Macrin—a 20-nm spherical dextran nanoparticle assembled from nontoxic polyglucose. Results: PET imaging using 64 Cu-Macrin faithfully reported accumulation of macrophages in the heart and lung of mice with myocardial infarction, sepsis, or pneumonia. Flow cytometry and confocal microscopy detected the near-infrared fluorescent version of the nanoparticle ( VT680 Macrin) primarily in tissue macrophages. In 5-day-old mice, 64 Cu-Macrin PET imaging quantified physiologically more numerous cardiac macrophages. Upon intravenous administration of 64 Cu-Macrin in rabbits and pigs, we detected heightened macrophage numbers in the infarcted myocardium, inflamed lung regions, and atherosclerotic plaques using a clinical PET/magnetic resonance imaging scanner. Toxicity studies in rats and human dosimetry estimates suggest that 64 Cu-Macrin is safe for use in humans. Conclusions: Taken together, these results indicate 64 Cu-Macrin could serve as a facile PET nanotracer to survey spatiotemporal macrophage dynamics during various physiological and pathological conditions. 64 Cu-Macrin PET imaging could stage inflammatory cardiovascular disease activity, assist disease management, and serve as an imaging biomarker for emerging macrophage-targeted therapeutics.

scholarly journals PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2289
Author(s):  
Naresh Damuka ◽  
Paul Czoty ◽  
Ashley Davis ◽  
Michael Nader ◽  
Susan Nader ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Neurological Disorders ◽  
Healthy Male ◽  
Time Activity ◽  
Positron Emission ◽  
Pet Ct ◽  
Scan Data ◽  
The Brain ◽  
Human Primate

Dysregulation of microtubules is commonly associated with several psychiatric and neurological disorders, including addiction and Alzheimer’s disease. Imaging of microtubules in vivo using positron emission tomography (PET) could provide valuable information on their role in the development of disease pathogenesis and aid in improving therapeutic regimens. We developed [11C]MPC-6827, the first brain-penetrating PET radiotracer to image microtubules in vivo in the mouse brain. The aim of the present study was to assess the reproducibility of [11C]MPC-6827 PET imaging in non-human primate brains. Two dynamic 0–120 min PET/CT imaging scans were performed in each of four healthy male cynomolgus monkeys approximately one week apart. Time activity curves (TACs) and standard uptake values (SUVs) were determined for whole brains and specific regions of the brains and compared between the “test” and “retest” data. [11C]MPC-6827 showed excellent brain uptake with good pharmacokinetics in non-human primate brains, with significant correlation between the test and retest scan data (r = 0.77, p = 0.023). These initial evaluations demonstrate the high translational potential of [11C]MPC-6827 to image microtubules in the brain in vivo in monkey models of neurological and psychiatric diseases.

scholarly journals Radiosynthesis of [18F]-Labelled Pro-Nucleotides (ProTides)

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 704
Author(s):  
Alessandra Cavaliere ◽  
Katrin C. Probst ◽  
Stephen J. Paisey ◽  
Christopher Marshall ◽  
Abdul K. H. Dheere ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Pet Imaging ◽  
Early Stage ◽  
Proof Of Concept ◽  
Synthesis Time ◽  
Positron Emission ◽  
Anti Cancer ◽  
Radiochemical Yields ◽  
Radiochemical Synthesis

Phosphoramidate pro-nucleotides (ProTides) have revolutionized the field of anti-viral and anti-cancer nucleoside therapy, overcoming the major limitations of nucleoside therapies and achieving clinical and commercial success. Despite the translation of ProTide technology into the clinic, there remain unresolved in vivo pharmacokinetic and pharmacodynamic questions. Positron Emission Tomography (PET) imaging using [18F]-labelled model ProTides could directly address key mechanistic questions and predict response to ProTide therapy. Here we report the first radiochemical synthesis of [18F]ProTides as novel probes for PET imaging. As a proof of concept, two chemically distinct radiolabelled ProTides have been synthesized as models of 3′- and 2′-fluorinated ProTides following different radiosynthetic approaches. The 3′-[18F]FLT ProTide was obtained via a late stage [18F]fluorination in radiochemical yields (RCY) of 15–30% (n = 5, decay-corrected from end of bombardment (EoB)), with high radiochemical purities (97%) and molar activities of 56 GBq/μmol (total synthesis time of 130 min.). The 2′-[18F]FIAU ProTide was obtained via an early stage [18F]fluorination approach with an RCY of 1–5% (n = 7, decay-corrected from EoB), with high radiochemical purities (98%) and molar activities of 53 GBq/μmol (total synthesis time of 240 min).

Percutaneous Intracerebral Navigation by Duty-Cycled Spinning of Flexible Bevel-Tipped Needles

Neurosurgery ◽  
2010 ◽  
Vol 67 (4) ◽  
pp. 1117-1123 ◽  
Author(s):  
Johnathan A Engh ◽  
Davneet S Minhas ◽  
Douglas Kondziolka ◽  
Cameron N Riviere
Keyword(s):  
Image Guidance ◽  
Neurological Diseases ◽  
Steering System ◽  
Needle Steering ◽  
Future Studies ◽  
Area Of Interest ◽  
Cadaver Testing ◽  
The Brain ◽  
Cadaveric Model

Abstract BACKGROUND: Intracerebral drug delivery using surgically placed microcatheters is a growing area of interest for potential treatment of a wide variety of neurological diseases, including tumors, neurodegenerative disorders, trauma, epilepsy, and stroke. Current catheter placement techniques are limited to straight trajectories. The development of an inexpensive system for flexible percutaneous intracranial navigation may be of significant clinical benefit. OBJECTIVE: Utilizing duty-cycled spinning of a flexible bevel-tipped needle, the authors devised and tested a means of achieving nonlinear trajectories for the navigation of catheters in the brain, which may be applicable to a wide variety of neurological diseases. METHODS: Exploiting the bending tendency of bevel-tipped needles due to their asymmetry, the authors devised and tested a means of generating curvilinear trajectories by spinning a needle with a variable duty cycle (ie, in on-off fashion). The technique can be performed using image guidance, and trajectories can be adjusted intraoperatively via joystick. Fifty-eight navigation trials were performed during cadaver testing to demonstrate the efficacy of the needle-steering system and to test its precision. RESULTS: The needle-steering system achieved a target acquisition error of 2 ± 1 mm, while demonstrating the ability to reach multiple targets from one burr hole using trajectories of varying curvature. CONCLUSION: The accuracy of the needle-steering system was demonstrated in a cadaveric model. Future studies will determine the safety of the device in vivo.

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