scholarly journals In Vivo MRI of Functionalized Iron Oxide Nanoparticles for Brain Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Tang Tang ◽  
Anthony Valenzuela ◽  
Fanny Petit ◽  
Sarah Chow ◽  
Kevin Leung ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Scavenger Receptor ◽  
Brain Inflammation ◽  
Necrosis Factor Alpha ◽  
Activated Microglia ◽  
Intracerebral Administration ◽  
Positron Emission ◽  
Imaging Probes ◽  
The Brain

Microglia are intrinsic components of the brain immune system and are activated in many central nervous system disorders. The ability to noninvasively image these cells would provide valuable information for both research and clinical applications. Today, most imaging probes for activated microglia are mainly designed for positron emission tomography (PET) and target translocator proteins that also reside on other cerebral cells. The PET images obtained are not specific for microglia-driven inflammation. Here, we describe a potential PET/MRI multimodal imaging probe that selectively targets the scavenger receptor class A (SR-A) expressed on activated microglia. These sulfated dextran-coated iron oxide (SDIO) nanoparticles are avidly taken up by microglia and appear to be nontoxic when administered intravenously in a mouse model. Intravenous administration of this SDIO demonstrated visualization by T2∗-weighted MRI of microglia activated by intracerebral administration of tumor necrosis factor alpha (TNF-α). The contrast was significantly enhanced by SDIO, whereas there was little to no contrast change in animals treated with nontargeted nanoparticles or untreated controls. Thus, SR-A targeting represents a promising strategy to image activated microglia in the brain.

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.

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 In vivo delivery of a fluorescent FPR2/ALX-targeted probe using focused ultrasound and microbubbles to image activated microglia

2020 ◽  
Vol 1 (5) ◽  
pp. 385-389
Author(s):  
Sophie V. Morse ◽  
Tamara Boltersdorf ◽  
Tiffany G. Chan ◽  
Felicity N. E. Gavins ◽  
James J. Choi ◽  
...  
Keyword(s):  
Neurological Disorders ◽  
Focused Ultrasound ◽  
Imaging Agent ◽  
Targeted Imaging ◽  
Activated Microglia ◽  
The Brain ◽  
In Vivo Delivery

Targeted imaging agent labels activated microglia when delivered into the brain with focused ultrasound and microbubbles – a tool to investigate inflammation in neurological disorders.

scholarly journals Developments in Tau PET Imaging

2014 ◽  
Vol 41 (5) ◽  
pp. 547-553 ◽  
Author(s):  
Eduardo Rigon Zimmer ◽  
Antoine Leuzy ◽  
Serge Gauthier ◽  
Pedro Rosa-Neto
Keyword(s):  
Therapeutic Interventions ◽  
Imaging Agents ◽  
Cognitive Assessments ◽  
Molecular Subgroup ◽  
Future Directions ◽  
Tau Imaging ◽  
Positron Emission ◽  
The Brain ◽  
Pet Radiopharmaceuticals

ABSTRACTThe presence of neurofibrillary tangles in the brain is a hallmark feature of several neurodegenerative diseases termed “tauopathies,” including Alzheimer’s disease (AD) and the tau molecular subgroup of frontotemporal lobar degeneration (FTLD-tau). Recently, several positron emission tomography (PET) radiopharmaceuticals targeting abnormal conformations of the tau protein have been developed. To date, six novel tau imaging agents—[18F]THK523, [18F]THK5105, [18F]THK5117, [18F]T807, [18F]T808, and [11C]PBB3—have been described and are considered promising as potential tau radioligands. Tau imaging agents offer the opportunity of in vivo topographical mapping and quantification of tau aggregates in parallel with clinical and cognitive assessments. As such, tau imaging is considered of key importance for progress toward earlier and more accurate diagnosis of tauopathies as well as for the monitoring of therapeutic interventions and drug development. Here, we shed light on the most important developments in tau radiopharmaceuticals, highlighting challenges, possibilities and future directions.

scholarly journals Diphenhydramine as a selective probe to study H+-antiporter function at the blood–brain barrier: Application to [11C]diphenhydramine positron emission tomography imaging

2016 ◽  
Vol 37 (6) ◽  
pp. 2185-2195 ◽  
Author(s):  
Sylvain Auvity ◽  
Hélène Chapy ◽  
Sébastien Goutal ◽  
Fabien Caillé ◽  
Benoit Hosten ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Positron Emission Tomography Imaging ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Tomography Imaging ◽  
Blood Brain ◽  
Positron Emission ◽  
The Brain

Diphenhydramine, a sedative histamine H1-receptor (H1R) antagonist, was evaluated as a probe to measure drug/H+-antiporter function at the blood–brain barrier. In situ brain perfusion experiments in mice and rats showed that diphenhydramine transport at the blood–brain barrier was saturable, following Michaelis–Menten kinetics with a Km = 2.99 mM and Vmax = 179.5 nmol s−1 g−1. In the pharmacological plasma concentration range the carrier-mediated component accounted for 77% of diphenhydramine influx while passive diffusion accounted for only 23%. [14C]Diphenhydramine blood–brain barrier transport was proton and clonidine sensitive but was influenced by neither tetraethylammonium, a MATE1 (SLC47A1), and OCT/OCTN (SLC22A1-5) modulator, nor P-gp/Bcrp (ABCB1a/1b/ABCG2) deficiency. Brain and plasma kinetics of [11C]diphenhydramine were measured by positron emission tomography imaging in rats. [11C]Diphenhydramine kinetics in different brain regions were not influenced by displacement with 1 mg kg−1 unlabeled diphenhydramine, indicating the specificity of the brain positron emission tomography signal for blood–brain barrier transport activity over binding to any central nervous system target in vivo. [11C]Diphenhydramine radiometabolites were not detected in the brain 15 min after injection, allowing for the reliable calculation of [11C]diphenhydramine brain uptake clearance (Clup = 0.99 ± 0.18 mL min−1 cm−3). Diphenhydramine is a selective and specific H+-antiporter substrate. [11C]Diphenhydramine positron emission tomography imaging offers a reliable and noninvasive method to evaluate H+-antiporter function at the blood–brain barrier.

Recent advances in molecular imaging probes for β-amyloid plaques

MedChemComm ◽  
2015 ◽  
Vol 6 (3) ◽  
pp. 391-402 ◽  
Author(s):  
Masahiro Ono ◽  
Hideo Saji
Keyword(s):  
Molecular Imaging ◽  
Optical Imaging ◽  
Amyloid Plaques ◽  
Recent Advances ◽  
Molecular Imaging Probes ◽  
Imaging Probes ◽  
Β Amyloid ◽  
The Brain

We review recent advances in our development of molecular imaging probes for PET, SPECT, and optical imaging for in vivo detection of β-amyloid plaques in the brain.

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 Scavenger Receptor-AI–Targeted Iron Oxide Nanoparticles for In Vivo MRI Detection of Atherosclerotic Lesions

2013 ◽  
Vol 33 (8) ◽  
pp. 1812-1819 ◽  
Author(s):  
Filip M.E. Segers ◽  
Brigit den Adel ◽  
Ilze Bot ◽  
Linda M. van der Graaf ◽  
Eric P. van der Veer ◽  
...  
Keyword(s):  
Iron Oxide ◽  
Iron Oxide Nanoparticles ◽  
Scavenger Receptor ◽  
Oxide Nanoparticles ◽  
Atherosclerotic Lesions
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