scholarly journals A Dual-Labeled Annexin A5 is not Suited for SPECT Imaging of Brain Cell Death in Experimental Murine Stroke

2014 ◽  
Vol 34 (9) ◽  
pp. e1-e7 ◽  
Author(s):  
Marietta Zille ◽  
Denise Harhausen ◽  
Marijke De Saint-Hubert ◽  
Roger Michel ◽  
Chris P Reutelingsperger ◽  
...  
Keyword(s):  
Cell Death ◽  
Fluorescence Microscopy ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Spect Imaging ◽  
Experimental Stroke ◽  
Emission Computed Tomography ◽  
Annexin A5

Cell death is one of the pathophysiological hallmarks after stroke. Markers to image cell death pathways in vivo are highly desirable. We previously showed that fluorescently labeled Annexin A5 (An×A5), which binds specifically to phosphatidylserine (PS) on dead/dying cells, can be used in experimental stroke for monitoring cell death with optical imaging. Here we investigated whether dual-labeled An×A5 (technetium and fluorescence label) can be used for single-photon emission computed tomography (SPECT) of cell death in the same model. C57Bl6/N mice were subjected to 60-minute middle cerebral artery occlusion (MCAO) and underwent SPECT imaging at 24, 48, and 72 hours afterwards. They were injected intravenously with either PS-binding An×A5 or the nonfunctional An×A5 (negative control), labeled with 99mTc and Alexa Fluor 568, respectively. After SPECT imaging, brain sections were cut for autoradiography and fluorescence microscopy. Ethanol-induced cell death in the femur muscle was used as positive control. We detected dual-labeled An×A5 in the model of ethanol-induced cell death in the femur muscle, but not after MCAO at any time point, either with SPECT or with ex vivo autoradiography or fluorescence microscopy. Dual-labeled An×A5 appears to be unsuited for visualizing death of brain cells in this MCAO model.

scholarly journals NIRF-Molecular Imaging with Synovial Macrophages-Targeting Vsig4 Nanobody for Disease Monitoring in a Mouse Model of Arthritis

2019 ◽  
Vol 20 (13) ◽  
pp. 3347 ◽  
Author(s):  
Fang Zheng ◽  
Siyu Luo ◽  
Zhenlin Ouyang ◽  
Jinhong Zhou ◽  
Huanye Mo ◽  
...  
Keyword(s):  
Fluorescence Microscopy ◽  
Near Infrared ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Joint Inflammation ◽  
Experimental Arthritis ◽  
Emission Computed Tomography ◽  
Nirf Imaging

Nanobody against V-set and Ig domain-containing 4 (Vsig4) on tissue macrophages, such as synovial macrophages, could visualize joint inflammation in multiple experimental arthritis models via single-photon emission computed tomography imaging. Here, we further addressed the specificity and assessed the potential for arthritis monitoring using near-infrared fluorescence (NIRF) Cy7-labeled Vsig4 nanobody (Cy7-Nb119). In vivo NIRF-imaging of collagen-induced arthritis (CIA) was performed using Cy7-Nb119. Signals obtained with Cy7-Nb119 or isotope control Cy7-NbBCII10 were compared in joints of naive mice versus CIA mice. In addition, pathological microscopy and fluorescence microscopy were used to validate the arthritis development in CIA. Cy7-Nb119 accumulated in inflamed joints of CIA mice, but not the naive mice. Development of symptoms in CIA was reflected in increased joint accumulation of Cy7-Nb119, which correlated with the conventional measurements of disease. Vsig4 is co-expressed with F4/80, indicating targeting of the increasing number of synovial macrophages associated with the severity of inflammation by the Vsig4 nanobody. NIRF imaging with Cy7-Nb119 allows specific assessment of inflammation in experimental arthritis and provides complementary information to clinical scoring for quantitative, non-invasive and economical monitoring of the pathological process. Nanobody labelled with fluorescence can also be used for ex vivo validation experiments using flow cytometry and fluorescence microscopy.

scholarly journals Dopamine D2/3 Receptor Availabilities and Evoked Dopamine Release in Striatum Differentially Predict Impulsivity and Novelty Preference in Roman High- and Low-Avoidance Rats

2020 ◽  
Author(s):  
Lidia Bellés ◽  
Andrea Dimiziani ◽  
Stergios Tsartsalis ◽  
Philippe Millet ◽  
François R Herrmann ◽  
...  
Keyword(s):  
Ventral Striatum ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Dorsal Striatum ◽  
Reaction Time Task ◽  
Emission Computed Tomography ◽  
Novelty Preference ◽  
Da Release

Abstract Background Impulsivity and novelty preference are both associated with an increased propensity to develop addiction-like behaviors, but their relationship and respective underlying dopamine (DA) underpinnings are not fully elucidated. Methods We evaluated a large cohort (n = 49) of Roman high- and low-avoidance rats using single photon emission computed tomography to concurrently measure in vivo striatal D2/3 receptor (D2/3R) availability and amphetamine (AMPH)-induced DA release in relation to impulsivity and novelty preference using a within-subject design. To further examine the DA-dependent processes related to these traits, midbrain D2/3-autoreceptor levels were measured using ex vivo autoradiography in the same animals. Results We replicated a robust inverse relationship between impulsivity, as measured with the 5-choice serial reaction time task, and D2/3R availability in ventral striatum and extended this relationship to D2/3R levels measured in dorsal striatum. Novelty preference was positively related to impulsivity and showed inverse associations with D2/3R availability in dorsal striatum and ventral striatum. A high magnitude of AMPH-induced DA release in striatum predicted both impulsivity and novelty preference, perhaps owing to the diminished midbrain D2/3-autoreceptor availability measured in high-impulsive/novelty-preferring Roman high-avoidance animals that may amplify AMPH effect on DA transmission. Mediation analyses revealed that while D2/3R availability and AMPH-induced DA release in striatum are both significant predictors of impulsivity, the effect of striatal D2/3R availability on novelty preference is fully mediated by evoked striatal DA release. Conclusions Impulsivity and novelty preference are related but mediated by overlapping, yet dissociable, DA-dependent mechanisms in striatum that may interact to promote the emergence of an addiction-prone phenotype.

scholarly journals Radionuclide imaging of apoptosis for clinical application

2021 ◽  
Author(s):  
Xiyi Qin ◽  
Han Jiang ◽  
Yu Liu ◽  
Hong Zhang ◽  
Mei Tian
Keyword(s):  
Cell Death ◽  
Radionuclide Imaging ◽  
Single Photon ◽  
Apoptotic Cell ◽  
Photon Emission ◽  
Early Response ◽  
Biochemical Changes ◽  
Emission Computed Tomography ◽  
Positron Emission

AbstractApoptosis was a natural, non-inflammatory, energy-dependent form of programmed cell death (PCD) that can be discovered in a variety of physiological and pathological processes. Based on its characteristic biochemical changes, a great number of apoptosis probes for single-photon emission computed tomography (SPECT) and positron emission tomography (PET) have been developed. Radionuclide imaging with these tracers were potential for the repetitive and selective detection of apoptotic cell death in vivo, without the need for invasive biopsy. In this review, we overviewed molecular mechanism and specific biochemical changes in apoptotic cells and summarized the existing tracers that have been used in clinical trials as well as their potentialities and limitations. Particularly, we highlighted the clinic applications of apoptosis imaging as diagnostic markers, early-response indicators, and prognostic predictors in multiple disease fields.

scholarly journals In Vivo Assessment of VCAM-1 Expression by SPECT/CT Imaging in Mice Models of Human Triple Negative Breast Cancer

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1039
Author(s):  
Montemagno ◽  
Dumas ◽  
Cavaillès ◽  
Ahmadi ◽  
Bacot ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Single Photon ◽  
Lung Metastases ◽  
Photon Emission ◽  
Spect Imaging ◽  
Emission Computed Tomography

Recent progress in breast cancer research has led to the identification of Vascular Cell Adhesion Molecule-1 (VCAM-1) as a key actor of metastatic colonization. VCAM-1 promotes lung-metastases and is associated with clinical early recurrence and poor outcome in triple negative breast cancer (TNBC). Our objective was to perform the in vivo imaging of VCAM-1 in mice models of TNBC. The Cancer Genomic Atlas (TCGA) database was analyzed to evaluate the prognostic role of VCAM-1 in TNBC. MDA-MB-231 (VCAM-1+) and control HCC70 (VCAM-1-) TNBC cells were subcutaneously xenografted in mice and VCAM-1 expression was assessed in vivo by single-photon emission computed tomography (SPECT) imaging using 99mTc-cAbVCAM1-5. Then, MDA-MB-231 cells were intravenously injected in mice and VCAM-1 expression in lung metastasis was assessed by SPECT imaging after 8 weeks. TCGA analysis showed that VCAM-1 is associated with a poor prognosis in TNBC patients. In subcutaneous tumor models, 99mTc-cAbVCAM1-5 uptake was 2-fold higher in MDA-MB-231 than in HCC70 (p < 0.01), and 4-fold higher than that of the irrelevant control (p < 0.01). Moreover, 99mTc-cAbVCAM1-5 uptake in MDA-MB-231 lung metastases was also higher than that of 99mTc-Ctl (p < 0.05). 99mTc-cAbVCAM1-5 is therefore a suitable tool to evaluate the role of VCAM-1 as a marker of tumor aggressiveness of TNBC.

scholarly journals Radioactive Labeling of Milk-Derived Exosomes with 99mTc and In Vivo Tracking by SPECT Imaging

Nanomaterials ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1062 ◽  
Author(s):  
María Isabel González ◽  
Pilar Martín-Duque ◽  
Manuel Desco ◽  
Beatriz Salinas
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Spect Imaging ◽  
Emission Computed Tomography ◽  
Histological Techniques ◽  
Non Invasive ◽  
Longitudinal Tracking ◽  
Pharmacokinetic Properties ◽  
Photon Emission Computed Tomography

Over the last decade, exosomes from diverse biological sources have been proposed as new natural platforms in drug delivery. Translation of these nanometric tools to clinical practice requires deep knowledge of their pharmacokinetic properties and biodistribution. The pharmacokinetic properties of exosomes are sometimes evaluated using biochemical and histological techniques that are considerably invasive. As an alternative, we present radiochemical labeling of milk-derived exosomes based on reduced 99mTc (IV) without modifying biological and physicochemical properties. This approach enables longitudinal tracking of natural exosomes by non-invasive single photon emission computed tomography (SPECT) imaging and the evaluation of their pharmacokinetic properties according to the route of administration.

scholarly journals In situ lymphoma imaging in a spontaneous mouse model using the Cerenkov Luminescence of F-18 and Ga-67 isotopes

2021 ◽  
Author(s):  
Zsombor Ritter ◽  
Katalin Zámbó ◽  
Péter Balogh ◽  
Dávid Szöllősi ◽  
Xinkai Jia ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Single Photon ◽  
Ex Vivo ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Advanced Stage ◽  
Terminal Stage ◽  
Imaging Results ◽  
67Ga Citrate

Abstract We aimed to study lymphoma diagnostics by Cerenkov luminescence imaging (CLI). We monitored the dissemination of a spontaneous high-grade mouse lymphoma (Bc.DLFL1) in early stage; advanced stage; and terminal stage with in vivo 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) / magnetic resonance imaging (MRI) and 67Ga-citrate single photon emission computed tomography (SPECT) / MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with Fluorine-18 and Gallium-67 to select infiltrated lymph nodes for tumor staging pathology was thus tested. At advanced stage, [18F]FDG PET/MRI plus ex vivo CLI allowed accurate detection of [18F]FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report the Cerenkov light emission of 67Ga. CLI with 67Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous [18F]FDG distribution in lymph nodes detected at sampling surgery has implications for tissue pathology processing and could direct therapy. The results with 67Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.

scholarly journals A Novel SPECT-Based Approach Reveals Early Mechanisms of Central and Peripheral Inflammation after Cerebral Ischemia

2015 ◽  
Vol 35 (12) ◽  
pp. 1921-1929 ◽  
Author(s):  
Krisztián Szigeti ◽  
Ildikó Horváth ◽  
Dániel S Veres ◽  
Bernadett Martinecz ◽  
Nikolett Lénárt ◽  
...  
Keyword(s):  
Brain Injury ◽  
Single Photon ◽  
Photon Emission ◽  
Experimental Stroke ◽  
Emission Computed Tomography ◽  
Peripheral Inflammation ◽  
Poor Outcome ◽  
Diethylene Triamine Pentaacetic Acid ◽  
Magnetic Resonance Imaging Mri

Inflammation that develops in the brain and peripheral organs after stroke contributes profoundly to poor outcome of patients. However, mechanisms through which inflammation impacts on brain injury and overall outcome are improperly understood, in part because the earliest inflammatory events after brain injury are not revealed by current imaging tools. Here, we show that single-photon emission computed tomography (NanoSPECT/CT Plus) allows visualization of blood brain barrier (BBB) injury after experimental stroke well before changes can be detected with magnetic resonance imaging (MRI). Early 99mTc-DTPA (diethylene triamine pentaacetic acid) signal changes predict infarct development and systemic inflammation preceding experimental stroke leads to very early perfusion deficits and increased BBB injury within 2 hours after the onset of ischemia. Acute brain injury also leads to peripheral inflammation and immunosuppression, which contribute to poor outcome of stroke patients. The SPECT imaging revealed early (within 2 hours) changes in perfusion, barrier function and inflammation in the lungs and the gut after experimental stroke, with good predictive value for the development of histopathologic changes at later time points. Collectively, visualization of early inflammatory changes after stroke could open new translational research avenues to elucidate the interactions between central and peripheral inflammation and to evaluate in vivo ‘multi-system’ effects of putative anti-inflammatory treatments.

Radioligands for PET and SPECT Imaging of the Central Noradrenergic System

CNS Spectrums ◽  
2001 ◽  
Vol 6 (8) ◽  
pp. 704-709 ◽  
Author(s):  
Jonathan McConathy ◽  
Clinton D. Kilts ◽  
Mark M. Goodman
Keyword(s):  
Single Photon ◽  
Photon Emission ◽  
Spect Imaging ◽  
Monoamine Oxidase A ◽  
Imaging Agents ◽  
Emission Computed Tomography ◽  
Noradrenergic System ◽  
Positron Emission ◽  
Central Noradrenergic System

ABSTRACTIn the central nervous system, the neurotransmitter norepinephrine is involved in normal physiology, neuropsychiatric disorders, and the effects of numerous drugs. Although alterations of the central noradrenergic system are involved in the pathophysiology and pharmacotherapy of mood disorders, the basis and nature of these changes remain unresolved. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging agents will be valuable for further elucidating the roles of norepinephrine in health and disease. This review discusses PET and SPECT radioligands that have been developed for the enzymes, receptors, and transporters involved in noradrenergic neurotransmission. Currently, imaging agents that exhibit specific in vivo uptake in the brain have been described for monoamine oxidase A and β-adrenergic receptors, but have not undergone detailed evaluation or experimental application. Based on the successful development and utilization of in vivo imaging agents for elements of the central dopaminergic and serotoninergic systems, PET and SPECT radioligands are expected to serve as new tools for studying the physiology, pathophysiology, and pharmacology of the central noradrenergic system.

Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Specific Binding ◽  
Specific Interaction ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mixed Effect ◽  
Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

scholarly journals Degradation of Drug Delivery Nanocarriers and Payload Release: A Review of Physical Methods for Tracing Nanocarrier Biological Fate

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 770
Author(s):  
Patrick M. Perrigue ◽  
Richard A. Murray ◽  
Angelika Mielcarek ◽  
Agata Henschke ◽  
Sergio E. Moya
Keyword(s):  
Drug Delivery ◽  
Laser Scanning ◽  
Single Photon ◽  
Photon Emission ◽  
Correlation Spectroscopy ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Emission Computed Tomography ◽  
Systemic Delivery

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.

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