Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction

2008 ◽  
Vol 104 (5) ◽  
pp. 1504-1512 ◽  
Author(s):  
Leszek Kalinowski ◽  
Lawrence W. Dobrucki ◽  
David F. Meoli ◽  
Donald P. Dione ◽  
Mehran M. Sadeghi ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ex Vivo ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Αvβ3 Integrin ◽  
Myocardial Uptake ◽  
Planar Imaging ◽  
Integrin Activation ◽  
Infarct Region

The αvβ3-integrin is expressed in angiogenic vessels in response to hypoxia and represents a potential novel target for imaging myocardial angiogenesis. This study evaluated the feasibility of noninvasively tracking hypoxia-induced αvβ3-integrin activation within the myocardium as a marker of angiogenesis early after myocardial infarction. Acute myocardial infarction was produced by coronary artery occlusion in rodent and canine studies. A novel 111In-labeled radiotracer targeted at the αvβ3-integrin (111In-RP748) was used to localize regions of hypoxia-induced angiogenesis early after infarction. In rodent studies, the specificity of 111In-RP748 for αvβ3-integrin was confirmed with a negative control compound (111In-RP790), and regional uptake of these compounds correlated with 201Tl perfusion and a 99mTc-labeled nitroimidazole (BRU59-21), which was used as a quantitative marker of myocardial hypoxia. The ex vivo analysis demonstrated that only 111In-RP748 was selectively retained in infarcted regions with reduced 201Tl perfusion and correlated with uptake of BRU59-21. In canine studies, myocardial uptake of 111In-RP748 was assessed using in vivo single-photon-emission computed tomography (SPECT), ex vivo planar imaging, and gamma well counting of myocardial tissue and correlated with 99mTc-labeled 2-methoxy-2-methyl-propyl-isonitrile (99mTc-sestamibi) perfusion. Dual-radiotracer in vivo SPECT imaging of 111In-RP748 and 99mTc-sestamibi provided visualization of 111In-RP748 uptake within the infarct region, which was confirmed by ex vivo planar imaging of excised myocardial slices. Myocardial 111In-RP748 retention was associated with histological evidence of αvβ3-integrin expression/activation in the infarct region. 111In-RP748 imaging provides a novel noninvasive approach for evaluation of hypoxia-induced αvβ3-integrin activation in myocardium early after infarction and may prove useful for directing and evaluating angiogenic therapies in patients with ischemic heart disease.

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 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.

Abstract 170: Inflammation Imaging in the Primate Heart Using 111 In-Labeled Anti-Tenascin-C Antibody

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Michiaki Hiroe ◽  
Naohide Ageyama ◽  
Yasuhiro Yasutomi ◽  
Hiroyuki Kurosawa ◽  
Ousuke Fujimoto ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Single Photon ◽  
Photon Emission ◽  
Border Zone ◽  
Myocardial Inflammation ◽  
Emission Computed Tomography ◽  
Myocardial Uptake ◽  
Dual Isotope ◽  
Tenascin C ◽  
Active Inflammation

Myocardial inflammation after myocardial infarction and myocarditis may cause cardiac remodeling, leading to congestive heart failure and arrhythmias. Tenascin-C (TNC), an extracellular matrix glycoprotein, is not normally expressed but specifically expressed associated with active inflammation. The aim of this study was to explore the myocardial expression of TNC after myocardial infarction in Macaca fascicularis (crab-eating monkey) using 111 In-labeled anti-TNC antibody ( 111 In-TNC-Fab’). The left coronary artery was permanently ligated in two monkies and 4 days later, we performed dual-isotope single-photon emission computed tomography imaging (SPECT) of 111 In-TNC-Fab’ and 99m Tc methoxy- isobutyl isonitrile (MIBI), and compared with those of an age-matched control. Then, dual autoradiography was compared with histology and immunostaining for TNC of the heart. Dual-isotope SPECT demonstrated the regional myocardial uptake of 111 In-TNC-Fab’ in the areas of decreased uptake of MIBI. On autoradiography, the radioactivities were observed in the border zone between the infarcted and the noninfarcted area of MI hearts. The hot spots corresponded with the positively immunostained areas. In contrast, no radioactivites of 111 In-TNC-Fab’ were detected in the control. These data clearly indicated that, using 111 In-TNC-Fab’, we can visualize the inflammatory lesions followed by myocardial infarction of the primate.

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 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 Efficient 1-Hour Technetium-99 m Pyrophosphate Imaging Protocol for the Diagnosis of Transthyretin Cardiac Amyloidosis

2020 ◽  
Vol 13 (2) ◽  
Author(s):  
Ahmad Masri ◽  
Syed Bukhari ◽  
Shahzad Ahmad ◽  
Ricardo Nieves ◽  
Yvonne S. Eisele ◽  
...  
Keyword(s):  
Cardiac Amyloidosis ◽  
Single Photon ◽  
Photon Emission ◽  
Tracer Uptake ◽  
Emission Computed Tomography ◽  
Myocardial Uptake ◽  
Planar Imaging ◽  
Imaging Protocol ◽  
Tertiary Center ◽  
Grade 3

Background: Technetium-99 m pyrophosphate protocols for transthyretin cardiac amyloidosis diagnosis have variably used 1- and 3-hour imaging time points. We investigated whether imaging at 1 hour with superior efficiency had comparable diagnostic accuracy as 3-hour imaging. Methods: This is a registry analysis of patients with suspected transthyretin cardiac amyloidosis referred for technetium-99 m pyrophosphate at a single tertiary center from June 2015 through January 2019. Patients underwent planar and single-photon emission computed tomography (SPECT) imaging at 1 and 3 hours. A positive Tc-99m pyrophosphate study was defined by the presence of diffuse myocardial tracer uptake on SPECT. For planar imaging, visual semiquantitative (grades 0-3, ≥2 considered positive) and quantitative heart to contralateral ratios (≥1.5 considered positive) were used. Results: Two hundred thirty-three patients (69% men; median age, 77 [69–83] years) underwent the study protocol. There were 60 (25.8%) patients with diffuse myocardial uptake, 1 (0.4%) with regional uptake, and 172 (73.8%) with no myocardial uptake. Results of SPECT were identical at 1 and 3 hours. Planar imaging at 1 hour had 98% sensitivity and 96% specificity. Planar grade 0 uptake or heart to contralateral ratio ≤1.2 and planar grade 3 uptake or heart to contralateral ratio ≥2.0 were always associated with negative and positive SPECT, respectively. For planar grades 1 and 2 uptake and heart to contralateral ratio 1.3 to 1.9, SPECT was needed to make a diagnosis. No patient with light-chain cardiac amyloidosis had positive SPECT. Conclusions: An efficient 1-hour technetium-99 m pyrophosphate protocol had comparable diagnostic performance to a 3-hour protocol.

scholarly journals Cell Transplantation Improves Ventricular Function After a Myocardial Infarction

Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Byung-Ok Kim ◽  
Hai Tian ◽  
Kriengchai Prasongsukarn ◽  
Jun Wu ◽  
Denis Angoulvant ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ventricular Function ◽  
Cell Transplantation ◽  
Single Photon ◽  
Culture Media ◽  
Heart Function ◽  
Photon Emission ◽  
Control Group ◽  
Emission Computed Tomography ◽  
Infarct Region

Background— Cell transplantation offers the promise in the restoration of ventricular function after an extensive myocardial infarction, but the optimal cell type remains controversial. Human unrestricted somatic stem cells (USSCs) isolated from umbilical cord blood have great potential to differentiate into myogenic cells and induce angiogenesis. The present study evaluated the effect of USSCs on myocardial regeneration and improvement of heart function after myocardial infarction in a porcine model. Method and Results— The distal left anterior descending artery of Yorkshire pigs (30 to 35 kg) was occluded by endovascular implantation of a coil. Four weeks after infarction, single-photon emission computed tomography technetium 99m sestamibi scans (MIBI) and echocardiography were performed. USSCs (100×10 6 ) or culture media were then directly injected into the infarcted region (n=8 per group). Pigs were immunosuppressed by daily administration of cyclosporin A. At 4 weeks after transplantation, MIBI and echocardiography were repeated and heart function was also assessed with a pressure-volume catheter. The infarcted myocardium and implanted cells were studied histologically. MIBI showed improved regional perfusion ( P <0.05) and wall motion ( P <0.05) of the infarct region in the transplant group compared with the control. Ejection fraction evaluated by both MIBI and echocardiography decreased in the control group but increased in the transplant group ( P <0.01). Scar thickness of the transplant group was higher than the control. The grafted cells were detected 4 weeks after transplantation by both immunohistochemistry and in situ hybridization. Conclusion— Engrafted USSCs were detected in the infarct region 4 weeks after cell transplantation, and the implanted cells improved regional and global function of the porcine heart after a myocardial infarction. This study suggests that the USSC implantation will be efficacious for cellular cardiomyoplasty.

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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