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https://www.readbyqxmd.com/read/28091604/polyglucose-nanoparticles-with-renal-elimination-and-macrophage-avidity-facilitate-pet-imaging-in-ischaemic-heart-disease
#1
Edmund J Keliher, Yu-Xiang Ye, Gregory R Wojtkiewicz, Aaron D Aguirre, Benoit Tricot, Max L Senders, Hannah Groenen, Francois Fay, Carlos Perez-Medina, Claudia Calcagno, Giuseppe Carlucci, Thomas Reiner, Yuan Sun, Gabriel Courties, Yoshiko Iwamoto, Hye-Yeong Kim, Cuihua Wang, John W Chen, Filip K Swirski, Hsiao-Ying Wey, Jacob Hooker, Zahi A Fayad, Willem J M Mulder, Ralph Weissleder, Matthias Nahrendorf
Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission tomography (PET) imaging with (18)F-Macroflor, a modified polyglucose nanoparticle with high avidity for macrophages. Due to its small size, Macroflor is excreted renally, a prerequisite for imaging with the isotope flourine-18...
January 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28042344/noninvasive-imaging-of-myocardial-inflammation-in-myocarditis-using-68-ga-tagged-mannosylated-human-serum-albumin-positron-emission-tomography
#2
Seung-Pyo Lee, Hyung-Jun Im, Shinae Kang, Seock-Jin Chung, Ye Seul Cho, Hyejeong Kang, Ho Seon Park, Do-Won Hwang, Jun-Bean Park, Jin-Chul Paeng, Gi-Jeong Cheon, Yun-Sang Lee, Jae Min Jeong, Yong-Jin Kim
The diagnosis of myocarditis traditionally relies on invasive endomyocardial biopsy but none of the imaging studies so far are specific for infiltration of the inflammatory cells itself. We synthesized (68)Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA) by conjugating human serum albumin with mannose, followed by conjugation with NOTA and labeling it with (68)Ga. The efficacy of (68)Ga-NOTA-MSA positron emission tomography (PET) for imaging myocardial inflammation was tested in a rat myocarditis model...
2017: Theranostics
https://www.readbyqxmd.com/read/27935825/microglia-activation-in-a-pediatric-rabbit-model-of-tuberculous-meningitis
#3
Elizabeth W Tucker, Supriya Pokkali, Zhi Zhang, Vincent P DeMarco, Mariah Klunk, Elizabeth S Smith, Alvaro A Ordonez, Marie-France Penet, Zaver Bhujwalla, Sanjay K Jain, Sujatha Kannan
Central nervous system (CNS) tuberculosis (TB) is the most severe form of extra-pulmonary TB and disproportionately affects young children where the developing brain has a unique host response. New Zealand white rabbits were infected with Mycobacterium tuberculosis via subarachnoid inoculation at postnatal day 4-8 and evaluated until 4-6 weeks post-infection. Control and infected rabbit kits were assessed for the development of neurological deficits, bacterial burden, and postmortem microbiologic and pathologic changes...
December 1, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27932558/petct-imaging-of-unstable-carotid-plaque-with-ga-68-labelled-somatostatin-receptor-ligand
#4
Ming Young Simon Wan, Raymond Endozo, Sofia Michopoulou, Robert Shortman, Manuel Rodriguez-Justo, Leon Menezes, Syed Yusuf, Toby Richards, Damian Wild, Beatrice Waser, Jean Claude Reubi, Ashley Groves
BACKGROUND: Ga68 labelled somatostatin receptor ligand PET imaging has recently been shown in preclinical and early human studies to have a potential role in the evaluation of vulnerable arterial plaques. We prospectively evaluated carotid plaque Ga68-DOTATATE uptake in patients with recent carotid events, assessed inter- and intra- observer variability of such measurements, and explored the mechanism of any plaque DOTATATE activity with immunohistochemistry in resected specimens. MATERIALS & METHODS: 20 consecutively consenting patients with recent symptomatic carotid events (transient ischaemic attack [TIA], stroke or amaurosis fugax), due for carotid endarterectomy were prospectively recruited...
December 8, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27930666/development-of-pet-imaging-to-visualize-activated-macrophages-accumulated-in-the-transplanted-ipsc-derived-cardiac-myocytes-of-allogeneic-origin-for-detecting-the-immune-rejection-of-allogeneic-cell-transplants-in-mice
#5
Noriyuki Kashiyama, Shigeru Miyagawa, Satsuki Fukushima, Takuji Kawamura, Ai Kawamura, Shohei Yoshida, Akima Harada, Tadashi Watabe, Yasukazu Kanai, Koichi Toda, Jun Hatazawa, Yoshiki Sawa
Allogeneic transplantation (Tx) of induced pluripotent stem cells (iPSCs) is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET) imaging targets translocator protein (TSPO), which is highly expressed on mitochondrial membrane, especially in activated macrophage...
2016: PloS One
https://www.readbyqxmd.com/read/27922859/fdg-pet-ct-for-monitoring-response-of-melanoma-to-the-novel-oncolytic-viral-therapy-talimogene-laherparepvec
#6
Matthew F Covington, Clara N Curiel, Lois Lattimore, Ryan J Avery, Phillip H Kuo
61-year-old woman with stage IIIa (T3a N1a M0) left lower leg melanoma with lesions suggestive of in-transit metastases 8 months following wide local excision and femoral nodal dissection. FDG-PET/CT demonstrated 5 FDG-avid in-transit nodal metastases in the distal left leg, confirmed on biopsy. Talimogene laherparepvec (T-VEC) oncolytic immunotherapy consisting of intralesional injections of modified herpes simplex virus-expressing granulocyte-macrophage colony-stimulating factor was completed over 6 months...
December 3, 2016: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/27914007/evaluation-of-68-ga-labeled-peptide-tracer-for-detection-of-gelatinase-expression-after-myocardial-infarction-in-rat
#7
Max Kiugel, Ville Kytö, Tiina Saanijoki, Heidi Liljenbäck, Olli Metsälä, Mia Ståhle, Johanna Tuomela, Xiang-Guo Li, Pekka Saukko, Juhani Knuuti, Anne Roivainen, Antti Saraste
BACKGROUND: Matrix metalloproteinases 2 and 9 (MMP-2/9) play a role in extracellular matrix remodeling after an ischemic myocardial injury. We evaluated (68)Ga-DOTA-peptide targeting MMP-2/9 for the detection of gelatinase expression after myocardial infarction (MI) in rat. METHODS: Rats were injected with 43 ± 7.7 MBq of (68)Ga-DOTA-peptide targeting MMP-2/9 at 7 days (n = 7) or 4 weeks (n = 8) after permanent coronary ligation or sham operation (n = 5 at both time points) followed by positron emission tomography (PET)...
December 2, 2016: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
https://www.readbyqxmd.com/read/27910074/evolutional-characterization-of-photochemically-induced-stroke-in-rats-a-multimodality-imaging-and-molecular-biological-study
#8
Nai-Wei Liu, Chien-Chih Ke, Yonghua Zhao, Yi-An Chen, Kim-Chuan Chan, David Tat-Wei Tan, Jhih-Shian Lee, You-Yin Chen, Tun-Wei Hsu, Ya-Ju Hsieh, Chi-Wei Chang, Bang-Hung Yang, Wen-Sheng Huang, Ren-Shyan Liu
Photochemically induced cerebral ischemia is an easy-manipulated, reproducible, relatively noninvasive, and lesion controllable model for translational study of ischemic stroke. In order to longitudinally investigate the characterization of the model, magnetic resonance imaging, (18)F-2-deoxy-glucose positron emission tomography, fluorescence, and bioluminescence imaging system were performed in correlation with triphenyl tetrazolium chloride (TTC), hematoxylin-eosin staining, and immunohistochemistry examinations of glial fibrillary acidic protein, CD68, NeuN, von willebrand factor, and α-smooth muscle actin in the infarct zone...
December 1, 2016: Translational Stroke Research
https://www.readbyqxmd.com/read/27884253/the-quest-for-new-approaches-in%C3%A2-myocarditis-and-inflammatory%C3%A2-cardiomyopathy
#9
REVIEW
Stephane Heymans, Urs Eriksson, Jukka Lehtonen, Leslie T Cooper
Myocarditis is a diverse group of heart-specific immune processes classified by clinical and histopathological manifestations. Up to 40% of dilated cardiomyopathy is associated with inflammation or viral infection. Recent experimental studies revealed complex regulatory roles for several microribonucleic acids and T-cell and macrophage subtypes. Although the prevalence of myocarditis remained stable between 1990 and 2013 at about 22 per 100,000 people, overall mortality from cardiomyopathy and myocarditis has decreased since 2005...
November 29, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27863083/promotion-of-neurological-recovery-in-rat-spinal-cord-injury-by-mesenchymal-stem-cells-loaded-on-nerve-guided-collagen-scaffold-through-increasing-alternatively-activated-macrophage-polarization
#10
Zhan Peng, Wei Gao, Bing Yue, Jie Jiang, Yong Gu, Jianwu Dai, Liang Chen, Qin Shi
Mesenchymal stem cells(MSCs)characterized by multi-differentiation potent and immunoregulatory have been used in the treatment of spinal cord injury (SCI), but the direct transplantation may limit its effectiveness due to quick diffusion. In addition, the role of macrophages in healing is being increasingly recognized because of the ability to polarize into pro- and anti-inflammatory phenotypes. In the present study, we developed the nerve-guide collagen scaffold (CS) and rat MSCs. After CS was confirmed to minimize MSCs distribution in vivo by the positron emission tomography (PET) imaging, the repair capacity of combined implantation of CS and MSCs and the effect on classically activated macrophage (M1)/alternatively activated macrophage (M2) polarization was assessed in a hemisected SCI rat model...
November 15, 2016: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/27849433/differential-regulation-of-macrophage-glucose-metabolism-by-macrophage-colony-stimulating-factor-and-granulocyte-macrophage-colony-stimulating-factor-implications-for-18-f-fdg-pet-imaging-of-vessel-wall-inflammation
#11
Sina Tavakoli, John D Short, Kevin Downs, Huynh Nga Nguyen, Yanlai Lai, Wei Zhang, Paul Jerabek, Beth Goins, Mehran M Sadeghi, Reto Asmis
Purpose To determine the divergence of immunometabolic phenotypes of macrophages stimulated with macrophage colony-stimulating factor (M-CSF) and granulocyte-M-CSF (GM-CSF) and its implications for fluorine 18 ((18)F) fluorodeoxyglucose (FDG) imaging of atherosclerosis. Materials and Methods This study was approved by the animal care committee. Uptake of 2-deoxyglucose and various indexes of oxidative and glycolytic metabolism were evaluated in nonactivated murine peritoneal macrophages (MΦ0) and macrophages stimulated with M-CSF (MΦM-CSF) or GM-CSF (MΦGM-CSF)...
November 16, 2016: Radiology
https://www.readbyqxmd.com/read/27799487/arterial-and-cellular-inflammation-in-patients-with-ckd
#12
Sophie J Bernelot Moens, Simone L Verweij, Fleur M van der Valk, Julian C van Capelleveen, Jeffrey Kroon, Miranda Versloot, Hein J Verberne, Henk A Marquering, Raphaël Duivenvoorden, Liffert Vogt, Erik S G Stroes
CKD associates with a 1.5- to 3.5-fold increased risk for cardiovascular disease. Both diseases are characterized by increased inflammation, and in patients with CKD, elevated C-reactive protein level predicts cardiovascular risk. In addition to systemic inflammation, local arterial inflammation, driven by monocyte-derived macrophages, predicts future cardiovascular events in the general population. We hypothesized that subjects with CKD have increased arterial and cellular inflammation, reflected by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography computed tomography (PET/CT) of the arterial wall and a migratory phenotype of monocytes...
October 31, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27791119/immune-cell-screening-of-a-nanoparticle-library-improves-atherosclerosis-therapy
#13
Jun Tang, Samantha Baxter, Arjun Menon, Amr Alaarg, Brenda L Sanchez-Gaytan, Francois Fay, Yiming Zhao, Mireille Ouimet, Mounia S Braza, Valerie A Longo, Dalya Abdel-Atti, Raphael Duivenvoorden, Claudia Calcagno, Gert Storm, Sotirios Tsimikas, Kathryn J Moore, Filip K Swirski, Matthias Nahrendorf, Edward A Fisher, Carlos Pérez-Medina, Zahi A Fayad, Thomas Reiner, Willem J M Mulder
Immunological complexity in atherosclerosis warrants targeted treatment of specific inflammatory cells that aggravate the disease. With the initiation of large phase III trials investigating immunomodulatory drugs for atherosclerosis, cardiovascular disease treatment enters a new era. We here propose a radically different approach: implementing and evaluating in vivo a combinatorial library of nanoparticles with distinct physiochemical properties and differential immune cell specificities. The library's nanoparticles are based on endogenous high-density lipoprotein, which can preferentially deliver therapeutic compounds to pathological macrophages in atherosclerosis...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27789718/imaging-the-cytokine-receptor-cxcr4-in-atherosclerotic-plaques-with-the-radiotracer-68ga-pentixafor-for-positron-emission-tomography
#14
Fabien Hyafil, Jaroslav Pelisek, Iina Laitinen, Margret Schottelius, Miriam Mohring, Yvonne Döring, Emiel Van der Vorst, Michael Kallmayer, Katja Steiger, Andreas Poschenrieder, Johannes Notni, Johannes Fischer, Christine Baumgartner, Christoph Rischpler, Stephan Nekolla, Christian Weber, Hans-Henning Eckstein, Hans-Jürgen Wester, Markus Schwaiger
: (68)Ga-pentixafor is a radiotracer for positron emission tomography (PET) that binds with nanomolar affinity to CXCR4. The CXCR4 receptor is expressed at the surface of inflammatory cells. The objective of the study was to analyze the ability of radiolabeled pentixafor to detect CXCR4 expression on inflammatory cells present in atherosclerotic plaques of an experimental rabbit model. METHODS: Atherosclerotic plaques were induced by endothelial abrasion of the right carotid artery and abdominal aorta of 7 rabbits fed an atherogenic diet...
October 27, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27765861/brain-fdg-pet-metabolic-abnormalities-in-patients-with-long-lasting-macrophagic-myofasciitis
#15
Axel Van Der Gucht, Mehdi Aoun Sebaiti, Eric Guedj, Jessie Aouizerate, Sabrina Yara, Romain Gherardi, Eva Evangelista, Julia Chalaye, Anne-Ségolène Cottereau, Antoine Verger, Anne-Catherine Bachoud-Levi, Emmanuel Itti, Francois Jerome Authier
PURPOSE: Macrophagic myofasciitis (MMF) is an emerging condition with specific muscle lesions characterized by an abnormal long-term persistence of aluminum hydroxide particles within macrophages at the site of previous immunization. Patients present with diffuse arthromyalgias, chronic fatigue, and cognitive dysfunction. The aim of this study was to characterize brain FDG-PET metabolic abnormalities in MMF patients, and the relation with cognitive dysfunction. METHODS: FDG-PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (mean age, 45...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27742831/gm-csf-induces-inflammatory-macrophages-by-regulating-glycolysis-and-lipid-metabolism
#16
Yi Rang Na, Gyo Jung Gu, Daun Jung, Young Won Kim, Juri Na, Jin Sun Woo, Joo Youn Cho, Hyewon Youn, Seung Hyeok Seok
GM-CSF induces proinflammatory macrophages, but the underlying mechanisms have not been studied thus far. In this study, we investigated the mechanisms of how GM-CSF induces inflammatory macrophages. First, we observed that GM-CSF increased the extent of LPS-induced acute glycolysis in murine bone marrow-derived macrophages. This directly correlates with an inflammatory phenotype because glycolysis inhibition by 2-deoxyglucose abolished GM-CSF-mediated increase of TNF-α, IL-1β, IL-6, and IL-12p70 synthesis upon LPS stimulation...
October 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27731409/leukocyte-trafficking-associated-vascular-adhesion-protein-1-is-expressed-and-functionally-active-in-atherosclerotic-plaques
#17
Johanna M U Silvola, Helena Virtanen, Riikka Siitonen, Sanna Hellberg, Heidi Liljenbäck, Olli Metsälä, Mia Ståhle, Tiina Saanijoki, Meeri Käkelä, Harri Hakovirta, Seppo Ylä-Herttuala, Pekka Saukko, Matti Jauhiainen, Tibor Z Veres, Sirpa Jalkanen, Juhani Knuuti, Antti Saraste, Anne Roivainen
Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27713140/neuroprotective-effects-of-cd4-cd25-foxp3-regulatory-t-cells-in-a-3xtg-ad-alzheimer-s-disease-model
#18
Hyunjung Baek, Minsook Ye, Geun-Hyung Kang, Chanju Lee, Gihyun Lee, Da Bin Choi, Jaehoon Jung, Hyunseong Kim, Seonhwa Lee, Jin Su Kim, Hyun-Ju Lee, Insop Shim, Jun-Ho Lee, Hyunsu Bae
Alzheimer's disease patients display neuropathological lesions, including the accumulation of amyloid-beta (Aβ) peptide and neurofibrillary tangles. Although the mechanisms causing the neurodegenerative process are largely unknown, increasing evidence highlights a critical role of immunity in the pathogenesis of Alzheimer's disease. In the present study, we investigated the role of regulatory T cells (Tregs) on Alzheimer's disease progression. First, we explored the effect of Tregs (CD4+CD25+ T cells) and Teffs (CD4+CD25- T cells) in an adoptive transfer model...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27686563/neuroinflammatory-component-of-gray-matter-pathology-in-multiple-sclerosis
#19
Elena Herranz, Costanza Giannì, Céline Louapre, Constantina A Treaba, Sindhuja T Govindarajan, Russell Ouellette, Marco L Loggia, Jacob A Sloane, Nancy Madigan, David Izquierdo-Garcia, Noreen Ward, Gabriel Mangeat, Tobias Granberg, Eric C Klawiter, Ciprian Catana, Jacob M Hooker, Norman Taylor, Carolina Ionete, Revere P Kinkel, Caterina Mainero
OBJECTIVE: In multiple sclerosis (MS), using simultaneous magnetic resonance-positron emission tomography (MR-PET) imaging with (11) C-PBR28, we quantified expression of the 18kDa translocator protein (TSPO), a marker of activated microglia/macrophages, in cortex, cortical lesions, deep gray matter (GM), white matter (WM) lesions, and normal-appearing WM (NAWM) to investigate the in vivo pathological and clinical relevance of neuroinflammation. METHODS: Fifteen secondary-progressive MS (SPMS) patients, 12 relapsing-remitting MS (RRMS) patients, and 14 matched healthy controls underwent (11) C-PBR28 MR-PET...
November 2016: Annals of Neurology
https://www.readbyqxmd.com/read/27662579/monocyte-subsets-in-blood-correlate-with-obesity-related-response-of-macrophages-to-biomaterials-in%C3%A2-vitro
#20
G S A Boersema, L Utomo, Y Bayon, N Kops, E van der Harst, J F Lange, Y M Bastiaansen-Jenniskens
Macrophages play a key role in the foreign body response. In this study it was investigated whether obesity affects the acute response of macrophages to biomaterials in vitro and whether this response is associated with biomarkers in blood. CD14 (+) monocytes were isolated from blood from obese and age and gender matched lean persons. Monocyte subsets were determined based on CD14 and CD16 on their surface. C-reactive protein (CRP) was measured in peripheral blood. The response of monocyte-derived macrophages to polypropylene (PP), polylactic acid (PLA), polyethylene terephthalate (PET) monofilament, and PET-multifilament (mPET) in culture was based on cytokine production...
December 2016: Biomaterials
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