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https://www.readbyqxmd.com/read/29332035/an-aspartyl-cathepsin-targeted-pet-agent-application-in-an-alzheimer-s-disease-mouse-model
#1
Jonatan A Snir, Mojmir Suchy, Geron A Bindseil, Michael Kovacs, Blaine A Chronik, Robert H E Hudson, Stephen H Pasternak, Robert Bartha
BACKGROUND: Early detection of Alzheimer's disease (AD) pathology is a serious challenge for both diagnosis and clinical trials. The aspartyl protease, Cathepsin D (CatD), is overexpressed in AD and could be a biomarker of disease. We have previously designed a unique contrast agent (CA) for dual-optical and magnetic resonance imaging of the activity of the CatD class of enzymes. OBJECTIVE: To compare the uptake and retention of a novel, more sensitive, and clinically-translatable 68Ga PET tracer targeting CatD activity in 5XFAD mice and non-Tg littermates...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29308904/pet-imaging-of-vcam-1-expression-and-monitoring-therapy-response-in-tumor-with-a-68ga-labeled-single-chain-variable-fragment
#2
Xiao Zhang, Chunbao Liu, Fan Hu, Yingying Zhang, Jing Wang, Yongheng Gao, Yaqun Jiang, Yongxue Zhang, Xiaoli Lan
Vascular cell adhesion molecule-1 (VCAM-1) is becoming an attractive candidate for targeting in tumor detection and therapy due to its involvement in tumorigenicity and metastasis. LY2409881, an IKK2 inhibitor, can trigger apoptosis of VCAM-1 positive melanoma cells. The aim of this study was to assess the use of the 68Ga-labeled single chain variable fragment (scFv) of VCAM-1 in detecting VCAM-1-positive tumor expression and monitoring the therapeutic effect of LY2409881. Melanoma cell lines, B16F10 and A375m, were sued as VCAM-1 overexpression and underexpression models, respectively...
January 8, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29306111/deuterated-18f-9-o-hexadeutero-3-fluoropropoxyl-dihydrotetrabenazine-d6-fp-dtbz-a-vesicular-monoamine-transporter-2-vmat2-imaging-agent
#3
Futao Liu, Seok Rye Choi, Zhihao Zha, Karl Ploessl, Lin Zhu, Hank F Kung
INTRODUCTION: Vesicular monoamine transporters 2 (VMAT2) in the brain serve as transporter for packaging monoamine in vesicles for normal CNS neurotransmission. Several VMAT2 imaging agents, [11C]-(+)-DTBZ, dihydrotetrabenazine and [18F]FP-(+)-DTBZ (9-O-fluoropropyl-(+)-dihydro tetrabenazine, a.k.a. [18F]AV-133), are useful for studying the changes in brain function related to monoamine transmission by in vivo imaging. Deuterated analogs have been reported targeting VMAT2 binding sites...
December 6, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29291493/89zr-for-antibody-labeling-and-in-vivo-studies-a-comparison-between-liquid-and-solid-target-production
#4
Gemma M Dias, Caterina F Ramogida, Julie Rousseau, Nicholas A Zacchia, Cornelia Hoehr, Paul Schaffer, Kuo-Shyan Lin, François Bénard
INTRODUCTION: Zirconium-89 (89Zr, t1/2=78.4h) liquid target (LT) production offers an approach to introduce this positron-emitting isotope to cyclotron centres without the need for a separate solid target (ST) production set up. We compared the production, purification, and antibody radiolabeling yields of 89Zr-(LT) and 89Zr-(ST), and assessed the feasibility of 89Zr-(LT) for preclinical PET/CT. METHODS: 89Zr-(ST) production was performed with an 89Y foil on a TR 19 cyclotron at 13...
November 16, 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29274431/trajectory-of-inflammatory-and-microglial-activation-markers-in-the-postnatal-rabbit-brain-following-intrauterine-endotoxin-exposure
#5
Zhi Zhang, Amar Jyoti, Bindu Balakrishnan, Monica Williams, Sarabdeep Singh, Diane C Chugani, Sujatha Kannan
BACKGROUND: Maternal infection is a risk factor for periventricular leukomalacia and cerebral palsy (CP) in neonates. We have previously demonstrated hypomyelination and motor deficits in newborn rabbits, as seen in patients with cerebral palsy, following maternal intrauterine endotoxin administration. This was associated with increased microglial activation, primarily involving the periventricular region (PVR). In this study we hypothesized that maternal intrauterine inflammation leads to a pro-inflammatory environment in the PVR that is associated with microglial activation in the first 2 postnatal weeks...
December 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29258847/ssssacute-in-vivo-effect-of-valproic-acid-on-the-gabaergic-system-in-rat-brain-a-11c-ro15-4513-micropet-study
#6
Freja Bertelsen, Anne M Landau, Karina H Vase, Jan Jacobsen, Jørgen Scheel-Krüger, Arne Møller
γ-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the nervous system acting mainly through GABAA receptors. In the presence of high levels of GABA, an allosteric shift in the GABAA receptors can change the affinity of benzodiazepine (BZD) ligands. Valproic acid (VPA) is an anticonvulsant that enhances the level of endogenous GABA in the brain. The BZD ligand, Ro15-4513 has a high affinity for GABAA receptors containing the α5 subunit and can be used to investigate the GABA shift in the brains of living rats after VPA exposure...
December 16, 2017: Brain Research
https://www.readbyqxmd.com/read/29244904/pharmacokinetics-of-the-cannabinoid-receptor-ligand-18-f-mk-9470-in-the-rat-brain-evaluation-of-models-using-micropet
#7
Isabelle Miederer, Hans-Georg Buchholz, Andrea Kronfeld, Stephan Maus, Veronika Weyer-Elberich, Philipp Mildenberger, Beat Lutz, Mathias Schreckenberger
PURPOSE: The positron emission tomography ligand [18 F]MK-9470 is an inverse agonist that binds reversibly and with high affinity to the cannabinoid type 1 receptor. Due to its slow brain kinetics, care is required in the definition of its dissociation rates from the receptor. The goal of this study was to investigate pharmacokinetic analysis methods using an arterial input function. METHODS: Five Sprague-Dawley rats received injections of 13 to 25 MBq of [18 F]MK-9470 and were scanned over a period of 90 min...
December 15, 2017: Medical Physics
https://www.readbyqxmd.com/read/29222502/pharmacokinetics-biodistribution-and-brain-retention-of-a-bispecific-antibody-based-pet-radioligand-for-imaging-of-amyloid-%C3%AE
#8
Dag Sehlin, Xiaotian T Fang, Silvio R Meier, Malin Jansson, Stina Syvänen
Monoclonal antibodies (mAbs) have not been used as positron emission tomography (PET) ligands for in vivo imaging of the brain because of their limited passage across the blood-brain barrier (BBB). However, due to their high affinity and specificity, mAbs may be an attractive option for brain PET if their brain distribution can be facilitated. In the present study, a F(ab')2 fragment of the amyloid-beta (Aβ) protofibril selective mAb158 was chemically conjugated to the transferrin receptor (TfR) antibody 8D3 to enable TfR mediated transcytosis across the BBB...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29204748/imaging-the-expression-of-glypican-3-in-hepatocellular-carcinoma-by-pet
#9
Zhen Wang, Yan-Jiang Han, Shun Huang, Meng Wang, Wen-Lan Zhou, Hong-Sheng Li, Quan-Shi Wang, Hu-Bing Wu
The glypican-3 (GPC3) receptor is overexpressed in hepatocellular carcinoma (HCC) and is a potential diagnostic and therapeutic target. GPC3-targeted molecular imaging will be helpful to differentiate diagnosis and guide therapy. In the present study, we will develop a novel PET probe for imaging the expression of GPC-3. L5 (sequence: RLNVGGTYFLTTRQ), a GPC3 targeting peptide, was labeled with 5-carboxyfluorescein (FAM) and 18F-fluoride. Cell binding tests were performed to identify the binding specificity of FAM-L5 and 18F radiolabeled peptide...
December 4, 2017: Amino Acids
https://www.readbyqxmd.com/read/29195550/a-three-time-point-method-for-assessing-kinetic-parameters-of-64cu-labeled-ramucirumab-trapping-in-vegfr-2-positive-lung-tumors
#10
Eric Laffon, Roger Marthan
OBJECTIVE: To describe a three-time-point method for estimating kinetic parameters involved in 64Cu-labeled Ramucirumab (64Cu-NOTA-RamAb) trapping of VEGFR-2 positive lung tumors. MATERIALS AND METHODS: Positron emission tomography (microPET) data of tumor-bearing mice for 64Cu-NOTA-RamAb trapping in VEGFR-2 positive HCC4006 tumor were used, involving tissue activity measurements acquired at 3, 24 and 48 h post-injection, without and with administration of RamAb blocking dose...
November 2017: Physica Medica: PM
https://www.readbyqxmd.com/read/29183855/pet-ct-imaging-of-3d-printed-devices-in-the-gastrointestinal-tract-of-rodents
#11
Alvaro Goyanes, Anxo Fernández-Ferreiro, Adil Majeed, Noemí Gomez-Lado, Atheer Awad, Andrea Luaces-Rodríguez, Simon Gaisford, Pablo Aguiar, Abdul W Basit
Fused deposition modelling (FDM) 3D printing (3DP) is a revolutionary technology with the potential to transform drug product design in both the pre-clinical and clinical arena. The objective of this pilot study was to explore the intestinal behaviour of four different polymer-based devices fabricated using FDM 3DP technology in rats. Small capsular devices of 8.6mm in length and 2.65mm in diameter were printed from polyvinyl alcohol-polyethylene glycol graft-copolymer (PVA-PEG copolymer, Kollicoat IR), hydroxypropylcellulose (HPC, Klucel), ethylcellulose (EC, Aqualon N7) and hypromellose acetate succinate (HPMCAS, Aquasolve-LG)...
November 25, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29167476/levodopa-induced-abnormal-involuntary-movements-correlate-with-altered-permeability-of-the-blood-brain-barrier-in-the-basal-ganglia
#12
Renata P Lerner, Veronica Francardo, Koji Fujita, Zisis Bimpisidis, Vincent A Jourdain, Chris C Tang, Stephen L Dewey, Thomas Chaly, M Angela Cenci, David Eidelberg
Chronic levodopa treatment leads to the appearance of dyskinesia in the majority of Parkinson's disease patients. Neurovascular dysregulation in putaminal and pallidal regions is thought to be an underlying feature of this complication of treatment. We used microPET to study unilaterally lesioned 6-hydroxydopamine rats that developed levodopa-induced abnormal involuntary movements (AIMs) after three weeks of drug treatment. Animals were scanned with [15O]-labeled water and [18F]-fluorodeoxyglucose, to map regional cerebral blood flow and glucose metabolism, and with [11C]-isoaminobutyric acid (AIB), to assess blood-brain-barrier (BBB) permeability, following separate injections of levodopa or saline...
November 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29160082/cyclic-versus-noncyclic-chelating-scaffold-for-89zr-labeled-zegfr-2377-affibody-bioconjugates-targeting-epidermal-growth-factor-receptor-overexpression
#13
Dominik Summer, Javad Garousi, Maryam Oroujeni, Bogdan Mitran, Ken G Andersson, Anzhelika Vorobyeva, John Löfblom, Anna Orlova, Vladimir Tolmachev, Clemens Decristoforo
Zirconium-89 is an emerging radionuclide for positron emission tomography (PET) especially for biomolecules with slow pharmacokinetics as due to its longer half-life, in comparison to fluorine-18 and gallium-68, imaging at late time points is feasible. Desferrioxamine B (DFO), a linear bifunctional chelator (BFC) is mostly used for this radionuclide so far but shows limitations regarding stability. Our group recently reported on fusarinine C (FSC) with similar zirconium-89 complexing properties but potentially higher stability related to its cyclic structure...
November 21, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29158822/liposomal-64-cu-pet-imaging-of-anti-vegf-drug-effects-on-liposomal-delivery-to-colon-cancer-xenografts
#14
Stephanie J Blocker, Kirk A Douglas, Lisa Anne Polin, Helen Lee, Bart S Hendriks, Enxhi Lalo, Wei Chen, Anthony F Shields
Liposomes (LP) deliver drug to tumors due to enhanced permeability and retention (EPR). LP were labeled with (64)Cu for positron emission tomography (PET) to image tumor localization. Bevacizumab (bev), a VEGF targeted antibody, may modify LP delivery by altering tumor EPR and this change can also be imaged. Objective: Assess the utility of (64)Cu-labeled LP for PET in measuring altered LP delivery early after treatment with bev. Methods: HT-29 human colorectal adenocarcinoma tumors were grown subcutaneously in SCID mice...
2017: Theranostics
https://www.readbyqxmd.com/read/29134505/upregulated-sphingosine-1-phosphate-receptor-1-expression-in-human-and-murine-atherosclerotic-plaques
#15
Hui Liu, Hongjun Jin, Junbin Han, Xuyi Yue, Hao Yang, Mohamed A Zayed, Robert J Gropler, Zhude Tu
PURPOSE: Dysregulation of sphingosine 1-phosphate receptor 1 (S1PR1) signaling contributes to inflammation-related pathophysiological changes in cardiovascular diseases including atherosclerosis (AS). S1PR1-targeting compounds significantly reduce lesion size in murine models of AS. Therefore, characterization of S1PR1 expression in vitro and in vivo in atherosclerotic plaque could enable mechanistic studies and inform S1PR1 targeted therapies. PROCEDURES: H&E staining and immunostaining studies were performed on variably diseased human femoral endarterectomy plaque specimens, as well as mouse aortic sections from ApoE(-/-) mice maintained on a high-fat diet (AS mice)...
November 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/29097913/pet-imaging-of-fshr-expression-in-tumors-with-68-ga-labeled-fsh1-peptide
#16
Donghui Pan, Guifeng Liu, Yuping Xu, Yanting Wang, Yuanyuan Yue, Lizhen Wang, Junjie Yan, Xinyu Wang, Runlin Yang, Min Yang
FSHR is an appealing target for cancer theranostics. Radiolabeled FSH1 and its derivatives have shown potential to in vivo detect FSHR expression. However, moderate labeling yields (~50% nondecay-corrected) may partially limit their wide use. (68)Ga is an excellent PET nuclide due to availability, nearly quantitative reaction, and short physical half-life. In this study, (68)Ga labeled FSH1 peptide was developed for imaging of FSHR in cancers. In vitro studies and MicroPET imaging were performed in PC-3 prostate tumor model...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29097911/micropet-ct-imaging-of-axl-downregulation-by-hsp90-inhibition-in-triple-negative-breast-cancer
#17
Wanqin Wang, Jun Zhao, Xiaoxia Wen, Curtis Chun-Jen Lin, Junjie Li, Qian Huang, Yongqiang Yu, Shiaw-Yih Lin, Chun Li
AXL receptor tyrosine kinase is overexpressed in a number of solid tumor types including triple-negative breast cancer (TNBC). AXL is considered an important regulator of epithelial-to-mesenchymal transition (EMT) and a potential therapeutic target for TNBC. In this work, we used microPET/CT with (64)Cu-labeled anti-human AXL antibody ((64)Cu-anti-hAXL) to noninvasively interrogate the degradation of AXL in vivo in response to 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent inhibitor of HSP90. 17-AAG treatment caused significant decline in AXL expression in orthotopic TNBC MDA-MB-231 tumors, inhibited EMT, and delayed tumor growth in vivo, resulting in significant reduction in tumor uptake of (64)Cu-anti-hAXL as clearly visualized by microPET/CT...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29080056/oxygen-15-labeled-co2-o2-and-co-pet-in-small-animals-evaluation-using-a-3d-mode-micropet-scanner-and-impact-of-reconstruction-algorithms
#18
Genki Horitsugi, Tadashi Watabe, Yasukazu Kanai, Hayato Ikeda, Hiroki Kato, Sadahiro Naka, Mana Ishibashi, Keiko Matsunaga, Kayako Isohashi, Eku Shimosegawa, Jun Hatazawa
BACKGROUND: Positron emission tomography (PET) studies using (15)O-labeled CO2, O2, and CO have been used in humans to evaluate cerebral blood flow (CBF), the cerebral oxygen extraction fraction (OEF), and the cerebral metabolic rate of oxygen (CMRO2) and cerebral blood volume (CBV), respectively. In preclinical studies, however, PET studies using (15)O-labeled gases are not widely performed because of the technical difficulties associated with handling labeled gases with a short half-life...
October 27, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/29077399/last-step-pd-mediated-11-c-co-labeling-of-a-moxestrol-conjugated-o-iodobenzyl-alcohol-from-model-experiments-to-in-vivo-positron-emission-tomography-studies
#19
Thomas Cornilleau, Mette Simonsen, Maylou Vang, Nada Taib-Maamar, Jean Dessolin, Hélène Audrain, Philippe Hermange, Eric Fouquet
The fast, efficient, and functional group tolerant last-step radiolabeling of bioconjugates is crucial for positron emission tomography (PET) applications. In this context, o-iodobenzyl alcohol based structures were identified as ideal tags for an easy Pd-catalyzed carbonylation after bioconjugation, and a moxestrol-conjugated precursor was chosen as the model compound for the further studies. Despite scale and time constraints, conditions developed with [(12)C]CO and [(13)C]CO were easily transferred to the (11)C isotope, and the desired radioactive product was obtained in amounts up to 740 MBq with radiochemical purities higher than 99%...
October 27, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29055123/disruption-of-behavior-and-brain-metabolism-in-artificially-reared-rats
#20
Elsa L Aguirre-Benítez, Mercedes G Porras, Leticia Parra, Jacquelina González-Ríos, Dafne F Garduño-Torres, Damaris Albores-García, Arturo Avendaño, Miguel A Ávila-Rodríguez, Angel I Melo, Ismael Jiménez-Estrada, Ma Eugenia Mendoza-Garrido, César Toriz, Daniel Diaz, Elizabeth Ibarra-Coronado, Karina Mendoza-Ángeles, Jesús Hernández-Falcón
Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning...
December 2017: Developmental Neurobiology
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