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https://www.readbyqxmd.com/read/28049619/synthesis-and-evaluation-of-1-cyclopropylmethyl-4-4-11-c-methoxyphenyl-piperidin-1-yl-2-oxo-1-2-dihydropyridine-3-carbonitrile-11-c-cmdc-for-pet-imaging-of-metabotropic-glutamate-receptor-2-in-the-rat-brain
#1
Yufei Ma, Katsushi Kumata, Joji Yui, Yiding Zhang, Tomoteru Yamasaki, Akiko Hatori, Masayuki Fujinaga, Nobuki Nengaki, Lin Xie, Hui Wang, Ming-Rong Zhang
Brain metabotropic glutamate receptor 2 (mGluR2) has been proposed as a therapeutic target for the treatment of schizophrenia-like symptoms arising from increased glutamate transmission in the forebrain. However, there does not exist a reliable tool for the study of mGluR2 in human neuroimaging. The purpose of this study was to radiosynthesize 1-(cyclopropylmethyl)-4-(4-[(11)C]methoxyphenyl)piperidin-1-yl-2-oxo-1,2-dihydropyridine-3-carbonitrile ([(11)C]CMDC) and evaluate its potential as a positron emission tomography (PET) radiotracer for imaging mGluR2 in the rat brain...
December 23, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28034351/synthesis-and-preliminary-evaluation-of-5-18f-fluoroleucine
#2
Bennett B Chin, Darryl McDougald, Douglas Weitzel, Thomas Hawk, Robert E Reiman, Michael R Zalutsky, Ganesan Vaidyanathan
BACKGROUND: Amino acid transporters, such as LAT1, are overexpressed in aggressive prostate and breast carcinomas, directly influencing pathways of growth and proliferation. OBJECTIVE: The purpose of this study is to synthesize and characterize a novel 18F labeled leucine analog, 5-[18F]fluoroleucine, as a potential imaging agent for aggressive tumors which may not be amenable to imaging by FDG PET. METHODS: 5-fluoroleucine was synthesized and characterized, and its 18F-labeled analog was synthesized from a mesylate precursor...
December 30, 2016: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/27995432/investigation-of-image-reconstruction-parameters-of-the-mediso-nanoscan-pc-small-animal-pet-ct-scanner-for-two-different-positron-emitters-under-nema-nu-4-2008-standards
#3
Anastasios Gaitanis, George A Kastis, Elena Vlastou, Penelope Bouziotis, Panayotis Verginis, Constantinos D Anagnostopoulos
PURPOSE: The Tera-Tomo 3D image reconstruction algorithm (a version of OSEM), provided with the Mediso nanoScan® PC (PET8/2) small-animal positron emission tomograph (PET)/x-ray computed tomography (CT) scanner, has various parameter options such as total level of regularization, subsets, and iterations. Also, the acquisition time in PET plays an important role. This study aims to assess the performance of this new small-animal PET/CT scanner for different acquisition times and reconstruction parameters, for 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) and Ga-68, under the NEMA NU 4-2008 standards...
December 19, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27992512/68ga-trap-rgd-3-hybrid-imaging-for-the-in-vivo-monitoring-of-%C3%AE-v%C3%A3-3-integrin-expression-as-biomarker-of-anti-angiogenic-therapy-effects-in-experimental-breast-cancer
#4
Philipp M Kazmierczak, Andrei Todica, Franz-Josef Gildehaus, Heidrun Hirner-Eppeneder, Matthias Brendel, Ralf S Eschbach, Magdalena Hellmann, Konstantin Nikolaou, Maximilian F Reiser, Hans-Jürgen Wester, Saskia Kropf, Axel Rominger, Clemens C Cyran
OBJECTIVES: To investigate 68Ga-TRAP-(RGD)3 hybrid imaging for the in vivo monitoring of αvß3-integrin expression as biomarker of anti-angiogenic therapy effects in experimental breast cancer. MATERIALS AND METHODS: Human breast cancer (MDA-MB-231) xenografts were implanted orthotopically into the mammary fat pads of n = 25 SCID mice. Transmission/emission scans (53 min to 90 min after i.v. injection of 20 MBq 68Ga-TRAP-(RGD)3) were performed on a dedicated small animal PET before (day 0, baseline) and after (day 7, follow-up) a 1-week therapy with the VEGF antibody bevacizumab or placebo (imaging cohort n = 13; therapy n = 7, control n = 6)...
2016: PloS One
https://www.readbyqxmd.com/read/27957722/dynamic-pet-evaluation-of-elevated-flt-level-after-sorafenib-treatment-in-mice-bearing-human-renal-cell-carcinoma-xenograft
#5
Naoyuki Ukon, Songji Zhao, Wenwen Yu, Yoichi Shimizu, Ken-Ichi Nishijima, Naoki Kubo, Yoshimasa Kitagawa, Nagara Tamaki, Kei Higashikawa, Hironobu Yasui, Yuji Kuge
BACKGROUND: Sorafenib, an oral multikinase inhibitor, has anti-proliferative and anti-angiogenic activities and is therapeutically effective against renal cell carcinoma (RCC). Recently, we have evaluated the tumor responses to sorafenib treatment in a RCC xenograft using [Methyl-(3)H(N)]-3'-fluoro-3'-deoxythythymidine ([(3)H]FLT). Contrary to our expectation, the FLT level in the tumor significantly increased after the treatment. In this study, to clarify the reason for the elevated FLT level, dynamic 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]FLT) positron emission tomography (PET) and kinetic studies were performed in mice bearing a RCC xenograft (A498)...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/27835825/a-useful-pet-probe-11-c-bu99008-with-ultra-high-specific-radioactivity-for-small-animal-pet-imaging-of-i2-imidazoline-receptors-in-the-hypothalamus
#6
Kazunori Kawamura, Yoko Shimoda, Joji Yui, Yiding Zhang, Tomoteru Yamasaki, Hidekatsu Wakizaka, Akiko Hatori, Lin Xie, Katsushi Kumata, Masayuki Fujinaga, Masanao Ogawa, Yusuke Kurihara, Nobuki Nengaki, Ming-Rong Zhang
INTRODUCTION: A positron emission tomography (PET) probe with ultra-high specific radioactivity (SA) enables measuring high receptor specific binding in brain regions by avoiding mass effect of the PET probe itself. It has been reported that PET probe with ultra-high SA can detect small change caused by endogenous or exogenous ligand. Recently, Kealey et al. developed [(11)C]BU99008, a more potent PET probe for I2-imidazoline receptors (I2Rs) imaging, with a conventional SA (mean 76GBq/μmol) showed higher specific binding in the brain...
February 2017: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27815661/improved-radiosynthesis-and-biological-evaluations-of-l-and-d-1-18-f-fluoroethyl-tryptophan-for-pet-imaging-of-ido-mediated-kynurenine-pathway-of-tryptophan-metabolism
#7
Yangchun Xin, Hancheng Cai
PURPOSE: Tryptophan metabolism via indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway plays a role in immunomodulation and has been emerging as a plausible target for cancer immunotherapy. Imaging IDO-mediated kynurenine pathway of tryptophan metabolism with positron emission tomography (PET) could provide valuable information for noninvasive assessment of cancer immunotherapy response. In this work, radiotracer 1-(2-[(18)F]fluoroethyl)-L-tryptophan (1-L-[(18)F]FETrp) and its enantioisomer 1-D-[(18)F]FETrp were synthesized and evaluated for PET imaging of IDO-mediated kynurenine pathway of tryptophan metabolism...
November 4, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27789717/performing-repeated-quantitative-small-animal-pet-studies-with-arterial-input-functions-is-routinely-feasible-in-rats
#8
Chi-Cheng Huang, Chun-Hu Wu, Ya-Yao Huang, Kai-Yuan Tzen, Szu-Fu Chen, Miao-Ling Tsai, Hsiao-MIng Wu
: Performing quantitative small animal positron emission tomography (qµPET) with arterial input function was considered technically challenging. Here, we introduce a catheterization procedure which keeps a rat physiologically stable for 1.5 months. We demonstrated the feasibility of qµPET by performing repeated (18)F-FDG qµPET to monitor the time-course of cerebral metabolic rates of glucose (cMRglc) variations in rats. METHODS: Aseptic surgeries were performed on two rats...
October 27, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/27779126/mr-compatibility-of-a-high-resolution-small-animal-pet-insert-operating-inside-a-7-t-mri
#9
J D Thiessen, E Shams, G Stortz, G Schellenberg, D Bishop, M S Khan, P Kozlowski, F Retière, V Sossi, C J Thompson, A L Goertzen
A full-ring PET insert consisting of 16 PET detector modules was designed and constructed to fit within the 114 mm diameter gradient bore of a Bruker 7 T MRI. The individual detector modules contain two silicon photomultiplier (SiPM) arrays, dual-layer offset LYSO crystal arrays, and high-definition multimedia interface (HDMI) cables for both signal and power transmission. Several different RF shielding configurations were assessed prior to construction of a fully assembled PET insert using a combination of carbon fibre and copper foil for RF shielding...
November 21, 2016: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/27770429/radiation-dosimetry-of-the-%C3%AE-4%C3%AE-2-nicotinic-receptor-ligand-18-f-flubatine-comparing-preclinical-pet-mri-and-pet-ct-to-first-in-human-pet-ct-results
#10
Mathias Kranz, Bernhard Sattler, Solveig Tiepolt, Stephan Wilke, Winnie Deuther-Conrad, Cornelius K Donat, Steffen Fischer, Marianne Patt, Andreas Schildan, Jörg Patt, René Smits, Alexander Hoepping, Jörg Steinbach, Osama Sabri, Peter Brust
BACKGROUND: Both enantiomers of [(18)F]flubatine are new radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[(18)F]flubatine compared to (-)-[(18)F]flubatine was its higher binding affinity suggesting that (+)-[(18)F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (-)-[(18)F]flubatine in early stages of Alzheimer's disease...
December 2016: EJNMMI Physics
https://www.readbyqxmd.com/read/27766592/measurement-of-cardiovascular-function-using-a-novel-view-sharing-pet-reconstruction-method-and-tracer-kinetic-analysis
#11
Paul R Territo, Amanda A Riley, Brian P McCarthy, Gary D Hutchins
Recent advancements in PET instrumentation have made the non-invasive assessment of cardiovascular function in small animals a reality. The majority of small animal PET systems use stationary detector gantries, thus affording high temporal resolution imaging of cardiac function. Systems designed to maximize spatial resolution and detection sensitivity employing rotating gantry designs are suboptimal when high temporal resolution imaging is needed. To overcome this limitation, the current work developed a novel view-sharing data analysis scheme suitable for dynamic cardiac PET imaging using (18)F-NaF as the tracer and tracer kinetic model analysis...
December 2016: EJNMMI Physics
https://www.readbyqxmd.com/read/27715017/radiosynthesis-and-preclinical-evaluation-of-18-f-fluoroglycosylated-octreotate-for-somatostatin-receptor-imaging
#12
Simone Maschauer, Marcus Heilmann, Carmen Wängler, Ralf Schirrmacher, Olaf Prante
Short synthetic octapeptide analogs derived from the native somatostatin peptides SST-14 and SST-28, namely, octreotate (TATE) or octreotide (TOC), bind with high affinity to somatostatin receptors (sstr), mainly to subtypes 2 and 5, which are expressed in high density on neuroendocrine tumors (NET). Therefore, radiolabeled TATE or TOC derivatives represent highly valuable imaging probes for NET diagnosis by positron emission tomography (PET). The aim of our study was the development of an (18)F-labeled octreotate analog as an alternative radiotracer for the clinically established (68)Ga-DOTATOC and (68)Ga-DOTATATE...
November 16, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/27693670/-18-f-fluoro-azomycin-2%C3%A2-deoxy-%C3%AE-d-ribofuranoside-a-new-imaging-agent-for-tumor-hypoxia-in-comparison-with-18-f-faza
#13
Anna Schweifer, Florian Maier, Walter Ehrlichmann, Denis Lamparter, Manfred Kneilling, Bernd J Pichler, Friedrich Hammerschmidt, Gerald Reischl
INTRODUCTION: Radiolabeled 2-nitroimidazoles (azomycins) are a prominent class of biomarkers for PET imaging of hypoxia. [(18)F]Fluoro-azomycin-α-arabinoside ([(18)F]FAZA) - already in clinical use - may be seen as α-configuration nucleoside, but enters cells only via diffusion and is not transported by cellular nucleoside transporters. To enhance image contrast in comparison to [(18)F]FAZA our objective was to (18)F-radiolabel an azomycin-2´-deoxyriboside with β-configuration ([(18)F]FAZDR, [(18)F]-β-8) to mimic nucleosides more closely and comparatively evaluate it versus [(18)F]FAZA...
December 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27566106/inhibition-of-rho-associated-kinase-1-2-attenuates-tumor-growth-in-murine-gastric-cancer
#14
Isabel Hinsenkamp, Sandra Schulz, Mareike Roscher, Anne-Maria Suhr, Björn Meyer, Bogdan Munteanu, Jens Fuchser, Stefan O Schoenberg, Matthias P A Ebert, Björn Wängler, Carsten Hopf, Elke Burgermeister
Gastric cancer (GC) remains a malignant disease with high mortality. Patients are frequently diagnosed in advanced stages where survival prognosis is poor. Thus, there is high medical need to find novel drug targets and treatment strategies. Recently, the comprehensive molecular characterization of GC subtypes revealed mutations in the small GTPase RHOA as a hallmark of diffuse-type GC. RHOA activates RHO-associated protein kinases (ROCK1/2) which regulate cell contractility, migration and growth and thus may play a role in cancer...
August 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27560354/a-dota-based-bisphosphonate-with-an-albumin-binding-moiety-for-delayed-body-clearance-for-bone-targeting
#15
Marian Meckel, Vojtěch Kubíček, Petr Hermann, Matthias Miederer, Frank Rösch
Radiolabeled bisphosphonates are commonly used in the diagnosis and therapy of bone metastases. Blood clearance of bisphosphonates is usually fast and only 30%-50% of the injected activity is retained in the skeleton, while most of the activity is excreted by the urinary tract. A longer blood circulation may enhance accumulation of bisphosphonate compounds in bone metastases. Therefore, a chemically modified macrocyclic bisphosphonate derivative with an additional human albumin binding entity was synthesized and pharmacokinetics of its complex was evaluated...
August 1, 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27494279/positron-range-in-tissue-equivalent-materials-experimental-micropet-studies
#16
H Alva-Sánchez, C Quintana-Bautista, A Martínez-Dávalos, M A Ávila-Rodríguez, M Rodríguez-Villafuerte
In this work an experimental investigation was carried out to study the effect that positron range has over positron emission tomography (PET) scans through measurements of the line spread function (LSF) in tissue-equivalent materials. Line-sources consisted of thin capillary tubes filled with (18)F, (13)N or (68)Ga water-solution inserted along the axis of symmetry of cylindrical phantoms constructed with the tissue-equivalent materials: lung (inhale and exhale), adipose tissue, solid water, trabecular and cortical bone...
September 7, 2016: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/27376889/enhanced-binding-of-necrosis-targeting-immunocytokine-nhs-il12-after-local-tumour-irradiation-in-murine-xenograft-models
#17
Franziska Eckert, Julia Schmitt, Daniel Zips, Marcel A Krueger, Bernd J Pichler, Stephen D Gillies, Wolfgang Strittmatter, Rupert Handgretinger, Karin Schilbach
PURPOSE: NHS-IL12 is an immunocytokine targeting necrotic tumour areas. IL12 shows anti-tumour activity. As local irradiation might induce additional necrosis in solid tumours, we aimed to evaluate the increase in intratumoural accumulation of NHS-IL12 after irradiation and correlate the findings with diffusion-weighted MRI studies in two xenograft models. METHODS: Human rhabdomyosarcoma (A204) and prostate cancer (PC3) cells were studied in vitro and as subcutaneous xenografts...
August 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27336295/-18-f-and-68-ga-labeled-neurotensin-peptides-for-pet-imaging-of-neurotensin-receptor-1
#18
Simone Maschauer, Jürgen Einsiedel, Harald Hübner, Peter Gmeiner, Olaf Prante
The neurotensin (NT) receptor-1 (NTS1) is overexpressed in a variety of carcinomas and is therefore an interesting target for imaging with positron emission tomography (PET). The aim of this study was the development of new NT derivatives based on the metabolically stable peptide sequence NLys-Lys-Pro-Tyr-Tle-Leu suitable for PET imaging. The NT peptides were synthesized by solid-phase supported peptide synthesis and elongated with respective chelators (NODA-GA, DOTA) for (68)Ga-labeling or propargylglycine for (18)F-labeling via copper-catalyzed azide-alkyne cycloaddition...
July 14, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27248781/design-of-a-small-molecule-drug-conjugate-for-prostate-cancer-targeted-theranostics
#19
Amit Kumar, Tara Mastren, Bin Wang, Jer-Tsong Hsieh, Guiyang Hao, Xiankai Sun
Targeted therapy has become an effective strategy of precision medicine for cancer treatment. Based on the success of antibody-drug conjugates (ADCs), here we report a theranostic design of small-molecule drug conjugates (T-SMDCs) for targeted imaging and chemotherapy of prostate cancer. The structure of T-SMDCs built upon a polyethylene glycol (PEG) scaffold consists of (i) a chelating moiety for positron emission tomography (PET) imaging when labeled with (68)Ga, a positron-emitting radioisotope; (ii) a prostate specific membrane antigen (PSMA) specific ligand for prostate cancer targeting; and (iii) a cytotoxic drug (DM1) for chemotherapy...
July 20, 2016: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/27247380/a-novel-thermoregulatory-role-for-pde10a-in-mouse-and-human-adipocytes
#20
Mohammed K Hankir, Mathias Kranz, Thorsten Gnad, Juliane Weiner, Sally Wagner, Winnie Deuther-Conrad, Felix Bronisch, Karen Steinhoff, Julia Luthardt, Nora Klöting, Swen Hesse, John P Seibyl, Osama Sabri, John T Heiker, Matthias Blüher, Alexander Pfeifer, Peter Brust, Wiebke K Fenske
Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small-animal PET/MRI and the novel radioligand [(18)F]-AQ28A, we found marked levels of PDE10A in interscapular brown adipose tissue (BAT) of mice. Pharmacological inactivation of PDE10A with the highly selective inhibitor MP-10 recruited BAT and potentiated thermogenesis in vivo In diet-induced obese mice, chronic administration of MP-10 caused weight loss associated with increased energy expenditure, browning of white adipose tissue, and improved insulin sensitivity...
2016: EMBO Molecular Medicine
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