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https://www.readbyqxmd.com/read/28646013/doxorubicin-effect-on-myocardial-metabolism-as-a-pre-requisite-for-subsequent-development-of-cardiac-toxicity-a-translational-18-f-fdg-pet-ct-observation
#1
Matteo Bauckneht, Giulia Ferrarazzo, Francesco Fiz, Silvia Morbelli, Matteo Sarocchi, Fabio Pastorino, Alberto Ghidella, Elena Pomposelli, Maurizio Miglino, Pietro Ameri, Laura Emionite, Flavia Ticconi, Eleonora Arboscello, Ambra Buschiazzo, Elena Augusta Massimelli, Salvatore Fiordoro, Anna Borra, Vanessa Cossu, Annalisa Bozzano, Adalberto Ibatici, Mirco Ponzoni, Paolo Spallarossa, Andrea Gallamini, Paolo Bruzzi, Gianmario Sambuceti, Cecilia Marini
The present translational study aimed to verify whether serial (18)F-fluoro-deoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated with intravenous administration of saline (n = 5), doxorubicin 5 mg/Kg (n = 5) or doxorubicin 7.5 mg/Kg (n = 5) and submitted to dynamic microPET scan to estimate left ventricular glucose consumption (LV-MRGlu) before and after chemotherapy. Thereafter, we retrospectively identified 69 patients successfully treated with Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) regimen for Hodgkin's Disease (HD) and submitted to four consecutive FDG-PET/CT scans...
June 23, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28619735/the-evolving-role-of-succinate-in-tumor-metabolism-an-18-f-fdg-based-study
#2
Philippe Garrigue, Aurore Bodin-Hullin, Laure Balasse, Samantha Fernandez, Wassim Essamet, Françoise Dignat-George, Karel Pacak, Benjamin Guillet, David Taieb
Objective: In recent years, inherited and acquired mutations in the TCA cycle enzymes have been reported in diverse cancers. Pheochromocytomas and paragangliomas (PPGLs) often exhibit dysregulation of glucose metabolism which is also driven by mutations in genes encoding the TCA cycle enzymes or by activation of hypoxia signaling. PPGLs associated with succinate dehydrogenase (SDH) deficiency are characterized by high (18)F-fluorodeoxyglucose ([(18)F]-FDG) avidity. This association is currently only partially explained...
June 15, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28619538/synthesis-and-biological-evaluation-of-2-3-4-dimethoxyphenyl-6-2-18-f-fluoroethoxy-benzothiazole-18-f-fedbt-for-pet-imaging-of-breast-cancer
#3
Geng-Ying Li, Daria D Vaulina, Jia-Je Li, Olga S Fedorova, Hsin-Ell Wang, Ren-Shyan Liu, Raisa N Krasikova, Chuan-Lin Chen
Given the ever-present demand for improved PET radiotracer in oncology imaging, we have synthesized 2-(3,4-dimethoxyphenyl)-6-(2-[(18)F]fluoroethoxy)benzothiazole ([(18)F]FEDBT), a fluorine-18-containing fluoroethylated benzothiazole to explore its utility as a PET imaging tracer. [(18)F]FEDBT was prepared via kryptofix-mediated nucleophilic substitution of the tosyl group precursor. Fractionated ethanol-based solid-phase (SPE cartridge-based) purification afforded [(18)F]FEDBT in 60% radiochemical yield (EOB), with radiochemical purity in excess of 98% and the specific activity was 35GBq/μmol...
May 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28613163/sinogram-blurring-matrix-estimation-from-point-sources-measurements-with-rank-one-approximation-for-fully-3d-pet
#4
Kuang Gong, Jian Zhou, Michel Tohme, Martin Judenhofer, Yongfeng Yang, Jinyi Qi
An accurate system matrix is essential in PET for reconstructing high quality images. To reduce storage size and image reconstruction time, we factor the system matrix into a product of a geometry projection matrix and a sinogram blurring matrix. The geometric projection matrix is computed analytically and the sinogram blurring matrix is estimated from point source measurements. Previously we have estimated a two dimensional (2D) blurring matrix for a preclinical PET scanner. The 2D blurring matrix only considers blurring effects within a transaxial sinogram and does not compensate for intersinogram blurring effects...
June 2, 2017: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28607591/pet-of-her2-expression-with-a-novel-18-fal-labeled-affibody
#5
Yuping Xu, Zhicheng Bai, Qianhuan Huang, Yunyun Pan, Donghui Pan, Lizhen Wang, Junjie Yan, Xinyu Wang, Runlin Yang, Min Yang
Background: Human epidermal growth factor receptor type 2 (HER2) is abundant in a wide variety of tumors and associated with the poor prognosis. Radiolabeled affibodies are potential candidates for detecting HER2-positive lesions. However, laborious multiple-step synthetic procedure and high abdomen background may hinder the widespread use. Herein, cysteinylated ZHER2:342 modified with a new hydrophilic linker (denoted as MZHER2:342) was designed and labeled using (18)FAl-NOTA strategies. The biologic efficacy of the novel tracer and its feasibilities for in vivo monitoring HER2 levels were also investigated in xenograft models with different HER2 expressions...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28486208/synthesis-and-preclinical-evaluation-of-11-c-ma-pb-1-for-in%C3%A2-vivo-imaging-of-brain-monoacylglycerol-lipase-magl
#6
Muneer Ahamed, Bala Attili, Daisy van Veghel, Maarten Ooms, Philippe Berben, Sofie Celen, Michel Koole, Lieven Declercq, Juha R Savinainen, Jarmo T Laitinen, Alfons Verbruggen, Guy Bormans
MAGL is a potential therapeutic target for oncological and psychiatric diseases. Our objective was to develop a PET tracer for in vivo quantification of MAGL. We report [(11)C]MA-PB-1 as an irreversible MAGL inhibitor PET tracer. The in vitro inhibitory activity, ex vivo distribution, brain kinetics and specificity of [(11)C]MA-PB-1 binding were studied. Ex vivo biodistribution and microPET showed good brain uptake which could be blocked by pretreatment with both MA-PB-1 and a structurally non-related MAGL inhibitor MJN110...
April 25, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28486147/multimodal-assessment-of-sers-nanoparticle-biodistribution-post-ingestion-reveals-new-potential-for-clinical-translation-of-raman-imaging
#7
Jos L Campbell, Elliott D SoRelle, Ohad Ilovich, Orly Liba, Michelle L James, Zhen Qiu, Valerie Perez, Carmel T Chan, Adam de la Zerda, Cristina Zavaleta
Despite extensive research and development, new nano-based diagnostic contrast agents have faced major barriers in gaining regulatory approval due to their potential systemic toxicity and prolonged retention in vital organs. Here we use five independent biodistribution techniques to demonstrate that oral ingestion of one such agent, gold-silica Raman nanoparticles, results in complete clearance with no systemic toxicity in living mice. The oral delivery mimics topical administration to the oral cavity and gastrointestinal (GI) tract as an alternative to intravenous injection...
August 2017: Biomaterials
https://www.readbyqxmd.com/read/28479199/radiosynthesis-and-evaluation-of-igf1r-pet-ligand-11-c-gsk1838705a
#8
Kiran Kumar Solingapuram Sai, Jaya Prabhakaran, Anirudh Sattiraju, J John Mann, Akiva Mintz, J S Dileep Kumar
Radiosynthesis and evaluation of [(11)C]GSK1838705A in mice using microPET and determination of specificity in human GBM UG87MR cells are described herein. The radioligand was synthesized by reacting desmethyl-GSK1838705A with [(11)C]CH3I using GE FX2MeI module in ∼5% yield (EOS), >95% radiochemical purity and a specific activity of 2.5±0.5Ci/μmol. MicroPET imaging in mice indicated that [(11)C]GSK1838705A penetrated blood brain barrier (BBB) and showed retention of radiotracer in brain. The radioligand exhibited high uptake in U87MG cells with >70% specific binding to IGF1R...
April 27, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28409338/fluorine-18-labeling-of-the-her2-targeting-single-domain-antibody-2rs15d-using-a-residualizing-label-and-preclinical-evaluation
#9
Zhengyuan Zhou, Ganesan Vaidyanathan, Darryl McDougald, Choong Mo Kang, Irina Balyasnikova, Nick Devoogdt, Angeline N Ta, Brian R McNaughton, Michael R Zalutsky
PURPOSE: Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts...
April 13, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28398234/down-regulated-drebrin-aggravates-cognitive-impairments-in-a-mouse-model-of-alzheimer-s-disease
#10
Yan Liu, Yanfeng Xu, Ling Zhang, Lan Huang, Pin Yu, Hua Zhu, Wei Deng, Chuan Qin
The developmentally regulated brain protein drebrin (Dbn) is a functional protein involved with long-term memory formation and is widely distributed in brain neurons, especially in the dendritic spines. A noticeable decline of this protein has been found in the hippocampus and cortex of patients with Alzheimer's disease (AD), yet the relationship between Dbn and AD has not been fully understood. In the present study, we examined how down-regulation of Dbn impacts the progression of AD in experimental animals...
April 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28393895/sex-differences-in-regional-brain-glucose-metabolism-following-opioid-withdrawal-and-replacement
#11
Giovanni C Santoro, Joseph Carrion, Krishna Patel, Crystal Vilchez, Jennifer Veith, Jonathan D Brodie, Stephen L Dewey
Methadone and buprenorphine are currently the most common pharmacological treatments for opioid dependence. Interestingly, the clinical response to these drugs appears to be sex specific. That is, females exhibit superior therapeutic efficacy, defined as extended periods of abstinence and longer time to relapse, compared with males. However, the underlying metabolic effects of opioid withdrawal and replacement have not been examined. Therefore, using (18)FDG and microPET, we measured differences in regional brain glucose metabolism in males and females following morphine withdrawal and subsequent methadone or buprenorphine replacement...
May 3, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28365375/preclinical-molecular-imaging-of-glutamatergic-and-dopaminergic-neuroreceptor-kinetics-in-obsessive-compulsive-disorder
#12
S Servaes, D Glorie, J Verhaeghe, S Stroobants, S Staelens
BACKGROUND: Molecular neuroimaging was applied in the quinpirole rat model for compulsive checking in OCD to visualize the D2- and mGluR5-receptor occupancy with Raclopride and ABP-688 microPET/CT. METHODS: Animals (n=48) were exposed to either saline (CTRL; 1mL/kg) or quinpirole (QP; dopamine D2-agonist, 0.5mg/kg) in a single injection (RAC and ABP acute groups) or twice-weekly during 7weeks (chronic group). Animals underwent PET/CT after the 1st injection (acute) or before initial exposure and following the 10th injection in week 5 (chronic)...
March 30, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28360206/her3-specific-biodistribution-and-tumor-uptake-of-89-zr-msb0010853-visualized-by-real-time-and-non-invasive-pet-imaging
#13
Frank-Jan Warnders, Anton Gt Terwisscha van Scheltinga, Christine Knuehl, Maarten van Roy, Erik F de Vries, Jos G W Kosterink, Elisabeth G E de Vries, Marjolijn N Lub-de Hooge
The human epidermal growth factor receptor (HER)3 is an interesting target for antitumor therapy. For optimal HER3 signaling inhibition a biparatopic Nanobody® construct (MSB0010853) was developed which binds two HER3 epitopes. In addition, MSB0010853 contains a third Nanobody that binds albumin to extend its circulation time. MSB0010853 is cross-reactive with HER3 and albumin of mouse origin. We aimed to gain insight in MSB0010853 biodistribution and tumor uptake by radiolabeling the Nanobody construct with (89)Zr...
March 30, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28347826/changes-in-cerebral-18-f-fdg-uptake-induced-by-acute-alcohol-administration-in-a-rat-model-of-alcoholism
#14
Juan D Gispert, Francisca P Figueiras, Valentina Vengeliene, José R Herance, Santiago Rojas, Rainer Spanagel
Several [(18)F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies...
June 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28302035/translational-multimodality-neuroimaging
#15
Sushil K Sharma
Recently high-resolution, noninvasive, multimodality in-vivo molecular imaging with PET, SPECT, CT and MRI, employing fusion algorithms has revolutionized personalized medicine. However, specific radiopharmaceuticals (RPs) for the accurate diagnosis and effective treatment of progressive neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, drug addiction, and other cognitive impairments still remain in developmental phase. Currently, multimodality fusion neuroimaging is utilized for the determination of: pharmacokinetics and pre-clinical development of radiopharmaceuticals (RPs); in-vivo monitoring of stem cell transplantation therapy; nicotinic acetylcholine receptors (nAChRs) investigations; and regional cerebral blood flow and glucose metabolism in cognitively-impaired subjects employing noninvasive microPET and nano-SPECT imaging...
March 15, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28255357/stat3-nf-%C3%AE%C2%BAb-regulated-lentiviral-tk-gcv-suicide-gene-therapy-for-cisplatin-resistant-triple-negative-breast-cancer
#16
Wei-Ying Kuo, Luen Hwu, Chun-Yi Wu, Jhih-Shian Lee, Chi-Wei Chang, Ren-Shyan Liu
Triple-negative breast cancer (TNBC) represents approximately 20% of all breast cancers and appears resistance to conventional cytotoxic chemotherapy, demonstrating a particularly poor prognosis and a significantly worse clinical outcome than other types of cancer. Suicide gene therapy has been used for the in vivo treatment of various solid tumors in recent clinical trials. In tumor microenvironment, STAT3/NF-κB pathways are constitutively activated in stromal cells as well as in cancer stem cells (CSCs)...
2017: Theranostics
https://www.readbyqxmd.com/read/28243322/targeting-metabolic-remodeling-in-triple-negative-breast-cancer-in-a-murine-model
#17
Verónica García-Castillo, Eduardo López-Urrutia, Octavio Villanueva-Sánchez, Miguel Á Ávila-Rodríguez, Alejandro Zentella-Dehesa, Carlo Cortés-González, César López-Camarillo, Nadia J Jacobo-Herrera, Carlos Pérez-Plasencia
Background: Chemotherapy is the backbone of systemic treatment for triple negative breast cancer (TNBC), which is one of the most relevant breast cancers molecular types due to the ability of tumor cells to develop drug resistance, highlighting the urgent need to design newer and safer drug combinations for treatment. In this context, to overcome tumor cell drug resistance, we employed a novel combinatorial treatment including Doxorubicin, Metformin, and Sodium Oxamate (DoxMetOx). Such pharmacological combination targets indispensable hallmarks of cancer-related to aerobic glycolysis and DNA synthesis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28239334/micropet-outperforms-beta-microprobes-in-determining-neuroreceptor-availability-under-pharmacological-restriction-for-cold-mass-occupancy
#18
Dorien Glorie, Stijn Servaes, Jeroen Verhaeghe, Tine Wyckhuys, Leonie Wyffels, Olivier Vanderveken, Sigrid Stroobants, Steven Staelens
Both non-invasive micro-positron emission tomography (μPET) and in situ beta-microprobes have the ability to determine radiotracer kinetics and neuroreceptor availability in vivo. Beta-microprobes were proposed as a cost-effective alternative to μPET, but literature revealed conflicting results most likely due to methodological differences and inflicted tissue damage. The current study has three main objectives: (i) evaluate the theoretical advantages of beta-microprobes; (ii) perform μPET imaging to assess the impact of (beta-micro)probe implantation on relative tracer delivery (R1) and receptor occupancy (non-displaceable binding potential, BPND) in the rat brain; and (iii) investigate whether beta-microprobe recordings produce robust results when a pharmacological restriction for cold mass dose (tracer dose condition) is imposed...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28184015/dual-pi3k-mtor-inhibition-in-colorectal-cancers-with-apc-and-pik3ca-mutations
#19
Tyler M Foley, Susan N Payne, Cheri A Pasch, Alex E Yueh, Dana R Van De Hey, Demetra P Korkos, Linda Clipson, Molly E Maher, Kristina A Matkowskyj, Michael A Newton, Dustin A Deming
Therapeutic targeting of the PI3K pathway is an active area of research in multiple cancer types, including breast and endometrial cancers. This pathway is commonly altered in cancer and plays an integral role in numerous vital cellular functions. Mutations in the PIK3CA gene, resulting in a constitutively active form of PI3K, often occur in colorectal cancer, though the population of patients who would benefit from targeting this pathway has yet to be identified. In human colorectal cancers, PIK3CA mutations most commonly occur concomitantly with loss of adenomatous polyposis coli (APC)...
February 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28179292/effect-of-androgen-on-normal-biodistribution-of-18-f-2-fluoro-5-methyl-1-beta-d-arabinofuranosyluracil-18f-fmau-in-athymic-non-tumor-bearing-male-mice
#20
Hossein Jadvar, Ryan Park, Li-Peng Yap, Kai Chen, Lindsey Hughes, Peter Conti
AIM: We assessed the association between the presence and absence of androgen on the normal biodistribution of the positron emission tomography (PET) cellular proliferation imaging biomarker, [(18)F]-2'-Fluoro-5-methyl-1-beta-D-arabinofuranosyluracil ((18)F-FMAU), in mice. MATERIALS AND METHODS: Non-castrated (n=4) and castrated (n=4) athymic non-tumor-bearing male mice served as models for presence and absence, respectively, of androgen. MicroPET-CT scans were performed 1 h following tail vein administration of 200 uCi of (18)F-FMAU...
February 2017: Anticancer Research
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