Sample records for assaying pet targets

  1. Predictive Assay For Cancer Targets

    Energy Technology Data Exchange (ETDEWEB)

    Suess, A; Nguyen, C; Sorensen, K; Montgomery, J; Souza, B; Kulp, K; Dugan, L; Christian, A


    Early detection of cancer is a key element in successful treatment of the disease. Understanding the particular type of cancer involved, its origins and probable course, is also important. PhIP (2-amino-1-methyl-6 phenylimidazo [4,5-b]pyridine), a heterocyclic amine produced during the cooking of meat at elevated temperatures, has been shown to induce mammary cancer in female, Sprague-Dawley rats. Tumors induced by PhIP have been shown to contain discreet cytogenetic signature patterns of gains and losses using comparative genomic hybridization (CGH). To determine if a protein signature exists for these tumors, we are analyzing expression levels of the protein products of the above-mentioned tumors in combination with a new bulk protein subtractive assay. This assay produces a panel of antibodies against proteins that are either on or off in the tumor. Hybridization of the antibody panel onto a 2-D gel of tumor or control protein will allow for identification of a distinct protein signature in the tumor. Analysis of several gene databases has identified a number of rat homologs of human cancer genes located in these regions of gain and loss. These genes include the oncogenes c-MYK, ERBB2/NEU, THRA and tumor suppressor genes EGR1 and HDAC3. The listed genes have been shown to be estrogen-responsive, suggesting a possible link between delivery of bio-activated PhIP to the cell nucleus via estrogen receptors and gene-specific PhIP-induced DNA damage, leading to cell transformation. All three tumors showed similar silver staining patterns compared to each other, while they all were different than the control tissue. Subsequent screening of these genes against those from tumors know to be caused by other agents may produce a protein signature unique to PhIP, which can be used as a diagnostic to augment optical and radiation-based detection schemes.

  2. Electroplated targets for production of unique PET radionuclides (United States)

    Bui, V.; Sheh, Y.; Finn, R.; Francesconi, L.; Cai, S.; Schlyer, D.; Wieland, B.


    The past decade has witnessed the applications of positron emission tomography (PET) evolving from a purely research endeavor to a procedure which has specific clinical applications in the areas of cardiology, neurology and oncology. The growth of PET has been facilitated by developments in both medical instrumentation and radiopharmaceutical chemistry efforts. Included in this latter effort has been the low energy accelerator production and processing of unique PET radionuclides appropriate for the radiolabeling of biomolecules, i.e. monoclonal antibodies and peptides. The development and application of electroplated targets of antimony and copper for the production of iodine-124 and gallium-66 respectively, utilizing the Memorial Sloan-Kettering Cancer Center (MSKCC) cyclotron are examples of target design and development applicable to many medical accelerators.

  3. The Dilemma of Target Delineation with PET/CT in Radiotherapy Planning for Malignant Tumors

    Institute of Scientific and Technical Information of China (English)


    Currently there are many unanswered questions concerning contouring a target with PET/CT in radiotherapy planning. Who should contour the PET volume-the radiation oncologist or the nuclear medicine physician? Which factors will contribute to the dual-observer variability between them? What should be taken as the optimal SUV threshold to demarcate a malignant tumor from the normal tissue? When the PET volume does not coincide with the local area CT findings, which portion should be contoured as the target? If a reginal lymph nodedraining area or a remote region is shown to be PET positive but CT negative, or PET negative but CT positive, how is the target identified and selected? Further studies concerning the relationship between PET/CT and the cancerous tissue are needed. The long-term clinical results showing an increased therapeutic ratio will finally verify the applicability of guidelines to contour the target with PET/CT in radiotherapy planning.

  4. Avian-specific real-time PCR assay for authenticity control in farm animal feeds and pet foods. (United States)

    Pegels, Nicolette; González, Isabel; García, Teresa; Martín, Rosario


    A highly sensitive TaqMan real-time PCR assay targeting the mitochondrial 12S rRNA gene was developed for detection of an avian-specific DNA fragment (68bp) in farm animal and pet feeds. The specificity of the assay was verified against a wide representation of animal and plant species. Applicability assessment of the avian real-time PCR was conducted through representative analysis of two types of compound feeds: industrial farm animal feeds (n=60) subjected to extreme temperatures, and commercial dog and cat feeds (n=210). Results obtained demonstrated the suitability of the real-time PCR assay to detect the presence of low percentages of highly processed avian material in the feed samples analysed. Although quantification results were well reproducible under the experimental conditions tested, an accurate estimation of the target content in feeds is impossible in practice. Nevertheless, the method may be useful as an alternative tool for traceability purposes within the framework of feed control.

  5. Using the CPTAC Assay Portal to identify and implement highly characterized targeted proteomics assays (United States)

    Whiteaker, Jeffrey R; Halusa, Goran N; Hoofnagle, Andrew N; Sharma, Vagisha; MacLean, Brendan; Yan, Ping; Wrobel, John A; Kennedy, Jacob; Mani, DR; Zimmerman, Lisa J; Meyer, Matthew R.; Mesri, Mehdi; Abbatiello, Susan E; Boja, Emily; Carr, Steven A.; Chan, Daniel W.; Chen, Xian; Chen, Jing; Davies, Sherri R; Ellis, Matthew J. C.; Fenyö, David; Hiltke, Tara; Ketchum, Karen A.; Kinsinger, Chris; Kuhn, Eric; Liebler, Daniel C.; Lin, De; Liu, Tao; Loss, Michael; MacCoss, Michael J; Qian, Wei-Jun; Rivers, Robert; Rodland, Karin D.; Ruggles, Kelly V; Scott, Mitchell G; Smith, Richard D.; Thomas, Stefani; Townsend, R. Reid; Whiteley, Gordon; Wu, Chaochao; Zhang, Hui; Zhang, Zhen; Rodriguez, Henry; Paulovich, Amanda G


    Summary The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI) has launched an Assay Portal ( to serve as an open-source repository of well-characterized targeted proteomic assays. The portal is designed to curate and disseminate highly characterized, targeted mass spectrometry (MS)-based assays by providing detailed assay performance characterization data, standard operating procedures, and access to reagents. Assay content is accessed via the portal through queries to find assays targeting proteins associated with specific cellular pathways, protein complexes, or specific chromosomal regions. The position of the peptide analytes for which there are available assays are mapped relative to other features of interest in the protein, such as sequence domains, isoforms, single nucleotide polymorphisms, and post-translational modifications. The overarching goals are to enable robust quantification of all human proteins and to standardize the quantification of targeted MS-based assays to ultimately enable harmonization of results over time and across laboratories. PMID:26867747

  6. Using the CPTAC Assay Portal to identify and implement highly characterized targeted proteomics assays

    Energy Technology Data Exchange (ETDEWEB)

    Whiteaker, Jeffrey R.; Halusa, Goran; Hoofnagle, Andrew N.; Sharma, Vagisha; MacLean, Brendan; Yan, Ping; Wrobel, John; Kennedy, Jacob; Mani, DR; Zimmerman, Lisa J.; Meyer, Matthew R.; Mesri, Mehdi; Boja, Emily; Carr, Steven A.; Chan, Daniel W.; Chen, Xian; Chen, Jing; Davies, Sherri; Ellis, Matthew; Fenyo, David; Hiltket, Tara; Ketchum, Karen; Kinsinger, Christopher; Kuhn, Eric; Liebler, Daniel; Liu, Tao; Loss, Michael; MacCoss, Michael; Qian, Weijun; Rivers, Robert; Rodland, Karin D.; Ruggles, Kelly; Scott, Mitchell; Smith, Richard D.; Thomas, Stefani N.; Townsend, Reid; Whiteley, Gordon; Wu, Chaochao; Zhang, Hui; Zhang, Zhen; Rodriguez, Henry; Paulovich, Amanda G.


    The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI) has launched an Assay Portal ( to serve as an open-source repository of well-characterized targeted proteomic assays. The portal is designed to curate and disseminate highly characterized, targeted mass spectrometry (MS)-based assays by providing detailed assay performance characterization data, standard operating procedures, and access to reagents. Assay content is accessed via the portal through queries to find assays targeting proteins associated with specific cellular pathways, protein complexes, or specific chromosomal regions. The position of the peptide analytes for which there are available assays are mapped relative to other features of interest in the protein, such as sequence domains, isoforms, single nucleotide polymorphisms, and post-translational modifications. The overarching goals are to enable robust quantification of all human proteins and to standardize the quantification of targeted MS-based assays to ultimately enable harmonization of results over time and across laboratories.

  7. Multimodal target correction by local bone registration: a PET/CT evaluation. (United States)

    Oliveira-Santos, Thiago; Weitzel, Thilo; Klaeser, Bernd; Krause, Thomas; Nolte, Lutz-Peter; Weber, Stefan; Reyes, Mauricio


    PET/CT guidance for percutaneous interventions allows biopsy of suspicious metabolically active bone lesions even when no morphological correlation is delineable in the CT images. Clinical use of PET/CT guidance with conventional step-by-step technique is time consuming and complicated especially in cases in which the target lesion is not shown in the CT image. Our recently developed multimodal instrument guidance system (IGS) for PET/CT improved this situation. Nevertheless, bone biopsies even with IGS have a trade-off between precision and intervention duration which is proportional to patient and personnel exposure to radiation. As image acquisition and reconstruction of PET may take up to 10 minutes, preferably only one time consuming combined PET/CT acquisition should be needed during an intervention. In case of required additional control images in order to check for possible patient movements/deformations, or to verify the final needle position in the target, only fast CT acquisitions should be performed. However, for precise instrument guidance accounting for patient movement and/or deformation without having a control PET image, it is essential to be able to transfer the position of the target as identified in the original PET/CT to a changed situation as shown in the control CT.

  8. PET

    DEFF Research Database (Denmark)

    Mariager, Rasmus Mølgaard; Schmidt, Regin; Heiberg, Morten Rievers

    PET handler om den hemmelige tjenestes arbejde under den kolde krig 1945-1989. Her fortæller Regin Schmidt, Rasmus Mariager og Morten Heiberg om de mest dramatiske og interessante sager fra PET's arkiv. PET er på flere måder en udemokratisk institution, der er sat til at vogte over demokratiet....... Dens virksomhed er skjult for offentligheden, den overvåger borgernes aktiviteter, og den registrerer følsomme personoplysninger. Historien om PET rejser spørgsmålet om, hvad man skal gøre, når befolkningen i et demokrati er kritisk indstillet over for overvågningen af lovlige politiske aktiviteter......, mens myndighederne mener, at det er nødvendigt for at beskytte demokratiet. PET er på en gang en fortælling om konkrete aktioner og begivenheder i PET's arbejde og et stykke Danmarkshistorie. Det handler om overvågning, spioner, politisk ekstremisme og international terrorisme.  ...

  9. Targets and assays for discovering novel antibacterial agents. (United States)

    Donadio, Stefano; Carrano, Lucia; Brandi, Letizia; Serina, Stefania; Soffientini, Adolfo; Raimondi, Elena; Montanini, Nicoletta; Sosio, Margherita; Gualerzi, Claudio O


    The increasing frequency of nosocomial infections due to multi-resistant pathogens exerts a significant toll and calls for novel and better antibiotics. Different approaches can be used in the search for novel antibiotics acting on drug-resistant bacterial pathogens. We present some considerations on valid bacterial targets to be used for searching new antibiotics, and how the information from bacterial genome sequences can assist in choosing the appropriate targets. Other factors to be considered in target selection are the chemical diversity available for screening and its uniqueness. We will conclude discussing our strategy for searching novel antibacterials. This is based on a large collection of microbial extracts as a source of chemical diversity and on the use of specific targets essential for the viability of bacterial pathogens. Two assay strategies have been implemented: a pathway-based assay, where a series of essential bacterial targets is screened in a single assay; and a binding assay, where many targets can be screened individually in the same format.

  10. Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs (United States)

    Gunn, Roger N; Summerfield, Scott G; Salinas, Cristian A; Read, Kevin D; Guo, Qi; Searle, Graham E; Parker, Christine A; Jeffrey, Phil; Laruelle, Marc


    The passage of drugs in and out of the brain is controlled by the blood–brain barrier (BBB), typically, using either passive diffusion across a concentration gradient or active transport via a protein carrier. In-vitro and preclinical measurements of BBB penetration do not always accurately predict the in-vivo situation in humans. Thus, the ability to assay the concentration of novel drug candidates in the human brain in vivo provides valuable information for derisking of candidate molecules early in drug development. Here, positron emission tomography (PET) measurements are combined with in-vitro equilibrium dialysis assays to enable assessment of transport and estimation of the free brain concentration in vivo. The PET and equilibrium dialysis data were obtained for 36 compounds in the pig. Predicted P-glycoprotein (P-gp) status of the compounds was consistent with the PET/equilibrium dialysis results. In particular, Loperamide, a well-known P-gp substrate, exhibited a significant concentration gradient consistent with active efflux and after inhibition of the P-gp process the gradient was removed. The ability to measure the free brain concentration and assess transport of novel compounds in the human brain with combined PET and equilibrium dialysis assays can be a useful tool in central nervous system (CNS) drug development. PMID:22274741

  11. Can FDG-PET assist in radiotherapy target volume definition of metastatic lymph nodes in head-and-neck cancer?

    NARCIS (Netherlands)

    Schinagl, D.A.X.; Hoffmann, A.L.; Vogel, W.V.; Dalen, J.A. van; Verstappen, S.M.M.; Oyen, W.J.G.; Kaanders, J.H.A.M.


    BACKGROUND AND PURPOSE: The role of FDG-PET in radiotherapy target volume definition of the neck was evaluated by comparing eight methods of FDG-PET segmentation to the current CT-based practice of lymph node assessment in head-and-neck cancer patients. MATERIALS AND METHODS: Seventy-eight head-and-

  12. F-18 Polyethyleneglycol stilbenes as PET imaging agents targeting A{beta} aggregates in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Wei [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Oya, Shunichi [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Kung Meiping [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Hou, Catherine [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States); Maier, Donna L. [Department of Neuroscience, AstraZeneca, Wilmington, DE 19850 (United States); Kung, Hank F. [Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104 (United States) and Department of Pharmacology, University of Pennsylvania, Philadelphia, PA 19104 (United States)]. E-mail:


    This paper describes a novel series of {sup 18}F-labeled polyethyleneglycol (PEG)-stilbene derivatives as potential {beta}-amyloid (A{beta}) plaque-specific imaging agents for positron emission tomography (PET). In these series of compounds, {sup 18}F is linked to the stilbene through a PEG chain, of which the number of ethoxy groups ranges from 2 to 5. The purpose of adding PEG groups is to lower the lipophilicity and improve bioavailability. The syntheses of the 'cold' compounds and the {sup 18}F-labeled PEG stilbene derivatives are successfully achieved. All of the fluorinated stilbenes displayed high binding affinities in an assay using postmortem AD brain homogenates (K {sub i}=2.9-6.7 nM). Labeling was successfully performed by a substitution of the mesylate group of 10a-d by [{sup 18}F]fluoride giving the target compounds [{sup 18}F]12a-d (EOS, specific activity, 900-1500 Ci/mmol; radiochemical purity >99%). In vivo biodistribution of these novel {sup 18}F ligands in normal mice exhibited excellent brain penetrations and rapid washouts after an intravenous injection (6.6-8.1 and 1.2-2.6% dose/g at 2 and 60 min, respectively). Autoradiography of postmortem AD brain sections of [{sup 18}F]12a-d confirmed the specific binding related to the presence of A{beta} plaques. In addition, in vivo plaque labeling can be clearly demonstrated with these {sup 18}F-labeled agents in transgenic mice (Tg2576), a useful animal model for Alzheimer's disease. In conclusion, the preliminary results strongly suggest these fluorinated PEG stilbene derivatives are suitable candidates as A{beta} plaque imaging agents for studying patients with Alzheimer's disease.

  13. 44gSc from metal calcium targets for PET

    DEFF Research Database (Denmark)

    Severin, Gregory; Gagnon, K.; Engle, J. W.;


    A low-cost and efficient method for producing pre-clinical scale quantities of 44gSc is presented. Production involves proton irradiation of natural unenriched calcium metal followed by rapid separation of radioscandium from the target using hydroxmate functionalized resin.© 2012 American Institu...

  14. [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

    DEFF Research Database (Denmark)

    Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø;


    -azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

  15. Full in-beam PET measurements of 62 MeV protons onto a PMMA target

    Energy Technology Data Exchange (ETDEWEB)

    Sportelli, G., E-mail: [Department of Physics “E. Fermi”, University of Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy); Straub, K.; Aiello, M.; Attanasi, F.; Belcari, N.; Camarlinghi, N. [Department of Physics “E. Fermi”, University of Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy); Cirrone, G.A.P.; Cuttone, G. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Via S. Sofia 62, I-95125 Catania (Italy); Ferretti, S. [Department of Physics “E. Fermi”, University of Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy); Marino, N. [Department of Physics “E. Fermi”, University of Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Pisa, Largo B. Pontecorvo 3, I-56127 Pisa (Italy); Department of Information Engineering, University of Pisa, Via G. Caruso 16, I-56122 Pisa (Italy); Nicolosi, D. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Via S. Sofia 62, I-95125 Catania (Italy); Romano, F. [Istituto Nazionale di Fisica Nucleare, Laboratori Nazionali del Sud, Via S. Sofia 62, I-95125 Catania (Italy); Museo Storico della Fisica e Centro Studi e Ricerche “E. Fermi”, I-00184 Roma Italy (Italy); and others


    Positron emission tomography (PET) is a valuable technique to monitor in situ and non-invasively the particle range in ion beam therapy exploiting the beta+ activity produced in nuclear interactions along the beam path within the target volume. Due to the high random rates and dead-time losses induced by the particle spills, as of to date data are usually acquired during beam pauses or after the irradiation. We have developed a new PET prototype with a faster photon discrimination component that reduces the front-end dead time, and a modularized acquisition system that parallelizes the sensitive detector area, so as to enable data acquisition also during therapeutic irradiation (full in-beam measurement). The PET system has been able to sustain the single photon count rates and acquire coincidences during the beam, in conditions of sub-clinical beam currents. A study on the paralyzation conditions and dead time losses under different beam currents is presented and the feasibility of a full in-beam PET scanner is discussed.

  16. Targeted microbubbles for imaging tumor angiogenesis: assessment of whole-body biodistribution with dynamic micro-PET in mice

    DEFF Research Database (Denmark)

    Willmann, Jürgen K; Cheng, Zhen; Davis, Corrine;


    To evaluate in vivo whole-body biodistribution of microbubbles (MBs) targeted to tumor angiogenesis-related vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by using dynamic micro-positron emission tomography (PET) in living mice....

  17. High performance ZnO:Al films deposited on PET substrates using facing target sputtering

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Tingting [Solar Film Laboratory, School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); Dong, Guobo, E-mail: [Solar Film Laboratory, School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); Gao, Fangyuan; Xiao, Yu [Solar Film Laboratory, School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); Chen, Qiang [Key Laboratory of Micro-nano Measurement-Manipulation and Physics (Ministry of Education), School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China); Diao, Xungang [Solar Film Laboratory, School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 100191 (China)


    ZnO:Al (ZAO) thin films have been deposited on flexible PET substrates using a plasma damage-free facing target sputtering system at room temperature. The structure, surface morphology, electrical and optical properties were investigated as a function of working power. All the samples have a highly preferred orientation of the c-axis perpendicular to the PET substrate and have a high quality surface. With increased working power, the carrier concentration changes slightly, the mobility increases at the beginning and decreases after it reaches a maximum value, in line with electrical conductivity. The figure of merit has been significantly improved with increasing of the working power. Under the optimized condition, the lowest resistivity of 1.3 × 10{sup −3} Ω cm with a sheet resistance of 29 Ω/□ and the relative visible transmittance above 93% in the visible region were obtained.

  18. Post-target produced [{sup 18}F]F{sub 2} in the production of PET radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Forsback, Sarita; Solin, Olof [Turku PET Centre, Turku (Finland). Radiopharmaceutical Chemistry Lab. and Accelerator Lab.


    Electrophilic radiofluorination was successfully carried out in the early years of PET radiochemistry due to its ease and fast reaction speed. However, at the present, the use of electrophilic methods is limited due to low specific activity (SA). Post-target produced [{sup 18}F]F{sub 2} has significantly higher SA compared to other electrophilic approaches, and it has been used in the production of clinical PET radiopharmaceuticals at the Turku PET Centre for years. Here, we summarize the synthesis and use of these radiopharmaceuticals, namely [{sup 18}F]FDOPA, [{sup 18}F] CFT, [{sup 18}F]EF5 and [{sup 18}F]FBPA.

  19. Guidelines to PET measurements of the target occupancy in the brain for drug development

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Varrone, Andrea; Gulyas, Balazs; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatric Research, Stockholm (Sweden); Salvadori, Piero [CNR Istituto di Fisiologia Clinica, Pisa (Italy); Gee, Antony [Kings College London, Department of Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Windhorst, Albert; Lammertsma, Adriaan A. [VU University Medical Center, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Vercouillie, Johnny [Universite Francois Rabelais de Tours, UMR Inserm U930, Tours (France); Bormans, Guy [KU Leuven, Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, Leuven (Belgium)


    This guideline summarizes the current view of the European Association of Nuclear Medicine Drug Development Committee. The purpose of this guideline is to guarantee a high standard of PET studies that are aimed at measuring target occupancy in the brain within the framework of development programs of drugs that act within the central nervous system (CNS drugs). This guideline is intended to present information specifically adapted to European practice. The information provided should be applied within the context of local conditions and regulations. (orig.)

  20. Targeting MT1-MMP as an ImmunoPET-Based Strategy for Imaging Gliomas.

    Directory of Open Access Journals (Sweden)

    A G de Lucas

    -specific-contrast imaging of MT1-MMP positive GBM tumors and provided strong evidence for utility of MT1-MMP-targeted immunoPET as an alternate to nonspecific imaging of GBM.

  1. Non-target activity detection by post-radioembolization yttrium-90 PET/CT: Image assessment technique and case examples

    Directory of Open Access Journals (Sweden)

    Yung Hsiang eKao


    Full Text Available High-resolution yttrium-90 (90Y imaging of post-radioembolization microsphere biodistribution may be achieved by conventional positron emission tomography with integrated computed tomography (PET/CT scanners that have time-of-flight capability. However, reconstructed 90Y PET/CT images have high background noise, making non-target activity detection technically challenging. This educational article describes our image assessment technique for non-target activity detection by 90Y PET/CT which qualitatively overcomes the problem of background noise. We present selected case examples of non-target activity in untargeted liver, stomach, gallbladder, chest wall and kidney, supported by angiography and 90Y bremsstrahlung single photon emission computed tomography with integrated computed tomography (SPECT/CT or technetium-99m macroaggregated albumin SPECT/CT.

  2. Non-Target Activity Detection by Post-Radioembolization Yttrium-90 PET/CT: Image Assessment Technique and Case Examples. (United States)

    Kao, Yung Hsiang; Tan, Andrew E H; Lo, Richard H G; Tay, Kiang Hiong; Tan, Bien Soo; Chow, Pierce K H; Ng, David C E; Goh, Anthony S W


    High resolution yttrium-90 ((90)Y) imaging of post-radioembolization microsphere biodistribution may be achieved by conventional positron emission tomography with integrated computed tomography (PET/CT) scanners that have time-of-flight capability. However, reconstructed (90)Y PET/CT images have high background noise, making non-target activity detection technically challenging. This educational article describes our image assessment technique for non-target activity detection by (90)Y PET/CT, which qualitatively overcomes the problem of background noise. We present selected case examples of non-target activity in untargeted liver, stomach, gallbladder, chest wall, and kidney, supported by angiography and (90)Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) or technetium-99m macroaggregated albumin SPECT/CT.

  3. Comparison of quantitative PCR assays for Escherichia coli targeting ribosomal RNA and single copy genes (United States)

    Aims: Compare specificity and sensitivity of quantitative PCR (qPCR) assays targeting single and multi-copy gene regions of Escherichia coli. Methods and Results: A previously reported assay targeting the uidA gene (uidA405) was used as the basis for comparing the taxono...

  4. Human biodistribution and radiation dosimetry of novel PET probes targeting the deoxyribonucleoside salvage pathway

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenberg, Johannes [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, Los Angeles, CA (United States); Medical University of Vienna, Department of Pediatrics, Vienna (Austria); Radu, Caius G.; Tran, Andrew Q.; Phelps, Michael E.; Satyamurthy, Nagichettiar [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, Los Angeles, CA (United States); Benz, Matthias; Fueger, Barbara; Czernin, Johannes; Schiepers, Christiaan [David Geffen School of Medicine, University of California, Department of Molecular and Medical Pharmacology, Ahmanson Biological Imaging Division, Los Angeles, CA (United States); Witte, Owen N. [David Geffen School of Medicine, University of California, Howard Hughes Medical Institute and Department of Microbiology, Immunology, and Molecular Genetics, Los Angeles, CA (United States)


    Deoxycytidine kinase (dCK) is a rate-limiting enzyme in deoxyribonucleoside salvage, a metabolic pathway involved in the production and maintenance of a balanced pool of deoxyribonucleoside triphosphates (dNTPs) for DNA synthesis. dCK phosphorylates and therefore activates nucleoside analogs such as cytarabine, gemcitabine, decitabine, cladribine, and clofarabine that are used routinely in cancer therapy. Imaging probes that target dCK might allow stratifying patients into likely responders and nonresponders with dCK-dependent prodrugs. Here we present the biodistribution and radiation dosimetry of three fluorinated dCK substrates, {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC, developed for positron emission tomography (PET) imaging of dCK activity in vivo. PET studies were performed in nine healthy human volunteers, three for each probe. After a transmission scan, the radiopharmaceutical was injected intravenously and three sequential emission scans acquired from the base of the skull to mid-thigh. Regions of interest encompassing visible organs were drawn on the first PET scan and copied to the subsequent scans. Activity in target organs was determined and absorbed dose estimated with OLINDA/EXM. The standardized uptake value was calculated for various organs at different times. Renal excretion was common to all three probes. Bone marrow had higher uptake for L-{sup 18}F-FAC and L-{sup 18}F-FMAC than {sup 18}F-FAC. Prominent liver uptake was seen in L-{sup 18}F-FMAC and L-{sup 18}F-FAC, whereas splenic activity was highest for {sup 18}F-FAC. Muscle uptake was also highest for {sup 18}F-FAC. The critical organ was the bladder wall for all three probes. The effective dose was 0.00524, 0.00755, and 0.00910 mSv/MBq for {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC, respectively. The biodistribution of {sup 18}F-FAC, L-{sup 18}F-FAC, and L-{sup 18}F-FMAC in humans reveals similarities and differences. Differences may be explained by different probe

  5. Trackable and Targeted Phage as Positron Emission Tomography (PET Agent for Cancer Imaging

    Directory of Open Access Journals (Sweden)

    Zibo Li, Qiaoling Jin, Chiunwei Huang, Siva Dasa, Liaohai Chen, Li-peng Yap, Shuanglong Liu, Hancheng Cai, Ryan Park, Peter S Conti


    Full Text Available The recent advancement of nanotechnology has provided unprecedented opportunities for the development of nanoparticle enabled technologies for detecting and treating cancer. Here, we reported the construction of a PET trackable organic nanoplatform based on phage particle for targeted tumor imaging. Method: The integrin αvβ3 targeted phage nanoparticle was constructed by expressing RGD peptides on its surface. The target binding affinity of this engineered phage particle was evaluated in vitro. A bifunctional chelator (BFC 1,4,7,10-tetraazadodecane-N,N',N",N"'-tetraacetic acid (DOTA or 4-((8-amino-3,6,10,13,16,19-hexaazabicyclo [6.6.6] icosane-1-ylamino methyl benzoic acid (AmBaSar was then conjugated to the phage surface for 64Cu2+ chelation. After 64Cu radiolabeling, microPET imaging was performed in U87MG tumor model and the receptor specificity was confirmed by blocking experiments. Results: The phage-RGD demonstrated target specificity based on ELISA experiment. According to the TEM images, the morphology of the phage was unchanged after the modification with BFCs. The labeling yield was 25 ± 4% for 64Cu-DOTA-phage-RGD and 46 ± 5% for 64Cu-AmBaSar-phage-RGD, respectively. At 1 h time point, 64Cu-DOTA-phage-RGD and 64Cu-AmBaSar-phage-RGD have comparable tumor uptake (~ 8%ID/g. However, 64Cu-AmBaSar-phage-RGD showed significantly higher tumor uptake (13.2 ± 1.5 %ID/g, P<0.05 at late time points compared with 64Cu-DOTA-phage-RGD (10 ± 1.2 %ID/g. 64Cu-AmBaSar-phage-RGD also demonstrated significantly lower liver uptake, which could be attributed to the stability difference between these chelators. There is no significant difference between two tracers regarding the uptake in kidney and muscle at all time points tested. In order to confirm the receptor specificity, blocking experiment was performed. In the RGD blocking experiment, the cold RGD peptide was injected 2 min before the administration of 64Cu-AmBaSar-phage-RGD. Tumor uptake was

  6. 3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate. (United States)

    Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard


    Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

  7. The development of PET/CT in determining gross tumor target volume of esophageal carcinoma in precise radiotherapy%PET/CT确定食管癌大体靶区的研究进展

    Institute of Scientific and Technical Information of China (English)

    张炜; 宋轶鹏; 姜翠芳


    随着功能影像及分子影像的发展,PET/CT逐渐成为辅助制定肿瘤最佳精确放疗计划的成像方式.许多研究支持18 F-FDG PET/CT用于精确放疗中食管癌的靶区勾画,然而18F-FDGPET/CT在食管癌靶区勾画中的有效性尚需进一步研究.该文主要对18F-FDG PET/CT用于食管癌原发病灶、区域转移淋巴结GTV勾画的应用价值及有效性等方面的研究进行综述.%As the development of functional and molecular imaging,PET/CT gradually becomes one of methods in optimizing cancer radiotherapy treatment planning.Currently,numerous hospitals routinely use 18F-FDG PET/CT for the delineation of target volume in esophageal carcinoma (EC).However,the validity of 18F-FDG PET/CT in the delineation of target volume for EC is limited and needs further clinical validation.This review focuses on the value and validity of 18F-FDG PET/CT in the delineation of gross tumor target volume of EC primary lesions and regional lymph nodes.

  8. Utility of FMISO PET in advanced head and neck cancer treated with chemoradiation incorporating a hypoxia-targeting chemotherapy agent

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, Melbourne (Australia); University of Melbourne, Department of Medicine, St Vincent' s Medical School, Melbourne (Australia); Rischin, Danny [University of Melbourne, Department of Medicine, St Vincent' s Medical School, Melbourne (Australia); Peter MacCallum Cancer Centre, Division of Haematology and Medical Oncology, Melbourne (Australia); Fisher, Richard [Peter MacCallum Cancer Centre, Centre for Biostatistics and Clinical Trials, Melbourne (Australia); Binns, David [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, Melbourne (Australia); Scott, Andrew M. [Austin Hospital, Centre for PET, and Ludwig Institute for Cancer Research, Melbourne (Australia); Peters, Lester J. [Peter MacCallum Cancer Centre, Division of Radiation Oncology, Melbourne (Australia)


    The purpose of the study was to evaluate [{sup 18}F]fluoromisonidazole (FMISO) PET in advanced head and neck cancer during hypoxia-targeting therapy. Fifteen of 16 patients in a phase I trial of chemoradiation plus tirapazamine (specific cytotoxin for hypoxic cells) in advanced (T3/4 and/or N2/3) head and neck cancer underwent serial [{sup 18}F]fluorodeoxyglucose (FDG) and FMISO PET. We have previously reported excellent early clinical outcome of these patients and now review FMISO PET results in the context of longer follow-up of this patient cohort. Based on blinded qualitative scoring by two readers, FMISO PET was positive in 13/15 patients at baseline: 12/15 of primary sites and 8/13 neck nodes were scored as positive. All sites of corresponding FDG and FMISO abnormality at baseline showed marked qualitative reduction of uptake within 4 weeks of commencing therapy, consistent with effective hypoxia-targeted therapy. With a median follow-up of 6.9 years, there have been only four locoregional failures, while three other patients have died of metachronous lung cancer. The 5-year overall survival was 50% (95% CI 27-73%), the 5-year failure-free survival was 44% (95% CI 22-68%) and the 5-year freedom from locoregional failure was 68% (95% CI 38-88%). The high prevalence of hypoxia demonstrated on FMISO PET imaging is consistent with the advanced disease stage of these patients and would be expected to predict an adverse prognosis. Evidence of the early resolution of FMISO abnormality during treatment, associated with excellent locoregional control in this patient cohort, supports further investigation of hypoxia-targeting agents in advanced head and neck cancer. (orig.)

  9. Separation of {sup 90}Nb from zirconium target for application in immuno-PET

    Energy Technology Data Exchange (ETDEWEB)

    Radchenko, V.; Roesch, F. [Mainz Univ. (Germany). Inst. of Nuclear Chemistry; Filosofov, D.V.; Bochko, O.K.; Lebedev, N.A.; Rakhimov, A.V. [Joint Institute for Nuclear Research, Dubna, Moscow Region (Russian Federation). Dzhelepov Laboratory of Nuclear Problems; Hauser, H.; Eisenhut, M. [German Cancer Research Center, Heidelberg (Germany). Radiopharmaceutical Chemistry; Aksenov, N.V.; Bozhikov, G.A. [Joint Institute for Nuclear Research, Dubna, Moscow Region (Russian Federation). Flerov Laboratory of Nuclear Reactions; Ponsard, B. [Belgian Nuclear Research Centre (SCKCEN), Mol (Belgium). Radioisotopes and NTD Silicon Production


    Fast progressing immuno-PET asks to explore new radionuclides. One of the promising candidates is {sup 90}Nb. It has a half-life of 14.6 h that allows visualizing and quantifying biological processes with medium and slow kinetics, such as tumor accumulation of antibodies and antibodies fragments or drug delivery systems and nanoparticles. {sup 90}Nb exhibits a positron branching of 53% and an average kinetic energy of emitted positrons of E{sub mean} = 0.35 MeV. Currently, radionuclide production routes and NbV labeling techniques are explored to turn this radionuclide into a useful imaging probe. However, efficient separation of {sup 90}Nb from irradiated targets remains in challenge. Ion exchange based separation of {sup 90}Nb from zirconium targets was investigated in systems AG 1 x 8 - HCl/H{sub 2}O{sub 2} and UTEVA-HCl. {sup 95}Nb (t{sub 1/2} = 35.0 d), {sup 95}Zr (t{sub 1/2} = 64.0 d) and {sup 92m}Nb (t{sub 1/2} = 10.15 d) were chosen for studies on distribution coefficients. Separation after AG 1 x 8 anion exchange yields 99% of {sup 90/95}Nb. Subsequent use of a solid-phase extraction step on UTEVA resin further decontaminates {sup 90/95}Nb from traces of zirconium with yields 95% of {sup 90/95}Nb. A semi-automated separation takes one hour to obtain an overall recovery of {sup 90/95}Nb of 90%. The amount of Zr was reduced by factor of 10{sup 8}. The selected separation provides rapid preparation (< 1 h) of high purity {sup 90}Nb appropriate for the synthesis of {sup 90}Nb-radiopharmaceuticals, relevant for purposes of immuno-PET. Applying the radioniobium obtained, {sup 90/95}Nb-labeling of a monoclonal antibody (rituximab) modified with desferrioxamine achieved labeling yields of > 90% after 1 h incubation at room temperature. (orig.)

  10. The impact of PET and SPECT on dosimetry for targeted radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Flux, G. [Dept. of Physics, Royal Marsden Hospital, London (United Kingdom); Bardies, M. [INSERM UMR 601, Nantes (France); Monsieurs, M. [Dept. Anatomy, Embryology, Histology and Medical Physics, Ghent Univ. (Belgium); Savolainen, S. [HUS, Medical Imaging Centre and Dept. of Physical Sciences, Univ. of Helsinki (Finland); Strand, S.E. [Medical Radiation Physics, Dept. of Clinical Sciences, Lund Univ (Sweden); Lassmann, M. [Klinik und Poliklinik fuer Nuklearmedizin der Univ. Wuerzburg (Germany)


    Targeted radionuclide therapy (TRT) is an increasingly used treatment modality for a range of cancers. To date, few treatments have involved the use of dosimetry either to plan treatment or to retrospectively ascertain the absorbed dose delivered during treatment. Also the correlation between absorbed dose and biological effect has been difficult to establish. Tomographic methods permit the determination of the activity volume on a macroscopic scale at different time points. Proper attenuation correction in tomographic imaging requires a patient-specific attenuation map. This can be obtained from scintillation-camera transmission scanning, CT, or by using segmented scatter-emission images. Attenuation corrections can be performed either on the projection images, on the reconstructed images, or as part of an iterative reconstruction method. The problem of image quantification for therapy radionuclides, particularly for I-131, is exacerbated by the fact that most cameras are optimised for diagnostic imaging with Tc-99m. In addition, problems may arise when high activities are to be measured due to count losses and mis-positioned events, because of insufficient pile-up and dead time correction methods. Sufficient image quantification, however, is only possible if all effects that degrade the quantitative content of the image have been corrected for. Monte Carlo simulations are an appealing tool that can help to model interactions occurring in the patient or in the detector system. This is helpful to develop and test correction techniques, or to help to define detectors better suited to quantitative imaging. PET is probably the most accurate imaging method for the determination of activity concentrations in tissue. PET imaging can be considered for pre-therapeutic treatment planning but ideally requires the use of a radioisotope from the same element as that used for treatment (e.g. I-124 for I-131; Y-86 for Y-90). Problems, however, are that - some of the positron

  11. SU-E-CAMPUS-I-06: Y90 PET/CT for the Instantaneous Determination of Both Target and Non-Target Absorbed Doses Following Hepatic Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Pasciak, A; Kao, J [University of Tennessee Medical Center, Knoxville, TN (United States)


    Purpose The process of converting Yttrium-90 (Y90) PET/CT images into 3D absorbed dose maps will be explained. The simple methods presented will allow the medical physicst to analyze Y90 PET images following radioembolization and determine the absorbed dose to tumor, normal liver parenchyma and other areas of interest, without application of Monte-Carlo radiation transport or dose-point-kernel (DPK) convolution. Methods Absorbed dose can be computed from Y90 PET/CT images based on the premise that radioembolization is a permanent implant with a constant relative activity distribution after infusion. Many Y90 PET/CT publications have used DPK convolution to obtain 3D absorbed dose maps. However, this method requires specialized software limiting clinical utility. The Local Deposition method, an alternative to DPK convolution, can be used to obtain absorbed dose and requires no additional computer processing. Pixel values from regions of interest drawn on Y90 PET/CT images can be converted to absorbed dose (Gy) by multiplication with a scalar constant. Results There is evidence that suggests the Local Deposition method may actually be more accurate than DPK convolution and it has been successfully used in a recent Y90 PET/CT publication. We have analytically compared dose-volume-histograms (DVH) for phantom hot-spheres to determine the difference between the DPK and Local Deposition methods, as a function of PET scanner point-spread-function for Y90. We have found that for PET/CT systems with a FWHM greater than 3.0 mm when imaging Y90, the Local Deposition Method provides a more accurate representation of DVH, regardless of target size than DPK convolution. Conclusion Using the Local Deposition Method, post-radioembolization Y90 PET/CT images can be transformed into 3D absorbed dose maps of the liver. An interventional radiologist or a Medical Physicist can perform this transformation in a clinical setting, allowing for rapid prediction of treatment efficacy by

  12. Fluorescence assays for monitoring RNA-ligand interactions and riboswitch-targeted drug discovery screening. (United States)

    Liu, J; Zeng, C; Zhou, S; Means, J A; Hines, J V


    Riboswitches and other noncoding regulatory RNA are intriguing targets for the development of therapeutic agents. A significant challenge in the drug discovery process, however, is the identification of potent compounds that bind the target RNA specifically and disrupt its function. Essential to this process is an effectively designed cascade of screening assays. A screening cascade for identifying compounds that target the T box riboswitch antiterminator element is described. In the primary assays, moderate to higher throughput screening of compound libraries is achieved by combining the sensitivity of fluorescence techniques with functionally relevant assays. Active compounds are then validated and the binding to target RNA further characterized in secondary assays. The cascade of assays monitor ligand-induced changes in the steady-state fluorescence of an attached dye or internally incorporated 2-aminopurine; the fluorescence anisotropy of an RNA complex; and, the thermal denaturation fluorescence profile of a fluorophore-quencher labeled RNA. While the assays described have been developed for T box riboswitch-targeted drug discovery, the fluorescence methods and screening cascade design principles can be applied to drug discovery efforts targeted toward other medicinally relevant noncoding RNA.

  13. SU-E-I-81: Targeting of HER2-Expressing Tumors with Dual PET-MR Imaging Probes

    Energy Technology Data Exchange (ETDEWEB)

    Xu, P; Peng, Y; Sun, M; Yang, X [Suzhou Institute of Biomedical Engineering and Technology Chinese Academy o, Suzhou, Jiangsu (China)


    Purpose: The detection of human epidermal growth factor receptor type 2 (HER2) expression in malignant tumors provides important information influencing patient management. Radionuclide in vivo imaging of HER2 may permit the detection of HER2 in both primary tumors and metastases by a single noninvasive procedure. Trastuzumab, effective in about 15 % of women with breast cancer, downregulates signalling through the Akt/PI3K and MAPK pathways.These pathways modulate metabolism which can be monitored by positron emission tomography (PET) and magnetic resonance imaging (MRI). Methods: The relationship between response of HER2 overexpressing tumours and changes in imaging PET or SPECT and MRI will be examined by a integrated bimodal imaging probe.Small (7 kDa) high-affinity anti-HER2 Affibody molecules and KCCYSL targeting peptide may be suitable tracers for visualization of HER2-expressing tumors. Peptide-conjugated iron oxide nanoparticles (Fe3O4 NPs) as MRI imaging and CB-TE2A as PET imaging are integrated into a single synthetic molecule in the HER2 positive cancer. Results: One of targeted contrast bimodal imaging probe agents was synthesized and evaluated to target HER2-expressing tumors in a HER2 positive rat model. We will report the newest results regarding the development of bimodal imaging probes. Conclusion: The preliminary results of the bimodal imaging probe presents high correlation of MRI signal and PET imaging intensity in vivo. This unique feature can hardly be obtained by single model contrast agents. It is envisioned that this bimodal agents can hold great potential for accurate detection of HER2-expressing tumors which are critical for clinical management of the disease.

  14. Quantification of Human Kallikrein-Related Peptidases in Biological Fluids by Multiplatform Targeted Mass Spectrometry Assays. (United States)

    Karakosta, Theano D; Soosaipillai, Antoninus; Diamandis, Eleftherios P; Batruch, Ihor; Drabovich, Andrei P


    Human kallikrein-related peptidases (KLKs) are a group of 15 secreted serine proteases encoded by the largest contiguous cluster of protease genes in the human genome. KLKs are involved in coordination of numerous physiological functions including regulation of blood pressure, neuronal plasticity, skin desquamation, and semen liquefaction, and thus represent promising diagnostic and therapeutic targets. Until now, quantification of KLKs in biological and clinical samples was accomplished by enzyme-linked immunosorbent assays (ELISA). Here, we developed multiplex targeted mass spectrometry assays for the simultaneous quantification of all 15 KLKs. Proteotypic peptides for each KLK were carefully selected based on experimental data and multiplexed in single assays. Performance of assays was evaluated using three different mass spectrometry platforms including triple quadrupole, quadrupole-ion trap, and quadrupole-orbitrap instruments. Heavy isotope-labeled synthetic peptides with a quantifying tag were used for absolute quantification of KLKs in sweat, cervico-vaginal fluid, seminal plasma, and blood serum, with limits of detection ranging from 5 to 500 ng/ml. Analytical performance of assays was evaluated by measuring endogenous KLKs in relevant biological fluids, and results were compared with selected ELISAs. The multiplex targeted proteomic assays were demonstrated to be accurate, reproducible, sensitive, and specific alternatives to antibody-based assays. Finally, KLK4, a highly prostate-specific protein and a speculated biomarker of prostate cancer, was unambiguously detected and quantified by immunoenrichment-SRM assay in seminal plasma and blood serum samples from individuals with confirmed prostate cancer and negative biopsy. Mass spectrometry revealed exclusively the presence of a secreted isoform and thus unequivocally resolved earlier disputes about KLK4 identity in seminal plasma. Measurements of KLK4 in either 41 seminal plasma or 58 blood serum samples

  15. Design, synthesis and evaluation of (18)F-labeled bradykinin B1 receptor-targeting small molecules for PET imaging. (United States)

    Zhang, Zhengxing; Kuo, Hsiou-Ting; Lau, Joseph; Jenni, Silvia; Zhang, Chengcheng; Zeisler, Jutta; Bénard, François; Lin, Kuo-Shyan


    Two fluorine-18 ((18)F) labeled bradykinin B1 receptor (B1R)-targeting small molecules, (18)F-Z02035 and (18)F-Z02165, were synthesized and evaluated for imaging with positron emission tomography (PET). Z02035 and Z02165 were derived from potent antagonists, and showed high binding affinity (0.93±0.44 and 2.80±0.50nM, respectively) to B1R. (18)F-Z02035 and (18)F-Z02165 were prepared by coupling 2-[(18)F]fluoroethyl tosylate with their respective precursors, and were obtained in 10±5 (n=4) and 22±14% (n=3), respectively, decay-corrected radiochemical yield with >99% radiochemical purity. (18)F-Z02035 and (18)F-Z02165 exhibited moderate lipophilicity (LogD7.4=1.10 and 0.59, respectively), and were stable in mouse plasma. PET imaging and biodistribution studies in mice showed that both tracers enabled visualization of the B1R-positive HEK293T::hB1R tumor xenografts with better contrast than control B1R-negative HEK293T tumors. Our data indicate that small molecule antagonists can be used as pharmacophores for the design of B1R-targeting PET tracers.

  16. Response to Deep Brain Stimulation in Three Brain Targets with Implications in Mental Disorders: A PET Study in Rats (United States)

    Casquero-Veiga, Marta; Hadar, Ravit; Pascau, Javier; Winter, Christine; Desco, Manuel; Soto-Montenegro, María Luisa


    Objective To investigate metabolic changes in brain networks by deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) and dorsomedial thalamus (DM) using positron emission tomography (PET) in naïve rats. Methods 43 male Wistar rats underwent stereotactic surgery and concentric bipolar platinum-iridium electrodes were bilaterally implanted into one of the three brain sites. [18F]-fluoro-2-deoxy-glucose-PET (18FDG-PET) and computed tomography (CT) scans were performed at the 7th (without DBS) and 9th day (with DBS) after surgery. Stimulation period matched tracer uptake period. Images were acquired with a small-animal PET-CT scanner. Differences in glucose uptake between groups were assessed with Statistical Parametric Mapping. Results DBS induced site-specific metabolic changes, although a common increased metabolic activity in the piriform cortex was found for the three brain targets. mPFC-DBS increased metabolic activity in the striatum, temporal and amygdala, and reduced it in the cerebellum, brainstem (BS) and periaqueductal gray matter (PAG). NAcc-DBS increased metabolic activity in the subiculum and olfactory bulb, and decreased it in the BS, PAG, septum and hypothalamus. DM-DBS increased metabolic activity in the striatum, NAcc and thalamus and decreased it in the temporal and cingulate cortex. Conclusions DBS induced significant changes in 18FDG uptake in brain regions associated with the basal ganglia-thalamo-cortical circuitry. Stimulation of mPFC, NAcc and DM induced different patterns of 18FDG uptake despite interacting with the same circuitries. This may have important implications to DBS research suggesting individualized target selection according to specific neural modulatory requirements. PMID:28033356

  17. The effect of PET/CT on cancer teatment strategies of argon-helium cryoablation targeted therapy%PET/CT对氩氦刀靶向治疗肿瘤策略的影响

    Institute of Scientific and Technical Information of China (English)

    李泉旺; 曹阳; 左明焕; 安超; 刘传波; 胡凯文


    目的 评价全身18F-FDG PET/CT在氩氦刀靶向治疗中的价值.方法回顾100例肿瘤患者冷冻治疗前目标病灶CT检查、全身PET/CT检查.结果 根据PET/CT和CT结果,100例患者中,肺内病灶53例,肝内病灶22例,盆腔病灶11例;23例临床分期改变,17例治疗计划改变.12例肺内病灶(12/53,22.64%)、3例肝内病灶(3/22,13.64%)、2例盆腔病灶(2/11,18.18%)治疗计划改变.结论 全身PET/CT可提供更多有效的信息,对制定氩氦刀冷冻治疗策略有显著指导意义.%Objective To observe the value of whole body 18F-FDG PET/CT in cryocare targeted cryoablation therapy.Methods Totolly 100 cancer patients were examined with CT and whole body PET/CT before therapy. Results According to PET/CT and CT, lung tumors were detected in 53 patients, liver neoplasms were found in 22 patients, while pelvic masses were shown in 11 patients. Clinical stage were changed in 23 cases, while the treatment plan were changed in 17 cases, including 12 cases of lung tumors (12/53, 22.64%), 3 casesof liver neoplasms (3/22, 13.64%) and 2 cases of pelvic masses (2/11, 18. 18 % ). Conclusion Whole body PET/CT can provide effective information for the treatment strategy of cryocare targeted cryoablation therapy.

  18. Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays (United States)

    de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra


    Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. PMID:27306095

  19. Threshold segmentation for PET target volume delineation in radiation treatment planning: the role of target-to-background ratio and target size. (United States)

    Brambilla, M; Matheoud, R; Secco, C; Loi, G; Krengli, M; Inglese, E


    A multivariable approach was adopted to study the dependence of the percentage threshold [TH(%)] used to define the boundaries of 18F-FDG positive tissue on emission scan duration (ESD) and activity at the start of acquisition (Aacq) for different target sizes and target-to-background (T/B) ratios. An anthropomorphic model, at least for counting rate characteristics, was used to study this dependence in conditions resembling the ones that can be encountered in the clinical studies. An annular ring of water bags of 3 cm thickness was fitted over an International Electro-technical Commission (IEC) phantom in order to obtain counting rates similar to those found in average patients. The scatter fraction of the modified IEC phantom was similar to the mean scatter fraction measured on patients, with a similar scanner. A supplemental set of microhollow spheres was positioned inside the phantom. The NEMA NU 2-2001 scatter phantom was positioned at the end of the IEC phantom to approximate the clinical situation of having activity that extends beyond the scanner field of view. The phantoms were filled with a solution of water and 18F (12 kBq/mL) and the spheres with various T/B ratios of 22.5, 10.3, and 3.6. Sequential imaging was performed to acquire PET images with varying background activity concentrations of about 12, 9, 6.4, 5.3, and 3.1 kBq/mL. The ESD was set to 60, 120, 180, and 240 s/bed. Data were fitted using two distinct multiple linear regression models for sphere ID 10 mm. The fittings of both models were good with an R2 of 0.86 in both cases. Neither ESD nor Aacq resulted as significant predictors of the TH(%). For sphere ID 10 mm the explanatory power of the target size and T/B ratio were reversed, the T/B ratio being now the most important predictor of the TH(%). Both the target size and T/B ratio play a major role in explaining the variance of the TH(%), throughout the whole range of target sizes and T/B ratios examined. Thus, algorithms aimed at

  20. Sensitive, simultaneous quantitation of two unlabeled DNA targets using a magnetic nanoparticle-enzyme sandwich assay. (United States)

    Zhang, Yue; Pilapong, Chalermchai; Guo, Yuan; Ling, Zhenlian; Cespedes, Oscar; Quirke, Philip; Zhou, Dejian


    We report herein the development of a simple, sensitive colorimetric magnetic nanoparticle (MNP)-enzyme-based DNA sandwich assay that is suitable for simultaneous, label-free quantitation of two DNA targets down to 50 fM level. It can also effectively discriminate single-nucleotide polymorphisms (SNPs) in genes associated with human cancers (KRAS codon 12/13 SNPs). This assay uses a pair of specific DNA probes, one being covalently conjugated to an MNP for target capture and the other being linked to an enzyme for signal amplification, to sandwich a DNA target, allowing for convenient magnetic separation and subsequent efficient enzymatic signal amplification for high sensitivity. Careful optimization of the MNP surfaces and assay conditions greatly reduced the background, allowing for sensitive, specific detection of as little as 5 amol (50 fM in 100 μL) of target DNA. Moreover, this sensor is robust, it can effectively discriminate cancer-specific SNPs against the wild-type noncancer target, and it works efficiently in 10% human serum. Furthermore, this sensor can simultaneously quantitate two different DNA targets by using two pairs of unique capture- and signal-DNA probes specific for each target. This general, simple, and sensitive DNA sensor appears to be well-suited for a wide range of genetics-based biosensing and diagnostic applications.

  1. Impact of 18-fluorodeoxyglucose positron emission tomography on computed tomography defined target volumes in radiation treatment planning of esophageal cancer: reduction in geographic misses with equal inter-observer variability: PET/CT improves esophageal target definition. (United States)

    Schreurs, L M A; Busz, D M; Paardekooper, G M R M; Beukema, J C; Jager, P L; Van der Jagt, E J; van Dam, G M; Groen, H; Plukker, J Th M; Langendijk, J A


    Target volume definition in modern radiotherapy is based on planning computed tomography (CT). So far, 18-fluorodeoxyglucose positron emission tomography (FDG-PET) has not been included in planning modality in volume definition of esophageal cancer. This study evaluates fusion of FDG-PET and CT in patients with esophageal cancer in terms of geographic misses and inter-observer variability in volume definition. In 28 esophageal cancer patients, gross, clinical and planning tumor volumes (GTV; CTV; PTV) were defined on planning CT by three radiation oncologists. After software-based emission tomography and computed tomography (PET/CT) fusion, tumor delineations were redefined by the same radiation-oncologists. Concordance indexes (CCI's) for CT and PET/CT based GTV, CTV and PTV were calculated for each pair of observers. Incorporation of PET/CT modified tumor delineation in 17/28 subjects (61%) in cranial and/or caudal direction. Mean concordance indexes for CT-based CTV and PTV were 72 (55-86)% and 77 (61-88)%, respectively, vs. 72 (47-99)% and 76 (54-87)% for PET/CT-based CTV and PTV. Paired analyses showed no significant difference in CCI between CT and PET/CT. Combining FDG-PET and CT may improve target volume definition with less geographic misses, but without significant effects on inter-observer variability in esophageal cancer.

  2. Impact of 18FDG-PET/CT on biological target volume (BTV) definition for treatment planning for non-small cell lung cancer patients (United States)

    Devic, Slobodan; Tomic, Nada; Faria, Sergio; Dean, Geoffrey; Lisbona, Robert; Parker, William; Kaufman, Chris; Podgorsak, Ervin B.


    This work represents our effort to test feasibility of FDG-based PET/CT on target volume delineation in radiotherapy treatment planning of NSCLC patients. Different methods have been developed to enable more precise target outlining using PET: Qualitative Visual Method, CTV=2.5 SUV units, linear SUV threshold function method, and CTV=40% Iso of Maximum Uptake Value. We are proposing reconstruction of three biological target volumes: necrotic BTV (same as PTV created by radiation oncologist using CT data), proliferating BTV (based on PET signal to background ratio 1:3) and hypoxic BTV (based on PET signal to background ratio of 1:19). Two IMRT plans were created and compared to the conventional treatment plan: "conservative" IMRT plan delivers 52.5 Gy to the necrotic BTV and 65 Gy to the hypoxic BTV; "radical" IMRT plan delivers 30 Gy to necrotic BTV, 52.5 Gy to proliferating BTV and 65 Gy to hypoxic BTV. Use of BTVs in IMRT plans is attractive because it increases dose to targets considered to need higher doses. It reduces considerably dose to heart and spinal cord, organs considered to limit dose escalation approaches in NSCLC treatment. "Conservative" IMRT approach can be understood as a PET/CT-based concomitant boost to the tumor expressing the highest FDG uptake. "Radical" plan implies deviation from the traditional uniform dose target coverage approach, with the intention of achieving better surrounding tissue sparing and ultimately allowing for dose escalation protocols relying on biologically based treatment planning.

  3. Evaluation of the combined effects of target size, respiratory motion and background activity on 3D and 4D PET/CT images

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sang-June; Ionascu, Dan; Killoran, Joseph; Chin, Lee; Berbeco, Ross [Department of Radiation Oncology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 (United States); Mamede, Marcelo; Gerbaudo, Victor H [Division of Nuclear Medicine, Department of Radiology, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States)], E-mail:


    Gated (4D) PET/CT has the potential to greatly improve the accuracy of radiotherapy at treatment sites where internal organ motion is significant. However, the best methodology for applying 4D-PET/CT to target definition is not currently well established. With the goal of better understanding how to best apply 4D information to radiotherapy, initial studies were performed to investigate the effect of target size, respiratory motion and target-to-background activity concentration ratio (TBR) on 3D (ungated) and 4D PET images. Using a PET/CT scanner with 4D or gating capability, a full 3D-PET scan corrected with a 3D attenuation map from 3D-CT scan and a respiratory gated (4D) PET scan corrected with corresponding attenuation maps from 4D-CT were performed by imaging spherical targets (0.5-26.5 mL) filled with {sup 18}F-FDG in a dynamic thorax phantom and NEMA IEC body phantom at different TBRs (infinite, 8 and 4). To simulate respiratory motion, the phantoms were driven sinusoidally in the superior-inferior direction with amplitudes of 0, 1 and 2 cm and a period of 4.5 s. Recovery coefficients were determined on PET images. In addition, gating methods using different numbers of gating bins (1-20 bins) were evaluated with image noise and temporal resolution. For evaluation, volume recovery coefficient, signal-to-noise ratio and contrast-to-noise ratio were calculated as a function of the number of gating bins. Moreover, the optimum thresholds which give accurate moving target volumes were obtained for 3D and 4D images. The partial volume effect and signal loss in the 3D-PET images due to the limited PET resolution and the respiratory motion, respectively were measured. The results show that signal loss depends on both the amplitude and pattern of respiratory motion. However, the 4D-PET successfully recovers most of the loss induced by the respiratory motion. The 5-bin gating method gives the best temporal resolution with acceptable image noise. The results based on

  4. Optimal de novo design of MRM experiments for rapid assay development in targeted proteomics. (United States)

    Bertsch, Andreas; Jung, Stephan; Zerck, Alexandra; Pfeifer, Nico; Nahnsen, Sven; Henneges, Carsten; Nordheim, Alfred; Kohlbacher, Oliver


    Targeted proteomic approaches such as multiple reaction monitoring (MRM) overcome problems associated with classical shotgun mass spectrometry experiments. Developing MRM quantitation assays can be time consuming, because relevant peptide representatives of the proteins must be found and their retention time and the product ions must be determined. Given the transitions, hundreds to thousands of them can be scheduled into one experiment run. However, it is difficult to select which of the transitions should be included into a measurement. We present a novel algorithm that allows the construction of MRM assays from the sequence of the targeted proteins alone. This enables the rapid development of targeted MRM experiments without large libraries of transitions or peptide spectra. The approach relies on combinatorial optimization in combination with machine learning techniques to predict proteotypicity, retention time, and fragmentation of peptides. The resulting potential transitions are scheduled optimally by solving an integer linear program. We demonstrate that fully automated construction of MRM experiments from protein sequences alone is possible and over 80% coverage of the targeted proteins can be achieved without further optimization of the assay.

  5. Current Status of Targets and Assays for Anti-HIV Drug Screening

    Institute of Scientific and Technical Information of China (English)


    HIV/AIDS is one of the most serious public health challenges globally. Despite the great efforts that are being devoted to prevent, treat and to better understand the disease, it is one of the main causes of morbidity and mortality worldwide. Currently, there are 30 drugs or combinations of drugs approved by FDA. Because of the side-effects, price and drug resistance, it is essential to discover new targets, to develop new technology and to find new anti-HIV drugs. This review summarizes the major targets and assays currently used in anti-HIV drug screening.

  6. 呼吸门控PET/CT对于肺癌放疗靶区勾画的指导%Guiding the target delineation in radiation therapy of lung cancer by respiratory gated PET/CT

    Institute of Scientific and Technical Information of China (English)

    张艳兰; 孙琦婷; 武萍; 郝新忠; 秦志星; 程鹏亮; 武志芳; 李思进


    目的 通过对肺部肿瘤进行呼吸门控PET/CT研究,给予肺部肿瘤放疗靶区勾画指导,最终使患者接受合理的照射靶区.方法 对20个恶性结节进行呼吸门控PET/CT与常规PET/CT采集,比较肺部不同位置结节的平均四维PET体积与三维PET体积的差别,以及平均四维CT体积与三维CT体积的差别.以平均四维体积与三维体积的相对差值作为体积间的差异,分别从结节位置、运动幅度研究其对四维体积与三维体积的影响.结果 用两种方法测得的平均四维PET体积比三维PET体积大17.2%.体积相对差值与结节呼吸运动幅度及结节位置有关.下肺和肺门病灶平均四维PET体积与三维PET体积的平均差值为26.5%,远远大于上肺和胸膜病灶的平均差值(2.7%).当结节呼吸运动幅度大于3 mm时,四维与三维PET体积差值的平均值为24.3%;小于3 mm时,平均值为1.8%.平均四维CT体积比三维CT体积大3.9%,体积差值范围为0.2~5.9 cm3,体积比值为1.10±0.32.只有在下肺,平均四维CT体积明显大于三维CT体积,平均差值为11.3%.结论 对于靠近肝脾的下肺结节,用平均四维PET勾画肿瘤靶区更精确些;对于肺门周围的结节,考虑平均四维PET体积作为肿瘤靶区;对于上肺和胸膜的结节,建议采用低剂量呼吸门控扫描且已经考虑了呼吸运动的平均四维CT体积勾画靶区.%Objective To give target outline guidance for lung tumor radiation therapy by respiratory gating (RG) four-dimensional PET/CT for lung cancer.Eventually reasonable radiation target regions in treatment planning are received by patients.Methods Twenty malignant nodules were studied by RG PET/CT and conventional PET/CT.The differences of gross tumor volume defined by average four-dimensional PET and three-dimensional PET were compared in different lung locations.Differences of gross tumor volume defined by average four-dimensional CT and three-dimensional CT were also

  7. Bacterial zoonoses transmitted by Household pets: State of the Art and Future perspectives for targeted research and policy actions

    NARCIS (Netherlands)

    Damborg, P.; Broens, E.M.; Chomel, B.B.; Guenther, S.; Pasmans, F.; Wagenaar, J.A.; Weese, J.S.; Wieler, L.H.; Windahl, U.; Vanrompay, D.; Guardabassi, L.


    The close contact between household pets and people offers favourable conditions for bacterial transmission. In this article, the aetiology, prevalence, transmission, impact on human health and preventative measures are summarized for selected bacterial zoonoses transmissible by household pets. Six

  8. Design, synthesis and validation of integrin {alpha}{sub 2}{beta}{sub 1}-targeted probe for microPET imaging of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chiun-Wei; Li, Zibo; Cai, Hancheng; Chen, Kai; Shahinian, Tony; Conti, Peter S. [University of Southern California, Department of Radiology, Los Angeles, CA (United States)


    The ability of PET to aid in the diagnosis and management of recurrent and/or disseminated metastatic prostate cancer may be enhanced by the development of novel prognostic imaging probes. Accumulating experimental evidence indicates that overexpression of integrin {alpha}{sub 2}{beta}{sub 1} may correlate with progression in human prostate cancer. In this study, {sup 64}Cu-labeled integrin {alpha}{sub 2}{beta}{sub 1}-targeted PET probes were designed and evaluated for the imaging of prostate cancer. DGEA peptides conjugated with a bifunctional chelator (BFC) were developed to image integrin {alpha}{sub 2}{beta}{sub 1} expression with PET in a subcutaneous PC-3 xenograft model. The microPET images were reconstructed by a two-dimensional ordered subsets expectation maximum algorithm. The average radioactivity accumulation within a tumor or an organ was quantified from the multiple region of interest volumes. The PET tracer demonstrated prominent tumor uptake in the PC-3 xenograft (integrin {alpha}{sub 2}{beta}{sub 1}-positive). The receptor specificity was confirmed in a blocking experiment. Moreover, the low tracer uptake in a CWR-22 tumor model (negative control) further confirmed the receptor specificity. The sarcophagine-conjugated DGEA peptide allows noninvasive imaging of tumor-associated {alpha}{sub 2}{beta}{sub 1} expression, which may be a useful PET probe for evaluating the metastatic potential of prostate cancer. (orig.)

  9. Influence of experience and qualification on PET-based target volume delineation. When there is no expert - ask your colleague

    Energy Technology Data Exchange (ETDEWEB)

    Doll, C.; Grosu, A.L.; Nestle, U. [University Medical Center Freiburg, Radiation Oncology Department, Freiburg/Breisgau (Germany); Duncker-Rohr, V. [University Medical Center Freiburg, Radiation Oncology Department, Freiburg/Breisgau (Germany); Ortenau Clinical Center Offenburg, Radiation Oncology Department, Offenburg (Germany); Ruecker, G. [University of Freiburg, Institute of Medical Biometry und Medical Informatics, Freiburg (Germany); Mix, M. [University Medical Center Freiburg, Nuclear Medicine Department, Freiburg (Germany); MacManus, M. [University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Ruysscher, D. de [University Hospital Leuven/KU Leuven, Department of Radiation Oncology, Leuven (Belgium); Vogel, W. [Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam (Netherlands); Eriksen, J.G. [Odense University Hospital, Department of Oncology, Odense (Denmark); Oyen, W. [Radboud University Nijmegen Medical Center, Department of Nuclear Medicine, Nijmegen (Netherlands); Weber, W. [University Medical Center Freiburg, Nuclear Medicine Department, Freiburg (Germany); Memorial Sloan-Kettering Cancer Center, Department of Radiology/Molecular Imaging and Therapy Service, New York (United States)


    The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. In contrast to automatic contouring, research on visual-manual delineation is scarce. The present study investigates the dependency of manual delineation on experience and qualification. A total of 44 international interdisciplinary observers each defined a [{sup 18}F]fluorodeoxyglucose (FDG)-PET based gross tumor volume (GTV) using the same PET/CT scan from a patient with lung cancer. The observers were ''experts'' (E; n = 3), ''experienced interdisciplinary pairs'' (EP; 9 teams of radiation oncologist (RO) + nuclear medicine physician (NP)), ''single field specialists'' (SFS; n = 13), and ''students'' (S; n = 10). Five automatic delineation methods (AM) were also included. Volume sizes and concordance indices within the groups (pCI) and relative to the experts (eCI) were calculated. E (pCI = 0.67) and EP (pCI = 0.53) showed a significantly higher agreement within the groups as compared to SFS (pCI = 0.43, p = 0.03, and p = 0.006). In relation to the experts, EP (eCI = 0.55) showed better concordance compared to SFS (eCI = 0.49) or S (eCI = 0.47). The intermethod variability of the AM (pCI = 0.44) was similar to that of SFS and S, showing poorer agreement with the experts (eCI = 0.35). The results suggest that interdisciplinary cooperation could be beneficial for consistent contouring. Joint delineation by a radiation oncologist and a nuclear medicine physician showed remarkable agreement and better concordance with the experts compared to other specialists. The relevant intermethod variability of the automatic algorithms underlines the need for further standardization and optimization in this field. (orig.) [German] Die Daten aus der Positronenemissionstomographie (PET) werden in vielen Kliniken routinemaessig zur

  10. Mass Spectrometry Based Ultrasensitive DNA Methylation Profiling Using Target Fragmentation Assay. (United States)

    Lin, Xiang-Cheng; Zhang, Ting; Liu, Lan; Tang, Hao; Yu, Ru-Qin; Jiang, Jian-Hui


    Efficient tools for profiling DNA methylation in specific genes are essential for epigenetics and clinical diagnostics. Current DNA methylation profiling techniques have been limited by inconvenient implementation, requirements of specific reagents, and inferior accuracy in quantifying methylation degree. We develop a novel mass spectrometry method, target fragmentation assay (TFA), which enable to profile methylation in specific sequences. This method combines selective capture of DNA target from restricted cleavage of genomic DNA using magnetic separation with MS detection of the nonenzymatic hydrolysates of target DNA. This method is shown to be highly sensitive with a detection limit as low as 0.056 amol, allowing direct profiling of methylation using genome DNA without preamplification. Moreover, this method offers a unique advantage in accurately determining DNA methylation level. The clinical applicability was demonstrated by DNA methylation analysis using prostate tissue samples, implying the potential of this method as a useful tool for DNA methylation profiling in early detection of related diseases.

  11. A phenotypic assay to identify Chikungunya virus inhibitors targeting the nonstructural protein nsP2. (United States)

    Lucas-Hourani, Marianne; Lupan, Alexandru; Desprès, Philippe; Thoret, Sylviane; Pamlard, Olivier; Dubois, Joëlle; Guillou, Catherine; Tangy, Frédéric; Vidalain, Pierre-Olivier; Munier-Lehmann, Hélène


    Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen responsible for an acute infection of abrupt onset, characterized by high fever, polyarthralgia, myalgia, headaches, chills, and rash. In 2006, CHIKV was responsible for an epidemic outbreak of unprecedented magnitude in the Indian Ocean, stressing the need for therapeutic approaches. Since then, we have acquired a better understanding of CHIKV biology, but we are still missing active molecules against this reemerging pathogen. We recently reported that the nonstructural nsP2 protein of CHIKV induces a transcriptional shutoff that allows the virus to block cellular antiviral response. This was demonstrated using various luciferase-based reporter gene assays, including a trans-reporter system where Gal4 DNA binding domain is fused to Fos transcription factor. Here, we turned this assay into a high-throughput screening system to identify small molecules targeting nsP2-mediated shutoff. Among 3040 molecules tested, we identified one natural compound that partially blocks nsP2 activity and inhibits CHIKV replication in vitro. This proof of concept suggests that similar functional assays could be developed to target other viral proteins mediating a cellular shutoff and identify innovative therapeutic molecules.

  12. Impact of [F-18]-fluoro-ethyl-tyrosine PET imaging on target definition for radiation therapy of high-grade glioma

    DEFF Research Database (Denmark)

    af Rosenschold, Per Munck; Costa, Junia; Engelholm, Svend Aage


    BACKGROUND: We sought to assess the impact of amino-acid (18)F-fluoro-ethyl-tyrosine (FET) positron emission tomography (PET) on the volumetric target definition for radiation therapy of high-grade glioma versus the current standard using MRI alone. Specifically, we investigated the influence...

  13. Influence of experience and qualification on PET-based target volume delineation. When there is no expert--ask your colleague

    DEFF Research Database (Denmark)

    Doll, C; Duncker-Rohr, V; Rücker, G;


    BACKGROUND AND PURPOSE: The integration of positron emission tomography (PET) information for target volume delineation in radiation treatment planning is routine in many centers. In contrast to automatic contouring, research on visual-manual delineation is scarce. The present study investigates ...

  14. Detection of early stage atherosclerotic plaques using PET and CT fusion imaging targeting P-selectin in low density lipoprotein receptor-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Ikuko, E-mail: [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Cardiovascular Medicine, Saga University, Saga (Japan); Hasegawa, Koki [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Department of Pathology and Experimental Medicine, Kumamoto University, Kumamoto (Japan); Wada, Yasuhiro [RIKEN Center for Molecular Imaging Science, Kobe (Japan); Hirase, Tetsuaki; Node, Koichi [Department of Cardiovascular Medicine, Saga University, Saga (Japan); Watanabe, Yasuyoshi, E-mail: [RIKEN Center for Molecular Imaging Science, Kobe (Japan)


    Highlights: ► P-selectin regulates leukocyte recruitment as an early stage event of atherogenesis. ► We developed an antibody-based molecular imaging probe targeting P-selectin for PET. ► This is the first report on successful PET imaging for delineation of P-selectin. ► P-selectin is a candidate target for atherosclerotic plaque imaging by clinical PET. -- Abstract: Background: Sensitive detection and qualitative analysis of atherosclerotic plaques are in high demand in cardiovascular clinical settings. The leukocyte–endothelial interaction mediated by an adhesion molecule P-selectin participates in arterial wall inflammation and atherosclerosis. Methods and results: A {sup 64}Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugated anti-P-selectin monoclonal antibody ({sup 64}Cu-DOTA-anti-P-selectin mAb) probe was prepared by conjugating an anti-P-selectin monoclonal antibody with DOTA followed by {sup 64}Cu labeling. Thirty-six hours prior to PET and CT fusion imaging, 3 MBq of {sup 64}Cu-DOTA-anti-P-selectin mAb was intravenously injected into low density lipoprotein receptor-deficient Ldlr-/- mice. After a 180 min PET scan, autoradiography and biodistribution of {sup 64}Cu-DOTA-anti-P-selectin monoclonal antibody was examined using excised aortas. In Ldlr-/- mice fed with a high cholesterol diet for promotion of atherosclerotic plaque development, PET and CT fusion imaging revealed selective and prominent accumulation of the probe in the aortic root. Autoradiography of aortas that demonstrated probe uptake into atherosclerotic plaques was confirmed by Oil red O staining for lipid droplets. In Ldlr-/- mice fed with a chow diet to develop mild atherosclerotic plaques, probe accumulation was barely detectable in the aortic root on PET and CT fusion imaging. Probe biodistribution in aortas was 6.6-fold higher in Ldlr-/- mice fed with a high cholesterol diet than in those fed with a normal chow diet. {sup 64}Cu-DOTA-anti-P-selectin m

  15. Rapid, targeted and culture-free viral infectivity assay in drop-based microfluidics. (United States)

    Tao, Ye; Rotem, Assaf; Zhang, Huidan; Chang, Connie B; Basu, Anindita; Kolawole, Abimbola O; Koehler, Stephan A; Ren, Yukun; Lin, Jeffrey S; Pipas, James M; Feldman, Andrew B; Wobus, Christiane E; Weitz, David A


    A key viral property is infectivity, and its accurate measurement is crucial for the understanding of viral evolution, disease and treatment. Currently viral infectivity is measured using plaque assays, which involve prolonged culturing of host cells, and whose measurement is unable to differentiate between specific strains and is prone to low number fluctuation. We developed a rapid, targeted and culture-free infectivity assay using high-throughput drop-based microfluidics. Single infectious viruses are incubated in a large number of picoliter drops with host cells for one viral replication cycle followed by in-drop gene-specific amplification to detect infection events. Using murine noroviruses (MNV) as a model system, we measure their infectivity and determine the efficacy of a neutralizing antibody for different variants of MNV. Our results are comparable to traditional plaque-based assays and plaque reduction neutralization tests. However, the fast, low-cost, highly accurate genomic-based assay promises to be a superior method for drug screening and isolation of resistant viral strains. Moreover our technique can be adapted to measuring the infectivity of other pathogens, such as bacteria and fungi.

  16. Impact of 18FDG-PET/CT on biological target volume (BTV) definition for treatment planning for non-small cell lung cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Devic, Slobodan [Medical Physics Department, McGill University Health Centre, Montreal, Que. (Canada)]. E-mail:; Tomic, Nada [Medical Physics Department, McGill University Health Centre, Montreal, Que. (Canada); Faria, Sergio [Radiation Oncology Department, McGill University Health Centre, Montreal, Que. (Canada); Dean, Geoffrey [Nuclear Medicine Department, McGill University Health Centre, Montreal, Que. (Canada); Lisbona, Robert [Nuclear Medicine Department, McGill University Health Centre, Montreal, Que. (Canada); Parker, William [Medical Physics Department, McGill University Health Centre, Montreal, Que. (Canada); Kaufman, Chris [Medical Physics Department, McGill University Health Centre, Montreal, Que. (Canada); Podgorsak, Ervin B. [Medical Physics Department, McGill University Health Centre, Montreal, Que. (Canada)


    This work represents our effort to test feasibility of FDG-based PET/CT on target volume delineation in radiotherapy treatment planning of NSCLC patients. Different methods have been developed to enable more precise target outlining using PET: Qualitative Visual Method, CTV=2.5 SUV units, linear SUV threshold function method, and CTV=40% Iso of Maximum Uptake Value. We are proposing reconstruction of three biological target volumes: necrotic BTV (same as PTV created by radiation oncologist using CT data), proliferating BTV (based on PET signal to background ratio 1:3) and hypoxic BTV (based on PET signal to background ratio of 1:19). Two IMRT plans were created and compared to the conventional treatment plan: 'conservative' IMRT plan delivers 52.5 Gy to the necrotic BTV and 65 Gy to the hypoxic BTV; 'radical' IMRT plan delivers 30 Gy to necrotic BTV, 52.5 Gy to proliferating BTV and 65 Gy to hypoxic BTV. Use of BTVs in IMRT plans is attractive because it increases dose to targets considered to need higher doses. It reduces considerably dose to heart and spinal cord, organs considered to limit dose escalation approaches in NSCLC treatment. 'Conservative' IMRT approach can be understood as a PET/CT-based concomitant boost to the tumor expressing the highest FDG uptake. 'Radical' plan implies deviation from the traditional uniform dose target coverage approach, with the intention of achieving better surrounding tissue sparing and ultimately allowing for dose escalation protocols relying on biologically based treatment planning.

  17. Using pathway modules as targets for assay development in xenobiotic screening. (United States)

    Judson, Richard S; Mortensen, Holly M; Shah, Imran; Knudsen, Thomas B; Elloumi, Fathi


    Toxicology and pharmaceutical research is increasingly making use of high throughout-screening (HTS) methods to assess the effects of chemicals on molecular pathways, cells and tissues. Whole-genome microarray analysis provides broad information on the response of biological systems to chemical exposure, but is not practical to use when thousands of chemicals need to be evaluated at multiple doses and time points, as well as across different tissues, species and life-stages. A useful alternative approach is to identify a focused set of genes that can give a coarse picture of systems-level responses and that can be scaled to the evaluation of thousands of chemicals and diverse biological contexts. We demonstrate a computational approach to select in vitro expression assay targets that are informative and broadly distributed in biological pathway space, using the concept of pathway modularity. Canonical pathways are decomposed into subnetworks (modules) of functionally-related genes based on rules such as co-regulated expression, protein-protein interactions, and coordinated physiological activity. Pathway modules are constructed using these rules but are then restricted by the bounds of canonical pathways. We demonstrate this approach using a subset of genes associated with tumor development and cancer progression. Target genes were identified for assay development, and then validated by using independent, published microarray data. The result is a targeted set of genes that are sensitive predictors of whether a chemical will perturb each pathway module. These selected genes could then form the basis for a battery to test for pathway-chemical interactions under many biological contexts using throughput expression-based assays.

  18. Genomic analysis of Campylobacter fetus subspecies: identification of candidate virulence determinants and diagnostic assay targets

    Directory of Open Access Journals (Sweden)

    Sanchez Daniel O


    Full Text Available Abstract Background Campylobacter fetus subspecies venerealis is the causative agent of bovine genital campylobacteriosis, asymptomatic in bulls the disease is spread to female cattle causing extensive reproductive loss. The microbiological and molecular differentiation of C. fetus subsp. venerealis from C. fetus subsp. fetus is extremely difficult. This study describes the analysis of the available C. fetus subsp. venerealis AZUL-94 strain genome (~75–80% to identify elements exclusively found in C. fetus subsp. venerealis strains as potential diagnostic targets and the characterisation of subspecies virulence genes. Results Eighty Kb of genomic sequence (22 contigs was identified as unique to C. fetus subsp. venerealis AZUL-94 and consisted of type IV secretory pathway components, putative plasmid genes and hypothetical proteins. Of the 9 PCR assays developed to target C. fetus subsp. venerealis type IV secretion system genes, 4 of these were specific for C. fetus subsp. venerealis biovar venerealis and did not detect C. fetus subsp. venerealis biovar intermedius. Two assays were specific for C. fetus subsp. venerealis AZUL-94 strain, with a further single assay specific for the AZUL-94 strain and C. fetus subsp. venerealis biovar intermedius (and not the remaining C. fetus subsp. venerealis biovar venerealis strains tested. C. fetus subsp. fetus and C. fetus subsp. venerealis were found to share most common Campylobacter virulence factors such as SAP, chemotaxis, flagellar biosynthesis, 2-component systems and cytolethal distending toxin subunits (A, B, C. We did not however, identify in C. fetus the full complement of bacterial adherence candidates commonly found in other Campylobacter spp. Conclusion The comparison of the available C. fetus subsp. venerealis genome sequence with the C. fetus subsp. fetus genome identified 80 kb of unique C. fetus subsp. venerealis AZUL94 sequence, with subsequent PCR confirmation demonstrating

  19. Yeast-based assay identifies novel Shh/Gli target genes in vertebrate development

    Directory of Open Access Journals (Sweden)

    Milla Luis A


    Full Text Available Abstract Background The increasing number of developmental events and molecular mechanisms associated with the Hedgehog (Hh pathway from Drosophila to vertebrates, suggest that gene regulation is crucial for diverse cellular responses, including target genes not yet described. Although several high-throughput, genome-wide approaches have yielded information at the genomic, transcriptional and proteomic levels, the specificity of Gli binding sites related to direct target gene activation still remain elusive. This study aims to identify novel putative targets of Gli transcription factors through a protein-DNA binding assay using yeast, and validating a subset of targets both in-vitro and in-vivo. Testing in different Hh/Gli gain- and loss-of-function scenarios we here identified known (e.g., ptc1 and novel Hh-regulated genes in zebrafish embryos. Results The combined yeast-based screening and MEME/MAST analysis were able to predict Gli transcription factor binding sites, and position mapping of these sequences upstream or in the first intron of promoters served to identify new putative target genes of Gli regulation. These candidates were validated by qPCR in combination with either the pharmacological Hh/Gli antagonist cyc or the agonist pur in Hh-responsive C3H10T1/2 cells. We also used small-hairpin RNAs against Gli proteins to evaluate targets and confirm specific Gli regulation their expression. Taking advantage of mutants that have been identified affecting different components of the Hh/Gli signaling system in the zebrafish model, we further analyzed specific novel candidates. Studying Hh function with pharmacological inhibition or activation complemented these genetic loss-of-function approaches. We provide evidence that in zebrafish embryos, Hh signaling regulates sfrp2, neo1, and c-myc expression in-vivo. Conclusion A recently described yeast-based screening allowed us to identify new Hh/Gli target genes, functionally important in

  20. Bioluminescent bioreporter assays for targeted detection of chemical and biological agents (United States)

    Ripp, Steven; Jegier, Pat; Johnson, Courtney; Moser, Scott; Islam, Syed; Sayler, Gary


    Bioluminescent bioreporters carrying the bacterial lux gene cassette have been well established for the sensing and monitoring of select chemical agents. Their ability to generate target specific visible light signals with no requirement for extraneous additions of substrate or other hands-on manipulations affords a real-time, repetitive assaying technique that is remarkable in its simplicity and accuracy. Although the predominant application of lux-based bioluminescent bioreporters has been towards chemical compound detection, novel genetic engineering schemes are yielding a variety of new bioreporter systems that extend the lux sensing mechanism beyond mere analyte discrimination. For example, the unique specificity of bacteriophage (bacterial viruses) has been exploited in lux bioluminescent assays for specific identification of foodborne bacterial pathogens such as Escherichia coli O157:H7. With the concurrent ability to interface bioluminescent bioreporter assays onto integrated circuit microluminometers (BBICs; bioluminescent bioreporter integrated circuits), the potential exists for the development of sentinel microchips that can function as environmental monitors for multiplexed recognition of chemical and biological agents in air, food, and water. The size and portability of BBIC biosensors may ultimately provide a deployable, interactive network sensing technology adaptable towards chem/bio defense.

  1. Cytotoxicity, tumor targeting and PET imaging of sub-5 nm KGdF4 multifunctional rare earth nanoparticles (United States)

    Cao, Xinmin; Cao, Fengwen; Xiong, Liqin; Yang, Yang; Cao, Tianye; Cai, Xi; Hai, Wangxi; Li, Biao; Guo, Yixiao; Zhang, Yimin; Li, Fuyou


    Ultrasmall sub-5 nm KGdF4 rare earth nanoparticles were synthesized as multifunctional probes for fluorescent, magnetic, and radionuclide imaging. The cytotoxicity of these nanoparticles in human glioblastoma U87MG and human non-small cell lung carcinoma H1299 cells was evaluated, and their application for in vitro and in vivo tumor targeted imaging has also been demonstrated.Ultrasmall sub-5 nm KGdF4 rare earth nanoparticles were synthesized as multifunctional probes for fluorescent, magnetic, and radionuclide imaging. The cytotoxicity of these nanoparticles in human glioblastoma U87MG and human non-small cell lung carcinoma H1299 cells was evaluated, and their application for in vitro and in vivo tumor targeted imaging has also been demonstrated. Electronic supplementary information (ESI) available: Details of the experimental section as well as EDXA, XRD, zeta potential, FTIR, TGA, stability, TEM, Z scanning, ICP-MS, and MicroPET/CT images. See DOI: 10.1039/c5nr03374h

  2. Medium to large scale radioisotope production for targeted radiotherapy using a small PET cyclotron

    DEFF Research Database (Denmark)

    Thisgaard, Helge; Jensen, Mikael; Elema, Dennis Ringkjøbing


    In recent years the use of radionuclides in targeted cancer therapy has increased. In this study we have developed a high-current solid target system and demonstrated that by the use of a typical low-energy medical cyclotron, it is possible to produce tens of GBq's of many unconventional radionuc......In recent years the use of radionuclides in targeted cancer therapy has increased. In this study we have developed a high-current solid target system and demonstrated that by the use of a typical low-energy medical cyclotron, it is possible to produce tens of GBq's of many unconventional...... radionuclides relevant for cancer therapy such as 64Cu and 119Sb locally at the hospitals....

  3. Development of a Loop-Mediated Isothermal Amplification Assay Targeting the mpb64 Gene for Diagnosis of Intraocular Tuberculosis (United States)

    Balne, Praveen Kumar; Barik, Manas Ranjan; Sharma, Savitri


    A loop-mediated isothermal amplification (LAMP) assay targeting the mpb64 gene for the diagnosis of intraocular tuberculosis was highly specific (100%), sensitive (85.7%), rapid, and easy to perform. The LAMP assay can be an alternative to conventional PCR for the diagnosis of ocular tuberculosis in resource-limited settings. PMID:23966513

  4. Natural product juglone targets three key enzymes from Helicobacter pylori: inhibition assay with crystal structure characterization

    Institute of Scientific and Technical Information of China (English)

    Yun-hua KONG; Liang ZHANG; Zheng-yi YANG; Cong HAN; Li-hong HU; Hua-liang JIANG; Xu SHEN


    Aim: To investigate the inhibition features of the natural product juglone (5-hydroxy-1,4-naphthoquinone) against the three key enzymes from Helicobacter pylori (cystathionine γ-synthase [HpCGS], malonyl-CoA:acyl carrier protein transacylase [HpFabD], and β-hydroxyacyl-ACP dehydratase [HpFabZ]). Methods: An enzyme inhibition assay against HpCGS was carded out by using a continuous coupled spectrophotometric assay approach. The inhibition assay of HpFabD was performed based on the α-ketoglutarate dehydrogenase-coupled system, while the inhibition assay for HpFabZ was monitored by detecting the decrease in absorbance at 260 nm with crotonoyl-CoA conversion to βhydroxybutyryl-CoA. The juglone/FabZ complex crystal was obtained by soaking juglone into the HpFabZ crystal, and the X-ray crystal structure of the complex was analyzed by molecular replacement approach. Results: Juglone was shown to potently inhibit HpCGS, HpFabD, and HpFabZ with the half maximal inhibitory concentration IC50 values of 7.0±0.7, 20±1, and 30±4 μmol/L, respectively. An inhibition-type study indicated that juglone was a non-competitive inhibitor of HpCGS against O-succi-nyl-L-homoserine (KI=αKI=24 μmol/L), an uncompetitive inhibitor of HpFabD against malonyl-CoA (αKI=7.4 μmol/L), and a competitive inhibitor of HpFabZ against crotonoyl-CoA (K,1=6.8 μtmol/L). Moreover, the crystal structure of the HpFabZ/juglone complex further revealed the essential binding pattern ofjuglone against HpFabZ at the atomic level. Conclusion: HpCGS, HpFabD, and HpFabZ are potential targets ofjuglone.

  5. Precision and linearity targets for validation of an IFNγ ELISPOT, cytokine flow cytometry, and tetramer assay using CMV peptides

    Directory of Open Access Journals (Sweden)

    Lyerly Herbert K


    Full Text Available Abstract Background Single-cell assays of immune function are increasingly used to monitor T cell responses in immunotherapy clinical trials. Standardization and validation of such assays are therefore important to interpretation of the clinical trial data. Here we assess the levels of intra-assay, inter-assay, and inter-operator precision, as well as linearity, of CD8+ T cell IFNγ-based ELISPOT and cytokine flow cytometry (CFC, as well as tetramer assays. Results Precision was measured in cryopreserved PBMC with a low, medium, or high response level to a CMV pp65 peptide or peptide mixture. Intra-assay precision was assessed using 6 replicates per assay; inter-assay precision was assessed by performing 8 assays on different days; and inter-operator precision was assessed using 3 different operators working on the same day. Percent CV values ranged from 4% to 133% depending upon the assay and response level. Linearity was measured by diluting PBMC from a high responder into PBMC from a non-responder, and yielded R2 values from 0.85 to 0.99 depending upon the assay and antigen. Conclusion These data provide target values for precision and linearity of single-cell assays for those wishing to validate these assays in their own laboratories. They also allow for comparison of the precision and linearity of ELISPOT, CFC, and tetramer across a range of response levels. There was a trend toward tetramer assays showing the highest precision, followed closely by CFC, and then ELISPOT; while all three assays had similar linearity. These findings are contingent upon the use of optimized protocols for each assay.

  6. Theranostic Approach for Metastatic Pigmented Melanoma Using ICF15002, a Multimodal Radiotracer for Both PET Imaging and Targeted Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Latifa Rbah-Vidal


    Full Text Available PURPOSE: This work reports, in melanoma models, the theranostic potential of ICF15002 as a single fluorinated and iodinated melanin-targeting compound. METHODS: Studies were conducted in the murine syngeneic B16BL6 model and in the A375 and SK-MEL-3 human xenografts. ICF15002 was radiolabeled with fluorine-18 for positron emission tomography (PET imaging and biodistribution, with iodine-125 for metabolism study, and iodine-131 for targeted radionuclide therapy (TRT. TRT efficacy was assessed by tumor volume measurement, with mechanistics and dosimetry parameters being determined in the B16BL6 model. Intracellular localization of ICF15002 was characterized by secondary ion mass spectrometry (SIMS. RESULTS: PET imaging with [18F]ICF15002 evidenced tumoral uptake of 14.33 ± 2.11%ID/g and 4.87 ± 0.93%ID/g in pigmented B16BL6 and SK-MEL-3 models, respectively, at 1 hour post inoculation. No accumulation was observed in the unpigmented A375 melanoma. SIMS demonstrated colocalization of ICF15002 signal with melanin polymers in melanosomes of the B16BL6 tumors. TRT with two doses of 20 MBq [131I]ICF15002 delivered an absorbed dose of 102.3 Gy to B16BL6 tumors, leading to a significant tumor growth inhibition [doubling time (DT of 2.9 ± 0.5 days in treated vs 1.8 ± 0.3 in controls] and a prolonged median survival (27 days vs 21 in controls. P53S15 phosphorylation and P21 induction were associated with a G2/M blockage, suggesting mitotic catastrophe. In the human SK-MEL-3 model, three doses of 25 MBq led also to a DT increase (26.5 ± 7.8 days vs 11.0 ± 3.8 in controls and improved median survival (111 days vs 74 in controls. CONCLUSION: Results demonstrate that ICF15002 fulfills suitable properties for bimodal imaging/TRT management of patients with pigmented melanoma.

  7. A comprehensive assay for targeted multiplex amplification of human DNA sequences. (United States)

    Krishnakumar, Sujatha; Zheng, Jianbiao; Wilhelmy, Julie; Faham, Malek; Mindrinos, Michael; Davis, Ronald


    We developed a robust and reproducible methodology to amplify human sequences in parallel for use in downstream multiplexed sequence analyses. We call the methodology SMART (Spacer Multiplex Amplification Reaction), and it is based, in part, on padlock probe technology. As a proof of principle, we used SMART technology to simultaneously amplify 485 human exons ranging from 100 to 500 bp from human genomic DNA. In multiple repetitions, >90% of the targets were successfully amplified with a high degree of uniformity, with 70% of targets falling within a 10-fold range and all products falling within a 100-fold range of each other in abundance. We used long padlock probes (LPPs) >300 bases in length for the assay, and the increased length of these probes allowed for the capture of human sequences up to 500 bp in length, which is optimal for capturing most human exons. To engineer the LPPs, we developed a method that generates ssDNA molecules with precise ends, using an appropriately designed dsDNA template. The template has appropriate restriction sites engineered into it that can be digested to generate nucleotide overhangs that are suitable for lambda exonuclease digestion, producing a single-stranded probe from dsDNA. The SMART technology is flexible and can be easily adapted to multiplex tens of thousands of target sequences in a single reaction.

  8. PET imaging in multiple sclerosis

    NARCIS (Netherlands)

    Faria, Daniele de Paula; Copray, Sjef; Buchpiguel, Carlos; Dierckx, Rudi; de Vries, Erik


    Positron emission tomography (PET) is a non-invasive technique for quantitative imaging of biochemical and physiological processes in animals and humans. PET uses probes labeled with a radioactive isotope, called PET tracers, which can bind to or be converted by a specific biological target and thus

  9. Human SRMAtlas: A Resource of Targeted Assays to Quantify the Complete Human Proteome. (United States)

    Kusebauch, Ulrike; Campbell, David S; Deutsch, Eric W; Chu, Caroline S; Spicer, Douglas A; Brusniak, Mi-Youn; Slagel, Joseph; Sun, Zhi; Stevens, Jeffrey; Grimes, Barbara; Shteynberg, David; Hoopmann, Michael R; Blattmann, Peter; Ratushny, Alexander V; Rinner, Oliver; Picotti, Paola; Carapito, Christine; Huang, Chung-Ying; Kapousouz, Meghan; Lam, Henry; Tran, Tommy; Demir, Emek; Aitchison, John D; Sander, Chris; Hood, Leroy; Aebersold, Ruedi; Moritz, Robert L


    The ability to reliably and reproducibly measure any protein of the human proteome in any tissue or cell type would be transformative for understanding systems-level properties as well as specific pathways in physiology and disease. Here, we describe the generation and verification of a compendium of highly specific assays that enable quantification of 99.7% of the 20,277 annotated human proteins by the widely accessible, sensitive, and robust targeted mass spectrometric method selected reaction monitoring, SRM. This human SRMAtlas provides definitive coordinates that conclusively identify the respective peptide in biological samples. We report data on 166,174 proteotypic peptides providing multiple, independent assays to quantify any human protein and numerous spliced variants, non-synonymous mutations, and post-translational modifications. The data are freely accessible as a resource at, and we demonstrate its utility by examining the network response to inhibition of cholesterol synthesis in liver cells and to docetaxel in prostate cancer lines.

  10. Treatment of Non-Small Cell Lung Cancer (NSCLC) Using CT in Combination with a PET Examination to Minimize the Clinical Target Volume of the Mediastinum

    Institute of Scientific and Technical Information of China (English)

    Yusheng Shi; Xiaogang Deng; Longhua Chen


    OBJECTIVE To decrease radiation injury of the esophagus and lungs by utilizing a CT scan in combination with PET tumor imaging in order to minimize the clinical target area of locally advanced non-small cell lung cancer, without preventive radiation on the lymphatic drainage area. METHODS Of 76 patients with locally advanced non-small cell lung cancer (NSCLC), 32 received a PET examination before radiotherapy. Preventive radiation was not conducted in the mediastinum area without lymphatic metastasis, which was confirmed by CT and PET. For the other 44 patients, preventive radiation was performed in the lymphatic drainage area. PET examinations showed that the clinical target volume of the patients was decreased on average to about one third. The radiation therapy for patients of the two groups was the same, I.e. The dose for accelerated fractionated irradiation was 3 Gy/time and 5 time/week. The preventive dose was 42 to 45 Gy/time, 14 to 15 time/week, with 3-week treatment, and the therapeutic dose was 60 to 63 Gy/time, 20 to 21 time/week, with a period of 4 to 5 weeks.RESULTS The rate of missed lymph nodes beyond the irradiation field was 6.3% and 4.5% respectively in the group with and without PET examination (P = 0.831). The incidence of acute radioactive esophagitis was 15.6 % and 45.5% in the two groups respectively (P = 0.006). The incidence of acute radiation pneumonia and long-term pulmonary fibrosis in the two groups was 6.3% and 9.1%, and 68.8% and 75.0%, respectively (P = 0.982 and P = 0.547).CONCLUSION The recurrence rate in the lymph nodes beyond the target area was not increased after minimizing the clinical target volume (CTV), whereas radioactive injury to the lungs and esophageal injury was reduced, and especially with a significant decrease in the rate of acute radioactive esophagitis. The method of CT in combination with PET for minimizing the mediastinal CTV is superior to the conventional preventive radiation of the mediastinum.

  11. CRISPR is an optimal target for the design of specific PCR assays for salmonella enterica serotypes Typhi and Paratyphi A.

    Directory of Open Access Journals (Sweden)

    Laetitia Fabre

    Full Text Available BACKGROUND: Serotype-specific PCR assays targeting Salmonella enterica serotypes Typhi and Paratyphi A, the causal agents of typhoid and paratyphoid fevers, are required to accelerate formal diagnosis and to overcome the lack of typing sera and, in some situations, the need for culture. However, the sensitivity and specificity of such assays must be demonstrated on large collections of strains representative of the targeted serotypes and all other bacterial populations producing similar clinical symptoms. METHODOLOGY: Using a new family of repeated DNA sequences, CRISPR (clustered regularly interspaced short palindromic repeats, as a serotype-specific target, we developed a conventional multiplex PCR assay for the detection and differentiation of serotypes Typhi and Paratyphi A from cultured isolates. We also developed EvaGreen-based real-time singleplex PCR assays with the same two sets of primers. PRINCIPAL FINDINGS: We achieved 100% sensitivity and specificity for each protocol after validation of the assays on 188 serotype Typhi and 74 serotype Paratyphi A strains from diverse genetic groups, geographic origins and time periods and on 70 strains of bacteria frequently encountered in bloodstream infections, including 29 other Salmonella serotypes and 42 strains from 38 other bacterial species. CONCLUSIONS: The performance and convenience of our serotype-specific PCR assays should facilitate the rapid and accurate identification of these two major serotypes in a large range of clinical and public health laboratories with access to PCR technology. These assays were developed for use with DNA from cultured isolates, but with modifications to the assay, the CRISPR targets could be used in the development of assays for use with clinical and other samples.

  12. The Diagnostic Value of 18F-FDG PET/CT in Association with Serum Tumor Marker Assays in Breast Cancer Recurrence and Metastasis

    Directory of Open Access Journals (Sweden)

    Ying Dong


    Full Text Available Background. After initial treatment of breast cancer (BC, monitoring locoregional recurrence and distant metastases is a great clinical challenge. Objective. To evaluate the efficacy of PET/CT in association with serum tumor makers in BC follow-up. Methods. Twenty-six women with a history of modified radical mastectomy were evaluated by 18F-FDG PET/CT. The results of PET/CT were compared with those of conventional imaging techniques (CITs (including mammography, chest radiography, CT, MRI, ultrasound, and bone scintigraphy. Serum tumor markers of CEA, CA 125, and CA 15-3 in the BC patients were also analyzed in association with the results of PET/CT. Results. Compared with CITs, PET/CT was more sensitive to detect the malignant foci and had better patient-based sensitivity and specificity. The mean CA 15-3 serum level was significantly higher in the confirmed positive patients of PET/CT results than in the confirmed negative ones, while there were no significant differences in the serum levels of CEA and CA 125 of both groups. Conclusion. PET/CT is a highly efficient tool for BC follow-up compared with CITs. The high serum levels of CA 15-3 in confirmed positive PET/CT patients indicated the clinical value of CA 15-3 in BC follow-up.

  13. PET imaging of angiogenesis after myocardial infarction/reperfusion using a one-step labeled integrin-targeted tracer {sup 18}F-AlF-NOTA-PRGD2

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Haokao [The Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China); National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Lang, Lixin; Guo, Ning; Quan, Qimeng; Hu, Shuo; Kiesewetter, Dale O.; Niu, Gang; Chen, Xiaoyuan [National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH), Laboratory of Molecular Imaging and Nanomedicine (LOMIN), Bethesda, MD (United States); Cao, Feng [The Fourth Military Medical University, Department of Cardiology, Xijing Hospital, Xi' an (China)


    The {alpha}{sub v}{beta}{sub 3} integrin represents a potential target for noninvasive imaging of angiogenesis. The purpose of this study was to evaluate a novel one-step labeled integrin {alpha}{sub v}{beta}{sub 3}-targeting positron emission tomography (PET) probe, {sup 18}F-AlF-NOTA-PRGD2, for angiogenesis imaging in a myocardial infarction/reperfusion (MI/R) animal model. Male Sprague-Dawley rats underwent 45-min transient left coronary artery occlusion followed by reperfusion. The myocardial infarction was confirmed by ECG, {sup 18}F-fluorodeoxyglucose (FDG) imaging, and cardiac ultrasound. In vivo PET imaging was used to determine myocardial uptake of {sup 18}F-AlF-NOTA-PRGD2 at different time points following reperfusion. The control peptide RAD was labeled with a similar procedure and used to confirm the specificity. Ex vivo autoradiographic analysis and CD31/CD61 double immunofluorescence staining were performed to validate the PET results. Myocardial origin of the {sup 18}F-AlF-NOTA-PRGD2 accumulation was confirmed by {sup 18}F-FDG and autoradiography. PET imaging demonstrated increased focal accumulation of {sup 18}F-AlF-NOTA-PRGD2 in the infarcted area which started at day 3 (0.28 {+-} 0.03%ID/g, p < 0.05) and peaked between 1 and 3 weeks (0.59 {+-} 0.16 and 0.55 {+-} 0.13%ID/g, respectively). The focal accumulation decreased but still kept at a higher level than the sham group after 4 months of reperfusion (0.31 {+-} 0.01%ID/g, p < 0.05). Pretreatment with unlabeled arginine-glycine-aspartic acid (RGD) peptide significantly decreased tracer uptake, indicating integrin specificity of this tracer. At 1 week after MI/R, uptake of the control tracer {sup 18}F-AlF-NOTA-RAD that does not bind to integrin, in the infarcted area, was only 0.21 {+-} 0.01%ID/g. Autoradiographic imaging showed the same trend of uptake in the myocardial infarction area. The time course of focal tracer uptake was consistent with the pattern of vascular density and integrin {beta

  14. Multimodality imaging with CT, MR and FDG-PET for radiotherapy target volume delineation in oropharyngeal squamous cell carcinoma


    Bird, David; Scarsbrook, Andrew F.; Sykes, Jonathan; Ramasamy, Satiavani; Subesinghe, Manil; Carey, Brendan; Wilson, Daniel J.; Roberts, Neil; McDermott, Gary; KARAKAYA, Ebru; BAYMAN, Evrim; Sen, Mehmet; Speight, Richard; Prestwich, Robin J. D.


    Background This study aimed to quantify the variation in oropharyngeal squamous cell carcinoma gross tumour volume (GTV) delineation between CT, MR and FDG PET-CT imaging. Methods A prospective, single centre, pilot study was undertaken where 11 patients with locally advanced oropharyngeal cancers (2 tonsil, 9 base of tongue primaries) underwent pre-treatment, contrast enhanced, FDG PET-CT and MR imaging, all performed in a radiotherapy treatment mask. CT, MR and CT-MR GTVs were contoured by ...

  15. Target volume definition in high-risk prostate cancer patients using sentinel node SPECT/CT and 18 F-choline PET/CT

    Directory of Open Access Journals (Sweden)

    Vees Hansjörg


    Full Text Available Abstract Background To assess the influence of sentinel lymph nodes (SNs SPECT/CT and 18 F-choline (18 F-FCH PET/CT in radiotherapy (RT treatment planning for prostate cancer patients with a high-risk for lymph node (LN involvement. Methods Twenty high-risk prostate cancer patients underwent a pelvic SPECT acquisition following a transrectal ultrasound guided injection of 99mTc-Nanocoll into the prostate. In all patients but one an 18 F-FCH PET/CT for RT treatment planning was performed. SPECT studies were coregistered with the respective abdominal CTs. Pelvic SNs localized on SPECT/CT and LN metastases detected by 18 F-FCH PET/CT were compared to standard pelvic clinical target volumes (CTV. Results A total of 104 pelvic SNs were identified on SPECT/CT (mean 5.2 SNs/patient; range 1–10. Twenty-seven SNs were located outside the standard pelvic CTV, 17 in the proximal common iliac and retroperitoneal regions above S1, 9 in the pararectal fat and 1 in the inguinal region. SPECT/CT succeeded to optimize the definition of the CTV and treatment plans in 6/20 patients due to the presence of pararectal SNs located outside the standard treatment volume. 18 F-FCH PET/CT identified abnormal tracer uptake in the iliac LN region in 2/19 patients. These abnormal LNs were negative on SPECT/CT suggesting a potential blockade of lymphatic drainage by metastatic LNs with a high tumour burden. Conclusions Multimodality imaging which combines SPECT/CT prostate lymphoscintigraphy and 18 F-FCH PET/CT identified SNs outside standard pelvic CTVs or highly suspicious pelvic LNs in 40% of high-risk prostate cancer patients, highlighting the potential impact of this approach in RT treatment planning.

  16. Tier-1 assays for assessing the toxicity of insecticidal proteins produced by genetically engineered plants to non-target arthropods. (United States)

    Li, Yun-He; Romeis, Jörg; Wu, Kong-Ming; Peng, Yu-Fa


    In assessing an insect-resistant genetically engineered (IRGE) crop before its commercialization, researchers normally use so-called "Tier-1 assays" as the initial step to determine the effects of the crop on non-target organisms. In these tests, the insecticidal proteins (IPs) produced by the IRGEs are added to the diets of test organisms in the laboratory. Test organisms in such assays can be directly exposed to much higher concentrations of the test IPs than they would encounter in the field. The results of Tier-1 assays are thus more conservative than those generated in studies in which the organisms are exposed to the IPs by feeding on IRGE plant tissue or in the case of predators or parasites, by feeding on invertebrate prey or hosts that have fed on IRGE plant tissue. In this report, we consider three important factors that must be considered in Tier-1 assays: (i) methods for delivery of the IP to the test organisms; (ii) the need for and selection of compounds used as positive controls; and (iii) methods for monitoring the concentration, stability and bioactivity of the IP during the assay. We also analyze the existing data from Tier-1 assays regarding the toxicity of Bt Cry proteins to non-target arthropod species. The data indicate that the widely used Bt proteins have no direct toxicity to non-target organisms.

  17. Comparison of Gull Feces-specific Assays Targeting the 16S rRNA Gene of Catellicoccus Marimammalium and Streptococcus spp. (United States)

    Two novel gull-specific qPCR assays were developed using 16S rRNA gene sequences from gull fecal clone libraries: a SYBR-green-based assay targeting Streptococcus spp. (i.e., gull3) and a TaqMan qPCR assay targeting Catellicoccus marimammalium (i.e., gull4). The main objectives ...

  18. Segmentation of biological target volumes on multi-tracer PET images based on information fusion for achieving dose painting in radiotherapy. (United States)

    Lelandais, Benoît; Gardin, Isabelle; Mouchard, Laurent; Vera, Pierre; Ruan, Su


    Medical imaging plays an important role in radiotherapy. Dose painting consists in the application of a nonuniform dose prescription on a tumoral region, and is based on an efficient segmentation of biological target volumes (BTV). It is derived from PET images, that highlight tumoral regions of enhanced glucose metabolism (FDG), cell proliferation (FLT) and hypoxia (FMiso). In this paper, a framework based on Belief Function Theory is proposed for BTV segmentation and for creating 3D parametric images for dose painting. We propose to take advantage of neighboring voxels for BTV segmentation, and also multi-tracer PET images using information fusion to create parametric images. The performances of BTV segmentation was evaluated on an anthropomorphic phantom and compared with two other methods. Quantitative results show the good performances of our method. It has been applied to data of five patients suffering from lung cancer. Parametric images show promising results by highlighting areas where a high frequency or dose escalation could be planned.

  19. Use of substitute Nonidet P-40 nonionic detergents in intracellular tubulin polymerization assays for screening of microtubule targeting agents. (United States)

    Sinha, Saptarshi; Field, Jessica J; Miller, John H


    Shell Chemical Company Nonidet P-40 has been used for decades in many biochemical assays as a nonionic, nondenaturing detergent; however, Shell no longer produces this product. Four commercially available substitutes were investigated and their activities titrated in an intracellular tubulin polymerization assay. Although claimed by the supply companies to be identical to the Shell Nonidet P-40, all four substitutes were about 10-fold more potent and needed to be diluted accordingly. As microtubule targeting drugs are a major class of anticancer agent, and many researchers use the intracellular tubulin polymerization assay, this information is important to help troubleshoot assay development with the new substitutes. As the Shell Nonidet P-40 has been used in many biochemical buffers, these results will be of general interest to the biochemical, cell, and molecular research community.

  20. PET-Based Thoracic Radiation Oncology. (United States)

    Simone, Charles B; Houshmand, Sina; Kalbasi, Anusha; Salavati, Ali; Alavi, Abass


    Fluorodeoxyglucose-PET is increasingly being integrated into multiple aspects of oncology. PET/computed tomography (PET/CT) has become especially important in radiation oncology. With the increasing use of advanced techniques like intensity-modulated radiation therapy and proton therapy, PET/CT scans have played critical roles in the target delineation of tumors for radiation oncologists delivering conformal treatment techniques. Use of PET/CT is well established in lung cancer and several other thoracic malignancies. This article details the current uses of PET/CT in thoracic radiation oncology with a focus on lung cancer and describes expected future roles of PET/CT for thoracic tumors.

  1. Analysis of Target Volume Definition Using CT, MRI and FDG-PET in Radiotherapy Treatment Planning of Anal Cancer

    DEFF Research Database (Denmark)

    Serup-Hansen, E.; Hendel, H. Westergreen; Johannesen, H. Hjorth;


    and MRI. The delineations of GTV were done twice for each imaging modality with a minimum of 3 months in between. Delineations on the CT and MRI were done by routine methods. For the PET part three different cut-off values were used: SUV 2.5, 40% and 50% of maximum SUV, respectively. The GTVs were...

  2. Employment of colorimetric enzyme assay for monitoring expression and solubility of GST fusion proteins targeted to inclusion bodies. (United States)

    Mačinković, Igor S; Abughren, Mohamed; Mrkic, Ivan; Grozdanović, Milica M; Prodanović, Radivoje; Gavrović-Jankulović, Marija


    High levels of recombinant protein expression can lead to the formation of insoluble inclusion bodies. These complex aggregates are commonly solubilized in strong denaturants, such as 6-8M urea, although, if possible, solubilization under milder conditions could facilitate subsequent refolding and purification of bioactive proteins. Commercially available GST-tag assays are designed for quantitative measurement of GST activity under native conditions. GST fusion proteins accumulated in inclusion bodies are considered to be undetectable by such assays. In this work, solubilization of recombinantly produced proteins was performed in 4M urea. The activity of rGST was assayed in 2M urea and it was shown that rGST preserves 85% of its activity under such denaturing conditions. A colorimetric GST activity assay with 1-chloro-2, 4-dinitrobenzene (CDNB) was examined for use in rapid detection of expression targeted to inclusion bodies and for the identification of inclusion body proteins which can be solubilized in low concentrations of chaotropic agents. Applicability of the assay was evaluated by tracking protein expression of two GST-fused allergens of biopharmaceutical value in E. coli, GST-Der p 2 and GST-Mus a 5, both targeted to inclusion bodies.

  3. Giardia & Pets (United States)

    ... body of water Young pets, like puppies and kittens, have a higher risk of illness than adult ... If your pet has persistent diarrhea, seek veterinary care. Diarrhea has different causes and could result in ...

  4. PET-based compartmental modeling of {sup 124}I-A33 antibody: quantitative characterization of patient-specific tumor targeting in colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zanzonico, Pat; O' Donoghue, Joseph A.; Humm, John L. [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Carrasquillo, Jorge A.; Pandit-Taskar, Neeta; Ruan, Shutian; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Smith-Jones, Peter [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Stony Brook School of Medicine, Departments of Psychiatry and Radiology, Stony Brook, NY (United States); Divgi, Chaitanya [Columbia University Medical Center, New York, NY (United States); Scott, Andrew M. [La Trobe University, Olivia Newton-John Cancer Research Institute, Melbourne (Australia); Kemeny, Nancy E.; Wong, Douglas; Scheinberg, David [Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY (United States); Fong, Yuman [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States); City of Hope, Department of Surgery, Duarte, CA (United States); Ritter, Gerd; Jungbluth, Achem; Old, Lloyd J. [Memorial Sloan Kettering Cancer Center, Ludwig Institute for Cancer Research, New York, NY (United States)


    The molecular specificity of monoclonal antibodies (mAbs) directed against tumor antigens has proven effective for targeted therapy of human cancers, as shown by a growing list of successful antibody-based drug products. We describe a novel, nonlinear compartmental model using PET-derived data to determine the ''best-fit'' parameters and model-derived quantities for optimizing biodistribution of intravenously injected {sup 124}I-labeled antitumor antibodies. As an example of this paradigm, quantitative image and kinetic analyses of anti-A33 humanized mAb (also known as ''A33'') were performed in 11 colorectal cancer patients. Serial whole-body PET scans of {sup 124}I-labeled A33 and blood samples were acquired and the resulting tissue time-activity data for each patient were fit to a nonlinear compartmental model using the SAAM II computer code. Excellent agreement was observed between fitted and measured parameters of tumor uptake, ''off-target'' uptake in bowel mucosa, blood clearance, tumor antigen levels, and percent antigen occupancy. This approach should be generally applicable to antibody-antigen systems in human tumors for which the masses of antigen-expressing tumor and of normal tissues can be estimated and for which antibody kinetics can be measured with PET. Ultimately, based on each patient's resulting ''best-fit'' nonlinear model, a patient-specific optimum mAb dose (in micromoles, for example) may be derived. (orig.)

  5. Pet Health (United States)

    Pets can add fun, companionship and a feeling of safety to your life. Before getting a pet, think carefully about which animal is best for ... is each family member looking for in a pet? Who will take care of it? Does anyone ...

  6. RT-PCR assay for detection of Lassa virus and related Old World arenaviruses targeting the L gene. (United States)

    Vieth, Simon; Drosten, Christian; Lenz, Oliver; Vincent, Martin; Omilabu, Sunday; Hass, Meike; Becker-Ziaja, Beate; ter Meulen, Jan; Nichol, Stuart T; Schmitz, Herbert; Günther, Stephan


    This study describes an RT-PCR assay targeting the L RNA segment of arenaviruses. Conserved regions were identified in the polymerase domain of the L gene on the basis of published sequences for Lassa virus, lymphocytic choriomeningitis virus (LCMV), Pichinde virus and Tacaribe virus, as well as 15 novel sequences for Lassa virus, LCMV, Ippy virus, Mobala virus and Mopeia virus determined in this study. Using these regions as target sites, a PCR assay for detection of all known Old World arenaviruses was developed and optimized. The concentration that yields 95% positive results in a set of replicate tests (95% detection limit) was determined to be 4290 copies of Lassa virus L RNA per ml of serum, corresponding to 30 copies per reaction. The ability of the assay to detect various Old World arenaviruses was demonstrated with in vitro transcribed RNA, material from infected cell cultures and samples from patients with Lassa fever and monkeys with LCMV-associated callitrichid hepatitis. The L gene PCR assay may be applicable: (i) as a complementary diagnostic test for Lassa virus and LCMV; (ii) to identify unknown Old World arenaviruses suspected as aetiological agents of disease; and (iii) for screening of potential reservoir hosts for unknown Old World arenaviruses.

  7. Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast



    To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 comp...

  8. 18F-FDG PET/CT联合肿瘤标志物对肺癌的诊断价值及SUVmax的临床意义%Diagnostic value of 18F-FDG PET/CT imaging plus serum tumor marker assays for pulmonary lesions and clinical significance of SUVmax

    Institute of Scientific and Technical Information of China (English)

    张铁梅; 张连民; 刘洋; 张真发; 王长利


    Objective To evaluate the diagnostic value of 18F-FDG positron emission tomography/computed tomography (PET/CT) plus serum tumor marker assay in lung cancer and explore the correlation between standard uptake value (SUVmax) with clinicopathologic factors in lung cancer.Methods A total of 177 cases of lung cancer diagnosed by radiography or computed tomography (CT) were recruited.18F-FDG PET/CT imaging and detection of three lung cancer related serum markers (carcinoembryonic antigen,CYFRA21-1 and neuron specific enolase) were performed within one week in all cases.The sensitivity,specificity and accuracy of those approaches were calculated through comparing the results with pathologic examinations.Also the associations between SUVtnax and clinicopathologic features were analyzed.Results Among them,145 patients were detected to have lung cancer by pathologic diagnosis while the other 32 patients had benign lung diseases.The sensitivity,specificity,accuracy of 18F-FDG PET/CT imaging,serum tumor markers and their combination in assessing lung cancers were 89.7%,78.1%,87.6% ; 89.7%,78.1%,87.6% and 96.6%,56.3%,89.3% respectively.The combination of 18F-FDG PET/CT and serum tumor markers in lung lesions showed significantly higher sensitivity than serum tumor markers and 18F-FDG PET/CT alone(P =0.000,P =0.002).Its accuracy was also significantly higher than those of tumor markers (P < 0.05).Compared with 18 F-FDG PET/CT alone,the accuracy was higher in combination group.But the difference showed no statistical significance (P > 0.05).SUVmax was significantly associated with tumor staging,tumor size and pathologic type.Conclusion The combination of 18 F-FDG PET/CT and tumor markers may improve the positive diagnostic rate of lung cancer.And SUVmax can help to evaluate tumor staging and determine pathological types.%目的 评价18氟脱氧葡萄糖(18F-FDG) PET/CT显像联合肿瘤标志物测定对肺部肿块良恶性鉴别的诊断价值,并进一

  9. A novel SERRS sandwich-hybridization assay to detect specific DNA target.

    Directory of Open Access Journals (Sweden)

    Cécile Feuillie

    Full Text Available In this study, we have applied Surface Enhanced Resonance Raman Scattering (SERRS technology to the specific detection of DNA. We present an innovative SERRS sandwich-hybridization assay that allows specific DNA detection without any enzymatic amplification, such as is the case with Polymerase Chain Reaction (PCR. In some substrates, such as ancient or processed remains, enzymatic amplification fails due to DNA alteration (degradation, chemical modification or to the presence of inhibitors. Consequently, the development of a non-enzymatic method, allowing specific DNA detection, could avoid long, expensive and inconclusive amplification trials. Here, we report the proof of concept of a SERRS sandwich-hybridization assay that leads to the detection of a specific chamois DNA. This SERRS assay reveals its potential as a non-enzymatic alternative technology to DNA amplification methods (particularly the PCR method with several applications for species detection. As the amount and type of damage highly depend on the preservation conditions, the present SERRS assay would enlarge the range of samples suitable for DNA analysis and ultimately would provide exciting new opportunities for the investigation of ancient DNA in the fields of evolutionary biology and molecular ecology, and of altered DNA in food frauds detection and forensics.

  10. Identifying New Drug Targets for Potent Phospholipase D Inhibitors: Combining Sequence Alignment, Molecular Docking, and Enzyme Activity/Binding Assays. (United States)

    Djakpa, Helene; Kulkarni, Aditya; Barrows-Murphy, Scheneque; Miller, Greg; Zhou, Weihong; Cho, Hyejin; Török, Béla; Stieglitz, Kimberly


    Phospholipase D enzymes cleave phospholipid substrates generating choline and phosphatidic acid. Phospholipase D from Streptomyces chromofuscus is a non-HKD (histidine, lysine, and aspartic acid) phospholipase D as the enzyme is more similar to members of the diverse family of metallo-phosphodiesterase/phosphatase enzymes than phospholipase D enzymes with active site HKD repeats. A highly efficient library of phospholipase D inhibitors based on 1,3-disubstituted-4-amino-pyrazolopyrimidine core structure was utilized to evaluate the inhibition of purified S. chromofuscus phospholipase D. The molecules exhibited inhibition of phospholipase D activity (IC50 ) in the nanomolar range with monomeric substrate diC4 PC and micromolar range with phospholipid micelles and vesicles. Binding studies with vesicle substrate and phospholipase D strongly indicate that these inhibitors directly block enzyme vesicle binding. Following these compelling results as a starting point, sequence searches and alignments with S. chromofuscus phospholipase D have identified potential new drug targets. Using AutoDock, inhibitors were docked into the enzymes selected from sequence searches and alignments (when 3D co-ordinates were available) and results analyzed to develop next-generation inhibitors for new targets. In vitro enzyme activity assays with several human phosphatases demonstrated that the predictive protocol was accurate. The strategy of combining sequence comparison, docking, and high-throughput screening assays has helped to identify new drug targets and provided some insight into how to make potential inhibitors more specific to desired targets.

  11. A novel quantitative PCR assay for the detection of Streptococcus pneumoniae using the competence regulator gene target comX. (United States)

    Habets, Marrit N; Cremers, Amelieke J H; Bos, Martine P; Savelkoul, Paul; Eleveld, Marc J; Meis, Jacques F; Hermans, Peter W M; Melchers, Willem J; de Jonge, Marien I; Diavatopoulos, Dimitri A


    Streptococcus pneumoniae is responsible for an estimated 1.6 million deaths worldwide every year. While rapid detection and timely treatment with appropriate antibiotics is preferred, this is often difficult due to the amount of time that detection with blood cultures takes. In this study, a novel quantitative PCR assay for the detection of Streptococcus pneumoniae was developed. To identify novel targets, we analysed the pneumococcal genome for unique, repetitive DNA sequences. This approach identified comX, which is conserved and present in duplicate copies in Streptococcus pneumoniae but not in other bacterial species. Comparison with lytA, the current 'gold standard' for detection by quantitative PCR, demonstrated an analytic specificity of 100% for both assays on a panel of 10 pneumococcal and 18 non-pneumococcal isolates, but a reduction of 3.5 quantitation cycle values (± 0.23 sem), resulting in an increased analytical detection rate of comX. We validated our assay on DNA extracted from the serum of 30 bacteraemic patients who were blood culture positive for Streptococcus pneumoniae and 51 serum samples that were culture positive for other bacteria. This resulted in a similar clinical sensitivity between the comX and lytA assays (47%) and in a diagnostic specificity of 98.2 and 100% for the lytA and comX assays, respectively. In conclusion, we have developed a novel quantitative PCR assay with increased analytical sensitivity for the detection of Streptococcus pneumoniae, which may be used to develop a rapid bedside test for the direct detection of Streptococcus pneumoniae in clinical specimens.

  12. A sensitive and rapid assay for homologous recombination in mosquito cells: impact of vector topology and implications for gene targeting

    Directory of Open Access Journals (Sweden)

    Zhao Yuguang


    Full Text Available Abstract Background Recent progress in insect transgenesis has been dramatic but existing transposon-based approaches are constrained by position effects and potential instability. Gene targeting would bring a number of benefits, however progress requires a better understanding of the mechanisms involved. Much can be learned in vitro since extrachromosomal recombination occurs at high frequency, facilitating the study of multiple events and the impact of structural changes among the recombining molecules. We have investigated homologous recombination in mosquito cells through restoration of luciferase activity from deleted substrates. The implications of this work for the construction of insect gene targeting vectors are discussed. Results We show that linear targeting vectors are significantly more efficient than circular ones and that recombination is stimulated by introducing double-strand breaks into, or near, the region of homology. Single-strand annealing represents a very efficient pathway but may not be feasible for targeting unbroken chromosomes. Using circular plasmids to mimic chromosomal targets, one-sided invasion appears to be the predominant pathway for homologous recombination. Non-homologous end joining reactions also occur and may be utilised in gene targeting if double-strand breaks are first introduced into the target site. Conclusions We describe a rapid, sensitive assay for extrachromosomal homologous recombination in mosquito cells. Variations in substrate topology suggest that single-strand annealing and one-sided invasion represent the predominant pathways, although non-homologous end joining reactions also occur. One-sided invasion of circular chromosomal mimics by linear vectors might therefore be used in vitro to investigate the design and efficiency of gene targeting strategies.

  13. Plasmodium serine hydroxymethyltransferase as a potential anti-malarial target: inhibition studies using improved methods for enzyme production and assay

    Directory of Open Access Journals (Sweden)

    Sopitthummakhun Kittipat


    Full Text Available Abstract Background There is an urgent need for the discovery of new anti-malarial drugs. Thus, it is essential to explore different potential new targets that are unique to the parasite or that are required for its viability in order to develop new interventions for treating the disease. Plasmodium serine hydroxymethyltransferase (SHMT, an enzyme in the dTMP synthesis cycle, is a potential target for such new drugs, but convenient methods for producing and assaying the enzyme are still lacking, hampering the ability to screen inhibitors. Methods Production of recombinant Plasmodium falciparum SHMT (PfSHMT and Plasmodium vivax SHMT (PvSHMT, using auto-induction media, were compared to those using the conventional Luria Bertani medium with isopropyl thio-β-D-galactoside (LB-IPTG induction media. Plasmodium SHMT activity, kinetic parameters, and response to inhibitors were measured spectrophotometrically by coupling the reaction to that of 5,10-methylenetetrahydrofolate dehydrogenase (MTHFD. The identity of the intermediate formed upon inactivation of Plasmodium SHMTs by thiosemicarbazide was investigated by spectrophotometry, high performance liquid chromatography (HPLC, and liquid chromatography-mass spectrometry (LC-MS. The active site environment of Plasmodium SHMT was probed based on changes in the fluorescence emission spectrum upon addition of amino acids and folate. Results Auto-induction media resulted in a two to three-fold higher yield of Pf- and PvSHMT (7.38 and 29.29 mg/L compared to that produced in cells induced in LB-IPTG media. A convenient spectrophotometric activity assay coupling Plasmodium SHMT and MTHFD gave similar kinetic parameters to those previously obtained from the anaerobic assay coupling SHMT and 5,10-methylenetetrahydrofolate reductase (MTHFR; thus demonstrating the validity of the new assay procedure. The improved method was adopted to screen for Plasmodium SHMT inhibitors, of which some were originally designed

  14. A T7 Endonuclease I Assay to Detect Talen-Mediated Targeted Mutation of HBV cccDNA. (United States)

    Bloom, Kristie; Ely, Abdullah; Arbuthnot, Patrick


    Gene editing using designer nucleases is now widely used in many fields of molecular biology. The technology is being developed for the treatment of viral infections such as persistant hepatitis B virus (HBV). The replication intermediate of HBV comprising covalently closed circular DNA (cccDNA) is stable and resistant to available licensed antiviral agents. Advancing gene editing as a means of introducing targeted mutations into cccDNA thus potentially offers the means to cure infection by the virus. Essentially, targeted mutations are initiated by intracellular DNA cleavage, then error-prone nonhomologous end joining results in insertions and deletions (indels) at intended sites. Characterization of these mutations is crucial to confirm activity of potentially therapeutic nucleases. A convenient tool for evaluation of the efficiency of target cleavage is the single strand-specific endonuclease, T7EI. Assays employing this enzyme entail initial amplification of DNA encompassing the targeted region. Thereafter the amplicons are denatured and reannealed to allow hybridization between indel-containing and wild-type sequences. Heteroduplexes that contain mismatched regions are susceptible to action by T7EI and cleavage of the hybrid amplicons may be used as an indicator of efficiency of designer nucleases. The protocol described here provides a method of isolating cccDNA from transfected HepG2.2.15 cells and evaluation of the efficiency of mutation by a transcription activator-like effector nuclease that targets the surface open reading frame of HBV.

  15. Functional Assays for Specific Targeting and Delivery of RNA Nanoparticles to Brain Tumor (United States)

    Lee, Tae Jin; Haque, Farzin; Vieweger, Mario; Yoo, Ji Young; Kaur, Balveen; Guo, Peixuan; Croce, Carlo M.


    Cumulative progress in nanoparticle development has opened a new era of targeted delivery of therapeutics to cancer cells and tissue. However, developing proper detection methods has lagged behind resulting in the lack of precise evaluation and monitoring of the systemically administered nanoparticles. RNA nanoparticles derived from the bacteriophage phi29 DNA packaging motor pRNA have emerged as a new generation of drugs for cancer therapy. Multifunctional RNA nanoparticles can be fabricated by bottom-up self-assembly of engineered RNA fragments harboring targeting (RNA aptamer or chemical ligand), therapeutic (siRNA, miRNA, ribozymes, and small molecule drugs), and imaging (fluorophore, radiolabels) modules. We have recently demonstrated that RNA nanoparticles can reach and target intracranial brain tumors in mice upon systemic injection with little or no accumulation in adjacent healthy brain tissues or in major healthy internal organs. Herein, we describe various functional imaging methods (fluorescence confocal microscopy, flow cytometry, fluorescence whole body imaging, and magnetic resonance imaging) to evaluate and monitor RNA nanoparticle targeting to intracranial brain tumors in mice. Such imaging techniques will allow in-depth evaluation of specifically delivered RNA therapeutics to brain tumors. PMID:25896001

  16. Multi-laboratory evaluations of the performance of Catellicoccus marimammalium PCR assays developed to target gull fecal sources (United States)

    Sinigalliano, Christopher D.; Ervin, Jared S.; Van De Werfhorst, Laurie C.; Badgley, Brian D.; Ballestée, Elisenda; Bartkowiaka, Jakob; Boehm, Alexandria B.; Byappanahalli, Muruleedhara N.; Goodwin, Kelly D.; Gourmelon, Michèle; Griffith, John; Holden, Patricia A.; Jay, Jenny; Layton, Blythe; Lee, Cheonghoon; Lee, Jiyoung; Meijer, Wim G.; Noble, Rachel; Raith, Meredith; Ryu, Hodon; Sadowsky, Michael J.; Schriewer, Alexander; Wang, Dan; Wanless, David; Whitman, Richard; Wuertz, Stefan; Santo Domingo, Jorge W.


    Here we report results from a multi-laboratory (n = 11) evaluation of four different PCR methods targeting the 16S rRNA gene of Catellicoccus marimammalium originally developed to detect gull fecal contamination in coastal environments. The methods included a conventional end-point PCR method, a SYBR® Green qPCR method, and two TaqMan® qPCR methods. Different techniques for data normalization and analysis were tested. Data analysis methods had a pronounced impact on assay sensitivity and specificity calculations. Across-laboratory standardization of metrics including the lower limit of quantification (LLOQ), target detected but not quantifiable (DNQ), and target not detected (ND) significantly improved results compared to results submitted by individual laboratories prior to definition standardization. The unit of measure used for data normalization also had a pronounced effect on measured assay performance. Data normalization to DNA mass improved quantitative method performance as compared to enterococcus normalization. The MST methods tested here were originally designed for gulls but were found in this study to also detect feces from other birds, particularly feces composited from pigeons. Sequencing efforts showed that some pigeon feces from California contained sequences similar to C. marimammalium found in gull feces. These data suggest that the prevalence, geographic scope, and ecology of C. marimammalium in host birds other than gulls require further investigation. This study represents an important first step in the multi-laboratory assessment of these methods and highlights the need to broaden and standardize additional evaluations, including environmentally relevant target concentrations in ambient waters from diverse geographic regions.

  17. Postnatal development of hypoplastic thymus in semi-lethal dwarf pet/pet males. (United States)

    Chiba, Junko; Suzuki, Hiroetsu; Aoyama, Hiroaki; Katayama, Kentaro; Suzuki, Katsushi


    The petit rat (pet/pet) is a new semi-lethal dwarf mutant with anomalies in the thymus and testes, defects inherited as a single autosomal recessive trait. At birth, these pet/pet rats show low birth weight and extremely small thymuses; at 140 days of age, their thymuses show abnormal involution. In the present study, we examined early postnatal development of hypoplastic pet/pet thymuses. In addition to being hypoplastic at birth, pet/pet thymus growth was almost completely impaired during the early postnatal period. As shown by cellular incorporation of BrdU, the mitotic activity was lower in pet/pet than in normal thymuses, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays showed that apoptosis occurred more often in pet/pet than in normal thymus cells during the first few days after birth. These results indicate that postnatal development of the hypoplastic pet/pet thymus is defective due to the reduced proliferation and increased apoptosis of thymic cells.

  18. Comparison of targeted peptide quantification assays for reductive dehalogenases by selective reaction monitoring (SRM) and precursor reaction monitoring (PRM). (United States)

    Schiffmann, Christian; Hansen, Rasmus; Baumann, Sven; Kublik, Anja; Nielsen, Per Halkjær; Adrian, Lorenz; von Bergen, Martin; Jehmlich, Nico; Seifert, Jana


    Targeted absolute protein quantification yields valuable information about physiological adaptation of organisms and is thereby of high interest. Especially for this purpose, two proteomic mass spectrometry-based techniques namely selective reaction monitoring (SRM) and precursor reaction monitoring (PRM) are commonly applied. The objective of this study was to establish an optimal quantification assay for proteins with the focus on those involved in housekeeping functions and putative reductive dehalogenase proteins from the strictly anaerobic bacterium Dehalococcoides mccartyi strain CBDB1. This microbe is small and slow-growing; hence, it provides little biomass for comprehensive proteomic analysis. We therefore compared SRM and PRM techniques. Eleven peptides were successfully quantified by both methods. In addition, six peptides were solely quantified by SRM and four by PRM, respectively. Peptides were spiked into a background of Escherichia coli lysate and the majority of peptides were quantifiable down to 500 amol absolute on column by both methods. Peptide quantification in CBDB1 lysate resulted in the detection of 15 peptides using SRM and 14 peptides with the PRM assay. Resulting quantification of five dehalogenases revealed copy numbers of <10 to 115 protein molecules per cell indicating clear differences in abundance of RdhA proteins during growth on hexachlorobenzene. Our results indicated that both methods show comparable sensitivity and that the combination of the mass spectrometry assays resulted in higher peptide coverage and thus more reliable protein quantification.

  19. Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including early detection of cancers (United States)

    Martinez, Jennifer S.; Swanson, Basil I.; Shively, John E.; Li, Lin


    An assay element is described including recognition ligands adapted for binding to carcinoembryonic antigen (CEA) bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of CEA is described including injecting a possible CEA-containing sample into a sensor cell including the assay element, maintaining the sample within the sensor cell for time sufficient for binding to occur between CEA present within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

  20. Development of a quantitative real-time PCR assay for detection of Vibrio tubiashii targeting the metalloprotease gene. (United States)

    Gharaibeh, Dima N; Hasegawa, Hiroaki; Häse, Claudia C


    Vibrio tubiashii has recently re-emerged as a pathogen of bivalve larvae, causing a marked increase in the mortality of these species within shellfish rearing facilities. This has resulted in substantial losses of seed production and thus created the need for specific as well as sensitive detection methods for this pathogen. In this project, quantitative PCR (qPCR) primers were developed and optimized based upon analysis of the V. tubiashii vtpA gene sequence, encoding a metalloprotease known to cause larval mortality. Standard curves were developed utilizing dilutions of known quantities of V. tubiashii cells that were compared to colony forming unit (CFU) plate counts. The assay was optimized for detection of vtpA with both lab-grown V. tubiashii samples and filter-captured environmental seawater samples seeded with V. tubiashii. In addition, the primers were confirmed to specifically detect only V. tubiashii when tested against a variety of non-target Vibrio species. Validation of the assay was completed by analyzing samples obtained from a shellfish hatchery. The development of this rapid and sensitive assay for quantitative detection of V. tubiashii will accurately determine levels of this bacterium in a variety of seawater samples, providing a useful tool for oyster hatcheries and a method to assess the presence of this bacterium in the current turbulent ocean environment.

  1. Senior Pets (United States)

    ... due to the normal aging process. Some behavior changes in older pets may be due to cognitive dysfunction, which is similar to senility in people. Common behavior changes in older pets that may be signs of cognitive dysfunction: easily disturbed by loud sounds unusually aggressive ...

  2. Lutetium oxyorthosilicate (LSO) intrinsic activity correction and minimal detectable target activity study for SPECT imaging with a LSO-based animal PET scanner (United States)

    Yao, Rutao; Ma, Tianyu; Shao, Yiping


    This work is part of a feasibility study to develop SPECT imaging capability on a lutetium oxyorthosilicate (LSO) based animal PET system. The SPECT acquisition was enabled by inserting a collimator assembly inside the detector ring and acquiring data in singles mode. The same LSO detectors were used for both PET and SPECT imaging. The intrinsic radioactivity of 176Lu in the LSO crystals, however, contaminates the SPECT data, and can generate image artifacts and introduce quantification error. The objectives of this study were to evaluate the effectiveness of a LSO background subtraction method, and to estimate the minimal detectable target activity (MDTA) of image object for SPECT imaging. For LSO background correction, the LSO contribution in an image study was estimated based on a pre-measured long LSO background scan and subtracted prior to the image reconstruction. The MDTA was estimated in two ways. The empirical MDTA (eMDTA) was estimated from screening the tomographic images at different activity levels. The calculated MDTA (cMDTA) was estimated from using a formula based on applying a modified Currie equation on an average projection dataset. Two simulated and two experimental phantoms with different object activity distributions and levels were used in this study. The results showed that LSO background adds concentric ring artifacts to the reconstructed image, and the simple subtraction method can effectively remove these artifacts—the effect of the correction was more visible when the object activity level was near or above the eMDTA. For the four phantoms studied, the cMDTA was consistently about five times of the corresponding eMDTA. In summary, we implemented a simple LSO background subtraction method and demonstrated its effectiveness. The projection-based calculation formula yielded MDTA results that closely correlate with that obtained empirically and may have predicative value for imaging applications.

  3. A targeted next-generation sequencing assay for the molecular diagnosis of genetic disorders with orodental involvement (United States)

    Prasad, Megana K; Geoffroy, Véronique; Vicaire, Serge; Jost, Bernard; Dumas, Michael; Le Gras, Stéphanie; Switala, Marzena; Gasse, Barbara; Laugel-Haushalter, Virginie; Paschaki, Marie; Leheup, Bruno; Droz, Dominique; Dalstein, Amelie; Loing, Adeline; Grollemund, Bruno; Muller-Bolla, Michèle; Lopez-Cazaux, Séréna; Minoux, Maryline; Jung, Sophie; Obry, Frédéric; Vogt, Vincent; Davideau, Jean-Luc; Davit-Beal, Tiphaine; Kaiser, Anne-Sophie; Moog, Ute; Richard, Béatrice; Morrier, Jean-Jacques; Duprez, Jean-Pierre; Odent, Sylvie; Bailleul-Forestier, Isabelle; Rousset, Monique Marie; Merametdijan, Laure; Toutain, Annick; Joseph, Clara; Giuliano, Fabienne; Dahlet, Jean-Christophe; Courval, Aymeric; El Alloussi, Mustapha; Laouina, Samir; Soskin, Sylvie; Guffon, Nathalie; Dieux, Anne; Doray, Bérénice; Feierabend, Stephanie; Ginglinger, Emmanuelle; Fournier, Benjamin; de la Dure Molla, Muriel; Alembik, Yves; Tardieu, Corinne; Clauss, François; Berdal, Ariane; Stoetzel, Corinne; Manière, Marie Cécile; Dollfus, Hélène; Bloch-Zupan, Agnès


    Background Orodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders. Methods We designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption. Results We discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases. Conclusions We have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease. Trial registration numbers NCT01746121 and NCT02397824. PMID:26502894

  4. Combining multiple FDG-PET radiotherapy target segmentation methods to reduce the effect of variable performance of individual segmentation methods

    Energy Technology Data Exchange (ETDEWEB)

    McGurk, Ross J. [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Bowsher, James; Das, Shiva K. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27705 (United States); Lee, John A [Molecular Imaging and Experimental Radiotherapy Unit, Universite Catholique de Louvain, 1200 Brussels (Belgium)


    Purpose: Many approaches have been proposed to segment high uptake objects in 18F-fluoro-deoxy-glucose positron emission tomography images but none provides consistent performance across the large variety of imaging situations. This study investigates the use of two methods of combining individual segmentation methods to reduce the impact of inconsistent performance of the individual methods: simple majority voting and probabilistic estimation. Methods: The National Electrical Manufacturers Association image quality phantom containing five glass spheres with diameters 13-37 mm and two irregularly shaped volumes (16 and 32 cc) formed by deforming high-density polyethylene bottles in a hot water bath were filled with 18-fluoro-deoxyglucose and iodine contrast agent. Repeated 5-min positron emission tomography (PET) images were acquired at 4:1 and 8:1 object-to-background contrasts for spherical objects and 4.5:1 and 9:1 for irregular objects. Five individual methods were used to segment each object: 40% thresholding, adaptive thresholding, k-means clustering, seeded region-growing, and a gradient based method. Volumes were combined using a majority vote (MJV) or Simultaneous Truth And Performance Level Estimate (STAPLE) method. Accuracy of segmentations relative to CT ground truth volumes were assessed using the Dice similarity coefficient (DSC) and the symmetric mean absolute surface distances (SMASDs). Results: MJV had median DSC values of 0.886 and 0.875; and SMASD of 0.52 and 0.71 mm for spheres and irregular shapes, respectively. STAPLE provided similar results with median DSC of 0.886 and 0.871; and median SMASD of 0.50 and 0.72 mm for spheres and irregular shapes, respectively. STAPLE had significantly higher DSC and lower SMASD values than MJV for spheres (DSC, p < 0.0001; SMASD, p= 0.0101) but MJV had significantly higher DSC and lower SMASD values compared to STAPLE for irregular shapes (DSC, p < 0.0001; SMASD, p= 0.0027). DSC was not significantly

  5. Real-Time PCR Assay Targeting the veA Gene for Quantification of Aspergillus carbonarius in Grapes. (United States)

    Kizis, Dimosthenis; Nychas, George-John E; Panagou, Efstathios Z


    In this work, a SYBR Green I real-time PCR method has been developed for the detection and quantification of Aspergillus carbonarius in grapes by targeting the veA gene with a primer pair (veAF4/veAR4) that specifically amplifies a 91-bp PCR product. The quantification of the fungal DNA was performed by generation of standard curves for two A. carbonarius strains, using spectrophotometrically measured DNA quantities (Log) with a linearity range from 50 to 5 × 10(-4) ng of DNA. A high positive correlation (R(2) > 0.99) between exponential increases of DNA and real-time PCR threshold cycles showed a high amplification efficiency for the assay (E values 100.06 and 101.51%, respectively). Quantification of the fungal genomic DNA in grape samples artificially inoculated with A. carbonarius conidia was successfully performed with a minimum threshold of 10(4) conidia per g of grape berry. The assay developed would allow reliable, specific, and efficient detection and quantification of A. carbonarius in grapes.

  6. Effect of peptide assay library size and composition in targeted data-independent acquisition-MS analyses. (United States)

    Parker, Sarah J; Venkatraman, Vidya; Van Eyk, Jennifer E


    The quantification of peptides using targeted analysis of data-independent acquisition MS (DIA-MS) is dependent on the size and characteristics of the assay library. We addressed several important questions on how library composition influences: (1) the number of peptides extracted from DIA-MS datasets, (2) the quality of these peptides and proteins, and (3) the biological conclusions inferred. To answer these questions we constructed five libraries from mouse vascular smooth muscle cell (VSMC) lysate, each unique in depth, input sample complexity, data acquisition mode (DDA-MS or DIA-MS), and precursor fragmentation mode (TOF-CID or Orbitrap HCD) and extracted them against the same eight DIA-MS files of VSMCs treated with vehicle or transforming growth factor β-1 (TGF-β1). We found that along with differences in peptide and protein composition, the fragments representing a given peptide differed between the libraries. Collectively these differences impacted both peak group score profile and protein abundance estimates. Surprisingly, there was little overlap in the TGF-β1 response proteome between libraries. We conclude that additional work is needed to optimize peptide assay library building for DIA-MS applications, particularly in terms of selecting optimal peptides and their respective fragments for protein quantification.

  7. uPAR-targeted optical near-infrared (NIR) fluorescence imaging and PET for image-guided surgery in head and neck cancer

    DEFF Research Database (Denmark)

    Christensen, Anders; Juhl, Karina; Persson, Morten


    xenograft tongue cancer model. EXPERIMENTAL DESIGN AND RESULTS: Tumor growth of tongue cancer was monitored by bioluminescence imaging (BLI) and MRI. Either ICG-Glu-Glu-AE105 (fluorescent agent) or 64Cu-DOTA-AE105 (PET agent) was injected systemically, and fluorescence imaging or PET/CT imaging...

  8. PET Imaging in Head and Neck Cancer Patients to Monitor Treatment Response: A Future Role for EGFR-Targeted Imaging

    NARCIS (Netherlands)

    Dijk, L.K. van; Boerman, O.C.; Kaanders, J.H.A.M.; Bussink, J.


    Approximately 50,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed worldwide each year and subsequently treated with surgery, chemotherapy, radiotherapy, and/or targeted therapy. The heterogeneity of the patient population in terms of treatment response drives the search f

  9. Targeted Peptide Measurements in Biology and Medicine: Best Practices for Mass Spectrometry-based Assay Development Using a Fit-for-Purpose Approach

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Steven A.; Abbateillo, Susan E.; Ackermann, Bradley L.; Borchers, Christoph H.; Domon, Bruno; Deutsch, Eric W.; Grant, Russel; Hoofnagle, Andrew N.; Huttenhain, Ruth; Koomen, John M.; Liebler, Daniel; Liu, Tao; MacLean, Brendan; Mani, DR; Mansfield, Elizabeth; Neubert, Hendrik; Paulovich, Amanda G.; Reiter, Lukas; Vitek, Olga; Aebersold, Ruedi; Anderson, Leigh N.; Bethem, Robert; Blonder, Josip; Boja, Emily; Botelho, Julianne; Boyne, Michael; Bradshaw, Ralph A.; Burlingame, Alma S.; Chan, Daniel W.; Keshishian, Hasmik; Kuhn, Eric; Kingsinger, Christopher R.; Lee, Jerry S.; Lee, Sang-Won; Moritz, Robert L.; Oses-Prieto, Juan; Rifai, Nader; Ritchie, James E.; Rodriguez, Henry; Srinivas, Pothur R.; Townsend, Reid; Van Eyk , Jennifer; Whiteley, Gordon; Wiita, Arun; Weintraub, Susan


    Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on the ability to generate reliable assays that uniquely and confidently identify target peptides in a sample. Unfortunately, there is a wide range of criteria being applied to say that an assay has been successfully developed. There is no consensus on what criteria are acceptable and little understanding of the impact of variable criteria on the quality of the results generated. Publications describing targeted MS assays for peptides frequently do not contain sufficient information for readers to establish confidence that the tests work as intended or to be able to apply the tests described in their own labs. Guidance must be developed so that targeted MS assays with established performance can be made widely distributed and applied by many labs worldwide. To begin to address the problems and their solutions, a workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays. Participants discussed the analytical goals of their experiments and the experimental evidence needed to establish that the assays they develop work as intended and are achieving the required levels of performance. Using this “fit-for-purpose” approach, the group defined three tiers of assays distinguished by their performance and extent of analytical characterization. Computational and statistical tools useful for the analysis of targeted MS results were described. Participants also detailed the information that authors need to provide in their manuscripts to enable reviewers and readers to clearly understand what procedures were performed and to evaluate the reliability of the peptide or protein quantification measurements reported. This paper presents a summary of the meeting and

  10. Positron Emission Tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.


    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET. 22 figs.

  11. Positron Emission Tomography (PET) (United States)

    Welch, M. J.


    Positron emission tomography (PET) assesses biochemical processes in the living subject, producing images of function rather than form. Using PET, physicians are able to obtain not the anatomical information provided by other medical imaging techniques, but pictures of physiological activity. In metaphoric terms, traditional imaging methods supply a map of the body's roadways, its, anatomy; PET shows the traffic along those paths, its biochemistry. This document discusses the principles of PET, the radiopharmaceuticals in PET, PET research, clinical applications of PET, the cost of PET, training of individuals for PET, the role of the United States Department of Energy in PET, and the futures of PET.

  12. Gene-targeted radiation therapy mediated by radiation-sensitive promoter in lung adenocarcinoma and the feasibility of micro-PET / CT in evaluation of therapeutic effectiveness in small animals

    Institute of Scientific and Technical Information of China (English)



    Objective To explore the combined anti-tumor effect of radiation therapy and gene-targeted suppression of tumor neovasculature in lung adenocarcinoma in vivo,and to explore the feasibility of micro-PET/CT in dynamic evaluation of treatment effectiveness.Methods Thirty5-6 week old male BALB/c nude mice were used in this study.The mouse models of xenotransplanted human

  13. Comparison of gull-specific assays targeting 16S rRNA gene of Catellicoccus marimammalium and Streptococcus spp. (United States)

    Gulls have been implicated as a source of fecal contamination in inland and coastal waters. Only one gull-specific assay is currently available (i.e., gull2 qPCR assay). This assay is based on the 16S rRNA gene of Catellicocclls marimammalium and has showed a high level of host-s...

  14. Methodologies for localizing loco-regional hypopharyngeal carcinoma recurrences in relation to FDG-PET positive and clinical radiation therapy target volumes

    DEFF Research Database (Denmark)

    Due, Anne Kirkebjerg; Korreman, Stine; Bentzen, Søren M;


    Focal methods to determine the source of recurrence are presented, tested for reproducibility and compared to volumetric approaches with respect to the number of recurrences ascribed to the FDG-PET positive and high dose volumes....

  15. Methodologies for localizing loco-regional hypopharyngeal carcinoma recurrences in relation to FDG-PET positive and clinical radiation therapy target volumes

    DEFF Research Database (Denmark)

    Due, Anne Kirkebjerg; Korreman, Stine Sofia; Tomé, Wolfgang;


    Focal methods to determine the source of recurrence are presented, tested for reproducibility and compared to volumetric approaches with respect to the number of recurrences ascribed to the FDG-PET positive and high dose volumes.......Focal methods to determine the source of recurrence are presented, tested for reproducibility and compared to volumetric approaches with respect to the number of recurrences ascribed to the FDG-PET positive and high dose volumes....

  16. Pitfalls of the MTT assay: Direct and off-target effects of inhibitors can result in over/underestimation of cell viability. (United States)

    Stepanenko, A A; Dmitrenko, V V


    The MTT assay (to a less degree MTS, XTT or WST) is a widely exploited approach for measuring cell viability/drug cytotoxicity. MTT reduction occurs throughout a cell and can be significantly affected by a number of factors, including metabolic and energy perturbations, changes in the activity of oxidoreductases, endo-/exocytosis and intracellular trafficking. Over/underestimation of cell viability by the MTT assay may be due to both adaptive metabolic and mitochondrial reprogramming of cells subjected to drug treatment-mediated stress and inhibitor off-target effects. Previously, imatinib, rottlerin, ursolic acid, verapamil, resveratrol, genistein nanoparticles and some polypeptides were shown to interfere with MTT reduction rate resulting in inconsistent results between the MTT assay and alternative assays. Here, to test the under/overestimation of viability by the MTT assay, we compared results derived from the MTT assay with the trypan blue exclusion assay after treatment of glioblastoma U251, T98G and C6 cells with three widely used inhibitors with the known direct and side effects on energy and metabolic homeostasis - temozolomide (TMZ), a DNA-methylating agent, temsirolimus (TEM), an inhibitor of mTOR kinase, and U0126, an inhibitor of MEK1/2 kinases. Inhibitors were applied shortly as in IC50 evaluating studies or long as in studies focusing on drug resistance acquisition. We showed that over/underestimation of cell viability by the MTT assay and its significance depends on a cell line, a time point of viability measurement and other experimental parameters. Furthermore, we provided a comprehensive survey of factors that should be accounted in the MTT assay. To avoid result misinterpretation, supplementation of the tetrazolium salt-based assays with other non-metabolic assays is recommended.

  17. Pathological validation of FLT PET-CT in delineating the biological target length of gross tumor in esophageal carcinoma%氟脱氧胸苷PET-CT勾划食管癌大体肿瘤生物靶区长度的病理对照研究

    Institute of Scientific and Technical Information of China (English)

    韩大力; 孙翔宇; 于甬华; 于金明; 钟小军; 付正; 穆殿斌; 张桂芳; 张百江; 李辉


    目的 应用术后病理作为对照判断氟脱氧胸苷(FLT)PET-CT检测食管癌大体肿瘤生物靶区长度的最佳方法 和最佳界值,并与FDG PET-CT、CT、食管钡餐和食管镜进行直接对照研究.方法 24例患者行FLT PET-CT检查,其中22例行FDG PET-CT检查对照,全部患者均常规行食管钡餐、食管镜检查并均接受食管癌根治切除术.FLT PET-CT长度采用肉眼法,记为L_(FLTvisual),和采用SUV 1.3、1.4、1.5以及SUV_(max)的20%、25%和30%分别记为L_(FLT1.3)、L_(FLT1.4)、L_(FLT1.5)、L_(FLT20%)、L_(FLT25%)、L_(FLT30%);FDG PET-CT长度采用肉眼法、SUV 2.5和SUV_(max)的40%分别记为L_(FDGviaual)、L_(FDG2.5)、L_(FDG40%).CT、食管钡餐和食管镜所测得病变长度分别记为L_(CT)、L_(Scopy)和L_(X-ray)分别与术后病理长度L_(Path)进行比较.结果 L_(Path)值为(4.90±2.14)cm,各检测方法 所得病变长度由小到大依次为L_(FDG40%)、L_(Scopy)、L_(X-ray)、L_(FLT1.5)、L_(CT)、L_(FLT30%)、L_(FLTvis)、L_(FLT1.4)、L_(FLT25%)、L_(FDG2.5)、L_(FDGvis)、L_(FLT1.3)、L_(FLT20%),均数分别为(3.85±1.52)、(4.46±2.23)、(4.63±2.37)、(4.64±2.38)、(4.69±1.85)、(4.75±2.19)、(4.85±2.33)、(4.87±2.35)、(5.05±2.20)、(5.08±2.19)、(5.10 ±2.22)、(5.21 ±2.40)、(5.53±2.17)cm,与L_(Path)的相关系数分别为0.91、0.93、0.88、0.95、0.90、0.81、0.96、0.96、0.80、0.99、0.99、0.95、0.79,P值均为0.000.L_(FLT1.4)和L_(FDG2.5)分别为最佳FLT PET-CT和FDG PET-CT长度,且L_(FDG2.5)与L_(FLT1.4)相似(t=1.23,P=0.232).结论 最接近食管癌病理长度的FLT PET-CT界值为SUV 1.4,而FDG PET-CT的为SUV 2.5,可作为客观和简便易行的半定量分析指标.%Objective To establish a optimal method and threshold of 3-deoxy-3-fluorothymidine (FLT) PET-CT in delineating the biological target length of gross tumor in esophageal carcinoma, and to compare FLT PET-CT with other imaging modalities including esophagoseopy, esophagography, CT and flu

  18. Targeted capture enrichment assay for non-invasive prenatal testing of large and small size sub-chromosomal deletions and duplications (United States)

    Tsangaras, Kyriakos; Kypri, Elena; Loizides, Charalambos; Ioannides, Marios; Achilleos, Achilleas; Mina, Petros; Keravnou, Anna; Sismani, Carolina; Koumbaris, George; Patsalis, Philippos C.


    Noninvasive prenatal testing (NIPT) using whole genome and targeted sequencing has become increasingly accepted for clinical detection of Trisomy 21 and sex chromosome aneuploidies. Few studies have shown that sub-chromosomal deletions or duplications associated with genetic syndromes can also be detected in the fetus noninvasively. There are still limitations on these methodologies such as the detection of variants of unknown clinical significance, high number of false positives, and difficulties to detect small aberrations. We utilized a recently developed targeted sequencing approach for the development of a NIPT assay, for large and small size deletions/duplications, which overcomes these existing limitations. Artificial pregnancies with microdeletion/microduplication syndromes were created by spiking DNA from affected samples into cell free DNA (cfDNA) from non-pregnant samples. Unaffected spiked samples and normal pregnancies were used as controls. Target Capture Sequences (TACS) for seven syndromes were designed and utilized for targeted capture enrichment followed by sequencing. Data was analyzed using a statistical pipeline to identify deletions or duplications on targeted regions. Following the assay development a proof of concept study using 33 normal pregnancies, 21 artificial affected and 17 artificial unaffected pregnancies was carried out to test the sensitivity and specificity of the assay. All 21 abnormal spiked-in samples were correctly classified as subchromosomal aneuploidies while the 33 normal pregnancies or 17 normal spiked-in samples resulted in a false positive result. We have developed an NIPT assay for the detection of sub-chromosomal deletions and duplications using the targeted capture enrichment technology. This assay demonstrates high accuracy, high read depth of the genomic region of interest, and can identify deletions/duplications as small as 0.5 Mb. NIPT of fetal microdeletion/microduplication syndromes can be of enormous benefit

  19. Pet Therapy. (United States)

    Kavanagh, Kim


    This resource guide presents information on a variety of ways that animals can be used as a therapeutic modality with people having disabilities. Aspects addressed include: pet ownership and selection criteria; dogs (including service dogs, hearing/signal dogs, seeing leader dogs, and social/specialty dogs); horseriding for both therapy and fun;…

  20. Planar optical waveguide based sandwich assay sensors and processes for the detection of biological targets including protein markers, pathogens and cellular debris (United States)

    Martinez, Jennifer S.; Swanson, Basil I.; Grace, Karen M.; Grace, Wynne K.; Shreve, Andrew P.


    An assay element is described including recognition ligands bound to a film on a single mode planar optical waveguide, the film from the group of a membrane, a polymerized bilayer membrane, and a self-assembled monolayer containing polyethylene glycol or polypropylene glycol groups therein and an assay process for detecting the presence of a biological target is described including injecting a biological target-containing sample into a sensor cell including the assay element, with the recognition ligands adapted for binding to selected biological targets, maintaining the sample within the sensor cell for time sufficient for binding to occur between selected biological targets within the sample and the recognition ligands, injecting a solution including a reporter ligand into the sensor cell; and, interrogating the sample within the sensor cell with excitation light from the waveguide, the excitation light provided by an evanescent field of the single mode penetrating into the biological target-containing sample to a distance of less than about 200 nanometers from the waveguide thereby exciting the fluorescent-label in any bound reporter ligand within a distance of less than about 200 nanometers from the waveguide and resulting in a detectable signal.

  1. Impact of target-to-background ratio, target size, emission scan duration, and activity on physical figures of merit for a 3D LSO-based whole body PET/CT scanner. (United States)

    Brambilla, M; Matheoud, R; Secco, C; Sacchetti, G; Comi, S; Rudoni, M; Carriero, A; Inglese, E


    The aim of our work is to describe the way in which physical figures of merit such as contrast-to-noise ratio (CNR) behave when varying acquisition parameters such as emission scan duration (ESD) or activity at the start of acquisition (A(acq)) that in clinical practice can be selected by the user, or object properties such as target dimensions or target-to-background (T/B) ratio, which depend uniquely on the intrinsic characteristics of the object being imaged. Figures of merit, used to characterize image quality and quantitative accuracy for a 3D-LSO based PET/CT scanner, were studied as a function of ESD and A(acq) for different target sizes and T/B ratios using a multivariate approach in a wide range of conditions approaching the ones that can be encountered in clinical practice. An annular ring of water bags of 3 cm thickness was fitted over an IEC phantom in order to obtain counting rates similar to those found in average patients. The average scatter fraction (SF) of the modified IEC phantom was similar to the mean SF measured on patients with a similar scanner. A supplemental set of micro-hollow spheres was positioned inside the phantom. The NEMA NU 2-2001 scatter phantom was positioned at the end of the IEC phantom to approximate the clinical situation of having activity that extends beyond the scanner. The phantoms were filled with a solution of water and 18F (12 kBq/mL) and the spheres with various T/B ratios of 22.5, 10.3, and 3.6. Sequential imaging was performed to acquire PET images with varying background activity concentrations of about 12, 9, 6.4, 5.3, and 3.1 kBq/mL, positioned on the linear portion of the phantom's NECR curve, well below peak NECR of 61.2 kcps that is reached at 31.8 kBq/mL. The ESD was set to 1, 2, 3, and 4 min/bed. With T/B ratios of 3.6, 10.3, and 22.5, the 13.0, 8.1, and 6.5 mm spheres were detectable for the whole ranges of background activity concentration and ESD, respectively. The ESD resulted as the most significant

  2. [¹⁸F]-fluorodeoxyglucose PET imaging of atherosclerosis

    DEFF Research Database (Denmark)

    Blomberg, Björn Alexander; Høilund-Carlsen, Poul Flemming


    [(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk of atheros......[(18)F]-fluorodeoxyglucose PET ((18)FDG PET) imaging has emerged as a promising tool for assessment of atherosclerosis. By targeting atherosclerotic plaque glycolysis, a marker for plaque inflammation and hypoxia, (18)FDG PET can assess plaque vulnerability and potentially predict risk...... of atherosclerosis-related disease, such as stroke and myocardial infarction. With excellent reproducibility, (18)FDG PET can be a surrogate end point in clinical drug trials, improving trial efficiency. This article summarizes key findings in the literature, discusses limitations of (18)FDG PET imaging...... of atherosclerosis, and reports recommendations to optimize imaging protocols....

  3. Analysis of in vitro bioactivity data extracted from drug discovery literature and patents: Ranking 1654 human protein targets by assayed compounds and molecular scaffolds

    Directory of Open Access Journals (Sweden)

    Southan Christopher


    Full Text Available Abstract Background Since the classic Hopkins and Groom druggable genome review in 2002, there have been a number of publications updating both the hypothetical and successful human drug target statistics. However, listings of research targets that define the area between these two extremes are sparse because of the challenges of collating published information at the necessary scale. We have addressed this by interrogating databases, populated by expert curation, of bioactivity data extracted from patents and journal papers over the last 30 years. Results From a subset of just over 27,000 documents we have extracted a set of compound-to-target relationships for biochemical in vitro binding-type assay data for 1,736 human proteins and 1,654 gene identifiers. These are linked to 1,671,951 compound records derived from 823,179 unique chemical structures. The distribution showed a compounds-per-target average of 964 with a maximum of 42,869 (Factor Xa. The list includes non-targets, failed targets and cross-screening targets. The top-278 most actively pursued targets cover 90% of the compounds. We further investigated target ranking by determining the number of molecular frameworks and scaffolds. These were compared to the compound counts as alternative measures of chemical diversity on a per-target basis. Conclusions The compounds-per-protein listing generated in this work (provided as a supplementary file represents the major proportion of the human drug target landscape defined by published data. We supplemented the simple ranking by the number of compounds assayed with additional rankings by molecular topology. These showed significant differences and provide complementary assessments of chemical tractability.

  4. Loop-Mediated Isothermal Amplification Assay Targeting the MOMP Gene for Rapid Detection of Chlamydia psittaci Abortus Strain

    Directory of Open Access Journals (Sweden)

    Guo-Zhen Lin, Fu-Ying Zheng, Ji-Zhang Zhou, Guang-Hua Wang, Xiao-An Cao, Xiao-Wei Gong and Chang-Qing Qiu*


    Full Text Available For rapid detection of the Chlamydia psittaci abortus strain, a loop-mediated isothermal amplification (LAMP assay was developed and evaluated in this study. The primers for the LAMP assay were designed on the basis of the main outer membrane protein (MOMP gene sequence of C. psittaci. Analysis showed that the assay could detect the abortus strain of C. psittaci with adequate specificity. The sensitivity of the test was the same as that of the nested-conventional PCR and higher than that of chick embryo isolation. Testing of 153 samples indicated that the LAMP assay could detect the genome of the C. psittaci abortus strain effectively in clinical samples. This assay is a useful tool for rapid diagnosis of C. psittaci infection in sheep, swine and cattle.

  5. Development of quantitative PCR assays targeting the 16S rRNA genes of Enterococcus spp. and their application to the identification of enterococcus species in environmental samples. (United States)

    Ryu, Hodon; Henson, Michael; Elk, Michael; Toledo-Hernandez, Carlos; Griffith, John; Blackwood, Denene; Noble, Rachel; Gourmelon, Michèle; Glassmeyer, Susan; Santo Domingo, Jorge W


    The detection of environmental enterococci has been determined primarily by using culture-based techniques that might exclude some enterococcal species as well as those that are nonculturable. To address this, the relative abundances of enterococci were examined by challenging fecal and water samples against a currently available genus-specific assay (Entero1). To determine the diversity of enterococcal species, 16S rRNA gene-based group-specific quantitative PCR (qPCR) assays were developed and evaluated against eight of the most common environmental enterococcal species. Partial 16S rRNA gene sequences of 439 presumptive environmental enterococcal strains were analyzed to study further the diversity of enterococci and to confirm the specificities of group-specific assays. The group-specific qPCR assays showed relatively high amplification rates with targeted species (>98%), although some assays cross-amplified with nontargeted species (1.3 to 6.5%). The results with the group-specific assays also showed that different enterococcal species co-occurred in most fecal samples. The most abundant enterococci in water and fecal samples were Enterococcus faecalis and Enterococcus faecium, although we identified more water isolates as Enterococcus casseliflavus than as any of the other species. The prevalence of the Entero1 marker was in agreement with the combined number of positive signals determined by the group-specific assays in most fecal samples, except in gull feces. On the other hand, the number of group-specific assay signals was lower in all water samples tested, suggesting that other enterococcal species are present in these samples. While the results highlight the value of genus- and group-specific assays for detecting the major enterococcal groups in environmental water samples, additional studies are needed to determine further the diversity, distributions, and relative abundances of all enterococcal species found in water.

  6. Clinical validation of the HPV-risk assay, a novel real-time PCR assay for detection of high-risk human papillomavirus DNA by targeting the E7 region. (United States)

    Hesselink, A T; Berkhof, J; van der Salm, M L; van Splunter, A P; Geelen, T H; van Kemenade, F J; Bleeker, M G B; Heideman, D A M


    The HPV-Risk assay is a novel real-time PCR assay targeting the E7 region of 15 high-risk human papillomavirus (HPV) types (i.e., HPV16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -67, and -68), and provides additional genotype information for HPV16 and HPV18. This study evaluated the clinical performance and reproducibility of the HPV-Risk assay with cervical scraping specimens and its utility with self-collected (cervico)vaginal specimens. The clinical performance of the HPV-Risk assay for cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) with cervical scraping specimens was evaluated by a noninferiority analysis, relative to high-risk HPV GP5+/6+ PCR, following international guidelines for HPV test requirements for cervical cancer screening. The HPV-Risk assay showed clinical sensitivity for CIN2+ of 97.1% (95% confidence interval [CI], 89.1 to 99.3%; 67/69 samples) and a clinical specificity for CIN2+ of 94.3% (95% CI, 92.5 to 95.7%; 777/824 samples). The clinical sensitivity and specificity were noninferior to those of GP5+/6+ PCR (noninferiority score test, P=0.006 and 0.0003, respectively). Intralaboratory reproducibility over time (99.5% [95% CI, 98.6 to 99.8%]; 544/547 samples, kappa=0.99) and interlaboratory agreement (99.2% [95% CI, 98.6 to 99.8%]; 527/531 samples, kappa=0.98) for the HPV-Risk assay with cervical scraping specimens were high. The agreement of the HPV-Risk assay results for self-collected (cervico)vaginal specimens and clinician-obtained cervical scraping specimens was also high, i.e., 95.9% (95% CI, 85.1 to 99.0%; 47/49 samples, kappa=0.90) for self-collected lavage samples and 91.6% (95% CI, 84.6 to 95.6%; 98/107 samples, kappa=0.82) for self-collected brush samples. In conclusion, the HPV-Risk assay meets the cross-sectional clinical and reproducibility criteria of the international guidelines for HPV test requirements and can be considered clinically validated for cervical screening purposes. The

  7. American Pet Culture

    Institute of Scientific and Technical Information of China (English)



    In America you can find dogs,cats, horses,monkeys, snakes and even pigs in almost every family.They are their pets.Americans love pets and look on them as a part of the family.Sometimes pet owners dress their pets in fashionable clothes.They even buy toys for their pets.Americans love their pets as their children, sometimes even better.

  8. Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

    Directory of Open Access Journals (Sweden)

    Francisco J. Romero Durán


    Full Text Available In a multi-target complex network, the links (Lij represent the interactions between the drug (di and the target (tj, characterized by different experimental measures (Ki, Km, IC50, etc. obtained in pharmacological assays under diverse boundary conditions (cj. In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%–90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human. Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1 assay in absence of neurotoxic agents; (2 in the presence of glutamate; and (3 in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.

  9. Access to a polymerase chain reaction assay method targeting 13 respiratory viruses can reduce antibiotics: a randomised, controlled trial

    Directory of Open Access Journals (Sweden)

    Lindh Magnus


    Full Text Available Abstract Background Viral respiratory infections are common worldwide and range from completely benign disease to life-threatening illness. Symptoms can be unspecific, and an etiologic diagnosis is rarely established because of a lack of suitable diagnostic tools. Improper use of antibiotics is common in this setting, which is detrimental in light of the development of bacterial resistance. It has been suggested that the use of diagnostic tests could reduce antibiotic prescription rates. The objective of this study was to evaluate whether access to a multiplex polymerase chain reaction (PCR assay panel for etiologic diagnosis of acute respiratory tract infections (ARTIs would have an impact on antibiotic prescription rate in primary care clinical settings. Methods Adult patients with symptoms of ARTI were prospectively included. Nasopharyngeal and throat swabs were analysed by using a multiplex real-time PCR method targeting thirteen viruses and two bacteria. Patients were recruited at 12 outpatient units from October 2006 through April 2009, and samples were collected on the day of inclusion (initial visit and after 10 days (follow-up visit. Patients were randomised in an open-label treatment protocol to receive a rapid or delayed result (on the following day or after eight to twelve days. The primary outcome measure was the antibiotic prescription rate at the initial visit, and the secondary outcome was the total antibiotic prescription rate during the study period. Results A total sample of 447 patients was randomised. Forty-one were excluded, leaving 406 patients for analysis. In the group of patients randomised for a rapid result, 4.5% (9 of 202 of patients received antibiotics at the initial visit, compared to 12.3% (25 of 204 (P = 0.005 of patients in the delayed result group. At follow-up, there was no significant difference between the groups: 13.9% (28 of 202 in the rapid result group and 17.2% (35 of 204 in the delayed result group (P

  10. PET Molecular Probes Targeting Folate Receptor%靶向叶酸受体的正电子分子探针研究进展

    Institute of Scientific and Technical Information of China (English)

    尹吉林; 王成; 王欣璐


    叶酸能与多种肿瘤细胞膜表面的叶酸受体(FR)特异性结合,通过FR介导的内吞作用进入细胞,为放射性核素选择性载带提供良好的途径。基于受体和配体间的高度亲和性,可将多种放射性核素与叶酸分子及其衍生物偶联,制备核医学显像探针。本文主要对非金属正电子核素(18 F、124 I)和金属正电子核素(68 Ga、44 Sc、152 Tb)标记的叶酸及其衍生物PET显像探针与炎症PET显像探针进行综述,并展望其临床前景。%Folic acid can combine specifically with folate receptors (FRs) which are over‐expressed on the epithelial cells of the tumor .The FRs are confirmed to be the tumor‐associated antigens that bind folate and folate conjugates with very high affinity and shuttle these bound molecules inside cells via an endocytic mechanism .The FR‐αis a tar‐get of critical value for nuclear imaging through using folate‐based radiotracers as it is expressed on several tumor types .Moreover ,employment of folate radiopharmaceuti‐cals for imaging of inflammatory diseases by targeting at FR‐βon activated macrophages holds promise as a further field of application .Based on these ,more and more resear‐ches focus on folate conjugates labeled with radionuclides for nuclear medicine imaging (including single photon emission computed tomography (SPECT ) and positron emis‐sion tomography (PET ) .These folate molecular probes are applied not only in cancer imaging but also in inflammation imaging .Hence ,folate‐based imaging agents may be useful for selection of patients w ho could profit from such new therapy concepts and for monitoring response to a particular treatment .This review was focused on the prepara‐tion and preclinical biological evaluation of the molecular probes which were labeled by positron nuclides (18 F ,124I ,68Ga ,44Sc ,152 Tb) ,and the clinical application of these molecular probes were discussed .

  11. Application of a seven-target pyrosequencing assay to improve the detection of neuraminidase inhibitor-resistant Influenza A(H3N2) viruses. (United States)

    Tamura, Daisuke; Okomo-Adhiambo, Margaret; Mishin, Vasiliy P; Guo, Zhu; Xu, Xiyan; Villanueva, Julie; Fry, Alicia M; Stevens, James; Gubareva, Larisa V


    National U.S. influenza antiviral surveillance incorporates data generated by neuraminidase (NA) inhibition (NI) testing of isolates supplemented with NA sequence analysis and pyrosequencing analysis of clinical specimens. A lack of established correlates for clinically relevant resistance to NA inhibitors (NAIs) hinders interpretation of NI assay data. Nonetheless, A(H3N2) viruses are commonly monitored for moderately or highly reduced inhibition in the NI assay and/or for the presence of NA markers E119V, R292K, and N294S. In 2012 to 2013, three drug-resistant A(H3N2) viruses were detected by NI assay among isolates (n = 1,424); all showed highly reduced inhibition by oseltamivir and had E119V. In addition, one R292K variant was detected among clinical samples (n = 1,024) by a 3-target pyrosequencing assay. Overall, the frequency of NAI resistance was low (0.16% [4 of 2,448]). To screen for additional NA markers previously identified in viruses from NAI-treated patients, the pyrosequencing assay was modified to include Q136K, I222V, and deletions encompassing residues 245 to 248 (del245-248) and residues 247 to 250 (del247-250). The 7-target pyrosequencing assay detected NA variants carrying E119V, Q136, and del245-248 in an isolate from an oseltamivir-treated patient. Next, this assay was applied to clinical specimens collected from hospitalized patients and submitted for NI testing but failed cell culture propagation. Of the 27 clinical specimens tested, 4 (15%) contained NA changes: R292K (n = 2), E119V (n = 1), and del247-250 (n = 1). Recombinant NAs with del247-250 or del245-248 conferred highly reduced inhibition by oseltamivir, reduced inhibition by zanamivir, and normal inhibition by peramivir and laninamivir. Our results demonstrated the benefits of the 7-target pyrosequencing assay in conducting A(H3N2) antiviral surveillance and testing for clinical care.

  12. Development of a robust DNA quality and quantity assessment qPCR assay for targeted next-generation sequencing library preparation. (United States)

    Dang, Jennifer; Mendez, Pedro; Lee, Sharon; Kim, James W; Yoon, Jun-Hee; Kim, Thomas W; Sailey, Charles J; Jablons, David M; Kim, Il-Jin


    Next-generation sequencing (NGS) is becoming a standard for genetic analyses of clinical samples. DNAs retrieved from formalin-fixed, paraffin-embedded (FFPE) tissue specimens are commonly degraded, and specimens such as core biopsies are sometimes too small to obtain enough DNA for NGS applications. Thus, it is important to measure both the DNA quantity and quality accurately from clinical samples. However, there is no standard method for DNA quantity and quality analyses for NGS library preparation. We tested four different methods (PicoGreen, Qubit® fluorometry, TaqMan and SYBR-Green-based qPCR assay) and compared each to RNase P TaqMan as a reference control. We found that SYBR-Green-based qPCR assay provides a consistent and accurate DNA quantification while keeping its cost relatively low and the throughput high. We designed a dual-probe SYBR-Green qPCR assay for DNA quantity and quality assessment for targeted NGS library preparation. This assay provides a Dscore (degradation score) of the interrogated DNA by analyzing two different sizes of amplicons. We show an example of a clinical sample with a very high Dscore (high degradation). With a regular DNA quantification, without considering the degradation status, no correct NGS libraries were obtained. However, after optimizing the library condition by considering its poor DNA quality, a reasonably good library and sequencing results were obtained. In summary, we developed and presented a new DNA quantity and quality analysis qPCR assay for the targeted NGS library preparation. This assay may be mostly efficient for the clinical samples with high degradation and poor DNA quality.

  13. Identification of Five Novel Salmonella Typhi-Specific Genes as Markers for Diagnosis of Typhoid Fever Using Single-Gene Target PCR Assays

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    Yuan Xin Goay


    Full Text Available Salmonella Typhi (S. Typhi causes typhoid fever which is a disease characterised by high mortality and morbidity worldwide. In order to curtail the transmission of this highly infectious disease, identification of new markers that can detect the pathogen is needed for development of sensitive and specific diagnostic tests. In this study, genomic comparison of S. Typhi with other enteric pathogens was performed, and 6 S. Typhi genes, that is, STY0201, STY0307, STY0322, STY0326, STY2020, and STY2021, were found to be specific in silico. Six PCR assays each targeting a unique gene were developed to test the specificity of these genes in vitro. The diagnostic sensitivities and specificities of each assay were determined using 39 S. Typhi, 62 non-Typhi Salmonella, and 10 non-Salmonella clinical isolates. The results showed that 5 of these genes, that is, STY0307, STY0322, STY0326, STY2020, and STY2021, demonstrated 100% sensitivity (39/39 and 100% specificity (0/72. The detection limit of the 5 PCR assays was 32 pg for STY0322, 6.4 pg for STY0326, STY2020, and STY2021, and 1.28 pg for STY0307. In conclusion, 5 PCR assays using STY0307, STY0322, STY0326, STY2020, and STY2021 were developed and found to be highly specific at single-gene target resolution for diagnosis of typhoid fever.

  14. Identification of Five Novel Salmonella Typhi-Specific Genes as Markers for Diagnosis of Typhoid Fever Using Single-Gene Target PCR Assays. (United States)

    Goay, Yuan Xin; Chin, Kai Ling; Tan, Clarissa Ling Ling; Yeoh, Chiann Ying; Ja'afar, Ja'afar Nuhu; Zaidah, Abdul Rahman; Chinni, Suresh Venkata; Phua, Kia Kien


    Salmonella Typhi (S. Typhi) causes typhoid fever which is a disease characterised by high mortality and morbidity worldwide. In order to curtail the transmission of this highly infectious disease, identification of new markers that can detect the pathogen is needed for development of sensitive and specific diagnostic tests. In this study, genomic comparison of S. Typhi with other enteric pathogens was performed, and 6 S. Typhi genes, that is, STY0201, STY0307, STY0322, STY0326, STY2020, and STY2021, were found to be specific in silico. Six PCR assays each targeting a unique gene were developed to test the specificity of these genes in vitro. The diagnostic sensitivities and specificities of each assay were determined using 39 S. Typhi, 62 non-Typhi Salmonella, and 10 non-Salmonella clinical isolates. The results showed that 5 of these genes, that is, STY0307, STY0322, STY0326, STY2020, and STY2021, demonstrated 100% sensitivity (39/39) and 100% specificity (0/72). The detection limit of the 5 PCR assays was 32 pg for STY0322, 6.4 pg for STY0326, STY2020, and STY2021, and 1.28 pg for STY0307. In conclusion, 5 PCR assays using STY0307, STY0322, STY0326, STY2020, and STY2021 were developed and found to be highly specific at single-gene target resolution for diagnosis of typhoid fever.

  15. Pet Problems at Home: Pet Problems in the Community. (United States)

    Soltow, Willow


    Discusses problems of pets in the community, examining the community's role related to disruptive pets and pet overpopulation. Also discusses pet problems at home, offering advice on selecting a pet, meeting a pet's needs, and disciplining pets. Includes a list of books, films/filmstrips, teaching materials, and various instructional strategies.…

  16. Validation of Bacteroidales quantitative PCR assays targeting human and animal fecal contamination in the public and domestic domains in India. (United States)

    Odagiri, Mitsunori; Schriewer, Alexander; Hanley, Kaitlyn; Wuertz, Stefan; Misra, Pravas R; Panigrahi, Pinaki; Jenkins, Marion W


    We compared host-associated Bacteroidales qPCR assays developed in the continental United States and Europe for the purpose of measuring the effect of improved sanitation on human fecal exposure in rural Indian communities where both human and animal fecal loading are high. Ten candidate Bacteroidales qPCR assays were tested against fecal samples (human, sewage, cow, buffalo, goat, sheep, dog and chicken) from a test set of 30 individual human, 5 sewage, and 60 pooled animal samples collected in coastal Odisha, India. The two universal/general Bacteroidales assays tested (BacUni, GenBac3) performed equally well, achieving 100% sensitivity on the test set. Across the five human-associated assays tested (HF183 Taqman, BacHum, HumM2, BacH, HF183 SYBR), we found low sensitivity (17 to 49%) except for HF183 SYBR (89%), and moderate to high cross-reactivity with dog (20 to 80%) and chicken fecal samples (60 to 100%). BacHum had the highest accuracy (67%), amplified all sewage samples within the range of quantification (ROQ), and did not cross-react with any fecal samples from cows, the most populous livestock animal in India. Of the ruminant- and cattle-associated assays tested (BacCow, CowM2), BacCow was more sensitive in detecting the full range of common Indian livestock animal fecal sources, while CowM2 only detected cow sources with 50% sensitivity. Neither assay cross-reacted with human sources. BacCan, the dog-associated assay tested, showed no cross-reactivity with human sources, and high sensitivity (90%) for dog fecal samples. Overall, our results indicate BacUni, BacHum, HumM2, BacCan and BacCow would be the most suitable MST assays to distinguish and quantify relative amounts of human-associated and livestock/domestic animal-associated contributions to fecal contamination in Odisha, India.

  17. Discovery of [¹¹C]MK-8193 as a PET tracer to measure target engagement of phosphodiesterase 10A (PDE10A) inhibitors. (United States)

    Cox, Christopher D; Hostetler, Eric D; Flores, Broc A; Evelhoch, Jeffrey L; Fan, Hong; Gantert, Liza; Holahan, Marie; Eng, Waisi; Joshi, Aniket; McGaughey, Georgia; Meng, Xiangjun; Purcell, Mona; Raheem, Izzat T; Riffel, Kerry; Yan, Youwei; Renger, John J; Smith, Sean M; Coleman, Paul J


    Phosphodiesterase 10A (PDE10A) inhibition has recently been identified as a potential mechanism to treat multiple symptoms that manifest in schizophrenia. In order to facilitate preclinical development and support key proof-of-concept clinical trials of novel PDE10A inhibitors, it is critical to discover positron emission tomography (PET) tracers that enable plasma concentration/PDE10A occupancy relationships to be established across species with structurally diverse PDE10A inhibitors. In this Letter, we describe how a high-throughput screening hit was optimized to provide [(11)C]MK-8193 (8j), a PET tracer that supports the determination of plasma concentration/PDE10A occupancy relationships for structurally diverse series of PDE10A inhibitors in both rat and rhesus monkey.


    Widespread planting of genetically modified crops with the Bt transgene pesticide has led to concern over non-target effects of Bt compounds in agroecosystems. While some research suggests that non-target organisms exposed to Bt toxin exhibit reduced fecundity and increased morta...

  19. Earthworm Comet Assay for Assessing the Risk of Weathered Petroleum Hydrocarbon Contaminated Soils: Need to Look Further than Target Contaminants. (United States)

    Ramadass, Kavitha; Palanisami, Thavamani; Smith, Euan; Mayilswami, Srinithi; Megharaj, Mallavarapu; Naidu, Ravi


    Earthworm toxicity assays contribute to ecological risk assessment and consequently standard toxicological endpoints, such as mortality and reproduction, are regularly estimated. These endpoints are not enough to better understand the mechanism of toxic pollutants. We employed an additional endpoint in the earthworm Eisenia andrei to estimate the pollutant-induced stress. In this study, comet assay was used as an additional endpoint to evaluate the genotoxicity of weathered hydrocarbon contaminated soils containing 520 to 1450 mg hydrocarbons kg(-1) soil. Results showed that significantly higher DNA damage levels (two to sixfold higher) in earthworms exposed to hydrocarbon impacted soils. Interestingly, hydrocarbons levels in the tested soils were well below site-specific screening guideline values. In order to explore the reasons for observed toxicity, the contaminated soils were leached with rainwater and subjected to earthworm tests, including the comet assay, which showed no DNA damage. Soluble hydrocarbon fractions were not found originally in the soils and hence no hydrocarbons leached out during soil leaching. The soil leachate's Electrical Conductivity (EC) decreased from an average of 1665 ± 147 to 204 ± 20 µS cm(-1). Decreased EC is due to the loss of sodium, magnesium, calcium, and sulphate. The leachate experiment demonstrated that elevated salinity might cause the toxicity and not the weathered hydrocarbons. Soil leaching removed the toxicity, which is substantiated by the comet assay and soil leachate analysis data. The implication is that earthworm comet assay can be included in future eco (geno) toxicology studies to assess accurately the risk of contaminated soils.

  20. Target Product Profile for a Diagnostic Assay to Differentiate between Bacterial and Non-Bacterial Infections and Reduce Antimicrobial Overuse in Resource-Limited Settings: An Expert Consensus. (United States)

    Dittrich, Sabine; Tadesse, Birkneh Tilahun; Moussy, Francis; Chua, Arlene; Zorzet, Anna; Tängdén, Thomas; Dolinger, David L; Page, Anne-Laure; Crump, John A; D'Acremont, Valerie; Bassat, Quique; Lubell, Yoel; Newton, Paul N; Heinrich, Norbert; Rodwell, Timothy J; González, Iveth J


    Acute fever is one of the most common presenting symptoms globally. In order to reduce the empiric use of antimicrobial drugs and improve outcomes, it is essential to improve diagnostic capabilities. In the absence of microbiology facilities in low-income settings, an assay to distinguish bacterial from non-bacterial causes would be a critical first step. To ensure that patient and market needs are met, the requirements of such a test should be specified in a target product profile (TPP). To identify minimal/optimal characteristics for a bacterial vs. non-bacterial fever test, experts from academia and international organizations with expertise in infectious diseases, diagnostic test development, laboratory medicine, global health, and health economics were convened. Proposed TPPs were reviewed by this working group, and consensus characteristics were defined. The working group defined non-severely ill, non-malaria infected children as the target population for the desired assay. To provide access to the most patients, the test should be deployable to community health centers and informal health settings, and staff should require 90% and >80% for sensitivity and specificity, respectively. Other key characteristics, to account for the challenging environment at which the test is targeted, included: i) time-to-result targeted and timely efforts by industry partners and academic institutions.

  1. Comparison of target volumes in radiotherapy defined on scanner and on PET-T.D.M. with {sup 18}F-F.D.G. in the frame of head and neck cancers; Comparaison des volumes cibles en radiotherapie definis sur scanner et sur TEP-TDM au 18F FDG dans le cadre des cancers de la tete et du cou

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    Henriques De Figueiredo, B.; Barret, O.; Allard, M.; Fernandez, P. [Service de medecine nucleaire, CHU de Pellegrin, Bordeaux, (France); Demeaux, H.; Maire, J.P.; Lagarde, P. [service de radiotherapie, hopital Saint-Andre, Bordeaux, (France); Kantor, G.; Richau, P. [departement de radiotherapie, institut Bergonie, Bordeaux, (France); De Mones Del Pujol, E. [service d' ORL, hopital Pellegrin, Bordeaux, (France)


    The objective is to study in a prospective way, in the frame of head and neck cancers, the impact of the positron computed tomography with {sup 18}F fluorodeoxyglucose (PET-F.D.G.) on the limitation of target volumes in radiotherapy. In conclusions, the gross tumor volume (G.T.V.) defined on PET is smaller than this one defined on scanner, that could be interesting in radiotherapy, in the perspective of a dose escalation. In addition, areas of discordance exist between the clinical target volumes (C.T.V.70 and C.T.V.50) defined on PET and on scanner. These discordances, synonyms of under or over estimation of target volumes, could have important clinical consequences in term of local control and toxicity. (N.C.)

  2. Multiplex Real-Time PCR Assay Targeting Eight Parasites Customized to the Korean Population: Potential Use for Detection in Diarrheal Stool Samples from Gastroenteritis Patients (United States)

    Won, Eun Jeong; Kim, Soo Hyun; Kee, Seung Jung; Shin, Jong Hee; Suh, Soon Pal; Chai, Jong Yil; Ryang, Dong Wook; Shin, Myung Geun


    Intestinal parasitic diseases occur worldwide and can cause diarrhea or gastroenteritis; however, their diagnosis is quite difficult, especially in low-endemism countries. We developed a multiplex real-time PCR assay for detection of eight intestinal parasites and prospectively evaluated it for patients with gastroenteritis. The assay targeted Cryptosporidium parvum, Giardia lamblia, Entamoeba histolytica, Blastocystis hominis, Dientamoeba fragilis, Clonorchis sinensis, Metagonimus yokogawai, and Gymnophalloides seoi. Performance characteristics were evaluated based on recovery after DNA extraction, analytical sensitivity, specificity, reproducibility, cross-reactivity, and interference characteristics. Clinical performance was validated against microscopy on 123 diarrheal samples. The assay demonstrated strong correlations between DNA concentrations and Ct values (R2, 0.9924–0.9998), and had a high PCR efficiency (83.3%–109.5%). Polymerase chain reactions detected as few as 10–30 copies of genomic DNA, and coefficient of variance was 0–7%. There was no cross-reactivity to the other 54 microorganisms tested. Interference occurred only in presence of high concentrations of erythrocytes or leukocytes. This assay had a higher correct identification rate (100.0% vs. 90.2%) and lower incorrect ID rate (0.0% vs. 9.8%) when compared to microscopy. Overall, this assay showed a higher sensitivity (100.0%; 95% confidence interval [CI] of 80.5–100.0) than microscopy (29.4%; 95% CI 10.31–55.96), and the specificity levels were comparable for both methods (100.0%; 95% CI 96.58–100.0). This newly developed multiplex real-time PCR assay offers a potential use for detecting intestinal parasitic pathogens customized to the Korean population. PMID:27861635

  3. A sandwich-hybridization assay for simultaneous determination of HIV and tuberculosis DNA targets based on signal amplification by quantum dots-PowerVision™ polymer coding nanotracers. (United States)

    Yan, Zhongdan; Gan, Ning; Zhang, Huairong; Wang, De; Qiao, Li; Cao, Yuting; Li, Tianhua; Hu, Futao


    A novel sandwich-hybridization assay for simultaneous electrochemical detection of multiple DNA targets related to human immune deficiency virus (HIV) and tuberculosis (TB) was developed based on the different quantum dots-PowerVision(TM) polymer nanotracers. The polymer nanotracers were respectively fabricated by immobilizing SH-labeled oligonucleotides (s-HIV or s-TB), which can partially hybrid with virus DNA (HIV or TB), on gold nanoparticles (Au NPs) and then modified with PowerVision(TM) (PV) polymer-encapsulated quantum dots (CdS or PbS) as signal tags. PV is a dendrimer enzyme linked polymer, which can immobilize abundant QDs to amplify the stripping voltammetry signals from the metal ions (Pb or Cd). The capture probes were prepared through the immobilization of SH-labeled oligonucleotides, which can complementary with HIV and TB DNA, on the magnetic Fe3O4@Au (GMPs) beads. After sandwich-hybridization, the polymer nanotracers together with HIV and TB DNA targets were simultaneously introduced onto the surface of GMPs. Then the two encoding metal ions (Cd(2+) and Pb(2+)) were used to differentiate two viruses DNA due to the different subsequent anodic stripping voltammetric peaks at -0.84 V (Cd) and -0.61 V (Pb). Because of the excellent signal amplification of the polymer nanotracers and the great specificity of DNA targets, this assay could detect targets DNA as low as 0.2 femtomolar and exhibited excellent selectivity with the dynamitic range from 0.5 fM to 500 pM. Those results demonstrated that this electrochemical coding assay has great potential in applications for screening more viruses DNA while changing the probes.

  4. Chemo-predictive assay for targeting cancer stem-like cells in patients affected by brain tumors.

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    Sarah E Mathis

    Full Text Available Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID, which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1 and a 5-month female (patient 2, affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity

  5. Development and implementation of a high-throughput compound screening assay for targeting disrupted ER calcium homeostasis in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Kamran Honarnejad

    Full Text Available Disrupted intracellular calcium homeostasis is believed to occur early in the cascade of events leading to Alzheimer's disease (AD pathology. Particularly familial AD mutations linked to Presenilins result in exaggerated agonist-evoked calcium release from endoplasmic reticulum (ER. Here we report the development of a fully automated high-throughput calcium imaging assay utilizing a genetically-encoded FRET-based calcium indicator at single cell resolution for compound screening. The established high-throughput screening assay offers several advantages over conventional high-throughput calcium imaging technologies. We employed this assay for drug discovery in AD by screening compound libraries consisting of over 20,000 small molecules followed by structure-activity-relationship analysis. This led to the identification of Bepridil, a calcium channel antagonist drug in addition to four further lead structures capable of normalizing the potentiated FAD-PS1-induced calcium release from ER. Interestingly, it has recently been reported that Bepridil can reduce Aβ production by lowering BACE1 activity. Indeed, we also detected lowered Aβ, increased sAPPα and decreased sAPPβ fragment levels upon Bepridil treatment. The latter findings suggest that Bepridil may provide a multifactorial therapeutic modality for AD by simultaneously addressing multiple aspects of the disease.

  6. Quantitative detection of pork in commercial meat products by TaqMan® real-time PCR assay targeting the mitochondrial D-loop region. (United States)

    Kim, Miju; Yoo, Insuk; Lee, Shin-Young; Hong, Yeun; Kim, Hae-Yeong


    The TaqMan® real-time PCR assay using the mitochondrial D-loop region was developed for the quantitative detection of pork in processed meat products. The newly designed primers and probe specifically amplified pork without any cross-reactivity with non-target animal species. The limit of detection of the real-time PCR assay was 0.1pg of heat-treated pork meat and 0.1% (w/w) pork meat in beef and chicken meat mixtures. The quantitative real-time PCR assay was applied to analyze the pork meat content in 22 commercial processed meat products including jerkies, press hams, sausages, hamburger patties and steaks, grilled short rib patties, and nuggets. The developed real-time PCR method was able to detect pork meat in various types of processed meat products that declared the use of pork meat on their label. All processed meat products that declared no use of pork meat showed a negative result in the assay. The method developed in this study showed sensitivity and specificity in the quantification of pork meat in commercial processed meat products.

  7. Detection of Morganella morganii, a prolific histamine former, by the polymerase chain reaction assay with 16S rDNA-targeted primers. (United States)

    Kim, Shin-Hee; An, Haejung; Field, Katharine G; Wei, Cheng-I; Velazquez, Jorge Barros; Ben-Gigirey, Begoña; Morrissey, Michael T; Price, Robert J; Pitta, Thomas P


    A polymerase chain reaction (PCR) assay for the rapid and sensitive detection of the most prolific histamine former, Morganella morganii, was developed. 16S rDNA targeted PCR primers were designed, and the primer specificity and sensitivity of the PCR assay were evaluated. The 16S rDNA sequence (1,503 bp) for M. morganii showed 95% identity to those for enteric bacteria, i.e., Enterobacter spp., Klebsiella spp., Citrobacter spp., Hafnia alvei, Proteus spp., and Providencia spp. The unique primers for M. morganii were designed on the basis of the variable regions in the 16S rDNA sequence. The primers showed positive reactions with all M. morganii strains tested. However, PCR amplification was not detected when the primers were tested with other enteric or marine bacteria. When the sensitivity of the assay was evaluated, M. morganii was detected at levels ranging from 10(6) to 10(8) CFU/ml in albacore homogenate after the PCR amplification. The sensitivity of the assay was greatly improved with the enrichment of samples, and 9 CFU of M. morganii per ml of albacore homogenate was detected after 6 h of enrichment at 37 degrees C.

  8. The morpho-PET with {sup 18}F-F.D.G. improves the definition of the target volume for the radiotherapy of child Hodgkin disease; Le morpho-TEP au 18F-FDG ameliore la definition du volume cible pour la radiotherapie des maladies de Hodgkin de l'enfant

    Energy Technology Data Exchange (ETDEWEB)

    Metwally, H.; Courbon, F.; David, I.; Blouet, A.; Izar, F.; Rives, M.; Filleron, T.; Vial, J.; Laprie, A. [Institut Claudius-Regaud, Toulouse, (France); Robert, A. [CHU Toulouse, (France)


    The objective is to study the impact of PET-T.D.M. images re-timing before chemotherapy with these ones of dosimetric scanner ( post chemotherapy) on the target volume determination and their inter observers variability among children receiving a closing radiotherapy for a Hodgkin disease. Conclusions: the inter observers variability for the clinical target volume (C.T.V.) definition is significantly reduced by the re-timing of initial PET-T.D.M. images on the ballistic scanner. This study illustrates the interest of the multidisciplinary cooperation between nuclear doctor and radiotherapist for the radiotherapy optimization. (N.C.)

  9. Enhancing PET Signal at Target Tissue in Vivo: Dendritic and Multimeric Tris(hydroxypyridinone) Conjugates for Molecular Imaging of αvβ3 Integrin Expression with Gallium-68. (United States)

    Imberti, Cinzia; Terry, Samantha Y A; Cullinane, Carleen; Clarke, Fiona; Cornish, Georgina H; Ramakrishnan, Nisha K; Roselt, Peter; Cope, Andrew P; Hicks, Rodney J; Blower, Philip J; Ma, Michelle T


    Tris(hydroxypyridinone) chelators conjugated to peptides can rapidly complex the positron-emitting isotope gallium-68 ((68)Ga) under mild conditions, and the resulting radiotracers can delineate peptide receptor expression at sites of diseased tissue in vivo. We have synthesized a dendritic bifunctional chelator containing nine 1,6-dimethyl-3-hydroxypyridin-4-one groups (SCN-HP9) that can coordinate up to three Ga(3+) ions. This derivative has been conjugated to a trimeric peptide (RGD3) containing three peptide groups that target the αvβ3 integrin receptor. The resulting dendritic compound, HP9-RGD3, can be radiolabeled in 97% radiochemical yield at a 3-fold higher specific activity than its homologues HP3-RGD and HP3-RGD3 that contain only a single metal binding site. PET scanning and biodistribution studies show that [(68)Ga(HP9-RGD3)] demonstrates higher receptor-mediated tumor uptake in animals bearing U87MG tumors that overexpress αvβ3 integrin than [(68)Ga(HP3-RGD)] and [(68)Ga(HP3-RGD3)]. However, concomitant nontarget organ retention of [(68)Ga(HP9-RGD3)] results in low tumor to nontarget organ contrast in PET images. On the other hand, the trimeric peptide homologue containing a single tris(hydroxypyridinone) chelator, [(68)Ga(HP3-RGD3)], clears nontarget organs and exhibits receptor-mediated uptake in mice bearing tumors and in mice with induced rheumatoid arthritis. PET imaging with [(68)Ga(HP3-RGD3)] enables clear delineation of αvβ3 integrin receptor expression in vivo.

  10. Pets and the immunocompromised person (United States)

    AIDS patients and pets; Bone marrow transplant patients and pets; Chemotherapy patients and pets ... systems may be advised to give up their pets to avoid getting diseases from the animals. People ...

  11. Trends in PET imaging

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    Moses, William W.


    Positron Emission Tomography (PET) imaging is a well established method for obtaining information on the status of certain organs within the human body or in animals. This paper presents an overview of recent trends PET instrumentation. Significant effort is being expended to develop new PET detector modules, especially those capable of measuring depth of interaction. This is aided by recent advances in scintillator and pixellated photodetector technology. The other significant area of effort is development of special purpose PET cameras (such as for imaging breast cancer or small animals) or cameras that have the ability to image in more than one modality (such as PET / SPECT or PET / X-Ray CT).

  12. Colorimetric microtiter plate receptor-binding assay for the detection of freshwater and marine neurotoxins targeting the nicotinic acetylcholine receptors (United States)

    Rubio, Fernando; Kamp, Lisa; Carpino, Justin; Faltin, Erin; Loftin, Keith A.; Molgó, Jordi; Aráoz, Rómulo


    Anatoxin-a and homoanatoxin-a, produced by cyanobacteria, are agonists of nicotinic acetylcholine receptors (nAChRs). Pinnatoxins, spirolides, and gymnodimines, produced by dinoflagellates, are antagonists of nAChRs. In this study we describe the development and validation of a competitive colorimetric, high throughput functional assay based on the mechanism of action of freshwater and marine toxins against nAChRs. Torpedo electrocyte membranes (rich in muscle-type nAChR) were immobilized and stabilized on the surface of 96-well microtiter plates. Biotinylated α-bungarotoxin (the tracer) and streptavidin-horseradish peroxidase (the detector) enabled the detection and quantitation of anatoxin-a in surface waters and cyclic imine toxins in shellfish extracts that were obtained from different locations across the US. The method compares favorably to LC/MS/MS and provides accurate results for anatoxin-a and cyclic imine toxins monitoring. Study of common constituents at the concentrations normally found in drinking and environmental waters, as well as the tolerance to pH, salt, solvents, organic and inorganic compounds did not significantly affect toxin detection. The assay allowed the simultaneous analysis of up to 25 samples within 3.5 h and it is well suited for on-site or laboratory monitoring of low levels of toxins in drinking, surface, and ground water as well as in shellfish extracts.

  13. Gene-targeted embryonic stem cells: real-time PCR assay for estimation of the number of neomycin selection cassettes

    Directory of Open Access Journals (Sweden)

    Mancini Cecilia


    Full Text Available Abstract In the preparation of transgenic murine ES cells it is important to verify the construct has a single insertion, because an ectopic neomycin phosphortransferase positive selection cassette (NEO may cause a position effect. During a recent work, where a knockin SCA28 mouse was prepared, we developed two assays based on Real-Time PCR using both SYBR Green and specific minor groove binder (MGB probes to evaluate the copies of NEO using the comparative delta-delta Ct method versus the Rpp30 reference gene. We compared the results from Southern blot, routinely used to quantify NEO copies, with the two Real-Time PCR assays. Twenty-two clones containing the single NEO copy showed values of 0.98 ± 0.24 (mean ± 2 S.D., and were clearly distinguishable from clones with two or more NEO copies. This method was found to be useful, easy, sensitive and fast and could substitute for the widely used, but laborious Southern blot method.

  14. Targeting post-infarct inflammation by PET imaging: comparison of {sup 68}Ga-citrate and {sup 68}Ga-DOTATATE with {sup 18}F-FDG in a mouse model

    Energy Technology Data Exchange (ETDEWEB)

    Thackeray, James T. [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Hannover Medical School, Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover (Germany); Bankstahl, Jens P.; Walte, Almut; Wittneben, Alexander; Bengel, Frank M. [Hannover Medical School, Department of Nuclear Medicine, Hannover (Germany); Wang, Yong; Korf-Klingebiel, Mortimer; Wollert, Kai C. [Hannover Medical School, Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover (Germany)


    Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. {sup 18}F-FDG PET has been used, but may be complicated by physiological myocyte uptake. We evaluated the potential of two alternative imaging targets: lactoferrin binding by {sup 68}Ga-citrate and somatostatin receptor binding by {sup 68}Ga-DOTATATE. C57Bl/6 mice underwent permanent coronary artery ligation. Serial PET imaging was performed 3 - 7 days after MI using {sup 68}Ga-citrate, {sup 68}Ga-DOTATATE, or {sup 18}F-FDG with ketamine/xylazine suppression of myocyte glucose uptake. Myocardial perfusion was evaluated by {sup 13}N-ammonia PET and cardiac geometry by contrast-enhanced ECG-gated CT. Mice exhibited a perfusion defect of 30 - 40 % (of the total left ventricle) with apical anterolateral wall akinesia and thinning on day 7 after MI. {sup 18}F-FDG with ketamine/xylazine suppression demonstrated distinct uptake in the infarct region, as well as in the border zone and remote myocardium. The myocardial standardized uptake value in MI mice was significantly higher than in healthy mice under ketamine/xylazine anaesthesia (1.9 ± 0.4 vs. 1.0 ± 0.1). {sup 68}Ga images exhibited high blood pool activity with no specific myocardial uptake up to 90 min after injection (tissue-to-blood contrast 0.9). {sup 68}Ga-DOTATATE was rapidly cleared from the blood, but myocardial SUV was very low (0.10 ± 0.03). Neither {sup 68}Ga nor {sup 68}Ga-DOTATATE is a useful alternative to {sup 18}F-FDG for PET imaging of myocardial inflammation after MI in mice. Among the three tested approaches, {sup 18}F-FDG with ketamine/xylazine suppression of cardiomyocyte uptake remains the most practical imaging marker of post-infarct inflammation. (orig.)

  15. FDG PET imaging dementia

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol [Kyungpook National University Medical School and Kyungpook National University Hospital, Daegu (Korea, Republic of)


    Dementia is a major burden for many countries including South Korea, where life expectancy is continuously growing and the proportion of aged people is rapidly growing. Neurodegenerative disorders, such as, Alzheimer disease, dementia with Lewy bodies, frontotemporal dementia. Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, Huntington disease, can cause dementia, and cerebrovascular disease also can cause dementia. Depression or hypothyroidism also can cause cognitive deficits, but they are reversible by management of underlying cause unlike the forementioned dementias. Therefore these are called pseudodementia. We are entering an era of dementia care that will be based upon the identification of potentially modifiable risk factors and early disease markers, and the application of new drugs postpone progression of dementias or target specific proteins that cause dementia. Efficient pharmacologic treatment of dementia needs not only to distinguish underlying causes of dementia but also to be installed as soon as possible. Therefore, differential diagnosis and early diagnosis of dementia are utmost importance. F-18 FDG PET is useful for clarifying dementing diseases and is also useful for early detection of the disease. Purpose of this article is to review the current value of FDG PET for dementing diseases including differential diagnosis of dementia and prediction of evolving dementia.

  16. Leptospirosis and Pets (United States)

    ... Bacterial Special Pathogens Branch (BSPB) BSPB Laboratory Submissions Pets Recommend on Facebook Tweet Share Compartir Leptospirosis is ... that can affect human and animals, including your pets. All animals can potentially become infected with Leptospirosis. ...

  17. Heart PET scan (United States)

    ... nuclear medicine scan; Heart positron emission tomography; Myocardial PET scan ... A PET scan requires a small amount of radioactive material (tracer). This tracer is given through a vein (IV), ...

  18. Specific detection and quantification of virulent/avirulent Phytophthora infestans isolates using a real-time PCR assay that targets polymorphisms of the Avr3a gene. (United States)

    Clément, J A J; Baldwin, T K; Magalon, H; Glais, I; Gracianne, C; Andrivon, D; Jacquot, E


    Molecular tools that allow intraspecific quantification and discrimination of pathogen isolates are useful to assess fitness of competitors during mixed infections. However, methods that were developed for quantifying Phytophthora infestans are only specific at the species level. Here, we reported a TaqMan-based real-time PCR assay allowing, according to the specificity of the used probes, an accurate quantification of different proportions of two genetically distinct clones of P. infestans in mixed fractions. Indeed, in addition to a primer specific to P. infestans, two primers and two TaqMan(®) probes that target single-nucleotide polymorphisms located in the Avr3a/avr3a virulence gene sequence were designed. The reliability of the method was tested on serially diluted fractions containing plasmid DNA with either the Avr3a or the avr3a sequences at concentrations ranging from 10(2) to 10(8)  copies per μl. Based on its specificity, sensitivity and repeatability, the proposed assay allowed a quantification of the targeted DNA sequence in fractions with a Avr3a/avr3a ratio in the range 1/99 to 99/1. The reliability of the test was also checked for counting zoospores. Applications for future research in P. infestans/host quantitative interactions were also discussed.

  19. Development of a robust cell-based high-throughput screening assay to identify targets of HIV-1 viral protein R dimerization

    Directory of Open Access Journals (Sweden)

    Zych C


    Full Text Available Courtney Zych,1 Alexander Domling,2 Velpandi Ayyavoo11Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; 2Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA, USAAbstract: Targeting protein–protein interactions (PPI is an emerging field in drug discovery. Dimerization and PPI are essential properties of human immunodeficiency virus (HIV-1 proteins, their mediated functions, and virus biology. Additionally, dimerization is required for the functional interaction of HIV-1 proteins with many host cellular components. In this study, a bimolecular fluorescence complementation (BiFC-based screening assay was developed that can quantify changes in dimerization, using HIV-1 viral protein R (Vpr dimerization as a "proof of concept." Results demonstrated that Venus Vpr (generated by BiFC Vpr constructs could be competed off in a dose-dependent manner using untagged, full-length Vpr as a competitor molecule. The change in signal intensity was measured quantitatively through flow cytometry and fluorescence microscopy in a high content screening assay. High content imaging was used to screen a library of small molecules for an effect on Vpr dimerization. Among the tested molecules, a few of the small molecules demonstrate an effect on Vpr dimerization in a dose-dependent manner.Keywords: BiFC, protein–protein interaction, HIV-1 Vpr, dimerization, drug targets

  20. Development of a quantitative real-time polymerase chain reaction assay to target a novel group of ammonia-producing bacteria found in poultry litter. (United States)

    Rothrock, M J; Cook, K L; Lovanh, N; Warren, J G; Sistani, K


    Ammonia production in poultry houses has serious implications for flock health and performance, nutrient value of poultry litter, and energy costs for running poultry operations. In poultry litter, the conversion of organic N (uric acid and urea) to NH(4)-N is a microbially mediated process. The urease enzyme is responsible for the final step in the conversion of urea to NH(4)-N. Cloning and analysis of 168 urease sequences from extracted genomic DNA from poultry litter samples revealed the presence of a novel, dominant group of ureolytic microbes (representing 90% of the urease clone library). Specific primers and a probe were designed to target this novel poultry litter urease producer (PLUP) group, and a new quantitative real-time PCR assay was developed. The assay allowed for the detection of 10(2) copies of target urease sequences per PCR reaction (approximately 1 x 10(4) cells per gram of poultry litter), and the reaction was linear over 8 orders of magnitude. Our PLUP group was present only in poultry litter and was not present in environmental samples from diverse agricultural settings. This novel PLUP group represented between 0.1 to 3.1% of the total microbial populations (6.0 x 10(6) to 2.4 x 10(8) PLUP cells per gram of litter) from diverse poultry litter types. The PLUP cell concentrations were directly correlated to the total cell concentrations in the poultry litter and were found to be influenced by the physical parameters of the litters (bedding material, moisture content, pH), as well as the NH(4)-N content of the litters, based on principal component analysis. Chemical parameters (organic N, total N, total C) were not found to be influential in the concentrations of our PLUP group in the diverse poultry litters Future applications of this assay could include determining the efficacy of current NH(4)-N-reducing litter amendments or in designing more efficient treatment protocols.

  1. Tumour targeting and radiation dose of radioimmunotherapy with {sup 90}Y-rituximab in CD20+ B-cell lymphoma as predicted by {sup 89}Zr-rituximab immuno-PET: impact of preloading with unlabelled rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Muylle, Kristoff [Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium); Universite Libre de Bruxelles, Department of Nuclear Medicine, Jules Bordet Institute, Brussels (Belgium); Flamen, Patrick; Guiot, Thomas; Ghanem, Ghanem; Meuleman, Nathalie; Bourgeois, Pierre; Vanderlinden, Bruno; Vaes, Melanie; Bron, Dominique [Universite Libre de Bruxelles, Jules Bordet Institute, Brussels (Belgium); Vugts, Danielle J.; Dongen, Guus A.M.S. van [VU University Medical Centre, Amsterdam (Netherlands); Everaert, Hendrik [Vrije Universiteit Brussel, UZ Brussel, Brussels (Belgium); Vrije Universiteit Brussel, MIMA Research Group, Brussels (Belgium)


    To compare using immuno-PET/CT the distribution of {sup 89}Zr-labelled rituximab without and with a preload of unlabelled rituximab to assess the impact of preloading with unlabelled rituximab on tumour targeting and radiation dose of subsequent radioimmunotherapy with {sup 90}Y-labelled rituximab in CD20+ B-cell lymphoma. Five patients with CD20+ B-cell lymphoma and progressive disease were prospectively enrolled. All patients underwent three study phases: initial dosimetric phase with baseline {sup 89}Zr-rituximab PET/CT imaging without a cold preload, followed 3 weeks later by a second dosimetric phase with administration of a standard preload (250 mg/m{sup 2}) of unlabelled rituximab followed by injection of {sup 89}Zr-rituximab, and a therapeutic phase 1 week later with administration of unlabelled rituximab followed by {sup 90}Y-rituximab. PET/CT imaging and tracer uptake by organs and lesions were assessed. With a cold rituximab preload, the calculated whole-body dose of {sup 90}Y-rituximab was similar (mean 0.87 mSv/MBq, range 0.82-0.99 mSv/MBq) in all patients. Without a preload, an increase in whole-body dose of 59 % and 87 % was noted in two patients with preserved circulating CD20+ B cells. This increase in radiation dose was primarily due to a 12.4-fold to 15-fold higher dose to the spleen without a preload. No significant change in whole-body dose was noted in the three other patients with B-cell depletion. Without a preload, consistently higher tumour uptake was noticed in patients with B-cell depletion. Administration of the standard preload of unlabelled rituximab impairs radioconjugate tumour targeting in the majority of patients eligible for radioimmunotherapy, that is patients previously treated with rituximab-containing therapeutic regimens. This common practice may need to be reconsidered and further evaluated as the rationale for this high preload has its origin in the ''prerituximab era''. (orig.)

  2. High-throughput Assays for MicroRNA Target Genes%MicroRNA靶基因的高通量鉴定方法

    Institute of Scientific and Technical Information of China (English)

    陈灵锋; 张均平; 王明席


    MicroRNAs(miRNAs)are a class of endogenous non-coding RNAs involved in the regulation of gene expression at the post-transcriptional level. miRNAs play pivotal roles in cell growth, development and disease pathogenesis. Therefore, to identify and validate miRNAs target genes regulated is essential to understand the functions of miRNAs in disease. miRNAs bind the complementary sequences of target mRN As to mediate translational repression or target degradation and gene silencing, both computer-aided predication and biological experimental screening can be used for target identification. The former may produce a large number of miRNA target genes with higher false positive genes to be further excluded by the biological experiments. The latter approaches can be further greatly facilitated with high-throughput multiple target screening assays, such as microarray, proteome analysis, or RNA ligase mediated rapid amplification of cDNA ends. The applications involving these assays were summarized and compared, together with the discussion on the further development of related technologies.%MicroRNAs (miRNAs)是一类内源性非编码小RNA,可在转录后水平调节基因的表达,在细胞生长、发育、疾病发生等过程中发挥着重要作用.明确miRNAs所调控的靶基因对阐明miRNAs的功能及在各种生命过程和疾病发生机制的角色非常关键.目前,鉴定miRNAs的靶基因的方法主要计算机预测方法和生物学实验方法.前者对miRNA靶基因的寻找作出巨大贡献,但常存在很多假阳性,必须通过生物学实验方法加以验证.后者涉及单靶基因鉴定技术和高通量多靶基因鉴定技术,高通量技术又包括基因芯片分析技术、蛋白质组学分析技术、RNA连接酶介导的cDNA末端扩增技术和生物化学法等.本文主要对这些高通量技术的应用、优劣进行归纳,并对其改进方向予以讨论.

  3. The application of PET imaging in psychoneuroimmunology research. (United States)

    Hannestad, Jonas


    Positron emission tomography (PET) imaging is a research tool that allows in vivo measurements of brain metabolism and specific target molecules. PET imaging can be used to measure these brain variables in a variety of species, including human and non-human primates, and rodents. PET imaging can therefore be combined with various experimental and clinical model systems that are commonly used in psychoneuroimmunology research.

  4. Potential of the microbial assay for risk assessment (MARA) for assessing ecotoxicological effects of herbicides to non-target organisms. (United States)

    Fai, Patricia Bi Asanga; Mbida, Mpoame; Demefack, Jean Marc; Yamssi, Cedric


    Many microbiotests that have been proposed for use in the risk assessment of environmental pollutants have the drawback of lacking relevant published data on various aspects of their test application possibilities and therefore do not receive the regulatory recognition which they may deserve. The MARA bioassay lacks published data for many relevant environmental pollutants, particularly pesticides and this may limit its use in regulatory framework. The present study has assessed the sensitivity of the MARA bioassay relative to other established bioassays (Daphnia magna and Oreochromis niloticus) to two widely used herbicide formulations: Roundup (having glyphosate as active ingredient) and Herbextra (with the active ingredient being 2,4-dichlorophenoxyacetic acid-2,4-D). Roundup was found to be more toxic than Herbextra in all three bioassays. The D. magna EC50 s obtained for Roundup and Herbextra were respectively 5.55 and 356.61 mg/l while the LC50 s for O. niloticus were 11.30 and 222,28 mg/l respectively. In the case of the MARA bioassay microbial toxic concentrations (MTCs) for individual species ranged from 6.85 to 468 mg/l with an overall mean MTC of 101.82 mg/l for glyphosate and from 74.67 to 13,333 mg/l for 2,4-D giving an overall mean MTC of 2855.88 mg/l. Although the overall MTCs from the MARA bioassay were much higher than the LC50 s and EC50 s from the fish and daphnia bioassays respectively, the most sensitive MARA organism for each of the herbicides had MTCs that were comparable to or lower than the corresponding endpoints from the other bioassays implying that the MARA assay is a potentially useful bioassay for risk assessment of pesticides.

  5. Meganuclease-driven targeted integration in CHO-K1 cells for the fast generation of HTS-compatible cell-based assays. (United States)

    Cabaniols, Jean-Pierre; Ouvry, Christine; Lamamy, Véronique; Fery, Isabelle; Craplet, Marie-Laure; Moulharat, Natacha; Guenin, Sophie-Pénélope; Bedut, Stéphane; Nosjean, Olivier; Ferry, Gilles; Devavry, Séverine; Jacqmarcq, Cécile; Lebuhotel, Céline; Mathis, Luc; Delenda, Christophe; Boutin, Jean A; Duchâteau, Philippe; Cogé, Francis; Pâques, Frédéric


    The development of cell-based assays for high-throughput screening (HTS) approaches often requires the generation of stable transformant cell lines. However, these cell lines are essentially created by random integration of a gene of interest (GOI) with no control over the level and stability of gene expression. The authors developed a targeted integration system in Chinese hamster ovary (CHO) cells, called the cellular genome positioning system (cGPS), based on the stimulation of homologous gene targeting by meganucleases. Five different GOIs were knocked in at the same locus in cGPS CHO-K1 cells. Further characterization revealed that the cGPS CHO-K1 system is more rapid (2-week protocol), efficient (all selected clones expressed the GOI), reproducible (GOI expression level variation of 12%), and stable over time (no change in GOI expression after 23 weeks of culture) than classical random integration. Moreover, in all cGPS CHO-K1 targeted clones, the recombinant protein was biologically active and its properties similar to the endogenous protein. This fast and robust method opens the door for creating large collections of cell lines of better quality and expressing therapeutically relevant GOIs at physiological levels, thereby enhancing the potential scope of HTS.

  6. Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation

    Directory of Open Access Journals (Sweden)

    Vinci Maria


    Full Text Available Abstract Background There is overwhelming evidence that in vitro three-dimensional tumor cell cultures more accurately reflect the complex in vivo microenvironment than simple two-dimensional cell monolayers, not least with respect to gene expression profiles, signaling pathway activity and drug sensitivity. However, most currently available three-dimensional techniques are time consuming and/or lack reproducibility; thus standardized and rapid protocols are urgently needed. Results To address this requirement, we have developed a versatile toolkit of reproducible three-dimensional tumor spheroid models for dynamic, automated, quantitative imaging and analysis that are compatible with routine high-throughput preclinical studies. Not only do these microplate methods measure three-dimensional tumor growth, but they have also been significantly enhanced to facilitate a range of functional assays exemplifying additional key hallmarks of cancer, namely cell motility and matrix invasion. Moreover, mutual tissue invasion and angiogenesis is accommodated by coculturing tumor spheroids with murine embryoid bodies within which angiogenic differentiation occurs. Highly malignant human tumor cells were selected to exemplify therapeutic effects of three specific molecularly-targeted agents: PI-103 (phosphatidylinositol-3-kinase (PI3K-mammalian target of rapamycin (mTOR inhibitor, 17-N-allylamino-17-demethoxygeldanamycin (17-AAG (heat shock protein 90 (HSP90 inhibitor and CCT130234 (in-house phospholipase C (PLCγ inhibitor. Fully automated analysis using a Celigo cytometer was validated for tumor spheroid growth and invasion against standard image analysis techniques, with excellent reproducibility and significantly increased throughput. In addition, we discovered key differential sensitivities to targeted agents between two-dimensional and three-dimensional cultures, and also demonstrated enhanced potency of some agents against cell migration

  7. Development of a sequence-characterized amplified region marker-targeted quantitative PCR assay for strain-specific detection of Oenococcus oeni during wine malolactic fermentation. (United States)

    Solieri, Lisa; Giudici, Paolo


    Control over malolactic fermentation (MLF) is a difficult goal in winemaking and needs rapid methods to monitor Oenococcus oeni malolactic starters (MLS) in a stressful environment such as wine. In this study, we describe a novel quantitative PCR (QPCR) assay enabling the detection of an O. oeni strain during MLF without culturing. O. oeni strain LB221 was used as a model to develop a strain-specific sequence-characterized amplified region (SCAR) marker derived from a discriminatory OPA20-based randomly amplified polymorphic DNA (RAPD) band. The 5' and 3' flanking regions and the copy number of the SCAR marker were characterized using inverse PCR and Southern blotting, respectively. Primer pairs targeting the SCAR sequence enabled strain-specific detection without cross amplification of other O. oeni strains or wine species of lactic acid bacteria (LAB), acetic acid bacteria (AAB), and yeasts. The SCAR-QPCR assay was linear over a range of cell concentrations (7 log units) and detected as few as 2.2 × 10(2) CFU per ml of red wine with good quantification effectiveness, as shown by the correlation of QPCR and plate counting results. Therefore, the cultivation-independent monitoring of a single O. oeni strain in wine based on a SCAR marker represents a rapid and effective strain-specific approach. This strategy can be adopted to develop easy and rapid detection techniques for monitoring the implantation of inoculated O. oeni MLS on the indigenous LAB population, reducing the risk of unsuccessful MLF.

  8. Detection of Salmonella in Shellfish Using SYBR Green™ I-Based Real-Time Multiplexed PCR Assay Targeting invA and spvB

    KAUST Repository

    Gangwar, Maulshree


    A SYBR Green™ I-based real-time multiplexed PCR assay was developed targeting invA and spvB for the detection of Salmonella strains in shellfish after both hns and invA genes were identified in all Salmonella strains. Simultaneously, the 16S rRNA gene was used as a PCR internal amplification control (IAC). All 89 Salmonella strains tested in this study exhibited amplification of invA, whereas only 21 (23. 6 %) were PCR positive for spvB. The sensitivity of detection of all three targeted genes was 1 ng, which is equivalent to approximately 105 colony-forming unit (CFU) of Salmonella enterica. The analysis showed specific PCR products that were identified by reproducible melt temperature profiles (invA, 84. 27 ± 1. 7 °C; spvB, 88. 76 ± 1. 0 °C; and 16S rRNA gene, 87. 16 ± 0. 8 °C). The sensitivity of detection was 10 pg purified DNA (invA) or 105 CFU in 1 mL pure culture of S. enterica ATCC 14028. The above molecular detection method for Salmonella strains was successfully applied to the oyster homogenates (food matrix). An initial inoculum of 106 and 102 CFU Salmonella in 1 ml seeded oyster tissue homogenate was detected by multiplexed PCR for all three genes after 5 and 24 h of enrichment, respectively. Natural oysters isolated from Gulf of Mexico during the winter months exhibited negative PCR amplification results suggesting the absence of Salmonella. In contrast to conventional PCR, real-time multiplex PCR assay developed in this study is rapid and sensitive and will help Interstate Shellfish Sanitation Conference undertake appropriate measures to monitor Salmonella in oysters, thereby preventing disease outbreaks and consequently protecting consumer health. © 2012 Springer Science+Business Media, LLC.

  9. Targeted Next Generation Sequencing as a Reliable Diagnostic Assay for the Detection of Somatic Mutations in Tumours Using Minimal DNA Amounts from Formalin Fixed Paraffin Embedded Material.

    Directory of Open Access Journals (Sweden)

    Wendy W J de Leng

    Full Text Available Targeted Next Generation Sequencing (NGS offers a way to implement testing of multiple genetic aberrations in diagnostic pathology practice, which is necessary for personalized cancer treatment. However, no standards regarding input material have been defined. This study therefore aimed to determine the effect of the type of input material (e.g. formalin fixed paraffin embedded (FFPE versus fresh frozen (FF tissue on NGS derived results. Moreover, this study aimed to explore a standardized analysis pipeline to support consistent clinical decision-making.We used the Ion Torrent PGM sequencing platform in combination with the Ion AmpliSeq Cancer Hotspot Panel v2 to sequence frequently mutated regions in 50 cancer related genes, and validated the NGS detected variants in 250 FFPE samples using standard diagnostic assays. Next, 386 tumour samples were sequenced to explore the effect of input material on variant detection variables. For variant calling, Ion Torrent analysis software was supplemented with additional variant annotation and filtering.Both FFPE and FF tissue could be sequenced reliably with a sensitivity of 99.1%. Validation showed a 98.5% concordance between NGS and conventional sequencing techniques, where NGS provided both the advantage of low input DNA concentration and the detection of low-frequency variants. The reliability of mutation analysis could be further improved with manual inspection of sequence data.Targeted NGS can be reliably implemented in cancer diagnostics using both FFPE and FF tissue when using appropriate analysis settings, even with low input DNA.

  10. Prospective evaluation of early treatment outcome in patients with meningiomas treated with particle therapy based on target volume definition with MRI and {sup 68}Ga-DOTATOC-PET

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E.; Welzel, Thomas; Habermehl, Daniel; Rieken, Stefan; Dittmar, Jan-Oliver; Kessel, Kerstin; Debus, Juergen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], e-mail:; Jaekel, Oliver [Heidelberg Ion Therapy Center (HIT), Heidelberg (Germany); Haberkorn, Uwe [Univ. Hospital of Heidelberg, Dept. of Nuclear Medicine, Heidelberg (Germany)


    Purpose: To evaluate early treatment results and toxicity in patients with meningiomas treated with particle therapy. Material and methods: Seventy patients with meningiomas were treated with protons (n = 38) or carbon ion radiotherapy (n = 26). Median age was 49 years. Median age at treatment was 55 years, 24 were male (34%), and 46 were female (66%). Histology was benign meningioma in 26 patients (37%), atypical in 23 patients (33%) and anaplastic in four patients (6%). In 17 patients (24%) with skull base meningiomas diagnosis was based on the typical appearance of a meningioma. For benign meningiomas, total doses of 52.2-57.6 GyE were applied with protons. For high-grade lesions, the boost volume was 18 GyE carbon ions, with a median dose of 50 GyE applied as highly conformal radiation therapy. Nineteen patients were treated as re-irradiation. Treatment planning with MRI and 68-Ga-DOTATOC-PET was evaluated. Results: Very low rates of side effects developed, including headaches, nausea and dizziness. No severe treatment-related toxicity was observed. Local control for benign meningiomas was 100%. Five of 27 patients (19%) developed tumor recurrence during follow-up. Of these, four patients had been treated as re-irradiation for recurrent high-risk meningiomas. Actuarial local control after re-irradiation of high-risk meningiomas was therefore 67% at six and 12 months. In patients treated with primary radiotherapy, only one of 13 patients (8%) developed tumor recurrence 17 months after radiation therapy (photon and carbon ion boost). Conclusion: Continuous prospective follow-up and development of novel study concepts are required to fully exploit the long-term clinical data after particle therapy for meningiomas. To date, it may be concluded that when proton therapy is available, meningioma patients can be offered a treatment at least comparable to high-end photon therapy.

  11. A comparison of two real-time polymerase chain reaction assays using hybridization probes targeting either 16S ribosomal RNA or a subsurface lipoprotein gene for detecting leptospires in canine urine. (United States)

    Gentilini, Fabio; Zanoni, Renato Giulio; Zambon, Elisa; Turba, Maria Elena


    Leptospires are excreted in the urine of infected animals, and the prompt detection of leptospiral DNA using polymerase chain reaction (PCR) is increasingly being used. However, contradictory data has emerged concerning the diagnostic accuracy of the most popular PCR assays that target either the 16S ribosomal RNA (rrs) or the subsurface lipoprotein (LipL32) genes. In order to clarify the effect of the gene target, a novel hydrolysis probe-based, quantitative real-time PCR (qPCR) assay targeting the LipL32 gene was developed, validated, and then compared directly to the previously described rrs hydrolysis probe-based qPCR using a convenience collection of canine urine samples. The novel LipL32 qPCR assay was linear from 5.9 × 10(6) to 59 genome equivalents per reaction. Both the LipL32 and the rrs qPCR assays showed a limit of detection of 10 target copies per reaction indicating an approximately equivalent analytical sensitivity. Both assays amplified all 20 pathogenic leptospiral strains tested but did not amplify a representative collection of bacteria commonly found in voided canine urine. When the field samples were assayed, 1 and 5 out of 184 samples yielded an amplification signal in the LipL32 and rrs assays, respectively. Nevertheless, when the limit of detection was considered as the cutoff for interpreting findings, the 4 discordant cases were judged as negative. In conclusion, our study confirmed that both LipL32 and rrs are suitable targets for qPCR for the detection of leptospiral DNA in canine urine. However, the rrs target requires the mandatory use of a cutoff value in order to correctly interpret spurious amplifications.

  12. PET studies in epilepsy


    Sarikaya, Ismet


    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. 18Fluoro-2-deoxyglucose (18F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients...

  13. Sensory analysis of pet foods. (United States)

    Koppel, Kadri


    Pet food palatability depends first and foremost on the pet and is related to the pet food sensory properties such as aroma, texture and flavor. Sensory analysis of pet foods may be conducted by humans via descriptive or hedonic analysis, pets via acceptance or preference tests, and through a number of instrumental analysis methods. Sensory analysis of pet foods provides additional information on reasons behind palatable and unpalatable foods as pets lack linguistic capabilities. Furthermore, sensory analysis may be combined with other types of information such as personality and environment factors to increase understanding of acceptable pet foods. Most pet food flavor research is proprietary and, thus, there are a limited number of publications available. Funding opportunities for pet food studies would increase research and publications and this would help raise public awareness of pet food related issues. This mini-review addresses current pet food sensory analysis literature and discusses future challenges and possibilities.

  14. Clinical PET application

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Moo; Hong, Song W.; Choi, Chang W.; Yang, Seong Dae [Korea Cancer Center Hospital, Seoul (Korea)


    PET gives various methabolic images, and is very important, new diagnostic modality in clinical oncology. In Korea Cancer Center Hospital, PET is installed as a research tool of long-mid-term atomic research project. For the efficient use of PET for clinical and research projects, income from the patients should be managed to get the raw material, equipment, manpower, and also for the clinical PET research. 1. Support the clinical application of PET in oncology. 2. Budgetary management of income, costs for raw material, equipment, manpower, and the clinical PET research project. In this year, 250 cases of PET images were obtained, which resulted total income of 180,000,000 won. 50,000,000 won was deposited for the 1998 PET clinical research. Second year PET clinical research should be managed under unified project. Increased demand for {sup 18}FDG in and outside KCCH need more than 2 times production of {sup 18}FDG in a day purchase of HPLC pump and {sup 68}Ga pin source which was delayed due to economic crisis, should be done early in 1998. (author). 2 figs., 3 tabs.

  15. Dynamic neurotransmitter interactions measured with PET

    Energy Technology Data Exchange (ETDEWEB)

    Schiffer, W.K.; Dewey, S.L.


    Positron emission tomography (PET) has become a valuable interdisciplinary tool for understanding physiological, biochemical and pharmacological functions at a molecular level in living humans, whether in a healthy or diseased state. The utility of tracing chemical activity through the body transcends the fields of cardiology, oncology, neurology and psychiatry. In this, PET techniques span radiochemistry and radiopharmaceutical development to instrumentation, image analysis, anatomy and modeling. PET has made substantial contributions in each of these fields by providing a,venue for mapping dynamic functions of healthy and unhealthy human anatomy. As diverse as the disciplines it bridges, PET has provided insight into an equally significant variety of psychiatric disorders. Using the unique quantitative ability of PET, researchers are now better able to non-invasively characterize normally occurring neurotransmitter interactions in the brain. With the knowledge that these interactions provide the fundamental basis for brain response, many investigators have recently focused their efforts on an examination of the communication between these chemicals in both healthy volunteers and individuals suffering from diseases classically defined as neurotransmitter specific in nature. In addition, PET can measure the biochemical dynamics of acute and sustained drug abuse. Thus, PET studies of neurotransmitter interactions enable investigators to describe a multitude of specific functional interactions in the human brain. This information can then be applied to understanding side effects that occur in response to acute and chronic drug therapy, and to designing new drugs that target multiple systems as opposed to single receptor types. Knowledge derived from PET studies can be applied to drug discovery, research and development (for review, see (Fowler et al., 1999) and (Burns et al., 1999)). Here, we will cover the most substantial contributions of PET to understanding

  16. Mobile PET Center Project (United States)

    Ryzhikova, O.; Naumov, N.; Sergienko, V.; Kostylev, V.


    Positron emission tomography is the most promising technology to monitor cancer and heart disease treatment. Stationary PET center requires substantial financial resources and time for construction and equipping. The developed mobile solution will allow introducing PET technology quickly without major investments.

  17. Pets and Pasteurella Infections (United States)

    ... water. When To Call Your Pediatrician If your child is bitten or scratched by a pet, wild animal, or any animal unknown to you, ... allowed to lick very young infants . Teach your child not to approach or touch unfamiliar pets or wild animals and never disturb an animal ...

  18. My Pet Rock (United States)

    Lark, Adam; Kramp, Robyne; Nurnberger-Haag, Julie


    Many teachers and students have experienced the classic pet rock experiment in conjunction with a geology unit. A teacher has students bring in a "pet" rock found outside of school, and the students run geologic tests on the rock. The tests include determining relative hardness using Mohs scale, checking for magnetization, and assessing luster.…

  19. PET/CT确定非小细胞肺癌三维适形放疗靶区的临床研究%Clinical study of PET/CT on delineation of the target volume for conformal radiation therapy in nonsmall-cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    胡学锋; 黄国森; 张良运; 冯彦林; 谭春明


    目的 探讨PET-CT检查对非小细胞肺癌(non-small-cell lung cancer,NSCLC)患者的分期与治疗方案的影响和PET/CT所确定的靶区(GTV)与病理学肿瘤大小的关系. 方法 2006年3月-2008年7月间37例接受手术或放疗的NSCLC患者,根据PET/CT检查结果,21例患者进入手术组(有手术指征),16例患者进入放疗组(无手术指征),手术组术前在PET/CT图像上确定肿瘤在冠状轴(X轴)、矢状轴(Y轴)、长轴(Z轴)三维径线上的大小,术后病理检查,确定肿瘤在X、Y、Z轴上的大小;TNM分期分别用CT、PET/CT分期与病理学分期.放疗组分别在PET/CT和CT横断图像上勾画原发灶和纵隔淋巴结GTV,软件自动运算PET/CT和模拟定位增强CT所勾画靶区的体积. 结果 19例(51.4%)的TNM分期在PET/CT检查后发生改变;12例(37.8%)的治疗方案因而发生变化.CT、PET/CT、病理确定的原发灶大小在X、Y轴上无显著差异(P值>0.05),Z轴上有显著差异(P值<0.05);放疗组16例患者中,PET/CT所勾画的GTVPET>GTVCT者共4例,因为PET/CT发现不符合CT诊断标准的纵隔淋巴结转移灶.GTVPET<GTVCT者共7例,主要是因为PET/CT排除了阻塞性肺炎和肺不张. 结论 PET/CT检查对分期与治疗方案的影响较大,PET/CT与病理学的肿瘤大小基本一致,PET/CT所确定的肿瘤大小可以作为病理学的GTV,勾画非小细胞肺癌放疗靶区PET/CT优于CT.%Objective To evaluate the influence to stage and the treatment planning in non - small cell lung cancer( NSCLC )by CT、PET/CT. To define the correlation of gross tumor volume( GTV )by PET/CT and pathology. Methods From March 2006 to July 2008,37 NSCLC patients were studied,21 cases received surgical resection and 16 cases received radiotherapy based on PET/CT. All patients had PET/CT scans of all body before surgery or radiotherapy and routine pathology examination after surgery. The tumor size at X( lateral direction )、Y ( ventrodorsal direction )and Z

  20. Usage of Recycled Pet

    Directory of Open Access Journals (Sweden)

    A. Ebru Tayyar


    Full Text Available The increasing industrialization, urbanization and the technological development have caused to increase depletion of the natural resources and environmental pollution's problem. Especially, for the countries which have not enough space recycling of the waste eliminating waste on regular basis or decreasing the amount and volume of waste have provided the important advantages. There are lots of studies and projects to develop both protect resources and prevent environmental pollution. PET bottles are commonly used in beverage industry and can be reused after physical and chemical recycling processes. Usage areas of recycled PET have been developed rapidly. Although recycled PET is used in plastic industry, composite industry also provides usage alternatives of recycled PET. Textile is a suitable sector for recycling of some plastics made of polymers too. In this study, the recycling technologies and applications of waste PET bottles have been investigated and scientific works in this area have been summarized.

  1. Software-based PET-MR image coregistration: combined PET-MRI for the rest of us

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, Matthew S.; Liu, Xinyang; Vyas, Pranav K.; Safdar, Nabile M. [Children' s National Health System, Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC (United States); Plishker, William; Zaki, George F. [IGI Technologies, Inc., College Park, MD (United States); Shekhar, Raj [Children' s National Health System, Sheikh Zayed Institute for Pediatric Surgical Innovation, Washington, DC (United States); IGI Technologies, Inc., College Park, MD (United States)


    With the introduction of hybrid positron emission tomography/magnetic resonance imaging (PET/MRI), a new imaging option to acquire multimodality images with complementary anatomical and functional information has become available. Compared with hybrid PET/computed tomography (CT), hybrid PET/MRI is capable of providing superior anatomical detail while removing the radiation exposure associated with CT. The early adoption of hybrid PET/MRI, however, has been limited. To provide a viable alternative to the hybrid PET/MRI hardware by validating a software-based solution for PET-MR image coregistration. A fully automated, graphics processing unit-accelerated 3-D deformable image registration technique was used to align PET (acquired as PET/CT) and MR image pairs of 17 patients (age range: 10 months-21 years, mean: 10 years) who underwent PET/CT and body MRI (chest, abdomen or pelvis), which were performed within a 28-day (mean: 10.5 days) interval. MRI data for most of these cases included single-station post-contrast axial T1-weighted images. Following registration, maximum standardized uptake value (SUV{sub max}) values observed in coregistered PET (cPET) and the original PET were compared for 82 volumes of interest. In addition, we calculated the target registration error as a measure of the quality of image coregistration, and evaluated the algorithm's performance in the context of interexpert variability. The coregistration execution time averaged 97±45 s. The overall relative SUV{sub max} difference was 7% between cPET-MRI and PET/CT. The average target registration error was 10.7±6.6 mm, which compared favorably with the typical voxel size (diagonal distance) of 8.0 mm (typical resolution: 0.66 mm x 0.66 mm x 8 mm) for MRI and 6.1 mm (typical resolution: 3.65 mm x 3.65 mm x 3.27 mm) for PET. The variability in landmark identification did not show statistically significant differences between the algorithm and a typical expert. We have presented a software

  2. Molecular detection and confirmation of Neisseria gonorrhoeae in urogenital and extragenital specimens using the Abbott CT/NG RealTime assay and an in-house assay targeting the porA pseudogene.

    LENUS (Irish Health Repository)

    Walsh, A


    Culture for detection of Neisseria gonorrhoeae (NG) is being replaced by molecular assays, but difficulties are observed with false positive and negatives results, especially for extragenital samples. This study evaluates the Abbott CT\\/NG Real-Time assay and a real-time porA pseudogene assay. Samples (n = 600) from a mixed prevalence Irish population include 164 male urines with corresponding urethral swabs, 58 endocervical swabs, 173 male pharyngeal swabs, 205 male rectal swabs, 36 NG clinical isolates and 26 commensal Neisseria species isolates. There was a 100% concordance between the Abbott CT\\/NG Real-Time and the porA assay. The positivity rate was 1.2%, 1.7%, 8.1% and 5.8% for FVU\\/urethral swabs, endocervical, pharyngeal and rectal swabs, respectively. These results were compared to culture and discrepancies were found with nine pharyngeal and three rectal swabs. Seven of the 12 discrepant positive samples were sequenced and were confirmed "true positives". The sensitivity and specificity of the molecular assays was 100%. The sensitivity of the culture-based testing was 100% for urogenital samples but 36% and 75% for pharyngeal and rectal swabs, respectively. The combined Abbott CT\\/NG and porA assays provide a valuable alternative to culture and also generate a significant increase in the diagnosis of pharyngeal and rectal NG infection.

  3. Diagnostic accuracy of real-time PCR assays targeting 16S rRNA and lipL32 genes for human leptospirosis in Thailand: a case-control study.

    Directory of Open Access Journals (Sweden)

    Janjira Thaipadungpanit

    Full Text Available BACKGROUND: Rapid PCR-based tests for the diagnosis of leptospirosis can provide information that contributes towards early patient management, but these have not been adopted in Thailand. Here, we compare the diagnostic sensitivity and specificity of two real-time PCR assays targeting rrs or lipL32 for the diagnosis of leptospirosis in northeast Thailand. METHODS/PRINCIPAL FINDINGS: A case-control study of 266 patients (133 cases of leptospirosis and 133 controls was constructed to evaluate the diagnostic sensitivity and specificity (DSe & DSp of both PCR assays. The median duration of illness prior to admission of cases was 4 days (IQR 2-5 days; range 1-12 days. DSe and DSp were determined using positive culture and/or microscopic agglutination test (MAT as the gold standard. The DSe was higher for the rrs assay than the lipL32 assay (56%, (95% CI 47-64% versus 43%, (95% CI 34-52%, p<0.001. No cases were positive for the lipL32 assay alone. There was borderline evidence to suggest that the DSp of the rrs assay was lower than the lipL32 assay (90% (95% CI 83-94% versus 93%, (95%CI 88-97%, p = 0.06. Nine controls gave positive reactions for both assays and 5 controls gave a positive reaction for the rrs assay alone. The DSe of the rrs and lipL32 assays were high in the subgroup of 39 patients who were culture positive for Leptospira spp. (95% and 87%, respectively, p = 0.25. CONCLUSIONS/SIGNIFICANCE: Early detection of Leptospira using PCR is possible for more than half of patients presenting with leptospirosis and could contribute to individual patient care.

  4. Imaging Alzheimer's disease pathophysiology with PET

    Directory of Open Access Journals (Sweden)

    Lucas Porcello Schilling

    Full Text Available ABSTRACT Alzheimer's disease (AD has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI, and dementia stages. Positron emission tomography (PET associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD.

  5. Automation of (64)Cu production at Turku PET Centre. (United States)

    Elomaa, Viki-Veikko; Jurttila, Jori; Rajander, Johan; Solin, Olof


    At Turku PET Centre automation for handling solid targets for the production of (64)Cu has been built. The system consists of a module for moving the target from the irradiation position into a lead transport shield and a robotic-arm assisted setup for moving the target within radiochemistry laboratory. The main motivation for designing automation arises from radiation hygiene.

  6. Performance and Verification of a Real-Time PCR Assay Targeting the gyrA Gene for Prediction of Ciprofloxacin Resistance in Neisseria gonorrhoeae. (United States)

    Hemarajata, P; Yang, S; Soge, O O; Humphries, R M; Klausner, J D


    In the United States, 19.2% of Neisseria gonorrhoeae isolates are resistant to ciprofloxacin. We evaluated a real-time PCR assay to predict ciprofloxacin susceptibility using residual DNA from the Roche Cobas 4800 CT/NG assay. The results of the assay were 100% concordant with agar dilution susceptibility test results for 100 clinical isolates. Among 76 clinical urine and swab specimens positive for N. gonorrhoeae by the Cobas assay, 71% could be genotyped. The test took 1.5 h to perform, allowing the physician to receive results in time to make informed clinical decisions.

  7. Micro-PET/CT Monitoring of Herpes Thymidine Kinase Suicide Gene Therapy in a Prostate Cancer Xenograft: The Advantage of a Cell-specific Transcriptional Targeting Approach

    Directory of Open Access Journals (Sweden)

    Mai Johnson


    Full Text Available Cancer gene therapy based on tissue-restricted expression of cytotoxic gene should achieve superior therapeutic index over an unrestricted method. This study compared the therapeutic effects of a highly augmented, prostate-specific gene expression method to a strong constitutive promoter-driven approach. Molecular imaging was coupled to gene therapy to ascertain real-time therapeutic activity. The imaging reporter gene (luciferase and the cytotoxic gene (herpes simplex thymidine kinase were delivered by adenoviral vectors injected directly into human prostate tumors grafted in SCID mice. Serial bioluminescence imaging, positron emission tomography, and computed tomography revealed restriction of gene expression to the tumors when prostate-specific vector was employed. In contrast, administration of constitutive active vector resulted in strong signals in the liver. Liver serology, tissue histology, and frail condition of animals confirmed liver toxicity suffered by the constitutive active cohorts, whereas the prostate-targeted group was unaffected. The extent of tumor killing was analyzed by apoptotic staining and human prostate marker (prostate-specific antigen. Overall, the augmented prostate-specific expression system was superior to the constitutive approach in safeguarding against systemic toxicity, while achieving effective tumor killing. Integrating noninvasive imaging into cytotoxic gene therapy will provide a useful strategy to monitor gene expression and therapeutic efficacy in future clinical protocols.

  8. SYBR Green real-time PCR-RFLP assay targeting the plasmodium cytochrome B gene--a highly sensitive molecular tool for malaria parasite detection and species determination. (United States)

    Xu, Weiping; Morris, Ulrika; Aydin-Schmidt, Berit; Msellem, Mwinyi I; Shakely, Delér; Petzold, Max; Björkman, Anders; Mårtensson, Andreas


    A prerequisite for reliable detection of low-density Plasmodium infections in malaria pre-elimination settings is the availability of ultra-sensitive and high-throughput molecular tools. We developed a SYBR Green real-time PCR restriction fragment length polymorphism assay (cytb-qPCR) targeting the cytochrome b gene of the four major human Plasmodium species (P. falciparum, P. vivax, P. malariae, and P. ovale) for parasite detection and species determination with DNA extracted from dried blood spots collected on filter paper. The performance of cytb-qPCR was first compared against four reference PCR methods using serially diluted Plasmodium samples. The detection limit of the cytb-qPCR was 1 parasite/μl (p/μl) for P. falciparum and P. ovale, and 2 p/μl for P. vivax and P. malariae, while the reference PCRs had detection limits of 0.5-10 p/μl. The ability of the PCR methods to detect low-density Plasmodium infections was then assessed using 2977 filter paper samples collected during a cross-sectional survey in Zanzibar, a malaria pre-elimination setting in sub-Saharan Africa. Field samples were defined as 'final positive' if positive in at least two of the five PCR methods. Cytb-qPCR preformed equal to or better than the reference PCRs with a sensitivity of 100% (65/65; 95%CI 94.5-100%) and a specificity of 99.9% (2910/2912; 95%CI 99.7-100%) when compared against 'final positive' samples. The results indicate that the cytb-qPCR may represent an opportunity for improved molecular surveillance of low-density Plasmodium infections in malaria pre-elimination settings.

  9. Combined PET/MRI

    DEFF Research Database (Denmark)

    Bailey, D. L.; Pichler, B. J.; Gückel, B.;


    This paper summarises key themes and discussions from the 4th international workshop dedicated to the advancement of the technical, scientific and clinical applications of combined positron emission tomography (PET)/magnetic resonance imaging (MRI) systems that was held in Tübingen, Germany, from...... February 23 to 27, 2015. Specifically, we summarise the three days of invited presentations from active researchers in this and associated fields augmented by round table discussions and dialogue boards with specific topics. These include the use of PET/MRI in cardiovascular disease, paediatrics, oncology......, neurology and multi-parametric imaging, the latter of which was suggested as a key promoting factor for the wider adoption of integrated PET/MRI. Discussions throughout the workshop and a poll taken on the final day demonstrated that attendees felt more strongly that PET/MRI has further advanced in both...

  10. Birds Kept as Pets (United States)

    ... Patients Infants and Young Children Publications & Materials Announcements Birds Kept as Pets Recommend on Facebook Tweet Share ... your hands whenever you play or work with birds Person washing their hands with soap and water. ...

  11. Clinical application of PET

    Energy Technology Data Exchange (ETDEWEB)

    Lomena, Francisco [Hospital Clinico Villarroel, Barcelona (Spain). Nuclear Medicine]. E-mail:; Soler, Marina [CETIR Grup Medic. Esplkugues de Llobregat, Barcelona (Spain). PET Unit


    Positron emission tomography (PET) is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT) and magnetic resonance imaging (MRI), which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption by the different organs and tissues of the mammalian body. Fluorodeoxyglucose-F 18 (FDG) PET has been proven to be a tracer adequate for clinical use in oncology and in many neurological diseases, with an excellent cost-efficiency ratio. The current PET-CT scanners can come to be the best tools for exploring patients who suffer from cancer.(author)

  12. PET studies in epilepsy. (United States)

    Sarikaya, Ismet


    Various PET studies, such as measurements of glucose, serotonin and oxygen metabolism, cerebral blood flow and receptor bindings are availabe for epilepsy. (18)Fluoro-2-deoxyglucose ((18)F-FDG) PET imaging of brain glucose metabolism is a well established and widely available technique. Studies have demonstrated that the sensitivity of interictal FDG-PET is higher than interictal SPECT and similar to ictal SPECT for the lateralization and localization of epileptogenic foci in presurgical patients refractory to medical treatments who have noncontributory EEG and MRI. In addition to localizing epileptogenic focus, FDG-PET provide additional important information on the functional status of the rest of the brain. The main limitation of interictal FDG-PET is that it cannot precisely define the surgical margin as the area of hypometabolism usually extends beyond the epileptogenic zone. Various neurotransmitters (GABA, glutamate, opiates, serotonin, dopamine, acethylcholine, and adenosine) and receptor subtypes are involved in epilepsy. PET receptor imaging studies performed in limited centers help to understand the role of neurotransmitters in epileptogenesis, identify epileptic foci and investigate new treatment approaches. PET receptor imaging studies have demonstrated reduced (11)C-flumazenil (GABAA-cBDZ) and (18)F-MPPF (5-HT1A serotonin) and increased (11)C-cerfentanil (mu opiate) and (11)C-MeNTI (delta opiate) bindings in the area of seizure. (11)C-flumazenil has been reported to be more sensitive than FDG-PET for identifying epileptic foci. The area of abnormality on GABAAcBDZ and opiate receptor images is usually smaller and more circumscribed than the area of hypometabolism on FDG images. Studies have demonstrated that (11)C-alpha-methyl-L-tryptophan PET (to study synthesis of serotonin) can detect the epileptic focus within malformations of cortical development and helps in differentiating epileptogenic from non-epileptogenic tubers in patients with tuberous

  13. PET/CT Artifacts


    Blodgett, Todd M.; Mehta, Ajeet S.; Mehta, Amar S.; Laymon, Charles M; Carney, Jonathan; Townsend, David W.


    There are several artifacts encountered in PET/CT imaging, including attenuation correction (AC) artifacts associated with using CT for attenuation correction. Several artifacts can mimic a 2-deoxy-2-[18F] fluoro-D-glucose (FDG) avid malignant lesions and therefore recognition of these artifacts is clinically relevant. Our goal was to identify and characterize these artifacts and also discuss some protocol variables that may affect image quality in PET/CT.

  14. Microbead agglutination based assays

    KAUST Repository

    Kodzius, Rimantas


    We report a simple and rapid room temperature assay for point-of-care (POC) testing that is based on specific agglutination. Agglutination tests are based on aggregation of microbeads in the presence of a specific analyte thus enabling the macroscopic observation. Such tests are most often used to explore antibody-antigen reactions. Agglutination has been used for protein assays using a biotin/streptavidin system as well as a hybridization based assay. The agglutination systems are prone to selftermination of the linking analyte, prone to active site saturation and loss of agglomeration at high analyte concentrations. We investigated the molecular target/ligand interaction, explaining the common agglutination problems related to analyte self-termination, linkage of the analyte to the same bead instead of different microbeads. We classified the agglutination process into three kinds of assays: a two- component assay, a three-component assay and a stepped three- component assay. Although we compared these three kinds of assays for recognizing DNA and protein molecules, the assay can be used for virtually any molecule, including ions and metabolites. In total, the optimized assay permits detecting analytes with high sensitivity in a short time, 5 min, at room temperature. Such a system is appropriate for POC testing.

  15. Comparative Study of a Real-Time PCR Assay Targeting senX3-regX3 versus Other Molecular Strategies Commonly Used in the Diagnosis of Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Rocio Sanjuan-Jimenez

    Full Text Available Nucleic acid amplification tests are increasingly used for the rapid diagnosis of tuberculosis. We undertook a comparative study of the efficiency and diagnostic yield of a real-time PCR senX3-regX3 based assay versus the classical IS6110 target and the new commercial methods.This single-blind prospective comparative study included 145 consecutive samples: 76 from patients with culture-confirmed tuberculosis (86.8% pulmonary and 13.2% extrapulmonary tuberculosis: 48.7% smear-positive and 51.3% smear-negative and 69 control samples (24 from patients diagnosed with non-tuberculous mycobacteria infections and 45 from patients with suspected tuberculosis which was eventually ruled out. All samples were tested by two CE-marked assays (Xpert®MTB/RIF and AnyplexTM plus MTB/NTM and two in-house assays targeting senX3-regX3 and the IS6110 gene.The detection limit ranged from 1.00E+01 fg for Anyplex, senX3-regX3 and IS6110 to 1.00E+04 fg for Xpert. All three Xpert, senX3-regX3 and IS6110 assays detected all 37 smear-positive cases. Conversely, Anyplex was positive in 34 (91.9% smear-positive cases. In patients with smear-negative tuberculosis, differences were observed between the assays; Xpert detected 22 (56.41% of the 39 smear-negative samples, Anyplex 24 (61.53%, senX3-regX3 28 (71.79% and IS6110 35 (89.74%. Xpert and senX3-regX3 were negative in all control samples; however, the false positive rate was 8.7% and 13% for Anyplex and IS6110, respectively. The overall sensitivity was 77.6%, 85.7%, 77.3% and 94.7% and the specificity was 100%, 100%, 90.8% and 87.0% for the Xpert, senX3-regX3, Anyplex and IS6110 assays, respectively.Real-time PCR assays targeting IS6110 lack the desired specificity. The Xpert MTB/RIF and in-house senX3-regX3 assays are both sensitive and specific for the detection of MTBC in both pulmonary and extrapulmonary samples. Therefore, the real time PCR senX3-regX3 based assay could be a useful and complementary tool in the

  16. First-in-human uPAR PET

    DEFF Research Database (Denmark)

    Persson, Morten; Skovgaard, Dorthe; Brandt-Larsen, Malene;


    of invasion, metastasis and indicates poor prognosis. uPAR PET imaging therefore holds promise to be a new and innovative method for improved cancer diagnosis, staging and individual risk stratification. The uPAR specific peptide AE105 was conjugated to the macrocyclic chelator DOTA and labeled with (64)Cu...... for targeted molecular imaging with PET. The safety, pharmacokinetic, biodistribution profile and radiation dosimetry after a single intravenous dose of (64)Cu-DOTA-AE105 were assessed by serial PET and computed tomography (CT) in 4 prostate, 3 breast and 3 bladder cancer patients. Safety assessment...

  17. PET/CT Based Dose Planning in Radiotherapy

    DEFF Research Database (Denmark)

    Berthelsen, Anne Kiil; Jakobsen, Annika Loft; Sapru, Wendy;


    This mini-review describes how to perform PET/CT based radiotherapy dose planning and the advantages and possibilities obtained with the technique for radiation therapy. Our own experience since 2002 is briefly summarized from more than 2,500 patients with various malignant diseases undergoing...... radiotherapy planning with PET/CT prior to the treatment. The PET/CT, including the radiotherapy planning process as well as the radiotherapy process, is outlined in detail. The demanding collaboration between mould technicians, nuclear medicine physicians and technologists, radiologists and radiology...... technologists, radiation oncologists, physicists, and dosimetrists is emphasized. We strongly believe that PET/CT based radiotherapy planning will improve the therapeutic output in terms of target definition and non-target avoidance and will play an important role in future therapeutic interventions in many...

  18. Salmonella: Dry Pet Foods and Pet Treats (FAQ) (United States)

    ... Literature Reviews Market Research Statistics Reference Guides Reports Salmonella: Dry Pet Foods and Pet Treats (FAQ) Originally ... 2008, there was a prolonged multistate outbreak of Salmonella enterica serotype Schwarzengrund infections in humans. A total ...

  19. Thin-target excitation functions and optimisation of NCA {sup 64}Cu and {sup 66,67}Ga production by deuteron induced nuclear reactions on natural zinc target, for radiometabolic therapy and for PET

    Energy Technology Data Exchange (ETDEWEB)

    Groppi, F. E-mail:; Bonardi, M.L.; Birattari, C.; Gini, L.; Mainardi, C.; Menapace, E.; Abbas, K.; Holzwarth, U.; Stroosnijder, R.M.F


    A novel method for production of No-Carrier-Added {sup 64}Cu and {sup 66,67}Ga has been developed, based on reactions induced by deuterons up to 19 MeV on Zn target. HPGe and beta (by LSC) spectrometries proved very effective to determine radionuclidic purity of {sup 64}Cu and {sup 66,67}Ga fractions. Experimental specific activity for {sup 64}Cu was measured by ET-AAS and was of the order of 700 MBq {center_dot} {mu}g{sup -1}. Radiochemical yields for {sup 64}Cu and {sup 66,67}Ga were >80% and >99%.

  20. A loop-mediated isothermal amplification (LAMP) assay targeting 16S rRNA gene for rapid detection of Anaplasma phagocytophilum infection in sheep and goats. (United States)

    Ning, Changshen; Wang, Jinhong; Zhang, Yan; Wang, Xiaoxing; Cui, Yanyan; Yan, Yaqun; Wang, Rongjun; Jian, Fuchun; Zhang, Longxian


    Anaplasma phagocytophilum is a zoonotic pathogen and the causative agent of human granulocytic anaplasmosis (HGA) in humans and tick-borne fever in various kinds of animals. In the present study, a loop-mediated isothermal amplification (LAMP) assay for rapid detection of A. phagocytophilum was developed using primers specific to 16S rRNA gene of this organism. The LAMP assay was performed at 65 C for 60 min and terminated at 80 C for 10 min. The optimal reaction conditions, under which no cross-reaction was observed with other closely related tick borne parasites (Anaplasma bovis, Anaplasma ovis, Theileria luwenshuni, Babesia motasi and Schistosoma japonicum) was established. The assay exhibited much higher sensitivity when compared with conventional PCR (1 copy vs 1000 copies). To evaluate the applicability of the LAMP assay, 94 sheep field blood samples were analyzed for A. phagocytophilum infection using LAMP, nested PCR and conventional PCR assay at the same time. A positive LAMP result was obtained from 53 of the 94 samples (56.4%), while only 12 (12.8%) and 3 (3.2%) were tested positive by nested PCR and conventional PCR, respectively. In conclusion, this LAMP assay is a specific, sensitive, and rapid method for the detection of A. phagocytophilum in sheep.

  1. Medical application of PET technology

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Sang Moo; Choi, C. W.; An, S. H.; Woo, K. S.; Chung, W. S.; Yang, S. D.; Jun, G. S. and others


    We performed following studies using PET technology: 1. Clinical usefulness of [{sup 18}F]FDG whole body PET in malignant disease 2. Clinical usefulness of quantitative evaluation of F-18-FDG 3. Pilot study of C-11 methionine PET in brain tumor 4. PET study in patients with Parkinson's disease 5. A study on the clinical myocardial PET image. PET gives various metabolic information for the living human body, and is very important, new diagnostic modality. The PET study will give us the information of cancer patients such as early detection of cancer, staging, recurrence detection and characterization of cancer. The quantitative analysis using PET could be applied to evaluate the pathophysiology of various diseases and develop new drugs and develop new radiopharmaceuticals.

  2. An Improved Multiplex Real-Time SYBR Green PCR Assay for Analysis of 24 Target Genes from 16 Bacterial Species in Fecal DNA Samples from Patients with Foodborne Illnesses. (United States)

    Kawase, Jun; Etoh, Yoshiki; Ikeda, Tetsuya; Yamaguchi, Keiji; Watahiki, Masanori; Shima, Tomoko; Kameyama, Mitsuhiro; Horikawa, Kazumi; Fukushima, Hiroshi; Goto, Ryoichi; Shirabe, Komei


    Here, we developed a new version of our original screening system (Rapid Foodborne Bacterial Screening 24; RFBS24), which can simultaneously detect 24 genes of foodborne pathogens in fecal DNA samples. This new version (RFBS24 ver. 5) detected all known stx2 subtypes, enterotoxigenic Escherichia coli (STh genotype), and Vibrio parahaemolyticus (trh2), which were not detected by the original RFBS24 assay. The detection limits of RFBS24 ver. 5 were approximately 5.6 × 10(-2)-5.6 × 10(-5) (ng DNA)/reaction, significantly lower (10- to 100-fold) than those of the original RFBS24 for the 22 target genes analyzed here. We also tested the new assay on fecal DNA samples from patients infected with Salmonella, Campylobacter, or enterohemorrhagic E. coli. The number of bacterial target genes detected by RFBS24 ver. 5 was greater than that detected by RFBS24. RFBS24 ver. 5 combined with an Ultra Clean Fecal DNA Isolation Kit showed adequate performance (sensitivity and specificity 89% and 100%, respectively, for Salmonella spp. and 100% and 83%, respectively, for Campylobacter jejuni) in terms of rapid detection of a causative pathogen during foodborne-illness outbreaks. Thus, RFBS24 ver. 5 is more useful than the previous assay system for detection of foodborne pathogens and offers quick simultaneous analysis of many targets and thus facilitates rapid dissemination of information to public health officials.

  3. Cognitive dysfunction in senior pets. (United States)

    Crowell-Davis, Sharon L


    Aging pets can experience declines in memory, learning, perception, and awareness. These pets may be disoriented, forget previously learned behaviors, develop new fears and anxiety, or change their interactions with people. When these changes are due to cognitive dysfunction, behavioral and environmental adjustments along with medical therapy can slow the progression and keep pets active longer.

  4. Sequential (gemcitabine/vinorelbine and concurrent (gemcitabine radiochemotherapy with FDG-PET-based target volume definition in locally advanced non-small cell lung cancer: first results of a phase I/II study

    Directory of Open Access Journals (Sweden)

    Stanzel Sven


    Full Text Available Abstract Background The aim of the study was to determine the maximal tolerated dose (MTD of gemcitabine every two weeks concurrent to radiotherapy, administered during an aggressive program of sequential and simultaneous radiochemotherapy for locally advanced, unresectable non-small cell lung cancer (NSCLC and to evaluate the efficacy of this regime in a phase II study. Methods 33 patients with histologically confirmed NSCLC were enrolled in a combined radiochemotherapy protocol. 29 patients were assessable for evaluation of toxicity and tumor response. Treatment included two cycles of induction chemotherapy with gemcitabine (1200 mg/m2 and vinorelbine (30 mg/m2 at day 1, 8 and 22, 29 followed by concurrent radiotherapy (2.0 Gy/d; total dose 66.0 Gy and chemotherapy with gemcitabine every two weeks at day 43, 57 and 71. Radiotherapy planning included [18F] fluorodeoxyglucose positron emission tomography (FDG PET based target volume definition. 10 patients were included in the phase I study with an initial gemcitabine dose of 300 mg/m2. The dose of gemcitabine was increased in steps of 100 mg/m2 until the MTD was realized. Results MTD was defined for the patient group receiving gemcitabine 500 mg/m2 due to grade 2 (next to grade 3 esophagitis in all patients resulting in a mean body weight loss of 5 kg (SD = 1.4 kg, representing 8% of the initial weight. These patients showed persisting dysphagia 3 to 4 weeks after completing radiotherapy. In accordance with expected complications as esophagitis, dysphagia and odynophagia, we defined the MTD at this dose level, although no dose limiting toxicity (DLT grade 3 was reached. In the phase I/II median follow-up was 15.7 months (4.1 to 42.6 months. The overall response rate after completion of therapy was 64%. The median overall survival was 19.9 (95% CI: [10.1; 29.7] months for all eligible patients. The median disease-free survival for all patients was 8.7 (95% CI: [2.7; 14.6] months. Conclusion

  5. PET/CT in radiation therapy planning; PET/CT in der Strahlentherapieplanung

    Energy Technology Data Exchange (ETDEWEB)

    Grosu, A.L. [Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany); Krause, B.J. [Klinik fuer Nuklearmedizin, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany); Nestle, U. [Klinik fuer Nuklearmedizin, Universitaetsklinikum des Saarlandes, Homburg/Saar (Germany)


    Regarding treatment planning in radiotherapy PET offers advantages in terms of tumor delineation and the description of biological processes. To define the real impact of this investigation in radiation treatment planning, following experimental, clinical and cost/benefit analysis are required. FDG-PET has a significant impact on GTV and PTV delineation in lung cancer and can detect lymph node involvement and differentiation of malignant tissue from atelectasis. In high-grade gliomas and meningiomas, methionine-PET helps to define the GTV and differentiate tumor from normal tissue. In head and neck cancer, cervix cancer and prostate cancer the value of FDG-PET for radiation treatment planning is still under investigation. For example, FDG-PET can be superior to CT and MRI in the detection of lymph node metastases in head and neck, unknown primary cancer and differentiation of viable tumor tissue after treatment. Therefore, it could play an important role in GTV definition and sparing of normal tissue. For other entities like gastro-intestinal cancer, lymphomas, sarcoma etc., the data of the literature are yet insufficient. The imaging of hypoxia, cell proliferation, angiogenesis, apoptosis and gene expression leads to the identification of different areas of a biologically heterogeneous tumor mass that can be individually targeted using IMRT. In addition, a biological dose distribution can be generated, the so-called dose painting. However, systematical experimental and clinical trials are necessary to validate this hypothesis. (orig.)

  6. Clinical application of pet

    Directory of Open Access Journals (Sweden)

    Francisco Lomeña


    Full Text Available Positron emission tomography (PET is an imaging modality that gives information on tissue metabolism and functionalism, different from other imaging techniques like computed tomography (CT and magnetic resonance imaging (MRI, which provide anatomical or structural information. PET has reached its development in biomedical research because of its capacity to use analogous compounds of many endogenous substance as tracers, and to measure, in vivo and in a non-invasive way, their consumption by the different organs and tissues of the mammalian body. Fluordeoxyglucose-F18 (FDG PET has been proven to be a tracer adequate for clinical use in oncology and in many neurological diseases, with an excellent cost-efficiency ratio. The current PET-CT scanners can come to be the best tools for exploring patients who suffer from cancer.A tomografia por emissão de pósitrons (PET é uma técnica de diagnóstico por imagem que fornece informação sobre o metabolismo e funcionamento dos tecidos, diferente de outras técnicas de imagens como tomografia computadorizada (TC e ressonância magnética (RM, as quais fornecem informações estruturais ou anatômicas. O PET alcançou seu desenvolvimento em investigação biomédica devido à sua capacidade de usar traçadores análogos a muitas substâncias endógenas e de medir in vivo e de forma não invasiva seu consumo em diferentes órgãos e tecidos dos mamíferos 18Fluordesoxiglicose (FDG PET tem provado ser uma exploração de uso clínico com excelente relação custo benefício em oncologia e em muitas doenças neurológicas. Os atuais tomógrafos por PET-CT podem chegar a ser a melhor ferramenta de diagnóstico nos pacientes que sofrem de câncer.

  7. PET/MR in oncology

    DEFF Research Database (Denmark)

    Balyasnikova, Svetlana; Löfgren, Johan; de Nijs, Robin


    of the challenges inherent in this new technology, but focus on potential applications for simultaneous PET/MR in the field of oncology. Methods and tracers for use with the PET technology will be familiar to most readers of this journal; thus this paper aims to provide a short and basic introduction to a number...... be applied together with PET increasing the amount of information about the tissues of interest. The potential clinical benefit of applying PET/MR in staging, radiotherapy planning and treatment evaluation in oncology, as well as the research perspectives for the use of PET/MR in the development of new...

  8. Imaging large vessel vasculitis with fully integrated PET/MRI: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Einspieler, Ingo; Pyka, Thomas; Eiber, Matthias [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich (Germany); Thuermel, Klaus; Wolfram, Sabine; Moog, Philipp [Technische Universitaet Muenchen, Klinikum rechts der Isar, Department of Nephrology, Munich (Germany); Reeps, Christian [Technische Universitaet Muenchen, Department of Vascular Surgery, Klinikum rechts der Isar, Munich (Germany); Essler, Markus [Rheinische Friedrich-Wilhelms-Universitaet, Department of Nuclear Medicine, Universitaetsklinikum Bonn, Bonn (Germany)


    The aim of this study was to evaluate the feasibility of hybrid [{sup 18}F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/MRI in patients with large vessel vasculitis (LVV) by comparing visual and quantitative parameters to that of PET/CT. Furthermore, the value of PET/MRI in disease activity and extent of LVV was assessed. A total of 16 [{sup 18}F]FDG PET/MRI and 12 [{sup 18}F]-FDG PET/CT examinations were performed in 12 patients with LVV. MRI of the vessel wall by T1-weighted and T2-weighted sequences was used for anatomical localization of FDG uptake and identification of morphological changes associated with LVV. In addition, contrast-enhanced (CE) magnetic resonance angiography (MRA) was performed. The vascular FDG uptake in the vasculitis group was compared to a reference group of 16 patients using a four-point visual score. Visual scores and quantitative parameters [maximum standardized uptake value (SUV{sub max}) and target to background ratio (TBR)] were compared between PET/MRI and PET/CT. Furthermore, correlations between C-reactive protein (CRP) and quantitative PET results, as well the extent of vasculitis in PET, MRI/CE-MRA and combined PET/MRI, were analysed. TBRs, SUV{sub max} values and visual scores correlated well between PET/MRI and PET/CT (r = 0.92, r = 0.91; r = 0.84, p < 0.05). There was no significant difference between both modalities concerning SUV{sub max} measurements and visual scores. In PET/MRI, PET alone revealed abnormal FDG uptake in 86 vascular regions. MRI/CE-MRA indicated 49 vessel segments with morphological changes related to vasculitis, leading to a total number of 95 vasculitis regions in combination with PET. Strong and significant correlations between CRP and disease extent in PET alone (r = 0.75, p = 0.0067) and PET/MRI (r = 0.92, p < 0.0001) in contrast to MRI/CE-MRA only were observed. Regarding disease activity, no significant correlations were seen between quantitative PET results and CRP, although there

  9. Use of PET/CT for staging and radiation therapy planning in patients with non-small cell lung cancer. (United States)

    Mac Manus, M P


    Positron emission tomography (PET) and more recently PET/computed tomography (CT) scanning represent major advances in the imaging of lung cancer and have an especially high impact on the management of patients who are candidates for potentially curative or "radical" radiotherapy (RT). This article reviews the current status of PET and PET/CT for staging patients before RT and considers the use of PET and PET/CT images for target volume definition. The relevant literature on the use of PET for staging lung cancer is reviewed and placed in the context of patients who are candidates for RT. Research that specifically considers the use of PET for RT planning is considered critically and some promising areas for future research are discussed. The available literature is almost exclusively devoted to non small cell lung cancer (NSCLC) with few relevant studies of small cell lung cancer (SCLC). The primary PET radiopharmaceutical shown to have value for staging and RT planning is 18F-fluorodeoxyglucose (FDG). In prospective studies where PET imaging was used to stage radical RT candidates, 25-30% of patients were excluded from radical therapy because of PET detected advanced disease. In all studies where "PET-assisted" and conventional target or treatment volumes were compared, there were major differences between PET and conventional volumes. Because PET-assisted staging is proven to be significantly more accurate than conventional staging and because all studies show major differences between PET-assisted and conventional treatment volumes in NSCLC, routine use of PET/CT for RT planning is recommended.

  10. PET/CT and vascular disease: Current concepts

    Energy Technology Data Exchange (ETDEWEB)

    Cavalcanti Filho, Jose Leite Gondim; Souza Leao Lima, Ronaldo de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Souza Machado Neto, Luiz de [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Kayat Bittencourt, Leonardo, E-mail: [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil); Cortes Domingues, Romeu [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Fonseca, Lea Mirian Barbosa da [CDPI and Multi-Imagem Clinics, Rio de Janeiro (Brazil); Department of Radiology, Rio de Janeiro Federal University (UFRJ), Rio de Janeiro (Brazil)


    Since its introduction in 2001, positron emission tomography associated to computed tomography (PET/CT) has been established as a standard tool in cancer evaluation. Being a multimodality imaging method, it combines in a single session the sensitivity granted by PET for detection of molecular targets within the picomolar range, with an underlying submilimetric resolution inherent to CT, that can precisely localize the PET findings. In this last decade, there have been new insights regarding the pathophysiology of atherosclerosis, particularly about plaque rupture and vascular remodeling. This has increased the interest for research on PET/CT in vascular diseases as a potential new diagnostic tool, since some PET molecular targets could identify diseases before the manifestation of gross anatomic features. In this review, we will describe the current applications of PET/CT in vascular diseases, emphasizing its usefulness in the settings of vasculitis, aneurysms, vascular graft infection, aortic dissection, and atherosclerosis/plaque vulnerability. Although not being properly peripheral vascular conditions, ischemic cardiovascular disease and cerebrovascular disease will be briefly addressed as well, due to their widespread prevalence and importance.

  11. Choosing a Pet

    Institute of Scientific and Technical Information of China (English)


    THE capital boasts countless markets of all kinds,but some of its insect,bird and pet markets immortalize Beijing culture and folkloric traditions.Don’t miss it! The Huasheng Tianqiao Market,south of the famous Panjiayuan Antique Market, was moved a few years ago and rebuilt in the

  12. Pets and Parasites (United States)

    ... to Be SafeTo avoid dog bites, teach your child how to behave around dogs.December 2010September editorial staffAvoiding SnakebitesRead Article >>Pets and AnimalsAvoiding SnakebitesLearn how to identify, treat, and ...

  13. PET's indsats under lup

    DEFF Research Database (Denmark)

    Hansen, Peer Henrik


    En undersøgelseskommission nedsat i 1999. Fem medlemmer skal undersøge PET's efterretningsvirksomhed i forhold til politiske partier, faglige konflikter og politisk ideologiske bevægelser i Danmark under den kolde krig. Kommissionens rapport forventes færdig næste år. Udgivelsesdato: 2. juli 2006...

  14. I Love Petting Zoos!

    Centers for Disease Control (CDC) Podcasts


    This Kidtastics podcast helps children learn about how to stay safe and healthy when visiting petting zoos and other animal exhibits.  Created: 3/23/2010 by Centers for Disease Control and Prevention (CDC).   Date Released: 3/23/2010.

  15. Cold Weather Pet Safety (United States)

    ... they can be knocked over, potentially starting a fire. Check your furnace before the cold weather sets in to make ... avoided because of the risk of burns or fire. Heated pet mats should also be used ... to burrow, get them back inside quickly because they are showing signs of ...

  16. PET and PET/CT in malignant melanoma; PET y PET/CT en melanoma maligno

    Energy Technology Data Exchange (ETDEWEB)

    Garcia O, J.R. [Nuclear Medicine and Molecular Imaging PET/CT, Centro Medico ABC, Mexico D.F. (Mexico)


    The advantages that it has the PET/CT are: 1. It diminishes mainly positive false lesions. It identifies physiologic accumulate places. 2. It diminishes in smaller grade false negative. Small injuries. Injuries with low grade concentration. Injure on intense activity areas. 3. Precise anatomical localization of accumulate places. 4. Reduction of the acquisition time. (Author)

  17. FDG PET/CT imaging as a biomarker in lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Meignan, Michel; Itti, Emmanuel [Hopitaux Universitaires Henri Mondor, Paris-Est Creteil University, LYSA Imaging, Department of Nuclear Medicine, Creteil (France); Gallamini, Andrea [Nice University, Research, Innovation and Statistic Department, Antoine Lacassagne Cancer Center, Nice (France); Scientific Research Committee, S. Croce Hospital, Cuneo (Italy); Younes, Anas [Memorial Sloan Kettering Cancer Center, Lymphoma Service, New York, NY (United States)


    FDG PET/CT has changed the management of FDG-avid lymphoma and is now recommended as the imaging technique of choice for staging and restaging. The need for tailoring therapy to reduce toxicity in patients with a favourable outcome and for improving treatment in those with high-risk factors requires accurate diagnostic methods and a new prognostic algorithm to identify different risk categories. New drugs are used in relapsed/refractory patients. The role of FDG PET/CT as a biomarker in this context is summarized in this review. New trends in FDG metabolic imaging in lymphoma are addressed including metabolic tumour volume measurement at staging and integrative PET which combines PET data with clinical and molecular markers or other imaging techniques. The quantitative approach for response assessment which is under investigation and is used in large ongoing trials is compared with visual criteria. The place of FDG in the era of targeted therapy is discussed. (orig.)

  18. Quantitative assessment of human and pet exposure to Salmonella associated with dry pet foods. (United States)

    Lambertini, Elisabetta; Buchanan, Robert L; Narrod, Clare; Ford, Randall M; Baker, Robert C; Pradhan, Abani K


    Recent Salmonella outbreaks associated with dry pet foods and treats highlight the importance of these foods as previously overlooked exposure vehicles for both pets and humans. In the last decade efforts have been made to raise the safety of this class of products, for instance by upgrading production equipment, cleaning protocols, and finished product testing. However, no comprehensive or quantitative risk profile is available for pet foods, thus limiting the ability to establish safety standards and assess the effectiveness of current and proposed Salmonella control measures. This study sought to develop an ingredients-to-consumer quantitative microbial exposure assessment model to: 1) estimate pet and human exposure to Salmonella via dry pet food, and 2) assess the impact of industry and household-level mitigation strategies on exposure. Data on prevalence and concentration of Salmonella in pet food ingredients, production process parameters, bacterial ecology, and contact transfer in the household were obtained through literature review, industry data, and targeted research. A probabilistic Monte Carlo modeling framework was developed to simulate the production process and basic household exposure routes. Under the range of assumptions adopted in this model, human exposure due to handling pet food is null to minimal if contamination occurs exclusively before extrusion. Exposure increases considerably if recontamination occurs post-extrusion during coating with fat, although mean ingested doses remain modest even at high fat contamination levels, due to the low percent of fat in the finished product. Exposure is highly variable, with the distribution of doses ingested by adult pet owners spanning 3Log CFU per exposure event. Child exposure due to ingestion of 1g of pet food leads to significantly higher doses than adult doses associated with handling the food. Recontamination after extrusion and coating, e.g., via dust or equipment surfaces, may also lead to

  19. A novel photoinduced electron transfer (PET) primer technique for rapid real-time PCR detection of Cryptosporidium spp

    Energy Technology Data Exchange (ETDEWEB)

    Jothikumar, N., E-mail:; Hill, Vincent R.


    Highlights: •Uses a single-labeled fluorescent primer for real-time PCR. •The detection sensitivity of PET PCR was comparable to TaqMan PCR. •Melt curve analysis can be performed to confirm target amplicon production. •Conventional PCR primers can be converted to PET PCR primers. -- Abstract: We report the development of a fluorescently labeled oligonucleotide primer that can be used to monitor real-time PCR. The primer has two parts, the 3′-end of the primer is complimentary to the target and a universal 17-mer stem loop at the 5′-end forms a hairpin structure. A fluorescent dye is attached to 5′-end of either the forward or reverse primer. The presence of guanosine residues at the first and second position of the 3′ dangling end effectively quenches the fluorescence due to the photo electron transfer (PET) mechanism. During the synthesis of nucleic acid, the hairpin structure is linearized and the fluorescence of the incorporated primer increases several-fold due to release of the fluorescently labeled tail and the absence of guanosine quenching. As amplicons are synthesized during nucleic acid amplification, the fluorescence increase in the reaction mixture can be measured with commercially available real-time PCR instruments. In addition, a melting procedure can be performed to denature the double-stranded amplicons, thereby generating fluorescence peaks that can differentiate primer dimers and other non-specific amplicons if formed during the reaction. We demonstrated the application of PET-PCR for the rapid detection and quantification of Cryptosporidium parvum DNA. Comparison with a previously published TaqMan® assay demonstrated that the two real-time PCR assays exhibited similar sensitivity for a dynamic range of detection of 6000–0.6 oocysts per reaction. PET PCR primers are simple to design and less-expensive than dual-labeled probe PCR methods, and should be of interest for use by laboratories operating in resource

  20. TAL effector specificity for base 0 of the DNA target is altered in a complex, effector- and assay-dependent manner by substitutions for the tryptophan in cryptic repeat -1.

    Directory of Open Access Journals (Sweden)

    Erin L Doyle

    Full Text Available TAL effectors are re-targetable transcription factors used for tailored gene regulation and, as TAL effector-nuclease fusions (TALENs, for genome engineering. Their hallmark feature is a customizable central string of polymorphic amino acid repeats that interact one-to-one with individual DNA bases to specify the target. Sequences targeted by TAL effector repeats in nature are nearly all directly preceded by a thymine (T that is required for maximal activity, and target sites for custom TAL effector constructs have typically been selected with this constraint. Multiple crystal structures suggest that this requirement for T at base 0 is encoded by a tryptophan residue (W232 in a cryptic repeat N-terminal to the central repeats that exhibits energetically favorable van der Waals contacts with the T. We generated variants based on TAL effector PthXo1 with all single amino acid substitutions for W232. In a transcriptional activation assay, many substitutions altered or relaxed the specificity for T and a few were as active as wild type. Some showed higher activity. However, when replicated in a different TAL effector, the effects of the substitutions differed. Further, the effects differed when tested in the context of a TALEN in a DNA cleavage assay, and in a TAL effector-DNA binding assay. Substitution of the N-terminal region of the PthXo1 construct with that of one of the TAL effector-like proteins of Ralstonia solanacearum, which have arginine in place of the tryptophan, resulted in specificity for guanine as the 5' base but low activity, and several substitutions for the arginine, including tryptophan, destroyed activity altogether. Thus, the effects on specificity and activity generated by substitutions at the W232 (or equivalent position are complex and context dependent. Generating TAL effector scaffolds with high activity that robustly accommodate sites without a T at position 0 may require larger scale re-engineering.

  1. Using a non-image-based medium-throughput assay for screening compounds targeting N-myristoylation in intracellular Leishmania amastigotes.

    Directory of Open Access Journals (Sweden)

    Daniel Paape


    Full Text Available We have refined a medium-throughput assay to screen hit compounds for activity against N-myristoylation in intracellular amastigotes of Leishmania donovani. Using clinically-relevant stages of wild type parasites and an Alamar blue-based detection method, parasite survival following drug treatment of infected macrophages is monitored after macrophage lysis and transformation of freed amastigotes into replicative extracellular promastigotes. The latter transformation step is essential to amplify the signal for determination of parasite burden, a factor dependent on equivalent proliferation rate between samples. Validation of the assay has been achieved using the anti-leishmanial gold standard drugs, amphotericin B and miltefosine, with EC50 values correlating well with published values. This assay has been used, in parallel with enzyme activity data and direct assay on isolated extracellular amastigotes, to test lead-like and hit-like inhibitors of Leishmania N-myristoyl transferase (NMT. These were derived both from validated in vivo inhibitors of Trypanosoma brucei NMT and a recent high-throughput screen against L. donovani NMT. Despite being a potent inhibitor of L. donovani NMT, the activity of the lead T. brucei NMT inhibitor (DDD85646 against L. donovani amastigotes is relatively poor. Encouragingly, analogues of DDD85646 show improved translation of enzyme to cellular activity. In testing the high-throughput L. donovani hits, we observed macrophage cytotoxicity with compounds from two of the four NMT-selective series identified, while all four series displayed low enzyme to cellular translation, also seen here with the T. brucei NMT inhibitors. Improvements in potency and physicochemical properties will be required to deliver attractive lead-like Leishmania NMT inhibitors.

  2. Rapid genotyping of cytomegalovirus in dried blood spots by multiplex real-time PCR assays targeting the envelope glycoprotein gB and gH genes. (United States)

    de Vries, Jutte J C; Wessels, Els; Korver, Anna M H; van der Eijk, Annemiek A; Rusman, Lisette G; Kroes, Aloys C M; Vossen, Ann C T M


    Genotyping of cytomegalovirus (CMV) is useful to examine potential differences in the pathogenicity of strains and to demonstrate coinfection with multiple strains involved in CMV disease in adults and congenitally infected newborns. Studies on genotyping of CMV in dried blood spots (DBS) are rare and have been hampered by the small amount of dried blood available. In this study, two multiplex real-time PCR assays for rapid gB and gH genotyping of CMV in DBS were developed. Validation of the assays with 39 CMV-positive plasma samples of transplant recipients and 21 urine specimens of congenitally infected newborns was successful in genotyping 100% of the samples, with gB1 and gB3 being the most prevalent genotypes. Multiple gB and gH genotypes were detected in 36% and 33% of the plasma samples, respectively. One urine sample from a newborn with symptomatic congenital CMV was positive for gB1 and gB2. DBS of congenitally infected newborns (n = 41) were tested using 9 μl of dried blood, and genotypes were detected in 81% (gB) and 73% (gH) of the samples, with gB3 being the most prevalent genotype. No clear association of specific genotypes with clinical outcome was observed. In conclusion, the CMV gB and gH PCR assays were found to be rapid, sensitive for detecting mixed infections, and suitable for direct usage on DBS. These assays are efficient tools for genotyping of CMV in DBS of congenitally infected newborns.

  3. Targeted Next Generation Sequencing as a Reliable Diagnostic Assay for the Detection of Somatic Mutations in Tumours Using Minimal DNA Amounts from Formalin Fixed Paraffin Embedded Material

    NARCIS (Netherlands)

    de Leng, Wendy W J; Gadellaa-Van Hooijdonk, Christa G.; Barendregt-Smouter, Françoise A S; Koudijs, Marco J.; Nijman, Ies; Hinrichs, John W.J.; Cuppen, Edwin; van Lieshout, Stef; Loberg, Robert D.; De Jonge, Maja; Voest, Emile E; De Weger, Roel A.; Steeghs, Neeltje; Langenberg, Marlies H G; Sleijfer, Stefan; Willems, Stefan M.; Lolkema, Martijn P.


    BACKGROUND: Targeted Next Generation Sequencing (NGS) offers a way to implement testing of multiple genetic aberrations in diagnostic pathology practice, which is necessary for personalized cancer treatment. However, no standards regarding input material have been defined. This study therefore aimed

  4. Tube-Forming Assays. (United States)

    Brown, Ryan M; Meah, Christopher J; Heath, Victoria L; Styles, Iain B; Bicknell, Roy


    Angiogenesis involves the generation of new blood vessels from the existing vasculature and is dependent on many growth factors and signaling events. In vivo angiogenesis is dynamic and complex, meaning assays are commonly utilized to explore specific targets for research into this area. Tube-forming assays offer an excellent overview of the molecular processes in angiogenesis. The Matrigel tube forming assay is a simple-to-implement but powerful tool for identifying biomolecules involved in angiogenesis. A detailed experimental protocol on the implementation of the assay is described in conjunction with an in-depth review of methods that can be applied to the analysis of the tube formation. In addition, an ImageJ plug-in is presented which allows automatic quantification of tube images reducing analysis times while removing user bias and subjectivity.

  5. Enzyme assays. (United States)

    Reymond, Jean-Louis; Fluxà, Viviana S; Maillard, Noélie


    Enzyme assays are analytical tools to visualize enzyme activities. In recent years a large variety of enzyme assays have been developed to assist the discovery and optimization of industrial enzymes, in particular for "white biotechnology" where selective enzymes are used with great success for economically viable, mild and environmentally benign production processes. The present article highlights the aspects of fluorogenic and chromogenic substrates, sensors, and enzyme fingerprinting, which are our particular areas of interest.

  6. An update on novel quantitative techniques in the context of evolving whole-body PET imaging

    DEFF Research Database (Denmark)

    Houshmand, Sina; Salavati, Ali; Hess, Søren;


    Since its foundation PET has established itself as one of the standard imaging modalities enabling the quantitative assessment of molecular targets in vivo. In the past two decades, quantitative PET has become a necessity in clinical oncology. Despite introduction of various measures...... for quantification and correction of PET parameters, there is debate on the selection of the appropriate methodology in specific diseases and conditions. In this review, we have focused on these techniques with special attention to topics such as static and dynamic whole body PET imaging, tracer kinetic modeling...

  7. Fundamentals of PET and PET/CT imaging. (United States)

    Basu, Sandip; Kwee, Thomas C; Surti, Suleman; Akin, Esma A; Yoo, Don; Alavi, Abass


    In this review, the fundamental principles of fluorodeoxyglucose (FDG) positron emission tomography (PET) and FDG PET/computed tomography (CT) imaging have been described. The basic physics of PET instrumentation, radiotracer chemistry, and the artifacts, as well as normal physiological or benign pathological variants, have been described and presented to the readers in a lucid manner to enable them an easy grasp of the fundamentals of the subject. Finally, we have outlined the current developments in quantitative PET imaging, including dual time point and delayed PET imaging, time-of-flight technology in PET imaging and partial volume correction, and global disease assessment with their potential of being incorporated into the assessment of benign and malignant disorders.

  8. Molecular detection and characterization of Cryptosporidium species in household dogs, pet shop puppies, and dogs kept in a school of veterinary nursing in Japan. (United States)

    Itoh, Naoyuki; Oohashi, Yoshino; Ichikawa-Seki, Madoka; Itagaki, Tadashi; Ito, Yoichi; Saeki, Hideharu; Kanai, Kazutaka; Chikazawa, Seishiro; Hori, Yasutomo; Hoshi, Fumio; Higuchi, Seiichi


    Members of Cryptosporidium species, which are protozoan parasites, are prevalent worldwide and can cause diarrhoea in both humans and animals, including dogs. In addition, the Cryptosporidium species harboured in dogs have the potential for zoonotic transmission. The purpose of the present study was to determine the prevalence of Cryptosporidium species infection and perform molecular characterization of isolates in household dogs, pet shop puppies, and dogs kept in a school of veterinary nursing in Japan. Fresh faecal samples were collected once from 529 household dogs (aged from 2 months to 18 years old, from 9 veterinary clinics located in 6 different regions), 471 pet shop puppies (≤ 3 months old, from 4 pet shops located in 2 different regions), and 98 dogs (aged from 2 to 11 years old) kept in a veterinary nursing school. A nested polymerase chain reaction (PCR) assay targeting the 18S rRNA gene was employed for the detection of Cryptosporidium species, and 111 random samples of PCR amplicons (approximately 500-bp) were sequenced for the molecular characterization of the isolates. The prevalences of Cryptosporidium species in household dogs, pet shop puppies, and veterinary nursing school dogs were 7.2%, 31.6%, and 18.4%, respectively. In household dogs, no significant correlation was observed between the prevalence of Cryptosporidium species and the age (≤ 6 months vs. >6 months), living conditions (indoor vs. outdoor), faecal conditions (formed vs. unformed), and location of residence. In pet shop puppies, the prevalence of Cryptosporidium species was not related to faecal condition; however, the prevalence significantly differed among the pet shops. All of the 111 sequence samples (26 from household dogs, 75 from pet shop puppies, and 10 from veterinary nursing school dogs) were identified as Cryptosporidium canis. The present study demonstrates a high prevalence of Cryptosporidium species infections in pet shop puppies and dogs of a veterinary nursing

  9. Targeting aphA : a new high-throughput screening assay identifies compounds that reduce prime virulence factors of Vibrio cholerae. (United States)

    Bolger, Galina; Roy, Sambit; Zapol'skii, Viktor A; Kaufmann, Dieter E; Schnürch, Michael; Mihovilovic, Marko D; Nandy, Ranjan K; Tegge, Werner


    A high-throughput screening (HTS) assay was developed for identifying compounds with inhibitory effect on aphA, one of the key regulators positively controlling Vibrio cholerae pathogenesis. An inhibitory effect on aphA was expected to lead to attenuation in the secretion of the major pathogenicity factors of V. cholerae, cholera toxin and toxin co-regulated pilus. The plasmid construct pAKSB was developed with a kanamycin resistance (KmR) gene under the control of the aphA -like promoter for conferring a KmR phenotype under aphA -expressing conditions. The HTS assay was performed to identify compounds with inhibitory effect on the growth of O139 V. cholerae MO10 carrying the construct pAKSB in growth medium containing Km (30 g ml-1), but not in its absence. Of 20 338 compounds screened, six compounds were identified to inhibit the pAKSB-induced KmR phenotype and these compounds caused transcriptional inhibition of aphA in V. cholerae O139 strain MO10 as well as variant V. cholerae O1 El Tor strain NM06-058. Of the three most active substances, compound 53760866 showed lowest half-maximal cytotoxicity in a eukaryotic cell viability assay and was characterized further. Compound 53760866 caused reduction in cholera toxin secretion and expression of TcpA in vitro. The in vitro virulence attenuation corroborated well in a suckling mouse model in vivo, which showed reduction of colonization by V. cholerae NM06-058 when co-administered with 53760866. The screening method and the compounds may lead to new preventive strategies for cholera by reducing the pathogenicity of V. cholerae .

  10. Immuno-PET Imaging of HER3 in a Model in which HER3 Signaling Plays a Critical Role.

    Directory of Open Access Journals (Sweden)

    Qinghua Yuan

    Full Text Available HER3 is overexpressed in various carcinomas including colorectal cancer (CRC, which is associated with poor prognosis, and is involved in the development of therapy resistance. Thus, an in vivo imaging technique is needed to evaluate the expression of HER3, an important therapeutic and diagnostic target. Here, we report successful HER3 PET imaging using a newly generated anti-human HER3 monoclonal antibody, Mab#58, and a mouse model of a HER3-overexpressing xenograft tumor. Furthermore, we assessed the role of HER3 signaling in CRC cancer tissue-originated spheroid (CTOS and applied HER3 imaging to detect endogenous HER3 in CTOS-derived xenografts. Cell binding assays of 89Zr-labeled Mab#58 using the HER3-overexpressing cell line HER3/RH7777 demonstrated that [89Zr]Mab#58 specifically bound to HER3/RH7777 cells (Kd = 2.7 nM. In vivo biodistribution study in mice bearing HER3/RH7777 and its parent cell xenografts showed that tumor accumulation of [89Zr]Mab#58 in HER3/RH7777 xenografts was significantly higher than that in the control from day 1 to day 4, tending to increase from day 1 to day 4 and reaching 12.2 ± 4.5%ID/g. Radioactivity in other tissues, including the control xenograft, decreased or remained unchanged from day 1 to day 6. Positron emission tomography (PET in the same model enabled clear visualization of HER3/RH7777 xenografts but not of RH7777 xenografts. CTOS growth assay and signaling assay revealed that CRC CTOS were dependent on HER3 signaling for their growth. In PET studies of mice bearing a CRC CTOS xenograft, the tumor was clearly visualized with [89Zr]Mab#58 but not with the 89Zr-labeled control antibody. Thus, tumor expression of HER3 was successfully visualized by PET with 89Zr-labeled anti-HER3 antibody in CTOS xenograft-bearing mice, a model that retains the properties of the patient tumor. Non-invasive targeting of HER3 by antibodies is feasible, and it is expected to be useful for cancer diagnosis and treatment.

  11. Are Pets Good For Us?

    Institute of Scientific and Technical Information of China (English)



    A pet animal keeps us feel happy.Pets can staywith us when we are left by ourselves,and pets in-vite us to love and be loved.Often a cat or dog cankeep us easy at time when human words don’t help.Pets also keep us get close to the more natural animalworld.Learning to care for a pet helps a child to growup into a loving man or woman who feels responsible(有责任的) towards those dependent (依靠) on him.A pet dog can make us believe in others for we cansee faithfulness (忠诚) in the dog.In fact,we keeppets not only fo...

  12. Targeted next generation sequencing as a reliable diagnostic assay for the detection of somatic mutations in tumours using minimal DNA amounts from formalin fixed paraffin embedded material

    NARCIS (Netherlands)

    W.W.J. de Leng (Wendy); C.G.M. Gadellaa-Van Hooijdonk (C. G M); F.A.S. Barendregt-Smouter (Françoise A.S.); M.J. Koudijs (Marco J.); I. Nijman (Ies); J.W.J. Hinrichs (John W.J.); E. Cuppen (Edwin); S. van Lieshout (Stef); R.D. Loberg (Robert D.); M.J.A. de Jonge (Maja); E.E. Voest (Emile); R.A. de Weger (Roel); N. Steeghs (Neeltje); M.H. Langenberg (Marlies); S. Sleijfer (Stefan); S.M. Willems (Stefan Martin); M.P. Lolkema (Martijn)


    textabstractBackground Targeted Next Generation Sequencing (NGS) offers a way to implement testing of multiple genetic aberrations in diagnostic pathology practice, which is necessary for personalized cancer treatment. However, no standards regarding input material have been defined. This study ther

  13. Development and evaluation of a four-tube real time multiplex PCR assay covering fourteen respiratory viruses, and comparison to its corresponding single target counterparts

    NARCIS (Netherlands)

    R.R. Jansen; J. Schinkel; S. Koekkoek; D. Pajkrt; M. Beld; M.D. de Jong; R. Molenkamp


    Multiplex real time PCR is increasingly used to diagnose respiratory viruses and has shown to be superior to traditional methods, like culture and antigen detection. However, comprehensive data on sensitivity, specificity and performance of the multiplex PCR compared to the single target PCR's is li

  14. Development of a robust cell-based high-throughput screening assay to identify targets of HIV-1 viral protein R dimerization

    NARCIS (Netherlands)

    Zych, Courtney; Dömling, A.; Ayyavoo, Velpandi


    Targeting protein-protein interactions (PPI) is an emerging field in drug discovery. Dimerization and PPI are essential properties of human immunodeficiency virus (HIV)-1 proteins, their mediated functions, and virus biology. Additionally, dimerization is required for the functional interaction of H

  15. Clinical evaluation of 4D PET motion compensation strategies for treatment verification in ion beam therapy (United States)

    Gianoli, Chiara; Kurz, Christopher; Riboldi, Marco; Bauer, Julia; Fontana, Giulia; Baroni, Guido; Debus, Jürgen; Parodi, Katia


    A clinical trial named PROMETHEUS is currently ongoing for inoperable hepatocellular carcinoma (HCC) at the Heidelberg Ion Beam Therapy Center (HIT, Germany). In this framework, 4D PET-CT datasets are acquired shortly after the therapeutic treatment to compare the irradiation induced PET image with a Monte Carlo PET prediction resulting from the simulation of treatment delivery. The extremely low count statistics of this measured PET image represents a major limitation of this technique, especially in presence of target motion. The purpose of the study is to investigate two different 4D PET motion compensation strategies towards the recovery of the whole count statistics for improved image quality of the 4D PET-CT datasets for PET-based treatment verification. The well-known 4D-MLEM reconstruction algorithm, embedding the motion compensation in the reconstruction process of 4D PET sinograms, was compared to a recently proposed pre-reconstruction motion compensation strategy, which operates in sinogram domain by applying the motion compensation to the 4D PET sinograms. With reference to phantom and patient datasets, advantages and drawbacks of the two 4D PET motion compensation strategies were identified. The 4D-MLEM algorithm was strongly affected by inverse inconsistency of the motion model but demonstrated the capability to mitigate the noise-break-up effects. Conversely, the pre-reconstruction warping showed less sensitivity to inverse inconsistency but also more noise in the reconstructed images. The comparison was performed by relying on quantification of PET activity and ion range difference, typically yielding similar results. The study demonstrated that treatment verification of moving targets could be accomplished by relying on the whole count statistics image quality, as obtained from the application of 4D PET motion compensation strategies. In particular, the pre-reconstruction warping was shown to represent a promising choice when combined with intra

  16. PET and Recycling

    Directory of Open Access Journals (Sweden)

    Funda Sevencan


    Full Text Available This review aims to clarify the need of decreasing the environmental effects caused by human and draw attention to the increasing environmental effects of plastics wastes. Plastics consist of organic molecules with high density molecules or polymers. Main resources of plastics are the residue of oil rafineries. Several advantages of plastics, have increased the usage continuously. Polyethylene Terephthalate (PET is the most commonly used plastics. PET is used to protect food, drinking water, fruit juice, alcoholic beverage, and food packing films. By the increasing interest on the environmental effects of plastic wastes, concerns on the recyclable packing materials also grew up. Also the daily use of recyclable containers consisting PET have increased. There are five steps for recycling of plastics. These steps are; using large amounts of plastics, collecting them in a big center, classifying and sorting the plastics, reproducing the polymers and obtaining new products with melted plastics. Providing a healthy recycling of plastics, the consumers should have knowledge and responsibility. The consumer should know what he/she has to do before putting the plastics in the recycling containers. Recycling containers and bags should be placed near the sources of plastic wastes. Consequently, the plastic wastes and environmental problems they cause will be on the agenda in future. [TAF Prev Med Bull. 2007; 6(4: 307-312

  17. Pet overpopulation: An economic analysis


    Coate, Stephen; Knight, Brian


    This paper considers the problem of pet overpopulation. It develops a tractable dynamic model whose positive predictions square well with key features of the current U.S. market for pets. The model is used to understand, from a welfare economic perspective, the sense in which there is \\overpopulation" of pets and the underlying causes of the problem. The paper also employs the model to consider what policies might be implemented to deal with the problem. A calibrated example is developed to i...

  18. PET radiopharmaceuticals for neuroreceptor imaging

    Institute of Scientific and Technical Information of China (English)


    Routine clinical PET radiopharmaceuticals for the noninvasive imaging of brain receptors, transporters,and enzymes are commonly labeled with positron emitting nuclides such as carbon-11 or fluorine-18. Certain minimal conditions need to be fulfilled for these PET ligands to be used as imaging agents in vivo. Some of these prerequisites are discussed and examples of the most useful clinical PET radiopharmaceuticals that have found application in the central nervous system are reviewed.

  19. Infections That Pets Carry (For Parents) (United States)

    ... Your 1- to 2-Year-Old Infections That Pets Carry KidsHealth > For Parents > Infections That Pets Carry ... how to protect your family from infections. How Pets Spread Infections Like people, all animals carry germs . ...

  20. Assays for calcitonin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.


    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is /sup 125/I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed.

  1. In vivo erythrocyte micronucleus assay III. Validation and regulatory acceptance of automated scoring and the use of rat peripheral blood reticulocytes, with discussion of non-hematopoietic target cells and a single dose-level limit test. (United States)

    Hayashi, Makoto; MacGregor, James T; Gatehouse, David G; Blakey, David H; Dertinger, Stephen D; Abramsson-Zetterberg, Lilianne; Krishna, Gopala; Morita, Takeshi; Russo, Antonella; Asano, Norihide; Suzuki, Hiroshi; Ohyama, Wakako; Gibson, Dave


    The in vivo micronucleus assay working group of the International Workshop on Genotoxicity Testing (IWGT) discussed new aspects in the in vivo micronucleus (MN) test, including the regulatory acceptance of data derived from automated scoring, especially with regard to the use of flow cytometry, the suitability of rat peripheral blood reticulocytes to serve as the principal cell population for analysis, the establishment of in vivo MN assays in tissues other than bone marrow and blood (for example liver, skin, colon, germ cells), and the biological relevance of the single-dose-level test. Our group members agreed that flow cytometric systems to detect induction of micronucleated immature erythrocytes have advantages based on the presented data, e.g., they give good reproducibility compared to manual scoring, are rapid, and require only small quantities of peripheral blood. Flow cytometric analysis of peripheral blood reticulocytes has the potential to allow monitoring of chromosome damage in rodents and also other species as part of routine toxicology studies. It appears that it will be applicable to humans as well, although in this case the possible confounding effects of splenic activity will need to be considered closely. Also, the consensus of the group was that any system that meets the validation criteria recommended by the IWGT (2000) should be acceptable. A number of different flow cytometric-based micronucleus assays have been developed, but at the present time the validation data are most extensive for the flow cytometric method using anti-CD71 fluorescent staining especially in terms of inter-laboratory collaborative data. Whichever method is chosen, it is desirable that each laboratory should determine the minimum sample size required to ensure that scoring error is maintained below the level of animal-to-animal variation. In the second IWGT, the potential to use rat peripheral blood reticulocytes as target cells for the micronucleus assay was discussed

  2. Use of DNA melting simulation software for in silico diagnostic assay design: targeting regions with complex melting curves and confirmation by real-time PCR using intercalating dyes

    Directory of Open Access Journals (Sweden)

    Saint Christopher P


    Full Text Available Abstract Background DNA melting curve analysis using double-stranded DNA-specific dyes such as SYTO9 produce complex and reproducible melting profiles, resulting in the detection of multiple melting peaks from a single amplicon and allowing the discrimination of different species. We compare the melting curves of several Naegleria and Cryptosporidium amplicons generated in vitro with in silico DNA melting simulations using the programs POLAND and MELTSIM., then test the utility of these programs for assay design using a genetic marker for toxin production in cyanobacteria. Results The SYTO9 melting curve profiles of three species of Naegleria and two species of Cryptosporidium were similar to POLAND and MELTSIM melting simulations, excepting some differences in the relative peak heights and the absolute melting temperatures of these peaks. MELTSIM and POLAND were used to screen sequences from a putative toxin gene in two different species of cyanobacteria and identify regions exhibiting diagnostic melting profiles. For one of these diagnostic regions the POLAND and MELTSIM melting simulations were observed to be different, with POLAND more accurately predicting the melting curve generated in vitro. Upon further investigation of this region with MELTSIM, inconsistencies between the melting simulation for forward and reverse complement sequences were observed. The assay was used to accurately type twenty seven cyanobacterial DNA extracts in vitro. Conclusion Whilst neither POLAND nor MELTSIM simulation programs were capable of exactly predicting DNA dissociation in the presence of an intercalating dye, the programs were successfully used as tools to identify regions where melting curve differences could be exploited for diagnostic melting curve assay design. Refinements in the simulation parameters would be required to account for the effect of the intercalating dye and salt concentrations used in real-time PCR. The agreement between the melting

  3. Extended suicide with a pet. (United States)

    Cooke, Brian K


    The combination of the killing of a pet and a suicide is a perplexing scenario that is largely unexplored in the literature. Many forensic psychiatrists and psychologists may be unaccustomed to considering the significance of the killing of a pet. The subject is important, however, because many people regard their pets as members of their family. A case is presented of a woman who killed her pet dog and herself by carbon monoxide poisoning. The purpose of this article is to provide an initial exploration of the topic of extended suicide with a pet. Forensic mental health evaluations may have a role in understanding the etiology of this event and in opining as to the culpability of individuals who attempt to or successfully kill a pet and then commit suicide. Because the scientific literature is lacking, there is a need to understand this act from a variety of perspectives. First, a social and anthropological perspective will be presented that summarizes the history of the practice of killing of one's pet, with a focus on the ancient Egyptians. A clinical context will examine what relationship animals have to mental illness. A vast body of existing scientific data showing the relevance of human attachment to pets suggests that conclusions from the phenomena of homicide-suicide and filicide-suicide are applicable to extended suicide with a pet. Finally, recommendations will be proposed for both clinical and forensic psychiatrists faced with similar cases.

  4. Current concepts in F18 FDG PET/CT-based Radiation Therapy planning for Lung Cancer

    Directory of Open Access Journals (Sweden)

    Percy eLee


    Full Text Available Radiation therapy is an important component of cancer therapy for early stage as well as locally advanced lung cancer. The use of F18 FDG PET/CT has come to the forefront of lung cancer staging and overall treatment decision-making. FDG PET/CT parameters such as standard uptake value and metabolic tumor volume provide important prognostic and predictive information in lung cancer. Importantly, FDG PET/CT for radiation planning has added biological information in defining the gross tumor volume as well as involved nodal disease. For example, accurate target delineation between tumor and atelectasis is facilitated by utilizing PET and CT imaging. Furthermore, there has been meaningful progress in incorporating metabolic information from FDG PET/CT imaging in radiation treatment planning strategies such as radiation dose escalation based on standard uptake value thresholds as well as using respiratory gated PET and CT planning for improved target delineation of moving targets. In addition, PET/CT based follow-up after radiation therapy has provided the possibility of early detection of local as well as distant recurrences after treatment. More research is needed to incorporate other biomarkers such as proliferative and hypoxia biomarkers in PET as well as integrating metabolic information in adaptive, patient-centered, tailored radiation therapy.

  5. A facile, sensitive, and highly specific trinitrophenol assay based on target-induced synergetic effects of acid induction and electron transfer towards DNA-templated copper nanoclusters. (United States)

    Li, Haiyin; Chang, Jiafu; Hou, Ting; Ge, Lei; Li, Feng


    Reliable, selective and sensitive approaches for trinitrophenol (TNP) detection are highly desirable with respect to national security and environmental protection. Herein, a simple and novel fluorescent strategy for highly sensitive and specific TNP assay has been successfully developed, which is based on the quenching of the fluorescent poly(thymine)-templated copper nanoclusters (DNA-CuNCs), through the synergetic effects of acid induction and electron transfer. Upon the addition of TNP, donor-acceptor complexes between the electron-deficient nitro-groups in TNP and the electron-donating DNA templates are formed, resulting in the close proximity between TNP and CuNCs. Moreover, the acidity of TNP contributes to the pH decrease of the system. These factors combine to dramatically quench the fluorescence of DNA-CuNCs, providing a "signal-off" strategy for TNP sensing. The as-proposed strategy demonstrates high sensitivity for TNP assay, and a detection limit of 0.03μM is obtained, which is lower than those reported by using organic fluorescent materials. More significantly, this approach shows outstanding selectivity over a number of TNP analogues, such as 2,4,6-trinitrotoluene (TNT), 2,4-dinitrotoluene (DNT), 2,4-dinitrophenol (DNP), 3-nitrophenol (NP), nitrobenzene (NB), phenol (BP), and toluene (BT). Compared with previous studies, this method does not need complex DNA sequence design, fluorescent dye labeling, or sophisticated organic reactions, rendering the strategy with additional advantages of simplicity and cost-effectiveness. In addition, the as-proposed strategy has been adopted for the detection of TNP in natural water samples, indicating its great potential to be applied in the fields of public safety and environmental monitoring.

  6. 靶向G蛋白偶联受体的高通量药物筛选方法%High-throughput screening assays for G-protein-coupled receptors-targeted drug discovery

    Institute of Scientific and Technical Information of China (English)

    李静; 谢欣


    G-protein-coupled receptors (GPCR) , also known as 7 trans-membrane receptors, are the largest family of cell surface receptors. GPCR mediate many important physiological functions and are among the most successful therapeutic targets for a broad spectrum of diseases. These receptors are the targets of > 50% of the current therapeutic agents on the market. Therefore, GPCR assay development and GPCR ligand screening remain the major focus of drug discovery research worldwide. In this review, we summarize the most widely used GPCR assays and recent advances in high-throughput screening technology for GPCR drug discovery.%G蛋白偶联受体( G-protein-coupled receptors,GPCR)是一类具有7次跨膜结构的膜蛋白.GPCR介导多种重要的生理功能,与很多疾病密切相关,是最重要的现代药物靶点家族.目前市场上有近50%的药物是以GPCR为靶点的.因此,GPCR分析方法和GPCR配体筛选方法的研究是当今世界新药研究的重点和热点.本文归纳介绍了近年来被广泛使用的GPCR药物发现方法,以及靶向GPCR高通量筛选技术的最新研究进展.

  7. Microfluidic reactor for the radiosynthesis of PET radiotracers

    Energy Technology Data Exchange (ETDEWEB)

    Gillies, J.M. [Cancer Research-UK/UMIST Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom)]. E-mail:; Prenant, C. [Cancer Research-UK/UMIST Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, PO Box 88, Manchester M60 1QD (United Kingdom); Chimon, G.N. [Cancer Research-UK/UMIST Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, PO Box 88, Manchester M60 1QD (United Kingdom); Smethurst, G.J. [Cancer Research-UK/UMIST Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Perrie, W. [Department of Engineering, University of Liverpool, Liverpool L69 3GH (United Kingdom); Hamblett, I. [Cancer Research-UK/UMIST Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Dekker, B. [Cancer Research-UK/UMIST Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Zweit, J. [Cancer Research-UK/UMIST Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, PO Box 88, Manchester M60 1QD (United Kingdom)


    Here we show the first application of a microfabricated reaction system to PET radiochemistry, we term 'microfluidic PET'. The short half-life of the positron emitting isotopes and the trace chemical quantities used in radiolabelling make PET radiochemistry amenable to miniaturisation. Microfluidic technologies are capable of controlling and transferring tiny quantities of liquids which allow chemical and biochemical assays to be integrated and carried out on a small scale. Such technologies provide distinct advantages over current methods of PET radiochemical synthesis. To demonstrate 'proof of principle' we have investigated the radiohalogenation of small and large molecular weight molecules using the microfluidic device. These reactions involved the direct radioiodination of the apoptosis marker Annexin V using iodine-124, the indirect radioiodination of the anti-cancer drug doxorubicin from a tin-butyl precursor and the radiosynthesis of 2-[{sup 18}F]FDG from a mannose triflate precursor and fluorine-18 and hence provide a test bed for microfluidic reactions. We demonstrate the rapid radioiodination of the protein Annexin V (40% radiochemical yield within 1 min) and the rapid radiofluorination of 2-[{sup 18}F]FDG (60% radiochemical yield within 4 s) using a polymer microreactor chip. Chromatographic analysis showed that the labelling efficiency of the unoptimised microfluidic chip is comparable to conventional PET radiolabelling reactions.

  8. PET and PET/CT in clinical cardiology

    Energy Technology Data Exchange (ETDEWEB)

    Won, Kyoung Sook [Keimyung University School of Medicine, Daegu (Korea, Republic of)


    Cardiac PET emerged as a powerful tool that allowed in vivo quantification of physiologic processes including myocardial perfusion and metabolism, as well as neuronal and receptor function for more than 25 years. Now PET imaging has been playing an important role in the clinical evaluation of patients with known or suspected ischemic heart disease. This important clinical role is expected to grow with the availability of PET/CT scanner that allow a true integration of structure and function. The objective of this review is to provide and update on the current and future role of PET in clinical cardiology with a special eye on the great opportunities now offered by PET/CT.

  9. SPECT and PET Imaging of Meningiomas

    Directory of Open Access Journals (Sweden)

    Varvara Valotassiou


    Full Text Available Meningiomas arise from the meningothelial cells of the arachnoid membranes. They are the most common primary intracranial neoplasms and represent about 20% of all intracranial tumors. They are usually diagnosed after the third decade of life and they are more frequent in women than in men. According to the World Health Organization (WHO criteria, meningiomas can be classified into grade I meningiomas, which are benign, grade II (atypical and grade III (anaplastic meningiomas, which have a much more aggressive clinical behaviour. Computed Tomography (CT and Magnetic Resonance Imaging (MRI are routinely used in the diagnostic workup of patients with meningiomas. Molecular Nuclear Medicine Imaging with Single Photon Emission Computed Tomography (SPECT and Positron Emission Tomography (PET could provide complementary information to CT and MRI. Various SPECT and PET tracers may provide information about cellular processes and biological characteristics of meningiomas. Therefore, SPECT and PET imaging could be used for the preoperative noninvasive diagnosis and differential diagnosis of meningiomas, prediction of tumor grade and tumor recurrence, response to treatment, target volume delineation for radiation therapy planning, and distinction between residual or recurrent tumour from scar tissue.

  10. Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation (United States)

    Wang, Yan; Zhang, Pei; An, Le; Ma, Guangkai; Kang, Jiayin; Shi, Feng; Wu, Xi; Zhou, Jiliu; Lalush, David S.; Lin, Weili; Shen, Dinggang


    Positron emission tomography (PET) has been widely used in clinical diagnosis for diseases and disorders. To obtain high-quality PET images requires a standard-dose radionuclide (tracer) injection into the human body, which inevitably increases risk of radiation exposure. One possible solution to this problem is to predict the standard-dose PET image from its low-dose counterpart and its corresponding multimodal magnetic resonance (MR) images. Inspired by the success of patch-based sparse representation (SR) in super-resolution image reconstruction, we propose a mapping-based SR (m-SR) framework for standard-dose PET image prediction. Compared with the conventional patch-based SR, our method uses a mapping strategy to ensure that the sparse coefficients, estimated from the multimodal MR images and low-dose PET image, can be applied directly to the prediction of standard-dose PET image. As the mapping between multimodal MR images (or low-dose PET image) and standard-dose PET images can be particularly complex, one step of mapping is often insufficient. To this end, an incremental refinement framework is therefore proposed. Specifically, the predicted standard-dose PET image is further mapped to the target standard-dose PET image, and then the SR is performed again to predict a new standard-dose PET image. This procedure can be repeated for prediction refinement of the iterations. Also, a patch selection based dictionary construction method is further used to speed up the prediction process. The proposed method is validated on a human brain dataset. The experimental results show that our method can outperform benchmark methods in both qualitative and quantitative measures.

  11. PET/CT-guided treatment planning for paediatric cancer patients: a simulation study of proton and conventional photon therapy

    DEFF Research Database (Denmark)

    Kornerup, Josefine S.; Brodin, N. P.; Bjork-Eriksson, T.;


    OBJECTIVE: To investigate the impact of including fluorine-18 fludeoxyglucose ((18)F-FDG) positron emission tomography (PET) scanning in the planning of paediatric radiotherapy (RT). METHODS: Target volumes were first delineated without and subsequently re-delineated with access to (18)F-FDG PET......) and estimated risk of secondary cancer (SC). RESULTS: Considerable deviations between CT- and PET/CT-guided target volumes were seen in 3 out of the 11 patients studied. However, averaging over the whole cohort, CT or PET/CT guidance introduced no significant difference in the shape or size of the target...... volumes, target dose coverage, irradiated volumes, estimated NTCP or SC risk, neither for IMPT nor 3DCRT. CONCLUSION: Our results imply that the inclusion of PET/CT scans in the RT planning process could have considerable impact for individual patients. There were no general trends of increasing...

  12. Neurotransmission imaging by PET

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Suhara, Tetsuya [National Inst. of Radiological Sciences, Chiba (Japan)


    PET studies on neurotransmission in psychological disorders to evaluate abnormal neurotransmission and therapeutic effects are thoroughly reviewed by type of major neurotransmitters. Studies on dopaminergic neurotransmission have focused on the function of dopamine D{sub 2} receptors, receptor subtypes, such as the D{sub 1} receptor, and ligands, such as transporters. PET studies of dopamine D{sub 2} receptor, which began in the early 1980s, have predominantly been performed in schizophrenia, and most have failed to detect any statistically significant differences between schizophrenia patients and controls. The studies in the early 1980s were performed by using [{sup 11}C]N-methyl-spiperone (NMSP) and [{sup 11}C]raclopride, ligands for striatal dopamine D{sub 2} receptors. [{sup 11}C]FLB457, which has much higher affinity for D{sub 2} receptors than raclopride, began to be used in the 1990s. Dopamine D{sub 2} occupancy after drug ingestion has also been investigated to clarify the mechanisms and effects of antipsychotic drugs, and there have also been studies on the effect of aging and personality traits on dopamine D{sub 2} receptor levels in healthy subjects. In studies on dopamine receptor subtypes other than D{sub 2}, dopamine D{sub 1} receptors have been studied in connection with assessments of cognitive functions. Most studies on dopamine transporters have been related to drug dependence. Serotonin 5-HT{sub 2A} receptors have been studied with [{sup 11}C]NMSP in schizophrenia patients, while studies of another serotonin receptor subtype, 5-HT{sub 1A} receptors, have been mainly conducted in patients with depression. [{sup 11}C]NMSP PET showed no difference between schizophrenia patients who had not undergone phamacotherapy and normal subjects. Because serotonin selective reuptake inhibitors (SSRIs) affect serotonin transporters, and abnormalities in serotonin transporters detected in mood disorders, PET ligands for serotonin transporters have increasingly

  13. Small Molecule PET-Radiopharmaceuticals

    NARCIS (Netherlands)

    Elsinga, Philip H.; Dierckx, Rudi A. J. O.


    This review describes several aspects required for the development of small molecule PET-tracers. Design and selection criteria are important to consider before starting to develop novel PET-tracers. Principles and latest trends in C-11 and F-18-radiochemistry are summarized. In addition an update o

  14. Innovations in PET/CT

    DEFF Research Database (Denmark)

    Levin Klausen, T; Høgild Keller, S; Vinter Olesen, O


    There has been a longstanding interest in positron emission tomography (PET) in combination with computed tomography (CT). Mostly because of the lack of structural information in PET which makes it difficult to assess the precise location of tissue with metabolic uptake, whereas CT can provide...

  15. Supplements for exotic pets. (United States)

    Mejia-Fava, Johanna; Colitz, Carmen M H


    The use of supplements has become commonplace in an effort to complement traditional therapy and as part of long-term preventive health plans. This article discusses historical and present uses of antioxidants, vitamins, and herbs. By complementing traditional medicine with holistic and alternative nutrition and supplements, the overall health and wellness of exotic pets can be enhanced and balanced. Further research is needed for understanding the strengths and uses of supplements in exotic species. Going back to the animals' origin and roots bring clinicians closer to nature and its healing powers.

  16. PET and PET/CT - relevance in breast cancer patients; PET und PET/CT - Stellenwert beim Mammakarzinom

    Energy Technology Data Exchange (ETDEWEB)

    Palmedo, H. [Klinik und Poliklinik fuer Nuklearmedizin, Universitaetsklinikum Bonn (Germany)


    Breast cancer is the most frequent malignant tumor of women in Germany. In spite of an increasing incidence mortality has slightly declined most likely due to improvements in diagnosis and therapy of the disease. FDG-PET has a high diagnostic accuracy for the detection of lymph node and distant metastases. However, PET is no alternative to axillary dissection or sentinel node biopsy because sensitivity for small lymph node metastases is limited. For N-staging, FDG-PET delivers valuable information if mammaria-interna or mediastinal lymph node disease has to be proven (1b-indication). Individually, PET can add important diagnostic information in patients with suspected distant metastases but unsuspicious or equivocal conventional imaging (2-indication). FDG-PET shows unique and favourable properties for early therapy monitoring during preoperative chemotherapy. Larger studies have to confirm these results. (orig.)

  17. Identification of Antiviral Agents Targeting Hepatitis B Virus Promoter from Extracts of Indonesian Marine Organisms by a Novel Cell-Based Screening Assay

    Directory of Open Access Journals (Sweden)

    Atsuya Yamashita


    Full Text Available The current treatments of chronic hepatitis B (CHB face a limited choice of vaccine, antibody and antiviral agents. The development of additional antiviral agents is still needed for improvement of CHB therapy. In this study, we established a screening system in order to identify compounds inhibiting the core promoter activity of hepatitis B virus (HBV. We prepared 80 extracts of marine organisms from the coral reefs of Indonesia and screened them by using this system. Eventually, two extracts showed high inhibitory activity (>95% and low cytotoxicity (66% to 77%. Solvent fractionation, column chromatography and NMR analysis revealed that 3,5-dibromo-2-(2,4-dibromophenoxy-phenol (compound 1 and 3,4,5-tribromo-2-(2,4-dibromophenoxy-phenol (compound 2, which are classified as polybrominated diphenyl ethers (PBDEs, were identified as anti-HBV agents in the extracts. Compounds 1 and 2 inhibited HBV core promoter activity as well as HBV production from HepG2.2.15.7 cells in a dose-dependent manner. The EC50 values of compounds 1 and 2 were 0.23 and 0.80 µM, respectively, while selectivity indexes of compound 1 and 2 were 18.2 and 12.8, respectively. These results suggest that our cell-based HBV core promoter assay system is useful to determine anti-HBV compounds, and that two PBDE compounds are expected to be candidates of lead compounds for the development of anti-HBV drugs.

  18. Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and Gastrointestinal Malignancies (United States)

    Fisher, Kevin E.; Zhang, Linsheng; Wang, Jason; Smith, Geoffrey H.; Newman, Scott; Schneider, Thomas M.; Pillai, Rathi N.; Kudchadkar, Ragini R.; Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Lawson, David H.; Delman, Keith A.; El-Rayes, Bassel F.; Wilson, Malania M.; Sullivan, H. Clifford; Morrison, Annie S.; Balci, Serdar; Adsay, N. Volkan; Gal, Anthony A.; Sica, Gabriel L.; Saxe, Debra F.; Mann, Karen P.; Hill, Charles E.; Khuri, Fadlo R.; Rossi, Michael R.


    We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines. PMID:26801070

  19. 68Ga-DOTA-NOC PET/CT detects somatostatin receptors expression in von hippel-lindau cerebellar disease. (United States)

    Ambrosini, Valentina; Campana, Davide; Allegri, Vincenzo; Opocher, Giuseppe; Fanti, Stefano


    A case of Von-Hippel Lindau (VHL) disease has been studied using 68Ga-DOTA-NOC PET/CT. PET/CT demonstrated the presence of somatostatin receptors within 2 focal areas in the cerebellum corresponding to the lesions detected by MRI. Considering the heterogeneous lesions localizations in VHL disease, PET/CT may be a useful imaging modality for diagnosing lesions of central nervous system and neuroendocrine lesions and for direct demonstration of somatostatin receptors for targeted treatment.

  20. [(18)F](2S,4R)4-Fluoroglutamine PET Detects Glutamine Pool Size Changes in Triple-Negative Breast Cancer in Response to Glutaminase Inhibition. (United States)

    Zhou, Rong; Pantel, Austin R; Li, Shihong; Lieberman, Brian P; Ploessl, Karl; Choi, Hoon; Blankemeyer, Eric; Lee, Hsiaoju; Kung, Hank F; Mach, Robert H; Mankoff, David A


    Glutaminolysis is a metabolic pathway adapted by many aggressive cancers, including triple-negative breast cancers (TNBC), to utilize glutamine for survival and growth. In this study, we examined the utility of [(18)F](2S,4R)4-fluoroglutamine ([(18)F]4F-Gln) PET to measure tumor cellular glutamine pool size, whose change might reveal the pharmacodynamic (PD) effect of drugs targeting this cancer-specific metabolic pathway. High glutaminase (GLS) activity in TNBC tumors resulted in low cellular glutamine pool size assayed via high-resolution (1)H magnetic resonance spectroscopy (MRS). GLS inhibition significantly increased glutamine pool size in TNBC tumors. MCF-7 tumors, with inherently low GLS activity compared with TNBC, displayed a larger baseline glutamine pool size that did not change as much in response to GLS inhibition. The tumor-to-blood-activity ratios (T/B) obtained from [(18)F]4F-Gln PET images matched the distinct glutamine pool sizes of both tumor models at baseline. After a short course of GLS inhibitor treatment, the T/B values increased significantly in TNBC, but did not change in MCF-7 tumors. Across both tumor types and after GLS inhibitor or vehicle treatment, we observed a strong positive correlation between T/B values and tumor glutamine pool size measured using MRS (r(2) = 0.71). In conclusion, [(18)F]4F-Gln PET tracked cellular glutamine pool size in breast cancers with differential GLS activity and detected increases in cellular glutamine pool size induced by GLS inhibitors. This study accomplished the first necessary step toward validating [(18)F]4F-Gln PET as a PD marker for GLS-targeting drugs. Cancer Res; 77(6); 1476-84. ©2017 AACR.

  1. Evaluation of two novel {sup 64}Cu-labeled RGD peptide radiotracers for enhanced PET imaging of tumor integrin α{sub v}β{sub 3}

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, Reinier; Graves, Stephen A.; Nickles, Robert J. [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); Czerwinski, Andrzej; Valenzuela, Francisco [Peptides International, Inc., Louisville, KY (United States); Chakravarty, Rubel; Yang, Yunan; England, Christopher G. [University of Wisconsin, Department of Radiology, Madison, WI (United States); Cai, Weibo [University of Wisconsin, Department of Medical Physics, Madison, WI (United States); University of Wisconsin, Department of Radiology, Madison, WI (United States); University of Wisconsin Carbone Cancer Center, Madison, WI (United States)


    Our goal was to demonstrate that suitably derivatized monomeric RGD peptide-based PET tracers, targeting integrin α{sub v}β{sub 3}, may offer advantages in image contrast, time for imaging, and low uptake in nontarget tissues. Two cyclic RGDfK derivatives, (PEG){sub 2}-c(RGDfK) and PEG{sub 4}-SAA{sub 4}-c(RGDfK), were constructed and conjugated to NOTA for {sup 64}Cu labeling. Their integrin α{sub v}β{sub 3}-binding properties were determined via a competitive cell binding assay. Mice bearing U87MG tumors were intravenously injected with each of the {sup 64}Cu-labeled peptides, and PET scans were acquired during the first 30 min, and 2 and 4 h after injection. Blocking and ex vivo biodistribution studies were carried out to validate the PET data and confirm the specificity of the tracers. The IC{sub 50} values of NOTA-(PEG){sub 2}-c(RGDfK) and NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) were 444 ± 41 nM and 288 ± 66 nM, respectively. Dynamic PET data of {sup 64}Cu-NOTA-(PEG){sub 2}-c(RGDfK) and {sup 64}Cu-NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) showed similar circulation t{sub 1/2} and peak tumor uptake of about 4 %ID/g for both tracers. Due to its marked hydrophilicity, {sup 64}Cu-NOTA-PEG{sub 4}-SAA{sub 4}-c(RGDfK) provided faster clearance from tumor and normal tissues yet maintained excellent tumor-to-background ratios. Static PET scans at later time-points corroborated the enhanced excretion of the tracer, especially from abdominal organs. Ex vivo biodistribution and receptor blocking studies confirmed the accuracy of the PET data and the integrin α{sub v}β{sub 3}-specificity of the peptides. Our two novel RGD-based radiotracers with optimized pharmacokinetic properties allowed fast, high-contrast PET imaging of tumor-associated integrin α{sub v}β{sub 3}. These tracers may facilitate the imaging of abdominal malignancies, normally precluded by high background uptake. (orig.)

  2. 18F-FET-PET in Primary Hyperparathyroidism

    DEFF Research Database (Denmark)

    Krakauer, Martin; Kjær, Andreas; Bennedbæk, Finn Noe


    Preoperative localisation of the diseased parathyroid gland(s) in primary hyperparathyroidism (PHP) is a prerequisite for subsequent minimally invasive surgery. Recently, as alternatives to conventional sestamibi parathyroid scintigraphy, the (11)C-based positron emission tomography (PET) tracers......-isotope parathyroid subtraction single photon emission computed tomography had determined the exact location of the parathyroid adenoma. A dynamic FET PET/CT scan was performed with subsequent visual evaluation and calculation of target-to-background (TBR; parathyroid vs. thyroid). The maximum TBR in the two patients...

  3. 36 CFR 2.15 - Pets. (United States)


    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 2.15 Section 2.15 Parks... USE AND RECREATION § 2.15 Pets. (a) The following are prohibited: (1) Possessing a pet in a public... area closed to the possession of pets by the superintendent. This subparagraph shall not apply to...

  4. 36 CFR 1002.15 - Pets. (United States)


    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Pets. 1002.15 Section 1002.15....15 Pets. (a) The following are prohibited: (1) Possessing a pet in a public building, public... possession of pets by the Board. This paragraph shall not apply to guide dogs accompanying visually...

  5. 7 CFR 502.11 - Pets. (United States)


    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 502.11 Section 502.11 Agriculture Regulations of... CONDUCT ON BELTSVILLE AGRICULTURE RESEARCH CENTER PROPERTY, BELTSVILLE, MARYLAND § 502.11 Pets. Pets... vaccinations. Pets that are the property of employees residing on BARC must be up to date on their...

  6. [(68) Ga]-HP-DO3A-nitroimidazole: a promising agent for PET detection of tumor hypoxia. (United States)

    Wu, Yunkou; Hao, Guiyang; Ramezani, Saleh; Saha, Debabrata; Zhao, Dawen; Sun, Xiankai; Sherry, A Dean


    The goal of this study is to evaluate a new (68) Ga-based imaging agent for detecting tumor hypoxia using positron emission tomography (PET). The new hypoxia targeting agent reported here, [(68) Ga]-HP-DO3A-nitroimidazole ([(68) Ga]-HP-DO3A-NI), was constructed by linking a nitroimidazole moiety with the macrocyclic ligand component of ProHance®, HP-DO3A. The hypoxia targeting capability of this agent was evaluated in A549 lung cancer cells in vitro and in SCID mice bearing subcutaneous A549 tumor xenografts. The cellular uptake assays showed that significantly more [(68) Ga]-HP-DO3A-NI accumulates in hypoxic tumor cells at 30, 60 and 120 min than in the same cells exposed to 21% O2 . The agent also accumulated in hypoxic tumors in vivo to give a tumor/muscle ratio (T/M) of 5.0 ± 1.2 (n = 3) as measured by PET at 2 h post-injection (p.i.). This was further confirmed by ex vivo biodistribution data. In addition, [(68) Ga]-HP-DO3A-NI displayed very favorable pharmacokinetic properties, as it was cleared largely through the kidneys with little to no accumulation in liver, heart or lung (%ID/g 68) Ga]-HP-DO3A, which lacks the nitroimidazole moiety, and by PET imaging of tumor-bearing mice breathing air versus 100% O2 . Given the commercial availability of cGMP (68) Ge/(68) Ga generators and the ease of (68) Ga labeling, the new agent could potentially be widely applied for imaging tumor hypoxia prior to radiation therapy.

  7. Weight Gain following Pallidal Deep Brain Stimulation: A PET Study


    Sauleau, Paul; Drapier, Sophie; Duprez, Joan; Houvenaghel, Jean-François; Dondaine, Thibaut; Haegelen, Claire; Drapier, Dominique; Jannin, Pierre; Robert, Gabriel; Le Jeune, Florence; Vérin, Marc


    The mechanisms behind weight gain following deep brain stimulation (DBS) surgery seem to be multifactorial and suspected depending on the target, either the subthalamic nucleus (STN) or the globus pallidus internus (GPi). Decreased energy expenditure following motor improvement and behavioral and/or metabolic changes are possible explanations. Focusing on GPi target, our objective was to analyze correlations between changes in brain metabolism (measured with PET) and weight gain following GPi...

  8. Non-Target Effects of Green Fluorescent Protein (GFP-Derived Double-Stranded RNA (dsRNA-GFP Used in Honey Bee RNA Interference (RNAi Assays

    Directory of Open Access Journals (Sweden)

    Francis M. F. Nunes


    Full Text Available RNA interference has been frequently applied to modulate gene function in organisms where the production and maintenance of mutants is challenging, as in our model of study, the honey bee, Apis mellifera. A green fluorescent protein (GFP-derived double-stranded RNA (dsRNA-GFP is currently commonly used as control in honey bee RNAi experiments, since its gene does not exist in the A. mellifera genome. Although dsRNA-GFP is not expected to trigger RNAi responses in treated bees, undesirable effects on gene expression, pigmentation or developmental timing are often observed. Here, we performed three independent experiments using microarrays to examine the effect of dsRNA-GFP treatment (introduced by feeding on global gene expression patterns in developing worker bees. Our data revealed that the expression of nearly 1,400 genes was altered in response to dsRNA-GFP, representing around 10% of known honey bee genes. Expression changes appear to be the result of both direct off-target effects and indirect downstream secondary effects; indeed, there were several instances of sequence similarity between putative siRNAs generated from the dsRNA-GFP construct and genes whose expression levels were altered. In general, the affected genes are involved in important developmental and metabolic processes associated with RNA processing and transport, hormone metabolism, immunity, response to external stimulus and to stress. These results suggest that multiple dsRNA controls should be employed in RNAi studies in honey bees. Furthermore, any RNAi studies involving these genes affected by dsRNA-GFP in our studies should use a different dsRNA control.

  9. [Interest of FDG-PET for lung cancer radiotherapy]. (United States)

    Thureau, S; Mezzani-Saillard, S; Modzelewski, R; Edet-Sanson, A; Dubray, B; Vera, P


    The recent advances in medical imaging have profoundly altered the radiotherapy of non-small cell lung cancers (NSCLC). A meta-analysis has confirmed the superiority of FDG PET-CT over CT for initial staging. FDG PET-CT improves the reproducibility of target volume delineation, especially close to the mediastinum or in the presence of atelectasia. Although not formally validated by a randomized trial, the reduction of the mediastinal target volume, by restricting the irradiation to FDG-avid nodes, is widely accepted. The optimal method of delineation still remains to be defined. The role of FDG PET-CT in monitoring tumor response during radiotherapy is under investigation, potentially opening the way to adapting the treatment modalities to tumor radiation sensitivity. Other tracers, such as F-miso (hypoxia), are also under clinical investigation. To avoid excessive delays, the integration of PET-CT in routine practice requires quick access to the imaging equipment, technical support (fusion and image processing) and multidisciplinary delineation of target volumes.

  10. Comparison of loop-mediated isothermal amplification (LAMP) and nested-PCR assay targeting the RE and B1 gene for detection of Toxoplasma gondii in blood samples of children with leukaemia. (United States)

    Fallahi, Shirzad; Seyyed Tabaei, Seyyed Javad; Pournia, Yadollah; Zebardast, Nozhat; Kazemi, Bahram


    Toxoplasmosis diagnosis constitutes an important measure for disease prevention and control. In this paper, a newly described DNA amplification technique, loop-mediated isothermal amplification (LAMP), and nested-PCR targeting the repeated element (RE) and B1 gene, were compared to each other for the detection of Toxoplasma gondii DNA in blood samples of children with leukaemia. One hundred ten blood samples from these patients were analyzed by LAMP and nested-PCR. Out of 50 seropositive samples (IgM+, IgG+), positive results were obtained with 92% and 86% on RE, B1-LAMP and 82% and 68% on RE, B1-nested PCR analyses, respectively. Of the 50 seronegative samples, three, two and one samples were detected positive by RE-LAMP, B1-LAMP and RE-nested PCR assays, respectively, while none were detected positive by B1-nested PCR. None of the 10 IgM-, IgG+ samples was detected positive after testing LAMP and nested-PCR assays in duplicate. This is the first report of a study in which the LAMP method was applied with high sensitivity and efficacy for the diagnosis of T. gonii in blood samples of children with leukaemia.

  11. Multi-atlas attenuation correction supports full quantification of static and dynamic brain PET data in PET-MR (United States)

    Mérida, Inés; Reilhac, Anthonin; Redouté, Jérôme; Heckemann, Rolf A.; Costes, Nicolas; Hammers, Alexander


    In simultaneous PET-MR, attenuation maps are not directly available. Essential for absolute radioactivity quantification, they need to be derived from MR or PET data to correct for gamma photon attenuation by the imaged object. We evaluate a multi-atlas attenuation correction method for brain imaging (MaxProb) on static [18F]FDG PET and, for the first time, on dynamic PET, using the serotoninergic tracer [18F]MPPF. A database of 40 MR/CT image pairs (atlases) was used. The MaxProb method synthesises subject-specific pseudo-CTs by registering each atlas to the target subject space. Atlas CT intensities are then fused via label propagation and majority voting. Here, we compared these pseudo-CTs with the real CTs in a leave-one-out design, contrasting the MaxProb approach with a simplified single-atlas method (SingleAtlas). We evaluated the impact of pseudo-CT accuracy on reconstructed PET images, compared to PET data reconstructed with real CT, at the regional and voxel levels for the following: radioactivity images; time-activity curves; and kinetic parameters (non-displaceable binding potential, BPND). On static [18F]FDG, the mean bias for MaxProb ranged between 0 and 1% for 73 out of 84 regions assessed, and exceptionally peaked at 2.5% for only one region. Statistical parametric map analysis of MaxProb-corrected PET data showed significant differences in less than 0.02% of the brain volume, whereas SingleAtlas-corrected data showed significant differences in 20% of the brain volume. On dynamic [18F]MPPF, most regional errors on BPND ranged from -1 to  +3% (maximum bias 5%) for the MaxProb method. With SingleAtlas, errors were larger and had higher variability in most regions. PET quantification bias increased over the duration of the dynamic scan for SingleAtlas, but not for MaxProb. We show that this effect is due to the interaction of the spatial tracer-distribution heterogeneity variation over time with the degree of accuracy of the attenuation maps. This

  12. Loop-mediated isothermal amplification assay targeting the blaCTX-M9 gene for detection of extended spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. (United States)

    Thirapanmethee, Krit; Pothisamutyothin, Kanokporn; Nathisuwan, Surakit; Chomnawang, Mullika T; Wiwat, Chanpen


    Extended-spectrum β-lactamases (ESBLs) produced by Enterobacteriaceae are one of the resistance mechanisms to most β-lactam antibiotics. ESBLs are currently a major problem in both hospitals and community settings worldwide. Rapid and reliable means of detecting ESBL-producing bacteria is necessary for identification, prevention and treatment. Loop-mediated isothermal amplification (LAMP) is a technique that rapidly amplifies DNA with high specificity and sensitivity under isothermal conditions. This study was aimed to develop a convenient, accurate and inexpensive method for detecting ESBL-producing bacteria by a LAMP technique. ESBLs-producing Escherichia coli and Klebsiella pneumoniae were isolated from a tertiary hospital in Bangkok, Thailand and reconfirmed by double-disk synergy test. A set of four specific oligonucleotide primers of LAMP for detection of bla(CTX-M9) gene was designed based on bla(CTX-M9) from E. coli (GenBank Accession No. AJ416345). The LAMP reaction was amplified under isothermal temperature at 63°C for 60 min. Ladder-like patterns of band sizes from 226 bp of the bla(CTX-M9) DNA target was observed. The LAMP product was further analyzed by restriction digestion with MboI and TaqI endonucleases. The fragments generated were approximately 168, 177 and 250 bp in size for MboI digestion and 165, 193, 229, 281 and 314 bp for TaqI digestion, which is in agreement with the predicted sizes. The sensitivity of the LAMP technique to bla(CTX-M9) was greater than that of the PCR method by at least 10,000-fold. These results showed that the LAMP primers specifically amplified only the bla(CTX-M9) gene. Moreover, the presence of LAMP amplicon was simply determined by adding SYBR Green I in the reaction. In conclusion, this technique for detection of ESBLs is convenient, reliable and easy to perform routinely in hospitals or laboratory units in developing countries.

  13. Transporter assays and assay ontologies: useful tools for drug discovery. (United States)

    Zdrazil, Barbara; Chichester, Christine; Zander Balderud, Linda; Engkvist, Ola; Gaulton, Anna; Overington, John P


    Transport proteins represent an eminent class of drug targets and ADMET (absorption, distribution, metabolism, excretion, toxicity) associated genes. There exists a large number of distinct activity assays for transport proteins, depending on not only the measurement needed (e.g. transport activity, strength of ligand–protein interaction), but also due to heterogeneous assay setups used by different research groups. Efforts to systematically organize this (divergent) bioassay data have large potential impact in Public-Private partnership and conventional commercial drug discovery. In this short review, we highlight some of the frequently used high-throughput assays for transport proteins, and we discuss emerging assay ontologies and their application to this field. Focusing on human P-glycoprotein (Multidrug resistance protein 1; gene name: ABCB1, MDR1), we exemplify how annotation of bioassay data per target class could improve and add to existing ontologies, and we propose to include an additional layer of metadata supporting data fusion across different bioassays.

  14. PET/TAC in Oncology; PET/TAC en Oncologia

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez V, A.M. [Especialista en Medicina Nuclear, Profa. Depto. Radiologia de la Facultad de Medicina, Universidad Complutense de Madrid, Madrid (Spain)


    From this presentation of PET-TAC in oncology the following advantages on the conventional PET are obtained: 1. More short study and stadium in one session. 2. It adds the information of both techniques. 3. Better localization of leisure: affected organ, stadium change (neck, mediastinum, abdomen). 4. Reduction of false positive (muscle, brown fat, atelectasis, pneumonias, intestine, urinary vials, etc.). 5. Reduction of negative false. 6. Reduction of not conclusive. 7. More understandable for other specialists. 8. Biopsies guide. 9. Planning radiotherapy.

  15. Image interpretation criteria for FDG PET/CT in multiple myeloma: a new proposal from an Italian expert panel. IMPeTUs (Italian Myeloma criteria for PET USe)

    Energy Technology Data Exchange (ETDEWEB)

    Nanni, Cristina; Rambaldi, Ilaria; Fanti, Stefano [AOU Policlinico S. Orsola-Malpighi, Nuclear Medicine, Bologna (Italy); Zamagni, Elena; Cavo, Michele [AOU Policlinico S. Orsola-Malpighi, Hematology, Bologna (Italy); Versari, Annibale [IRCSS, Nuclear Medicine, S. Maria Nuova Hospital, Reggio Emilia (Italy); Chauvie, Stephane [Santa Croce e Carle Hospital, Medical Physics Unit, Cuneo (Italy); Bianchi, Andrea [Santa Croce e Carle Hospital, Nuclear Medicine, Cuneo (Italy); Rensi, Marco [AOU S.Maria della Misericordia, Nuclear Medicine, Udine (Italy); Bello, Marilena [AO Citta della Salute e della Scienza, Nuclear Medicine, Torino (Italy); Gallamini, Andrea [A Lacassagne Cancer Center, Research and Innovation Department, Nice (France); Patriarca, Francesca [Udine University, Hematologic Clinic, Udine (Italy); Gay, Francesca [University of Torino, Myeloma Unit, Division of Hematology, Torino (Italy); Gamberi, Barbara [IRCCS, Hematology Unit, Azienda Ospedaliera ASMN, Reggio Emilia (Italy)


    FDG PET/CT is able to detect active disease in patients with multiple myeloma (MM) and can be helpful for staging and assessing therapy response, but no standard interpretation criteria have been proposed for the evaluation of FDG PET/CT in MM. A group of Italian nuclear medicine physicians and haematologists met to propose new visual interpretation criteria to standardize FDG PET/CT evaluation in MM patients (Italian Myeloma criteria for PET USe; IMPeTUs) and the reproducibility of these criteria was tested. This Italian multicentre protocol was set up as a subprotocol of EMN02, an international prospective multicentre trial of the European Myeloma Network. The criteria were agreed at multidisciplinary consensus meetings. They include a description of the metabolic state of the bone marrow (BM), number and site of focal PET-positive lesions, the number of osteolytic lesions, and the presence and site of extramedullary disease, paramedullary disease and fractures. A visual degree of uptake was defined for the target lesion and extramedullary lesions according to modified Deauville criteria. MM patients who had undergone FDG PET/CT at baseline (PET-0), after induction (PET-AI) and at the end of treatment (PET-EoT) were enrolled. The patients had been prospectively enrolled in EMN02 and their PET scans were a posteriori reinterpreted in a blinded independent central review process managed by WIDEN registered. Five expert nuclear medicine physicians scored the scans according to the new criteria. A case was considered read when four out of the five reviewers completed the report. Concordance among reviewers on different metrics was calculated using Krippendorff's alpha coefficient. A total of 17 consecutive patients were enrolled. On PET-0, the alpha coefficients for the BM score, the score for the hottest focal lesion, the number of focal lesions and the number of lytic lesions were 0.33 and 0.47, 0.40 and 0.32, respectively. On PET-AI, the alpha coefficients

  16. Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5-HT7 Receptor

    DEFF Research Database (Denmark)

    Herth, Matthias M; Andersen, Valdemar L; Hansen, Hanne D;


    We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent (11)C-labeling and in vivo...

  17. Preliminary results of a prototype C-shaped PET designed for an in-beam PET system (United States)

    Kim, Hyun-Il; Chung, Yong Hyun; Lee, Kisung; Kim, Kyeong Min; Kim, Yongkwon; Joung, Jinhun


    Positron emission tomography (PET) can be utilized in particle beam therapy to verify the dose distribution of the target volume as well as the accuracy of the treatment. We present an in-beam PET scanner that can be integrated into a particle beam therapy system. The proposed PET scanner consisted of 14 detector modules arranged in a C-shape to avoid blockage of the particle beam line by the detector modules. Each detector module was composed of a 9×9 array of 4.0 mm×4.0 mm×20.0 mm LYSO crystals optically coupled to four 29-mm-diameter PMTs using the photomultiplier-quadrant-sharing (PQS) technique. In this study, a Geant4 Application for Tomographic Emission (GATE) simulation study was conducted to design a C-shaped PET scanner and then experimental evaluation of the proposed design was performed. The spatial resolution and sensitivity were measured according to NEMA NU2-2007 standards and were 6.1 mm and 5.61 cps/kBq, respectively, which is in good agreement with our simulation, with an error rate of 12.0%. Taken together, our results demonstrate the feasibility of the proposed C-shaped in-beam PET system, which we expect will be useful for measuring dose distribution in particle therapy.

  18. Preliminary results of a prototype C-shaped PET designed for an in-beam PET system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun-Il [Department of Radiation Convergence Engineering, Yonsei University, Wonju 220-710 (Korea, Republic of); Chung, Yong Hyun, E-mail: [Department of Radiation Convergence Engineering, Yonsei University, Wonju 220-710 (Korea, Republic of); Lee, Kisung [Department of Bio-convergence Engineering, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Science, Seoul 139-706 (Korea, Republic of); Kim, Yongkwon; Joung, Jinhun [Nucare Medical System, Inc., Incheon 406-840 (Korea, Republic of)


    Positron emission tomography (PET) can be utilized in particle beam therapy to verify the dose distribution of the target volume as well as the accuracy of the treatment. We present an in-beam PET scanner that can be integrated into a particle beam therapy system. The proposed PET scanner consisted of 14 detector modules arranged in a C-shape to avoid blockage of the particle beam line by the detector modules. Each detector module was composed of a 9×9 array of 4.0 mm×4.0 mm×20.0 mm LYSO crystals optically coupled to four 29-mm-diameter PMTs using the photomultiplier-quadrant-sharing (PQS) technique. In this study, a Geant4 Application for Tomographic Emission (GATE) simulation study was conducted to design a C-shaped PET scanner and then experimental evaluation of the proposed design was performed. The spatial resolution and sensitivity were measured according to NEMA NU2-2007 standards and were 6.1 mm and 5.61 cps/kBq, respectively, which is in good agreement with our simulation, with an error rate of 12.0%. Taken together, our results demonstrate the feasibility of the proposed C-shaped in-beam PET system, which we expect will be useful for measuring dose distribution in particle therapy.

  19. WE-G-BRF-06: Positron Emission Tomography (PET)-Guided Dynamic Lung Tumor Tracking for Cancer Radiotherapy: First Patient Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Yang, J; Loo, B; Graves, E [Stanford University, Stanford, CA (United States); Yamamoto, T [UC Davis School of Medicine, Sacramento, CA (United States); Keall, P [University of Sydney, Camperdown (Australia)


    Purpose: PET-guided dynamic tumor tracking is a novel concept of biologically targeted image guidance for radiotherapy. A dynamic tumor tracking algorithm based on list-mode PET data has been developed and previously tested on dynamic phantom data. In this study, we investigate if dynamic tumor tracking is clinically feasible by applying the method to lung cancer patient PET data. Methods: PET-guided tumor tracking estimates the target position of a segmented volume in PET images reconstructed continuously from accumulated coincidence events correlated with external respiratory motion, simulating real-time applications, i.e., only data up to the current time point is used to estimate the target position. A target volume is segmented with a 50% threshold, consistently, of the maximum intensity in the predetermined volume of interest. Through this algorithm, the PET-estimated trajectories are quantified from four lung cancer patients who have distinct tumor location and size. The accuracy of the PET-estimated trajectories is evaluated by comparing to external respiratory motion because the ground-truth of tumor motion is not known in patients; however, previous phantom studies demonstrated sub-2mm accuracy using clinically derived 3D tumor motion. Results: The overall similarity of motion patterns between the PET-estimated trajectories and the external respiratory traces implies that the PET-guided tracking algorithm can provide an acceptable level of targeting accuracy. However, there are variations in the tracking accuracy between tumors due to the quality of the segmentation which depends on target-to-background ratio, tumor location and size. Conclusion: For the first time, a dynamic tumor tracking algorithm has been applied to lung cancer patient PET data, demonstrating clinical feasibility of real-time tumor tracking for integrated PET-linacs. The target-to-background ratio is a significant factor determining accuracy: screening during treatment planning would

  20. 10 "Poison Pills" for Pets (United States)

    ... Care Animal Welfare Veterinary Careers Public Health 10 "Poison Pills" for Pets Anyone who takes medication prescribed ... of all phone calls to the ASPCA Animal Poison Control Center (APCC) are about human medications. Your ...

  1. Take Care with Pet Reptiles (United States)

    ... Past Emails CDC Features Take Care with Pet Reptiles and Amphibians Language: English Español (Spanish) Recommend on ... messages, and helpful resources. Safe Handling Tips for Reptiles and Amphibians Always wash your hands thoroughly after ...

  2. PET and PET/CT in tumour of undetermined origin; PET y PET/CT en tumor de origen indeterminado

    Energy Technology Data Exchange (ETDEWEB)

    Garcia O, J.R. [Nuclear Medicine and Molecular Imaging, PET/CT, Centro Medico ABC, Mexico D.F. (Mexico)


    In this presentation the following conclusions were obtained regarding the use of PET and PET/CT in patient with cancer of unknown primary: 1. Detection of the primary one in 1/3 at 1/2 of patient. 2. It detects metastases in other places in 50%. 3. It changes the initial therapy planned in 1/3 at 1/2 of patient. 4. Useful in initial phases of protocol study to limit the other procedures. After standard evaluation. Before advanced protocol. 5. PET/CT study increases the % of primary detection, although in a non significant way vs. PET. 6. They are required more studies to value their utility to a more objective manner. (Author)

  3. Pathology-based validation of FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schinagl, Dominic A.X. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Radboud University Nijmegen Medical Centre, Department of Radiation Oncology (874), P.O. Box 9101, Nijmegen (Netherlands); Span, Paul N.; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Hoogen, Frank J.A. van den [Radboud University Nijmegen Medical Centre, Department of Otorhinolaryngology, Head and Neck Surgery, Nijmegen (Netherlands); Merkx, Matthias A.W. [Radboud University Nijmegen Medical Centre, Department of Oral and Maxillofacial Surgery, Nijmegen (Netherlands); Slootweg, Piet J. [Radboud University Nijmegen Medical Centre, Department of Pathology, Nijmegen (Netherlands); Oyen, Wim J.G. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands)


    FDG PET is increasingly incorporated into radiation treatment planning of head and neck cancer. However, there are only limited data on the accuracy of radiotherapy target volume delineation by FDG PET. The purpose of this study was to validate FDG PET segmentation tools for volume assessment of lymph node metastases from head and neck cancer against the pathological method as the standard. Twelve patients with head and neck cancer and 28 metastatic lymph nodes eligible for therapeutic neck dissection underwent preoperative FDG PET/CT. The metastatic lymph nodes were delineated on CT (Node{sub CT}) and ten PET segmentation tools were used to assess FDG PET-based nodal volumes: interpreting FDG PET visually (PET{sub VIS}), applying an isocontour at a standardized uptake value (SUV) of 2.5 (PET{sub SUV}), two segmentation tools with a fixed threshold of 40 % and 50 %, and two adaptive threshold based methods. The latter four tools were applied with the primary tumour as reference and also with the lymph node itself as reference. Nodal volumes were compared with the true volume as determined by pathological examination. Both Node{sub CT} and PET{sub VIS} showed good correlations with the pathological volume. PET segmentation tools using the metastatic node as reference all performed well but not better than PET{sub VIS}. The tools using the primary tumour as reference correlated poorly with pathology. PET{sub SUV} was unsatisfactory in 35 % of the patients due to merging of the contours of adjacent nodes. FDG PET accurately estimates metastatic lymph node volume, but beyond the detection of lymph node metastases (staging), it has no added value over CT alone for the delineation of routine radiotherapy target volumes. If FDG PET is used in radiotherapy planning, treatment adaptation or response assessment, we recommend an automated segmentation method for purposes of reproducibility and interinstitutional comparison. (orig.)

  4. PET-CT工作原理及应用%Principle and application of PET-CT

    Institute of Scientific and Technical Information of China (English)

    张秀文; 张永寿; 刘乃智


    Objective: PET-CT is to use to achieve image fusion of PET and CT in the same machine, is functional imaging equipment. With the rapid spread of its application, it goes beyond the existing areas of PET alone and separate CT for medical research and clinical diagnostics, it provides a great convenience. Methods: PET is deferent with CT in the imaging principle, the combination of these two equipment can get the image of anatomical structure, abundant physiological and biochemical functions. It can provide the quantitative, qualitative diagnostic basis for the identify and locate the precise location of tumors. Results: PET-CT fusion images can be used to describe the role of disease on the biochemical processes, identify physiological and pathological uptake. It can detect the early onset of signs of disease anatomical evidence and even very small subclinical tumor correctly. It has an important value in determining the clinical radiotherapy planning target volume, the detection process of treatment drugs and radiation effects to provide the best treatment options to improve the clinical cure rate. Conclusion: The work is in good condition or not determines by the maintenance. Firstly we should clear the equipment requirements of the environment in the process of routine maintenance carefully. Maintain equipment environment requires qualified engineering and technical personnel familiar with every aspect of the usually diligent maintenance, did not miss any possible hazards to more good to ensure that the operation of the equipment.%目的:PET-CT实现了同机图像融合,是一种功能性医学影像学设备,通过了解其工作原理,掌握设备的日常维护方法,为医学研究和临床诊断提供便利.方法:分别介绍PET与CT两种设备同机组合的不同成像原理以及设备应用时对环境的要求.结果:了解PET-CT的工作原理,掌握一般维护保养项目和方法,使PET-CT融合影像为临床正确确定放疗的计划靶区、

  5. Nutritional sustainability of pet foods. (United States)

    Swanson, Kelly S; Carter, Rebecca A; Yount, Tracy P; Aretz, Jan; Buff, Preston R


    Sustainable practices meet the needs of the present without compromising the ability of future generations to meet their needs. Applying these concepts to food and feed production, nutritional sustainability is the ability of a food system to provide sufficient energy and essential nutrients required to maintain good health in a population without compromising the ability of future generations to meet their nutritional needs. Ecological, social, and economic aspects must be balanced to support the sustainability of the overall food system. The nutritional sustainability of a food system can be influenced by several factors, including the ingredient selection, nutrient composition, digestibility, and consumption rates of a diet. Carbon and water footprints vary greatly among plant- and animal-based ingredients, production strategy, and geographical location. Because the pet food industry is based largely on by-products and is tightly interlinked with livestock production and the human food system, however, it is quite unique with regard to sustainability. Often based on consumer demand rather than nutritional requirements, many commercial pet foods are formulated to provide nutrients in excess of current minimum recommendations, use ingredients that compete directly with the human food system, or are overconsumed by pets, resulting in food wastage and obesity. Pet food professionals have the opportunity to address these challenges and influence the sustainability of pet ownership through product design, manufacturing processes, public education, and policy change. A coordinated effort across the industry that includes ingredient buyers, formulators, and nutritionists may result in a more sustainable pet food system.

  6. Are Pets in the Bedroom a Problem? (United States)

    Krahn, Lois E; Tovar, M Diane; Miller, Bernie


    The presence of pets in the bedroom can alter the sleep environment in ways that could affect sleep. Data were collected by questionnaire and interview from 150 consecutive patients seen at the Center for Sleep Medicine, Mayo Clinic in Arizona. Seventy-four people (49%) reported having pets, with 31 (41% of pet owners) having multiple pets. More than half of pet owners (56%) allowed their pets to sleep in the bedroom. Fifteen pet owners (20%) described their pets as disruptive, whereas 31 (41%) perceived their pets as unobtrusive or even beneficial to sleep. Health care professionals working with patients with sleep concerns should inquire about the presence of companion animals in the sleep environment to help them find solutions and optimize their sleep.

  7. Advances in Clinical PET/MRI Instrumentation. (United States)

    Herzog, Hans; Lerche, Christoph


    In 2010, the first whole-body PET/MRI scanners installed for clinical use were the sequential Philips PET/MRI with PMT-based, TOF-capable technology and the integrated simultaneous Siemens PET/MRI. Avalanche photodiodes as non-magneto-sensitive readout electronics allowed PET integrated within the MRI. The experiences with these scanners showed that improvements of software aspects, such as attenuation correction, were necessary and that efficient protocols combining optimally PET and MRI must be still developed. In 2014, General Electric issued an integrated PET/MRI with SiPM-based PET detectors, allowing TOF-PET. Looking at the MRI components of current PET/MR imaging systems, primary improvements come from sequences and new coils.

  8. Do carotid MR surface coils affect PET quantification in PET/MR imaging?

    Energy Technology Data Exchange (ETDEWEB)

    Willemink, Martin J; Eldib, Mootaz [Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (United States); Leiner, Tim [Department of Radiology, University Medical Center Utrecht, Utrecht (Netherlands); Fayad, Zahi A; Mani, Venkatesh [Translational and Molecular Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY (United States)


    To evaluate the effect of surface coils for carotid MR imaging on PET quantification in a clinical simultaneous whole-body PET/MR scanner. A cylindrical phantom was filled with a homogeneous 2L water-FDG mixture at a starting dose of 301.2MBq. Clinical PET/MR and PET/CT systems were used to acquire PET-data without a coil (reference standard) and with two carotid MRI coils (Siemens Special Purpose 8-Channel and Machnet 4-Channel Phased Array). PET-signal attenuation was evaluated with Osirix using 51 (PET/MR) and 37 (PET/CT) circular ROIs. Mean and maximum standardized uptake values (SUVs) were quantified for each ROI. Furthermore, SUVs of PET/MR and PET/CT were compared. For validation, a patient was scanned with an injected dose of 407.7MBq on both a PET/CT and a PET/MR system without a coil and with both coils. PET/MR underestimations were -2.2% (Siemens) and -7.8% (Machnet) for SUVmean, and -1.2% (Siemens) and -3.3% (Machnet) for SUVmax, respectively. For PET/CT, underestimations were -1.3% (Siemens) and -1.4% (Machnet) for SUVmean and -0.5% (both Siemens and Machnet) for SUVmax, respectively using no coil data as reference. Except for PET/CT SUVmax values all differences were significant. SUVs differed significantly between PET/MR and PET/CT with SUVmean values of 0.51-0.55 for PET/MR and 0.68-0.69 for PET/CT, respectively. The patient examination showed that median SUVmean values measured in the carotid arteries decreased from 0.97 without a coil to 0.96 (Siemens) and 0.88 (Machnet). Carotid surface coils do affect attenuation correction in both PET/MR and PET/CT imaging. Furthermore, SUVs differed significantly between PET/MR and PET/CT.

  9. FDG-PET/CT response evaluation during EGFR-TKI treatment in patients with NSCLC

    Institute of Scientific and Technical Information of China (English)

    Matthijs; H; van; Gool; Tjeerd; S; Aukema; Koen; J; Hartemink; Renato; A; Valdés; Olmos; Houke; M; Klomp; Harm; van; Tinteren


    Over recent years,[18F]-fluorodeoxyglucose positron emission tomography acquired together with low dose computed tomography(FDG-PET/CT)has proven its role as a staging modality in patients with non-small cell lung cancer(NSCLC).The purpose of this review was to present the evidence to use FDG-PET/CT for response evaluation in patients with NSCLC,treated with epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKI).All published articles from 1November 2003 to 1 November 2013 reporting on 18FFDG-PET response evaluation during EGFR-TKI treatment in patients with NSCLC were collected.In total 7studies,including data of 210 patients were eligible for analyses.Our report shows that FDG-PET/CT responseduring EGFR-TKI therapy has potential in targeted treatment for NSCLC.FDG-PET/CT response is associated with clinical and radiologic response and with survival.Furthermore FDG-PET/CT response monitoring can be performed as early as 1-2 wk after initiation of EGFR-TKI treatment.Patients with substantial decrease of metabolic activity during EGFR-TKI treatment will probably benefit from continued treatment.If metabolic response does not occur within the first weeks of EGFR-TKI treatment,patients may be spared(further)unnecessary toxicity of ineffective treatment.Refining FDG-PET response criteria may help the clinician to decide on continuation or discontinuation of targeted treatment.

  10. PET/CT fusion in radiotherapy treatment planning of head and neck cancer%PET/CT对头颈部肿瘤放射治疗计划的作用

    Institute of Scientific and Technical Information of China (English)

    向作林; 曾昭冲; 吴铮; 管一晖; 刘建军; 陈刚


    目的 探讨PET/CT对头颈部肿瘤放射治疗计划的作用.方法 16例头颈部肿瘤患者行PET/CT和定位CT检查,根据检查结果对16例患者进行TNM分期,比较其分期结果.将定位CT图像传入三维治疗计划系统(TPS),在定位CT图像上勾画大体肿瘤体积(GTV),即CT-GTV;参考PET/CT融合图像在定位CT图像上勾画PET/CT-GTV,比较PET/CT-GTV和CT-GTV.采用Stata 7.0软件分析数据,t检验用于比较PET/CT-GTV和CT-GTV.结果 PET/CT使7例患者TNM分期发生改变.PET/CT-GTV和CT-GTV中位值分别为84.3(46~364)cm3和116.2(58~472)cm3,差异有统计学意义(t=-4.3186, P=0.0005).结论 PET/CT能提高头颈部肿瘤分期和肿瘤靶区定位的准确性.%Objective The aim of this study was to investigate the value of PET/CT in radiation treatment planning of head and neck cancer. Methods Sixteen patients with head and neck cancer underwent PET/CT and enhanced CT imaging. TNM stage was analyzed based on PET/CT and CT. Gross tumor volume (GTV) of PET/CT (PET/CT-GTV) and CT (CT-GTV) were analyzed. Stata 7.0 was used for data analysis, PET/CT-GTV and CT-GTV were compared with t test. Results Based on PET/CT, changes in TNM stage occurred in 7 patients. The median PET/CT-GTV and CT-GTV were 84.3(46~364)cm3 and 116.2(58~472)cm3, respectively, which had a statistically significant difference (t=-4.3186, P=0.0005). Conclusion PET/CT can increase the accuracy of staging and defining the field and target volumes for radiation therapy of head and neck cancer.

  11. Parasites, pets, and people. (United States)

    Marx, M B


    It is important for the family physician to understand that patients' relationships with their pets play an important role in helping maintain mental and physical health yet provide the potential for causing illness in the patient. Toxocara canis (dog roundworm) and Toxocara cati (cat roundworm) are the ascarids most commonly responsible for VLM and ocular larva migrans in humans. These roundworms live in their adult stage in the small intestine of the dog and cat where their eggs are passed in the feces. The eggs containing the infective larva are very sticky, thus an infant crawling around on the floor can easily pick these up on fingers that almost invariably end up in the mouth. Infections are usually mild and asymptomatic but with a persistent eosinophilia. Ocular larva migrans is the form usually occurring in older children and adults. Some public health veterinarians recommend that a puppy or kitten should not be obtained as a companion for a child who is not old enough to read, thus bypassing the crawling and toddler stages. Hookworm eggs, shed in the feces of infected dogs or cats, develop into the infective second stage within a week. Humans are usually infected when bare areas of skin such as bare feet or the torso come in contact with soil contaminated with the larvae. The second-stage larvae are able to penetrate the intact skin of humans and the foot pads of dogs and cats. In the United States, the common dog hookworm, A. caninum, is a widespread parasite. Human intestinal ancylostomiasis caused by this species is rare, with only six cases recorded in the literature. Infection in humans or animals by the common tapeworm of dogs and cats (Dipylidium caninum) requires ingestion of the intermediate host, the dog or cat flea containing the larva (cysticercoids) of the agent. Many cases in humans are asymptomatic. Dipylidiasis affects mainly infants and young children who may swallow a flea that hops up while the infant is crawling on the floor or fondling

  12. Longitudinal monitoring adipose-derived stem cell survival by PET imaging hexadecyl-4-{sup 124}I-iodobenzoate in rat myocardial infarction model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Hwan [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Woo, Sang-Keun; Lee, Kyo Chul; An, Gwang Il [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Pandya, Darpan [Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu (Korea, Republic of); Park, Noh Won; Nahm, Sang-Soep; Eom, Ki Dong [College of Veterinary Medicine, Konkuk University, Seoul (Korea, Republic of); Kim, Kwang Il; Lee, Tae Sup [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Chan Wha [School of Life Sciences and Biotechnology, Korea University, Seoul (Korea, Republic of); Kang, Joo Hyun [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Yoo, Jeongsoo, E-mail: [Department of Molecular Medicine, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu (Korea, Republic of); Lee, Yong Jin, E-mail: [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)


    Highlights: • We developed a safe, simple and appropriate stem cell labeling method with {sup 124}I-HIB. • ADSC survival can be monitored with PET in MI model via direct labeling. • Tracking of ADSC labeled with {sup 124}I-HIB was possible for 3 days in MI model using PET. • ADSC viability and differentiation were not affected by {sup 124}I-HIB labeling. • Survival of ADSC in living bodies can be longitudinally tracked with PET imaging. - Abstract: This study aims to monitor how the change of cell survival of transplanted adipose-derived stem cells (ADSCs) responds to myocardial infarction (MI) via the hexadecyl-4-{sup 124}I-iodobenzoate ({sup 124}I-HIB) mediated direct labeling method in vivo. Stem cells have shown the potential to improve cardiac function after MI. However, monitoring of the fate of transplanted stem cells at target sites is still unclear. Rat ADSCs were labeled with {sup 124}I-HIB, and radiolabeled ADSCs were transplanted into the myocardium of normal and MI model. In the group of {sup 124}I-HIB-labeled ADSC transplantation, in vivo imaging was performed using small-animal positron emission tomography (PET)/computed tomography (CT) for 9 days. Twenty-one days post-transplantation, histopathological analysis and apoptosis assay were performed. ADSC viability and differentiation were not affected by {sup 124}I-HIB labeling. In vivo tracking of the {sup 124}I-HIB-labeled ADSCs was possible for 9 and 3 days in normal and MI model, respectively. Apoptosis of transplanted cells increased in the MI model compared than that in normal model. We developed a direct labeling agent, {sup 124}I-HIB, and first tried to longitudinally monitor transplanted stem cell to MI. This approach may provide new insights on the roles of stem cell monitoring in living bodies for stem cell therapy from pre-clinical studies to clinical trials.

  13. Real-time qPCR is a powerful assay to estimate the 171 R/Q alleles at the PrP locus directly in a flock's raw milk: a comparison with the targeted next-generation sequencing. (United States)

    Feligini, Maria; Bongioni, Graziella; Brambati, Eva; Amadesi, Alessandra; Cambuli, Caterina; Panelli, Simona; Bonacina, Cesare; Galli, Andrea


    The hazard to human health represented by transmissible spongiform encephalopathies in sheep is one of the major reasons for implementing the genetic selection plan to break down prion diseases. The problem is particularly important because of the risk of disease transmission from ewe to lamb via milk or colostrum. In order to establish an active and convenient monitoring of the flocks already undergone genetic selection and thus, indirectly increase consumers' security, the challenge of the work was quantifying the classical scrapie risk in bulk milk. A new quantitative real-time PCR assay for the estimation of the 171 R and Q allelic frequencies in a DNA pool representative of all the lactating ewes present in a flock was optimized and validated "in field". The repeatability range was 3.69-5.27 for R and 4.20-5.75 for Q. The ruggedness of the allele frequencies resulted 4.26 for R and 4.77 for Q. Regarding the validation "in field", none of the considered sources of variability (flock, month, number of genotyped animals and somatic cell count) showed a significant effect on flock and milk at the linear model. The targeted next-generation sequencing was also tested to evaluate its applicability in this context. Results show that the real-time PCR assay could represent a valid tool for the determination of 171 R/Q allele frequencies in bulk milk. The implementation of a service for breeder self-control along the production chain would aim to increase the production of high-security dairy products, while monitoring over time of the effects of genetic selection in the flocks.

  14. Fluorine-18 labeled tracers for PET studies in the neurosciences

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yu-Shin; Fowler, J.S.


    This chapter focuses on fluorine-18, the positron emitter with the longest half-life, the lowest positron energy and probably, the most challenging chemistry. The incorporation of F-18 into organic compounds presents many challenges, including: the need to synthesize and purify the compound within a 2--3 hour time frame; the limited number of labeled precursor molecules; the need to work on a microscale; and the need to produce radiotracers which are chemically and radiochemically pure, sterile and pyrogen-free, and suitable for intravenous injection. The PET method and F-18 labeling of organic molecules are described followed by highlights of the applications of F-18 labeled compounds in the neurosciences and neuropharmacology. It is important to emphasize the essential and pivotal role that organic synthesis has played in the progression of the PET field over the past twenty years from one in which only a handful of institutions possessed the instrumentation and staff to carry out research to the present-day situation where there are more than 200 PET centers worldwide. During this period PET has become an important scientific tool in the neurosciences, cardiology and oncology. It is important to point out that PET is by no means a mature field. The fact that a hundreds of different F-18 labeled compounds have been developed but only a few possess the necessary selectivity and sensitivity in vivo to track a specific biochemical process illustrates this and underscores a major difficulty in radiotracer development, namely the selection of priority structures for synthesis and the complexities of the interactions between chemical compounds and living systems. New developments in rapid organic synthesis are needed in order to investigate new molecular targets and to improve the quantitative nature of PET experiments.

  15. Markerless 3D Head Tracking for Motion Correction in High Resolution PET Brain Imaging

    DEFF Research Database (Denmark)

    Olesen, Oline Vinter

    images. Incorrect motion correction can in the worst cases result in wrong diagnosis or treatment. The evolution of a markerless custom-made structured light 3D surface tracking system is presented. The system is targeted at state-of-the-art high resolution dedicated brain PET scanners with a resolution...... significantly. The results were similar to motion correction using an integrated commercial marker-based system. Furthermore, phantom studies were performed supporting the system’s abilities for PET motion correction....

  16. PET/MRI in the infarcted mouse heart with the Cambridge split magnet

    Energy Technology Data Exchange (ETDEWEB)

    Buonincontri, Guido, E-mail: [Wolfson Brain Imaging Centre, University of Cambridge, Box 65, Addenbrooke' s Hospital, Hills Road, Cambridge, CB2 0QQ (United Kingdom); Sawiak, Stephen J. [Wolfson Brain Imaging Centre, University of Cambridge, Box 65, Addenbrooke' s Hospital, Hills Road, Cambridge, CB2 0QQ (United Kingdom); Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge (United Kingdom); Methner, Carmen; Krieg, Thomas [Department of Medicine, University of Cambridge, Cambridge (United Kingdom); Hawkes, Robert C.; Adrian Carpenter, T. [Wolfson Brain Imaging Centre, University of Cambridge, Box 65, Addenbrooke' s Hospital, Hills Road, Cambridge, CB2 0QQ (United Kingdom)


    Chronic heart failure, as a result of acute myocardial infarction, is a leading cause of death worldwide. Combining diagnostic imaging modalities may aid the direct assessment of experimental treatments targeting heart failure in vivo. Here we present preliminary data using the Cambridge combined PET/MRI imaging system in a mouse model of acute myocardial infarction. The split-magnet design can deliver uncompromised MRI and PET performance, for better assessment of disease and treatment in a preclinical environment.

  17. Multiobjective waste management optimization strategy coupling life cycle assessment and genetic algorithms: application to PET bottles


    Komly, Claude-Emma; Azzaro-Pantel, Catherine; Hubert, Antoine; Pibouleau, Luc; Archambault, Valérie


    International audience; A mathematical model based on life-cycle assessment (LCA) results is developed to assess the environmental efficiency of the end-of-life management of polyethylene terephthalate (PET) bottles. For this purpose, multiobjective optimization and decision support tools are used to define optimal targets for efficient waste management. The global environmental impacts associated with the treatment of PET bottles from their cradle to their ultimate graves (incineration, land...

  18. MO-FG-303-08: PET-Detectable Bimetallic (Zn@Au) Nanoparticles for Radiotherapy and Molecular Imaging Applications

    Energy Technology Data Exchange (ETDEWEB)

    Cho, J; Cho, S [UT MD Anderson Cancer Center, Houston, TX (United States); Wang, M; Zubarev, E [Rice University, Houston, TX - Texas (United States); Gonzalez-Lepera, C [University of Texas MD Anderson Cancer Center, Houston, TX - Texas (United States)


    Purpose: A technical challenge in clinical translation of GNP-mediated radiotherapy is lack of in-vivo imaging tools for monitoring biodistribution of GNPs. While several modalities (x-ray fluorescence, photoacoustic, etc.) are investigated, we propose a potentially more effective technique based on PET imaging. We developed Zn@Au NPs whose Zn core acts as positron emitters when activated by protons, while the Au shell plays the original role for GNP-mediated radiosensitization. Methods: Spherical Zn NPs (∼7nm diameter) were synthesized and then coated with ∼7nm thick Au layer to make Zn@Au NPs (∼20nm diameter). A water slurry containing 29mg of Zn@Au NPs was deposited (<10µm thickness) on a thin cellulose target and subsequently baked to remove the water. The cellulose matrix was placed in an aluminum target holder and irradiated with 14.5MeV protons from a GE PETtrace cyclotron with 4µA for 5min. After irradiation the cellulose matrix with the NPs was placed in a dose calibrator to assay radioactivity. Gamma spectroscopy using a HPGe detector was conducted on a very small fraction (<1mg) of the irradiated NPs. Results: We measured 158µCi of activity 32min after end of bombardment (EOB) using 66Ga setting on the dose calibrator (contribution from the cellulose matrix is negligible) which decreased to 2µCi over a 24hrs period. A gamma spectrum started one hour after EOB on the small fraction and acquired for 700sec showed a strong peak at 511keV (∼40,000 counts) with several other peaks (highest peak <1200 counts) of smaller magnitude. Conclusion: Strong 511keV gamma emission from proton-activated Zn cores can potentially be utilized to image the biodistribution of Zn@Au NPs using a PET scanner. The developed Zn@Au NPs are expected to retain radiosensitizing capability similar to solid GNPs, while observable through PET imaging for human-sized objects. Moreover, bioconjugated PET-detectable GNPs would allow a new option to perform molecular imaging.

  19. Quantitative PET imaging with the 3T MR-BrainPET

    Energy Technology Data Exchange (ETDEWEB)

    Weirich, C., E-mail: [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany); Scheins, J.; Lohmann, P.; Tellmann, L. [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany); Byars, L.; Michel, C. [Siemens Healthcare, Molecular Imaging, Knoxville, TN (United States); Rota Kops, E.; Brenner, D.; Herzog, H.; Shah, N.J. [Forschungszentrum Jülich, Institute of Neuroscience and Medicine – 4, Juelich (Germany)


    The new hybrid imaging technology of MR-PET allows for simultaneous acquisition of versatile MRI contrasts and the quantitative metabolic imaging with PET. In order to achieve the quantification of PET images with minimal residual error the application of several corrections is crucial. In this work we present our results on quantification with the 3T MR BrainPET scanner.

  20. Exercises in PET Image Reconstruction (United States)

    Nix, Oliver

    These exercises are complementary to the theoretical lectures about positron emission tomography (PET) image reconstruction. They aim at providing some hands on experience in PET image reconstruction and focus on demonstrating the different data preprocessing steps and reconstruction algorithms needed to obtain high quality PET images. Normalisation, geometric-, attenuation- and scatter correction are introduced. To explain the necessity of those some basics about PET scanner hardware, data acquisition and organisation are reviewed. During the course the students use a software application based on the STIR (software for tomographic image reconstruction) library 1,2 which allows them to dynamically select or deselect corrections and reconstruction methods as well as to modify their most important parameters. Following the guided tutorial, the students get an impression on the effect the individual data precorrections have on image quality and what happens if they are forgotten. Several data sets in sinogram format are provided, such as line source data, Jaszczak phantom data sets with high and low statistics and NEMA whole body phantom data. The two most frequently used reconstruction algorithms in PET image reconstruction, filtered back projection (FBP) and the iterative OSEM (ordered subset expectation maximation) approach are used to reconstruct images. The exercise should help the students gaining an understanding what the reasons for inferior image quality and artefacts are and how to improve quality by a clever choice of reconstruction parameters.

  1. Pet Meds Sending Kids to the ER (United States)

    ... Health and Human Services. More Health News on: Child Safety Pet Health Poisoning Recent Health News Related MedlinePlus Health Topics Child Safety Pet Health Poisoning About MedlinePlus Site Map FAQs Customer ...

  2. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian;


    Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases...... described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...

  3. PET for Staging of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)



    FDG-PET is of clinical value especially for detection of distant metastases or recurrent esophageal cancer. For the staging of primary tumor or locoregional lymph node metastasis PET is currently not suitable.

  4. Can FDG PET predict radiation treatment outcome in head and neck cancer? Results of a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Schinagl, Dominic A.X.; Span, Paul N.; Kaanders, Johannes H.A.M. [Radboud University Nijmegen Medical Centre, Department of Radiation Oncology, Nijmegen (Netherlands); Oyen, Wim J. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands)


    In head and neck cancer (HNC) various treatment strategies have been developed to improve outcome, but selecting patients for these intensified treatments remains difficult. Therefore, identification of novel pretreatment assays to predict outcome is of interest. In HNC there are indications that pretreatment tumour {sup 18}F-fluorodeoxyglucose (FDG) uptake may be an independent prognostic factor. The aim of this study was to assess the prognostic value of FDG uptake and CT-based and FDG PET-based primary tumour volume measurements in patients with HNC treated with (chemo)radiotherapy. A total of 77 patients with stage II-IV HNC who were eligible for definitive (chemo)radiotherapy underwent coregistered pretreatment CT and FDG PET. The gross tumour volume of the primary tumour was determined on the CT (GTV{sub CT}) and FDG PET scans. Five PET segmentation methods were applied: interpreting FDG PET visually (PET{sub VIS}), applying an isocontour at a standardized uptake value (SUV) of 2.5 (PET{sub 2.5}), using fixed thresholds of 40% and 50% (PET{sub 40%}, PET{sub 50%}) of the maximum intratumoral FDG activity (SUV{sub MAX}) and applying an adaptive threshold based on the signal-to-background (PET{sub SBR}). Mean FDG uptake for each PET-based volume was recorded (SUV{sub mean}). Subsequently, to determine the metabolic volume, the integrated SUV was calculated as the product of PET-based volume and SUV{sub mean}. All these variables were analysed as potential predictors of local control (LC), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS). In oral cavity/oropharynx tumours PET{sub VIS} was the only volume-based method able to predict LC. Both PET{sub VIS} and GTV{sub CT} were able to predict DMFS, DFS and OS in these subsites. Integrated SUVs were associated with LC, DMFS, DFS and OS, while SUV{sub mean} and SUV{sub MAX} were not. In hypopharyngeal/laryngeal tumours none of the

  5. Cost-effectiveness of PET and PET/Computed Tomography

    DEFF Research Database (Denmark)

    Gerke, Oke; Hermansson, Ronnie; Hess, Søren


    measure by means of incremental cost-effectiveness ratios when considering the replacement of the standard regimen by a new diagnostic procedure. This article discusses economic assessments of PET and PET/computed tomography reported until mid-July 2014. Forty-seven studies on cancer and noncancer......The development of clinical diagnostic procedures comprises early-phase and late-phase studies to elucidate diagnostic accuracy and patient outcome. Economic assessments of new diagnostic procedures compared with established work-ups indicate additional cost for 1 additional unit of effectiveness...

  6. 18 F-FDG PET/CT 确定局部晚期非小细胞肺癌加量放疗靶区的可行性%A feasibility study for boost target delineation using 18 F-FDG PET/CT in local advanced non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    高昂; 王世江; 付正; 孙新东; 于金明; 孟雪


    Objective To evaluate whether during-radiotherapy or post-radiotherapy 18 F-FDG uptake locations within tumour can be identified by a pre-radiotherapy scan for non-small cell lung cancer,and to explore the optimal biological sub-volume of the primary tumor for dose escalation.Methods 18 F-FDG PET/CT scans were performed at pre-radio-therapy,during-radiotherapy (40 Gy)or post-radiotherapy.The region of interests were auto-delineated using the 40%-70% maximal standardized uptake value (SUVmax )thresholds using pre-radiotherapy scan.Overlap fractions between pre-radiotherapy scan and during-radiotherapy or post-radiotherapy scan were calculated.Then,a Spearman correlation was used to analyze the correlations between the volumes of the region of interests and sensitivities of radiotherapy. Results The 50% SUVmax-delineated region of interests had large overlap fractions with the 40% SUVmax-delineated and manual-delineated regions of high uptake at during-radiotherapy,with the values being (74.3 ±15.9)% and (84.4 ±15.3)%,respectively.The overlap fractions of 50% SUVmax-delineated region of interests and the 80% SUVmax-delineated regions of high uptake at post-radiotherapy were more than 72%.The volume of 50% SUVmax-delineated region of interests was smaller than the gross tumor volume (GTV),with the value of being (29.4 ±12.3)%.However, the 50% SUVmax-delineated region of interests had no correlations with the sensitivities of radiotherapy.Conclusion A 18 F-FDG PET/CT scan at pre-radiotherapy can identify the high 18 F-FDG uptake regions at during-radiotherapy and post-radiotherapy.The 50% SUVmax-delineated volume may be a suitable region for dose boosting.%目的:评价局部晚期非小细胞肺癌患者,放疗前18 F-FDG 高代谢区能否识别放疗中及放疗后高代谢区,并探讨局部加量的最佳生物学亚靶区。方法在放疗前、放疗中(40 Gy)和/或放疗后,分别行18 F-FDG PET/CT扫描。利用放疗前原发灶内40

  7. PET and SPECT in neurology

    Energy Technology Data Exchange (ETDEWEB)

    Dierckx, Rudi A.J.O. [Groningen University Medical Center (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Ghent Univ. (Belgium). Dept. of Radiology and Nuclear Medicine; Vries, Erik F.J. de; Waarde, Aren van [Groningen University Medical Center (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Otte, Andreas (ed.) [Univ. of Applied Sciences Offenburg (Germany). Faculty of Electrical Engineering and Information Technology


    PET and SPECT in Neurology highlights the combined expertise of renowned authors whose dedication to the investigation of neurological disorders through nuclear medicine technology has achieved international recognition. Classical neurodegenerative disorders are discussed as well as cerebrovascular disorders, brain tumors, epilepsy, head trauma, coma, sleeping disorders, and inflammatory and infectious diseases of the CNS. The latest results in nuclear brain imaging are detailed. Most chapters are written jointly by a clinical neurologist and a nuclear medicine specialist to ensure a multidisciplinary approach. This state-of-the-art compendium will be valuable to anybody in the field of neuroscience, from the neurologist and the radiologist/nuclear medicine specialist to the interested general practitioner and geriatrician. It is the second volume of a trilogy on PET and SPECT imaging in the neurosciences, the other volumes covering PET and SPECT in psychiatry and in neurobiological systems.

  8. Respiratory gating in cardiac PET

    DEFF Research Database (Denmark)

    Lassen, Martin Lyngby; Rasmussen, Thomas; Christensen, Thomas E


    of our study was to compare the resulting imaging quality by the use of a time-based respiratory gating system in two groups administered either adenosine or dipyridamole as the pharmacological stress agent. METHODS AND RESULTS: Forty-eight patients were randomized to adenosine or dipyridamole cardiac...... stress (82)RB-PET. Respiratory rates and depths were measured by a respiratory gating system in addition to registering actual respiratory rates. Patients undergoing adenosine stress showed a decrease in measured respiratory rate from initial to later scan phase measurements [12.4 (±5.7) vs 5.6 (±4......BACKGROUND: Respiratory motion due to breathing during cardiac positron emission tomography (PET) results in spatial blurring and erroneous tracer quantification. Respiratory gating might represent a solution by dividing the PET coincidence dataset into smaller respiratory phase subsets. The aim...

  9. Particle Accelerators for PET radionuclides

    DEFF Research Database (Denmark)

    Jensen, Mikael


    The requirements set for particle accelerators for production of radioactive isotopes for PET can easily be derived from first principles. The simple general need is for proton beams with energy in the region 10–20 MeV and current 20–100 microAmps. This is most reliably and cost-effectively achie......The requirements set for particle accelerators for production of radioactive isotopes for PET can easily be derived from first principles. The simple general need is for proton beams with energy in the region 10–20 MeV and current 20–100 microAmps. This is most reliably and cost...... different manufacturers will be discussed the light of what is actually needed for a given PET site operation. Alternatives to the conventional cyclotron have been proposed and tested but have at present very limited use. These alternatives will be discussed, as well as the future possibilities of supplying...

  10. 36 CFR 13.1106 - Pets. (United States)


    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.1106 Section 13.1106 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... Provisions § 13.1106 Pets. Pets are prohibited except— (a) On the Bartlett Cove Public Use Dock; (b) On...

  11. Pets in the family: practical approaches. (United States)

    Hodgson, Kate; Darling, Marcia


    Adapting family life cycle theory to include pets provides veterinarians with a framework for understanding and reinforcing the human-animal bond. The family genogram with pets is a practice tool that identifies all people and pets in the family, enhancing the practice of One Health at the community level.

  12. 7 CFR 503.11 - Pets. (United States)


    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 503.11 Section 503.11 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON PLUM ISLAND ANIMAL DISEASE CENTER § 503.11 Pets. No pets or animals of any kind may be...

  13. 36 CFR 13.978 - Pets. (United States)


    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.978 Section 13.978 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... (fda) § 13.978 Pets. Possessing a pet is prohibited— (a) In the FDA, except in public parking areas,...

  14. 7 CFR 500.10 - Pets. (United States)


    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 500.10 Section 500.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE NATIONAL ARBORETUM Conduct on U.S. National Arboreturm Property § 500.10 Pets. Pets brought upon...

  15. 36 CFR 13.1310 - Pets. (United States)


    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.1310 Section 13.1310... SYSTEM UNITS IN ALASKA Special Regulations-Kenai Fjords National Park General Provisions § 13.1310 Pets. (a) Pets are prohibited— (1) In the Exit Glacier Developed Area except in the parking lot, on...

  16. 36 CFR 13.1234 - Pets. (United States)


    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Pets. 13.1234 Section 13.1234 Parks, Forests, and Public Property NATIONAL PARK SERVICE, DEPARTMENT OF THE INTERIOR NATIONAL PARK... § 13.1234 Pets. Possessing a pet in the BCDA is prohibited....

  17. The modification behaviour for Si implanted PET

    Institute of Scientific and Technical Information of China (English)

    吴瑜光; 张通和; 刘安东; 张旭; 周固


    Polyethylene terephthalate (PET) has been modified by Si ion implantation with a dose ranging from 1 × 1016 to 2 × 1017 ions /cm2 using a metal vapor vacuum arc(MEVVA)source. The surface morphology was observed by atomic force microscopy (AFM). The change in the microstructure of Si implanted PET was observed with a transmission electron microscope (TEM). It is believed that the change would improve the conductive properties and wear resistance. The electrical properties of PET have been improved via Si ion implantation. The resistivity of implanted PET decreased obviously with an increase in ion dose. When Si ion dose was 2 × 1017 cm?2, the resistivity of PET could be less than 7.9 Ω@m. The surface hardness and modulus increased obviously. The mechanical property of the implanted PET has been modified greatly. The hardness and modulus of Si implanted PET with a dose of 2 × 1017/cm2 are 12.5 and 2.45 times greater than those of pristine PET, respectively. The area of cutting groove for Si implanted PET is narrower and shallower than those of the unimplanted PET. So the wear resistance is greatly raised. In comparison with metal ion implantation, the improvement of mechanical properties is obvious in ion implantation into PET. Si ion beam modification mechanism of PET is discussed.

  18. Pet therapy: dogs de-stress students. (United States)

    Young, Judith S


    Research supports the efficacy of the human-animal bond and pet therapy in a variety of settings. At nursing students' request at one school, the author began offering pet therapy prior to examinations. Anecdotal evidence of a study with the author's Golden Retriever, Goldilocks, demonstrates that pet therapy can reduce test anxiety and improve nursing student performance.


    NARCIS (Netherlands)



    As a result of a Guide-Questionnaire distributed among all European PET centers an inventory of the European PET instrumentation has become available in a data base. An overview and analysis of the European PET equipment, cyclotrons, scanners and software, together with some global information on th

  20. PET imaging of {alpha}{sub v}{beta}{sub 3} integrin expression in tumours with {sup 68}Ga-labelled mono-, di- and tetrameric RGD peptides

    Energy Technology Data Exchange (ETDEWEB)

    Dijkgraaf, Ingrid; Franssen, Gerben M.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Yim, Cheng-Bin [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, P.O. Box 9101, Nijmegen (Netherlands); Utrecht University, Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht (Netherlands); Schuit, Robert C. [VU University Medical Centre, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); Luurtsema, Gert [University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Hanzeplein 1, P.O. Box 30.001, Groningen (Netherlands); Liu, Shuang [Purdue University, School of Health Sciences, West Lafayette, IN (United States)


    Due to the restricted expression of {alpha}{sub v}{beta}{sub 3} in tumours, {alpha}{sub v}{beta}{sub 3} is considered a suitable receptor for tumour targeting. In this study the {alpha}{sub v}{beta}{sub 3}-binding characteristics of {sup 68}Ga-labelled monomeric, dimeric and tetrameric RGD peptides were determined and compared with their {sup 111}In-labelled counterparts. A monomeric (E-c(RGDfK)), a dimeric (E-[c(RGDfK)]{sub 2}) and a tetrameric (E{l_brace}E[c(RGDfK)]{sub 2}{r_brace}{sub 2}) RGD peptide were synthesised, conjugated with DOTA and radiolabelled with {sup 68}Ga. In vitro {alpha}{sub v}{beta}{sub 3}-binding characteristics were determined in a competitive binding assay. In vivo {alpha}{sub v}{beta}{sub 3}-targeting characteristics of the compounds were assessed in mice with subcutaneously growing SK-RC-52 xenografts. In addition, microPET images were acquired using a microPET/CT scanner. The IC{sub 50} values for the Ga(III)-labelled DOTA-E-c(RGDfK), DOTA-E-[c(RGDfK)]{sub 2} and DOTA-E{l_brace}E[c(RGDfK)]{sub 2}{r_brace}{sub 2} were 23.9 {+-} 1.22, 8.99 {+-} 1.20 and 1.74 {+-} 1.18 nM, respectively, and were similar to those of the In(III)-labelled mono-, di- and tetrameric RGD peptides (26.6 {+-} 1.15, 3.34 {+-} 1.16 and 1.80 {+-} 1.37 nM, respectively). At 2 h post-injection, tumour uptake of the {sup 68}Ga-labelled mono-, di- and tetrameric RGD peptides (3.30 {+-} 0.30, 5.24 {+-} 0.27 and 7.11 {+-} 0.67%ID/g, respectively) was comparable to that of their {sup 111}In-labelled counterparts (2.70 {+-} 0.29, 5.61 {+-} 0.85 and 7.32 {+-} 2.45%ID/g, respectively). PET scans were in line with the biodistribution data. On all PET scans, the tumour could be clearly visualised. The integrin affinity and the tumour uptake followed the order of DOTA-tetramer > DOTA-dimer > DOTA-monomer. The {sup 68}Ga-labelled tetrameric RGD peptide has excellent characteristics for imaging of {alpha}{sub v} {beta}{sub 3} expression with PET. (orig.)

  1. F-18 Labeled Diabody-Luciferase Fusion Proteins for Optical-ImmunoPET

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Anna M


    The goal of the proposed work is to develop novel dual-labeled molecular imaging probes for multimodality imaging. Based on small, engineered antibodies called diabodies, these probes will be radioactively tagged with Fluorine-18 for PET imaging, and fused to luciferases for optical (bioluminescence) detection. Performance will be evaluated and validated using a prototype integrated optical-PET imaging system, OPET. Multimodality probes for optical-PET imaging will be based on diabodies that are dually labeled with 18F for PET detection and fused to luciferases for optical imaging. 1) Two sets of fusion proteins will be built, targeting the cell surface markers CEA or HER2. Coelenterazine-based luciferases and variant forms will be evaluated in combination with native substrate and analogs, in order to obtain two distinct probes recognizing different targets with different spectral signatures. 2) Diabody-luciferase fusion proteins will be labeled with 18F using amine reactive [18F]-SFB produced using a novel microwave-assisted, one-pot method. 3) Sitespecific, chemoselective radiolabeling methods will be devised, to reduce the chance that radiolabeling will inactivate either the target-binding properties or the bioluminescence properties of the diabody-luciferase fusion proteins. 4) Combined optical and PET imaging of these dual modality probes will be evaluated and validated in vitro and in vivo using a prototype integrated optical-PET imaging system, OPET. Each imaging modality has its strengths and weaknesses. Development and use of dual modality probes allows optical imaging to benefit from the localization and quantitation offered by the PET mode, and enhances the PET imaging by enabling simultaneous detection of more than one probe.

  2. F-18-FDG-PET Confined Radiotherapy of Locally Advanced NSCLC With Concomitant Chemotherapy: Results of the PET-PLAN Pilot Trial

    Energy Technology Data Exchange (ETDEWEB)

    Fleckenstein, Jochen [Department of Radiotherapy and Radiation Oncology, Saarland University Medical School, Homburg (Germany); Hellwig, Dirk [Department of Nuclear Medicine, Saarland University Medical School, Homburg (Germany); Kremp, Stephanie [Department of Radiotherapy and Radiation Oncology, Saarland University Medical School, Homburg (Germany); Grgic, Aleksandar [Department of Nuclear Medicine, Saarland University Medical School, Homburg (Germany); Groeschel, Andreas [Department of Internal Medicine V, Saarland University Medical School, Homburg (Germany); Kirsch, Carl-Martin [Department of Nuclear Medicine, Saarland University Medical School, Homburg (Germany); Nestle, Ursula [Department of Nuclear Medicine, Saarland University Medical School, Homburg (Germany); Clinic for Radiotherapy, University Hospital, Freiburg (Germany); Ruebe, Christian, E-mail: [Department of Radiotherapy and Radiation Oncology, Saarland University Medical School, Homburg (Germany)


    Purpose: The integration of fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the process of radiotherapy (RT) planning of locally advanced non-small-cell lung cancer (NSCLC) may improve diagnostic accuracy and minimize interobserver variability compared with target volume definition solely based on computed tomography. Furthermore, irradiating only FDG-PET-positive findings and omitting elective nodal regions may allow dose escalation by treating smaller volumes. The aim of this prospective pilot trial was to evaluate the therapeutic safety of FDG-PET-based RT treatment planning with an autocontour-derived delineation of the primary tumor. Methods and Materials: Eligible patients had Stages II-III inoperable NSCLC, and simultaneous, platinum-based radiochemotherapy was indicated. FDG-PET and computed tomography acquisitions in RT treatment planning position were coregistered. The clinical target volume (CTV) included the FDG-PET-defined primary tumor, which was autodelineated with a source-to-background algorithm, plus FDG-PET-positive lymph node stations. Limited by dose restrictions for normal tissues, prescribed total doses were in the range of 66.6 to 73.8 Gy. The primary endpoint was the rate of out-of-field isolated nodal recurrences (INR). Results: As per intent to treat, 32 patients received radiochemotherapy. In 15 of these patients, dose escalation above 66.6 Gy was achieved. No Grade 4 toxicities occurred. After a median follow-up time of 27.2 months, the estimated median survival time was 19.3 months. During the observation period, one INR was observed in 23 evaluable patients. Conclusions: FDG-PET-confined target volume definition in radiochemotherapy of NSCLC, based on a contrast-oriented source-to-background algorithm, was associated with a low risk of INR. It might provide improved tumor control because of dose escalation.

  3. Competitive advantage of PET/MRI. (United States)

    Jadvar, Hossein; Colletti, Patrick M


    Multimodality imaging has made great strides in the imaging evaluation of patients with a variety of diseases. Positron emission tomography/computed tomography (PET/CT) is now established as the imaging modality of choice in many clinical conditions, particularly in oncology. While the initial development of combined PET/magnetic resonance imaging (PET/MRI) was in the preclinical arena, hybrid PET/MR scanners are now available for clinical use. PET/MRI combines the unique features of MRI including excellent soft tissue contrast, diffusion-weighted imaging, dynamic contrast-enhanced imaging, fMRI and other specialized sequences as well as MR spectroscopy with the quantitative physiologic information that is provided by PET. Most evidence for the potential clinical utility of PET/MRI is based on studies performed with side-by-side comparison or software-fused MRI and PET images. Data on distinctive utility of hybrid PET/MRI are rapidly emerging. There are potential competitive advantages of PET/MRI over PET/CT. In general, PET/MRI may be preferred over PET/CT where the unique features of MRI provide more robust imaging evaluation in certain clinical settings. The exact role and potential utility of simultaneous data acquisition in specific research and clinical settings will need to be defined. It may be that simultaneous PET/MRI will be best suited for clinical situations that are disease-specific, organ-specific, related to diseases of the children or in those patients undergoing repeated imaging for whom cumulative radiation dose must be kept as low as reasonably achievable. PET/MRI also offers interesting opportunities for use of dual modality probes. Upon clear definition of clinical utility, other important and practical issues related to business operational model, clinical workflow and reimbursement will also be resolved.

  4. Coprological survey in pet reptiles in Italy. (United States)

    Papini, R; Manetti, C; Mancianti, F


    Faecal samples were collected from 324 pet reptiles showing no clinical signs, including 28 saurian species (n=192), three ophidian species (n=74) and three chelonian species (n=58). Samples were examined for the presence of intestinal parasites by direct smear and faecal flotation, while direct immunofluorescence assays were used to reveal the presence of Cryptosporidium oocysts and Giardia cysts. Overall, 57.4 per cent of the reptiles were harbouring intestinal parasites. These included oxyurids (16 per cent), coccidia (12.3 per cent), flagellates (9.3 per cent), strongyles (6.8 per cent), coccidia plus oxyurids (4.9 per cent), coccidia plus flagellates (1.8 per cent), coccidia plus strongyles (1.8 per cent), oxyurids plus strongyles (1.2 per cent), oxyurids plus flagellates (1.2 per cent), Cryptosporidium species (1.2 per cent) and strongyles plus flagellates (0.6 per cent). Intestinal parasites were more prevalent in saurians than in ophidians and chelonians, in insectivores than in carnivores, omnivores and herbivores, and in wild-caught than in captive-born reptiles. A highly significant difference was observed for saurians versus chelonians (odds ratio [OR]=2.20, 95 per cent confidence interval [CI] 1.21 to 3.99), insectivores versus herbivores (OR=2.38, 95 per cent CI 1.26 to 4.49) and in wild-caught versus captive-born pet reptiles (OR=2.36, 95 per cent CI 1.27 to 4.40).

  5. Comparison of planning target volumes based on combination of 18F-FDG PET-CT and 4DCT in thoracic esophageal cancer%PET与四维CT图像结合构建胸段食管癌计划靶体积研究

    Institute of Scientific and Technical Information of China (English)

    李彦康; 郭延娈; 张棚; 李建彬


    目的 比较基于三维CT(three-dimensional CT,3DCT)、四维CT (4DCT)与基于正电子发射计算机断层显像(positron emission tomograpay CT,PET-CT)结合4DCT所构建胸段食管癌原发肿瘤计划靶体积(planning target vol-ume,PTV)位置及体积的差异性.方法 选取2012-12-01-2014-02-28在山东省肿瘤医院放疗科序贯完成3DCT、4DCT和脱氧葡萄糖(fluorodeoxyglucose,FDG) PET-CT胸部定位扫描,且PET图像原发肿瘤最大标准化摄取值(max-imum standardized uptake value,SUVmax)≥2.0的18例胸段食管癌患者.将3DCT图像所得大体肿瘤体积(gross tumorvolume,GTV)上下方向外扩30 mm,横向方向外扩5 mm得到临床靶体积(clinical target volume,CTV3D);CTV3D各方向外扩10 mm得到计划靶体积(planning target volume,PTV3D);内肿瘤靶体积(internal target volume,ITV4D)通过4DCT 10个时相CTV获得;将ITV4D各方向外扩5 mm得到PTV4D;基于SUV≥20% SUVmx得到内生物靶体积(inter-nal biological target volume,IBTVPET20%),将ITV4D与IBTVPET20%通过布尔逻辑运算得到ITVPETT;将ITVPT各方向外扩5 mm得到PTV4r.结果 PTV3D显著大于PTV4D和PTVPETT,P值分别为<0.001和0.044;PTVPT显著大于PTV4D,P=0.048.PTV3D对PTVPETT的包含度(degree of inclusion,DI;0.70±0.05)显著大于PTV3D对PTV4D的DI(0.69±0.06),P=0.042;PTV4D对PTV3D的DI(0.96±0.03)与PTVPETT对PTV3D的DI(0.95士0.03)间差异无统计学意义,P=0.118.结论 在构建胸段食管癌靶区时,利用PET与4DCT图像结合不仅改变了肿瘤PTV的大小,而且改变了空间位置及其形状.将二者结合,也许能够为食管癌放疗靶区构建提供借鉴.

  6. Palliative care and compound in household pets. (United States)

    Gaskins, Jessica L


    Palliative care is not a term solely used for humans when discussing health care; the term is also used when discussing veterinary patients. Pets are considered part of the family by pet owners, and they have a special relationship that only another pet owner can fully understand. This article discusses some of the healthcare problems that affect pets (and their owners), statistics on the most commonly used medications for veterinary patients, quality of life, and discussions on the veterinary pharmacist-owner-palliative pet relationship and how compounding pharmacists can prepare patient-specific medications.

  7. Tumor 18 F-FDG heterogeneity assessed by PET image texture analysis and its impact on target delineation for esophageal squamous cell carcinoma%食管鳞癌18F-FDG PET图像异质性及其对放疗靶区勾画影响分析

    Institute of Scientific and Technical Information of China (English)

    吴培培; 胡善亮; 房玉芝; 董鑫哲; 邢力刚; 孙晓蓉; 尹勇; 于金明


    目的:探讨18氟-氟代脱氧葡萄糖(18F-fluorodeoxyglueose,18F-FDG) PET图像异质性对食管癌放疗靶区勾画的影响.方法:28例经病理确诊为食管鳞癌初治患者治疗前行18F-FDG PET/CT扫描.通过视觉法和三维图像纹理参数(能量和熵)分析获得FDG摄取异质性.CT图像上勾画出肿瘤靶区(GTVcT).PET图像上肿瘤靶区采用自动勾画法,分别采用40% SUVmax阈值勾画(GTVPET40%)和标准化摄取值(standardized uptake value,SUV)=2.5绝对值阈值勾画(GTVPET2.5).分析FDG摄取异质性与不同方法勾画肿瘤靶区体积差值间的相关性.结果:3种方法获得的肿瘤靶区差异有统计学意义,GTVCT为(45.00±43.40) cm3明显大于GTVPET40%的(20.42±16.12) cm3和GTVPET2.5 (35.88±36.33) cm3,其中GTVcT与GTVPET40%差异有统计学意义,t=4.34,P=0.00;GTVCT与GTVPET2.5差异有统计学意义,t=4.80,P=0.00;GTVPET40%与GTVPET2.5:差异有统计学意义,t=3.59,P=0.00.肿瘤摄取异质性与传统代谢参数SUVmax和SUVmean及靶区体积间存在相关性,丨r丨 =0.41,P≤0.03.GTVPET40%和GTVPET2.5之间的差异与熵呈正相关,r=0.41,P=0.029;与能量负相关,r=-0.39,P=0.04.视觉评分与GTVPET40%和GTVPET25之间的百分率差值也存在相关性,r=0.59,P=0.001.结论:PET图像上靶区勾画受到FDG摄取异质性的影响,特别是异质性较大的肿瘤.PET精确靶区勾画方法需要考虑到肿瘤异质性的影响.%OBJECTIVE:To evaluate new PET image parameters,FDG uptake heterogeneity defined by texture analysis or visual scoring,and its impact on target volume delineation for squamous cell esophageal cancer (SCEC).METHODS:Patients with newly diagnosed and pathologically proved SCEC (n =28) were received whole body 18 F-FDG PET/CT scanning before treatments.Intra-tumor 18F_FDG uptake heterogeneity was accessed by visual scoring and three-dimensional image texture feature (entropy and energy).Tumor volumes were delineated on the CT (GTVcT) and PET

  8. The MiniPET: a didactic PET system (United States)

    Pedro, R.; Silva, J.; Gurriana, L.; Silva, J. M.; Maio, A.; Soares Augusto, J.


    The MiniPET project aims to design and build a small PET system. It consists of two 4 × 4 matrices of 16 LYSO scintillator crystals and two PMTs with 16 channels resulting in a low cost system with the essential functionality of a clinical PET instrument. It is designed to illustrate the physics of the PET technique and to provide a didactic platform for the training of students and nuclear imaging professionals as well as for scientific outreach. The PET modules can be configured to test for the coincidence of 511 keV gamma rays. The model has a flexible mechanical setup [1] and can simulate 14 diferent ring geometries, from a configuration with as few as 18 detectors per ring (ring radius phi=51 mm), up to a geometry with 70 detectors per ring (phi=200 mm). A second version of the electronic system [2] allowed measurement and recording of the energy deposited in 4 detector channels by photons from a 137Cs radioactive source and by photons resulting of the annihilation of positrons from a 22Na radioactive source. These energy spectra are used for detector performance studies, as well as angular dependency studies. In this paper, the mechanical setup, the front-end high-speed analog electronics, the digital acquisition and control electronics implemented in a FPGA, as well as the data-transfer interface between the FPGA board and a host PC are described. Recent preliminary results obtained with the 4 active channels in the prototype are also presented.

  9. Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jin Ho; Choi, Yong, E-mail:; Jung, Jiwoong; Kim, Sangsu; Lim, Hyun Keong; Im, Ki Chun [Department of Electronic Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 121-742 (Korea, Republic of); Oh, Chang Hyun; Park, Hyun-wook [Department of Electrical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Kim, Kyung Min; Kim, Jong Guk [Korea Institute of Radiological and Medical Science, 75 Nowon-ro, Nowon-gu, Seoul 139-709 (Korea, Republic of)


    Purpose: The purpose of this study was to develop a dual-modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain. Methods: The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger-mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom-made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold-plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh-type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array-embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3-T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom-made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired. Results: No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal-to-noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was

  10. Geo-PET: A novel generic organ-pet for small animal organs and tissues (United States)

    Sensoy, Levent

    Reconstructed tomographic image resolution of small animal PET imaging systems is improving with advances in radiation detector development. However the trend towards higher resolution systems has come with an increase in price and system complexity. Recent developments in the area of solid-state photomultiplication devices like silicon photomultiplier arrays (SPMA) are creating opportunities for new high performance tools for PET scanner design. Imaging of excised small animal organs and tissues has been used as part of post-mortem studies in order to gain detailed, high-resolution anatomical information on sacrificed animals. However, this kind of ex-vivo specimen imaging has largely been limited to ultra-high resolution muCT. The inherent limitations to PET resolution have, to date, excluded PET imaging from these ex-vivo imaging studies. In this work, we leverage the diminishing physical size of current generation SPMA designs to create a very small, simple, and high-resolution prototype detector system targeting ex-vivo tomographic imaging of small animal organs and tissues. We investigate sensitivity, spatial resolution, and the reconstructed image quality of a prototype small animal PET scanner designed specifically for imaging of excised murine tissue and organs. We aim to demonstrate that a cost-effective silicon photomultiplier (SiPM) array based design with thin crystals (2 mm) to minimize depth of interaction errors might be able to achieve sub-millimeter resolution. We hypothesize that the substantial decrease in sensitivity associated with the thin crystals can be compensated for with increased solid angle detection, longer acquisitions, higher activity and wider acceptance energy windows (due to minimal scatter from excised organs). The constructed system has a functional field of view (FoV) of 40 mm diameter, which is adequate for most small animal specimen studies. We perform both analytical (3D-FBP) and iterative (ML-EM) methods in order to

  11. Effect of Attenuation Correction on Regional Quantification Between PET/MR and PET/CT

    DEFF Research Database (Denmark)

    Teuho, Jarmo; Johansson, Jarkko; Linden, Jani;


    UNLABELLED: A spatial bias in brain PET/MR exists compared with PET/CT, because of MR-based attenuation correction. We performed an evaluation among 4 institutions, 3 PET/MR systems, and 4 PET/CT systems using an anthropomorphic brain phantom, hypothesizing that the spatial bias would be minimized...... with CT-based attenuation correction (CTAC). METHODS: The evaluation protocol was similar to the quantification of changes in neurologic PET studies. Regional analysis was conducted on 8 anatomic volumes of interest (VOIs) in gray matter on count-normalized, resolution-matched, coregistered data. On PET....../MR systems, CTAC was applied as the reference method for attenuation correction. RESULTS: With CTAC, visual and quantitative differences between PET/MR and PET/CT systems were minimized. Intersystem variation between institutions was +3.42% to -3.29% in all VOIs for PET/CT and +2.15% to -4.50% in all VOIs...

  12. PET and SPECT in psychiatry

    Energy Technology Data Exchange (ETDEWEB)

    Dierckx, Rudi A.J.O. [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging; Ghent Univ. (Belgium); Otte, Andreas [Univ. of Applied Sciences Offenburg (Germany). Faculty of Electrical Engineering and Information Technology; Vries, Erik F.J. de; Waarde, Aren van (eds.) [University Medical Center Groningen (Netherlands). Dept. of Nuclear Medicine and Molecular Imaging


    Covers classical psychiatric disorders as well as other subjects such as suicide, sleep, eating disorders, and autism. Emphasis on a multidisciplinary approach. Written by internationally acclaimed experts. PET and SPECT in Psychiatry showcases the combined expertise of renowned authors whose dedication to the investigation of psychiatric disease through nuclear medicine technology has achieved international recognition. The classical psychiatric disorders as well as other subjects - such as suicide, sleep, eating disorders, and autism - are discussed and the latest results in functional neuroimaging are detailed. Most chapters are written jointly by a clinical psychiatrist and a nuclear medicine expert to ensure a multidisciplinary approach. This state of the art compendium will be valuable to all who have an interest in the field of neuroscience, from the psychiatrist and the radiologist/nuclear medicine specialist to the interested general practitioner and cognitive psychologist. It is the first volume of a trilogy on PET and SPECT imaging in the neurosciences; other volumes will focus on PET and SPECT in neurology and PET and SPECT of neurobiological systems.

  13. SPECT og PET i neurobiologien

    DEFF Research Database (Denmark)

    Paulson, O.B.; Lassen, N.A.


    PET (positron emission tomography) and SPECT (single photon emission computed tomography) are isotopic methods in which the distribution is registered of radiolabelled tracers given in such small amounts that they are without effect on the organism or the organism's disposal of them. Thus, a series...

  14. [68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning

    Directory of Open Access Journals (Sweden)

    Bamberg Michael


    Full Text Available Abstract Purpose The observation that human meningioma cells strongly express somatostatin receptor (SSTR 2 was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT. Patients and Methods In 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI and planning-computed tomography (CT was complemented with data from [68Ga]-DOTA-D Phe1-Tyr3-Octreotide (DOTATOC-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan®. Initial gross tumor volume (GTV definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package. Results The integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%. There were major changes of the clinical target volume (CTV which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV-MRI/CT was larger than the GTV-PET in 10 patients (38%, smaller in 13 patients (50% and almost the same in 3 patients (12%. Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible. Conclusion DOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery.

  15. Activity assay of membrane transport proteins

    Institute of Scientific and Technical Information of China (English)

    Hao Xie


    Membrane transport proteins are integral membrane proteins and considered as potential drug targets. Activity assay of transport proteins is essential for developing drugs to target these proteins. Major issues related to activity assessment of transport proteins include availability of transporters,transport activity of transporters, and interactions between ligands and transporters. Researchers need to consider the physiological status of proteins (bound in lipid membranes or purified), availability and specificity of substrates, and the purpose of the activity assay (screening, identifying, or comparing substrates and inhibitors) before choosing appropriate assay strategies and techniques. Transport proteins bound in vesicular membranes can be assayed for transporting substrate across membranes by means of uptake assay or entrance counterflow assay. Alternatively, transport proteins can be assayed for interactions with ligands by using techniques such as isothermal titration calorimetry, nuclear magnetic resonance spectroscopy, or surface plasmon resonance. Other methods and techniques such as fluorometry, scintillation proximity assay, electrophysiological assay, or stopped-flow assay could also be used for activity assay of transport proteins. In this paper the major strategies and techniques for activity assessment of membrane transport proteins are reviewed.

  16. PET-Based Personalized Management in Clinical Oncology: An Unavoidable Path for the Foreseeable Future. (United States)

    Basu, Sandip; Alavi, Abass


    It is imperative that the thrust of clinical practice in the ensuing years would be to develop personalized management model for various disorders. PET-computed tomography (PET-CT) based molecular functional imaging has been increasingly utilized for assessment of tumor and other nonmalignant disorders and has the ability to explore disease phenotype on an individual basis and address critical clinical decision making questions related to practice of personalized medicine. Hence, it is essential to make a concerted systematic effort to explore and define the appropriate place of PET-CT in personalized clinical practice in each of malignancies, which would strengthen the concept further. The potential advantages of PET based disease management can be classified into broad categories: (1) Traditional: which includes assessment of disease extent such as initial disease staging and restaging, treatment response evaluation particularly early in the course and thus PET-CT response adaptive decision for continuing the same regimen or switching to salvage schedules; there has been continuous addition of newer application of PET based disease restaging in oncological parlance (eg, Richter transformation); (2) Recent and emerging developments: this includes exploring tumor biology with FDG and non-FDG PET tracers. The potential of multitracer PET imaging (particularly new and novel tracers, eg, 68Ga-DOTA-TOC/NOC/TATE in NET, 68Ga-PSMA and 18F-fluorocholine in prostate carcinoma, 18F-fluoroestradiol in breast carcinoma) has provided a scientific basis to stratify and select appropriate targeted therapies (both radionuclide and nonradionuclide treatment), a major boost for individualized disease management in clinical oncology. Integrating the molecular level information obtained from PET with structural imaging further individualizing treatment plan in radiation oncology, precision of interventions and biopsies of a particular lesion and forecasting disease prognosis.

  17. High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Andrew V Oleinikov


    Full Text Available Plasmodium falciparum-infected erythrocytes bind endothelial receptors to sequester in vascular beds, and binding to ICAM1 has been implicated in cerebral malaria. Binding to ICAM1 may be mediated by the variant surface antigen family PfEMP1: for example, 6 of 21 DBLbetaC2 domains from the IT4 strain PfEMP1 repertoire were shown to bind ICAM1, and the PfEMP1 containing these 6 domains are all classified as Group B or C type. In this study, we surveyed binding of ICAM1 to 16 DBLbetaC2 domains of the 3D7 strain PfEMP1 repertoire, using a high throughput Bioplex assay format. Only one DBL2betaC2 domain from the Group A PfEMP1 PF11_0521 showed strong specific binding. Among these 16 domains, DBL2betaC2(PF11_0521 best preserved the residues previously identified as conserved in ICAM1-binding versus non-binding domains. Our analyses further highlighted the potential role of conserved residues within predominantly non-conserved flexible loops in adhesion, and, therefore, as targets for intervention. Our studies also suggest that the structural/functional DBLbetaC2 domain involved in ICAM1 binding includes about 80 amino acid residues upstream of the previously suggested DBLbetaC2 domain. DBL2betaC2(PF11_0521 binding to ICAM1 was inhibited by immune sera from east Africa but not by control US sera. Neutralizing antibodies were uncommon in children but common in immune adults from east Africa. Inhibition of binding was much more efficient than reversal of binding, indicating a strong interaction between DBL2betaC2(PF11_0521 and ICAM1. Our high throughput approach will significantly accelerate studies of PfEMP1 binding domains and protective antibody responses.

  18. PET in cerebrovascular disease; PET bei zerebrovaskulaeren Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Herholz, K. [Neurologische Universitaetsklinik der Univ. Koeln (Germany)]|[Max-Planck-Institut fuer Neurologische Forschung, Koeln (Germany)


    Tissue viability is of particular interest in acute cerebral ischemia because it may be preserved if reperfusion can be achieved rapidly, e.g. by acute thrombolysis. Measurements of regional cerebral blood flow (CBF) and oxygen consumption by PET can assess tissue viability, and they have substantially increased our knowledge of th pathophysiology of ischemic stroke and the associated penumbra. Widerspread clinical application in acute stroke, however, is unlikely because of the large logistic and personnel resources required. In chronic cerebrovascular disease, measurement of regional CBF and glucose metabolism, which is usually coupled, provide detailed insights in disturbance of cortical function, e.g. due to deafferentiation, and contribute to differentiation of dementia types. Chronic misery perfusion, i.e. reduced perfusion that does not match the metabolic demand of the tissue, can be demonstrated by PET. It may be found in some patients with high-grade arterial stenoses. Less severe impairment of brain perfusion can be demonstrated by measurement of the cerebrovascular reserve capacity. The most frequent clinical situations can be assessed by less demanding procedures, e.g. by SPECT. In conclusion, PET has its role in cerebrovascular disease primarily within scientific studies, where high resolution and absolute quantitation of physiological variables are essential. (orig.). 65 refs. [Deutsch] Beim akuten ischaemischen Insult ist die Vitalitaet des Gewebes von besonderem Interesse, da sie durch rasche Reperfusion, z.B. durch Thrombolyse, erhalten bleiben kann. Messungen der zerebralen Durchblutung und des Sauerstoffumsatzes mittels PET geben darueber wesentliche Aufschluesse, und sie sind wichtig fuer das Verstaendnis der Pathophysiologie ischaemischer Infarkte und der Penumbra mit kritischer Perfusion beim Menschen. Ihre breitere Anwendung in der klinischen Patientenversorgung kommt allerdings wegen des hohen Aufwandes derzeit kaum in Betracht. Bei

  19. The application of 18F-fluorodeoxyglucose PET/CT in radiotherapy of pancreatic cancer%18 F-氟脱氧葡萄糖PET/CT在胰腺癌放疗中的应用

    Institute of Scientific and Technical Information of China (English)

    贾臻; 张火俊


    18F- fluorodeoxyglucose (FDG) PET/CT has important application value in ra-diotherapy of pancreatic cancer. Compared with the traditional imaging examination, PET/CT can improve the accuracy of diagnosis and staging of pancreatic cancer before radiotherapy. During radio-therapy, PET/CT can improve the accuracy of target volume delineation and reduce the adverse effects of irradiation in normal adjacent tissues. Regions of tumor metabolic activity following radio-therapy can be predicted from the baseline PET/CT and treatment planning could be changed. Meanwhile, PET/CT could evaluate the efficacy and prognosis of radiotherapy. With the develop-ment of systematic research, 18F-FDG PET/CT will play an increasingly important role in radiothera-py of pancreatic cancer.%18 F-氟脱氧葡萄糖PET/CT在胰腺癌的放疗中具有重要的应用价值。 PET/CT较常规影像学检查能提高胰腺癌放疗前的诊断及分期准确性。在放疗过程中,以PET/CT检查为基础的靶区勾画能够准确地覆盖肿瘤组织及保护周围正常组织,同时可以按照其所提示的肿瘤代谢活性调整放疗计划。 PET/CT还能够进行放疗的疗效评估及预后评判。相信随着研究的进展,18 F-氟脱氧葡萄糖PET/CT将在胰腺癌放疗中发挥越来越重要的作用。

  20. Application of PET/CT Image Segmentation Technology in Formulating Radiotherapy Plan of Lung Cancer%PET/CT图像分割技术在肺癌放疗计划中的应用

    Institute of Scientific and Technical Information of China (English)

    彭莹莹; 张书旭; 余辉; 张国前; 周露; 周祥


    Objective To investigate the inlfuence on radiotherapy planning of lung cancer with the PET/CT segmentation technology.Methods 12 patients with non-metastatic lung cancer were scanned by PET/CT. The PET targets were segmented by automatic segmenting program written independently based on PCNN model.According to CT images and PET/CT images, the tumor targets were delineated manually by ocular estimating, radiotherapy planning was formulated with the same parameters, the targets volume and dose distribution were compared and analyzed.Results The differences between automatic segmentation target area and manual delineation target area of PET weren’t of statistical signiifcance (P>0.05), which proved the PET automatic segmentation method was more accurate and reliable. Statistically signiifcant differences (P0.05) in the quantity difference of spinal cords, hearts and esophaguses.Conclusion PET/CT image segmentation improves the accuracy of tumor target delineation. The radiotherapy planning based on target segmentation can reduce the illuminated scope of normal tissues and the incidence rate of complications.%目的:探讨PET/CT图像分割技术对肺癌放疗计划制定的影响。方法对12例无转移的肺癌患者行PET/CT扫描。采用自主编写的基于PCNN模型的自动分割程序对PET靶区进行分割处理,再分别以CT图像、PET/CT图像为依据采用目测法手动勾画肿瘤靶区,以相同参数制定调强放疗计划,对比分析靶区体积和剂量分布。结果 PET自动分割靶区与PET手动勾画靶区之间未见统计学差异(P>0.05),分割方法准确可靠;与CT手动勾画靶区之间差异有统计学意义(P0.05)。结论 PET/CT图像分割技术提高了肿瘤靶区勾画的准确性,依据分割靶区制订的放疗计划能降低正常组织受照范围,减少并发症的发生率。

  1. Controlled in situ formation of polyacrylamide hydrogel on PET surface via SI-ARGET-ATRP for wound dressings

    Energy Technology Data Exchange (ETDEWEB)

    Nazari Pour, Sedigheh [Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, Canada R3T 2N2 (Canada); Ghugare, Shivkumar V. [Department of Textile Science, Faculty of Human Ecology, University of Manitoba, Winnipeg, Canada R3T 2N2 (Canada); Wiens, Richard; Gough, Kathleen [Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, Canada R3T 2N2 (Canada); Liu, Song, E-mail: [Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, Canada R3T 2N2 (Canada); Department of Textile Science, Faculty of Human Ecology, University of Manitoba, Winnipeg, Canada R3T 2N2 (Canada); Department of Biosystems Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, Canada R3T 2N2 (Canada)


    Graphical abstract: - Highlights: • We grow poly(acrylamide) (PAM) hydrgol from a polymer surface in a controlled way. • Divinyl crosslinker doesn't compromise the control chain growth feature of ARGET-ATRP. • ATR-FTIR-FPA images (spatial resolution 220 nm) reveal a uniform grafting of PAM. • PAM grafted wound dressing can be dual functional: low-adherent and antibacterial. - Abstract: Well-defined polyacrylamide (PAM) hydrogel was synthesized on the surface of poly(ethylene terephthalate) (PET) film via surface-initiated activators regenerated by electron transfer atom transfer radical polymerization (SI-ARGET-ATRP). Following the deposition of an ATRP initiator (2-bromoisobutyrylbromide) on PET film, PAM hydrogel was grafted from the functionalized PET surface via ARGET-ATRP. XPS and FTIR-ATR confirmed that PAM hydrogel was successfully grafted on the PET surface. Results from AFM, SEM, and FTIR-FPA microscopic investigations showed that PAM hydrogel uniformly covers the surface of PET film. The grafting yield increases linearly with increasing reaction time, indicating that the growth of PAM hydrogel on the surface of PET is well controlled. In a cell adhesion assay, PAM hydrogel grafted PET films (PAM hydrogel-g-PET) showed low adhesion to keratinocyte cells. To impart PAM hydrogel-g-PET with antibacterial function, AgNPs were self-assembled along the amide side chains of PAM hydrogel. AgNPs loaded-PAM hydrogel-g-PET shows 99% reduction in the number of multidrug-resistant Pseudomonas aeruginosa within 3 h contact.

  2. New SPECT and PET Radiopharmaceuticals for Imaging Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Oyebola O. Sogbein


    Full Text Available Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT myocardial perfusion imaging (MPI with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET and magnetic resonance imaging (MRI continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed.

  3. The Current and Evolving Role of PET in Personalized Management of Lung Cancer. (United States)

    Mena, Esther; Yanamadala, Anusha; Cheng, Gang; Subramaniam, Rathan M


    Using tumor genomic profiling information has revolutionized the landscape of personalized treatment of lung cancer. The management of lung cancer and non-small cell lung cancer particularly is influenced by discoveries of activating mutations in epidermal growth factor receptor and targeted therapies with tyrosine kinase inhibitors, fusion genes involving anaplastic lymphoma kinase, and targeted therapies for Kristen-Rat-Sarcoma and MET protooncogenes. PET imaging plays an important role in assessing the biologic behavior of lung cancer and defining response to therapy. This review summarizes genomic discoveries in lung cancer and their implications for functional PET imaging.

  4. PET/MRI and PET/CT in advanced gynaecological tumours: initial experience and comparison

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Marcelo A.; Schulthess, Gustav von; Veit-Haibach, Patrick [University Hospital Zurich, Department Medical Radiology, Nuclear Medicine, Zurich (Switzerland); University Hospital Zurich, Department Medical Radiology, Diagnostic and Interventional Radiology, Zurich (Switzerland); University of Zurich, Zurich (Switzerland); Kubik-Huch, Rahel A.; Freiwald-Chilla, Bianka [Kantonsspital Baden AG, Department of Radiology, Baden (Switzerland); Hauser, Nik [Kantonsspital Baden AG, Department of Gynaecology, Baden (Switzerland); Froehlich, Johannes M. [Guerbet AG, Zurich (Switzerland)


    To compare the diagnostic accuracy of PET/MRI and PET/CT for staging and re-staging advanced gynaecological cancer patients as well as identify the potential benefits of each method in such a population. Twenty-six patients with suspicious or proven advanced gynaecological cancer (12 ovarian, seven cervical, one vulvar and four endometrial tumours, one uterine metastasis, and one primary peritoneal cancer) underwent whole-body imaging with a sequential trimodality PET/CT/MR system. Images were analysed regarding primary tumour detection and delineation, loco-regional lymph node staging, and abdominal/extra-abdominal distant metastasis detection (last only by PET/CT). Eighteen (69.2 %) patients underwent PET/MRI for primary staging and eight patients (30.8 %) for re-staging their gynaecological malignancies. For primary tumour delineation, PET/MRI accuracy was statistically superior to PET/CT (p < 0.001). Among the different types of cancer, PET/MRI presented better tumour delineation mainly for cervical (6/7) and endometrial (2/3) cancers. PET/MRI for local evaluation as well as PET/CT for extra-abdominal metastases had therapeutic consequences in three and one patients, respectively. PET/CT detected 12 extra-abdominal distant metastases in 26 patients. PET/MRI is superior to PET/CT for primary tumour delineation. No differences were found in detection of regional lymph node involvement and abdominal metastases detection. (orig.)

  5. Veterinarians' role for pet owners facing pet loss


    Fernandez-Mehler, P.; Gloor, P.; Sager, E.; Lewis, F.I.; Glaus, T. M


    Owners' satisfaction with, and expectations from, their veterinarians around euthanasia, including questions on disposal of pet remains subject to animal species, clients' gender, age, family conditions, area of living and type of veterinary clinic visited were evaluated by questionnaire. Questionnaires were to be filled out by clients consecutively visiting the individual practices and hospitals for any kind of consultations. Of 2350 questionnaires distributed, 2008 were returned and availab...

  6. Preclinical PET Neuroimaging of [11C]Bexarotene

    Directory of Open Access Journals (Sweden)

    Benjamin H. Rotstein PhD


    Full Text Available Activation of retinoid X receptors (RXRs has been proposed as a therapeutic mechanism for the treatment of neurodegeneration, including Alzheimer's and Parkinson's diseases. We previously reported radiolabeling of a Food and Drug Administration-approved RXR agonist, bexarotene, by copper-mediated [11C]CO2 fixation and preliminary positron emission tomography (PET neuroimaging that demonstrated brain permeability in nonhuman primate with regional binding distribution consistent with RXRs. In this study, the brain uptake and saturability of [11C]bexarotene were studied in rats and nonhuman primates by PET imaging under baseline and greater target occupancy conditions. [11C]Bexarotene displays a high proportion of nonsaturable uptake in the brain and is unsuitable for RXR occupancy measurements in the central nervous system.

  7. A novel vision-based PET bottle recycling facility (United States)

    He, Xiangyu; He, Zaixing; Zhang, Shuyou; Zhao, Xinyue


    Post-consumer PET bottle recycling is attracting increasing attention due to its value as an energy conservation and environmental protection measure. Sorting by color is a common method in bottle recycling; however, manual operations are unstable and time consuming. In this paper, we design a vision-based facility to perform high-speed bottle sorting. The proposed facility consists mainly of electric and mechanical hardware and image processing software. To solve the recognition problem of isolated and overlapped bottles, we propose a new shape descriptor and utilize the support vector data description classifier. We use color names to represent the colors in the real world in order to avoid problems introduced by colors that are similar. The facility is evaluated by the target error, outlier error and total error. The experimental results demonstrate that the facility we developed is capable of recycling various PET bottles.

  8. PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Tagawa, Scott T; Goldsmith, Stanley J;


    Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...... disease (ideal for antigen access and antibody delivery). Furthermore, prostate cancer is also radiation sensitive. Prostate-specific membrane antigen is expressed by virtually all prostate cancers, and represents an attractive target for RIT. Antiprostate-specific membrane antigen RIT demonstrates...... of anatomic, functional, and molecular imaging information. Positron emission tomography (PET)/computed tomography (CT) in oncology is emerging as an important imaging tool. The most common radiotracer for PET/CT in oncology, (18)F-fluorodeoxyglucose (FDG), is not very useful in the imaging of prostate cancer...

  9. Feasibility of simultaneous PET/MR of the carotid artery: first clinical experience and comparison to PET/CT

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Knudsen, Andreas; Hag, Anne Mette Fisker;


    The study aimed at comparing PET/MR to PET/CT for imaging the carotid arteries in patients with known increased risk of atherosclerosis. Six HIV-positive men underwent sequential PET/MR and PET/CT of the carotid arteries after injection of 400 MBq of 18F-FDG. PET/MR was performed a median of 131 ...

  10. Comparison between PET/MR and PET/CT in evaluation of oncological patients%PET/MR与PET/CT的对比研究

    Institute of Scientific and Technical Information of China (English)

    徐白萱; 富丽萍; 关志伟; 尹大一; 刘家金; 杨晖; 张锦明; 陈英茂; 安宁豫


    Objective To verify the feasibility of the integrated PET/MR for oncological applications by comparing PET/MR with PET/CT in terms of lesion detection and quantitative measurement.Methods A total of 277 patients (165 males,112 females,average age (52.9± 12.6) years) voluntarily participated in this same-day PET/CT and PET/MR comparative study.The time interval between the two studies was 15-35 min.PET/CT images were acquired and reconstructed following standard protocols.PET/MR covered the body trunk with a sequence combination of transverse T1 weighted imaging (WI) 3D-volumetric interpolated breath-hold,T2WI turbo spin echo with fat saturation,diffusion-weighted imaging,and simultaneous PET acquisition.PET images were reconstructed by vender-provided attenuation correction methods.The results of PET/CT and PET/MR were regarded as positive if any modality (CT,PET or MRI) was positive.SUVmax was obtained by the manually drawn ROI.Detection rates were compared with x2 test and SUVmax from the two modalities was analyzed with Spearman correlation analysis.Results A total of 353 lesions were detected in 220 patients.Compared to PET/CT,PET/MR revealed 30 additional true-positive lesions,while missed 6.The detection rates between PET/CT and PET/MR were significantly different (P<0.05).The lesion-based and patient-based consistency was 89.8% (317/353) and 85.9% (189/220),respectively.There were significant correlations of SUVmax between PET/MR and PET/CT for lesions(rs =0.91,P<0.01) and for normal tissues(rs =0.62-0.76,all P<0.01).Conclusions With reference to PET/CT,integrated PET/MR may provide comparable semi-quantitative measurements of pathological lesions as well as normal tissues.Integrated PET/MR may be more effective to detect lesions in abdomen and pelvis.%目的 通过与PET/CT在病灶检测及定量分析方面的比较,论证PET/MR一体机应用于临床的可行性.方法 2012年5月至2013年2月共300例患者同天间隔15 ~ 35 min行PET

  11. FDG PET and PET/CT: EANM procedure guidelines for tumour PET imaging: version 1.0

    DEFF Research Database (Denmark)

    Boellaard, Ronald; O'Doherty, Mike J; Weber, Wolfgang A;


    The aim of this guideline is to provide a minimum standard for the acquisition and interpretation of PET and PET/CT scans with [18F]-fluorodeoxyglucose (FDG). This guideline will therefore address general information about[18F]-fluorodeoxyglucose (FDG) positron emission tomography......-computed tomography (PET/CT) and is provided to help the physician and physicist to assist to carrying out,interpret, and document quantitative FDG PET/CT examinations,but will concentrate on the optimisation of diagnostic quality and quantitative information....

  12. Barcoded microchips for biomolecular assays. (United States)

    Zhang, Yi; Sun, Jiashu; Zou, Yu; Chen, Wenwen; Zhang, Wei; Xi, Jianzhong Jeff; Jiang, Xingyu


    Multiplexed assay of analytes is of great importance for clinical diagnostics and other analytical applications. Barcode-based bioassays with the ability to encode and decode may realize this goal in a straightforward and consistent manner. We present here a microfluidic barcoded chip containing several sets of microchannels with different widths, imitating the commonly used barcode. A single barcoded microchip can carry out tens of individual protein/nucleic acid assays (encode) and immediately yield all assay results by a portable barcode reader or a smartphone (decode). The applicability of a barcoded microchip is demonstrated by human immunodeficiency virus (HIV) immunoassays for simultaneous detection of three targets (anti-gp41 antibody, anti-gp120 antibody, and anti-gp36 antibody) from six human serum samples. We can also determine seven pathogen-specific oligonucleotides by a single chip containing both positive and negative controls.

  13. PET/MRI in cancer patients

    DEFF Research Database (Denmark)

    Kjær, Andreas; Loft, Annika; Law, Ian


    Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear...... described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision...... that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations....

  14. Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

    Directory of Open Access Journals (Sweden)

    Tadashi Watabe

    Full Text Available PURPOSE: Acetylcholinesterase (AChE inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11C-Donepezil (DNP and the AChE activity in the normal rat, with special focus on the adrenal glands. METHODS: The distribution of (11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g. A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11C-DNP (45.0 ± 10.7 MBq. The whole-body distribution of the (11C-DNP PET was evaluated based on the Vt (total distribution volume by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. RESULTS: The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11C-DNP in the body (following the liver (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3, respectively, indicating that the distribution of (11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively, indicating high activity of AChE in the adrenal glands. CONCLUSIONS: We demonstrated the whole-body distribution of (11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

  15. Child vs. Pet: The Effect of Abortion Legalization on the Demand for Pets


    Youjin Hahn; Liang Choon Wang; Hee-Seung Yang


    This paper examines whether abortion legalization led to increased demand for pets in the United States. We compare women living in early-legalizing states, whose peak childbearing years occurred in the early 1970s, to women in other states and cohorts and estimate their likelihood of pet ownership and time spent on pets after their peak childbearing years were over. We find the probability of owning any pet is approximately 9.6 percentage points higher for women affected by abortion legaliza...

  16. Joint PET-MR respiratory motion models for clinical PET motion correction (United States)

    Manber, Richard; Thielemans, Kris; Hutton, Brian F.; Wan, Simon; McClelland, Jamie; Barnes, Anna; Arridge, Simon; Ourselin, Sébastien; Atkinson, David


    Patient motion due to respiration can lead to artefacts and blurring in positron emission tomography (PET) images, in addition to quantification errors. The integration of PET with magnetic resonance (MR) imaging in PET-MR scanners provides complementary clinical information, and allows the use of high spatial resolution and high contrast MR images to monitor and correct motion-corrupted PET data. In this paper we build on previous work to form a methodology for respiratory motion correction of PET data, and show it can improve PET image quality whilst having minimal impact on clinical PET-MR protocols. We introduce a joint PET-MR motion model, using only 1 min per PET bed position of simultaneously acquired PET and MR data to provide a respiratory motion correspondence model that captures inter-cycle and intra-cycle breathing variations. In the model setup, 2D multi-slice MR provides the dynamic imaging component, and PET data, via low spatial resolution framing and principal component analysis, provides the model surrogate. We evaluate different motion models (1D and 2D linear, and 1D and 2D polynomial) by computing model-fit and model-prediction errors on dynamic MR images on a data set of 45 patients. Finally we apply the motion model methodology to 5 clinical PET-MR oncology patient datasets. Qualitative PET reconstruction improvements and artefact reduction are assessed with visual analysis, and quantitative improvements are calculated using standardised uptake value (SUVpeak and SUVmax) changes in avid lesions. We demonstrate the capability of a joint PET-MR motion model to predict respiratory motion by showing significantly improved image quality of PET data acquired before the motion model data. The method can be used to incorporate motion into the reconstruction of any length of PET acquisition, with only 1 min of extra scan time, and with no external hardware required.

  17. The Therapeutic Value of Pets



    While domestic pets are capable of transmitting disease and inflicting injury, they may also be of benefit to human health. Studies suggest that companion animals, in addition to their well-known role as helpers to the handicapped, may alleviate depression, solace the lonely, facilitate psycho-therapy, socialize criminals, lower blood pressure, increase survivorship from myocardial infarction and ease the social pain of aging in our society.

  18. Critical Care of Pet Birds. (United States)

    Jenkins, Jeffrey Rowe


    Successful care of the critical pet bird patient is dependent on preparation and planning and begins with the veterinarian and hospital staff. An understanding of avian physiology and pathophysiology is key. Physical preparation of the hospital or clinic includes proper equipment and understanding of the procedures necessary to provide therapeutic and supportive care to the avian patient. An overview of patient intake and assessment, intensive care environment, and fluid therapy is included.

  19. A precise investigation of the 76Br decay for PET imaging (United States)

    Moran, K.; Lister, C. J.; Chowdhury, P.; McCutchan, E. A.; Sonzogni, A.; Broder, B.; Nickles, R. J.; Ellison, P.; Zhu, S.; Greene, J. P.


    Radioisotopes are used in over 14 million medical imaging and therapy procedures each year. New isotopes are constantly introduced to optimize targeting or decay radiation. The dose of internal radiation is calculated from data which in some cases have not been updated for several decades. A thorough investigation of these isotopes using modern technologies and improved analysis techniques is vital to ensure accurate quantification of dose to patients. In this work, we explore the decay of 76Br, a β+ emitter for PET (positron emission tomography), which is used with 77Br for therapy. A sample containing several isotopes of interest, including 76,77Br, was produced at the University of Wisconsin Medical School, shipped to Argonne National Lab, and assayed for 7 days using the Gammasphere detector array, running both analog and digital data acquisition systems simultaneously. More than 6 terabytes of data were collected from the 1MBq source. Analysis of this data set shows new strength to high-lying levels, and allows a reappraisal of the received dose as well as an investigation of count-rate advantages of digital Gammasphere. Supported by US DOE under Grant DE-FG02-94ER40848 and Contracts No. DE-AC02-06CH11357 and No. DE-AC02-98CH10946.

  20. If My Child Has Asthma, Can We Keep Our Pet? (United States)

    ... Have someone other than your child wash and brush your pet every week (this is advisable for cats as well as dogs). Encourage everyone in the family to wash their hands after playing with your pet. Keep your pet ...

  1. SU-E-J-222: Evaluation of Deformable Registration of PET/CT Images for Cervical Cancer Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Y; Turian, J; Templeton, A; Kiel, K; Chu, J [Rush University Medical Center, Chicago, IL (United States); Kadir, T [Mirada Medical Ltd., Oxford, Oxfordshire (United Kingdom)


    Purpose: PET/CT provides important functional information for radiotherapy targeting of cervical cancer. However, repeated PET/CT procedures for external beam and subsequent brachytherapy expose patients to additional radiation and are not cost effective. Our goal is to investigate the possibility of propagating PET-active volumes for brachytherapy procedures through deformable image registration (DIR) of earlier PET/CT and ultimately to minimize the number of PET/CT image sessions required. Methods: Nine cervical cancer patients each received their brachytherapy preplanning PET/CT at the end of EBRT with a Syed template in place. The planning PET/CT was acquired on the day of brachytherapy treatment with the actual applicator (Syed or Tandem and Ring) and rigidly registered. The PET/CT images were then deformably registered creating a third (deformed) image set for target prediction. Regions of interest with standardized uptake values (SUV) greater than 65% of maximum SUV were contoured as target volumes in all three sets of PET images. The predictive value of the registered images was evaluated by comparing the preplanning and deformed PET volumes with the planning PET volume using Dice's coefficient (DC) and center-of-mass (COM) displacement. Results: The average DCs were 0.12±0.14 and 0.19±0.16 for rigid and deformable predicted target volumes, respectively. The average COM displacements were 1.9±0.9 cm and 1.7±0.7 cm for rigid and deformable registration, respectively. The DCs were improved by deformable registration, however, both were lower than published data for DIR in other modalities and clinical sites. Anatomical changes caused by different brachytherapy applicators could have posed a challenge to the DIR algorithm. The physiological change from interstitial needle placement may also contribute to lower DC. Conclusion: The clinical use of DIR in PET/CT for cervical cancer brachytherapy appears to be limited by applicator choice and requires

  2. The AX-PET project Demonstration of a high resolution axial 3D PET

    CERN Document Server

    Bolle, E; Casella, C; Chesi, E; Clinthorne, N; Cochran, E; De Leo, R; Dissertori, G; Djambazov, G; Fanti, V; Honscheid, K; Huh, S; Johnson, I; Joram, C; Kagan, H; Lustermann, W; Meddi, F; Nappi, E; Nessi-Tedaldi, F; Oliver, J F; Pauss, P; Rafecas, M; Renker, D; Rudge, A; Schinzel, D; Schneider, T; Seguinot, J; Smith, S; Solevi, P; Stapnes, S; Weilhammer, P


    The AX-PET is a new geometrical concept for a high resolution 3D PET scanner, based on matrices of axially oriented LYSO crystals interleaved by stacks of WLS, both individually read out by G-APDs. A PET demonstrator, based on two detector modules used in coincidence, is currently under construction.

  3. 4D offline PET-based treatment verification in scanned ion beam therapy: a phantom study (United States)

    Kurz, Christopher; Bauer, Julia; Unholtz, Daniel; Richter, Daniel; Stützer, Kristin; Bert, Christoph; Parodi, Katia


    At the Heidelberg Ion-Beam Therapy Center, patient irradiation with scanned proton and carbon ion beams is verified by offline positron emission tomography (PET) imaging: the {β+} -activity measured within the patient is compared to a prediction calculated on the basis of the treatment planning data in order to identify potential delivery errors. Currently, this monitoring technique is limited to the treatment of static target structures. However, intra-fractional organ motion imposes considerable additional challenges to scanned ion beam radiotherapy. In this work, the feasibility and potential of time-resolved (4D) offline PET-based treatment verification with a commercial full-ring PET/CT (x-ray computed tomography) device are investigated for the first time, based on an experimental campaign with moving phantoms. Motion was monitored during the gated beam delivery as well as the subsequent PET acquisition and was taken into account in the corresponding 4D Monte-Carlo simulations and data evaluation. Under the given experimental conditions, millimeter agreement between the prediction and measurement was found. Dosimetric consequences due to the phantom motion could be reliably identified. The agreement between PET measurement and prediction in the presence of motion was found to be similar as in static reference measurements, thus demonstrating the potential of 4D PET-based treatment verification for future clinical applications.

  4. PET-Computed Tomography in Veterinary Medicine. (United States)

    Randall, Elissa K


    PET/CT is an advanced imaging modality that is becoming more commonly used in veterinary medicine. It is most commonly used to image patients with cancer, and the most frequently used radiopharmaceutical is F-18 FDG. F-18 FDG is a glucose analog that highlights areas of increased glucose metabolism on the PET images. CT images provide excellent anatomic depiction and aid in interpretation of the PET data. Many types of cancer are hypermetabolic on PET/CT scans, but normal structures and areas of inflammation are also hypermetabolic, so knowledge of normal imaging and cytologic or histopathologic evaluation of lesions is essential.

  5. Radiology for PET/CT reporting

    Energy Technology Data Exchange (ETDEWEB)

    Nanni, Cristina; Fanti, Stefano; Zanoni, Lucia [Univ. Hospital Sant Orsola-Malpighi, Bologna (Italy). Dept. of Nuclear Medicine


    Offers rapid access to slice by slice CT descriptions of anatomical structures from PET/CT studies. Presents images and descriptions of CT findings that may be detected while reviewing PET/CT scans. Includes principal MRI findings in diseases susceptible to PET/CT evaluation. Reading PET/CT scans is sometimes challenging. Not infrequently, abnormal findings on CT images are functionally silent and therefore difficult for nuclear medicine practitioners to interpret. Furthermore, in general only a low-dose CT scan is produced as part of the combined PET/CT study, and the resulting CT images may prove suboptimal for image interpretation. This atlas is designed to enable nuclear medicine practitioners who routinely read PET/CT scans to recognize the most common CT abnormalities. Slice-by-slice descriptions are provided of anatomical structures as visualized on CT scans obtained in PET/CT studies. The CT findings that may be detected while reviewing PET/CT scans of various body regions and conditions are then illustrated and fully described. The concluding section of the book is devoted to the principal MRI findings in diseases which cannot be evaluated using PETs/CTs.

  6. Advances in time-of-flight PET. (United States)

    Surti, Suleman; Karp, Joel S


    This paper provides a review and an update on time-of-flight PET imaging with a focus on PET instrumentation, ranging from hardware design to software algorithms. We first present a short introduction to PET, followed by a description of TOF PET imaging and its history from the early days. Next, we introduce the current state-of-art in TOF PET technology and briefly summarize the benefits of TOF PET imaging. This is followed by a discussion of the various technological advancements in hardware (scintillators, photo-sensors, electronics) and software (image reconstruction) that have led to the current widespread use of TOF PET technology, and future developments that have the potential for further improvements in the TOF imaging performance. We conclude with a discussion of some new research areas that have opened up in PET imaging as a result of having good system timing resolution, ranging from new algorithms for attenuation correction, through efficient system calibration techniques, to potential for new PET system designs.

  7. Advances in time-of-flight PET (United States)

    Surti, Suleman; Karp, Joel S.


    This paper provides a review and an update on time-of-flight PET imaging with a focus on PET instrumentation, ranging from hardware design to software algorithms. We first present a short introduction to PET, followed by a description of TOF PET imaging and its history from the early days. Next, we introduce the current state-of-art in TOF PET technology and briefly summarize the benefits of TOF PET imaging. This is followed by a discussion of the various technological advancements in hardware (scintillators, photo-sensors, electronics) and software (image reconstruction) that have led to the current widespread use of TOF PET technology, and future developments that have the potential for further improvements in the TOF imaging performance. We conclude with a discussion of some new research areas that have opened up in PET imaging as a result of having good system timing resolution, ranging from new algorithms for attenuation correction, through efficient system calibration techniques, to potential for new PET system designs. PMID:26778577

  8. SU-E-J-270: Study of PET Response to HDR Brachytherapy of Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hobbs, R; Le, Y; Armour, E; Efron, J; Azad, N; Wahl, R; Gearhart, S; Herman, J [Johns Hopkins University, Baltimore, MD (United States)


    Purpose: Dose-response studies in radiation therapy are typically using single response values for tumors across ensembles of tumors. Using the high dose rate (HDR) treatment plan dose grid and pre- and post-therapy FDG-PET images, we look for correlations between voxelized dose and FDG uptake response in individual tumors. Methods: Fifteen patients were treated for localized rectal cancer using 192Ir HDR brachytherapy in conjunction with surgery. FDG-PET images were acquired before HDR therapy and 6–8 weeks after treatment (prior to surgery). Treatment planning was done on a commercial workstation and the dose grid was calculated. The two PETs and the treatment dose grid were registered to each other using non-rigid registration. The difference in PET SUV values before and after HDR was plotted versus absorbed radiation dose for each voxel. The voxels were then separated into bins for every 400 cGy of absorbed dose and the bin average values plotted similarly. Results: Individual voxel doses did not correlate with PET response; however, when group into tumor subregions corresponding to dose bins, eighty percent of the patients showed a significant positive correlation (R2 > 0) between PET uptake difference in the targeted region and the absorbed dose. Conclusion: By considering larger ensembles of voxels, such as organ average absorbed dose or the dose bins considered here, valuable information may be obtained. The dose-response correlations as measured by FDG-PET difference potentially underlines the importance of FDG-PET as a measure of response, as well as the value of voxelized information.

  9. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.


    stem cell imaging is proposed to circumvent the major limitation of in vitro radiolabeling – the eventual radiolabel decay. Stable transduction of stem cells in vitro would allow for the selection of high quality stem cells with optimal functional parameters of the transduced reporter systems. The use of a long-lived radioisotope 124I to label a highly specific reporter gene probe will allow for ex vivo labeling of stem cells and their imaging immediately after injection and during the following next week. The use of short-lived radioisotopes (i.e., 18F) to label highly specific reporter gene probes will allow repetitive PET imaging for the assessment of to stem cell migration, targeting, differentiation, and long-term viability of stem cell-derived tissues. Qualifications of the research team and resources. An established research team of experts in various disciplines has been assembled at MD Anderson Cancer Center (MDACC) over the past two years including the PI, senior co-investigators and collaborators. The participants of this team are recognized internationally to be among the leaders in their corresponding fields of research and clinical medicine. The resources at MDACC are exceptionally well developed and have been recently reinforced by the installation of a microPET and microSPECT/CT cameras, and a 7T MRI system for high resolution animal imaging; and by integrating a synthetic chemistry core for the development and production of precursors for radiolabeling.

  10. Seroprevalence of Toxoplasma gondii infection in pet dogs in Kunming, Southwest China

    Directory of Open Access Journals (Sweden)

    Duan Gang


    Full Text Available Abstract Background Toxoplasmosis is a zoonotic parasitic disease caused by the protozoan Toxoplasma gondii, which infects almost all warm-blooded animals, including humans, with a worldwide distribution. However, little is known of T. gondii seroprevalence in pet dogs in Kunming, the capital of Yunnan Province, southwest China. The objective of this investigation was to estimate the seroprevalence of T. gondii infection in pet dogs in this area. Methods A total of 611 serum samples were collected from 7 pet hospitals in Kunming, and assayed for T. gondii antibodies by the indirect haemagglutination (IHA using a commercially-marked kit. Results 132 (21.6% pet dogs were positive for T. gondii antibodies, and the seroprevalence ranged from 17.3% to 34.7% among different sampling regions, the difference was statistically significant (P T. gondii seroprevalence in female and male dogs were 20.8% and 22.4%, respectively, the difference was not statistically significant (P > 0.05. The seroprevalence ranged from 17.5% to 23.6% among different age groups, but the difference was not statistically significant (P > 0.05, and there were no interactions in statistics (P > 0.05 between gender and age of pet dogs in the region. Conclusions The findings of the present survey indicate high T. gondii seroprevalance in pet dogs in Kunming, southwest China, posing significant public health concern. It is necessary to enhance integrated strategies and measures to prevent and control T. gondii infection in pet dogs in this area.

  11. PET-guided delineation of radiation therapy treatment volumes: a survey of image segmentation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Zaidi, Habib [Geneva University Hospital, Division of Nuclear Medicine, Geneva 4 (Switzerland); Geneva University, Geneva Neuroscience Center, Geneva (Switzerland); El Naqa, Issam [Washington University School of Medicine, Department of Radiation Oncology, St. Louis, MO (United States)


    Historically, anatomical CT and MR images were used to delineate the gross tumour volumes (GTVs) for radiotherapy treatment planning. The capabilities offered by modern radiation therapy units and the widespread availability of combined PET/CT scanners stimulated the development of biological PET imaging-guided radiation therapy treatment planning with the aim to produce highly conformal radiation dose distribution to the tumour. One of the most difficult issues facing PET-based treatment planning is the accurate delineation of target regions from typical blurred and noisy functional images. The major problems encountered are image segmentation and imperfect system response function. Image segmentation is defined as the process of classifying the voxels of an image into a set of distinct classes. The difficulty in PET image segmentation is compounded by the low spatial resolution and high noise characteristics of PET images. Despite the difficulties and known limitations, several image segmentation approaches have been proposed and used in the clinical setting including thresholding, edge detection, region growing, clustering, stochastic models, deformable models, classifiers and several other approaches. A detailed description of the various approaches proposed in the literature is reviewed. Moreover, we also briefly discuss some important considerations and limitations of the widely used techniques to guide practitioners in the field of radiation oncology. The strategies followed for validation and comparative assessment of various PET segmentation approaches are described. Future opportunities and the current challenges facing the adoption of PET-guided delineation of target volumes and its role in basic and clinical research are also addressed. (orig.)

  12. Demons versus level-set motion registration for coronary 18F-sodium fluoride PET (United States)

    Rubeaux, Mathieu; Joshi, Nikhil; Dweck, Marc R.; Fletcher, Alison; Motwani, Manish; Thomson, Louise E.; Germano, Guido; Dey, Damini; Berman, Daniel S.; Newby, David E.; Slomka, Piotr J.


    Ruptured coronary atherosclerotic plaques commonly cause acute myocardial infarction. It has been recently shown that active microcalcification in the coronary arteries, one of the features that characterizes vulnerable plaques at risk of rupture, can be imaged using cardiac gated 18F-sodium fluoride (18F-NaF) PET. We have shown in previous work that a motion correction technique applied to cardiac-gated 18F-NaF PET images can enhance image quality and improve uptake estimates. In this study, we further investigated the applicability of different algorithms for registration of the coronary artery PET images. In particular, we aimed to compare demons vs. level-set nonlinear registration techniques applied for the correction of cardiac motion in coronary 18F-NaF PET. To this end, fifteen patients underwent 18F-NaF PET and prospective coronary CT angiography (CCTA). PET data were reconstructed in 10 ECG gated bins; subsequently these gated bins were registered using demons and level-set methods guided by the extracted coronary arteries from CCTA, to eliminate the effect of cardiac motion on PET images. Noise levels, target-to-background ratios (TBR) and global motion were compared to assess image quality. Compared to the reference standard of using only diastolic PET image (25% of the counts from PET acquisition), cardiac motion registration using either level-set or demons techniques almost halved image noise due to the use of counts from the full PET acquisition and increased TBR difference between 18F-NaF positive and negative lesions. The demons method produces smoother deformation fields, exhibiting no singularities (which reflects how physically plausible the registration deformation is), as compared to the level-set method, which presents between 4 and 8% of singularities, depending on the coronary artery considered. In conclusion, the demons method produces smoother motion fields as compared to the level-set method, with a motion that is physiologically

  13. Head and neck imaging with PET and PET/CT: artefacts from dental metallic implants

    Energy Technology Data Exchange (ETDEWEB)

    Goerres, Gerhard W.; Hany, Thomas F.; Kamel, Ehab; von Schulthess, Gustav K.; Buck, Alfred [Division of Nuclear Medicine, Department of Radiology, University Hospital Zurich (Switzerland)


    Germanium-68 based attenuation correction (PET{sub Ge68}) is performed in positron emission tomography (PET) imaging for quantitative measurements. With the recent introduction of combined in-line PET/CT scanners, CT data can be used for attenuation correction. Since dental implants can cause artefacts in CT images, CT-based attenuation correction (PET{sub CT}) may induce artefacts in PET images. The purpose of this study was to evaluate the influence of dental metallic artwork on the quality of PET images by comparing non-corrected images and images attenuation corrected by PET{sub Ge68} and PET{sub CT}. Imaging was performed on a novel in-line PET/CT system using a 40-mAs scan for PET{sub CT} in 41 consecutive patients with high suspicion of malignant or inflammatory disease. In 17 patients, additional PET{sub Ge68} images were acquired in the same imaging session. Visual analysis of fluorine-18 fluorodeoxyglucose (FDG) distribution in several regions of the head and neck was scored on a 4-point scale in comparison with normal grey matter of the brain in the corresponding PET images. In addition, artefacts adjacent to dental metallic artwork were evaluated. A significant difference in image quality scoring was found only for the lips and the tip of the nose, which appeared darker on non-corrected than on corrected PET images. In 33 patients, artefacts were seen on CT, and in 28 of these patients, artefacts were also seen on PET imaging. In eight patients without implants, artefacts were seen neither on CT nor on PET images. Direct comparison of PET{sub Ge68} and PET{sub CT} images showed a different appearance of artefacts in 3 of 17 patients. Malignant lesions were equally well visible using both transmission correction methods. Dental implants, non-removable bridgework etc. can cause artefacts in attenuation-corrected images using either a conventional {sup 68}Ge transmission source or the CT scan obtained with a combined PET/CT camera. We recommend that the

  14. Hypoxia in Head and Neck Cancer in Theory and Practice: A PET-Based Imaging Approach

    Directory of Open Access Journals (Sweden)

    Loredana G. Marcu


    Full Text Available Hypoxia plays an important role in tumour recurrence among head and neck cancer patients. The identification and quantification of hypoxic regions are therefore an essential aspect of disease management. Several predictive assays for tumour oxygenation status have been developed in the past with varying degrees of success. To date, functional imaging techniques employing positron emission tomography (PET have been shown to be an important tool for both pretreatment assessment and tumour response evaluation during therapy. Hypoxia-specific PET markers have been implemented in several clinics to quantify hypoxic tumour subvolumes for dose painting and personalized treatment planning and delivery. Several new radiotracers are under investigation. PET-derived functional parameters and tracer pharmacokinetics serve as valuable input data for computational models aiming at simulating or interpreting PET acquired data, for the purposes of input into treatment planning or radio/chemotherapy response prediction programs. The present paper aims to cover the current status of hypoxia imaging in head and neck cancer together with the justification for the need and the role of computer models based on PET parameters in understanding patient-specific tumour behaviour.

  15. Positron emission tomography (PET) in psychiatry. PET in der Psychiatrie

    Energy Technology Data Exchange (ETDEWEB)

    Herholz, K. (Max-Planck-Institut fuer Neurologische Forschung und Neurologische Klinik der Universitaet Koeln (Germany))


    Currently, clinical PET is mainly useful in psychiatry and related areas for differential diagnosis of dementia. In dementia of Alzheimer type reductions of glucose metabolism are found mainly in the temporoparietal assocaiton cortex, in Pick's disease mainly in the frontal cortex, and in Huntington's disease in the striatum. Other demential diseases usually show less toposelective metabolic impairment. In the future, new diagnostic possibilities may arise from analysis of functional stimulation of specific brain areas and from the use of ligands for specific neurotransmitter systems. (orig.)

  16. Role of FDG-PET and PET/CT in the diagnosis of prolonged febrile states

    Energy Technology Data Exchange (ETDEWEB)

    Jaruskova, M.; Belohlavek, O. [Na Homolce Hospital, PET Center, Prague 5 (Czech Republic)


    The role of FDG-PET and PET/CT in patients whose main symptom is prolonged fever has not yet been defined. We addressed this topic in a retrospective study. A total of 124 patients (referred between May 2001 and December 2004) with fever of unknown origin or prolonged fever due to a suspected infection of a joint or vascular prosthesis were included in the study. The patients underwent either FDG-PET or FDG-PET/CT scanning. Sixty-seven patients had a negative focal FDG-PET finding; in this group the method was regarded as unhelpful in determining a diagnosis, and no further investigation was pursued. We tried to obtain clinical confirmation for all patients with positive PET findings. Fifty-seven (46%) patients had positive FDG-PET findings. In six of them no further clinical information was available. Fifty-one patients with positive PET findings and 118 patients in total were subsequently evaluated. Systemic connective tissue disease was confirmed in 17 patients, lymphoma in three patients, inflammatory bowel disease in two patients, vascular prosthesis infection in seven patients, infection of a hip or knee replacement in seven patients, mycotic aneurysm in two patients, abscess in four patients and AIDS in one patient. In eight (16%) patients the finding was falsely positive. FDG-PET or PET/CT contributed to establishing a final diagnosis in 84% of the 51 patients with positive PET findings and in 36% of all 118 evaluated patients with prolonged fever. (orig.)

  17. PET and PET/CT imaging for the earliest detection and treatment of colorectal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, Kevin [Michigan State Univ., Pontiac, MI (United States). POH Medical Center; Kotlyarov, Eduard [Michigan State Univ., Pontiac, MI (United States). POH Medical Center; Georgetown Univ. (United States)


    Approximately 150,000 new cases of colorectal cancer are diagnosed each year with the life time risk of developing colon caner in developed nations being 4.6% in men and 3.2% in women. Screening patients is essential early detection of colon carcinoma to aid in complete resection. Unfortunately current screening methods carry with them poor patient compliance. PET and PET/CT may be a significant part of this screening solution. The authors reviewed and analyzed the English language articles and case reports identified on Medline during the last 10 years. PET and PET/CT results for colorectal carcinoma were tabulated and presented for the fifth Scientific Meeting of the Brazilian Society of Nuclear Biosciences. Though most studies have been retrospective analysis in using PET for staging for other malignant processes the cases that have identified additional uptake in the colon are important. The accuracy when utilizing PET and PET/CT in this screening method has a sensitivity between 65 and 90% with a specificity of 84 to 90% and a positive predictive value 71 to 78%. Early stages of malignancies and pre-cancerous polyps avidly accumulates F-18 Deoxyfluoro glucose allowing us to conclude that whole body PET and PET/CT is an essential component in the work up, staging or treatment monitoring in colon carcinoma. We have to continue to accumulate data for possible introduction for whole body PET and PET/CT scanning for colon carcinoma and precancerous polyps.(author)

  18. Enhancing hydrophilicity and water permeability of PET track-etched membranes by advanced oxidation process

    Energy Technology Data Exchange (ETDEWEB)

    Korolkov, Ilya V.; Mashentseva, Anastassiya A. [Institute of Nuclear Physics, Ibrahimov Str., 1, 050032 Almaty (Kazakhstan); The L.N. Gumilyov Eurasian National University, Satpaev Str., 5, 010008 Astana (Kazakhstan); Güven, Olgun [Department of Chemistry, Hacettepe University, 06800 Beytepe, Ankara (Turkey); Zdorovets, Maxim V. [Institute of Nuclear Physics, Ibrahimov Str., 1, 050032 Almaty (Kazakhstan); The L.N. Gumilyov Eurasian National University, Satpaev Str., 5, 010008 Astana (Kazakhstan); Taltenov, Abzal A. [The L.N. Gumilyov Eurasian National University, Satpaev Str., 5, 010008 Astana (Kazakhstan)


    In this study we present results on the application of advanced oxidation systems for effective and non-toxic oxidation of poly(ethylene terephthalate) track-etched membranes (PET TeMs) to improve their wettability and water transport properties. Two oxidizing systems: H{sub 2}O{sub 2} under UV irradiation (H{sub 2}O{sub 2}/UV) and Fenton system under visible light (Fenton/H{sub 2}O{sub 2}/Vis) were compared. The surface of functionalized PET TeMs was characterized by using colorimetric assay, contact angle measurements and X-ray photoelectron spectroscopy (XPS). Results clearly showed that water permeability of PET TeMs treated with H{sub 2}O{sub 2}/UV was improved by 28 ± 5% compared with etched-only membrane, the same parameter was found to increase by 13 ± 4% in the case of Fenton/H{sub 2}O{sub 2}/Vis treatment. The proposed oxidation technique is very simple, environment friendly and not requiring special equipment or expensive chemicals. The surface hydrophilicity of the membranes stored for 360 days in air between paper sheets was analyzed by contact angle test, colorimetric assay to measure concentration of carboxylic groups on the surface with toluidine blue and XPS analysis. The hydrophilic properties of oxidized PET TeMs were found to be stable for a long period of time.

  19. Enhancing hydrophilicity and water permeability of PET track-etched membranes by advanced oxidation process (United States)

    Korolkov, Ilya V.; Mashentseva, Anastassiya A.; Güven, Olgun; Zdorovets, Maxim V.; Taltenov, Abzal A.


    In this study we present results on the application of advanced oxidation systems for effective and non-toxic oxidation of poly(ethylene terephthalate) track-etched membranes (PET TeMs) to improve their wettability and water transport properties. Two oxidizing systems: H2O2 under UV irradiation (H2O2/UV) and Fenton system under visible light (Fenton/H2O2/Vis) were compared. The surface of functionalized PET TeMs was characterized by using colorimetric assay, contact angle measurements and X-ray photoelectron spectroscopy (XPS). Results clearly showed that water permeability of PET TeMs treated with H2O2/UV was improved by 28 ± 5% compared with etched-only membrane, the same parameter was found to increase by 13 ± 4% in the case of Fenton/H2O2/Vis treatment. The proposed oxidation technique is very simple, environment friendly and not requiring special equipment or expensive chemicals. The surface hydrophilicity of the membranes stored for 360 days in air between paper sheets was analyzed by contact angle test, colorimetric assay to measure concentration of carboxylic groups on the surface with toluidine blue and XPS analysis. The hydrophilic properties of oxidized PET TeMs were found to be stable for a long period of time.

  20. Oncological nuclear medicine: from antibody to PET

    Energy Technology Data Exchange (ETDEWEB)

    Tsuneo, Saga; Takako, Furukawa [National Institute of Radiological Sciences, Dept. of Diagnostic Imaging, Molecular Imaging Center, Inage-ku, Chiba (Japan)


    Department of Diagnostic Imaging has recently established in the Molecular Imaging Center of the National Institute of Radiological Sciences. The major aim of the department is to develop novel molecular imaging probes and to establish functional imaging methods of various cancers. The department consists of three sections; 1) biomolecule section (find out optimal biomolecule as the target of cancer imaging), 2) molecular diagnosis section (develop imaging method using specific molecular probe), and 3) clinical diagnosis section (applying molecular imaging modalities to cancer patients). In the present lecture, I would like to review my experiences in various aspects of cancer imaging using nuclear medicine procedures, which might be important in the research in the new department. The talk includes; 1) characteristics and limitations of cancer targeting with radiolabeled anti-cancer monoclonal antibodies and the attempts to overcome the limitations including pre-targeting strategy, 2 ) application of a newly synthesized polyamine (dendrimer) to the delivery and imaging of oligo-DNA and cancer treatment, 3) transfection of Na '/I - sym-porter gene to add iodide uptake mechanism to non-thyroid cancer cells for the wider application of radioiodine therapy, which is now also used as a promising reporter gene in gene therapy, and 4) basic and clinical study of PET metabolic imaging with fluorodeoxyglucose (FDG) and fluoro-thymidine (FLT) to evaluate the characteristics of various cancers. Although these modalities can not directly visualize molecular processes occurring in cancer cells, we can evaluate the imaging results with the insight of molecular biology, and the experiences of these modalities can be the bases for the future development of molecular imaging of malignant tumors. (author)

  1. Radiolabelling and PET brain imaging of the a1-adrenoceptor antagonist Lu AE43936

    DEFF Research Database (Denmark)

    Risgaard, Rune; Ettrup, Anders Janusz; Balle, Thomas;


    Cerebral α₁-adrenoceptors are a common target for many antipsychotic drugs. Thus, access to positron emission tomography (PET) brain imaging of α₁-adrenoceptors could make important contributions to the understanding of psychotic disorders as well as to the pharmacokinetics and occupancy of drugs...

  2. Quantitative Techniques in PET-CT Imaging

    NARCIS (Netherlands)

    Basu, Sandip; Zaidi, Habib; Holm, Soren; Alavi, Abass


    The appearance of hybrid PET/CT scanners has made quantitative whole body scanning of radioactive tracers feasible. This paper deals with the novel concepts for assessing global organ function and disease activity based on combined functional (PET) and structural (CT or MR) imaging techniques, their

  3. 7 CFR 501.10 - Pets. (United States)


    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Pets. 501.10 Section 501.10 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL RESEARCH SERVICE, DEPARTMENT OF AGRICULTURE CONDUCT ON U.S. MEAT ANIMAL RESEARCH CENTER, CLAY CENTER, NEBRASKA § 501.10 Pets. Animals shall be...

  4. Welfare of non-traditional pets. (United States)

    Schuppli, C A; Fraser, D; Bacon, H J


    The keeping of non-traditional or 'exotic' pets has been growing in popularity worldwide. In addition to the typical welfare challenges of keeping more traditional pet species like dogs and cats, ensuring the welfare of non-traditional pets is complicated by factors such as lack of knowledge, difficulties meeting requirements in the home and where and how animals are obtained. This paper uses examples of different species to highlight three major welfare concerns: ensuring that pets under our care i) function well biologically, ii) are free from negative psychological states and able to experience normal pleasures, and iii) lead reasonably natural lives. The keeping of non-traditional pets also raises ethical concerns about whether the animal poses any danger to others (e.g. transmission of zoonotic diseases) and whether the animal might cause environmental damage (e.g. invading non-native habitats when released). The authors used these considerations to create a checklist, which identifies and organises the various concerns that may arise over keeping non-traditional species as pets. An inability to address these concerns raises questions about how to mitigate them or even whether or not certain species should be kept as pets at all. Thus, the authors propose five categories, which range from relatively unproblematic pet species to species whose keeping poses unacceptable risks to the animals, to humans, or to the environment. This approach to the evaluation and categorisation of species could provide a constructive basis for advocacy and regulatory actions.

  5. Integrating Pet Therapy into Daily School Life (United States)

    Brous, Miriam T.


    Stories abound in literature of the ways that people and their pets have fostered and created valuable relationships. More recently, research has shown a strong impact from the pet relationship in health-related settings. Positive changes have been seen in people developing resilience, self-reliance, and in making progress in treatment. Children…

  6. Evaluating College Student Interest in Pet Therapy (United States)

    Adamle, Kathleen N.; Riley, Tracy A.; Carlson, Tracey


    The first year of college can be extremely stressful, especially for students residing on campus. Objective: The authors obtained information from college freshmen about their relationships with pets and investigated interest in a pet therapy program as social support for transient stressful periods. Participants: As part of a university…

  7. Kinetic modeling in PET imaging of hypoxia

    DEFF Research Database (Denmark)

    Li, Fan; Jørgensen, Jesper Tranekjær; Hansen, Anders E


    Tumor hypoxia is associated with increased therapeutic resistance leading to poor treatment outcome. Therefore the ability to detect and quantify intratumoral oxygenation could play an important role in future individual personalized treatment strategies. Positron Emission Tomography (PET) can...... analysis for PET imaging of hypoxia....

  8. Choline-PET/CT for imaging prostate cancer; Cholin-PET/CT zur Bildgebung des Prostatakarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Krause, Bernd Joachim [Klinik- und Poliklinik fuer Nuklearmedizin, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany); Treiber, U.; Schwarzenboeck, S.; Souvatzoglou, M. [Klinik fuer Urologie, Klinikum rechts der Isar, Technische Univ. Muenchen (Germany)


    PET and PET/CT using [{sup 11}C]- and [{sup 18}F]-labelled choline derivatives are increasingly being used for imaging of prostate cancer. The value of PET and PET/CT with [{sup 11}C]- and [{sup 18}F]-labelled choline derivates in biochemical recurrence of prostate cancer has been examined in many studies and demonstrates an increasing importance. Primary prostate cancer can be detected with moderate sensitivity using PET and PET/CT using [{sup 11}C]- and [{sup 18}F]-labelled choline derivatives - the differentiation between benign prostatic hyperplasia, prostatitis or high-grade intraepithelial neoplasia (HGPIN) is not always possible. At the present time [{sup 11}C]choline PET/CT is not recommended in the primary setting but may be utilized in clinically suspected prostate cancer with repeatedly negative prostate biopsies, in preparation of a focused re-biopsy. Promising results have been obtained for the use of PET and PET/CT with [{sup 11}C]- and [{sup 18}F]-labelled choline derivates in patients with biochemical recurrence. The detection rate of choline PET and PET/CT for local, regional, and distant recurrence in patients with a biochemical recurrence shows a linear correlation with PSA values at the time of imaging and reaches about 75% in patients with PSA > 3 ng/mL. At PSA values below 1 ng/mL, the recurrence can be diagnosed with choline PET/CT in approximately 1/3 of the patients. PET and PET/CT with [{sup 11}C]- and [{sup 18}F]choline derivates can be helpful for choosing a therapeutic strategy in the sense of an individualized treatment: since an early diagnosis of recurrence is crucial to the choice of optimal treatment. The localization of the site of recurrence - local recurrence, lymph node metastasis or systemic dissemination - has important influence on the therapy regimen. (orig.)

  9. FDG-PET response-adapted therapy

    DEFF Research Database (Denmark)

    Hutchings, Martin


    , response-adapted treatment. Several ongoing or recently completed trials have investigated the use of FDG-PET/CT for early response-adapted HL therapy. The results are encouraging, but the data are immature, and PET response-adapted HL therapy is discouraged outside the setting of clinical trials. PET......Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is the most accurate tool for staging, treatment monitoring, and response evaluation in Hodgkin lymphoma (HL). Early determination of treatment sensitivity by FDG-PET is the best tool to guide individualized....../CT looks promising for selection of therapy in relapsed and refractory disease, but the role in this setting is still unclear....

  10. Development of scintillation materials for PET scanners

    CERN Document Server

    Korzhik, Mikhail; Annenkov, Alexander N; Borissevitch, Andrei; Dossovitski, Alexei; Missevitch, Oleg; Lecoq, Paul


    The growing demand on PET methodology for a variety of applications ranging from clinical use to fundamental studies triggers research and development of PET scanners providing better spatial resolution and sensitivity. These efforts are primarily focused on the development of advanced PET detector solutions and on the developments of new scintillation materials as well. However Lu containing scintillation materials introduced in the last century such as LSO, LYSO, LuAP, LuYAP crystals still remain the best PET species in spite of the recent developments of bright, fast but relatively low density lanthanum bromide scintillators. At the same time Lu based materials have several drawbacks which are high temperature of crystallization and relatively high cost compared to alkali-halide scintillation materials. Here we describe recent results in the development of new scintillation materials for PET application.

  11. Precision Medicine and PET/Computed Tomography: Challenges and Implementation. (United States)

    Subramaniam, Rathan M


    Precision Medicine is about selecting the right therapy for the right patient, at the right time, specific to the molecular targets expressed by disease or tumors, in the context of patient's environment and lifestyle. Some of the challenges for delivery of precision medicine in oncology include biomarkers for patient selection for enrichment-precision diagnostics, mapping out tumor heterogeneity that contributes to therapy failures, and early therapy assessment to identify resistance to therapies. PET/computed tomography offers solutions in these important areas of challenges and facilitates implementation of precision medicine.

  12. Development of a novel enzyme-linked immunosorbent assay targeting a neo-epitope generated by cathepsin-mediated turnover of type III collagen and its application in chronic obstructive pulmonary disease

    DEFF Research Database (Denmark)

    Rasmussen, Daniel Guldager Kring; Sand, Jannie Marie Bülow; Karsdal, Morten Asser


    fragments (C3C) was developed for assessment in serum and plasma. The assay was biologically validated in serum from patients with chronic obstructive pulmonary disease (COPD). Serological levels of C3C were significantly elevated in patients with COPD compared to healthy controls (p = 0.0006). Levels of C3...

  13. Bimodal Imaging Probes for Combined PET and OI: Recent Developments and Future Directions for Hybrid Agent Development

    Directory of Open Access Journals (Sweden)

    Uwe Seibold


    Full Text Available Molecular imaging—and especially positron emission tomography (PET—has gained increasing importance for diagnosis of various diseases and thus experiences an increasing dissemination. Therefore, there is also a growing demand for highly affine PET tracers specifically accumulating and visualizing target structures in the human body. Beyond the development of agents suitable for PET alone, recent tendencies aim at the synthesis of bimodal imaging probes applicable in PET as well as optical imaging (OI, as this combination of modalities can provide clinical advantages. PET, due to the high tissue penetration of the γ-radiation emitted by PET nuclides, allows a quantitative imaging able to identify and visualize tumors and metastases in the whole body. OI on the contrary visualizes photons exhibiting only a limited tissue penetration but enables the identification of tumor margins and infected lymph nodes during surgery without bearing a radiation burden for the surgeon. Thus, there is an emerging interest in bimodal agents for PET and OI in order to exploit the potential of both imaging techniques for the imaging and treatment of tumor diseases. This short review summarizes the available hybrid probes developed for dual PET and OI and discusses future directions for hybrid agent development.

  14. Effects of Withania somnifera and Tinospora cordifolia extracts on the side population phenotype of human epithelial cancer cells: toward targeting multidrug resistance in cancer. (United States)

    Maliyakkal, Naseer; Appadath Beeran, Asmy; Balaji, Sai A; Udupa, Nayanabhirama; Ranganath Pai, Sreedhara; Rangarajan, Annapoorni


    Recent reports suggest the existence of a subpopulation of stem-like cancer cells, termed as cancer stem cells (CSCs), which bear functional and phenotypic resemblance with the adult, tissue-resident stem cells. Side population (SP) assay based on differential efflux of Hoechst 33342 has been effectively used for the isolation of CSCs. The drug resistance properties of SP cells are typically due to the increased expression of ABC transporters leading to drug efflux. Conventionally used chemotherapeutic drugs may often leads to an enrichment of SP, revealing their inability to target the drug-resistant SP and CSCs. Thus, identification of agents that can reduce the SP phenotype is currently in vogue in cancer therapeutics. Withania somnifera (WS) and Tinospora cordifolia (TC) have been used in Ayurveda for treating various diseases, including cancer. In the current study, we have investigated the effects of ethanolic (ET) extracts of WS and TC on the cancer SP phenotype. Interestingly, we found significant decrease in SP on treatment with TC-ET, but not with WS-ET. The SP-inhibitory TC-ET was further fractionated into petroleum ether (TC-PET), dichloromethane (TC-DCM), and n-butyl alcohol (TC-nBT) fractions using bioactivity-guided fractionation. Our data revealed that TC-PET and TC-DCM, but not TC-nBT, significantly inhibited SP in a dose-dependent manner. Furthermore, flow cytometry-based functional assays revealed that TC-PET and TC-DCM significantly inhibited ABC-B1 and ABC-G2 transporters and sensitized cancer cells toward chemotherapeutic drug-mediated cytotoxicity. Thus, the TC-PET and TC-DCM may harbor phytochemicals with the potential to reverse the drug-resistant phenotype, thus improving the efficacy of cancer chemotherapy.

  15. Microfluidic technology for PET radiochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Gillies, J.M. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom)]. E-mail:; Prenant, C. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, P.O. Box 88, Manchester, M60 1QD (United Kingdom); Chimon, G.N. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, P.O. Box 88, Manchester, M60 1QD (United Kingdom); Smethurst, G.J. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); Dekker, B.A. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); Zweit, J. [Cancer Research-UK/University of Manchester Radiochemical Targeting and Imaging Group, Paterson Institute for Cancer Research, Manchester, M20 4BX (United Kingdom); School of Chemical Engineering and Analytical Sciences, University of Manchester, P.O. Box 88, Manchester, M60 1QD (United Kingdom)


    This paper describes the first application of a microfabricated reaction system to positron emission tomography (PET) radiochemistry. We have applied microfluidic technology to synthesise PET radiopharmaceuticals using {sup 18}F and {sup 124}I as labels for fluorodeoxyglucose (FDG) and Annexin-V, respectively. These reactions involved established methods of nucleophilic substitution on a mannose triflate precursor and direct iodination of the protein using iodogen as an oxidant. This has demonstrated a proof of principle of using microfluidic technology to radiochemical reactions involving low and high molecular weight compounds. Using microfluidic reactions, [{sup 18}F]FDG was synthesised with a 50% incorporation of the available F-18 radioactivity in a very short time of 4 s. The radiolabelling efficiency of {sup 124}I Annexin-V was 40% after 1 min reaction time. Chromatographic analysis showed that such reaction yields are comparable to conventional methods, but in a much shorter time. The yields can be further improved with more optimisation of the microfluidic device itself and its fluid mixing profiles. This demonstrates the potential for this technology to have an impact on rapid and simpler radiopharmaceutical synthesis using short and medium half-life radionuclides.

  16. The spatial distribution of pet dogs and pet cats on the island of Ireland

    Directory of Open Access Journals (Sweden)

    More Simon J


    Full Text Available Abstract Background There is considerable international research regarding the link between human demographics and pet ownership. In several international studies, pet ownership was associated with household demographics including: the presence of children in the household, urban/rural location, level of education and age/family structure. What is lacking across all these studies, however, is an understanding of how these pets are spatially distributed throughout the regions under study. This paper describes the spatial distribution of pet dog and pet cat owning households on the island of Ireland. Results In 2006, there were an estimated 640,620 pet dog owning households and 215,542 pet cat owning households in Ireland. These estimates are derived from logistic regression modelling, based on household composition to determine pet dog ownership and the type of house to determine pet cat ownership. Results are presented using chloropleth maps. There is a higher density of pet dog owning households in the east of Ireland and in the cities than the west of Ireland and rural areas. However, in urban districts there are a lower proportion of households owning pet dogs than in rural districts. There are more households with cats in the urban areas, but the proportion of households with cats is greater in rural areas. Conclusions The difference in spatial distribution of dog ownership is a reflection of a generally higher density of households in the east of Ireland and in major cities. The higher proportion of ownership in the west is understandable given the higher proportion of farmers and rural dwellings in this area. Spatial representation allows us to visualise the impact of human household distribution on the density of both pet dogs and pet cats on the island of Ireland. This information can be used when analysing risk of disease spread, for market research and for instigating veterinary care.

  17. FDG-PET and PET/CT in the diagnostic work-up of breast cancer; FDG-PET und PET/CT in der Diagnostik des Mammakarzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Haug, A.; Tiling, R. [Klinik und Poliklinik fuer Nuklearmedizin, Klinikum Innenstadt, Ludwig-Maximilians-Univ. Muenchen (Germany)


    In screening mammography is the best method, followed by biopsy in suspect findings. Ultrasound is used in combination with mammography. In difficult cases like preoperative exclusion of multicentric disease, silicon implants and differentation between scar and local recurrence MRI has gained widespread acceptation. Scintimammography may be useful in nondiagnostic or equivocal findings in mammography due to dense breast parenchyma to monitor neoadjuvant chemotherapy of LABC, but is not recommended for routine use. FDG-PET showed to have a high sensitivity in the diagnosis of primary breast cancer. But there are limitations in the detection of tumors smaller than 10 mm and of lobular carcinomas. For screening its accuracy does not appear sufficient. FDG-PET may help improving the diagnosis of primary breast cancer in particular cases. The diagnostic accuracy of FDG-PET axillary lymph node staging has shown to be not sufficient. Especially small or micrometastases are missed frequently due to the low spatial resolution of PET. Diagnostic accuracy is not high enough to replace histopathological evaluation after surgical (sentinel) lymph node dissection. In the diagnosis of distant lymphatic and hematological metastases a high sensitivity and specificity of PET was reported. FDG-PET may be useful in staging women with high risk of presenting metastases like women with locally advanced breast cancer, but is not implemented in clinical routine, yet. FDG-PET shows a high potential to predict the therapeutic outcome of neoadjuvant chemotherapy very early and with high accuracy. But PET fails to detect microscopic residual tumor in case of complete clinical response. In the diagnosis of local recurrence PET is only useful in equivocal findings in mammography due to breast implant or posttherapeutic scars. A high sensitivity and specificity of FDG-PET in diagnosing metastases was reported. Especially in case of unclearly elevated tumor markers PET is recommended

  18. Feasibility of simultaneous PET/MR of the carotid artery

    DEFF Research Database (Denmark)

    Ripa, Rasmus S; Knudsen, Andreas; Hag, Anne Mette F


    between PET data acquired using the PET/MR system compared to the PET/CT system. The mean difference for SUVmean was -0.18 (p bias towards lower values using the PET/MR system. The 95% limits of agreement were -0.55 to 0...

  19. Colorimetric protein assay techniques. (United States)

    Sapan, C V; Lundblad, R L; Price, N C


    There has been an increase in the number of colorimetric assay techniques for the determination of protein concentration over the past 20 years. This has resulted in a perceived increase in sensitivity and accuracy with the advent of new techniques. The present review considers these advances with emphasis on the potential use of such technologies in the assay of biopharmaceuticals. The techniques reviewed include Coomassie Blue G-250 dye binding (the Bradford assay), the Lowry assay, the bicinchoninic acid assay and the biuret assay. It is shown that each assay has advantages and disadvantages relative to sensitivity, ease of performance, acceptance in the literature, accuracy and reproducibility/coefficient of variation/laboratory-to-laboratory variation. A comparison of the use of several assays with the same sample population is presented. It is suggested that the most critical issue in the use of a chromogenic protein assay for the characterization of a biopharmaceutical is the selection of a standard for the calibration of the assay; it is crucial that the standard be representative of the sample. If it is not possible to match the standard with the sample from the perspective of protein composition, then it is preferable to use an assay that is not sensitive to the composition of the protein such as a micro-Kjeldahl technique, quantitative amino acid analysis or the biuret assay. In a complex mixture it might be inappropriate to focus on a general method of protein determination and much more informative to use specific methods relating to the protein(s) of particular interest, using either specific assays or antibody-based methods. The key point is that whatever method is adopted as the 'gold standard' for a given protein, this method needs to be used routinely for calibration.

  20. Value of PET/CT and MR Lymphography in Treatment of Prostate Cancer Patients With Lymph Node Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Fortuin, Ansje S., E-mail: [Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Deserno, Willem M.L.L.G. [Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Meijer, Hanneke J.M. [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Jager, Gerrit J. [Department of Radiology, Jeroen Bosch Hospital' s, Hertogenbosch (Netherlands); Takahashi, Satoru; Debats, Oscar A. [Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Reske, Sven N.; Schick, Christian [Department of Nuclear Medicine, University of Ulm, Ulm (Germany); Krause, Bernd J. [Department of Nuclear Medicine, Technische Universitaet Muenchen, Muenchen (Germany); Oort, Inge van; Witjes, Alfred J. [Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Hoogeveen, Yvonne L. [Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Lin, Emile N.J.Th. van [Department of Radiation Oncology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands); Barentsz, Jelle O. [Department of Radiology, Radboud University Nijmegen Medical Centre, Nijmegen (Netherlands)


    Purpose: To determine the clinical value of two novel molecular imaging techniques: {sup 11}C-choline positron emission tomography (PET)/computed tomography (CT) and ferumoxtran-10 enhanced magnetic resonance imaging (magnetic resonance lymphography [MRL]) for lymph node (LN) treatment in prostate cancer (PCa) patients. Therefore, we evaluated the ability of PET/CT and MRL to assess the number, size, and location of LN metastases in patients with primary or recurrent PCa. Methods and Materials: A total of 29 patients underwent MRL and PET/CT for LN evaluation. The MRL and PET/CT data were analyzed independently. The number, size, and location of the LN metastases were determined. The location was described as within or outside the standard clinical target volume for elective pelvic irradiation as defined by the Radiation Therapy Oncology Group. Subsequently, the results from MRL and PET/CT were compared. Results: Of the 738 LNs visible on MRL, 151 were positive in 23 of 29 patients. Of the 132 LNs visible on PET/CT, 34 were positive in 13 of 29 patients. MRL detected significantly more positive LNs (p < 0.001) in more patients than PET/CT (p = 0.002). The mean diameter of the detected suspicious LNs on MRL was significantly smaller than those detected by PET/CT, 4.9 mm and 8.4 mm, respectively (p < 0.0001). In 14 (61%) of 23 patients, suspicious LNs were found outside the clinical target volume with MRL and in 4 (31%) of 13 patients with PET/CT. Conclusion: In patients with PCa, both molecular imaging techniques, MRL and {sup 11}C-choline PET/CT, can detect LNs suspicious for metastasis, irrespective of the existing size and shape criteria for CT and conventional magnetic resonance imaging. On MRL and PET/CT, 61% and 31% of the suspicious LNs were located outside the conventional clinical target volume. Therefore, these techniques could help to individualize treatment selection and enable image-guided radiotherapy for patients with PCa LN metastases.

  1. Synthesis of 18F-c(RGDfK) as Integrin αvβ3 Targeted PET Tracer via Click Chemsitry with Cu( I ) Catalyst Systems%整合素αvβ3靶向PET探针18F-c(RGDfK)在Cu(I)催化体系中的点击合成

    Institute of Scientific and Technical Information of China (English)

    施玲丽; 李剑波; 王成; 贾丽娜; 汪勇先; 张岚


    As one of the most important types of Click chemistry, copper-catalyzed 1,3-dipolar cycloaddition reaction has attracted great attention. In this study, 2-[ l8F]fluoroethyl azide( [ 18F]FEA) was synthesized by nucleophilic substitution of 18F-. Then, [l8F]fluoroethyl-1 H-1 ,2,3-triazole-4-c(RGDfK) [18F-c(RGDfK) ] was radio-synthesized as integrin αvβ3 targeted PET tracer fast and efficiently via Click reaction of [ 18F] FEA with propioloyl c( RGDfK). Three catalyst systems of click reaction were investigated: CuS04/NaVc, Cul(s) and CuI/NH4OH, the last two have been used in peptide-click-labeling for the first time. While CuS04/NaVc catalysing the Click reaction, the total radio-chemistry yield of 18F-c( RGDfK) was 62% and the synthesis time was about 60 min(decay-corrected). Click chemistry has demonstrated to be an extraordinarily efficient and convenient method for the preparation of 18F labeled peptides.%通过2-叠氮乙基对甲苯磺酸酯的18 F-亲核取代反应,制备了[18F]2-氟叠氮乙烷,并与丙炔酸修饰的c(RGDfK)反应,采用常用的CuSO4/NaVc催化体系,并尝试了CuI(s)和CuI/NH4OH 2种催化体系,通过点击化学方法合成了整合素αvβ3靶向PET探针[18 F]氟乙基-1,4-取代1,2,3-三唑c(RGDfK)[ 18F-c(RGDfK)].在CuSO4/NaVc的催化下,18 F-c(RGDfK)的总合成时间约为60 min,总收率62%(从[18F]F-起计,经过衰变校正).实验结果表明,点击化学方法高效便捷,适于多肽的18F标记.

  2. Postapplication Fipronil Exposure Following Use on Pets. (United States)

    Cochran, R C; Yu, Liu; Krieger, R I; Ross, J H


    Fipronil is a pyrazole acaricide and insecticide that may be used for insect, tick, lice, and mite control on pets. Residents' short-term and long-term postapplication exposures to fipronil, including secondary environmental exposures, were estimated using data from chemical-specific studies. Estimations of acute (24-h) absorbed doses for residents were based on U.S. Environmental Protection Agency (U.S. EPA) 2012 standard operating procedures (SOPs) for postapplication exposure. Chronic exposures were not estimated for residential use, as continuous, long-term application activities were unlikely to occur. Estimated acute postapplication absorbed doses were as high as 0.56 μg/kg-d for toddlers (1-2 yr) in households with treated pets based on current U.S. EPA SOPs. Acute toddler exposures estimated here were fivefold larger in comparison to adults. Secondary exposure from the household environment in which a treated pet lives that is not from contacting the pet, but from contacting the house interior to which pet residues were transferred, was estimated based on monitoring socks worn by pet owners. These secondary exposures were more than an order of magnitude lower than those estimated from contacting the pet and thus may be considered negligible.

  3. PET/CT in cancer: moderate sample sizes may suffice to justify replacement of a regional gold standard

    DEFF Research Database (Denmark)

    Gerke, Oke; Poulsen, Mads Hvid; Bouchelouche, Kirsten


    PURPOSE: For certain cancer indications, the current patient evaluation strategy is a perfect but locally restricted gold standard procedure. If positron emission tomography/computed tomography (PET/CT) can be shown to be reliable within the gold standard region and if it can be argued that PET....../CT also performs well in adjacent areas, then sample sizes in accuracy studies can be reduced. PROCEDURES: Traditional standard power calculations for demonstrating sensitivities of both 80% and 90% are shown. The argument is then described in general terms and demonstrated by an ongoing study...... of metastasized prostate cancer. RESULTS: An added value in accuracy of PET/CT in adjacent areas can outweigh a downsized target level of accuracy in the gold standard region, justifying smaller sample sizes. CONCLUSIONS: If PET/CT provides an accuracy benefit in adjacent regions, then sample sizes can be reduced...

  4. Novel Strategy for Preparing Dual-Modality Optical/PET Imaging Probes via Photo-Click Chemistry. (United States)

    Sun, Lingyi; Ding, Jiule; Xing, Wei; Gai, Yongkang; Sheng, Jing; Zeng, Dexing


    Preparation of small molecule based dual-modality probes remains a challenging task due to the complicated synthetic procedure. In this study, a novel concise and generic strategy for preparing dual-modality optical/PET imaging probes via photo-click chemistry was developed, in which the diazole photo-click linker functioned not only as a bridge between the targeting-ligand and the PET imaging moiety, but also as the fluorophore for optical imaging. A dual-modality AE105 peptidic probe was successfully generated via this strategy and subsequently applied in the fluorescent staining of U87MG cells and the (68)Ga based PET imaging of mice bearing U87MG xenograft. In addition, dual-modality monoclonal antibody cetuximab has also been generated via this strategy and labeled with (64)Cu for PET imaging studies, broadening the application of this strategy to include the preparation of macromolecule based imaging probes.

  5. Synthesis and In Vitro Evaluation of Oxindole Derivatives as Potential Radioligands for 5-HT7 Receptor Imaging with PET

    DEFF Research Database (Denmark)

    Herth, Matthias Manfred; Volk, Balázs; Pallagi, Katalin;


    The most recently discovered serotonin (5-HT) receptor subtype, 5-HT(7), is considered to be associated with several CNS disorders. Noninvasive in vivo positron emission tomography (PET) studies of cerebral 5-HT(7) receptors could provide a significant advance in the understanding...... of the neurobiology and eventual dysfunctions of the 5-HT(7) receptor. To date, no appropriate 5-HT(7) receptor PET ligand has been developed. Here, we modified known 5-HT(7) selective phenylpiperazinyl-butyloxindole derivatives so that they may be labeled either with carbon-11 or fluorine-18. A set of potential 5-HT......(7) ligands for PET molecular imaging was successfully synthesized. Two compounds (10 and 14) were tested against a range of targets. Both compounds display a promising in vitro profile with respect to PET imaging of the 5-HT(7) receptor in thalamic regions....

  6. Challenges in integrating 18FDG PET-CT into radiotherapy planning of head and neck cancer. (United States)

    Dandekar, P; Partridge, M; Kazi, R; Nutting, C; Harrington, K; Newbold, K


    Radiotherapy forms one of the major treatment modalities for head and neck cancers (HNC), and precision radiotherapy techniques, such as intensity-modulated radiotherapy require accurate target delineation to ensure success of the treatment. Conventionally used imaging modalities, such as X-ray computed tomography (CT) and magnetic resonance imaging are used to delineate the tumor. Imaging, such as positron emission tomography (PET)-CT, which combines the functional and anatomic modalities, is increasingly being used in the management of HNC. Currently, 18-fluorodeoxyglucose is the most commonly used radioisotope, which is accumulated in areas of high glucose uptake, such as the tumor tissue. Because most disease recurrences are within the high-dose radiotherapy volume, defining a biological target volume for radiotherapy boost is an attractive approach to improve the results. There are many challenges in employing the PET-CT for radiotherapy planning, such as patient positioning, target edge definition, and use of new PET tracers, which represent various functional properties, such as hypoxia, protein synthesis, and proliferation. The role of PET-CT for radiotherapy planning is ever expanding and more clinical data underlining the advantages and challenges in this approach are emerging. In this article, we review the current clinical evidence for the application of functional imaging to radiotherapy planning and discuss some of the current challenges and possible solutions that have been suggested to date.

  7. A Prospective Study of {sup 18}FDG-PET With CT Coregistration for Radiation Treatment Planning of Lymphomas and Other Hematologic Malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Terezakis, Stephanie A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Schöder, Heiko [Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Kowalski, Alexander; McCann, Patrick [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Lim, Remy; Turlakov, Alla [Department of Nuclear Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Gonen, Mithat [Department of Statistics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Barker, Chris; Goenka, Anuj; Lovie, Shona [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Yahalom, Joachim, E-mail: [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)


    Purpose: This prospective single-institution study examined the impact of positron emission tomography (PET) with the use of 2-[{sup 18}F] fluoro-2-deoxyglucose and computed tomography (CT) scan radiation treatment planning (TP) on target volume definition in lymphoma. Methods and Materials: 118 patients underwent PET/CT TP during June 2007 to May 2009. Gross tumor volume (GTV) was contoured on CT-only and PET/CT studies by radiation oncologists (ROs) and nuclear medicine physicians (NMPs) for 95 patients with positive PET scans. Treatment plans and dose-volume histograms were generated for CT-only and PET/CT for 95 evaluable sites. Paired t test statistics and Pearson correlation coefficients were used for analysis. Results: 70 (74%) patients had non-Hodgkin lymphoma, 10 (11%) had Hodgkin lymphoma, 12 (10%) had plasma-cell neoplasm, and 3 (3%) had other hematologic malignancies. Forty-three (45%) presented with relapsed/refractory disease. Forty-five (47%) received no prior chemotherapy. The addition of PET increased GTV as defined by ROs in 38 patients (median, 27%; range, 5%-70%) and decreased GTV in 41 (median, 39.5%; range, 5%-80%). The addition of PET increased GTV as defined by NMPs in 27 patients (median, 26.5%; range, 5%-95%) and decreased GTV in 52 (median, 70%; range, 5%-99%). The intraobserver correlation between CT-GTV and PET-GTV was higher for ROs than for NMPs (0.94, P<.01 vs 0.89, P<.01). On the basis of Bland-Altman plots, the PET-GTVs defined by ROs were larger than those defined by NMPs. On evaluation of clinical TPs, only 4 (4%) patients had inadequate target coverage (D95 <95%) of the PET-GTV defined by NMPs. Conclusions: Significant differences between the RO and NMP volumes were identified when PET was coregistered to CT for radiation planning. Despite this, the PET-GTV defined by ROs and NMPs received acceptable prescription dose in nearly all patients. However, given the potential for a marginal miss, consultation with an experienced PET

  8. Comparing life cycle energy and GHG emissions of bio-based PET, recycled PET, PLA and man-made cellulosics

    NARCIS (Netherlands)

    Shen, L.; Worrell, E.; Patel, M.K.


    The purpose of this paper is to review the environmental profiles of petrochemical PET, (partially) bio-based PET, recycled PET, and recycled (partially) bio-based PET, and compare them with other bio-based materials, namely PLA (polylactic acid, a bio-based polyester) and man-made cellulose fibers

  9. Feasibility of simultaneous PET/MR of the carotid artery: first clinical experience and comparison to PET/CT

    DEFF Research Database (Denmark)

    Ripa, Rasmus Sejersten; Knudsen, Andreas; Hag, Anne Mette Fisker


    between PET data acquired using the PET/MR system compared to the PET/CT system. The mean difference for SUVmean was -0.18 (p bias towards lower values using the PET/MR system. The 95% limits of agreement were -0.55 to 0...

  10. Clinical Application of {sup 18}F-FDG PET in Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Il Ki [College of Medicine, Hanyang University, Seoul (Korea, Republic of); Kim, Jae Seung [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)


    Primary brain tumor accounts for 1.4% of entire cancer. For males between the ages of 15 and 34 years, central nervous system tumors account for the leading cause of cancer death. 18F-FDG PET has been reported that it can provide important diagnostic information relating to tumor grading and differentiation from non- tumorous condition. In addition, the degree of FDG metabolism carries prognostic significance. By mapping the metabolic pattern of heterogeneous tumors, 18F-FDG PET can aid in targeting for stereotactic biopsy by selecting the subregions within the tumor that are most hypermetabolic and potentially have the highest grade. According to clinical research data, FDG PET is expected to be a helpful diagnostic tool in the management of brain tumors.

  11. Detection of cranial meningiomas: comparison of {sup 68}Ga-DOTATOC PET/CT and contrast-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Afshar-Oromieh, Ali; Giesel, Frederik L.; Haberkorn, Uwe; Haufe, Sabine; Kratochwil, Clemens [University Hospital of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Linhart, Heinz G. [DKFZ, National Center for Tumor Diseases (NCT), Heidelberg (Germany); Combs, Stephanie E. [University Hospital of Heidelberg, Department of Radiation Oncology and Therapy, Heidelberg (Germany); Podlesek, Dino [University Hospital of Dresden, Department of Neurosurgery, Dresden (Germany); Eisenhut, Michael [DKFZ, Department of Radiopharmacy, Heidelberg (Germany)


    PET imaging with somatostatin receptor ligands, such as {sup 68}Ga-DOTATOC, is a well-established method for detection and target volume definition of meningiomas prior to radiotherapy. Since DOTATOC PET delivers a higher contrast between meningiomas and surrounding tissues than MRI, we conducted a retrospective analysis to compare the diagnostic accuracy of contrast-enhanced MRI (CE-MRI) with {sup 68}Ga-DOTATOC PET/CT in patients with cranial meningiomas prior to radiotherapy. Over a period of 6 years, 134 patients (20-82 years of age, 107 women and 27 men) underwent cranial CE-MRI and {sup 68}Ga-DOTATOC PET/CT. To compare the two methods, the lesions considered typical of meningiomas visually were counted and analysed with respect to their location and SUVmax. In the 134 patients investigated by both modalities, 190 meningiomas were detected by {sup 68}Ga-DOTATOC PET/CT and 171 by CE-MRI. With knowledge of the PET/CT data, the MRI scans were reinvestigated, which led to the detection of 4 of the 19 incidental meningiomas, resulting in an overall detection rate of 92 % of the meningioma lesions that were found by PET/CT. Ga-DOTATOC PET/CT demonstrated an improved sensitivity in meningioma detection when compared to CE-MRI. Tumours adjacent to the falx cerebri, located at the skull base or obscured by imaging artefacts or calcification are particularly difficult to detect by MRI. Therefore {sup 68}Ga-DOTATOC PET/CT may provide additional information in patients with uncertain or equivocal results on MRI or could help to confirm a diagnosis of meningioma based on MRI or could help to confirm MRI-based diagnosis of meningiomas in cases of biopsy limitations. It is possible that not only radiotherapy and surgical planning, but also follow-up strategies would benefit from this imaging modality. (orig.)

  12. Tryptophan PET predicts spatial and temporal patterns of post-treatment glioblastoma progression detected by contrast-enhanced MRI. (United States)

    Bosnyák, Edit; Kamson, David O; Robinette, Natasha L; Barger, Geoffrey R; Mittal, Sandeep; Juhász, Csaba


    Amino acid PET is increasingly utilized for the detection of recurrent gliomas. Increased amino acid uptake is often observed outside the contrast-enhancing brain tumor mass. In this study, we evaluated if non-enhancing PET+ regions could predict spatial and temporal patterns of subsequent MRI progression in previously treated glioblastomas. Twelve patients with a contrast-enhancing area suspicious for glioblastoma recurrence on MRI underwent PET scanning with the amino acid radiotracer alpha-[(11)C]-methyl-L-tryptophan (AMT). Brain regions showing increased AMT uptake in and outside the contrast-enhancing volume were objectively delineated to include high uptake consistent with glioma (as defined by previous studies). Volume and tracer uptake of such non-enhancing PET+ regions were compared to spatial patterns and timing of subsequent progression of the contrast-enhancing lesion, as defined by serial surveillance MRI. Non-enhancing PET+ volumes varied widely across patients and extended up to 24 mm from the edge of MRI contrast enhancement. In ten patients with clear progression of the contrast-enhancing lesion, the non-enhancing PET+ volumes predicted the location of new enhancement, which extended beyond the PET+ brain tissue in six. In two patients, with no PET+ area beyond the initial contrast enhancement, MRI remained stable. There was a negative correlation between AMT uptake in non-enhancing brain and time to subsequent progression (r = -0.77, p = 0.003). Amino acid PET imaging could complement MRI not only for detecting glioma recurrence but also predicting the location and timing of subsequent tumor progression. This could support decisions for surgical intervention or other targeted therapies for recurrent gliomas.

  13. Practical use and implementation of PET in children in a hospital PET centre

    Energy Technology Data Exchange (ETDEWEB)

    Borgwardt, Lise; Larsen, Helle Jung; Pedersen, Kate; Hoejgaard, Liselotte [Department of Clinical Physiology, Nuclear Medicine and PET, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen (Denmark)


    Children are not just small adults - they differ in their psychology, normal physiology and pathophysiology, and various aspects should be considered when planning a positron emission tomography (PET) scan in a child. PET in children is a growing area, and this article describes the practical use and implementation of PET in children in a hospital PET centre. It is intended to be of use to nuclear medicine departments implementing or starting to implement PET scans in children. Topics covered are: dealing with children, dosimetry, organisation within the department and relations with other departments, preparation of the child (provision of information to the child and parents and the fasting procedure), the imaging procedure (resting, tracer injection, positioning, sedation and bladder emptying) and pitfalls in the interpretation of PET scans in children, including experiences with telemedicine. (orig.)

  14. Practical use and implementation of PET in children in a hospital PET centre

    DEFF Research Database (Denmark)

    Borgwardt, Lise; Larsen, Helle Jung; Pedersen, Kate;


    Children are not just small adults-they differ in their psychology, normal physiology and pathophysiology, and various aspects should be considered when planning a positron emission tomography (PET) scan in a child. PET in children is a growing area, and this article describes the practical use......, preparation of the child (provision of information to the child and parents and the fasting procedure), the imaging procedure (resting, tracer injection, positioning, sedation and bladder emptying) and pitfalls in the interpretation of PET scans in children, including experiences with telemedicine....... and implementation of PET in children in a hospital PET centre. It is intended to be of use to nuclear medicine departments implementing or starting to implement PET scans in children. Topics covered are: dealing with children, dosimetry, organisation within the department and relations with other departments...

  15. Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast PET

    Directory of Open Access Journals (Sweden)

    B. B. Koolen


    Full Text Available Positron emission tomography (PET, with or without integrated computed tomography (CT, using 18F-fluorodeoxyglucose (FDG is based on the principle of elevated glucose metabolism in malignant tumors, and its use in breast cancer patients is frequently being investigated. It has been shown useful for classification, staging, and response monitoring, both in primary and recurrent disease. However, because of the partial volume effect and limited resolution of most whole-body PET scanners, sensitivity for the visualization of small tumors is generally low. To improve the detection and quantification of primary breast tumors with FDG PET, several dedicated breast PET devices have been developed. In this nonsystematic review, we shortly summarize the value of whole-body PET/CT in breast cancer and provide an overview of currently available dedicated breast PETs.

  16. Design of a functional cyclic HSV1-TK reporter and its application to PET imaging of apoptosis (United States)

    Wang, Zhe; Wang, Fu; Hida, Naoki; Kiesewetter, Dale O; Tian, Jie; Niu, Gang; Chen, Xiaoyuan


    Positron emission tomography (PET) is a sensitive and noninvasive imaging method that is widely used to explore molecular events in living subjects. PET can precisely and quantitatively evaluate cellular apoptosis, which has a crucial role in various physiological and pathological processes. In this protocol, we describe the design and use of an engineered cyclic herpes simplex virus 1–thymidine kinase (HSV1-TK) PET reporter whose kinase activity is specifically switched on by apoptosis. The expression of cyclic TK (cTK) in healthy cells leads to inactive product, whereas the activation of apoptosis through the caspase-3 pathway cleaves cTK, thus restoring its activity and enabling PET imaging. In addition to detailing the design and construction of the cTK plasmid in this protocol, we include assays for evaluating the function and specificity of the cTK reporter in apoptotic cells, such as assays for measuring the cell uptake of PET tracer in apoptotic cells, correlating doxorubicin (Dox)-induced cell apoptosis to cTK function recovery, and in vivo PET imaging of cancer cell apoptosis, and we also include corresponding data acquisition methods. The time to build the entire cTK reporter is ~2–3 weeks. The selection of a stable cancer cell line takes ~4–6 weeks. The time to implement assays regarding cTK function in apoptotic cells and the in vivo imaging varies depending on the experiment. The cyclization strategy described in this protocol can also be adapted to create other reporter systems for broad biomedical applications. PMID:25927390

  17. Absolute nuclear material assay (United States)

    Prasad, Manoj K [Pleasanton, CA; Snyderman, Neal J [Berkeley, CA; Rowland, Mark S [Alamo, CA


    A method of absolute nuclear material assay of an unknown source comprising counting neutrons from the unknown source and providing an absolute nuclear material assay utilizing a model to optimally compare to the measured count distributions. In one embodiment, the step of providing an absolute nuclear material assay comprises utilizing a random sampling of analytically computed fission chain distributions to generate a continuous time-evolving sequence of event-counts by spreading the fission chain distribution in time.

  18. Molecular PET Imaging of Cyclophosphamide Induced Apoptosis with 18F-ML-8

    Directory of Open Access Journals (Sweden)

    Shaobo Yao


    Full Text Available In this paper, a novel small-molecular apoptotic PET imaging probe, 18F-ML-8 with a malonate motif structure, is presented and discussed. After study, the small tracer that belongs to a member of ApoSense family is proved to be capable of imaging merely apoptotic regions in the CTX treated tumor-bearing mice. The experimental result is further confirmed by in vitro cell binding assays and TUNEL staining assay. As a result, 18F-ML-8 could be used for noninvasive visualization of apoptosis induced by antitumor chemotherapy.

  19. Work on PETS Developed at CIEMAT

    CERN Document Server

    Sanchez, Laura; Calero, Jesus; Carrillo, David; Gavela, Daniel; Gutierrez, Jose Luis; Lara, Alvaro; Rodriguez, Enrique; Toral, Fernando; Doebert, Steffen; Riddone, Germana; Samoshkin, Alexandre


    CIEMAT has been working on the RF power extractor so-called PETS (Power Extraction and Transfer Structure) for the CLIC Test Facility 3 (CTF3) since 2007. The first contribution has been installed at the Test Beam Line (TBL). Additionally, a new PETS configuration is presently under fabrication at CIEMAT and will be installed in the Test Module at CTF3. This paper describes the PETS prototypes design, fabrication and assembly techniques. The characterization of the devices with low RF power is also described.

  20. [New pets, allergens and allergic dermatitis]. (United States)

    Brajon, D; Waton, J; Schmutz, J-L; Barbaud, A


    The number of household pets increased greatly during the twentieth century, with the numbers of new pets (NP, i.e. any pet other than cats and dogs) rising especially sharply over the last decade. Contact with such animals, whose owners do not always know how to look after them properly, expose the population to new risks such as trauma, infection and allergy. While the most common allergies are respiratory, allergic skin reactions, both immediate and delayed, may also result from contact with these new allergens. The animal itself or its environment may be the cause. Herein, we review NPs and reports of allergic dermatitis associated with them.

  1. The Heritage of Radiotracers for PET (United States)

    Fowler, J. S.; Wolf, A. P.


    The history of PET research clearly demonstrates that it is advances in chemistry coupled with a detailed examination of the biochemistry of new radiotracers which has allowed the PET method to be applied to new areas of biology and medicine. Radiotracers whose regional distribution reflects glucose metabolism, neutrotransmitter activity and enzyme activity have all required the development of rapid synthetic methods for the radiotracers themselves and the characterization of their biochemical behavior. This article traces some of the advances in the production of labeled precursors and in radiotracer synthesis and evaluation which have shaped the rapidly expanding application of PET to problems in the neurosciences, in cardiology and in oncology.

  2. PET/MR Imaging in Musculoskeletal Disorders

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Jensen, Karl Erik; Loft, Annika


    There is emerging evidence suggesting that PET/MR imaging will have a role in many aspects of musculoskeletal imaging. The synergistic potential of hybrid PET/MR imaging in terms of acquiring anatomic, molecular, and functional data simultaneously seems advantageous in the diagnostic workup......, treatment planning and monitoring, and follow-up of patients with musculoskeletal malignancies, and may also prove helpful in assessment of musculoskeletal infectious and inflammatory disorders. The application of more sophisticated MR imaging sequences and PET radiotracers other than FDG in the diagnostic...... workup and follow-up of patients with musculoskeletal disorders should be explored....

  3. Bacterial Zoonoses Transmitted by Household Pets

    DEFF Research Database (Denmark)

    Damborg, Peter Panduro; Broens, E.M.; Chomel, B.B.;


    to estimate the burden of human disease attributable to pets and to identify risk behaviours facilitating transmission, and (3) education of those in charge of pets, animal caretakers, veterinarians and human medical healthcare practitioners on the potential zoonotic risks associated with exposure to pets....... Disease-specific recommendations include incentives to undertake research aimed at the development of new diagnostic tests, veterinary-specific antimicrobial products and vaccines, as well as initiatives to promote best practices in veterinary diagnostic laboratories and prudent antimicrobial usage....

  4. Recent progress of PET in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Na NIU


    Full Text Available Alzheimer's disease is the most common cause of dementia in the current elderly population. PET can detect pathophysiological changes in Alzheimer's disease with different radiotracers. This paper will focus on evaluating the value of 18F-FDG, amyloid and tau protein PET imaging in Alzheimer's disease. PET has been demonstrated to play an important role in the research of etiology, early diagnosis, differential dignosis, prognosis and medical treatment of Alzheimer's disease. doi: 10.3969/j.issn.1672-6731.2014.03.007

  5. PET Imaging of Skull Base Neoplasms. (United States)

    Mittra, Erik S; Iagaru, Andrei; Quon, Andrew; Fischbein, Nancy


    The utility of 18-F-fluorodeoxyglucose-positron emission tomography (PET) and PET/CT for the evaluation of skull base tumors is incompletely investigated, as a limited number of studies specifically focus on this region with regard to PET imaging. Several patterns can be ascertained, however, by synthesizing the data from various published reports and cases of primary skull base malignancies, as well as head and neck malignancies that extend secondarily to the skull base, including nasopharyngeal carcinoma, nasal cavity and paranasal sinus tumors, parotid cancers, and orbital tumors.

  6. Changes in topological organization of functional PET brain network with normal aging. (United States)

    Liu, Zhiliang; Ke, Lining; Liu, Huafeng; Huang, Wenhua; Hu, Zhenghui


    Recent studies about brain network have suggested that normal aging is associated with alterations in coordinated patterns of the large-scale brain functional and structural systems. However, age-related changes in functional networks constructed via positron emission tomography (PET) data are still barely understood. Here, we constructed functional brain networks composed of 90 regions in younger (mean age 36.5 years) and older (mean age 56.3 years) age groups with PET data. 113 younger and 110 older healthy individuals were separately selected for two age groups, from a physical examination database. Corresponding brain functional networks of the two groups were constructed by thresholding average cerebral glucose metabolism correlation matrices of 90 regions and analysed using graph theoretical approaches. Although both groups showed normal small-world architecture in the PET networks, increased clustering and decreased efficiency were found in older subjects, implying a degeneration process that brain system shifts from a small-world network to regular one along with normal aging. Moreover, normal senescence was related to changed nodal centralities predominantly in association and paralimbic cortex regions, e.g. increasing in orbitofrontal cortex (middle) and decreasing in left hippocampus. Additionally, the older networks were about equally as robust to random failures as younger counterpart, but more vulnerable against targeted attacks. Finally, methods in the construction of the PET networks revealed reasonable robustness. Our findings enhanced the understanding about the topological principles of PET networks and changes related to normal aging.

  7. Experimental validation of gallium production and isotope-dependent positron range correction in PET (United States)

    Fraile, L. M.; Herraiz, J. L.; Udías, J. M.; Cal-González, J.; Corzo, P. M. G.; España, S.; Herranz, E.; Pérez-Liva, M.; Picado, E.; Vicente, E.; Muñoz-Martín, A.; Vaquero, J. J.


    Positron range (PR) is one of the important factors that limit the spatial resolution of positron emission tomography (PET) preclinical images. Its blurring effect can be corrected to a large extent if the appropriate method is used during the image reconstruction. Nevertheless, this correction requires an accurate modelling of the PR for the particular radionuclide and materials in the sample under study. In this work we investigate PET imaging with 68Ga and 66Ga radioisotopes, which have a large PR and are being used in many preclinical and clinical PET studies. We produced a 68Ga and 66Ga phantom on a natural zinc target through (p,n) reactions using the 9-MeV proton beam delivered by the 5-MV CMAM tandetron accelerator. The phantom was imaged in an ARGUS small animal PET/CT scanner and reconstructed with a fully 3D iterative algorithm, with and without PR corrections. The reconstructed images at different time frames show significant improvement in spatial resolution when the appropriate PR is applied for each frame, by taking into account the relative amount of each isotope in the sample. With these results we validate our previously proposed PR correction method for isotopes with large PR. Additionally, we explore the feasibility of PET imaging with 68Ga and 66Ga radioisotopes in proton therapy.

  8. Experimental validation of gallium production and isotope-dependent positron range correction in PET

    Energy Technology Data Exchange (ETDEWEB)

    Fraile, L.M., E-mail: [Grupo de Física Nuclear, Dpto. Física Atómica, Molecular y Nuclear, Universidad Complutense de Madrid (Spain); Herraiz, J.L.; Udías, J.M.; Cal-González, J.; Corzo, P.M.G.; España, S.; Herranz, E.; Pérez-Liva, M.; Picado, E.; Vicente, E. [Grupo de Física Nuclear, Dpto. Física Atómica, Molecular y Nuclear, Universidad Complutense de Madrid (Spain); Muñoz-Martín, A. [Centro de Microanálisis de Materiales, Universidad Autónoma de Madrid, E-28049 Madrid (Spain); Vaquero, J.J. [Departamento de Bioingeniería e Ingeniería Aeroespacial, Universidad Carlos III de Madrid (Spain)


    Positron range (PR) is one of the important factors that limit the spatial resolution of positron emission tomography (PET) preclinical images. Its blurring effect can be corrected to a large extent if the appropriate method is used during the image reconstruction. Nevertheless, this correction requires an accurate modelling of the PR for the particular radionuclide and materials in the sample under study. In this work we investigate PET imaging with {sup 68}Ga and {sup 66}Ga radioisotopes, which have a large PR and are being used in many preclinical and clinical PET studies. We produced a {sup 68}Ga and {sup 66}Ga phantom on a natural zinc target through (p,n) reactions using the 9-MeV proton beam delivered by the 5-MV CMAM tandetron accelerator. The phantom was imaged in an ARGUS small animal PET/CT scanner and reconstructed with a fully 3D iterative algorithm, with and without PR corrections. The reconstructed images at different time frames show significant improvement in spatial resolution when the appropriate PR is applied for each frame, by taking into account the relative amount of each isotope in the sample. With these results we validate our previously proposed PR correction method for isotopes with large PR. Additionally, we explore the feasibility of PET imaging with {sup 68}Ga and {sup 66}Ga radioisotopes in proton therapy.

  9. Seroprevalence and genotype of Chlamydia in pet parrots in China. (United States)

    Zhang, N-Z; Zhang, X-X; Zhou, D-H; Huang, S-Y; Tian, W-P; Yang, Y-C; Zhao, Q; Zhu, X-Q


    Parrots are one of the most popular pet birds in China, and can harbour Chlamydia which has significance for human and animal health. We investigated, by indirect haemagglutination assay, the seroprevalence of Chlamydia infection in four species of parrots, namely budgerigars (Melopsittacus undulatus), lovebirds (Agapornis sp.), cockatiels (Nymphicus hollandicus) and Alexandrine parakeets (Psittacula eupatria) that were collected from Weifang and Beijing cities, North China and explored the association between potential risk factors and chlamydial seropositivity. We further determined the genotype of Chlamydia in 21 fresh faecal samples based on the ompA sequence by reconstruction of phylogenetic relationships. Of the 311 parrots examined, 35·37% (95% confidence interval 30·06-40·68) were seropositive, and species, gender, age, season and geographical location were identified as risk factors. Two PCR-positive samples represented Chlamydia psittaci genotype A. The occurrence of C. psittaci genotype A in the droppings of two pet parrots in China suggests potential environmental contamination with Chlamydiaceae and may raise a public health concern.

  10. Endoparasite Infections in Pet and Zoo Birds in Italy

    Directory of Open Access Journals (Sweden)

    Roberto Papini


    Full Text Available Faecal samples were individually collected from pet (=63 and zoo (=83 birds representing 14 orders and 63 species. All the samples were examined by faecal flotation technique. In a subgroup of samples (=75, molecular assays were also used to detect Cryptosporidium oocysts and Giardia duodenalis cysts. Overall, 35.6% of the birds harboured parasites (42.2% of zoo birds and 27% of pet birds, including Strongyles-Capillarids (8.9%, Ascaridia (6.8%, Strongyles (5.5%, G. duodenalis Assemblage A (5.3%, Coccidia (4.1%, Cryptosporidium (4%, Porrocaecum (2.7%, Porrocaecum-Capillarids (2%, and Syngamus-Capillarids (0.7%. The zoonotic G. duodenalis Assemblage A and Cryptosporidium were exclusively found in Psittaciformes, with prevalences of 10.3% and 7.7% within this bird group. Zoo birds were more likely to harbor mixed infections (OR = 14.81 and symptomatic birds to be parasitized (OR = 4.72. Clinicians should be aware of the public health implications posed by zoonotic G. duodenalis Assemblages and Cryptosporidium species in captive birds.

  11. False-Positive FDG PET Uptake-the Role of PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Rosenbaum, Sandra J.; Lind, Thomas; Bockisch, Andreas [University of Essen, Department of Nuclear Medicine, Essen (Germany); Antoch, Gerald [University of Essen, Department of Radiology, Essen (Germany)


    Positron emission tomography (PET) is a powerful molecular imaging technique for the human body-imaging applications currently available. As altered glucose metabolism is characteristic for many malignancies, FDG-PET is mostly used in oncology for staging and therapy control. Although PET is a sensitive tool for detecting malignancy, FDG uptake is not tumor specific. It can also be seen in healthy tissue or in benign disease as inflammation or posttraumatic repair and could be mistaken for cancer. The experienced nuclear medicine physician mostly manages to differentiate malignant from non-malignant FDG uptake, but some findings may remain ambiguous. In these cases, the difficulties in differentiating physiologic variants or benign causes of FDG uptake from tumor tissue can often be overcome by combined PET and CT (PET/CT) as anatomic information is added to the metabolic data. Thus, PET/CT improves the diagnostic accuracy compared to PET alone and helps to avoid unnecessary surgery/therapy. However, PET/CT involves other sources of artifacts that may occur when using CT for attenuation correction of PET or by patient motion caused by respiration or bowel movements. (orig.)

  12. Development of a PET Scanner for Simultaneously Imaging Small Animals with MRI and PET

    Directory of Open Access Journals (Sweden)

    Christopher J Thompson


    Full Text Available Recently, positron emission tomography (PET is playing an increasingly important role in the diagnosis and staging of cancer. Combined PET and X-ray computed tomography (PET-CT scanners are now the modality of choice in cancer treatment planning. More recently, the combination of PET and magnetic resonance imaging (MRI is being explored in many sites. Combining PET and MRI has presented many challenges since the photo-multiplier tubes (PMT in PET do not function in high magnetic fields, and conventional PET detectors distort MRI images. Solid state light sensors like avalanche photo-diodes (APDs and more recently silicon photo-multipliers (SiPMs are much less sensitive to magnetic fields thus easing the compatibility issues. This paper presents the results of a group of Canadian scientists who are developing a PET detector ring which fits inside a high field small animal MRI scanner with the goal of providing simultaneous PET and MRI images of small rodents used in pre-clinical medical research. We discuss the evolution of both the crystal blocks (which detect annihilation photons from positron decay and the SiPM array performance in the last four years which together combine to deliver significant system performance in terms of speed, energy and timing resolution.

  13. Dedicated brain PET system of PET/MR for brain research

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Li; Liu, Yaqiang; Ma, Tianyu; Wang, Shi; Wei, Qingyang; Xu, Tianpeng [Institute of Medical Physics, Department of Engineering Physics, Tsinghua University, Beijing (China)


    This work is to replace PET ring in human brain PET/MR system with a dedicated wearable PET insert, aimed at improving both patient feasibility and system performance for brain imaging. The designed PET/MR system includes two parts: the inside parts, including a radio frequency (RF) coil and PET ring, are mounted on patient’s head, and the outside part, a MR imager, is dependent of patient. The RF coil is the innermost layer, surrounded by an outer PET-ring layer. They are supported by a MRcompatible structure. And both RF coil and PET detectors are placed inside a standard clinical 3-T MR imager. From the design of the system we can infer that some advantages can be achieved. First, high sensitivity will be achieved with the same amount crystals as the PET ring is more close to region-of-interest area, at a reduced cost. Second, by using a 2-layer depth of interaction (DOI) detector, the parallax effect can be minimized. The resolution will benefit from short positron range caused by magnetic field and smaller ring diameter will also reduce the effect of non-collinearity. Thirdly, as the PET ring is mounted on head, impact of patient motion will be reduced.

  14. Combined PET/MRI scanner (United States)

    Schlyer, David; Woody, Craig L.; Rooney, William; Vaska, Paul; Stoll, Sean; Pratte, Jean-Francois; O'Connor, Paul


    A combined PET/MRI scanner generally includes a magnet for producing a magnetic field suitable for magnetic resonance imaging, a radiofrequency (RF) coil disposed within the magnetic field produced by the magnet and a ring tomograph disposed within the magnetic field produced by the magnet. The ring tomograph includes a scintillator layer for outputting at least one photon in response to an annihilation event, a detection array coupled to the scintillator layer for detecting the at least one photon outputted by the scintillator layer and for outputting a detection signal in response to the detected photon and a front-end electronic array coupled to the detection array for receiving the detection signal, wherein the front-end array has a preamplifier and a shaper network for conditioning the detection signal.

  15. Molecular Imaging Challenges With PET

    CERN Document Server

    Lecoq, P


    The future trends in molecular imaging and associated challenges for in-vivo functional imaging are illustrated on the basis of a few examples, such as atherosclerosis vulnerable plaques imaging or stem cells tracking. A set of parameters are derived to define the specifications of a new generation of in-vivo imaging devices in terms of sensitivity, spatial resolution and signal-to-noise ratio. The limitations of strategies used in present PET scanners are discussed and new approaches are proposed taking advantage of recent progress on materials, photodetectors and readout electronics. A special focus is put on metamaterials, as a new approach to bring more functionality to detection devices. It is shown that the route is now open towards a fully digital detector head with very high photon counting capability over a large energy range, excellent timing precision and possibility of imaging the energy deposition process.

  16. Optimization of PET scanner geometry

    Energy Technology Data Exchange (ETDEWEB)

    Adam, Lars-Eric; Karp, J.S. [Univ. of Pennsylvania, Department of Radiology, Philadelphia, PA (United States)


    Modern positron emission tomographs (PET), when used for 3D imaging, have a wide open gantry without intra plane septa and only little shielding. In order to reduce the scatter contamination from activity inside and outside the field-of-view (FOV), and to block radiation originating from activity outside-the-FOV, we have investigated the implementation of septa and additional patient shielding on our existing whole body PET scanner. A series of Monte Carlo simulations, based on EGS4, were performed to predict the potential benefits. Our simulations include point and line sources at various radial and axial positions in the FOV of the scanner, and different sized uniform cylinders (up to 100 cm long and 50 cm in diameter). The scanner itself is based on 6 continuous NaI(Tl) crystals, an axial FOV of 25.6 cm, a ring diameter of 90 cm, and a transaxial FOV of 56 cm. The results show that septa can reduce the relative scatter fraction and effectively block radiation from outside-the-FOV, but they also reduce the sensitivity for true events, leading to a decrease of the trues-to-singles ratio that is not desirable. The use of septa is only advantageous for large objects, if the loss of true events is compensated for by increasing the injected activity. Patient shields that are mounted outside-the-FOV reduce the contamination from scattered and single events without interfering with true events. They are more effective for objects with a small diameter and less effective for objects with a large diameter. (author)

  17. Production of an 15O beam using a stable oxygen ion beam for in-beam PET imaging (United States)

    Mohammadi, Akram; Yoshida, Eiji; Tashima, Hideaki; Nishikido, Fumihiko; Inaniwa, Taku; Kitagawa, Atsushi; Yamaya, Taiga


    In advanced ion therapy, the 15O ion beam is a promising candidate to treat hypoxic tumors and simultaneously monitor the delivered dose to a patient using PET imaging. This study aimed at production of an 15O beam by projectile fragmentation of a stable 16O beam in an optimal material, followed by in-beam PET imaging using a prototype OpenPET system, which was developed in the authors' group. The study was carried out in three steps: selection of the optimal target based on the highest production rate of 15O fragments; experimental production of the beam using the optimal target in the Heavy Ion Medical Accelerator Chiba (HIMAC) secondary beam course; and realization of in-beam PET imaging for the produced beam. The optimal target evaluations were done using the Monte Carlo simulation code PHITS. The fluence and mean energy of the secondary particles were simulated and the optimal target was selected based on the production rate of 15O fragments. The highest production rate of 15O was observed for a liquid hydrogen target, 3.27% for a 53 cm thick target from the 16O beam of 430 MeV/u. Since liquid hydrogen is not practically applicable in the HIMAC secondary beam course a hydrogen-rich polyethylene material, which was the second optimal target from the simulation results, was selected as the experimental target. Three polyethylene targets with thicknesses of 5, 11 or 14 cm were used to produce the 15O beam without any degrader in the beam course. The highest production rate was measured as around 0.87% for the 11 cm thick polyethylene target from the 16O beam of 430 MeV/u when the angular acceptance and momentum acceptance were set at ±13 mrad and ±2.5%, respectively. The purity of the produced beam for the three targets were around 75%, insufficient for clinical application, but it was increased to 97% by inserting a wedge shape aluminum degrader with a thickness of 1.76 cm into the beam course and that is sufficiently high. In-beam PET imaging was also

  18. Processing and characterization of extruded PET and its r-PET and MWCNT nanocomposite thin films by spin coating

    Indian Academy of Sciences (India)

    Arvind R Singh; Vineeta D Deshpande


    The objective of the present study was basic understanding of the formation of thin film morphology by spin coating using reorganized polyethylene terephthalate (r-PET) and multiwalled carbon nanotubes (MWCNTs) as fillers in PET. A study of the correlation between physical properties of the PET films and its surface morphology was carried out using atomic force microscopy-based power spectral density (PSD) analysis. No significant work of surface analysis, using PSD of thin films of PET has been reported till date. Dilute solution of PET, PET with 3 wt% (r-PET) and PET with 3 wt% (2 wt% r-PET + 1 wt% MWCNT) filler were prepared using trifluoroacetic acid (TFA) as a solvent and thin films were fabricated on glass substrate by the optimized spin coating technique. Preparation of r-PET and r-PET+ MWCNT fillers was obtained by the precipitation method using TFA as a solvent and acetone as an antisolvent. The samples before spin coating were extruded and for comparison, a film of non-extruded PET was also prepared. Structural studies by Fourier transform infrared and X-ray diffraction show higher degree of crystallinity in r-PET and decrease in chain entanglements. Owing to the crystallizing behaviour of r-PET, it allows better dispersion of MWCNT in the polymer matrix as compared with PET. The samples with fillers of MWCNT show more compact and unique mesh-like globular structure, indicating application for electromagnetic shielding foams and fibres.

  19. Infections That Pets Carry (For Parents) (United States)

    ... rodents — including hamsters and gerbils — as well as fish can place kids at risk for: Lymphocytic choriomeningitis ... especially if your pet goes outdoors. Reviewed by: Stephen C. Eppes, MD Date reviewed: October 2016 previous ...

  20. Cardiovascular physiology and diseases of pet birds. (United States)

    Pees, Michael; Krautwald-Junghanns, Maria-Elisabeth


    Avian cardiac disease in pet birds occurs more often than previously assumed. The article focuses on anatomic peculiarities of the avian cardiovascular system and common diseases. Diagnostic possibilities are demonstrated, and therapeutic measures are discussed.

  1. Autism spectrum disorder and pet therapy. (United States)

    Siewertsen, Caitlin M; French, Emma D; Teramoto, Masaru


    Autism Spectrum Disorder (ASD) encompasses a wide range of social and mental afflictions that are difficult to treat. Due to a lack of established treatments for ASD, alternative therapies have been the primary form of intervention. One of these alternatives is pet therapy, a field that has experienced growing interest and has recently accumulated studies that investigate its efficacy. This article reviews and summarizes that effectiveness as well as the findings and limitations associated with pet therapy for ASD. The majority of research on ASD and pet therapy has examined children and has primarily used dogs and horses for therapy. Studies have shown positive effects for the therapy, including high satisfaction rates among the participants' families. Major limitations of studies in the current literature include the lack of control groups and small sample sizes. Future research should incorporate better study designs and large samples to validate pet therapy as an appropriate treatment for ASD.

  2. FDG PET/CT in cancer

    DEFF Research Database (Denmark)

    Petersen, Henrik; Holdgaard, Paw Christian; Madsen, Poul Henning


    use of PET/CT in the RSD with these recommendations. This article summarizes the results. METHODS: A Work Group appointed a professional Subgroup which made Clinician Groups conduct literature reviews on six selected cancers responsible for 5,768 (62.6 %) of 9,213 PET/CT scans in the RSD in 2012......-recommendable" indications, respectively. RESULTS: Of 11,729 citations, 1,729 were considered for review, and 204 were included. The evidence suggested usefulness of PET/CT in lung, lymphoma, melanoma, head and neck, and colorectal cancers, whereas evidence was sparse in gynaecological cancers. The agreement between actual...... use of PET/CT and literature-based recommendations was high in the first five mentioned cancers in that 96.2 % of scans were made for grade A or B indications versus only 22.2 % in gynaecological cancers. CONCLUSION: Evidence-based usefulness was reported in five of six selected cancers; evidence...

  3. PET/MRI. Methodology and clinical applications

    Energy Technology Data Exchange (ETDEWEB)

    Carrio, Ignasi [Autonomous Univ. of Barcelona, Hospital Sant Pau (Spain). Dept. Medicina Nuclear; Ros, Pablo (ed.) [Univ. Hospitals Case, Medical Center, Cleveland, OH (United States). Dept. of Radiology


    Provides detailed information on the methodology and equipment of MRI-PET. Covers a wide range of clinical applications in oncology, cardiology, and neurology. Written by an international group of experts in MRI and PET. PET/MRI is an exciting novel diagnostic imaging modality that combines the precise anatomic and physiologic information provided by magnetic resonance imaging (MRI) with the molecular data obtained with positron emission tomography (PET). PET/MRI offers the promise of a simplified work flow, reduced radiation, whole-body imaging with superior soft tissue contrast, and time of flight physiologic information. It has been described as the pathway to molecular imaging in medicine. In compiling this textbook, the editors have brought together a truly international group of experts in MRI and PET. The book is divided into two parts. The first part covers methodology and equipment and comprises chapters on basic molecular medicine, development of specific contrast agents, MR attenuation and validation, quantitative MRI and PET motion correction, and technical implications for both MRI and PET. The second part of the book focuses on clinical applications in oncology, cardiology, and neurology. Imaging of major neoplasms, including lymphomas and tumors of the breast, prostate, and head and neck, is covered in individual chapters. Further chapters address functional and metabolic cardiovascular examinations and major central nervous system applications such as brain tumors and dementias. Risks, safety aspects, and healthcare costs and impacts are also discussed. This book will be of interest to all radiologists and nuclear medicine physicians who wish to learn more about the latest developments in this important emerging imaging modality and its applications.

  4. The history of cerebral PET scanning (United States)

    Portnow, Leah H.; Vaillancourt, David E.; Okun, Michael S.


    Objective: To review the discoveries underpinning the introduction of cerebral PET scanning and highlight its modern applications. Background: Important discoveries in neurophysiology, brain metabolism, and radiotracer development in the post–World War II period provided the necessary infrastructure for the first cerebral PET scan. Methods: A complete review of the literature was undertaken to search for primary and secondary sources on the history of PET imaging. Searches were performed in PubMed, Google Scholar, and select individual journal Web sites. Written autobiographies were obtained through the Society for Neuroscience Web site at A reference book on the history of radiology, Naked to the Bone, was reviewed to corroborate facts and to locate references. The references listed in all the articles and books obtained were reviewed. Results: The neurophysiologic sciences required to build cerebral PET imaging date back to 1878. The last 60 years have produced an evolution of technological advancements in brain metabolism and radiotracer development. These advancements facilitated the development of modern cerebral PET imaging. Several key scientists were involved in critical discoveries and among them were Angelo Mosso, Charles Roy, Charles Sherrington, John Fulton, Seymour Kety, Louis Sokoloff, David E. Kuhl, Gordon L. Brownell, Michael Ter-Pogossian, Michael Phelps, and Edward Hoffman. Conclusions: Neurophysiology, metabolism, and radiotracer development in the postwar era synergized the development of the technology necessary for cerebral PET scanning. Continued use of PET in clinical trials and current developments in PET-CT/MRI hybrids has led to advancement in diagnosis, management, and treatment of neurologic disorders. PMID:23460618

  5. Sea otter health: challenging a pet hypothesis (United States)

    Lafferty, Kevin D.


    A recent series of studies on tagged sea otters (Enhydra lutris nereis) challenges the hypothesis that sea otters are sentinels of a dirty ocean, in particular, that pet cats are the main source of exposure to Toxoplasma gondii in central California. Counter to expectations, sea otters from unpopulated stretches of coastline are less healthy and more exposed to parasites than city-associated otters. Ironically, now it seems that spillover from wildlife, not pets, dominates spatial patterns of disease transmission.

  6. Development of robotic plasma radiochemical assays for positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Alexoff, D.L.; Shea, C.; Fowler, J.S.; Gatley, S.J.; Schlyer, D.J. [Brookhaven National Lab., Upton, NY (United States). Dept. of Chemistry


    A commercial laboratory robot system (Zymate PyTechnology II Laboratory Automation System; Zymark Corporation, Hopkinton, MA) was interfaced to standard and custom laboratory equipment and programmed to perform rapid radiochemical analyses for quantitative PET studies. A Zymark XP robot arm was used to carry out the determination of unchanged (parent) radiotracer in plasma using only solid phase extraction methods. Robotic throughput for the assay of parent radiotracer in plasma is 4--6 samples/hour depending on the radiotracer. Robotic assays of parent compound in plasma were validated for the radiotracers [{sup 11}C]Benztropine, [{sup 11}C]cocaine, [{sup 11}C]clorgyline, [{sup 11}C]deprenyl, [{sup 11}C]methadone, [{sup 11}C]methylphenidate, [{sup 11}C]raclorpride, and [{sup 11}C]SR46349B. A simple robot-assisted methods development strategy has been implemented to facilitate the automation of plasma assays of new radiotracers.

  7. PeneloPET, a Monte Carlo PET simulation tool based on PENELOPE: features and validation

    Energy Technology Data Exchange (ETDEWEB)

    Espana, S; Herraiz, J L; Vicente, E; Udias, J M [Grupo de Fisica Nuclear, Departmento de Fisica Atomica, Molecular y Nuclear, Universidad Complutense de Madrid, Madrid (Spain); Vaquero, J J; Desco, M [Unidad de Medicina y CirugIa Experimental, Hospital General Universitario Gregorio Maranon, Madrid (Spain)], E-mail:


    Monte Carlo simulations play an important role in positron emission tomography (PET) imaging, as an essential tool for the research and development of new scanners and for advanced image reconstruction. PeneloPET, a PET-dedicated Monte Carlo tool, is presented and validated in this work. PeneloPET is based on PENELOPE, a Monte Carlo code for the simulation of the transport in matter of electrons, positrons and photons, with energies from a few hundred eV to 1 GeV. PENELOPE is robust, fast and very accurate, but it may be unfriendly to people not acquainted with the FORTRAN programming language. PeneloPET is an easy-to-use application which allows comprehensive simulations of PET systems within PENELOPE. Complex and realistic simulations can be set by modifying a few simple input text files. Different levels of output data are available for analysis, from sinogram and lines-of-response (LORs) histogramming to fully detailed list mode. These data can be further exploited with the preferred programming language, including ROOT. PeneloPET simulates PET systems based on crystal array blocks coupled to photodetectors and allows the user to define radioactive sources, detectors, shielding and other parts of the scanner. The acquisition chain is simulated in high level detail; for instance, the electronic processing can include pile-up rejection mechanisms and time stamping of events, if desired. This paper describes PeneloPET and shows the results of extensive validations and comparisons of simulations against real measurements from commercial acquisition systems. PeneloPET is being extensively employed to improve the image quality of commercial PET systems and for the development of new ones.

  8. Can body volume be determined by PET?

    Energy Technology Data Exchange (ETDEWEB)

    Hentschel, Michael; Paul, Dominik; Mix, Michael; Moser, Ernst; Brink, Ingo [University Hospital Freiburg, Division of Nuclear Medicine, Section of Positron Emission Tomography, Freiburg (Germany); Korsten-Reck, Ulrike [University Hospital Freiburg, Division of Sports Medicine, Freiburg (Germany); Mueller, Frank [PET-Institute Rhein-Neckar, Ludwigshafen (Germany); Merk, Stefan [Kantonsspital Basel, Division of Nuclear Medicine, Basel (Switzerland)


    To avoid dependence on body weight, the standardised uptake value (SUV) in positron emission tomography (PET) can instead be normalised to the lean body mass (LBM), which can be determined from body volume and mass. This study was designed to answer the following questions: Firstly, can the total body volume in principle be determined using PET? Secondly, is the precision of this measurement comparable to that achieved using an established standard method. Ten patients were examined during oncological whole-body PET examinations. The whole-body volume of the patients was determined from the transmission scan in PET. Air displacement plethysmography with BOD POD was used for comparison as the standard method of volume determination. In all patients, the whole-body volumes could be determined using PET and the standard method. Bland and Altman [23] analysis for agreement between the volumes determined by the two methods (presentation of differences vs means) revealed a very small difference of -0.14 l. With a mean patient volume of 71.81{+-}15.93 l, the relative systematic error is only <0.1%. On this basis, equality of the volume values determined by the two methods can be assumed. PET can be used as a supplementary method for experimental determination of whole-body volume and total body fat in tumour patients. The fat content can be used to calculate the LBM and to determine body weight-independent SUVs (SUV{sub LBM}). (orig.)

  9. PET and SPECT imaging in veterinary medicine. (United States)

    LeBlanc, Amy K; Peremans, Kathelijne


    Veterinarians have gained increasing access to positron emission tomography (PET and PET/CT) imaging facilities, allowing them to use this powerful molecular imaging technique for clinical and research applications. SPECT is currently being used more in Europe than in the United States and has been shown to be useful in veterinary oncology and in the evaluation of orthopedic diseases. SPECT brain perfusion and receptor imaging is used to investigate behavioral disorders in animals that have interesting similarities to human psychiatric disorders. This article provides an overview of the potential applications of PET and SPECT. The use of commercially available and investigational PET radiopharmaceuticals in the management of veterinary disease has been discussed. To date, most of the work in this field has utilized the commercially available PET tracer, (18)F-fluorodeoxyglucose for oncologic imaging. Normal biodistribution studies in several companion animal species (cats, dogs, and birds) have been published to assist in lesion detection and interpretation for veterinary radiologists and clinicians. Studies evaluating other (18)F-labeled tracers for research applications are underway at several institutions and companion animal models of human diseases are being increasingly recognized for their value in biomarker and therapy development. Although PET and SPECT technologies are in their infancy for clinical veterinary medicine, increasing access to and interest in these applications and other molecular imaging techniques has led to a greater knowledge and collective body of expertise for veterinarians worldwide. Initiation and fostering of physician-veterinarian collaborations are key components to the forward movement of this field.

  10. Pet fur color and texture classification (United States)

    Yen, Jonathan; Mukherjee, Debarghar; Lim, SukHwan; Tretter, Daniel


    Object segmentation is important in image analysis for imaging tasks such as image rendering and image retrieval. Pet owners have been known to be quite vocal about how important it is to render their pets perfectly. We present here an algorithm for pet (mammal) fur color classification and an algorithm for pet (animal) fur texture classification. Per fur color classification can be applied as a necessary condition for identifying the regions in an image that may contain pets much like the skin tone classification for human flesh detection. As a result of the evolution, fur coloration of all mammals is caused by a natural organic pigment called Melanin and Melanin has only very limited color ranges. We have conducted a statistical analysis and concluded that mammal fur colors can be only in levels of gray or in two colors after the proper color quantization. This pet fur color classification algorithm has been applied for peteye detection. We also present here an algorithm for animal fur texture classification using the recently developed multi-resolution directional sub-band Contourlet transform. The experimental results are very promising as these transforms can identify regions of an image that may contain fur of mammals, scale of reptiles and feather of birds, etc. Combining the color and texture classification, one can have a set of strong classifiers for identifying possible animals in an image.

  11. Sustainable Engineering and Improved Recycling of PET for High-Value Applications: Transforming Linear PET to Lightly Branched PET with a Novel, Scalable Process (United States)

    Pierre, Cynthia; Torkelson, John


    A major challenge for the most effective recycling of poly(ethylene terephthalate) concerns the fact that initial melt processing of PET into a product leads to substantial degradation of molecular weight. Thus, recycled PET has insufficient melt viscosity for reuse in high-value applications such as melt-blowing of PET bottles. Academic and industrial research has tried to remedy this situation by synthesis and use of ``chain extenders'' that can lead to branched PET (with higher melt viscosity than the linear recycled PET) via condensation reactions with functional groups on the PET. Here we show that simple processing of PET via solid-state shear pulverization (SSSP) leads to enhanced PET melt viscosity without need for chemical additives. We hypothesize that this branching results from low levels of chain scission accompanying SSSP, leading to formation of polymeric radicals that participate in chain transfer and combination reactions with other PET chains and thereby to in situ branch formation. The pulverized PET exhibits vastly enhanced crystallization kinetics, eliminating the need to employ cold crystallization to achieve maximum PET crystallinity. Results of SSSP processing of PET will be compared to results obtained with poly(butylene terephthalate).

  12. Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging

    Directory of Open Access Journals (Sweden)

    Vadim Bernard-Gauthier


    Full Text Available Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET imaging have been synthesized and evaluated as diagnostic imaging probes for cancer characterization. Given that inhibitor coverage of the kinome is continuously expanding, in vivo PET imaging will likely find increasing applications for therapy monitoring and receptor density studies both in- and outside of oncological conditions. Early investigated radiolabeled inhibitors, which are mostly based on clinically approved tyrosine kinase inhibitor (TKI isotopologues, have now entered clinical trials. Novel radioligands for cancer and PET neuroimaging originating from novel but relevant target kinases are currently being explored in preclinical studies. This article reviews the literature involving radiotracer design, radiochemistry approaches, biological tracer evaluation and nuclear imaging results of radiolabeled kinase inhibitors for PET reported between 2010 and mid-2015. Aspects regarding the usefulness of pursuing selective vs. promiscuous inhibitor scaffolds and the inherent challenges associated with intracellular enzyme imaging will be discussed.

  13. Imaging with {sup 124}I in differentiated thyroid carcinoma: is PET/MRI superior to PET/CT?

    Energy Technology Data Exchange (ETDEWEB)

    Binse, I.; Poeppel, T.D.; Ruhlmann, M.; Gomez, B.; Bockisch, A.; Rosenbaum-Krumme, S.J. [University of Duisburg-Essen, Medical Faculty, Department of Nuclear Medicine, Essen (Germany); Umutlu, L. [University of Duisburg-Essen, Medical Faculty, Department of Radiology, Essen (Germany)


    The aim of this study was to compare integrated PET/CT and PET/MRI for their usefulness in detecting and categorizing cervical iodine-positive lesions in patients with differentiated thyroid cancer using {sup 124}I as tracer. The study group comprised 65 patients at high risk of iodine-positive metastasis who underwent PET/CT (low-dose CT scan, PET acquisition time 2 min; PET/CT{sub 2}) followed by PET/MRI of the neck 24 h after {sup 124}I administration. PET images from both modalities were analysed for the numbers of tracer-positive lesions. Two different acquisition times were used for the comparisons, one matching the PET/CT{sub 2} acquisition time (2 min, PET/MRI{sub 2}) and the other covering the whole MRI scan time (30 min, PET/MRI{sub 30}). Iodine-positive lesions were categorized as metastasis, thyroid remnant or inconclusive according to their location on the PET/CT images. Morphological information provided by MRI was considered for evaluation of lesions on PET/MRI and for volume information. PET/MRI{sub 2} detected significantly more iodine-positive metastases and thyroid remnants than PET/CT{sub 2} (72 vs. 60, p = 0.002, and 100 vs. 80, p = 0.001, respectively), but the numbers of patients with at least one tumour lesion identified were not significantly different (21/65 vs. 17/65 patients). PET/MRI{sub 30} tended to detect more PET-positive metastases than PET/MRI{sub 2} (88 vs. 72), but the difference was not significant (p = 0.07). Of 21 lesions classified as inconclusive on PET/CT, 5 were assigned to metastasis or thyroid remnant when evaluated by PET/MRI. Volume information was available in 34 % of iodine-positive metastases and 2 % of thyroid remnants on PET/MRI. PET/MRI of the neck was found to be superior to PET/CT in detecting iodine-positive lesions. This was attributed to the higher sensitivity of the PET component, Although helpful in some cases, we found no substantial advantage of PET/MRI over PET/CT in categorizing iodine

  14. Indikationer for anvendelse af PET eller PET/CT hos patienter med brystkræft

    DEFF Research Database (Denmark)

    Bernsdorf, Mogens; Graff, Jesper


    PET and PET/CT, using 18F-fluoro-2-deoxy-D-glucose, are not suited for primary diagnostics of small tumours or lymph node metastases to the axilla. In return, the method has a high sensitivity and specificity regarding the detection of loco-regional recurrence and metastases to mediastinal lymph...

  15. Comparison of C-11-methionine PET and F-18-fluorodeoxyglucose PET in differentiated thyroid cancer

    NARCIS (Netherlands)

    Phan, Ha T. T.; Jager, Pieter L.; Plukker, John T. M.; Wolffenbuttel, Bruce H. R.; Dierckx, Rudi A.; Links, Thera P.


    Background The purpose of this prospective study is to evaluate the possibility of C-11-methionine (Met) PET compared with F-18-fluorodeoxyglucose (FDG) PET for the detection of recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC). Materials and methods Twenty patient

  16. MR-based PET motion correction procedure for simultaneous MR-PET neuroimaging of human brain.

    Directory of Open Access Journals (Sweden)

    Marcus Görge Ullisch

    Full Text Available Positron Emission Tomography (PET images are prone to motion artefacts due to the long acquisition time of PET measurements. Recently, simultaneous magnetic resonance imaging (MRI and PET have become available in the first generation of Hybrid MR-PET scanners. In this work, the elimination of artefacts due to head motion in PET neuroimages is achieved by a new approach utilising MR-based motion tracking in combination with PET list mode data motion correction for simultaneous MR-PET acquisitions. The method comprises accurate MR-based motion measurements, an intra-frame motion minimising and reconstruction time reducing temporal framing algorithm, and a list mode based PET reconstruction which utilises the Ordinary Poisson Algorithm and avoids axial and transaxial compression. Compared to images uncorrected for motion, an increased image quality is shown in phantom as well as in vivo images. In vivo motion corrected images show an evident increase of contrast at the basal ganglia and a good visibility of uptake in tiny structures such as superior colliculi.

  17. Role of FDG-PET and PET/CT in the diagnosis and management of vasculitis

    Energy Technology Data Exchange (ETDEWEB)

    Zerizer, Imene; Tan, Kathryn; Khan, Sameer; Barwick, Tara [Department of Nuclear Medicine, Imperial College Healthcare, Hammersmith Hospital, Du Cane Road, London (United Kingdom); Marzola, Maria Cristina [Department of Nuclear Medicine, PET/CT Centre, Radiology and Medical Physics, ' Santa Maria della Misericordia' Hospital, Rovigo (Italy); Rubello, Domenico [Department of Nuclear Medicine, PET/CT Centre, Radiology and Medical Physics, ' Santa Maria della Misericordia' Hospital, Rovigo (Italy)], E-mail:; Al-Nahhas, Adil [Department of Nuclear Medicine, Imperial College Healthcare, Hammersmith Hospital, Du Cane Road, London (United Kingdom)


    Purpose: to investigate the role of FDG-PET and PET/CT in the evaluation of vasculitis. Materials and methods: a systematic revision of the papers published in PubMed/Medline until December 2009 was done. Results: FDG-PET and PET/CT have been proven to be valuable in the diagnosis of large-vessel vasculitis, especially giant cells arteritis with sensitivity values ranging 77% to 92%, and specificity values ranging 89% to 100%. In particular, FDG-PET/CT has demonstrated the potential to non-invasively diagnose the onset of the vasculitis earlier than traditional anatomical imaging techniques, thus enabling prompt treatment. False positive results mainly occur in the differential diagnosis between vasculitis and atherosclerotic vessels in elderly patients. Another area where FDG-PET/CT is gaining wider acceptance is in monitoring response to therapy; it can reliably detect the earliest changes of disease improvement post-therapy, and persistent activity is an indicator of non-responders to therapy. A few data have been reported about medium/small vessel vasculitis. Discussion: FDG-PET and PET/CT have proven utility: (a) in the initial diagnosis of patients suspected of having vasculitis particularly in those who present with non-specific symptoms; (b) in the identification of areas of increased FDG uptake in which a biopsy should be done for obtaining a diagnosis; (c) in evaluating the extent of the disease; (d) in assessing response to treatment.

  18. Combined therapy with RAD001 e BEZ235 overcomes resistance of PET immortalized cell lines to mTOR inhibition. (United States)

    Passacantilli, Ilaria; Capurso, Gabriele; Archibugi, Livia; Calabretta, Sara; Caldarola, Sara; Loreni, Fabrizio; Delle Fave, Gianfranco; Sette, Claudio


    Pancreatic endocrine tumors (PETs) are characterised by an indolent behaviour in terms of tumor growth. However, most patients display metastasis at diagnosis and no cure is currently available. Since the PI3K/AKT/mTOR axis is deregulated in PETs, the mTOR inhibitor RAD001 represents the first line treatment. Nevertheless, some patients do not respond to treatments and most acquire resistance. Inhibition of mTOR leads to feedback re-activation of PI3K activity, which may promote resistance to RAD001. Thus, PI3K represents a novel potential target for PETs. We tested the impact of three novel PI3K inhibitors (BEZ235, BKM120 and BYL719) on proliferation of PET cells that are responsive (BON-1) or unresponsive (QGP-1) to RAD001. BEZ235 was the most efficient in inhibiting proliferation in PET cells. Furthermore, combined treatment with BEZ235 and RAD001 exhibited synergic effects and was also effective in BON-1 that acquired resistance to RAD001 (BON-1 RR). Analysis of PI3K/AKT/mTOR pathway showed that RAD001 and BEZ235 only partially inhibited mTOR-dependent phosphorylation of 4EBP1. By contrast, combined therapy with the two inhibitors strongly inhibited phosphorylation of 4EBP1, assembly of the translational initiation complex and protein synthesis. Thus, combined treatment with BEZ235 may represent suitable therapy to counteract primary and acquired resistance to RAD001 in PETs.

  19. Pretargeted PET Imaging Using a Site-Specifically Labeled Immunoconjugate. (United States)

    Cook, Brendon E; Adumeau, Pierre; Membreno, Rosemery; Carnazza, Kathryn E; Brand, Christian; Reiner, Thomas; Agnew, Brian J; Lewis, Jason S; Zeglis, Brian M


    In recent years, both site-specific bioconjugation techniques and bioorthogonal pretargeting strategies have emerged as exciting technologies with the potential to improve the safety and efficacy of antibody-based nuclear imaging. In the work at hand, we have combined these two approaches to create a pretargeted PET imaging strategy based on the rapid and bioorthogonal inverse electron demand Diels-Alder reaction between a (64)Cu-labeled tetrazine radioligand ((64)Cu-Tz-SarAr) and a site-specifically modified huA33-trans-cyclooctene immunoconjugate ((ss)huA33-PEG12-TCO). A bioconjugation strategy that harnesses enzymatic transformations and strain-promoted azide-alkyne click chemistry was used to site-specifically append PEGylated TCO moieties to the heavy chain glycans of the colorectal cancer-targeting huA33 antibody. Preclinical in vivo validation studies were performed in athymic nude mice bearing A33 antigen-expressing SW1222 human colorectal carcinoma xenografts. To this end, mice were administered (ss)huA33-PEG12-TCO via tail vein injection and-following accumulation intervals of 24 or 48 h-(64)Cu-Tz-SarAr. PET imaging and biodistribution studies reveal that this strategy clearly delineates tumor tissue as early as 1 h post-injection (6.7 ± 1.7%ID/g at 1 h p.i.), producing images with excellent contrast and high tumor-to-background activity concentration ratios (tumor:muscle = 21.5 ± 5.6 at 24 h p.i.). Furthermore, dosimetric calculations illustrate that this pretargeting approach produces only a fraction of the overall effective dose (0.0214 mSv/MBq; 0.079 rem/mCi) of directly labeled radioimmunoconjugates. Ultimately, this method effectively facilitates the high contrast pretargeted PET imaging of colorectal carcinoma using a site-specifically modified immunoconjugate.

  20. PET and PET-CT. State of the art and future prospects; PET e PET- TC. Stato dell'arte e prospettive future

    Energy Technology Data Exchange (ETDEWEB)

    Fanti, Stefano; Franchi, Roberto [Policlinico S. Orsola-Malpighi, Bologna (Italy). U.O. di medicina legale; Battista, Giuseppe; Monetti, Nino; Canini, Romeo [Bologna Univ., Bologna (Italy). Dipartimento clinico di scienze radiologiche e istocitopatologiche


    Fluoro-deoxyglucose positron emission tomography (FDG PET) enables the in vivo study of tissue metabolism, and thus is able to identify malignant tumours as hypermetabolic lesions by an increase in tracer uptake. Many papers have demonstrated both the relevant impact of FDG PET on staging of many cancers and the superior accuracy of the technique compared with conventional diagnostic methods for pre-treatment evaluation, therapy response evaluation and relapse identification. In particular PET was found useful in identifying lymph nodal and metastatic spread. thus altering patient management in more than 30% of cases. PET images, however, provide limited anatomical data, which in regions such as the head and neck, mediastinum and pelvic cavity is a significant drawback. The exact localization of lesions may also be difficult in some cases, on the basis of PET images alone. The introduction of combined PET-computed tomography (PET-CT) scanners enables the almost simultaneous acquisition of transmission and emission images, thus obtaining optimal fusion images in a very short time. PET-CT fusion images enable lesions to be located, reducing false positive studies and increasing accuracy; the overall duration of examination may also be reduced. On the basis of both literature data and our experience we established the clinical indications when PET-CT may be particularly useful, in comparison with PET alone. It should also be underlined that the use of PET-CT is almost mandatory for new traces such as C-choline and C-methionine; these new tracers may be applied for studying tumours not assessable with FDG, such as prostate cancer. In conclusion PET-CT is at present the most advanced method for metabolic imaging, and is capable of precisely localizing and assessing tumours; fusion images reduce false positive and inconclusive studies, thus increasing diagnostic accuracy. [Italian] La PET con FDG F-18 ha consentito di studiare il metabolismo dei tessuti in vivo e di

  1. Transgenic Animal Mutation Assays

    Institute of Scientific and Technical Information of China (English)

    Tao Chen; Ph.D.D.A.B.T.


    @@ The novel transgenic mouse and rat mutation assays have provided a tool for analyzing in vivo mutation in any tissue, thus permitting the direct comparison of cancer incidence with mutant frequency.

  2. Cell viability assays: introduction. (United States)

    Stoddart, Martin J


    The measurement of cell viability plays a fundamental role in all forms of cell culture. Sometimes it is the main purpose of the experiment, such as in toxicity assays. Alternatively, cell viability can be used to -correlate cell behaviour to cell number, providing a more accurate picture of, for example, anabolic -activity. There are wide arrays of cell viability methods which range from the most routine trypan blue dye exclusion assay to highly complex analysis of individual cells, such as using RAMAN microscopy. The cost, speed, and complexity of equipment required will all play a role in determining the assay used. This chapter aims to provide an overview of many of the assays available today.

  3. Impact of FDG-PET/CT for the Detection of Unknown Primary Tumours in Patients with Cervical Lymph Node Metastases

    Directory of Open Access Journals (Sweden)

    İnanç Karapolat


    Full Text Available Objective: Because the detection of the primary tumour is of importance to optimize the patient’s management and allows a targeted therapy, the performance of hybrid positron emission tomography–computed tomography (PET/CT using fluorodeoxyglucose (FDG in the detection of primary tumors and unrecognized metastases with cervical lymph node metastases were evaluated in a retrospective study. Material and Methods: Twenty patients with cervical lymph node metastases of unknown primary tumors underwent staging with FDG-PET/CT. All underwent head and neck examinations, computed tomography (CT, and/or magnetic resonance imaging (MRI, panendoscopies, and biopsies of head and neck mucosal sites. The diagnostic accuracy of FDG-PET/CT in detecting primary tumors was compared with that of histopathology and clinical follow-up. The ability of FDG-PET/CT to detect distant metastases was also tested. Results: PET/CT was positive with an increased FDG uptake suggesting the potential primary site in 45% of patients (9/20. PET/CT findings were true positive in 7, true negative in 10, false positive in 2, and false negative in 1 patients, resulting in a sensitivity of 87%, a specificity of 83%, an accuracy of 85%, a positive predictive value of 77% and a negative predictive value of 90%. Also, PET/CT showed distant metastases in seven patients. Conclusion: FDG-PET/CT can be successfully used for the identification of the primary site and distant metastases in patients with cervical lymph node metastases from an unknown primary cancer. (MIRT 2012;21:63-68

  4. Present and future of PET and PET/CT in gynaecologic malignancies

    Energy Technology Data Exchange (ETDEWEB)

    Musto, Alessandra [Department of Nuclear Medicine, PET Center, Policlinico Sant' Orsola Malpighi, Bologna University, Bologna (Italy); Rampin, Lucia [Department of Nuclear Medicine, PET Center, Radiology, Medical Physics, Santa Maria della Misericordia Hospital, viale tre martiri 140, 45100 Rovigo (Italy); Nanni, Cristina [Department of Nuclear Medicine, PET Center, Policlinico Sant' Orsola Malpighi, Bologna University, Bologna (Italy); Marzola, Maria Cristina [Department of Nuclear Medicine, PET Center, Radiology, Medical Physics, Santa Maria della Misericordia Hospital, viale tre martiri 140, 45100 Rovigo (Italy); Fanti, Stefano [Department of Nuclear Medicine, PET Center, Policlinico Sant' Orsola Malpighi, Bologna University, Bologna (Italy); Rubello, Domenico, E-mail: [Department of Nuclear Medicine, PET Center, Radiology, Medical Physics, Santa Maria della Misericordia Hospital, viale tre martiri 140, 45100 Rovigo (Italy)


    Objectives: To review the published data in literature on patients affected by gynaecological malignancies to establish the role of {sup 18}F-FDG positron emission tomography (PET) and PET/CT in comparison to conventional imaging (CI). Materials and methods: All papers specifically addressed to the role of {sup 18}F-FDG PET and PET/CT in gynaecological malignancies published on PubMed/Medline, in abstracts from the principal international congresses, in the guidelines from national Societies that had appeared in literature until November 2009 were considered for the purpose of the present study. Results and conclusions: The use of {sup 18}F-FDG PET, and even more of {sup 18}F-FDG PET/CT, is increasing in the follow up of patients with gynaecologic malignancies and suspected recurrent disease: there is evidence in the literature that {sup 18}F-FDG PET/CT has a higher sensitivity than CI in depicting occult metastatic spread. An interesting issue is represented by patients with ovarian cancer with an increase of the specific biomarker, CA-125, and negative/inconclusive findings at CI. The use of {sup 18}F-FDG PET in differential diagnosis and staging is more controversial, but there is some evidence that a baseline PET examination performed before commencing therapy, for staging purpose, is also useful to evaluate the response to chemoradiation treatment. In several papers it has been suggested a relevant role of {sup 18}F-FDG PET/CT in evaluating the entity of response to treatment and therefore to plan the subsequent therapeutic strategy.

  5. New Rapid Spore Assay (United States)

    Kminek, Gerhard; Conley, Catharine


    The presentation will detail approved Planetary Protection specifications for the Rapid Spore Assay for spacecraft components and subsystems. Outlined will be the research and studies on which the specifications were based. The research, funded by ESA and NASA/JPL, was conducted over a period of two years and was followed by limited cleanroom studies to assess the feasibility of this assay during spacecraft assembly.

  6. Dose prescription and treatment planning based on FMISO-PET hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Toma-Dasu, Iuliana; Antonovic, Laura (Medical Radiation Physics, Stockholm Univ. and Karolinska Institutet, Stockholm (Sweden)), E-mail:; Uhrdin, Johan (RaySearch Laboratories AB, Stockholm (Sweden)); Dasu, Alexandru (Dept. of Radiation Physics UHL, County Council of Oestergoetland, Linkoeping (Sweden); Radiation Physics, Dept. of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping Univ., Linkoeping (Sweden)); Nuyts, Sandra; Dirix, Piet; Haustermans, Karin (Leuven Univ. Hospitals, Gasthuisberg, Dept. of Radiotherapy, Leuven (Belgium)); Brahme, Anders (Dept. of Oncology and Pathology, Karolinska Institutet, Stockholm (Sweden))


    Purpose. The study presents the implementation of a novel method for incorporating hypoxia information from PET-CT imaging into treatment planning and estimates the efficiency of various optimization approaches. Its focuses on the feasibility of optimizing treatment plans based on the non-linear conversion of PET hypoxia images into radiosensitivity maps from the uptake properties of the tracers used. Material and methods. PET hypoxia images of seven head-and-neck cancer patients were used to determine optimal dose distributions needed to counteract the radiation resistance associated with tumor hypoxia assuming various scenarios regarding the evolution of the hypoxic compartment during the treatment. A research planning system for advanced studies has been used to optimize IMRT plans based on hypoxia information from patient PET images. These resulting plans were compared in terms of target coverage for the same fulfilled constraints regarding the organs at risk. Results. The results of a planning study indicated the clinical feasibility of the proposed method for treatment planning based on PET hypoxia. Antihypoxic strategies would lead to small improvements in all the patients, but higher effects are expected for the fraction of patients with hypoxic tumors. For these, individualization of the treatment based on hypoxia PET imaging could lead to improved treatment outcome while creating the premises for limiting the irradiation of the surrounding normal tissues. Conclusions. The proposed approach offers the possibility of improved treatment results as it takes into consideration the heterogeneity and the dynamics of the hypoxic regions. It also provides early identification of the clinical cases that might benefit from dose escalation as well as the cases that could benefit from other counter-hypoxic measures

  7. 18-FDG PET/CT assessment of basal cell carcinoma with vismodegib. (United States)

    Thacker, Curtis A; Weiss, Glen J; Tibes, Raoul; Blaydorn, Lisa; Downhour, Molly; White, Erica; Baldwin, Jason; Hoff, Daniel D; Korn, Ronald L


    The use of 18-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT) in subjects with advanced basal cell carcinoma (BCC) has not been fully explored due to the rarity of disease presentation. This study evaluated PET/CTs from subjects with advanced BCC participating in a phase I dose-escalation clinical trial of vismodegib. Fourteen subjects with BCC were imaged with 18-FDG PET/CT for lesion identification and response categorizing (European Organisation for Research and Treatment for Cancer [EORTC] and PET response criteria in solid tumors [PERCIST] 1.0). Several parameters including metabolic activity of target lesions, site of disease presentation and spread, treatment response, and prognostic significance of metabolic activity following therapy were evaluated. All subjects exhibited at least one hypermetabolic lesion. Most subjects had only four organ systems involved at study enrollment: skin-muscle (93%), lung (57%), lymph nodes (29%), and bone (21%). SUVmax measured across all lesions decreased (median 33%, SD ± 45%) following therapy with metabolic activity normalizing or disappearing in 42% of lesions. No significant difference was observed between EORTC and PERCIST 1.0. Subjects that demonstrated at least a 33% reduction in SUVmax from baseline had a significantly longer progression-free survival (PFS) (median 17 months, 95% confidence interval [CI] ±4 months vs. 9 months, 95% CI ±5 months, P = 0.038) and overall survival (OS) (median 24 months, 95% CI ±4 months vs. 17 months, 95% CI ±13 months, P = 0.019). BCC lesions are hypermetabolic on 18-FDG PET/CT. A decrease in SUVmax was associated with improved PFS and OS. These results further support the incorporation of 18-FDG PET/CT scans in advanced BCC management.

  8. Preclinical Evaluation of a Potential GSH Ester Based PET/SPECT Imaging Probe DT(GSHMe₂ to Detect Gamma Glutamyl Transferase Over Expressing Tumors.

    Directory of Open Access Journals (Sweden)

    Harleen Khurana

    Full Text Available Gamma Glutamyl Transferase (GGT is an important biomarker in malignant cancers. The redox processes ensuing from GGT-mediated metabolism of extracellular GSH are implicated in critical aspects of tumor cell biology. Reportedly, Glutathione monoethyl ester (GSHMe is a substrate of GGT, which has been used for its rapid transport over glutathione. Exploring GGT to be an important target, a homobivalent peptide system, DT(GSHMe2 was designed to target GGT-over expressing tumors for diagnostic purposes. DT(GSHMe2 was synthesized, characterized and preclinically evaluated in vitro using toxicity, cell binding assays and time dependent experiments. Stable and defined radiochemistry with 99mTc and 68Ga was optimized for high radiochemical yield. In vivo biodistribution studies were conducted for different time points along with scintigraphic studies of radiolabeled DT(GSHMe2 on xenografted tumor models. For further validation, in silico docking studies were performed on GGT (hGGT1, P19440. Preclinical in vitro evaluations on cell lines suggested minimal toxicity of DT(GSHMe2 at 100 μM concentration. Kinetic analysis revealed transport of 99mTc-DT(GSHMe2 occurs via a saturable high-affinity carrier with Michaelis constant (Km of 2.25 μM and maximal transport rate velocity (Vmax of 0.478 μM/min. Quantitative estimation of GGT expression from western blot experiments showed substantial expression with 41.6 ± 7.07 % IDV for tumor. Small animal micro PET (Positron Emission Tomography/CT(Computed Tomography coregistered images depicted significantly high uptake of DT(GSHMe2 at the BMG-1 tumor site. ROI analysis showed high tumor to contra lateral muscle ratio of 9.33 in PET imaging studies. Avid accumulation of radiotracer was observed at tumor versus inflammation site at 2 h post i.v. injection in an Ehrlich Ascites tumor (EAT mice model, showing evident specificity for tumor. We propose DT(GSHMe2 to be an excellent candidate for prognostication and

  9. PET/MRI in head and neck cancer: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Platzek, Ivan; Laniado, Michael [Dresden University Hospital, Department of Radiology, Dresden (Germany); Beuthien-Baumann, Bettina [Dresden University Hospital, Department of Nuclear Medicine, Dresden (Germany); Schneider, Matthias [Dresden University Hospital, Oral and Maxillofacial Surgery, Dresden (Germany); Gudziol, Volker [Dresden University Hospital, Department of Otolaryngology, Dresden (Germany); Langner, Jens; Schramm, Georg; Hoff, Joerg van den [Institute of Bioinorganic and Radiopharmaceutical Chemistry, Helmholtz-Zentrum Dresden-Rossendorf, Dresden (Germany); Kotzerke, Joerg [Dresden University Hospital, Nuclear Medicine, Dresden (Germany)


    To evaluate the feasibility of PET/MRI (positron emission tomography/magnetic resonance imaging) with FDG ({sup 18}F-fluorodeoxyglucose) for initial staging of head and neck cancer. The study group comprised 20 patients (16 men, 4 women) aged between 52 and 81 years (median 64 years) with histologically proven squamous cell carcinoma of the head and neck region. The patients underwent a PET scan on a conventional scanner and a subsequent PET/MRI examination on a whole-body hyb