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  1. Plasma membrane ordering agent pluronic F-68 (PF-68) reduces neurotransmitter uptake and release and produces learning and memory deficits in rats

    Science.gov (United States)

    Clarke, M. S.; Prendergast, M. A.; Terry, A. V. Jr

    1999-01-01

    A substantial body of evidence indicates that aged-related changes in the fluidity and lipid composition of the plasma membrane contribute to cellular dysfunction in humans and other mammalian species. In the CNS, reductions in neuronal plasma membrane order (PMO) (i.e., increased plasma membrane fluidity) have been attributed to age as well as the presence of the beta-amyloid peptide-25-35, known to play an important role in the neuropathology of Alzheimer's disease (AD). These PMO increases may influence neurotransmitter synthesis, receptor binding, and second messenger systems as well as signal transduction pathways. The effects of neuronal PMO on learning and memory processes have not been adequately investigated, however. Based on the hypothesis that an increase in PMO may alter a number of aspects of synaptic transmission, we investigated several neurochemical and behavioral effects of the membrane ordering agent, PF-68. In cell culture, PF-68 (nmoles/mg SDS extractable protein) reduced [3H]norepinephrine (NE) uptake into differentiated PC-12 cells as well as reduced nicotine stimulated [3H]NE release. The compound (800-2400 microg/kg, i.p., resulting in nmoles/mg SDS extractable protein in the brain) decreased step-through latencies and increased the frequencies of crossing into the unsafe side of the chamber in inhibitory avoidance training. In the Morris water maze, PF-68 increased the latencies and swim distances required to locate a hidden platform and reduced the time spent and distance swam in the previous target quadrant during transfer (probe) trials. PF-68 did not impair performance of a well-learned working memory task, the rat delayed stimulus discrimination task (DSDT), however. Studies with 14C-labeled PF-68 indicated that significant (pmoles/mg wet tissue) levels of the compound entered the brain from peripheral (i.p.) injection. No PF-68 related changes were observed in swim speeds or in visual acuity tests in water maze experiments, rotorod

  2. Novel behavior of heat of micellization of pluronics F68 and F88 in aqueous solutions.

    Science.gov (United States)

    Tsui, Hung-Wei; Hsu, Ya-Huei; Wang, Jing-Han; Chen, Li-Jen

    2008-12-16

    It is well understood that the heat of micellization for surfactants is monotonically decreased along with an increase in temperature. However, this behavior for polymeric surfactants has never been carefully examined. In this study, the heat of micellization of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers (Pluronics F68 and F88) in water as a function of temperature is carefully examined by using a high-sensitivity differential scanning calorimeter (HSDSC). The critical micelle temperature (CMT) decreases along with an increase in the concentration of Pluronic F68 (or F88). The heat of micellization decreases along with an increase in the temperature, as expected, when the CMT is higher than 55 and 42 degrees C for Pluronics F68 and F88, respectively. It is interesting to observe that the heat of micellization increases along with the temperature while the temperature is below 55 and 42 degrees C for Pluronics F68 and F88, respectively. The enthalpy-entropy compensation phenomenon for the micellization of Pluronics F68 and F88 in connection with the hydrophobicity is discussed.

  3. Vitamin E succinate-conjugated F68 micelles for mitoxantrone delivery in enhancing anticancer activity

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    Liu Y

    2016-07-01

    Full Text Available Yuling Liu,1,* Yingqi Xu,2,* Minghui Wu,3 Lijiao Fan,1 Chengwei He,2 Jian-Bo Wan,2 Peng Li,2 Meiwan Chen,2 Hui Li11Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China; 2State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People’s Republic of China; 3Department of Cell Biology and Anatomy, School of Medicine, University of Florida, Gainesville, FL, USA *These authors contributed equally to this work Abstract: Mitoxantrone (MIT is a chemotherapeutic agent with promising anticancer efficacy. In this study, Pluronic F68-vitamine E succinate (F68-VES amphiphilic polymer micelles were developed for delivering MIT and enhancing its anticancer activity. MIT-loaded F68–VES (F68–VES/MIT micelles were prepared via the solvent evaporation method with self-assembly under aqueous conditions. F68–VES/MIT micelles were found to be of optimal particle size with the narrow size distribution. Transmission electron microscopy images of F68–VES/MIT micelles showed homogeneous spherical shapes and smooth surfaces. F68–VES micelles had a low critical micelle concentration value of 3.311 mg/L, as well as high encapsulation efficiency and drug loading. Moreover, F68–VES/MIT micelles were stable in the presence of fetal bovine serum for 24 hours and maintained sustained drug release in vitro. Remarkably, the half maximal inhibitory concentration (IC50 value of F68–VES/MIT micelles was lower than that of free MIT in both MDA-MB-231 and MCF-7 cells (two human breast cancer cell lines. In addition, compared with free MIT, there was an increased trend of apoptosis and cellular uptake of F68–VES/MIT micelles in MDA-MB-231 cells. Taken together, these results indicated that F68–VES polymer micelles were able to effectively deliver MIT and largely improve its potency in cancer therapy. Keywords: F68, vitamin E

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

    International Nuclear Information System (INIS)

    Thackeray, James T.; Bankstahl, Jens P.; Walte, Almut; Wittneben, Alexander; Bengel, Frank M.; Wang, Yong; Korf-Klingebiel, Mortimer; Wollert, Kai C.

    2015-01-01

    Imaging of inflammation early after myocardial infarction (MI) is a promising approach to the guidance of novel molecular interventions that support endogenous healing processes. 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 68 Ga-citrate and somatostatin receptor binding by 68 Ga-DOTATATE. C57Bl/6 mice underwent permanent coronary artery ligation. Serial PET imaging was performed 3 - 7 days after MI using 68 Ga-citrate, 68 Ga-DOTATATE, or 18 F-FDG with ketamine/xylazine suppression of myocyte glucose uptake. Myocardial perfusion was evaluated by 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. 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). 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). 68 Ga-DOTATATE was rapidly cleared from the blood, but myocardial SUV was very low (0.10 ± 0.03). Neither 68 Ga nor 68 Ga-DOTATATE is a useful alternative to 18 F-FDG for PET imaging of myocardial inflammation after MI in mice. Among the three tested approaches, 18 F-FDG with ketamine/xylazine suppression of cardiomyocyte uptake remains the most practical imaging marker of post-infarct inflammation. (orig.)

  5. 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)

    2014-08-12

    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.)

  6. Studies of adsorber materials for preparing 68Ge/68Ga generators

    International Nuclear Information System (INIS)

    Brambilla, Tania de Paula

    2013-01-01

    The 68 Ga is a promising radionuclide for nuclear medicine, decaying by positron emission with an abundance of 89%, with physical half-life of 68 minutes, which is compatible with the pharmacokinetics of many biomolecules and low molecular weight substrates. Another important feature is its availability through a generator system, where the parent radionuclide, 68 Ge (t 1/2 = 270.95 days) is adsorbed on a column and the daughter, 68 Ga, is eluted in an ionic form 68Ga 3+ . The development of 68 Ge/ 68 Ga generators began in the 60s, but its clinical use began to be acceptable and relevant only recently. The method of separation of 68 Ge and 68 Ga most used is the ion-exchange chromatographic system, due to its practical operation, but other generator systems have been proposed, such as solvent extraction and evaporation technique. Currently, 68 Ge/ 68 Ga generators are commercially available using inorganic matrices columns prepared with TiO 2 or SnO 2 as well using organic resin. The efficiency of 68 Ga elution ranges from 70% to 80%, decreasing over time. The 68 Ge breakthrough varies from 10 -2 to10 -3 % or lower in a fresh generator, but there is an increase in the levels of contamination after long periods of use. Even with all the technological advances in the development of 68 Ge/ 68 Ga generators in the past decades, the 68 Ga eluted from commercial generators is not suitable for direct use in humans and some improvements in the systems need to be made to reduce the 68 Ge breakthrough and chemical impurities levels. The main objective of this work was to develop a 68 Ge/ 68 Ga generator system is which 68 Ga could be eluted with quality required for clinical use. The chemical behavior of Ge and Ga was evaluated on various inorganic adsorbents materials. Two types of 68 Ge/ 68 Ga generator systems were developed using TiO 2 as adsorbent material: elution system with manual pressure and vacuum controlled. The efficiencies of the generators were similar to

  7. Clinical applications of Gallium-68

    International Nuclear Information System (INIS)

    Banerjee, Sangeeta Ray; Pomper, Martin G.

    2013-01-01

    Gallium-68 is a positron-emitting radioisotope that is produced from a 68 Ge/ 68 Ga generator. As such it is conveniently used, decoupling radiopharmacies from the need for a cyclotron on site. Gallium-68-labeled peptides have been recognized as a new class of radiopharmaceuticals showing fast target localization and blood clearance. 68 Ga-DOTATOC, 8 Ga-DOTATATE, 68 Ga-DOTANOC, are the most prominent radiopharmaceuticals currently in use for imaging and differentiating lesions of various somatostatin receptor subtypes, overexpressed in many neuroendocrine tumors. There has been a tremendous increase in the number of clinical studies with 68 Ga over the past few years around the world, including within the United States. An estimated ∼10,000 scans are being performed yearly in Europe at about 100 centers utilizing 68 Ga-labeled somatostatin analogs within clinical trials. Two academic sites within the US have also begun to undertake human studies. This review will focus on the clinical experience of selected, well-established and recently applied 68 Ga-labeled imaging agents used in nuclear medicine. - Highlights: ► A summary of the emerging clinical uses of 68 Ga-based radiopharmaceuticals is provided. ► 68 Ga-PET may prove as or more clinically robust than the corresponding 18 F-labeled agents. ► 68 Ga-radiopeptides were studied for targeting of somatostatin receptors subtypes. ► 68 Ga-DOTATOC, 68 Ga-DOTATATE, 68 Ga-DOTANOC, are currently in clinical trials

  8. Tick-Borne Transmission of Murine Gammaherpesvirus 68

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    Valeria Hajnická

    2017-10-01

    Full Text Available Herpesviruses are a large group of DNA viruses infecting mainly vertebrates. Murine gammaherpesvirus 68 (MHV68 is often used as a model in studies of the pathogenesis of clinically important human gammaherpesviruses such as Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. This rodent virus appears to be geographically widespread; however, its natural transmission cycle is unknown. Following detection of MHV68 in field-collected ticks, including isolation of the virus from tick salivary glands and ovaries, we investigated whether MHV68 is a tick-borne virus. Uninfected Ixodes ricinus ticks were shown to acquire the virus by feeding on experimentally infected laboratory mice. The virus survived tick molting, and the molted ticks transmitted the virus to uninfected laboratory mice on which they subsequently fed. MHV68 was isolated from the tick salivary glands, consistent with transmission via tick saliva. The virus survived in ticks without loss of infectivity for at least 120 days, and subsequently was transmitted vertically from one tick generation to the next, surviving more than 500 days. Furthermore, the F1 generation (derived from F0 infected females transmitted MHV68 to uninfected mice on which they fed, with MHV68 M3 gene transcripts detected in blood, lung, and spleen tissue of mice on which F1 nymphs and F1 adults engorged. These experimental data fulfill the transmission criteria that define an arthropod-borne virus (arbovirus, the largest biological group of viruses. Currently, African swine fever virus (ASFV is the only DNA virus recognized as an arbovirus. Like ASFV, MHV68 showed evidence of pathogenesis in ticks. Previous studies have reported MHV68 in free-living ticks and in mammals commonly infested with I. ricinus, and neutralizing antibodies to MHV68 have been detected in large mammals (e.g., deer including humans. Further studies are needed to determine if these reports are the result of tick-borne transmission

  9. A Novel Docetaxel-Loaded Poly (ɛ-Caprolactone)/Pluronic F68 Nanoparticle Overcoming Multidrug Resistance for Breast Cancer Treatment

    Science.gov (United States)

    Mei, Lin; Zhang, Yangqing; Zheng, Yi; Tian, Ge; Song, Cunxian; Yang, Dongye; Chen, Hongli; Sun, Hongfan; Tian, Yan; Liu, Kexin; Li, Zhen; Huang, Laiqiang

    2009-12-01

    Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ɛ-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere® in the MCF-7 TAX30 cell culture, but the differences were not significant ( p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere® ( p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer.

  10. Comparison of 68Ga-DOTA-Siglec-9 and 18F-Fluorodeoxyribose-Siglec-9: Inflammation Imaging and Radiation Dosimetry.

    Science.gov (United States)

    Virtanen, Helena; Silvola, Johanna M U; Autio, Anu; Li, Xiang-Guo; Liljenbäck, Heidi; Hellberg, Sanna; Siitonen, Riikka; Ståhle, Mia; Käkelä, Meeri; Airaksinen, Anu J; Helariutta, Kerttuli; Tolvanen, Tuula; Veres, Tibor Z; Saraste, Antti; Knuuti, Juhani; Jalkanen, Sirpa; Roivainen, Anne

    2017-01-01

    Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of inflammation-inducible vascular adhesion protein-1 (VAP-1). We compared 68 Ga-DOTA- and 18 F-fluorodeoxyribose- (FDR-) labeled Siglec-9 motif peptides for PET imaging of inflammation. Methods . Firstly, we examined 68 Ga-DOTA-Siglec-9 and 18 F-FDR-Siglec-9 in rats with skin/muscle inflammation. We then studied 18 F-FDR-Siglec-9 for the detection of inflamed atherosclerotic plaques in mice and compared it with previous 68 Ga-DOTA-Siglec-9 results. Lastly, we estimated human radiation dosimetry from the rat data. Results . In rats, 68 Ga-DOTA-Siglec-9 (SUV, 0.88 ± 0.087) and 18 F-FDR-Siglec-9 (SUV, 0.77 ± 0.22) showed comparable ( P = 0.29) imaging of inflammation. In atherosclerotic mice, 18 F-FDR-Siglec-9 detected inflamed plaques with a target-to-background ratio (1.6 ± 0.078) similar to previously tested 68 Ga-DOTA-Siglec-9 ( P = 0.35). Human effective dose estimates for 68 Ga-DOTA-Siglec-9 and 18 F-FDR-Siglec-9 were 0.024 and 0.022 mSv/MBq, respectively. Conclusion . Both tracers are suitable for PET imaging of inflammation. The easier production and lower cost of 68 Ga-DOTA-Siglec-9 present advantages over 18 F-FDR-Siglec-9, indicating it as a primary choice for clinical studies.

  11. Multicenter comparison of 18F-FDG and 68Ga-DOTA-peptide PET/CT for pulmonary carcinoid.

    Science.gov (United States)

    Lococo, Filippo; Perotti, Germano; Cardillo, Giuseppe; De Waure, Chiara; Filice, Angelina; Graziano, Paolo; Rossi, Giulio; Sgarbi, Giorgio; Stefanelli, Antonella; Giordano, Alessandro; Granone, Pierluigi; Rindi, Guido; Versari, Annibale; Rufini, Vittoria

    2015-03-01

    The aims of this study were to retrospectively evaluate and compare the detection rate (DR) of 68Ga-DOTA-peptide and 18F-FDG PET/CT in the preoperative workup of patients with pulmonary carcinoid (PC) and to assess the utility of various functional indices obtained with the 2 tracers in predicting the histological characterization of PC, that is, typical versus atypical. Thirty-three consecutive patients with confirmed PC referred for 18F-FDG and 68Ga-DOTA-peptide PET/CT in 2 centers between January 2009 and April 2013 were included. The semiquantitative evaluation included the SUV max, the SUV of the tumor relative to the maximal liver uptake for 18F-FDG (SUV T/L) or the maximal spleen uptake for 68Ga-DOTA-peptides (SUV T/S), the ratio between SUV max of 68Ga-DOTA-peptides PET/CT, and the SUV max of 18F-FDG PET/CT (SUV max ratio). Histology was used as reference standard. Definitive diagnosis consisted of 23 typical carcinoids (TCs) and 10 atypical carcinoids. 18F-FDG PET/CT was positive in 18 cases and negative in 15 (55% DR). 68Ga-DOTA-peptide PET/CT was positive in 26 cases and negative in 7 (79% DR). In the subgroup analysis, 68Ga-DOTA-peptide PET/CT was superior in detecting TC (91% DR; P DOTA-peptide PET/CT findings. In the subgroup analysis, the SUV max ratio seems to be the most accurate index in predicting TC. Both methods should be performed when PC is suspected or when the histological subtype is undefined.

  12. GhWRKY68 reduces resistance to salt and drought in transgenic Nicotiana benthamiana.

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    Haihong Jia

    Full Text Available The WRKY transcription factors modulate numerous physiological processes, including plant growth, development and responses to various environmental stresses. Currently, our understanding of the functions of the majority of the WRKY family members and their possible roles in signalling crosstalk is limited. In particular, very few WRKYs have been identified and characterised from an economically important crop, cotton. In this study, we characterised a novel group IIc WRKY gene, GhWRKY68, which is induced by different abiotic stresses and multiple defence-related signalling molecules. The β-glucuronidase activity driven by the GhWRKY68 promoter was enhanced after exposure to drought, salt, abscisic acid (ABA and H2O2. The overexpression of GhWRKY68 in Nicotiana benthamiana reduced resistance to drought and salt and affected several physiological indices. GhWRKY68 may mediate salt and drought responses by modulating ABA content and enhancing the transcript levels of ABA-responsive genes. GhWRKY68-overexpressing plants exhibited reduced tolerance to oxidative stress after drought and salt stress treatments, which correlated with the accumulation of reactive oxygen species (ROS, reduced enzyme activities, elevated malondialdehyde (MDA content and altered ROS-related gene expression. These results indicate that GhWRKY68 is a transcription factor that responds to drought and salt stresses by regulating ABA signalling and modulating cellular ROS.

  13. Development of 68Ge/68Ga Generator using 30 MeV Cyclotron

    International Nuclear Information System (INIS)

    Goo, Hur Min; Dae, Yang Seung; Hoon, Park Jeong; Dae, Park Yong; Je, Lee Eun; Bae, Kong Young; Kim, In Jong; Lee, Jin Woo; Hyun, Yu Kook

    2012-05-01

    The purpose of this research is to develop the 68 Ge/ 68 Ga generator where daughter nuclide 68 Ga can be eluted according to the designated periods from the resin which holds mother nuclide 68 Ge absorbed and to develop the 68 Ga utilization technology. 1. Target development for 68 Ge target and production of 68 Ge - Target designed for 68 Ge production with 30 MeV cyclotron - Target body material evaluation and proton beam irradiation 2. Separation of 68 Ge and development of column material and extraction system for 68 Ge/ 68 Ga separation - Development of 68 Ge separation method from nat Ga target - Development of absorbents for generator using stable isotope 3. Development of 68 Ga labelled radiopharmaceutical - Development of 68 Ga labelled benzamide derivative for diagnosis of melanoma - Development of 68 Ga dendrimer complex using nano-technology 4. Development of shield case for 68 Ge/ 68 Ga generator

  14. Studies on the preparation of {sup 68}Ge-{sup 68}Ga generator with inorganic materials

    Energy Technology Data Exchange (ETDEWEB)

    Brambilla, Tania P.; Osso Junior, Joao A., E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    {sup 68}Ga as a positron emitter is of great interest because of some important advantages. It has a physical half-life of 67.71 min, which is compatible with the pharmacokinetics of many radiopharmaceuticals of low molecular weight. Other important characteristic is its cyclotron-independent availability via the {sup 68}Ge-{sup 68}Ga radionuclide generator system. In Brazil only one positron emitter radionuclide is produced, {sup 18}F, and the medical class has a great interest in using {sup 68}Ga labeled molecules, in particular peptides such as DOTA-octriotide. A project for developing a home made {sup 68}Ge-{sup 68}Ga is under way at IPEN-CNEN/SP. The aim of this work is to develop an efficient and simplified generator system of {sup 68}Ge-{sup 68}Ga that offers {sup 68}Ga{sup 3+} adequate for clinical use. Initial results will be reported concerning the behavior of Ge and Ga in adsorbers such as calcined acid and basic Al{sub 2}O{sub 3}, HZO (hydrous zirconium oxide), TiO{sub 2}, microspheres of Zr (Zr mic) and microspheres of Al (Al mic). Adsorption studies were carried out using {gamma}-emitting tracers, {sup 67}Ga and {sup 68}Ga and chemical tracer, GeO{sub 2}. The samples containing {sup 67}/{sup 68}Ga were analysed using a dose calibrator CRC-15R from Capintec and the samples containing Ge were evaluated by the Optical Emission Spectrometry using Inductively Coupled Plasma (ICP-OES). The ICP-OES equipment used was a Varian Vista-MPX from Varian and calibration curves for Ge were constructed in the range of 0.2 to 1.0 {mu}g.mL{sup -1}. The use of basic Al{sub 2}O{sub 3}, TiO{sub 2}, HZO and Zr mic showed the more promising results. (author)

  15. Meningiomas: A Comparative Study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for Molecular Imaging in Mice

    Science.gov (United States)

    Soto-Montenegro, María Luisa; Peña-Zalbidea, Santiago; Mateos-Pérez, Jose María; Oteo, Marta; Romero, Eduardo; Morcillo, Miguel Ángel; Desco, Manuel

    2014-01-01

    Purpose The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three 68Ga-DOTA-labeled somatostatin analogues (68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE) using PET/CT in a murine model with subcutaneous meningioma xenografts. Methods The experiment was performed with 16 male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH-157MN). 68Ga-DOTATOC, 68Ga-DOTANOC, and 68Ga-DOTATATE were produced in a FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT scanner. The SUVmax of the liver and muscle, and the tumor-to-liver (T/L) and tumor-to-muscle (T/M) SUV ratios were computed. Kinetic analysis was performed using Logan graphical analysis for a two-tissue reversible compartmental model, and the volume of distribution (Vt) was determined. Results Hepatic SUVmax and Vt were significantly higher with 68Ga-DOTANOC than with 68Ga-DOTATOC and 68Ga-DOTATATE. No significant differences between tracers were found for SUVmax in tumor or muscle. No differences were found in the T/L SUV ratio between 68Ga-DOTATATE and 68Ga-DOTATOC, both of which had a higher fraction than 68Ga-DOTANOC. The T/M SUV ratio was significantly higher with 68Ga-DOTATATE than with 68Ga-DOTATOC and 68Ga-DOTANOC. The Vt for tumor was higher with 68Ga-DOTATATE than with 68Ga-DOTANOC and relatively similar to that of 68Ga-DOTATOC. Conclusions This study demonstrates, for the first time, the ability of the three radiolabeled somatostatin analogues tested to image a human meningioma cell line. Although Vt was relatively similar with 68Ga-DOTATATE and 68Ga-DOTATOC, uptake was higher with 68Ga-DOTATATE in the tumor than with 68Ga-DOTANOC and 68Ga-DOTATOC, suggesting a higher diagnostic value of 68Ga-DOTATATE for detecting meningiomas. PMID:25369268

  16. Meningiomas: a comparative study of 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE for molecular imaging in mice.

    Directory of Open Access Journals (Sweden)

    María Luisa Soto-Montenegro

    Full Text Available The goal of this study was to compare the tumor uptake kinetics and diagnostic value of three (68Ga-DOTA-labeled somatostatin analogues ((68Ga-DOTATOC, (68Ga-DOTANOC, and (68Ga-DOTATATE using PET/CT in a murine model with subcutaneous meningioma xenografts.The experiment was performed with 16 male NUDE NU/NU mice bearing xenografts of a human meningioma cell line (CH-157MN. (68Ga-DOTATOC, (68Ga-DOTANOC, and (68Ga-DOTATATE were produced in a FASTLab automated platform. Imaging was performed on an Argus small-animal PET/CT scanner. The SUVmax of the liver and muscle, and the tumor-to-liver (T/L and tumor-to-muscle (T/M SUV ratios were computed. Kinetic analysis was performed using Logan graphical analysis for a two-tissue reversible compartmental model, and the volume of distribution (Vt was determined.Hepatic SUVmax and Vt were significantly higher with (68Ga-DOTANOC than with (68Ga-DOTATOC and (68Ga-DOTATATE. No significant differences between tracers were found for SUVmax in tumor or muscle. No differences were found in the T/L SUV ratio between (68Ga-DOTATATE and (68Ga-DOTATOC, both of which had a higher fraction than (68Ga-DOTANOC. The T/M SUV ratio was significantly higher with (68Ga-DOTATATE than with (68Ga-DOTATOC and (68Ga-DOTANOC. The Vt for tumor was higher with (68Ga-DOTATATE than with (68Ga-DOTANOC and relatively similar to that of (68Ga-DOTATOC.This study demonstrates, for the first time, the ability of the three radiolabeled somatostatin analogues tested to image a human meningioma cell line. Although Vt was relatively similar with (68Ga-DOTATATE and (68Ga-DOTATOC, uptake was higher with (68Ga-DOTATATE in the tumor than with (68Ga-DOTANOC and (68Ga-DOTATOC, suggesting a higher diagnostic value of (68Ga-DOTATATE for detecting meningiomas.

  17. Probing the semi-magicity of $^{68}$Ni via the $^{66}$Ni(t,p)$^{68}$Ni two-neutron transfer reaction in inverse kinematics

    CERN Document Server

    AUTHOR|(CDS)2079390; Van Duppen, Piet

    The region around the nucleus $^{68}$Ni, with a shell closure for its protons at Z=28 and a harmonic oscillator shell gap for its neutrons at N=40, has drawn considerable interest over the past decades. $^{68}$Ni has properties that are typical for a doubly-magic nucleus, such as a high excitation energy and low B($E2:2^{+} \\rightarrow 0^{+}$) transition probability for the first excited 2$^{+}$ level and a 0$^{+}$ level as the first excited state. However, it has been suggested that the magic properties of $^{68}$Ni arise due to the fact that the N=40 separates the negative parity $pf$-shell from the positive parity 1$g_{9/2}$ orbital, and indeed, recent mass measurements have not revealed a clear N = 40 energy gap. Despite all additional information that was acquired over the last decade the specific role of the N=40 is not yet understood and a new experimental approach to study $^{68}$Ni was proposed. Namely, a two-neutron transfer reaction on $^{66}$Ni to characterize and disentangle the structure of the ...

  18. Comparison of (68)Ga-DOTA-Tyr(3)-octreotide and (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography in neuroendocrine tumor patients.

    Science.gov (United States)

    Putzer, D; Gabriel, M; Kendler, D; Henninger, B; Knoflach, M; Kroiss, A; Vonguggenberg, E; Warwitz, B; Virgolini, I J

    2010-02-01

    (68)Ga-DOTA-Tyr3-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) and (18)F-fluoro-L-dihydroxyphenylalanine PET ((18)F-DOPA PET) are emerging modalities for imaging of neuroendocrine tumors. This study reports our initial experiences with these two PET modalities on initial diagnosis, staging and restaging in NET patients. Fifteen patients with NET underwent both (68)Ga-DOTA-TOC and (18)F-DOPA PET as well as computed tomography (CT). Image findings were compared on a patient-basis (pathological uptake: yes/no) as well as on a lesion-basis. Contrast-enhanced CT and histological follow-up served as gold standard. Furthermore, imaging results were matched with tumor marker levels and quantitative tracer uptake by the tumor lesions. When comparing (68)Ga-DOTA-TOC and (18)F-DOPA PET, each modality showed a sensitivity of 64% and a specificity of 100% on a patient-based analysis. (68)Ga-DOTA-TOC PET and (18)F-DOPA PET showed equal findings in 7 out of 15 patients and disagreement in 8 patients. (68)Ga-DOTA-TOC revealed more metastases than (18)F-DOPA PET in 6 patients, while (18)F-DOPA PET detected more metastases than (68)Ga-DOTA-TOC in 4 patients. By (68)Ga-DOTA-TOC PET, 208 malignant lesions were detected, while by (18)F-DOPA only 86 lesions were found, and in CT 124, respectively. (68)Ga-DOTA-TOC and (18)F-DOPA PET are useful tools in the detection and staging of NET lesions. Our initial results allow the conclusion that (68)Ga-DOTA-TOC PET may have a stronger clinical impact in NET patients, as it does not only offer diagnostic information, but is decisive for the further treatment management, i. e. PRRT, as well.

  19. Continuation of comprehensive quality control of the itG 68Ge/68Ga generator and production of 68Ga-DOTATOC and 68Ga-PSMA-HBED-CC for clinical research studies.

    Science.gov (United States)

    Amor-Coarasa, Alejandro; Kelly, James M; Gruca, Monika; Nikolopoulou, Anastasia; Vallabhajosula, Shankar; Babich, John W

    2017-10-01

    Performance of a second itG 68 Ge/ 68 Ga generator system and production of 68 Ga-DOTATOC and 68 Ga-PSMA-HBED-CC were tested over one year as an accompaniment to a previously published study (J Nucl Med. 2016;57:1402-1405). Performance of a 1951MBq 68 Ge/ 68 Ga generator was characterized and the eluate used for preparation of 68 Ga-DOTATOC and 68 Ga-PSMA-HBED-CC. Weekly elution profiles of 68 Ga elution yield and 68 Ge breakthrough were determined. 68 Ga elution yields averaged 82% (61.8-98.4%) and 68 Ge breakthrough averaged 0.002% (0.0007% to 0.004%). The radiochemical purities of 68 Ga-DOTATOC and 68 Ga-PSMA-HBED-CC were determined by HPLC analysis to be >98% and specific activity was 12.6 and 42GBq/μmol, respectively. 68 Ge contamination in the product was under the detection limit (0.00001%). Final sterile, pyrogen-free formulation of 68 Ga-DOTATOC and 68 Ga-PSMA-HBED-CC in physiologic saline with 5%-7% ethanol was achieved. Performance of a 68 Ge/ 68 Ga generator was studied over one year with satisfactory results. The generator eluate was used to synthesize 68 Ga-DOTATOC and 68 Ga-PSMA-HBED-CC on a routine basis in high purity. Copyright © 2017. Published by Elsevier Inc.

  20. Pilot study of 68Ga-DOTA-F(ab?)2-trastuzumab in patients with breast cancer

    OpenAIRE

    Beylergil, Volkan; Morris, Patrick G.; Smith-Jones, Peter M.; Modi, Shanu; Solit, David; Hudis, Clifford A.; Lu, Yang; O?Donoghue, Joseph; Lyashchenko, Serge K.; Carrasquillo, Jorge A.; Larson, Steven M.; Akhurst, Timothy J.

    2013-01-01

    Objective 68Ga-1,4,7,10-Tetraazacyclododecane-N,N?,N??,N???-tetraacetic acid (DOTA)-F(ab?)2-trastuzumab [68Ga-DOTA-F(ab?)2-trastuzumab] has been developed at our institution as a positron imaging reagent for assessing human epidermal growth factor receptor 2 (HER2) expression status by in-vivo imaging. Initial studies on animals demonstrated promising results in the monitoring of treatment response to heat shock protein 90-targeted drugs that inhibit the client protein HER2. We report here ou...

  1. Production of a 68Ge/68Ga generator

    International Nuclear Information System (INIS)

    Behrouz Shirazi; Behrouz Fateh; Mohammad Mirzaii; Gholamreza Aslani

    2004-01-01

    Background: Gallium-68 is a radioisotope with a half life of 68 min. As it has a specific decay mode, it is a positron emitter and hence, it is popularly used in nuclear medicine. The only way to obtain these nuclides is to produced the mother nuclease which is Germanium - 68. There are many nuclear reactions from which the Germanium - 68 is obtained, however, the best reaction is 69Ga (p,2n)68Ge. Materials and Methods: The cross section of this nuclear reaction was calculated with the ALICE-91 Code and the result was compared with the practical work done by other researchers. The comparing result was an acceptable one. Having the cross sections in mind, the best proton energy was calculated to be between 20-25 MeV Further research showed that Ga2O3 is the best type of target material. Therefore, it was necessary to design and make a suitable target holder for these k/nd of compositions, which for the very first time in Iran was done at Atomic Energy Organization of Iran (AEOI). The thickness of the target, bearing in mind the rate of energy loss in side the target material, was calculated with the SRIM Code and the Ga2O3 tablets were made with FT-IR instruments at Nuclear Research Center for Agriculture and Medicine (NRCAM). They were then bombarded with the 20, 21 and 22.5 MeV proton energy and the beam currents of 1.4, 7.5 and 13.3 μA.Two weeks after the bombardment the radio chemical separation of Germanium - 68 was done with concentrated acid HNO3 and applying heat. Then, the acid solution was evaporated till dried, after that, an EDTA solution (0.005 M, pH = 11) was added to recover the Germanium - 68. By passing the EDTA solution through the A12O3 column, Germanium - 68 radioisotope was adsorbed.Then another solution of EDTA (0.005 M, PH=11) was passed thorough the loaded column, almost all the natural Gallium impurities were removed.In this project the behavior of natural Gallium was studied via adding Gallium-67 as a tracer which it's half life is about

  2. Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    Haug, Alexander; Auernhammer, Christoph J.; Goeke, Burkhard; Waengler, Bjoern; Tiling, Reinhold; Bartenstein, Peter; Poepperl, Gabriele; Schmidt, Gerwin

    2009-01-01

    To compare the diagnostic impact of 68 Ga-DOTA-TATE and 18 F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). PET/CT using both 68 Ga-DOTA-TATE and 18 F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Patient-based sensitivities were 96% for 68 Ga-DOTA-TATE PET and 56% for 18 F-DOPA PET. 68 Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by 18 F-DOPA PET. Overall, 68 Ga-DOTA-TATE was superior to 18 F-DOPA in 13 patients (two patients showed fewer positive tumour regions with 18 F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of 18 F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive 18 F-DOPA uptake. In patients positive for 18 F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). In this study 68 Ga-DOTA-TATE PET proved clearly superior to 18 F-DOPA PET for detection and staging of NET. 18 F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that 18 F-DOPA PET should be employed in patients with NET with negative 68 Ga-DOTA-TATE PET and elevated plasma serotonin. (orig.)

  3. Reduction of 68Ge activity containing liquid waste from 68Ga PET chemistry in nuclear medicine and radiopharmacy by solidification.

    Science.gov (United States)

    de Blois, Erik; Chan, Ho Sze; Roy, Kamalika; Krenning, Eric P; Breeman, Wouter A P

    PET with 68 Ga from the TiO 2 - or SnO 2 - based 68 Ge/ 68 Ga generators is of increasing interest for PET imaging in nuclear medicine. In general, radionuclidic purity ( 68 Ge vs. 68 Ga activity) of the eluate of these generators varies between 0.01 and 0.001%. Liquid waste containing low amounts of 68 Ge activity is produced by eluting the 68 Ge/ 68 Ga generators and residues from PET chemistry. Since clearance level of 68 Ge activity in waste may not exceed 10 Bq/g, as stated by European Directive 96/29/EURATOM, our purpose was to reduce 68 Ge activity in solution from >10 kBq/g to <10 Bq/g; which implies the solution can be discarded as regular waste. Most efficient method to reduce the 68 Ge activity is by sorption of TiO 2 or Fe 2 O 3 and subsequent centrifugation. The required 10 Bq per mL level of 68 Ge activity in waste was reached by Fe 2 O 3 logarithmically, whereas with TiO 2 asymptotically. The procedure with Fe 2 O 3 eliminates ≥90% of the 68 Ge activity per treatment. Eventually, to simplify the processing a recirculation system was used to investigate 68 Ge activity sorption on TiO 2 , Fe 2 O 3 or Zeolite. Zeolite was introduced for its high sorption at low pH, therefore 68 Ge activity containing waste could directly be used without further interventions. 68 Ge activity containing liquid waste at different HCl concentrations (0.05-1.0 M HCl), was recirculated at 1 mL/min. With Zeolite in the recirculation system, 68 Ge activity showed highest sorption.

  4. A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma

    International Nuclear Information System (INIS)

    Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna; Frech, Andreas; Fraedrich, Gustav; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias

    2013-01-01

    18 F-Fluoro-l-dihydroxyphenylalanine ( 18 F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by 68 Ga-DOTA-Tyr 3 -octreotide ( 68 Ga-DOTA-TOC) PET. Therefore, we compared 68 Ga-DOTA-TOC and 18 F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with 68 Ga-DOTA-TOC PET and 18 F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV max ) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, 68 Ga-DOTA-TOC PET and 18 F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of 68 Ga-DOTA-TOC was 100 % and that of 18 F-DOPA PET was 56.0 %. Overall, 68 Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and 18 F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of 68 Ga-DOTA-TOC PET was 100 % (McNemar, P 18 F-DOPA PET was 71.1 % (McNemar, P max (mean ± SD) of all 32 concordant lesions was 67.9 ± 61.5 for 68 Ga-DOTA-TOC PET and 11.8 ± 7.9 for 18 F-DOPA PET (Mann-Whitney U test, P 68 Ga-DOTA-TOC PET may be superior to 18 F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically

  5. Validation of 68Ge/68Ga generator processing by chemical purification for routine clinical application of 68Ga-DOTATOC

    International Nuclear Information System (INIS)

    Asti, Mattia; De Pietri, Giovanni; Fraternali, Alessandro; Grassi, Elisa; Sghedoni, Roberto; Fioroni, Federica; Roesch, Frank; Versari, Annibale; Salvo, Diana

    2008-01-01

    Introduction: Imaging of somatostatin receptor expressing tumours has been greatly enhanced by the use of 68 Ga-DOTATOC and PET/CT. Methods: In this work, a purification method for the 68 Ge/ 68 Ga generator eluate and a method to produce 68 Ga-DOTATOC suitable for clinical use were evaluated. The generator eluate was purified and concentrated on a cation-exchange cartridge in HCl/acetone media. The efficacy of this procedure in eliminating metal impurities from the 68 Ga solution was investigated by ICP-MS. The radiotracer quality was evaluated by radio-TLC, GC and γ-ray spectrometry. Results: 68 Ga-DOTATOC preparations (n=33) were carried out with a mean synthesis yield of 59.3±2.8% (not corrected for decay) and a batch activity ranging from 555 to 296 MBq. The radiochemical and radionuclidic purity were >98% and 99.9999%, respectively. With this purification process, >95% of the Fe(III), Zn(II) and Mn(II) were eliminated from the solution. Conclusions: 68 Ga-DOTATOC produced with this method can be efficiently used in nuclear medicine departments for PET evaluations

  6. Averaged cross sections for the reactions 68Zn(n,p)68gCu and 68Zn(n,p)68mCu for a 235U fission neutron spectrum

    International Nuclear Information System (INIS)

    Kestelman, A.J.; Ribeiro Guevara, S.; Arribere, M.A.; Cohen, I.M.

    2007-01-01

    Making use of the method developed in our laboratory for the simultaneous determination of cross sections leading to both the ground and metastable states, we have measured the 68 Zn(n,p) 68g Cu and 68 Zn(n,p) 68m Cu reactions, using Zn enriched to 99.4% in its isotope 68 Zn. The measured cross sections are (15.04±0.35) and (3.69±0.30) μb for the ground and metastable state, respectively. However, a direct determination of the cross section leading to the metastable state gives a value of (4.75±0.38) μb. A possible reason for this discrepancy-which is outside experimental uncertainties-is that some tabulated values used in our calculations for the decay parameters of 68g Cu and 68m Cu, have either larger than quoted, or unknown systematic, uncertainties

  7. Disposal of radioactive contaminated waste from Ga-68-PET. Calculation of a clearance level for Ge-68+; Entsorgung radioaktiv kontaminierter Reststoffe aus der Ga-68-PET. Berechnung eines Freigabewertes fuer Ge-68+

    Energy Technology Data Exchange (ETDEWEB)

    Solle, Alexander; Wanke, Carsten; Geworksi, Lilli [Medizinische Hochschule Hannover (Germany). Stabsstelle Strahlenschutz und Abt. Medizinische Physik

    2017-05-01

    Ga-68-labeled radiotracers, particularly used for the detection of neuroendocrine tumors by means of Ga-68-DOTA-TATE or -DOTA-TOC or for the diagnosis of prostate cancer by means of Ga-68-labeled antigens (Ga 68-PSMA), become increasingly important. In addition to the high sensitivity and specificity of these radiopharmaceuticals, the short-lived radionuclide Ga-68 offers almost ideal nuclear characteristics for use in PET. Ga-68 is obtained from a germanium-gallium-generator system, so that the availability of Ga-68-labeled radiotracers is independent of an on-site-cyclotron regardless of the short half-life of Ga-68 of about 68 minutes. Regarding the disposal of the radioactively contaminated waste from the preparation of the radiopharmaceutical, the eluted Ga-68 has to be considered to be additionally contaminated with its parent nuclide Ge-68. Due to this production-related impurity in combination with the short half-life of Ga-68, the radioactive waste has to be considered to be contaminated with Ge-68 and Ga-68 in radioactive equilibrium (hereafter referred to as Ge-68+). As there are no clearance levels for Ge-68+ given in the German Radiation Protection Ordinance, this work presents a method to calculate the missing value basing on a recommendation of the German Radiation Protection Commission in combination with simple geometric models of practical radiation protection. Regarding the relevant exposure scenarios, a limit value for the unrestricted clearance of Ge-68+ of 0.4 Bq/g was determined.

  8. 68Ga-DOTATATE PET/CT imaging of indeterminate pulmonary nodules and lung cancer.

    Directory of Open Access Journals (Sweden)

    Ronald Walker

    Full Text Available 18F-FDG PET/CT is widely used to evaluate indeterminate pulmonary nodules (IPNs. False positive results occur, especially from active granulomatous nodules. A PET-based imaging agent with superior specificity to 18F-FDG for IPNs, is badly needed, especially in areas of endemic granulomatous nodules. Somatostatin receptors (SSTR are expressed in many malignant cells including small cell and non-small cell lung cancers (NSCLCs. 68Ga-DOTATATE, a positron emitter labeled somatostatin analog, combined with PET/CT imaging, may improve the diagnosis of IPNs over 18F-FDG by reducing false positives. Our study purpose was to test this hypothesis in our region with high endemic granulomatous IPNs.We prospectively performed 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT scans in the same 30 patients with newly diagnosed, treatment-naïve lung cancer (N = 14 or IPNs (N = 15 and one metastatic nodule. 68Ga-DOTATATE SUVmax levels at or above 1.5 were considered likely malignant. We analyzed the scan results, correlating with ultimate diagnosis via biopsy or 2-year chest CT follow-up. We also correlated 68Ga-DOTATATE uptake with immunohistochemical (IHC staining for SSTR subtype 2A (SSTR2A in pathological specimens.We analyzed 31 lesions in 30 individuals, with 14 (45% being non-neuroendocrine lung cancers and 1 (3% being metastatic disease. McNemar's result comparing the two radiopharmaceuticals (p = 0.65 indicates that their accuracy of diagnosis in this indication are equivalent. 68Ga-DOTATATE was more specific (94% compared to 81% and less sensitive 73% compared to 93% than 18F-FDG. 68Ga-DOTATATE uptake correlated with SSTR2A expression in tumor stroma determined by immunohistochemical (IHC staining in 5 of 9 (55% NSCLCs.68Ga-DOTATATE and 18F-FDG PET/CT had equivalent accuracy in the diagnosis of non-neuroendocrine lung cancer and 68Ga-DOTATATE was more specific than 18F-FDG for the diagnosis of IPNs. IHC staining for SSTR2A receptor expression correlated with

  9. PSA-Stratified Performance of 18F- and 68Ga-PSMA PET in Patients with Biochemical Recurrence of Prostate Cancer.

    Science.gov (United States)

    Dietlein, Felix; Kobe, Carsten; Neubauer, Stephan; Schmidt, Matthias; Stockter, Simone; Fischer, Thomas; Schomäcker, Klaus; Heidenreich, Axel; Zlatopolskiy, Boris D; Neumaier, Bernd; Drzezga, Alexander; Dietlein, Markus

    2017-06-01

    Several studies outlined the sensitivity of 68 Ga-labeled PET tracers against the prostate-specific membrane antigen (PSMA) for localization of relapsed prostate cancer in patients with renewed increase in the prostate-specific antigen (PSA), commonly referred to as biochemical recurrence. Labeling of PSMA tracers with 18 F offers numerous advantages, including improved image resolution, longer half-life, and increased production yields. The aim of this study was to assess the PSA-stratified performance of the 18 F-labeled PSMA tracer 18 F-DCFPyL and the 68 Ga-labeled reference 68 Ga-PSMA-HBED-CC. Methods: We examined 191 consecutive patients with biochemical recurrence according to standard acquisition protocols using 18 F-DCFPyL ( n = 62, 269.8 MBq, PET scan at 120 min after injection) or 68 Ga-PSMA-HBED-CC ( n = 129, 158.9 MBq, 60 min after injection). We determined PSA-stratified sensitivity rates for both tracers and corrected our calculations for Gleason scores using iterative matched-pair analyses. As an orthogonal validation, we directly compared tracer distribution patterns in a separate cohort of 25 patients, sequentially examined with both tracers. Results: After prostatectomy ( n = 106), the sensitivity of both tracers was significantly associated with absolute PSA levels ( P = 4.3 × 10 -3 ). Sensitivity increased abruptly, when PSA values exceeded 0.5 μg/L ( P = 2.4 × 10 -5 ). For a PSA less than 3.5 μg/L, most relapses were diagnosed at a still limited stage ( P = 3.4 × 10 -6 ). For a PSA of 0.5-3.5 μg/L, PSA-stratified sensitivity was 88% (15/17) for 18 F-DCFPyL and 66% (23/35) for 68 Ga-PSMA-HBED-CC. This significant difference was preserved in the Gleason-matched-pair analysis. Outside of this range, sensitivity was comparably low (PSA PSA > 3.5 μg/L). After radiotherapy ( n = 85), tracer sensitivity was largely PSA-independent. In the 25 patients examined with both tracers, distribution patterns of 18 F-DCFPyL and 68 Ga-PSMA-HBED-CC were

  10. A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma.

    Science.gov (United States)

    Kroiss, Alexander; Putzer, Daniel; Frech, Andreas; Decristoforo, Clemens; Uprimny, Christian; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias; Fraedrich, Gustav; Virgolini, Irene Johanna

    2013-12-01

    (18)F-Fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTA-TOC) PET. Therefore, we compared (68)Ga-DOTA-TOC and (18)F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with (68)Ga-DOTA-TOC PET and (18)F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, (68)Ga-DOTA-TOC PET and (18)F-DOPA PET each had a per-patient and per-lesion detection rate of 100% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of (68)Ga-DOTA-TOC was 100% and that of (18)F-DOPA PET was 56.0%. Overall, (68)Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and (18)F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of (68)Ga-DOTA-TOC PET was 100% (McNemar, P TOC PET and 11.8 ± 7.9 for (18)F-DOPA PET (Mann-Whitney U test, P TOC PET may be superior to (18)F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically inoperable tumours and metastatic or multifocal disease.

  11. Production of prototype 68Ge/68Ga generator in Iran

    International Nuclear Information System (INIS)

    Shirazi, B.; Fateh, B.; Mirzaii, M.; Aslani, Gh. R.

    2007-01-01

    Ga-68 is a radioisotope material with a half life of 68 min. As it has a specific decay mode, it is a positron emitter and hence, is popularly used in nuclear medicine. The only way to obtain these nuclides is to produce the mother nuclease which is Germanium-68. There are many nuclear reactions from which the Ge-68 is obtained, however, the best reaction is 6 9 G a(p, 2n) 6 8 G e . The cross section of this nuclear reaction was calculated with the ALICE-91 Code and the result was compared with the practical work made by other researchers, and it was acceptable. Having the cross sections in mind, the best proton energy was calculated to be between 20-25 MeV. Further research showed that Ga 2 O 3 is the best type of target material. Therefore, it was necessary to design and make a suitable target holder for these kind of compositions, which for the first time in Iran was demonstrated in the Atomic Energy Organization of Iran. The thickness of the target, bearing in mind the rate of energy loss inside the target material, was calculated with the SRIM Code and the Ga 2 O 3 tablets were made with FT-IR facilities at the Nuclear Research Center for Agriculture and Medicine (NRCAM). They were, then bombarded with 22.5 MeV proton energy and the beam currents of 2 and 10 μA. Two weeks after the bombardment the radio chemical separation of Ge-68 was accompolished with concentrated acid HN0 3 and by applying heat. Then, the acid solution was evaporated till dried, after that, an EDTA solution (0.005 M, pH=11) was added to recover the Ge-68. By passing the EDTA solution with the rate of 0.5 ml/min through the AI 2 O 3 column, the Ge-68 radioisotope was observed. Then, about 50 ml of EDTA (0.005 M, pH=11) was passed through the loaded column, where almost all the natural Gallium impurities were removed. The prepared generators were milked many times with EDTA solution (0.005 M, pH=8) and the leakage of Ge-68 nuclease and natural Gallium were determined. The average of the

  12. "6"8Gallium-arginine-glycine-aspartic acid and "1"8F-fluorodeoxyglucose position emission tomography/computed tomography in chondroblastic osteosarcoma of the skull

    International Nuclear Information System (INIS)

    Orunmuyi, Akintunde; Modiselle, Moshe; Lengana, Thabo; Ebenhan, Thomas; Vorster, Mariza; Sathekge, Mike

    2017-01-01

    We report the case of a 32 year-old male with Chondroblastic Osteosarcoma of the skull, which was imaged with both "1"8[F]fluorodeoxyglucose ("1"8F-FDG) positron emission tomography/computed tomography (PET/CT) and "6"8Gallium-arginine-glycine-aspartic acid ("6"8Ga-RGD) PET/CT. The "1"8F-FDG PET/CT did not demonstrate the tumour, whereas the "6"8Ga-RGD PET/CT clearly depicted a left-sided frontal tumour. "6"8Ga-RGD PET/CT may be a clinically useful imaging modality for early detection of recurrent osteosarcoma, considering the limitations of "1"8F-FDG PET in a setting of low glycolytic activity

  13. {sup 68}Gallium-arginine-glycine-aspartic acid and {sup 18}F-fluorodeoxyglucose position emission tomography/computed tomography in chondroblastic osteosarcoma of the skull

    Energy Technology Data Exchange (ETDEWEB)

    Orunmuyi, Akintunde; Modiselle, Moshe; Lengana, Thabo; Ebenhan, Thomas; Vorster, Mariza; Sathekge, Mike [Dept. of Nuclear MedicineUniversity of Pretoria and Steve Biko Academic Hospital, Pretoria (South Africa)

    2017-09-15

    We report the case of a 32 year-old male with Chondroblastic Osteosarcoma of the skull, which was imaged with both {sup 18}[F]fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) and {sup 68}Gallium-arginine-glycine-aspartic acid ({sup 68}Ga-RGD) PET/CT. The {sup 18}F-FDG PET/CT did not demonstrate the tumour, whereas the {sup 68}Ga-RGD PET/CT clearly depicted a left-sided frontal tumour. {sup 68}Ga-RGD PET/CT may be a clinically useful imaging modality for early detection of recurrent osteosarcoma, considering the limitations of {sup 18}F-FDG PET in a setting of low glycolytic activity.

  14. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation.

    Science.gov (United States)

    Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg; Detlefsen, Sönke; Brusgaard, Klaus; Rasmussen, Lars; Melikyan, Maria; Ekström, Klas; Globa, Evgenia; Rasmussen, Annett Helleskov; Hovendal, Claus; Christesen, Henrik Thybo

    2018-02-01

    Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.

  15. Enterovirus D68

    Science.gov (United States)

    Non-polio enterovirus ... Centers for Disease Control and Prevention website. Enterovirus D68. www.cdc.gov/non-polio-enterovirus/about/ev-d68.html#us . Updated October 20, 2017. Accessed October 26, 2017. Romero JR, Modlin ...

  16. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism. A blinded evaluation

    International Nuclear Information System (INIS)

    Dahl Christiansen, Charlotte; Helleskov Rasmussen, Annett; Petersen, Henrik; Lerberg Nielsen, Anne; Detlefsen, Soenke; Brusgaard, Klaus; Rasmussen, Lars; Hovendal, Claus; Melikyan, Maria; Ekstroem, Klas; Globa, Evgenia; Christesen, Henrik Thybo

    2018-01-01

    Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3 -octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged. (orig.)

  17. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism. A blinded evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Dahl Christiansen, Charlotte; Helleskov Rasmussen, Annett [Hans Christian Andersen Children' s Hospital, Odense University Hospital, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Petersen, Henrik; Lerberg Nielsen, Anne [Odense University Hospital, Department of Nuclear Medicine, Odense (Denmark); Detlefsen, Soenke [University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Department of Pathology, Odense (Denmark); Brusgaard, Klaus [Odense University Hospital, Department of Clinical Genetics, Odense (Denmark); Rasmussen, Lars; Hovendal, Claus [Odense University Hospital, Department of Abdominal Surgery, Odense (Denmark); Melikyan, Maria [Endocrine Research Centre, Moscow (Russian Federation); Ekstroem, Klas [Karolinska Hospital, Astrid Lindgren Children' s Hospital, Stockholm (Sweden); Globa, Evgenia [MOH of Ukraine, Ukrainian Center of Endocrine Surgery, Endocrine Organs and Tissue Transplantation, Kyiv (Ukraine); Christesen, Henrik Thybo [Hans Christian Andersen Children' s Hospital, Odense University Hospital, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Odense Pancreas Center (OPAC), Odense (Denmark); Odense University Hospital, Department of Paediatrics, Odense C (Denmark)

    2018-02-15

    Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3 -octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV{sub max}) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV{sub max} ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV{sub max} cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged. (orig.)

  18. Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

    International Nuclear Information System (INIS)

    Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

    2008-01-01

    18 F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18 F-DOPA and 68 Ga-DOTA-NOC are more accurate for disease assessment and 68 Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare 68 Ga-DOTA-NOC and 18 F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18 F-DOPA and 68 Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68 Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18 F-DOPA PET was positive in 9/13. On a lesions basis, 68 Ga-DOTA-NOC identified more lesions than 18 F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68 Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18 F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that 68 Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18 F-DOPA. (orig.)

  19. Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours.

    Science.gov (United States)

    Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

    2008-08-01

    (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.

  20. Preliminary PET/CT Imaging with Somatostatin Analogs [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC.

    Science.gov (United States)

    Satpati, Drishty; Shinto, Ajit; Kamaleshwaran, K K; Sarma, Haladhar Dev; Dash, Ashutosh

    2017-12-01

    Somatostatin receptor positron emission tomography/X-ray computed tomography (SSTR-PET/CT) is a well-established technique for staging and detection of neuroendocrine tumors (NETs). Ga-68-labeled DOTA-conjugated octreotide analogs are the privileged radiotracers for diagnosis and therapeutic monitoring of NETs. Hence, we were interested in assessing the influence of promising, newer variant DOTAGA on the hydrophilicity, pharmacokinetics, and lesion pick-up of somatostatin analogs. Herein, the potential of ([ 68 Ga]DOTAGA, Tyr 3 , Thr 8 ) octreotide ([ 68 Ga]DOTAGA-TATE) and ([ 68 Ga]DOTAGA, Tyr 3 ) octreotide ([ 68 Ga]DOTAGA-TOC) as NET imaging agents has been investigated. Amenability of [ 68 Ga]DOTAGA-(TATE/TOC) to kit-type formulation has been demonstrated. Biodistribution studies were carried out in normal rats at 1 h post-injection (p.i.). [ 68 Ga]DOTAGA-(TATE/TOC) PET/CT scans were carried out in patients (70-170 MBq, 1 h p.i.) with histologically confirmed well-differentiated NETs. [ 68 Ga]DOTAGA-TATE exhibited hydrophilicity similar to [ 68 Ga]DOTA-TATE (log P = -3.51 vs -3.69) whereas [ 68 Ga]DOTAGA-TOC was more hydrophilic than [ 68 Ga]DOTA-TOC (log P = -3.27 vs -2.93). [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE showed almost identical blood and kidney uptake in normal rats whereas significantly fast clearance (p TOC also demonstrated rapid clearance from blood and kidneys (p TOC. The metastatic lesions in NET patients were well identified by [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTAGA-TOC. The phenomenal analogy was observed between [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE as well as between [ 68 Ga]DOTAGA-TOC and [ 68 Ga]DOTA-TOC in biodistribution studies in rats. The good lesion detection ability of the two radiotracers indicates their potential as NET imaging radiotracers.

  1. A retrospective comparison between {sup 68}Ga-DOTA-TOC PET/CT and {sup 18}F-DOPA PET/CT in patients with extra-adrenal paraganglioma

    Energy Technology Data Exchange (ETDEWEB)

    Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Frech, Andreas; Fraedrich, Gustav [Innsbruck Medical University, Department of Vascular Surgery, Innsbruck (Austria); Gasser, Rudolf Wolfgang [Innsbruck Medical University, Department of Internal Medicine I, Innsbruck (Austria); Shulkin, Barry Lynn [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Url, Christoph [Innsbruck Medical University, Department of Otorhinolaryngology, Innsbruck (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Prommegger, Rupert [Sanatorium Kettenbruecke, Department of Surgery, Innsbruck (Austria); Sprinzl, Georg Mathias [State Clinic St. Poelten, Department of Otorhinolaryngology, St. Poelten (Austria)

    2013-12-15

    {sup 18}F-Fluoro-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by {sup 68}Ga-DOTA-Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) PET. Therefore, we compared {sup 68}Ga-DOTA-TOC and {sup 18}F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV{sub max}) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of {sup 68}Ga-DOTA-TOC was 100 % and that of {sup 18}F-DOPA PET was 56.0 %. Overall, {sup 68}Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and {sup 18}F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of {sup 68}Ga-DOTA-TOC PET was 100 % (McNemar, P < 0.5), and that of {sup 18}F-DOPA PET was 71.1 % (McNemar, P < 0.001). The SUV{sub max} (mean {+-} SD) of all 32 concordant lesions was 67.9 {+-} 61.5 for {sup 68}Ga-DOTA-TOC PET and 11.8 {+-} 7.9 for {sup 18}F-DOPA PET (Mann-Whitney U test, P < 0.0001). {sup 68}Ga-DOTA-TOC PET

  2. Averaged cross sections for the reactions {sup 68}Zn(n,p){sup 68g}Cu and {sup 68}Zn(n,p){sup 68m}Cu for a {sup 235}U fission neutron spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Kestelman, A.J. [Laboratorio de Analisis por Activacion Neutronica, Centro Atomico Bariloche e Instituto Balseiro, Comision Nacional de Energia Atomica y Universidad Nacional de Cuyo, 8400 Bariloche (Argentina)]. E-mail: kestelma@cab.cnea.gov.ar; Ribeiro Guevara, S. [Laboratorio de Analisis por Activacion Neutronica, Centro Atomico Bariloche e Instituto Balseiro, Comision Nacional de Energia Atomica y Universidad Nacional de Cuyo, 8400 Bariloche (Argentina); Arribere, M.A. [Laboratorio de Analisis por Activacion Neutronica, Centro Atomico Bariloche e Instituto Balseiro, Comision Nacional de Energia Atomica y Universidad Nacional de Cuyo, 8400 Bariloche (Argentina); Cohen, I.M. [Universidad Tecnologica Nacional, Facultad Regional Buenos Aires, Medrano 951 (C1179AAQ) Buenos Aires (Argentina)

    2007-07-15

    Making use of the method developed in our laboratory for the simultaneous determination of cross sections leading to both the ground and metastable states, we have measured the {sup 68}Zn(n,p){sup 68g}Cu and {sup 68}Zn(n,p){sup 68m}Cu reactions, using Zn enriched to 99.4% in its isotope {sup 68}Zn. The measured cross sections are (15.04{+-}0.35) and (3.69{+-}0.30) {mu}b for the ground and metastable state, respectively. However, a direct determination of the cross section leading to the metastable state gives a value of (4.75{+-}0.38) {mu}b. A possible reason for this discrepancy-which is outside experimental uncertainties-is that some tabulated values used in our calculations for the decay parameters of {sup 68g}Cu and {sup 68m}Cu, have either larger than quoted, or unknown systematic, uncertainties.

  3. Comparison of [68Ga]Ga-PSMA-11 PET/CT with [18F]NaF PET/CT in the evaluation of bone metastases in metastatic prostate cancer patients prior to radionuclide therapy.

    Science.gov (United States)

    Uprimny, Christian; Svirydenka, Anna; Fritz, Josef; Kroiss, Alexander Stephan; Nilica, Bernhard; Decristoforo, Clemens; Haubner, Roland; von Guggenberg, Elisabeth; Buxbaum, Sabine; Horninger, Wolfgang; Virgolini, Irene Johanna

    2018-05-16

    The purpose of this study was to investigate the diagnostic performance of 68 Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [ 18 F]sodium fluoride ( 18 F-NaF) PET/CT. Sixteen metastatic PC patients with known skeletal metastases, who underwent both 68 Ga-PSMA-11 PET/CT and 18 F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on 18 F-NaF PET and 68 Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUV max ) and compared to background activity of normal bone. In addition, SUV max values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan. In contrast to 468 PET-positive lesions suggestive of bone metastases on 18 F-NaF PET, only 351 of the lesions were also judged positive on 68 Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on 18 F-NaF PET compared to 68 Ga-PSMA-11 PET, showing a median SUV max of 27.0 and 6.0, respectively (p PET, with a median SUV max of 1.0 in comparison to 2.7 on 18 F-NaF PET; however, tumour to background ratio was significantly higher on 18 F-NaF PET (9.8 versus 5.9 on 68 Ga-PSMA-11 PET; p = 0.042). Based on morphologic lesion characterisation on CT, 18 F-NaF PET revealed median SUV max values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on 68 Ga-PSMA-11 PET median SUV max values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between 18 F-NaF PET and 68 Ga-PSMA-11 PET was significantly higher in osteosclerotic (p

  4. Effect of the positron range of 18F, 68Ga and 124I on PET/CT in lung-equivalent materials.

    Science.gov (United States)

    Kemerink, Gerrit J; Visser, Mariëlle G W; Franssen, Renee; Beijer, Emiel; Zamburlini, Mariangela; Halders, Servé G E A; Brans, Boudewijn; Mottaghy, Felix M; Teule, Gerrit J J

    2011-05-01

    The aim of this study was to investigate the effect of positron range on visualization and quantification in (18)F, (68)Ga and (124)I positron emission tomography (PET)/CT of lung-like tissue. Different sources were measured in air, in lung-equivalent foams and in water, using a clinical PET/CT and a microPET system. Intensity profiles and curves with the cumulative number of annihilations were derived and numerically characterized. (68)Ga and (124)I gave similar results. Their intensity profiles in lung-like foam had a peak similar to that for (18)F, and tails of very low intensity, but extending over distances of centimetres and containing a large fraction of all annihilations. For 90% recovery, volumes of interest with diameters up to 50 mm were required, and recovery within the 10% intensity isocontour was as low as 30%. In contrast, tailing was minor for (18)F. Lung lesions containing (18)F, (68)Ga or (124)I will be visualized similarly, and at least as sharp as in soft tissue. Nevertheless, for quantification of (68)Ga and (124)I large volumes of interest are needed for complete activity recovery. For clinical studies containing noise and background, new quantification approaches may have to be developed.

  5. 40 CFR 68.73 - Mechanical integrity.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.73 Mechanical integrity. (a) Application. Paragraphs (b) through (f) of this section apply to the following process equipment: (1) Pressure... shall establish and implement written procedures to maintain the on-going integrity of process equipment...

  6. Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]traces, [11C/[18F]-HTP)

    International Nuclear Information System (INIS)

    Ambrosini, A.; Morgini, J.J.; Nanni, C.; Castellucci, P.; Fanti, S.

    2015-01-01

    Neuroendocrine neoplasms (NEN) functional imaging is an evolving field that witnessed major advances in the past two decades. The routine use of PET/CT with an array of new radiotracers to specifically study NEN resulted in an increase in lesions detection. Currently, PET radiopharmaceuticals for NEN imaging include both metabolic ([18F]DOPA, [18F]FDG, [11C]/[18F]-HTP) and receptor-mediated compounds ([68Ga]DOTA-peptides). Discussion is still on-going regarding the clinical setting that may benefit the most from the use of one tracer over the other. [68Ga]DOTA-peptides are accurate for the detection of well differentiated NEN and are increasingly employed. Moreover, providing data on somatostatin receptors expression on NEN cells, they represent a fundamental procedure to be performed before starting therapy, as well as to guide treatment, with either hot or cold somatostatin analogues. The easy and economic synthesis process also favours their clinical employment even in centres without an on-site cyclotron. [18F]DOPA is accurate for studying well differentiated tumours however the difficult and expensive synthesis have limited its clinical employment. It currently can be successfully used for imaging tumours with variable to low expression of SSR (medullary thyroid carcinoma, neuroblastoma, pheocromocytoma), that cannot be accurately studied with [68Ga]DOTA-peptides. [11C]/[18F]-HTP has also been proposed to image well differentiated NEN, on the basis of serotonin pathway activity, for which [11C]/[18F]-HTP can be used as precursor. However, although preliminary data are encouraging, the feasibility of its widespread clinical use is still under discussion, mainly limited by a complex synthesis process and more proven advantages over other currently employed compounds. This review aims to provide an overview of the current status and clinical application of PET tracers to image well differentiated NEN and to focus on the still open-issues of debate

  7. Development of a nano-zirconia based {sup 68}Ge/{sup 68}Ga generator for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarty, Rubel [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Shukla, Rakesh [Chemistry Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Ram, Ramu [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Tyagi, Avesh Kumar [Chemistry Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Dash, Ashutosh, E-mail: adash@barc.gov.i [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai-400085 (India); Venkatesh, Meera [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai-400085 (India)

    2011-05-15

    Introduction: Most of the commercially available {sup 68}Ge/{sup 68}Ga generator systems are not optimally designed for direct applications in a clinical context. We have developed a nano-zirconia based {sup 68}Ge/{sup 68}Ga generator system for accessing {sup 68}Ga amenable for the preparation of radiopharmaceuticals. Methods: Nano-zirconia was synthesized by the in situ reaction of zirconyl chloride with ammonium hydroxide in alkaline medium. The physical characteristics of the material were studied by various analytical techniques. A 740 MBq (20 mCi) {sup 68}Ge/{sup 68}Ga generator was developed using this sorbent and its performance was evaluated for a period of 1 year. The suitability of {sup 68}Ga for labeling biomolecules was ascertained by labeling DOTA-TATE with {sup 68}Ga. Results: The material synthesized was nanocrystalline with average particle size of {approx}7 nm, pore-size of {approx}4 A and a high surface area of 340{+-}10 m{sup 2} g{sup -1}. {sup 68}Ga could be regularly eluted from this generator in 0.01N HCl medium with an overall radiochemical yield >80% and with high radionuclidic (<10{sup -5}% of {sup 68}Ge impurity) and chemical purity (<0.1 ppm of Zr, Fe and Mn ions). The compatibility of the product for preparation of {sup 68}Ga-labeled DOTA-TATE under the optimized reaction conditions was found to be satisfactory in terms of high labeling yields (>99%). The generator gave a consistent performance with respect to the elution yield and purity of {sup 68}Ga over a period of 1 year. Conclusions: The feasibility of preparing an efficient {sup 68}Ge/{sup 68}Ga generator which can directly be used for biomedical applications has been demonstrated.

  8. [Disposal of radioactive contaminated waste from Ga-68-PET - calculation of a clearance level for Ge-68].

    Science.gov (United States)

    Solle, Alexander; Wanke, Carsten; Geworski, Lilli

    2017-03-01

    Ga-68-labeled radiotracers, particularly used for the detection of neuroendocrine tumors by means of Ga-68-DOTA-TATE or -DOTA-TOC or for the diagnosis of prostate cancer by means of Ga-68-labeled antigens (Ga 68-PSMA), become increasingly important. In addition to the high sensitivity and specificity of these radiopharmaceuticals, the short-lived radionuclide Ga-68 offers almost ideal nuclear characteristics for use in PET. Ga-68 is obtained from a germanium-gallium-generator system, so that the availability of Ga-68-labeled radiotracers is independent of an on-site-cyclotron regardless of the short half-life of Ga-68 of about 68minutes. Regarding the disposal of the radioactively contaminated waste from the preparation of the radiopharmaceutical, the eluted Ga-68 has to be considered to be additionally contaminated with its parent nuclide Ge-68. Due to this production-related impurity in combination with the short half-life of Ga-68, the radioactive waste has to be considered to be contaminated with Ge-68 and Ga-68 in radioactive equilibrium (hereafter referred to as Ge-68+). As there are no clearance levels for Ge-68+ given in the German Radiation Protection Ordinance, this work presents a method to calculate the missing value basing on a recommendation of the German Radiation Protection Commission in combination with simple geometric models of practical radiation protection. Regarding the relevant exposure scenarios, a limit value for the unrestricted clearance of Ge-68+ of 0.4 Bq/g was determined. Copyright © 2016. Published by Elsevier GmbH.

  9. Disposal of radioactive contaminated waste from Ga-68-PET. Calculation of a clearance level for Ge-68+

    International Nuclear Information System (INIS)

    Solle, Alexander; Wanke, Carsten; Geworksi, Lilli

    2017-01-01

    Ga-68-labeled radiotracers, particularly used for the detection of neuroendocrine tumors by means of Ga-68-DOTA-TATE or -DOTA-TOC or for the diagnosis of prostate cancer by means of Ga-68-labeled antigens (Ga 68-PSMA), become increasingly important. In addition to the high sensitivity and specificity of these radiopharmaceuticals, the short-lived radionuclide Ga-68 offers almost ideal nuclear characteristics for use in PET. Ga-68 is obtained from a germanium-gallium-generator system, so that the availability of Ga-68-labeled radiotracers is independent of an on-site-cyclotron regardless of the short half-life of Ga-68 of about 68 minutes. Regarding the disposal of the radioactively contaminated waste from the preparation of the radiopharmaceutical, the eluted Ga-68 has to be considered to be additionally contaminated with its parent nuclide Ge-68. Due to this production-related impurity in combination with the short half-life of Ga-68, the radioactive waste has to be considered to be contaminated with Ge-68 and Ga-68 in radioactive equilibrium (hereafter referred to as Ge-68+). As there are no clearance levels for Ge-68+ given in the German Radiation Protection Ordinance, this work presents a method to calculate the missing value basing on a recommendation of the German Radiation Protection Commission in combination with simple geometric models of practical radiation protection. Regarding the relevant exposure scenarios, a limit value for the unrestricted clearance of Ge-68+ of 0.4 Bq/g was determined.

  10. CD68/macrosialin: not just a histochemical marker.

    Science.gov (United States)

    Chistiakov, Dimitry A; Killingsworth, Murry C; Myasoedova, Veronika A; Orekhov, Alexander N; Bobryshev, Yuri V

    2017-01-01

    CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells. Cell-specific CD68 expression and differentiated expression levels are determined by the complex interplay between transcription factors, regulatory transcriptional elements, and epigenetic factors. Human CD68 and its mouse ortholog macrosialin belong to the family of LAMP proteins located in the lysosomal membrane and share many structural similarities such as the presence of the LAMP-like domain. Except for a second LAMP-like domain present in LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to the cell surface. However, the role of CD68 as a scavenger receptor remains to be confirmed. It seems that CD68 is not involved in binding bacterial/viral pathogens, innate, inflammatory or humoral immune responses, although it may potentially be involved in antigen processing/presentation. CD68 could be functionally important in osteoclasts since its deletion leads to reduced bone resorption capacity. The role of CD68 in atherosclerosis is contradictory.

  11. Functional imaging in differentiating bronchial masses: an initial experience with a combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan.

    Science.gov (United States)

    Kumar, Arvind; Jindal, Tarun; Dutta, Roman; Kumar, Rakesh

    2009-10-01

    To evaluate the role of combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan in differentiating bronchial tumors observed in contrast enhanced computed tomography scan of chest. Prospective observational study. Place of study: All India Institute of Medical Sciences, New Delhi, India. 7 patients with bronchial mass detected in computed tomography scan of the chest were included in this study. All patients underwent (18)F-FDG PET-CT scan, (68)Ga DOTA-TOC PET-CT scan and fiberoptic bronchoscope guided biopsy followed by definitive surgical excision. The results of functional imaging studies were analyzed and the results are correlated with the final histopathology of the tumor. Histopathological examination of 7 bronchial masses revealed carcinoid tumors (2 typical, 1 atypical), inflammatory myofibroblastic tumor (1), mucoepidermoid carcinoma (1), hamartoma (1), and synovial cell sarcoma (1). The typical carcinoids had mild (18)F-FDG uptake and high (68)Ga DOTA-TOC uptake. Atypical carcinoid had moderate uptake of (18)F-FDG and high (68)Ga DOTA-TOC uptake. Inflammatory myofibroblastic tumor showed high uptake of (18)F-FDG and no uptake of (68)Ga DOTA-TOC. Mucoepidermoid carcinoma showed mild (18)F-FDG uptake and no (68)Ga DOTA-TOC uptake. Hamartoma showed no uptake on either scans. Synovial cell sarcoma showed moderate (18)F-FDG uptake and mild focal (68)Ga DOTA-TOC uptake. This initial experience with the combined use of (18)F-FDG and (68)Ga DOTA-TOC PET-CT scan reveals different uptake patterns in various bronchial tumors. Bronchoscopic biopsy will continue to be the gold standard; however, the interesting observations made in this study merits further evaluation of the utility of the combination of (18)F-FDG PET-CT scan and (68)Ga DOTA-TOC PET-CT scan in larger number of patients with bronchial masses.

  12. Development of 68Ga-Glycopeptide as an Imaging Probe for Tumor Angiogenesis

    Directory of Open Access Journals (Sweden)

    Ning Tsao

    2011-01-01

    Full Text Available Objective. This study was aimed to study tissue distribution and tumor imaging potential of 68Ga-glycopeptide (GP in tumor-bearing rodents by PET. Methods. GP was synthesized by conjugating glutamate peptide and chitosan. GP was labeled with 68Ga chloride for in vitro and in vivo studies. Computer outlined region of interest (counts per pixel of the tumor and muscle (at the symmetric site was used to determine tumor-to-muscle count density ratios. To ascertain the feasibility of 68Ga-GP in tumor imaging in large animals, PET/CT imaging of 68Ga-GP and 18F-FDG were conducted in New Zealand white rabbits bearing VX2 tumors. Standard uptake value of tumors were determined by PET up to 45 min. To determine blood clearance and half-life of 68Ga-GP, blood samples were collected from 10 seconds to 20 min. Results. Radiochemical purity of 68Ga-GP determined by instant thin-layer chromatography was >95%. Tumor uptake values (SUV for 68Ga-GP and 18F-FDG in New Zealand white rabbits bearing VX2 tumors were 3.25 versus 7.04. PET images in tumor-bearing rats and rabbits confirmed that 68Ga-GP could assess tumor uptake. From blood clearance curve, the half-life of 68Ga-GP was 1.84 hr. Conclusion Our data indicate that it is feasible to use 68Ga-GP to assess tumor angiogenesis.

  13. In vitro and in vivo evaluation of selected 68Ga-siderophores for infection imaging

    International Nuclear Information System (INIS)

    Petrik, Milos; Haas, Hubertus; Schrettl, Markus; Helbok, Anna; Blatzer, Michael; Decristoforo, Clemens

    2012-01-01

    Introduction: Siderophores are low-molecular-mass iron chelators serving as iron transporters for almost all bacteria, fungi and some plants. Iron is an essential element for majority of organisms and plays an important role in virulence of pathogenic organisms. 68 Ga is a positron emitter with complexing properties comparable to those of Fe(III) and readily available from a generator. Initial studies with 68 Ga-triacetylfusarinine C (TAFC) showed excellent targeting properties in a rat infection model. We report here on the in vitro and in vivo evaluation of other siderophores radiolabelled with 68 Ga as potential radiopharmaceuticals for infection imaging. Methods: 68 Ga labelling was performed using acetate buffer. Stability, log P and protein binding values were determined. In vitro uptake was tested using iron-deficient and iron-sufficient Aspergillus fumigatus (A.f.) cultures. Biodistribution of 68 Ga-siderophores was studied in Balb/c mice. Results: Significant differences among studied siderophores were observed in labelling efficiency, stability and protein binding. Uptake in A.f. cultures was highly dependent on iron load and type of the siderophore. In mice, 68 Ga-TAFC and 68 Ga-ferrioxamine E (FOXE) showed rapid renal excretion and low blood values even at a short period after injection; in contrast, 68 Ga-ferricrocin and 68 Ga-ferrichrome revealed high retention in blood and 68 Ga-fusarinine C showed very high kidney retention. Conclusions: Some of the studied siderophores bind 68 Ga with high affinity and stability, especially 68 Ga-TAFC and 68 Ga-FOXE. Low values of protein binding, high and specific uptake in A.f., and excellent in vivo biodistribution make them favourable agents for Aspergillus infection imaging.

  14. Comparison of 68Ga-OPS202 (68Ga-NODAGA-JR11) and 68Ga-DOTATOC (68Ga-Edotreotide) PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors: Evaluation of Sensitivity in a Prospective Phase II Imaging Study.

    Science.gov (United States)

    Nicolas, Guillaume P; Schreiter, Nils; Kaul, Felix; Uiters, John; Bouterfa, Hakim; Kaufmann, Jens; Erlanger, Tobias E; Cathomas, Richard; Christ, Emanuel; Fani, Melpomeni; Wild, Damian

    2017-11-30

    Radiolabeled somatostatin receptor (sst) agonists are integral to the diagnosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs), but detection rates, especially of liver metastases, remain disappointing even with PET/CT. 68 Ga-OPS202 ( 68 Ga-NODAGA-JR11), a novel radiolabeled sst antagonist with a high affinity for sst 2 , has the potential to perform better than sst agonists. Here we present the results of the Phase II component of a Phase I/II study, which evaluated the sensitivity of 68 Ga-OPS202 PET/CT compared with the reference compound, 68 Ga-DOTATOC (sst agonist). Methods: Patients received a single intravenous administration of 68 Ga-DOTATOC (15 µg peptide) and 68 Ga-OPS202 (15 µg peptide at visit 1; 50 µg peptide at visit 2) with an activity of 150 MBq. Whole-body PET/CT acquisitions were performed 1 h post injection on the same calibrated PET/CT scanner. Diagnostic efficacy measures were compared against contrast medium-enhanced CT or MRI as gold standard. Two independent blinded experts read the scans and both outcomes were combined for analysis. Results: Twelve consecutive patients with G1 or G2 GEP-NETs took part in this prospective study. Image contrast for matched malignant liver lesions was significantly higher for 68 Ga-OPS202 scans than for the 68 Ga-DOTATOC scan: median of the mean [interquartile] tumor-to-normal-liver SUV max ratios for 15 µg and 50 µg 68 Ga-OPS202 (5.3 [2.9 - 5.7] and 4.3 [3.4 - 6.3], respectively) were significantly higher than for 68 Ga-DOTATOC (1.9 [1.4 - 2.9]; P = 0.004 and P = 0.008, respectively). The higher tumor-to-background ratio of 68 Ga-OPS202 resulted not only in a higher detection rate of liver metastases, but also in a significantly higher lesion-based overall sensitivity with the antagonist than with 68 Ga-DOTATOC PET/CT: 94% and 88% for 50 µg and 15 µg 68 Ga-OPS202 and 59% for 15 µg 68 Ga-DOTATOC, respectively (pPET/CT and 68 Ga DOTATOC PET/CT were similar (approximately 98%). There were no

  15. Isolation of potential probiotic Lactobacillus oris HMI68 from mother's milk with cholesterol-reducing property.

    Science.gov (United States)

    Anandharaj, Marimuthu; Sivasankari, Balayogan

    2014-08-01

    The objective of this study was to evaluate the probiotic properties of Lactobacillus strains isolated from mother's milk and their effects on cholesterol assimilation. In this study 120 isolates from mother's milk were phenotypically and genotypically characterized. Among these, only 6 predominant strains were identified as Lactobacillus spp. The following parameters were selected as important test variables in model stomach passage survival trials: acid and bile tolerance, antimicrobial activity, antibiotic susceptibility and cholesterol reduction. Results showed that the considerable variation existed among six strains. Moreover, the strain HMI68 is the most acid-tolerant and the HMI28 and HMI74 is the most acid-sensitive of all strains tested. HMI118 did not grow at 0.5% and 1% bile concentration after 5 h but the HMI68 and HMI43 showed some tolerance to such bile concentration. The differences found in the growth rate were not significant (P > 0.05). HMI68 showed resistance to most of the antibiotics as well as antagonistic activity against the tested pathogens. The amount of cholesterol reduction is increased when the media supplemented with bile salts. HMI68 assimilate 61.05 ± 0.05 μg/ml cholesterol with the presence of 0.3% bile salt this could be significantly decreased by 25.41 ± 1.09 μg/ml without bile salt. HMI68 was identified to be Lactobacillus oris HMI68 and 16S rRNA sequence was deposited in the National Center for Biotechnological Information (GenBank). For the first time the cholesterol-reducing property of L. oris isolated from mother's milk were investigated in this study. Therefore the effective L. oris HMI68 strain was regarded as a candidate probiotic. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  16. Prospective comparison of {sup 68}Ga-DOTATATE and {sup 18}F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

    Energy Technology Data Exchange (ETDEWEB)

    Archier, Aurelien; Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Inserm UMR1068 Marseille Cancerology Research Center, Institut Paoli-Calmettes, Marseille (France); Varoquaux, Arthur; Beschmout, Eva [Aix-Marseille University, Department of Medical Imaging, Conception Hospital, Marseille (France); Garrigue, Philippe; Guillet, Benjamin [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, Department of Radiopharmacy, La Timone and North University Hospital, Marseille (France); Montava, Marion; Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Guerin, Carole; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Gabriel, Sophie [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Morange, Isabelle; Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Barlier, Anne [Aix-Marseille, University, Laboratory of Biochemistry and Molecular Biology, Conception Hospital, Marseille (France); Loundou, Anderson [Aix-Marseille University, Department of Public Health, Marseille (France); Pacak, Karel [National Institutes of Health, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD (United States)

    2016-07-15

    Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of {sup 68}Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. {sup 68}Ga-DOTATATE, {sup 18}F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). {sup 68}Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than {sup 18}F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). {sup 68}Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on {sup 68}Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). {sup 68}Ga-DOTATATE PET/CT is the most sensitive tool in the

  17. Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides.

    Science.gov (United States)

    de Blois, Erik; Sze Chan, Ho; Naidoo, Clive; Prince, Deidre; Krenning, Eric P; Breeman, Wouter A P

    2011-02-01

    PET scintigraphy with (68)Ga-labelled analogs is of increasing interest in Nuclear Medicine and performed all over the world. Here we report the characteristics of the eluate of SnO(2)-based (68)Ge/(68)Ga generators prepared by iThemba LABS (Somerset West, South Africa). Three purification and concentration techniques of the eluate for labelling DOTA-TATE and concordant SPE purifications were investigated. Characteristics of 4 SnO(2)-based generators (range 0.4-1 GBq (68)Ga in the eluate) and several concentration techniques of the eluate (HCl) were evaluated. The elution profiles of SnO(2)-based (68)Ge/(68)Ga generators were monitored, while [HCl] of the eluens was varied from 0.3-1.0 M. Metal ions and sterility of the eluate were determined by ICP. Fractionated elution and concentration of the (68)Ga eluate were performed using anion and cation exchange. Concentrated (68)Ga eluate, using all three concentration techniques, was used for labelling of DOTA-TATE. (68)Ga-DOTA-TATE-containing solution was purified and RNP increased by SPE, therefore also 11 commercially available SPE columns were investigated. The amount of elutable (68)Ga activity varies when the concentration of the eluens, HCl, was varied, while (68)Ge activity remains virtually constant. SnO(2)-based (68)Ge/(68)Ga generator elutes at 0.6 M HCl >100% of the (68)Ga activity at calibration time and ±75% after 300 days. Eluate at discharge was sterile and Endotoxins were 80%). Highest desorption for cation purification was obtained using a solution containing 90% acetone at increasing molarity of HCl, resulted in a (68)Ga desorption of 68±8%. With all (68)Ge/(68)Ga generators and for all 3 purification methods a SA up to 50 MBq/nmol with >95% incorporation (ITLC) and RCP (radiochemical purity) by HPLC ±90% could be achieved. Purification and concentration of the eluate with anion exchange has the benefit of more elutable (68)Ga with 1 M HCl as eluens. The additional washing step of the anion column

  18. 40 CFR 68.15 - Management.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Management. 68.15 Section 68.15... ACCIDENT PREVENTION PROVISIONS General § 68.15 Management. (a) The owner or operator of a stationary source with processes subject to Program 2 or Program 3 shall develop a management system to oversee the...

  19. [68Ga]DOTATATE PET/MRI and [18F]FDG PET/CT are complementary and superior to diffusion-weighted MR imaging for radioactive-iodine-refractory differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Vrachimis, Alexis; Stegger, Lars; Wenning, Christian; Noto, Benjamin; Konnert, Julia Renate; Riemann, Burkhard; Weckesser, Matthias; Burg, Matthias Christian; Allkemper, Thomas; Heindel, Walter; Schaefers, Michael

    2016-01-01

    The purpose of this study was to determine whether [ 68 Ga]DOTATATE PET/MRI with diffusion-weighted imaging (DWI) can replace or complement [ 18 F]FDG PET/CT in patients with radioactive-iodine (RAI)-refractory differentiated thyroid cancer (DTC). The study population comprised 12 patients with elevated thyroglobulin and a negative RAI scan after thyroidectomy and RAI remnant ablation who underwent both [ 18 F]FDG PET/CT and [ 68 Ga]DOTATATE PET/MRI within 8 weeks of each other. The presence of recurrent cancer was evaluated on a per-patient, per-organ and per-lesion basis. Histology, and prior and follow-up examinations served as the standard of reference. Recurrent or metastatic tumour was confirmed in 11 of the 12 patients. [ 68 Ga]DOTATATE PET(/MRI) correctly identified the tumour burden in all 11 patients, whereas in one patient local relapse was missed by [ 18 F]FDG PET/CT. In the lesion-based analysis, overall lesion detection rates were 79/85 (93 %), 69/85 (81 %) and 27/82 (33 %) for [ 18 F]FDG PET/CT, [ 68 Ga]DOTATATE PET/MRI and DWI, respectively. [ 18 F]FDG PET(/CT) was superior to [ 68 Ga]DOTATATE PET(/MRI) in the overall evaluation and in the detection of pulmonary metastases. In the detection of extrapulmonary metastases, [ 68 Ga]DOTATATE PET(/MRI) showed a higher sensitivity than [ 18 F]FDG PET(/CT), at the cost of lower specificity. DWI achieved only poor sensitivity and was significantly inferior to [ 18 F]FDG PET in the lesion-based evaluation in the detection of both extrapulmonary and pulmonary metastases. [ 18 F]FDG PET/CT was more sensitive than [ 68 Ga]DOTATATE PET/MRI in the evaluation of RAI-refractory DTC, mostly because of its excellent ability to detect lung metastases. In the evaluation of extrapulmonary lesions, [ 68 Ga]DOTATATE PET(/MRI) was more sensitive and [ 18 F]FDG PET(/CT) more specific. Furthermore, DWI did not provide additional information and cannot replace [ 18 F]FDG PET for postoperative monitoring of patients with

  20. 40 CFR 68.12 - General requirements.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS General § 68.12 General requirements. (a) General requirements. The... the five-year accident history for the process as provided in § 68.42 of this part and submit it in... §§ 68.150 to 68.185. The RMP shall include a registration that reflects all covered processes. (b...

  1. Delineating sites of failure following post-prostatectomy radiation treatment using 68Ga-PSMA-PET.

    Science.gov (United States)

    Byrne, Keelan; Eade, Thomas; Kneebone, Andrew; Guo, Linxin; Hsiao, Ed; Schembri, Geoff; Kwong, Carolyn; Hunter, Julia; Emmett, Louise; Hruby, George

    2018-02-01

    To identify sites of failure with 68 Ga-PSMA-PET (PSMA-PET) imaging in patients who have Biochemical Failure (BF) following post-prostatectomy radiotherapy. Between June 2006 and January 2016, 409 men received post prostatectomy intensity modulated radiation treatment (IMRT) with protocolised planning. 310 patients received radiation treatment (RT) to the Prostate Fossa (PF) alone and 99 patients received RT to PF and pelvic lymphatics (PF + LN) usually in combination with androgen deprivation (AD) therapy. Any failure not detected on conventional imaging was delineated with PSMA-PET scanning. Sites of failure were characterised as in-field (PF ± LN), or out of field (nodal alone, distant metastatic alone (visceral or bone) or multi-site failure). Nodal failure was further divided into pelvic failure and/or distant failure. 119 men developed BF, defined as a PSA rise of >0.2 or greater, above post-RT nadir. Freedom from BF was 71% in the PF group and 70% in the PF + LN group, with median follow up of 52 and 44 months respectively. AD was used concomitantly in 13% of the PF group and 92% of the PF + LN group. 81 patients with BF (68%) had PSMA-PET imaging performed as per study intent, 67 (80%) of whom had PSMA avid disease identified. PSMA-PET delineated in-field failure occurred in 2/50 (4%) of the PF group and 1/17 (6%) in the PF + LN group. Nodal failure alone was 33/50 (66%) for the PF group vs 7/17 (41%) for the PF + LN group. For the nodal only failure patients, 18/33 (55%) had pelvic-only nodal failure in the PF group compared to 1/7 (14%) in the PF + LN group (p = 0.03). 16 (32%) of the PSMA avid failures in the PF group would have been encompassed by standard pelvic lymphatic radiotherapy volumes. Post-prostatectomy radiation treatment resulted in excellent in-field control rates. Isolated pelvic nodal failure was rare in those receiving radiotherapy to the prostatic fossa and pelvic nodes but accounted for one third of

  2. Quantitative analysis and comparison study of [18F]AlF-NOTA-PRGD2, [18F]FPPRGD2 and [68Ga]Ga-NOTA-PRGD2 using a reference tissue model.

    Directory of Open Access Journals (Sweden)

    Ning Guo

    Full Text Available With favorable pharmacokinetics and binding affinity for α(vβ(3 integrin, (18F-labeled dimeric cyclic RGD peptide ([(18F]FPPRGD2 has been intensively used as a PET imaging probe for lesion detection and therapy response monitoring. A recently introduced kit formulation method, which uses an (18F-fluoride-aluminum complex labeled RGD tracer ([(18F]AlF-NOTA-PRGD2, provides a strategy for simplifying the labeling procedure to facilitate clinical translation. Meanwhile, an easy-to-prepare (68Ga-labeled NOTA-PRGD2 has also been reported to have promising properties for imaging integrin α(vβ(3. The purpose of this study is to quantitatively compare the pharmacokinetic parameters of [(18F]FPPRGD2, [(18F]AlF-NOTA-PRGD2, and [(68Ga]Ga-NOTA-PRGD2. U87MG tumor-bearing mice underwent 60-min dynamic PET scans following the injection of three tracers. Kinetic parameters were calculated using Logan graphical analysis with reference tissue. Parametric maps were generated using voxel-level modeling. All three compounds showed high binding potential (Bp(ND = k(3/k(4 in tumor voxels. [(18F]AlF-NOTA-PRGD2 showed comparable Bp(ND value (3.75±0.65 with those of [(18F]FPPRGD2 (3.39±0.84 and [(68Ga]Ga-NOTA-PRGD2 (3.09±0.21 (p>0.05. Little difference was found in volume of distribution (V(T among these three RGD tracers in tumor, liver and muscle. Parametric maps showed similar kinetic parameters for all three tracers. We also demonstrated that the impact of non-specific binding could be eliminated in the kinetic analysis. Consequently, kinetic parameter estimation showed more comparable results among groups than static image analysis. In conclusion, [(18F]AlF-NOTA-PRGD2 and [(68Ga]Ga-NOTA-PRGD2 have comparable pharmacokinetics and quantitative parameters compared to those of [(18F]FPPRGD2. Despite the apparent difference in tumor uptake (%ID/g determined from static images and clearance pattern, the actual specific binding component extrapolated from kinetic

  3. Arabidopsis MYB68 in development and responses to environmental cues

    DEFF Research Database (Denmark)

    Feng, Caiping; Andreasson, E.; Maslak, A.

    2004-01-01

    The Arabidopsis MYB68 gene encodes a MYB family protein with N-terminal R2R3 DNA-binding domains. Analyses of MYB68 expression by RNA blot and a transposant gene-trap MYB68::GUS reporter indicated that MYB68 is expressed specifically in root pericycle cells. Root cultures of the myb68 mutant......, caused by the gene trap insertion in the first MYB68 exon, produced increased biomass and lignin levels compared to wild type. Under high temperature regimes, MYB68::GUS activity was elevated in roots, while vegetative growth of myb68 mutants was reduced compared to wild type. These data suggest that MYB...

  4. 68Ga-triacetylfusarinine C and 68Ga-ferrioxamine E for Aspergillus infection imaging: uptake specificity in various microorganisms

    NARCIS (Netherlands)

    Petrik, M.; Haas, H. de; Laverman, P.; Schrettl, M.; Franssen, G.M.; Blatzer, M.; Decristoforo, C.

    2014-01-01

    (68)Ga-triacetylfusarinine C ((68)Ga-TAFC) and (68)Ga-ferrioxamine E ((68)Ga-FOXE) showed excellent targeting properties in Aspergillus fumigatus rat infection model. Here, we report on the comparison of specificity towards different microorganisms and human lung cancer cells (H1299).The in vitro

  5. 7 CFR 3570.68 - Selection process.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Selection process. 3570.68 Section 3570.68 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, DEPARTMENT OF AGRICULTURE COMMUNITY PROGRAMS Community Facilities Grant Program § 3570.68 Selection process. Each request...

  6. Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide

    International Nuclear Information System (INIS)

    Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Uprimny, Christian; Guggenberg, Elisabeth von; Decristoforo, Clemens; Warwitz, Boris; Virgolini, Irene Johanna; Traub-Weidinger, Tatjana; Widmann, Gerlig

    2013-01-01

    The aim of this study was to evaluate the impact of 68 Ga-labelled DOTA 0 -lanreotide ( 68 Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or 68 Ga-labelled DOTA 0 ,Tyr 3 -octreotide ( 68 Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or 68 Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent 68 Ga-DOTA-LAN PET to evaluate a treatment option with 90 Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 ± 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. 68 Ga-DOTA-LAN and 68 Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of 68 Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p 68 Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p 68 Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV max ) regarding the primary tumour in 25 patients (p 68 Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. 68 Ga-DOTA-TOC revealed more tumour sites than 68 Ga-DOTA-LAN (106 vs 53). The tumour to background ratios for tumour and liver calculated from SUV max measurements were significantly higher for 68 Ga-DOTA-TOC than 68 Ga

  7. Study on synthesis of {sup 68}GeO{sub 2} and behavior of {sup 68}Ga{sup 3+} Generator column

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Gun Gyun; Lee, Jun Young; Hur, Min Gu; Yang, Srung Dae; Park, Jeong Hoon [Radiation Instrumentation Research Division, Korea Atomic Energy Research Institute (KAERI), Daejeon (Korea, Republic of); Kim, Sang Wook [Dept. of Advanced Materials Chemistry, Dongguk University, Gyeongju (Korea, Republic of)

    2017-02-15

    {sup 68}Ga has emerged as a promising candidate for non-invasive diagnostic imaging within Positron Emission Tomography (PET) because of its advantageous radiochemical characteristics (t{sub 1/2}= 68 min, β{sup +} yield ⁓89%). {sup 68}Ga forms a stable chelation with various ligands and it is possible to be quickly and easily study using a {sup 68}Ge/{sup 68}Ga generator. Commercial {sup 68}Ge/{sup 68}Ga generators are chromatographic system using the inorganic materials such as alumina and tin dioxide which are employed as column matrixes for {sup 68}Ge. In this study, we tried out to make {sup 68}Ge/{sup 68}Ga generator system with the {sup 68}GeO{sub 2} microstructures for column matrix. {sup 68}Ge tends to have stable bond with oxide as {sup 68}GeO{sub 2} microstructures. The {sup 68}GeO{sub 2} has been synthesized by hydrolysis of GeCl{sub 4} (sol-gel method) and characterized by X-ray diffraction and scanning electron microscope for geometrical analysis. The stability of GeO{sub 2} was tested using eluent with diverse solvents (water, ethanol and 0.1 N HCl). The radioactivity of {sup 68}Ga{sup 3+} in eluate through GeO{sub 2} was measured to prove a function as column material for a generation eluate through GeO{sub 2} was measured to prove a function as column material for a generator.

  8. 40 CFR 68.120 - Petition process.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Regulated Substances for Accidental Release Prevention § 68.120 Petition process. (a) Any person may petition the Administrator to modify, by addition or deletion, the... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Petition process. 68.120 Section 68...

  9. 41 CFR 105-68.995 - Principal.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Principal. 105-68.995 Section 105-68.995 Public Contracts and Property Management Federal Property Management Regulations System...-GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 105-68.995 Principal. Principal means— (a...

  10. Somatostatin receptor PET in neuroendocrine tumours: 68Ga-DOTA0,Tyr3-octreotide versus 68Ga-DOTA0-lanreotide.

    Science.gov (United States)

    Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Traub-Weidinger, Tatjana; Uprimny, Christian; von Guggenberg, Elisabeth; Decristoforo, Clemens; Warwitz, Boris; Widmann, Gerlig; Virgolini, Irene Johanna

    2013-02-01

    The aim of this study was to evaluate the impact of (68)Ga-labelled DOTA(0)-lanreotide ((68)Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or (68)Ga-labelled DOTA(0),Tyr(3)-octreotide ((68)Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or (68)Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent (68)Ga-DOTA-LAN PET to evaluate a treatment option with (90)Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 ± 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. (68)Ga-DOTA-LAN and (68)Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of (68)Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for (68)Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. (68)Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV(max)) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to (68)Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. (68)Ga-DOTA-TOC revealed more tumour sites than (68)Ga

  11. 40 CFR 68.155 - Executive summary.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Executive summary. 68.155 Section 68...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.155 Executive summary. The owner or operator shall provide in the RMP an executive summary that includes a brief description of the following...

  12. Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1.

    Science.gov (United States)

    Hendricks, Louie; Aziz, Monowar; Yang, Weng-Lang; Nicastro, Jeffrey; Coppa, Gene F; Symons, Marc; Wang, Ping

    2017-02-01

    Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation. The purity of BMDN was verified by flow cytometry with CD11b/Gr-1 staining. Neutrophils were stimulated with N-formylmethionine-leucine-phenylalanine (f-MLP) (10 nM) in the presence or absence of MSP68 at 10 nM or cecal ligation and puncture (CLP) was used to induce sepsis, and MSP68 was administered at 1 mg/kg intravenously. Cytoskeletal organization was assessed by phalloidin staining, followed by analysis using fluorescence microscopy. Activity of the Rac1 GTPase in f-MLP or CLP-activated BMDN in the presence or absence of MSP68 was assessed by GTPase enzyme-linked immunosorbent assay. Mitogen-activated protein (MAP) kinase activity was determined by western blot densitometry. BMDN treatment with f-MLP increased cytoskeletal remodeling as revealed by the localization of filamentous actin to the periphery of the neutrophil. By contrast, cells pretreated with MSP68 had considerably reduced filamentous actin polymerization. Cytoskeletal spreading is associated with the activation of the small GTPase Rac1. We found BMDN-treated with f-MLP or that were exposed to sepsis by CLP had increased Rac1 signaling, whereas the cells pretreated with MSP68 had significantly reduced Rac1 activation (P Rac1-MAP kinase-mediated neutrophil motility. Thus, MSP68 is a novel therapeutic candidate for regulating inflammation and tissue damage caused

  13. The study on Ge-68 production

    International Nuclear Information System (INIS)

    Yang, Seung Dae; Kim, Sang Wook; Hur, Min Goo

    2009-06-01

    The Ge-68 is a correction source of PET and is used in radiopharmaceuticals synthesis. This project is mainly aimed to produce the Ge-68. Based on this project results, the local Ge-68 production can be possible and the revitalization of the radioisotope utilization research areas can be accomplished. The characteristics of the Ge-68 and Ga-68 are obtained and analyzed. The production conditions are also developed, and the domestic and overseas status of the art are considered. The stacked foil target is designed using Al disc and dried Ga 2 O 3 powder, and the irradiation target is also designed. The cross section of the nat. Ga(p,xn) 68 Ge reaction is obtained using the developed target. The separation experiment of cold Ge/Ga in the H 2 SO 4 -HCl solution are carried out as a simulation experiment of the radioactive Ge/Ga sources. The separation of Ge/Ga by liquid extraction of CCl 4 in 8M HCl is also accomplished. And the synthesis experiment of the Hematophorphyrin-Ga complex is performed

  14. Radiation exposure to nuclear medicine personnel handling positron emitters from 68Ge/68Ga generator

    International Nuclear Information System (INIS)

    Dwivedi, Durgesh Kumar; Snehlata; Kumar, Rakesh; Naswa, Niraj; Sharma, Punit; Malhotra, Arun; Bandopadhayaya, Guru Pad; Bal, Chandrashekhar; Dwivedi, Alok Kumar; Lochab, Satya Pal; Pant, Gauri Shankar

    2011-01-01

    To measure the radiation exposure to nuclear medicine personnel during synthesis and injection to the patients of 68 Ga 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-1-Nal -octreotide (NOC)- (DOTA-NOC) using ring thermoluminescence dosimeters (TLDs). Synthesis of 68 Ga DOTA-NOC was done on a semi-automated system. Finger doses were measured during synthesis and injection of 68 Ga DOTA-NOC. The occupational workers wore TLDs at the base of ring finger of both hands. The finger doses of two radio chemists were measured during synthesis of 68 Ga DOTA-NOC while that of a physician during its injection to the patients. Duration of the study was eight months and a total of 20 samples were prepared. During synthesis, the mean dose to base of left ring finger was 3.02 ± 1.01 mSv and to base of right ring finger was 1.96 ±0.86 mSv. Mean dose to base of left ring finger was 1.26 ± 0.35 mSv while that to base of right ring finger was 1.03 ± 0.13 mSv during injection. The mean dose was observed to be higher during synthesis than injection. However, the difference was not significant (P = 0.27 and P = 0.18, respectively). Overall mean finger dose of left hand was 2.43 ±1.21 mSv, whereas for the right hand the same was 1.65±0.82 mSv. Finger doses to radio chemists during semi-automated synthesis of 68 Ga DOTA-NOC and that to the physician involved in injection of 68 Ga DOTA-NOC were found to be within permissible limits. Ring dosimeters must be worn for the safety of the nuclear medicine personnel involved in synthesis and injection of 68 Ga DOTA-NOC. (author)

  15. A Comparative 68Ga-Citrate and 68Ga-Chloride PET/CT Imaging of Staphylococcus aureus Osteomyelitis in the Rat Tibia

    Directory of Open Access Journals (Sweden)

    Petteri Lankinen

    2018-01-01

    Full Text Available There may be some differences in the in vivo behavior of 68Ga-chloride and 68Ga-citrate leading to different accumulation profiles. This study compared 68Ga-citrate and 68Ga-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n=32. Two weeks after surgery, PET/CT imaging was performed on consecutive days using 68Ga-citrate or 68Ga-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUVmax of 68Ga-chloride and 68Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp. were significantly higher (P=0.0019 and P=0.0020, resp. than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.. In osteomyelitic tibias, the SUVmax of 68Ga-citrate was significantly higher than the uptake of 68Ga-chloride (P=0.0017. In animals with uncomplicated bone healing, no difference in the SUVmax of 68Ga-chloride or 68Ga-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of 68Ga-citrate for PET imaging of osteomyelitis.

  16. 40 CFR 68.90 - Applicability.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Emergency Response § 68.90 Applicability. (a) Except as provided in... processes shall comply with the requirements of § 68.95. (b) The owner or operator of stationary source...

  17. In Vivo Imaging of Experimental Melanoma Tumors using the Novel Radiotracer 68Ga-NODAGA-Procainamide (PCA).

    Science.gov (United States)

    Kertész, István; Vida, András; Nagy, Gábor; Emri, Miklós; Farkas, Antal; Kis, Adrienn; Angyal, János; Dénes, Noémi; Szabó, Judit P; Kovács, Tünde; Bai, Péter; Trencsényi, György

    2017-01-01

    The most aggressive form of skin cancer is the malignant melanoma. Because of its high metastatic potential the early detection of primary melanoma tumors and metastases using non-invasive PET imaging determines the outcome of the disease. Previous studies have already shown that benzamide derivatives, such as procainamide (PCA) specifically bind to melanin pigment. The aim of this study was to synthesize and investigate the melanin specificity of the novel 68 Ga-labeled NODAGA-PCA molecule in vitro and in vivo using PET techniques. Procainamide (PCA) was conjugated with NODAGA chelator and was labeled with Ga-68 ( 68 Ga-NODAGA-PCA). The melanin specificity of 68 Ga-NODAGA-PCA was tested in vitro , ex vivo and in vivo using melanotic B16-F10 and amelanotic Melur melanoma cell lines. By subcutaneous and intravenous injection of melanoma cells tumor-bearing mice were prepared, on which biodistribution studies and small animal PET/CT scans were performed for 68 Ga-NODAGA-PCA and 18 FDG tracers. 68 Ga-NODAGA-PCA was produced with high specific activity (14.9±3.9 GBq/µmol) and with excellent radiochemical purity (98%PCA uptake of B16-F10 cells was significantly ( p ≤0.01) higher than Melur cells. Ex vivo biodistribution and in vivo PET/CT studies using subcutaneous and metastatic tumor models showed significantly ( p ≤0.01) higher 68 Ga-NODAGA-PCA uptake in B16-F10 primary tumors and lung metastases in comparison with amelanotic Melur tumors. In experiments where 18 FDG and 68 Ga-NODAGA-PCA uptake of B16-F10 tumors was compared, we found that the tumor-to-muscle (T/M) and tumor-to-lung (T/L) ratios were significantly ( p ≤0.05 and p ≤0.01) higher using 68 Ga-NODAGA-PCA than the 18 FDG accumulation. Our novel radiotracer 68 Ga-NODAGA-PCA showed specific binding to the melanin producing experimental melanoma tumors. Therefore, 68 Ga-NODAGA-PCA is a suitable diagnostic radiotracer for the detection of melanoma tumors and metastases in vivo .

  18. Reduction of 68Ge activity containing liquid waste from 68Ga PET chemistry in nuclear medicine and radiopharmacy by solidification

    NARCIS (Netherlands)

    E. de Blois (Erik); H.S. Chan (Ho Sze); K. Roy (Kamalika); E.P. Krenning (Eric); W.A.P. Breeman (Wouter)

    2011-01-01

    textabstractPET with68Ga from the TiO2- or SnO2- based68Ge/68Ga generators is of increasing interest for PET imaging in nuclear medicine. In general, radionuclidic purity (68Ge vs.68Ga activity) of the eluate of these generators varies between 0.01 and 0.001%. Liquid waste containing low amounts

  19. 40 CFR 68.185 - Certification.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Certification. 68.185 Section 68.185 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL... certification that, to the best of the signer's knowledge, information, and belief formed after reasonable...

  20. 40 CFR 68.54 - Training.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Training. 68.54 Section 68.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL... operator may certify in writing that the employee has the required knowledge, skills, and abilities to...

  1. Determination of 68Ga production parameters by different reactions ...

    Indian Academy of Sciences (India)

    Gallium-68 (1/2 = 68 min, + = 89%) is an important positron-emitting radionuclide for positron emission tomography and used in nuclear medicine for diagnosing tumours. This study gives a suitable reaction to produce 68Ga. Gallium-68 excitation function via 68Zn(, ) 68Ga, 68Zn(, 2) 68Ga, 70Zn(, 3) 68Ga and ...

  2. 40 CFR 68.71 - Training.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Training. 68.71 Section 68.71 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL... June 21, 1999 an owner or operator may certify in writing that the employee has the required knowledge...

  3. Role of {sup 68}Ga-DOTATOC PET-CT in the diagnosis and staging of pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rakesh; Sharma, Punit; Karunanithi, Sellam; Naswa, Niraj; Lata, Sneh; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Garg, Pramod [All India Institute of Medical Sciences, Department of Gastroenterology and Human Nutrition, New Delhi (India); Sharma, Raju; Thulkar, Sanjay [All India Institute of Medical Sciences, Department of Radiodiagnosis, New Delhi (India)

    2011-11-15

    The objective of the present study was to evaluate the role of {sup 68}Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide ({sup 68}Ga-DOTATOC) positron emission tomography computed tomography (PET-CT) for detection and staging of pancreatic neuroendocrine tumours (NETs). Twenty patients with clinically suspected and/or histopathologically proven pancreatic NET underwent {sup 68}Ga-DOTATOC PET-CT imaging for staging and /or localisation of primary lesion. They also underwent contrast enhanced CT (CECT) and 8 patients underwent {sup 18}F-FDG PET-CT. SUVmax of primary and metastatic lesions were measured. Results were verified with histopathology for primary tumour and with clinical follow up/MRI and /or biopsy for metastatic disease. Results of {sup 68}Ga-DOTATOC PET-CT were compared to CECT and {sup 18}F-FDG PET-CT. {sup 68}Ga-DOTATOC PET-CT correctly localised primary in all 20, CECT in 15 and {sup 18}F-FDG PET-CT in 2 patients. {sup 68}Ga-DOTATOC PET-CT demonstrated metastases in 13 patients, CECT in 7 and {sup 18}F-FDG PET-CT in 2. {sup 68}Ga-DOTATOC PET-CT emerged as the best investigation with 100% sensitivity and PPV for detecting primary tumour and metastatic disease. The detection rate of CECT was lower than {sup 68}Ga-DOTATOC PET-CT, both for primary tumour (20vs.15) or metastatic disease (13vs.7). {sup 18}F-FDG PET-CT performed poorly for primary and metastasis. Ga-DOTATOC PET-CT is a very useful imaging investigation for diagnosing and staging pancreatic NET. (orig.)

  4. Characteristics of SnO{sub 2}-based {sup 68}Ge/{sup 68}Ga generator and aspects of radiolabelling DOTA-peptides

    Energy Technology Data Exchange (ETDEWEB)

    Blois, Erik de; Chan, Ho Sze [Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam (Netherlands); Naidoo, Clive; Prince, Deidre [iThemba Labs, Somerset West, Republic of South Africa (South Africa); Krenning, Eric P. [Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam (Netherlands); Department of Internal Medicine, Erasmus MC Rotterdam, Rotterdam (Netherlands); Breeman, Wouter A.P., E-mail: w.a.p.breeman@erasmusmc.n [Department of Nuclear Medicine, Erasmus MC Rotterdam, Rotterdam (Netherlands)

    2011-02-15

    Objectives: PET scintigraphy with {sup 68}Ga-labelled analogs is of increasing interest in Nuclear Medicine and performed all over the world. Here we report the characteristics of the eluate of SnO{sub 2}-based {sup 68}Ge/{sup 68}Ga generators prepared by iThemba LABS (Somerset West, South Africa). Three purification and concentration techniques of the eluate for labelling DOTA-TATE and concordant SPE purifications were investigated. Methods: Characteristics of 4 SnO{sub 2}-based generators (range 0.4-1 GBq {sup 68}Ga in the eluate) and several concentration techniques of the eluate (HCl) were evaluated. The elution profiles of SnO{sub 2}-based {sup 68}Ge/{sup 68}Ga generators were monitored, while [HCl] of the eluens was varied from 0.3-1.0 M. Metal ions and sterility of the eluate were determined by ICP. Fractionated elution and concentration of the {sup 68}Ga eluate were performed using anion and cation exchange. Concentrated {sup 68}Ga eluate, using all three concentration techniques, was used for labelling of DOTA-TATE. {sup 68}Ga-DOTA-TATE-containing solution was purified and RNP increased by SPE, therefore also 11 commercially available SPE columns were investigated. Results: The amount of elutable {sup 68}Ga activity varies when the concentration of the eluens, HCl, was varied, while {sup 68}Ge activity remains virtually constant. SnO{sub 2}-based {sup 68}Ge/{sup 68}Ga generator elutes at 0.6 M HCl >100% of the {sup 68}Ga activity at calibration time and {+-}75% after 300 days. Eluate at discharge was sterile and Endotoxins were <0.5 EU/mL, RNP was always <0.01%. Metal ions in the eluate were <10 ppm (in total). Highest desorption for anion purification was obtained with the 30 mg Oasis WAX column (>80%). Highest desorption for cation purification was obtained using a solution containing 90% acetone at increasing molarity of HCl, resulted in a {sup 68}Ga desorption of 68{+-}8%. With all {sup 68}Ge/{sup 68}Ga generators and for all 3 purification methods a

  5. 44 CFR 68.11 - Determination.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Determination. 68.11 Section... § 68.11 Determination. The board shall render its written decision within 45 days after the conclusion... Administrator for review and approval. The Administrator shall make the final base flood elevation determination...

  6. Feasibility and availability of 68Ga-labelled peptides

    International Nuclear Information System (INIS)

    Decristoforo, Clemens; Pickett, Roger D.; Verbruggen, Alfons

    2012-01-01

    68 Ga has attracted tremendous interest as a radionuclide for PET based on its suitable half-life of 68 min, high positron emission yield and ready availability from 68 Ge/ 68 Ga generators, making it independent of cyclotron production. 68 Ga-labelled DOTA-conjugated somatostatin analogues, including DOTA-TOC, DOTA-TATE and DOTA-NOC, have driven the development of technologies to provide such radiopharmaceuticals for clinical applications mainly in the diagnosis of somatostatin receptor-expressing tumours. We summarize the issues determining the feasibility and availability of 68 Ga-labelled peptides, including generator technology, 68 Ga generator eluate postprocessing methods, radiolabelling, automation and peptide developments, and also quality assurance and regulatory aspects. 68 Ge/ 68 Ga generators based on SnO 2 , TiO 2 or organic matrices are today routinely supplied to nuclear medicine departments, and a variety of automated systems for postprocessing and radiolabelling have been developed. New developments include improved chelators for 68 Ga that could open new ways to utilize this technology. Challenges and limitations in the on-site preparation and use of 68 Ga-labelled peptides outside the marketing authorization track are also discussed. (orig.)

  7. 21 CFR 640.68 - Processing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Processing. 640.68 Section 640.68 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS ADDITIONAL... deterioration or contamination. Prior to filling, the final container shall be marked or identified by number or...

  8. Assessing Glomerular Filtration in Small Animals Using [68Ga]DTPA and [68Ga]EDTA with PET Imaging.

    Science.gov (United States)

    Gündel, Daniel; Pohle, Ulrike; Prell, Erik; Odparlik, Andreas; Thews, Oliver

    2018-06-01

    Determining the glomerular filtration rate (GFR) is essential for clinical medicine but also for pre-clinical animal studies. Functional imaging using positron emission tomography (PET) allows repetitive almost non-invasive measurements. The aim of the study was the development and evaluation of easily synthesizable PET tracers for GFR measurements in small animals. Diethylenetriaminepentaacetic acid (DTPA) and ethylenediaminetetraacetic acid (EDTA) were labeled with Ga-68. The binding to blood cells and plasma proteins was tested in vitro. The distribution of the tracers in rats was analyzed by PET imaging and ex vivo measurements. From the time-activity-curve of the blood compartment (heart) and the total tracer mass excreted by the kidney, the GFR was calculated. These values were compared directly with the inulin clearance in the same animals. Both tracers did not bind to blood cells. [ 68 Ga]DPTA but not [ 68 Ga]EDTA showed strong binding to plasma proteins. For this reason, [ 68 Ga]DPTA stayed much longer in the blood and only 30 % of the injected dose was eliminated by the kidney within 60 min whereas the excretion of [ 68 Ga]EDTA was 89 ± 1 %. The calculated GFR using [ 68 Ga]EDTA was comparable to the measured inulin clearance in the same animal. Using [ 68 Ga]-DPTA, the measurements led to values which were 80 % below the normal GFR. The results also revealed that definition of the volume of interest for the blood compartment affects the calculation and may lead to a slight overestimation of the GFR. [ 68 Ga]EDTA is a suitable tracer for GFR calculation from PET imaging in small animals. It is easy to be labeled, and the results are in good accordance with the inulin clearance. [ 68 Ga]DTPA led to a marked underestimation of GFR due to its strong binding to plasma proteins and is therefore not an appropriate tracer for GFR measurements.

  9. Comparison of the prognostic values of {sup 68}Ga-DOTANOC PET/CT and {sup 18}F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Punit; Naswa, Niraj; Kc, Sudhir Suman; Yadav, Yashwant; Kumar, Rakesh; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Alvarado, Luis Andres; Dwivedi, Alok Kumar [Texas Tech University Health Sciences Center, Division of Biostatistics and Epidemiology, El Paso, TX (United States); Ammini, Ariachery C. [All India Institute of Medical Sciences, Department of Endocrinology and Metabolism, New Delhi (India)

    2014-12-15

    To determine the prognostic value of {sup 68}Ga-DOTANOC PET/CT in patients with well-differentiated neuroendocrine tumor (NET), and to compare the prognostic value with that of {sup 18}F-FDG PET/CT and other conventional clinicopathological prognostic factors. Data from 37 consecutive patients (age 46.6 ± 13.5 years, 51 % men) with well-differentiated NET who underwent {sup 68}Ga-DOTANOC PET/CT and {sup 18}F-FDG PET/CT were analyzed. All patients underwent a baseline visit with laboratory and radiological examinations. Clinical and imaging follow-up was performed in all patients. Progression-free survival (PFS) was measured from the date of the first PET/CT scan to the first documentation of progression of disease. {sup 68}Ga-DOTANOC PET/CT was positive in 37 of the 37 patients and {sup 18}F-FDG PET/CT was positive in 21. During follow-up 10 patients (27 %) showed progression of disease and 27 (73 %) showed no progression (24 stable disease, 3 partial response). The median follow-up was 25 months (range 2 - 52 months). Among the variables evaluated none was significantly different between the progressive disease and nonprogressive disease groups, with only SUVmax on {sup 68}Ga-DOTANOC PET/CT being borderline significant (P = 0.073). In the univariate analysis for PFS outcome, SUVmax on {sup 68}Ga-DOTANOC PET/CT (HR 0.122, 95 % CI 0.019 - 0.779; P = 0.026) and histopathological tumor grade (HR 4.238, 95 % CI 1.058 - 16.976; P = 0.041) were found to be associated with PFS. Other factors including age, sex, primary site, Ki-67 index, TNM stage, {sup 18}F-FDG PET/CT status (positive/negative), SUVmax on {sup 18}F-FDG PET/CT and type of treatment were not significant. In multivariable analysis, only SUVmax on {sup 68}Ga-DOTANOC PET/CT was found to be an independent positive predictor of PFS (HR 0.122, 95 % CI 0.019 - 0.779; P = 0.026). SUVmax measured on {sup 68}Ga-DOTANOC PET/CT is an independent, positive prognostic factor in patients with well-differentiated NET and

  10. [68Ga]pentixafor for CXCR4 imaging in a PC-3 prostate cancer xenograft model - comparison with [18F]FDG PET/CT, MRI and ex vivo receptor expression.

    Science.gov (United States)

    Schwarzenböck, Sarah M; Stenzel, Jan; Otto, Thomas; Helldorff, Heike V; Bergner, Carina; Kurth, Jens; Polei, Stefan; Lindner, Tobias; Rauer, Romina; Hohn, Alexander; Hakenberg, Oliver W; Wester, Hans J; Vollmar, Brigitte; Krause, Bernd J

    2017-11-10

    The aim was to characterize the properties of [ 68 Ga]Pentixafor as tracer for prostate cancer imaging in a PC-3 prostate cancer xenograft mouse model and to investigate its correlation with [ 18 F]FDG PET/CT, magnetic resonance imaging (MRI) and ex vivo analyses. Static [ 68 Ga]Pentixafor and [ 18 F]FDG PET as well as morphological/ diffusion weighted MRI and 1 H MR spectroscopy was performed. Imaging data were correlated with ex vivo biodistribution and CXCR4 expression in PC-3 tumors (immunohistochemistry (IHC), mRNA analysis). Flow cytometry was performed for evaluation of localization of CXCR4 receptors ( in vitro PC-3 cell experiments). Tumor uptake of [ 68 Ga]Pentixafor was significantly lower compared to [ 18 F]FDG. Ex vivo CXCR4 mRNA expression of tumors was shown by PCR. Only faint tumor CXCR4 expression was shown by IHC (immuno reactive score of 3). Accordingly, flow cytometry of PC-3 cells revealed only a faint signal, cell membrane permeabilisation showed a slight signal increase. There was no significant correlation of [ 68 Ga]Pentixafor tumor uptake and ex vivo receptor expression. Spectroscopy showed typical spectra of prostate cancer. PC-3 tumor uptake of [ 68 Ga]Pentixafor was existent but lower compared to [ 18 F]FDG. No significant correlation of ex vivo tumor CXCR4 receptor expression and [ 68 Ga]Pentixafor tumor uptake was shown. CXCR4 receptor expression on the surface of PC-3 cells was existent but rather low possibly explaining the limited [ 68 Ga]Pentixafor tumor uptake; receptor localization in the interior of PC-3 cells is presumable as shown by cell membrane permeabilisation. Further studies are necessary to define the role of [ 68 Ga]Pentixafor in prostate cancer imaging.

  11. 40 CFR 68.165 - Offsite consequence analysis.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Offsite consequence analysis. 68.165 Section 68.165 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.165 Offsite consequence...

  12. 7 CFR 1753.68 - Purchasing special equipment.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Purchasing special equipment. 1753.68 Section 1753.68... AGRICULTURE TELECOMMUNICATIONS SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Purchase and Installation of Special Equipment § 1753.68 Purchasing special equipment. (a) General. (1) Equipment purchases are...

  13. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism

    DEFF Research Database (Denmark)

    Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg

    2018-01-01

    (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. Methods: PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUVmax) by two independent examiners......, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Results: Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed...... in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut...

  14. 41 CFR 105-68.920 - Civil judgment.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Civil judgment. 105-68... Administration 68-GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 105-68.920 Civil judgment. Civil judgment means the disposition of a civil action by any court of competent jurisdiction...

  15. 47 CFR 68.108 - Incidence of harm.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Incidence of harm. 68.108 Section 68.108 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) CONNECTION OF TERMINAL EQUIPMENT TO THE TELEPHONE NETWORK Conditions on Use of Terminal Equipment § 68.108 Incidence of...

  16. Study of high spin states in 68Zn and 68Ga using (α,pγ) and (α,nγ) reactions

    International Nuclear Information System (INIS)

    Berthet, Bernard.

    1976-01-01

    Yrast levels of 68 Zn and 6 Ga have been studied via the reactions 65 Cu(α,pγ) 68 Zn, 65 Cu(α,nγ) 68 Ga at Esub(α)=12-21MeV and 66 Zn(α,pnγ) 68 Ga at Esub(α)=25-40MeV. The level schemes have been established by means of relative yield functions, electronic timing measurements, prompt and delayed γ-γ coincidences, angular distributions and directional orientation coincidences. Spin up to 8 were assigned to observed states, for 68 Zn. For 68 Ga, spins up to 11 + were assigned to level up to 4MeV excitation and the higher ones were interpreted by coupling a 67 Ga core with a 1gsub(9/2) neutron [fr

  17. Evaluation and comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET/CT imaging in well-differentiated thyroid cancer.

    Science.gov (United States)

    Ocak, Meltem; Demirci, Emre; Kabasakal, Levent; Aygun, Aslan; Tutar, Rumeysa O; Araman, Ahmet; Kanmaz, Bedii

    2013-11-01

    Somatostatin receptor (Sstr) scintigraphy with radiolabelled somatostatin analogues has been used extensively for the diagnosis and therapy of Sstr-expressing tumours. It has been shown that well-differentiated thyroid cancer (WDTC) cells have a high expression of Sstr2, Sstr3 and Sstr5. Hence, WDTC cells could be an ideal target for the evaluation of lesion uptake of Ga-68 DOTA-1-NaI3-octreotide (DOTA-NOC), which has a high affinity not only to Sstr2 but also to Sstr3 and Sstr5. The aim of the present study was to evaluate the value of Ga-68 DOTA-NOC as a target for Sstr2-expressing, Sstr3-expressing and Sstr5-expressing tumours in WDTC patients and to compare the results with those of Ga-68 DOTA-TATE in the same patient population. Thirteen patients with WDTC were included in our study: nine with papillary thyroid cancer, three with Hurthle cell carcinoma and one with follicular thyroid carcinoma. All patients had elevated serum thyroglobulin levels and negative post-therapeutic I-131 whole-body scans, which were obtained after the last radioiodine treatment. All patients had undergone two consecutive PET imaging studies with Ga-68 DOTA-D-Phe1-Tyr3-octreotate (DOTA-TATE) and Ga-68 DOTA-NOC, respectively. All images were evaluated visually, and maximum standardized uptake values were calculated. Both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC PET images gave comparable results. Among the 13 patients, imaging with both Ga-68 DOTA-TATE and Ga-68 DOTA-NOC gave negative results in five (38%) patients and positive results in eight (62%) patients. A total of 45 lesions were identified on Ga-68 DOTA-TATE images and 42 on Ga-68 DOTA-NOC images; three lesions were missed. Lesion uptake was significantly higher on Ga-68 DOTA-TATE images. Maximum standardized uptake values of Ga-68 DOTA-TATE and Ga-68 DOTA-NOC were 12.9±9.1 and 6.3±4.1 (n=54, PDOTA-TATE has a higher lesion uptake even in WDTC patients and may have potential advantage over Ga-68 DOTA-NOC.

  18. 41 CFR 105-68.905 - Affiliate.

    Science.gov (United States)

    2010-07-01

    ... management, ownership, or principal employees as the excluded person. ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Affiliate. 105-68.905 Section 105-68.905 Public Contracts and Property Management Federal Property Management Regulations System...

  19. Exploring Alternative Radiolabeling Strategies for Sialic Acid-Binding Immunoglobulin-Like Lectin 9 Peptide: [68Ga]Ga- and [18F]AlF-NOTA-Siglec-9

    Directory of Open Access Journals (Sweden)

    Olli Moisio

    2018-01-01

    Full Text Available Amino acid residues 283–297 from sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9 form a cyclic peptide ligand targeting vascular adhesion protein-1 (VAP-1. VAP-1 is associated with the transfer of leukocytes from blood to tissues upon inflammation. Therefore, analogs of Siglec-9 peptide are good candidates for visualizing inflammation non-invasively using positron emission tomography (PET. Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA-conjugated Siglec-9 has been evaluated extensively for this purpose. Here, we explored two alternative strategies for radiolabeling Siglec-9 peptide using a 1,4,7-triazacyclononane-triacetic acid (NOTA-chelator to bind [68Ga]Ga or [18F]AlF. The radioligands were evaluated by in vivo PET imaging and ex vivo γ-counting of turpentine-induced sterile skin/muscle inflammation in Sprague-Dawley rats. Both tracers showed clear accumulation in the inflamed tissues. The whole-body biodistribution patterns of the tracers were similar.

  20. High spin states in 66,68Ge

    International Nuclear Information System (INIS)

    Hermkens, U.; Becker, F.; Eberth, J.; Freund, S.; Mylaeus, T.; Skoda, S.; Teichert, W.; Werth, A. v.d.

    1992-01-01

    High spin states of 66,68 Ge have been investigated at the FN Tandem accelerator of the University of Koeln via the reactions 40 Ca( 32 S,α2p,4p) 66,68 Ge at a beam energy of 100 MeV and 58 Ni( 16 O,α2p) 68 Ge at 65 MeV. The OSIRIS spectrometer with 12 escape suppressed Ge detectors was used to measure γγ coincidences and γ-ray angular distributions. In 66 Ge ( 68 Ge) 33 (22) new levels were found and 63 (62) new γ-transitions were placed in the level scheme. Both nuclei show a rather complicated but similar excitation pattern, ruled by the interplay of quasiparticle and collective degrees of freedom. The results are compared to the recently published EXVAM calculations for 68 Ge. (orig.)

  1. Recommended administered activities for {sup 68}Ga-labelled peptides in paediatric nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Machado, J.S.; Beykan, S.; Lassmann, M. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Herrmann, K. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); David Geffen School of Medicine at UCLA, Department of Molecular and Medical Pharmacology, Los Angeles, CA (United States)

    2016-10-15

    The aim of this study was to establish a method for determining administered activities for {sup 68}Ga-labelled peptides. Dose calculations were based on the weight-independent effective dose model proposed by the EANM paediatric dosage card for use in paediatric nuclear medicine. Previously published time-integrated activity coefficients for {sup 68}Ga-DOTATATE, {sup 68}Ga-DOTATOC and {sup 68}Ga-pentixafor were used to calculate age-independent effective doses. Consequently, the corresponding weight-dependent effective dose coefficients were rescaled according to the formalism of the EANM dosage card to determine the radiopharmaceutical class of {sup 68}Ga-labelled peptides (''multiples'') and to calculate the baseline activities based on an upper limit for administered activity (185 MBq) in an adult. All calculated normalization factors suggest that the {sup 68}Ga-labelled peptides are class ''B'' radiopharmaceuticals. The baseline activity for all compounds is 12.8 MBq. In analogy to {sup 18}F-fluoride, we recommend a minimum activity of 14 MBq. For paediatric nuclear medicine applications involving {sup 68}Ga-labelled peptides, we suggest determining administered activities based on the formalism proposed in this work. The corresponding effective doses from these procedures will remain age-independent. (orig.)

  2. 40 CFR 68.81 - Incident investigation.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Incident investigation. 68.81 Section 68.81 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... appropriate knowledge and experience to thoroughly investigate and analyze the incident. (d) A report shall be...

  3. 44 CFR 68.9 - Admissible evidence.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Admissible evidence. 68.9 Section 68.9 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT OF... admissible. (b) Documentary and oral evidence shall be admissible. (c) Admissibility of non-expert testimony...

  4. Impact of ICRP publication 68

    International Nuclear Information System (INIS)

    Carter, M.W.; Woods, D.A.

    1996-01-01

    ICRP Publication 61 was a temporary replacement for ICRP Publication 30. It gave ALIs but not the underlying dose conversion factors. ICRP Publication 68 has now been issued to replace Publication 61; it contains the dose conversion factors but not the ALIs, so comparison is impossible without carrying out calculations. This paper presents comparisons between the two publications and calculates the ICRP Publication 68 ALIs for some of the more common radionuclides. (author)

  5. (67/68)Ga-labeling agent that liberates (67/68)Ga-NOTA-methionine by lysosomal proteolysis of parental low molecular weight polypeptides to reduce renal radioactivity levels.

    Science.gov (United States)

    Uehara, Tomoya; Rokugawa, Takemi; Kinoshita, Mai; Nemoto, Souki; Fransisco Lazaro, Guerra Gomez; Hanaoka, Hirofumi; Arano, Yasushi

    2014-11-19

    The renal localization of gallium-67 or gallium-68 ((67/68)Ga)-labeled low molecular weight (LMW) probes such as peptides and antibody fragments constitutes a problem in targeted imaging. Wu et al. previously showed that (67)Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bz-NOTA)-conjugated methionine ((67)Ga-NOTA-Met) was rapidly excreted from the kidney in urine following lysosomal proteolysis of the parental (67)Ga-NOTA-Bz-SCN-disulfide-stabilized Fv fragment (Bioconjugate Chem., (1997) 8, 365-369). In the present study, a new (67/68)Ga-labeling reagent for LMW probes that liberates (67/68)Ga-NOTA-Met was designed, synthesized, and evaluated using longer-lived (67)Ga in order to reduce renal radioactivity levels. We employed a methionine-isoleucine (MI) dipeptide bond as the cleavable linkage. The amine residue of MI was coupled with SCN-Bz-NOTA for (67)Ga-labeling, while the carboxylic acid residue of MI was derivatized to maleimide for antibody conjugation in order to synthesize NOTA-MI-Mal. A Fab fragment of the anti-Her2 antibody was thiolated with iminothiolane, and NOTA-MI-Mal was conjugated with the antibody fragment by maleimide-thiol chemistry. The Fab fragment was also conjugated with SCN-Bz-NOTA (NOTA-Fab) for comparison. (67)Ga-NOTA-MI-Fab was obtained at radiochemical yields of over 95% and was stable in murine serum for 24 h. In the biodistribution study using normal mice, (67)Ga-NOTA-MI-Fab registered significantly lower renal radioactivity levels from 1 to 6 h postinjection than those of (67)Ga-NOTA-Fab. An analysis of urine samples obtained 6 h after the injection of (67)Ga-NOTA-MI-Fab showed that the majority of radioactivity was excreted as (67)Ga-NOTA-Met. In the biodistribution study using tumor-bearing mice, the tumor to kidney ratios of (67)Ga-NOTA-MI-Fab were 4 times higher (6 h postinjection) than those of (67)Ga-NOTA-Fab. Although further studies including the structure of radiometabolites and

  6. Enterovirus D68 disease and molecular epidemiology in Australia.

    Science.gov (United States)

    Levy, Avram; Roberts, Jason; Lang, Jurissa; Tempone, Simone; Kesson, Alison; Dofai, Alfred; Daley, Andrew J; Thorley, Bruce; Speers, David J

    2015-08-01

    Enterovirus D68 (EV-D68) has received considerable recent attention as a cause of widespread respiratory illness. Neurological syndromes such as acute flaccid paralysis following EV-D68 infection have also been reported in a small number of cases. To summarize the clinical and epidemiological characteristics of laboratory confirmed EV-D68 cases in Australia. We combined EV-D68 data acquired through laboratory surveillance in Western Australia with cases from national enterovirus surveillance and regional acute flaccid paralysis (AFP) surveillance. Clinical data was obtained for EV-D68 cases and capsid protein sequences were used for phylogenetic analysis. Sporadic cases of EV-D68 were recorded in Australia since 2008, with peaks in activity during 2011 and 2013. EV-D68 was primarily associated with respiratory disease, but was also detected in cerebrospinal fluid of one patient and faeces of two patients presenting with AFP. EV-D68 has been circulating in Western Australia and is likely to have also been present in the wider region for a number of years, causing primarily respiratory disease. Detection of EV-D68 in cerebrospinal fluid of one patient and in faeces of two AFP cases reinforces the association between EV-D68 and neurological disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Feasibility and availability of {sup 68}Ga-labelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Decristoforo, Clemens [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); European Directorate of Quality of Medicines, Group 14, Radioactive Compounds, The European Pharmacopeia, Strasbourg (France); Pickett, Roger D. [GE Healthcare, Little Chalfont (United Kingdom); European Directorate of Quality of Medicines, Group 14, Radioactive Compounds, The European Pharmacopeia, Strasbourg (France); Verbruggen, Alfons [University of Leuven, Laboratory of Radiopharmacy, Department of Pharmaceutical Sciences, Leuven (Belgium); European Directorate of Quality of Medicines, Group 14, Radioactive Compounds, The European Pharmacopeia, Strasbourg (France)

    2012-02-15

    {sup 68}Ga has attracted tremendous interest as a radionuclide for PET based on its suitable half-life of 68 min, high positron emission yield and ready availability from {sup 68}Ge/{sup 68}Ga generators, making it independent of cyclotron production. {sup 68}Ga-labelled DOTA-conjugated somatostatin analogues, including DOTA-TOC, DOTA-TATE and DOTA-NOC, have driven the development of technologies to provide such radiopharmaceuticals for clinical applications mainly in the diagnosis of somatostatin receptor-expressing tumours. We summarize the issues determining the feasibility and availability of {sup 68}Ga-labelled peptides, including generator technology, {sup 68}Ga generator eluate postprocessing methods, radiolabelling, automation and peptide developments, and also quality assurance and regulatory aspects. {sup 68}Ge/{sup 68}Ga generators based on SnO{sub 2}, TiO{sub 2} or organic matrices are today routinely supplied to nuclear medicine departments, and a variety of automated systems for postprocessing and radiolabelling have been developed. New developments include improved chelators for {sup 68}Ga that could open new ways to utilize this technology. Challenges and limitations in the on-site preparation and use of {sup 68}Ga-labelled peptides outside the marketing authorization track are also discussed. (orig.)

  8. Applications of a Ga-68/Ge-68 generator system to brain imaging using a multiwire proportional chamber positron camera

    International Nuclear Information System (INIS)

    Hattner, R.S.; Lim, C.B.; Swann, S.J.; Kaufman, L.; Chu, D.; Perez-Mendez, V.

    1976-01-01

    A Ge-68/Ga-68 generator system has been applied to brain imaging in conjunction with a novel coincidence detection based positron camera. The camera consists of two opposed large area multiwire proportional chamber (MWPC) detectors interfaced to multichannel lead converter plates. Event localization is effected of delay lines. Ten patients with brain lesions have been studied 1-2 hours after the administration of Ga-68 formulated as DTPA. The images were compared to conventional brain scans, and to x-ray section scans (CAT). The positron studies have shown significant mitigation of confusing superficial activity resulting from craniotomy compared to conventional brain scans. Central necrosis of lesions observed in positron images, but not in the conventional scans has been confirmed in CAT. The economy of MWPC positron cameras combined with the ideal characteristics of the Ge-68/Ga-68 generator promise a cost efficient imaging system for the future

  9. 7 CFR 29.68 - Advance information.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Advance information. 29.68 Section 29.68 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... part of the contents of such certificate may be tel- egraphed or telephoned to him as his expense...

  10. Comparison of {sup 68}Ga-DOTATATE and {sup 68}Ga-DOTANOC PET/CT imaging in the same patient group with neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, Levent [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Cerrahpasa Tip Fakultesi, Nukleer Tip Anabilim Dali, Aksaray, Istanbul (Turkey); Demirci, Emre; Uslu, Ilhami; Kanmaz, Bedii [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Ocak, Meltem; Araman, Ahmet; Ozsoy, Yildiz [Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Decristoforo, Clemens [Medical University of Innsbruck, Clinical Department of Nuclear Medicine, Innsbruck (Austria)

    2012-08-15

    Recent studies have suggested that positron emission tomography (PET) imaging with {sup 68}Ga-labelled DOTA-somatostatin analogues (SST) like octreotide and octreotate is useful in diagnosing neuroendocrine tumours (NETs) and has superior value over both CT and planar and single photon emission computed tomography (SPECT) somatostatin receptor scintigraphy (SRS). The aim of the present study was to evaluate the role of {sup 68}Ga-DOTA-1-NaI{sup 3}-octreotide ({sup 68}Ga-DOTANOC) in patients with SST receptor-expressing tumours and to compare the results of {sup 68}Ga-DOTA-D-Phe{sup 1}-Tyr{sup 3}-octreotate ({sup 68}Ga-DOTATATE) in the same patient population. Twenty SRS were included in the study. Patients' age (n = 20) ranged from 25 to 75 years (mean 55.4 {+-} 12.7 years). There were eight patients with well-differentiated neuroendocrine tumour (WDNET) grade1, eight patients with WDNET grade 2, one patient with poorly differentiated neuroendocrine carcinoma (PDNEC) grade 3 and one patient with mixed adenoneuroendocrine tumour (MANEC). All patients had two consecutive PET studies with {sup 68}Ga-DOTATATE and {sup 68}Ga-DOTANOC. All images were evaluated visually and maximum standardized uptake values (SUV{sub max}) were also calculated for quantitative evaluation. On visual evaluation both tracers produced equally excellent image quality and similar body distribution. The physiological uptake sites of pituitary and salivary glands showed higher uptake in {sup 68}Ga-DOTATATE images. Liver and spleen uptake values were evaluated as equal. Both {sup 68}Ga-DOTATATE and {sup 68}Ga-DOTANOC were negative in 6 (30 %) patients and positive in 14 (70 %) patients. In {sup 68}Ga-DOTANOC images only 116 of 130 (89 %) lesions could be defined and 14 lesions were missed because of lack of any uptake. SUV{sub max} values of lesions were significantly higher on {sup 68}Ga-DOTATATE images. Our study demonstrated that the images obtained by {sup 68}Ga-DOTATATE and {sup 68}Ga

  11. Selected Ga-68-siderophores versus Ga-68-colloid and Ga-68-citrate: biodistribution and small animal imaging in mice

    Czech Academy of Sciences Publication Activity Database

    Petřík, M.; Vlčková, A.; Nový, Z.; Urbánek, Lubor; Haas, H.; Decristoforo, C.

    2015-01-01

    Roč. 159, č. 1 (2015), s. 60-66 ISSN 1213-8118 R&D Projects: GA MŠk(CZ) LO1304 Institutional support: RVO:61389030 Keywords : gallium-68 * siderophores * colloid Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.924, year: 2015

  12. 41 CFR 105-68.1005 - State.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false State. 105-68.1005...-GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Definitions § 105-68.1005 State. (a) State means— (1) Any of the states of the United States; (2) The District of Columbia; (3) The Commonwealth of Puerto...

  13. Parametric Net Influx Rate Images of 68Ga-DOTATOC and 68Ga-DOTATATE: Quantitative Accuracy and Improved Image Contrast.

    Science.gov (United States)

    Ilan, Ezgi; Sandström, Mattias; Velikyan, Irina; Sundin, Anders; Eriksson, Barbro; Lubberink, Mark

    2017-05-01

    68 Ga-DOTATOC and 68 Ga-DOTATATE are radiolabeled somatostatin analogs used for the diagnosis of somatostatin receptor-expressing neuroendocrine tumors (NETs), and SUV measurements are suggested for treatment monitoring. However, changes in net influx rate ( K i ) may better reflect treatment effects than those of the SUV, and accordingly there is a need to compute parametric images showing K i at the voxel level. The aim of this study was to evaluate parametric methods for computation of parametric K i images by comparison to volume of interest (VOI)-based methods and to assess image contrast in terms of tumor-to-liver ratio. Methods: Ten patients with metastatic NETs underwent a 45-min dynamic PET examination followed by whole-body PET/CT at 1 h after injection of 68 Ga-DOTATOC and 68 Ga-DOTATATE on consecutive days. Parametric K i images were computed using a basis function method (BFM) implementation of the 2-tissue-irreversible-compartment model and the Patlak method using a descending aorta image-derived input function, and mean tumor K i values were determined for 50% isocontour VOIs and compared with K i values based on nonlinear regression (NLR) of the whole-VOI time-activity curve. A subsample of healthy liver was delineated in the whole-body and K i images, and tumor-to-liver ratios were calculated to evaluate image contrast. Correlation ( R 2 ) and agreement between VOI-based and parametric K i values were assessed using regression and Bland-Altman analysis. Results: The R 2 between NLR-based and parametric image-based (BFM) tumor K i values was 0.98 (slope, 0.81) and 0.97 (slope, 0.88) for 68 Ga-DOTATOC and 68 Ga-DOTATATE, respectively. For Patlak analysis, the R 2 between NLR-based and parametric-based (Patlak) tumor K i was 0.95 (slope, 0.71) and 0.92 (slope, 0.74) for 68 Ga-DOTATOC and 68 Ga-DOTATATE, respectively. There was no bias between NLR and parametric-based K i values. Tumor-to-liver contrast was 1.6 and 2.0 times higher in the parametric

  14. 7 CFR 929.68 - Effective time.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Effective time. 929.68 Section 929.68 Agriculture... Effective time. The provisions of this part, and of any amendment thereto, shall become effective at such time as the Secretary may declare above his signature and shall continue in force until terminated in...

  15. 40 CFR 68.168 - Five-year accident history.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Five-year accident history. 68.168 Section 68.168 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.168 Five-year accident history...

  16. Direct comparison of 68Ga-DOTA-TOC and 18F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle

    OpenAIRE

    Nilica, Bernhard; Waitz, Dietmar; Stevanovic, Vlado; Uprimny, Christian; Kendler, Dorota; Buxbaum, Sabine; Warwitz, Boris; Gerardo, Llanos; Henninger, Benjamin; Virgolini, Irene; Rodrigues, Margarida

    2016-01-01

    Purpose To determine the value of 68Ga-DOTA-TOC and 18F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT). Methods We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined 68Ga-DOTA-TOC and 18F-FDG PET/CT studies. 68Ga-DOTA-TOC PET/CT was performed before PRRT, 3?months after completion of PRRT and after a further 6???9 months. 18F-FDG PET/CT was do...

  17. 40 CFR 61.68 - Emission monitoring.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Emission monitoring. 61.68 Section 61....68 Emission monitoring. (a) A vinyl chloride monitoring system is to be used to monitor on a... monitoring system(s) used to meet the requirement in paragraph (a) of this section is to be a device which...

  18. 41 CFR 50-204.68 - Hydrogen.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Hydrogen. 50-204.68..., Vapors, Fumes, Dusts, and Mists § 50-204.68 Hydrogen. The in-plant transfer, handling, storage, and utilization of hydrogen shall be in accordance with Compressed Gas Association Pamphlets G-5.1-1961 and G-5.2...

  19. High spin states in 68Zn

    International Nuclear Information System (INIS)

    Bruandet, J.-F.; Berthet, B.; Morand, C.; Gironi, A.; Longequeue, J.-P.; Tsan Ung Chan.

    1976-01-01

    Yrast levels of 68 Zn have been investigated via measurements of excitation functions and angular distributions of single γ-rays and of γ-γ coincidences. Following the 65 Cu(α,pγ) 68 Zn reaction with α particle energies between 12-21MeV. Spin up to J=8 were assigned to observed states [fr

  20. 68Ga-Based Radiopharmaceuticals: Production and Application Relationship

    Directory of Open Access Journals (Sweden)

    Irina Velikyan

    2015-07-01

    Full Text Available The contribution of 68Ga to the promotion and expansion of clinical research and routine positron emission tomography (PET for earlier better diagnostics and individualized medicine is considerable. The potential applications of 68Ga-comprising imaging agents include targeted, pre-targeted and non-targeted imaging. This review discusses the key aspects of the production of 68Ga and 68Ga-based radiopharmaceuticals in the light of the impact of regulatory requirements and endpoint pre-clinical and clinical applications.

  1. 27 CFR 19.68 - Other businesses.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Other businesses. 19.68... Activities Not Subject to This Part § 19.68 Other businesses. The appropriate TTB officer may authorize the carrying on of other businesses (not specifically prohibited by 26 U.S.C. 5601(a)(6)) on premises of plants...

  2. Når vi taler om 68

    DEFF Research Database (Denmark)

    Jensen, Henrik; Metz, Georg

    Når vi taler om 68 er en intellektuel samtale mellem to ligeværdige gentlemen og skallesmækkere. En essayistisk dyst om porno, RAF, Pittelkow og livsfilosofi......Når vi taler om 68 er en intellektuel samtale mellem to ligeværdige gentlemen og skallesmækkere. En essayistisk dyst om porno, RAF, Pittelkow og livsfilosofi...

  3. Prospective evaluation of 68Ga-DOTANOC PET-CT in differentiated thyroid cancer patients with raised thyroglobulin and negative 131I-whole body scan: comparison with 18F-FDG PET-CT

    International Nuclear Information System (INIS)

    Kundu, Parveen; Lata, Sneh; Sharma, Punit; Singh, Harmandeep; Malhotra, Arun; Bal, Chandrasekhar

    2014-01-01

    The purpose of the study was to evaluate the role of 68 Ga-DOTANOC PET-CT in differentiated thyroid cancer (DTC) patients with negative 131 I-whole body scan (WBS) along with serially increasing serum thyroglobulin (Tg), and compare the same with 18 F-FDG PET-CT. Sixty two DTC patients with serially rising Tg levels and negative 131 I-WBS were prospectively enrolled. All patients underwent 68 Ga-DOTANOC PET-CT and 18 F-FDG PET-CT within an interval of two weeks. PET-CT analysis was done on a per-patient basis, location wise and lesion wise. All PET-CT lesions were divided into four categories-local, nodal, pulmonary and skeletal. Histopathology and/or serial serum Tg level, clinical and imaging follow up (minimum-1 year) were used as a reference standard. Ga-DOTANOC PET-CT demonstrated disease in 40/62 (65 %) patients and 18 F-FDG PET-CT in 45/62 (72 %) patients, with no significant difference on McNemar analysis (p = 0.226). Per-patient sensitivity and specificity of 68 Ga-DOTANOC PET-CT was 78.4 %, 100 %, and for 18 F-FDG PET-CT was 86.3 %, 90.9 %, respectively. Out of 186 lesions detected by both PET-CTs, 121/186 (65 %) lesions were seen on 68 Ga-DOTANOC PET-CT and 168/186 (90.3 %) lesions on 18 F-FDG PET-CT (p 68 Ga-DOTANOC PET-CT and 18 F-FDG PET-CT for detection of local disease (k = 0.92), while moderate agreement was noted for nodal and pulmonary disease (k = 0.67). 68 Ga-DOTANOC PET-CT changed management in 21/62 (34 %) patients and 18 F-FDG PET-CT in 17/62 (27 %) patients. Ga-DOTANOC PET-CT is inferior to 18 F-FDG PET-CT on lesion based but not on patient based analysis for detection of recurrent/residual disease in DTC patients with negative WBS scan and elevated serum Tg levels. It can also help in selection of potential candidates for peptide receptor radionuclide therapy. (orig.)

  4. 29 CFR 801.68 - Authority of the Secretary.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Authority of the Secretary. 801.68 Section 801.68 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR OTHER LAWS APPLICATION... of Decision and Order of Administrative Law Judge § 801.68 Authority of the Secretary. (a) The...

  5. Direct comparison of 68Ga-DOTA-TOC and 18F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle

    International Nuclear Information System (INIS)

    Nilica, Bernhard; Waitz, Dietmar; Uprimny, Christian; Kendler, Dorota; Buxbaum, Sabine; Warwitz, Boris; Gerardo, Llanos; Virgolini, Irene; Rodrigues, Margarida; Stevanovic, Vlado; Henninger, Benjamin

    2016-01-01

    To determine the value of 68 Ga-DOTA-TOC and 18 F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT). We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined 68 Ga-DOTA-TOC and 18 F-FDG PET/CT studies. 68 Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 - 9 months. 18 F-FDG PET/CT was done within 2 months of 68 Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months). All patients were 68 Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 18 F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were 18 F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were 18 F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were 18 F-FDG-negative initially but 18 F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were 18 F-FDG-positive initially but 18 F-FDG-negative during follow-up (group 4). 18 F-FDG PET showed more and/or larger metastases than 68 Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 - 82 % from the first to the last follow-up investigation. In NET patients, the presence of 18 F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with 18 F-FDG-negative NET may show 18 F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have 18 F-FDG-positive tumours. Therefore, 18 F-FDG PET/CT is a complementary tool to 68 Ga-DOTA-TOC PET/CT with clinical relevance for molecular investigation

  6. Direct comparison of (68)Ga-DOTA-TOC and (18)F-FDG PET/CT in the follow-up of patients with neuroendocrine tumour treated with the first full peptide receptor radionuclide therapy cycle.

    Science.gov (United States)

    Nilica, Bernhard; Waitz, Dietmar; Stevanovic, Vlado; Uprimny, Christian; Kendler, Dorota; Buxbaum, Sabine; Warwitz, Boris; Gerardo, Llanos; Henninger, Benjamin; Virgolini, Irene; Rodrigues, Margarida

    2016-08-01

    To determine the value of (68)Ga-DOTA-TOC and (18)F-FDG PET/CT for initial and follow-up evaluation of patients with neuroendocrine tumour (NET) treated with peptide receptor radionuclide therapy (PRRT). We evaluated 66 patients who had histologically proven NET and underwent both PRRT and three combined (68)Ga-DOTA-TOC and (18)F-FDG PET/CT studies. (68)Ga-DOTA-TOC PET/CT was performed before PRRT, 3 months after completion of PRRT and after a further 6 - 9 months. (18)F-FDG PET/CT was done within 2 months of (68)Ga-DOTA-TOC PET/CT. Follow-up ranged from 11.8 to 80.0 months (mean 34.5 months). All patients were (68)Ga-DOTA-TOC PET-positive initially and at follow-up after the first full PRRT cycle. Overall, 62 of the 198 (18)F-FDG PET studies (31 %) were true-positive in 38 of the 66 patients (58 %). Of the 66 patients, 28 (5 grade 1, 23 grade 2) were (18)F-FDG-negative initially and during follow-up (group 1), 24 (5 grade 1, 13 grade 2, 6 grade 3) were (18)F-FDG-positive initially and during follow-up (group 2), 9 patients (2 grade 1, 6 grade 2, 1 grade 3) were (18)F-FDG-negative initially but (18)F-FDG-positive during follow-up (group 3), and 5 patients (all grade 2) were (18)F-FDG-positive initially but (18)F-FDG-negative during follow-up (group 4).(18)F-FDG PET showed more and/or larger metastases than (68)Ga-DOTA-TOC PET in five patients of group 2 and four patients of group 3, all with progressive disease. In three patients with progressive disease who died during follow-up tumour SUVmax increased by 41 - 82 % from the first to the last follow-up investigation. In NET patients, the presence of (18)F-FDG-positive tumours correlates strongly with a higher risk of progression. Initially, patients with (18)F-FDG-negative NET may show (18)F-FDG-positive tumours during follow-up. Also patients with grade 1 and grade 2 NET may have (18)F-FDG-positive tumours. Therefore, (18)F-FDG PET/CT is a complementary tool to (68)Ga-DOTA-TOC PET/CT with clinical

  7. Enterovirus D68 in Viet Nam (2009-2015).

    Science.gov (United States)

    Ny, Nguyen Thi Han; Anh, Nguyen To; Hang, Vu Thi Ty; Nguyet, Lam Anh; Thanh, Tran Tan; Ha, Do Quang; Minh, Ngo Ngoc Quang; Ha, Do Lien Anh; McBride, Angela; Tuan, Ha Manh; Baker, Stephen; Tam, Pham Thi Thanh; Phuc, Tran My; Huong, Dang Thao; Loi, Tran Quoc; Vu, Nguyen Tran Anh; Hung, Nguyen Van; Minh, Tran Thi Thuy; Xang, Nguyen Van; Dong, Nguyen; Nghia, Ho Dang Trung; Chau, Nguyen Van Vinh; Thwaites, Guy; van Doorn, H Rogier; Anscombe, Catherine; Le Van, Tan

    2017-01-01

    Since 1962, enterovirus D68 (EV-D68) has been implicated in multiple outbreaks and sporadic cases of respiratory infection worldwide, but especially in the USA and Europe with an increasing frequency between 2010 and 2014. We describe the detection, associated clinical features and molecular characterization of EV-D68 in central and southern Viet Nam between 2009 and 2015. Enterovirus/rhinovirus PCR positive respiratory or CSF samples taken from children and adults with respiratory/central nervous system infections in Viet Nam were tested by an EV-D68 specific PCR. The included samples were derived from 3 different observational studies conducted at referral hospitals across central and southern Viet Nam between 2009 and 2015. Whole-genome sequencing was carried out using a MiSeq based approach. Phylogenetic reconstruction and estimation of evolutionary rate and recombination were carried out in BEAST and Recombination Detection Program, respectively. EV-D68 was detected in 21/625 (3.4%) enterovirus/rhinovirus PCR positive respiratory samples but in none of the 15 CSF. All the EV-D68 patients were young children (age range: 11.8 - 24.5 months) and had moderate respiratory infections. Phylogenetic analysis suggested that the Vietnamese sequences clustered with those from Asian countries, of which 9 fell in the B1 clade, and the remaining sequence was identified within the A2 clade. One intra sub-clade recombination event was detected, representing the second reported recombination within EV-D68. The evolutionary rate of EV-D68 was estimated to be 5.12E -3 substitutions/site/year. Phylogenetic analysis indicated that the virus was imported into Viet Nam in 2008. We have demonstrated for the first time EV-D68 has been circulating at low levels in Viet Nam since 2008, associated with moderate acute respiratory infection in children. EV-D68 in Viet Nam is most closely related to Asian viruses, and clusters separately from recent US and European viruses that were

  8. Comparison of Ga-68 DOTA-TATE and Ga-68 DOTA-LAN PET/CT imaging in the same patient group with neuroendocrine tumours: preliminary results.

    Science.gov (United States)

    Demirci, Emre; Ocak, Meltem; Kabasakal, Levent; Araman, Ahmet; Ozsoy, Yildiz; Kanmaz, Bedii

    2013-08-01

    Recent studies have suggested that PET imaging with Ga-68-labelled DOTA-somatostatin analogues such as octreotide and octreotate is useful in diagnosing neuroendocrine tumours (NETs) and has superior value over both computed tomography and planar and SPECT somatostatin receptor scintigraphy. The aim of the present study was to evaluate the role of Ga-68 DOTA-lanreotide (Ga-68-DOTA-LAN) in patients with somatostatin receptor (sst)-expressing tumours and to compare the results of Ga-68 DOTA-D-Phe1-Tyr3-octreotate (Ga-68-DOTA-TATE) in the same patient population. Twelve patients with NETs who were referred to our department for somatostatin receptor scintigraphy were included in the study. There were four patients with well-differentiated neuroendocrine tumour (WDNET) grade 1, two patients with WDNET grade 2, and three patients with poorly differentiated neuroendocrine carcinoma (PDNEC) grade 3. There was also one patient with medullary thyroid cancer, one patient with meningioma and one patient with MEN-1. All patients underwent two consecutive PET imaging studies with Ga-68-DOTA-TATE and Ga-68 DOTA-LAN. All images were evaluated visually, and maximum standardized uptake value was calculated for quantitative evaluation. On visual examination of maximum intensity projection images, GA-68 DOTA-LAN was seen to have high background activity and high bone marrow uptake. Both tracers defined 67 lesions. Ga-68 DOTA-TATE images revealed 63 (94%) clearly defined lesions, missing four lesions. In contrast, Ga-68 DOTA-LAN images defined only 23 (44%) lesions, missing 44 (56%) lesions. Thirty-two bone lesions were detected on Ga-68-DOTA-TATE images. Among them, only 11 (34%) were positive on Ga-68 DOTA-LAN images, whereas 21 (66%) were negative. When we evaluated liver, mediastinum and gastrointestinal tract lesions, Ga-68 DOTA-LAN was seen to be positive for 12 (34%) lesions and negative for 23 (66%) lesions. Although the results are preliminary, the image quality obtained by

  9. 核蛋白Sam68的原核表达及鉴定%Prokaryotic Expression and Identification of Nuclear Protein Sam68

    Institute of Scientific and Technical Information of China (English)

    张华; 陈宁; 丁筠; 邹德华; 潘子夜; 李鹏飞; 李丽阳; 肖丽杰; 曹宏伟

    2017-01-01

    为了构建pGEX-4T-1-Sam68原核表达载体,表达并鉴定GST-Sam68融合蛋白,采用PCR扩增Sam68基因,插入pGEX-4T-1的EcoR I和Sal I位点,并转化Rosetta(DE3)大肠杆菌,IPTG诱导表达,SDS-PAGE和Western Blot验证蛋白表达,GST pull-down技术验证Sam68的结合活性.酶切和测序结果证实Sam68基因正确插入pGEX-4T-1载体中,载体能够在Rosetta(DE3)细胞中正确表达,且纯化的GST-Sam68蛋白具有与PI3K p85特异结合的活性,说明成功构建了原核表达载体pGEX-4T-1-Sam68.

  10. Liver and kidney imaging with Ga-68-labeled dihydroxyanthraquinones

    International Nuclear Information System (INIS)

    Schuhmacher, J.; Maier-Borst, W.; Wellman, H.N.

    1980-01-01

    This paper describes the preparation of alizarin (1,2-dihydroxyanthraquinone) and alizarin red S (sodium 1,2-dihydroxyanthraquinone-3-sulfonate) labeled with Ga-68, which is obtained from a new high-yield Ge-68 → Ga-68 generator. The uptake of Ga-68 alizarin by liver and spleen RES was studied in rats, dogs, and humans, and amounted to 80 to 85% of the administered dose within 5 min after i.v. injection. Gallium-68 alizarin red S was preferentially accumulated in the renal parenchyma to an extent of 70% within 2 hr after i.v. administration. Complete labeling of 1 mCi Ga-68 was achieved by 100 μg of each compound, amounts that are without any known measurable harm to humans

  11. Somatostatin receptor PET in neuroendocrine tumours: {sup 68}Ga-DOTA{sup 0},Tyr{sup 3}-octreotide versus {sup 68}Ga-DOTA{sup 0}-lanreotide

    Energy Technology Data Exchange (ETDEWEB)

    Putzer, Daniel; Kroiss, Alexander; Waitz, Dietmar; Gabriel, Michael; Uprimny, Christian; Guggenberg, Elisabeth von; Decristoforo, Clemens; Warwitz, Boris; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Traub-Weidinger, Tatjana [Vienna Medical University, Department of Nuclear Medicine, Vienna (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria)

    2013-03-15

    The aim of this study was to evaluate the impact of {sup 68}Ga-labelled DOTA{sup 0}-lanreotide ({sup 68}Ga-DOTA-LAN) on the diagnostic assessment of neuroendocrine tumour (NET) patients with low to moderate uptake on planar somatostatin receptor (SSTR) scintigraphy or {sup 68}Ga-labelled DOTA{sup 0},Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) positron emission tomography (PET). Fifty-three patients with histologically confirmed NET and clinical signs of progressive disease, who had not qualified for peptide receptor radionuclide therapy (PRRT) on planar SSTR scintigraphy or {sup 68}Ga-DOTA-TOC PET (n = 38) due to lack of tracer uptake, underwent {sup 68}Ga-DOTA-LAN PET to evaluate a treatment option with {sup 90}Y-labelled lanreotide according to the MAURITIUS trial. The included patients received 150 {+-} 30 MBq of each radiopharmaceutical intravenously. PET scans were acquired 60-90 min after intravenous bolus injection. Image results from both PET scans were compared head to head, focusing on the intensity of tracer uptake in terms of treatment decision. CT was used for morphologic correlation of tumour lesions. To further evaluate the binding affinities of each tracer, quantitative and qualitative values were calculated for target lesions. {sup 68}Ga-DOTA-LAN and {sup 68}Ga-DOTA-TOC both showed equivalent findings in 24/38 patients when fused PET/CT images were interpreted. The sensitivity, specificity and accuracy of {sup 68}Ga-DOTA-LAN in comparison to CT were 0.63, 0.5 and 0.62 (n = 53; p < 0.0001) and for {sup 68}Ga-DOTA-TOC in comparison to CT 0.78, 0.5 and 0.76 (n = 38; p < 0.013), respectively. {sup 68}Ga-DOTA-TOC showed a significantly higher maximum standardized uptake value (SUV{sub max}) regarding the primary tumour in 25 patients (p < 0.003) and regarding the liver in 30 patients (p < 0.009) compared to {sup 68}Ga-DOTA-LAN. Corresponding values of both PET scans for tumour and liver did not show any significant correlation. {sup 68}Ga

  12. Management strategies of enterovirus D68 outbreaks: current perspectives

    Directory of Open Access Journals (Sweden)

    Milhano N

    2018-03-01

    Full Text Available Natacha Milhano, Kaja Sverdrup Borge, Karoline Bragstad, Susanne G Dudman Domain for Environmental Health and Infectious Disease Control, Norwegian Institute of Public Health, Oslo, Norway Abstract: Following its discovery in California in 1962, enterovirus D68 (EV-D68 was reported only sporadically around the world. In August 2014, a marked increase of EV-D68 cases in young children with severe respiratory infections was reported in the USA and Canada and later in Europe and Asia. Some of these cases were also found to be associated with acute flaccid paralysis, which exacerbated public health concern, and has since triggered international efforts to strengthen both EV-D68 and acute flaccid paralysis surveillance systems. This review summarizes the current knowledge on EV-D68, offering an overview of EV-D68 epidemiology, clinical presentations, diagnostic methodologies, and treatment strategies, as well as surveillance and outbreak management. Keywords: enterovirus D68, AFP, diagnostics, treatment, surveillance, outbreak 

  13. Investigation of the imaging characteristics of the ALBIRA II small animal PET system for {sup 18}F, {sup 68}Ga and {sup 64}Cu

    Energy Technology Data Exchange (ETDEWEB)

    Attarwala, Ali Asgar; Hardiansyah, Deni [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Heidelberg Univ., Mannheim (Germany). Dept. of Radiation Oncology; Karanja, Yvonne Wanjiku; Romano, Chiara [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Roscher, Mareike; Waengler, Bjoern [Heidelberg Univ., Mannheim (Germany). Molecular Imaging and Radiochemistry; Glatting, Gerhard [Heidelberg Univ., Mannheim (Germany). Medical Radiation Physics/Radiation Protection; Ulm Univ. (Germany). Dept. of Nuclear Medicine

    2017-08-01

    In this study the performance characteristics of the Albira II PET sub-system and the response of the system for the following radionuclides {sup 18}F, {sup 68}Ga and {sup 64}Cu was analyzed. The Albira II tri-modal system (Bruker BioSpin MRI GmbH, Ettlingen, Germany) is a pre-clinical device for PET, SPECT and CT. The PET sub-system uses single continuous crystal detectors of lutetium yttrium orthosilicate (LYSO). The detector assembly consists of three rings of 8 detector modules. The transaxial field of view (FOV) has a diameter of 80 mm and the axial FOV is 148 mm. A NEMA NU-4 image quality phantom (Data Spectrum Corporation, Durham, USA) having five rods with diameters of 1, 2, 3, 4 and 5 mm and a uniform central region was used. Measurements with {sup 18}F, {sup 68}Ga and {sup 64}Cu were performed in list mode acquisition over 10 h. Data were reconstructed using a maximum-likelihood expectation-maximization (MLEM) algorithm with iteration numbers between 5 and 50. System sensitivity, count rate linearity, convergence and recovery coefficients were analyzed. The sensitivities for the entire FOV (non-NEMA method) for {sup 18}F, {sup 68}Ga and {sup 64}Cu were (3.78 ± 0.05)%, (3.97 ± 0.18)% and (3.79 ± 0.37)%, respectively. The sensitivity based on the NEMA protocol using the {sup 22}Na point source yielded (5.53 ± 0.06)%. Dead-time corrected true counts were linear for activities ≤7 MBq ({sup 18}F and {sup 68}Ga) and ≤17 MBq ({sup 64}Cu) in the phantom. The radial, tangential and axial full widths at half maximum (FWHMs) were 1.52, 1.47 and 1.48 mm. Recovery coefficients for the uniform region with a total activity of 8 MBq in the phantom were (0.97 ± 0.05), (0.98 ± 0.06), (0.98 ± 0.06) for {sup 18}F, {sup 68}Ga and {sup 64}Cu, respectively. The Albira II pre-clinical PET system has an adequate sensitivity range and the system linearity is suitable for the range of activities used for pre-clinical imaging. Overall, the system showed a favorable image

  14. 40 CFR 68.65 - Process safety information.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.65 Process safety... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Process safety information. 68.65... compilation of written process safety information before conducting any process hazard analysis required by...

  15. Glycosaminoglycan interactions in murine gammaherpesvirus-68 infection.

    Directory of Open Access Journals (Sweden)

    Laurent Gillet

    2007-04-01

    Full Text Available Glycosaminoglycans (GAGs commonly participate in herpesvirus entry. They are thought to provide a reversible attachment to cells that promotes subsequent receptor binding. Murine gamma-herpesvirus-68 (MHV-68 infection of fibroblasts and epithelial cells is highly GAG-dependent. This is a function of the viral gp150, in that gp150-deficient mutants are much less GAG-dependent than wild-type. Here we show that the major MHV-68 GAG-binding protein is not gp150 but gp70, a product of ORF4. Surprisingly, ORF4-deficient MHV-68 showed normal cell binding and was more sensitive than wild-type to inhibition by soluble heparin rather than less. Thus, the most obvious viral GAG interaction made little direct contribution to infection. Indeed, a large fraction of the virion gp70 had its GAG-binding domain removed by post-translational cleavage. ORF4 may therefore act mainly to absorb soluble GAGs and prevent them from engaging gp150 prematurely. In contrast to gp70, gp150 bound poorly to GAGs, implying that it provides little in the way of adhesion. We hypothesize that it acts instead as a GAG-sensitive switch that selectively activates MHV-68 entry at cell surfaces.

  16. Global emergence of enterovirus D68

    DEFF Research Database (Denmark)

    Holm-Hansen, Charlotte Carina; Midgley, Sofie Elisabeth; Fischer, Thea Kølsen

    2016-01-01

    be assessed in terms of capacity and ability to detect and report any upsurge of respiratory viruses such as enterovirus D68 in a timely manner, and focus should be paid to development of preventive measures against these emerging enteroviruses that have potential for severe disease.......Since its discovery in California in 1962, reports of enterovirus D68 have been infrequent. Before 2014, infections were confirmed in only 699 people worldwide. In August, 2014, two paediatric hospitals in the USA reported increases in the number of patients with severe respiratory illness......, with an over-representation in children with asthma. Shortly after, the authorities recognised a nationwide outbreak, which then spread to Canada, Europe, and Asia. In 2014, more than 2000 cases of enterovirus D68 were reported in 20 countries. Concurrently, clusters of children with acute flaccid paralysis...

  17. The effect of purification of Ga-68-labeled exendin on in vivo distribution

    NARCIS (Netherlands)

    Brom, M.; Franssen, G.M.; Joosten, L.; Gotthardt, M.; Boerman, O.C.

    2016-01-01

    BACKGROUND: Ga-labeled radiotracers are increasingly used for PET imaging. During the labeling procedure, formation of (68)Ga-colloid may occur. Upon i.v. injection, (68)Ga-colloid will accumulate rapidly in the liver, spleen, and bone marrow, resulting in reduced target-to-background ratios. In

  18. 2014 outbreak of enterovirus D68 in North America.

    Science.gov (United States)

    Messacar, Kevin; Abzug, Mark J; Dominguez, Samuel R

    2016-05-01

    Enterovirus D68 (EV-D68) is an emerging picornavirus which causes severe respiratory disease, predominantly in children. In 2014, the largest and most widespread outbreak of EV-D68 described to date was reported in North America. Hospitals throughout the United States and Canada reported surges in patient volumes and resource utilization from August to October, 2014. In the US a total of 1,153 infections were confirmed in 49 states, although this is an underestimate of the likely millions of cases that occurred but were not tested. EV-D68 was detected in 14 patients who died; the role of the virus in these deaths is unknown. A possible association between EV-D68 and cases of acute flaccid paralysis with spinal cord gray matter lesions, known as acute flaccid myelitis, was observed during the outbreak and is under investigation. The 2014 outbreak of EV-D68 in North America demonstrates the public health importance of this emerging pathogen. © 2015 Wiley Periodicals, Inc.

  19. Surfactant-assisted dispersion of carbon nanotubes: mechanism of stabilization and biocompatibility of the surfactant

    Science.gov (United States)

    Singh, Raman Preet; Jain, Sanyog; Ramarao, Poduri

    2013-10-01

    Nanoparticles (NPs) are thermodynamically unstable system and tend to aggregate to reduce free energy. The aggregation property of NPs results in inhomogeneous exposure of cells to NPs resulting in variable cellular responses. Several types of surfactants are used to stabilize NP dispersions and obtain homogenous dispersions. However, the effects of these surfactants, per se, on cellular responses are not completely known. The present study investigated the application of Pluronic F68 (PF68) for obtaining stable dispersion of NPs using carbon nanotubes as model NPs. PF68-stabilized NP suspensions are stable for long durations and do not show signs of aggregation or settling during storage or after autoclaving. The polyethylene oxide blocks in PF68 provide steric hindrance between adjacent NPs leading to stable NP dispersions. Further, PF68 is biocompatible in nature and does not affect integrity of mitochondria, lysosomes, DNA, and nuclei. Also, PF68 neither induce free radical or cytokine production nor does it interfere with cellular uptake mechanisms. The results of the present study suggest that PF68-assisted dispersion of NPs produced suspensions, which are stable after autoclaving. Further, PF68 does not interfere with normal physiological functions suggesting its application in nanomedicine and nanotoxicity evaluation.

  20. Surfactant-assisted dispersion of carbon nanotubes: mechanism of stabilization and biocompatibility of the surfactant

    International Nuclear Information System (INIS)

    Singh, Raman Preet; Jain, Sanyog; Ramarao, Poduri

    2013-01-01

    Nanoparticles (NPs) are thermodynamically unstable system and tend to aggregate to reduce free energy. The aggregation property of NPs results in inhomogeneous exposure of cells to NPs resulting in variable cellular responses. Several types of surfactants are used to stabilize NP dispersions and obtain homogenous dispersions. However, the effects of these surfactants, per se, on cellular responses are not completely known. The present study investigated the application of Pluronic F68 (PF68) for obtaining stable dispersion of NPs using carbon nanotubes as model NPs. PF68-stabilized NP suspensions are stable for long durations and do not show signs of aggregation or settling during storage or after autoclaving. The polyethylene oxide blocks in PF68 provide steric hindrance between adjacent NPs leading to stable NP dispersions. Further, PF68 is biocompatible in nature and does not affect integrity of mitochondria, lysosomes, DNA, and nuclei. Also, PF68 neither induce free radical or cytokine production nor does it interfere with cellular uptake mechanisms. The results of the present study suggest that PF68-assisted dispersion of NPs produced suspensions, which are stable after autoclaving. Further, PF68 does not interfere with normal physiological functions suggesting its application in nanomedicine and nanotoxicity evaluation

  1. Surfactant-assisted dispersion of carbon nanotubes: mechanism of stabilization and biocompatibility of the surfactant

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Raman Preet, E-mail: ramanpreetsingh@hotmail.com [Evalueserve SEZ (Gurgaon) Pvt. Ltd. (India); Jain, Sanyog [National Institute of Pharmaceutical Education and Research, Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics (India); Ramarao, Poduri, E-mail: ramaraop@yahoo.com [Central University of Punjab, School of Basic and Applied Sciences (India)

    2013-10-15

    Nanoparticles (NPs) are thermodynamically unstable system and tend to aggregate to reduce free energy. The aggregation property of NPs results in inhomogeneous exposure of cells to NPs resulting in variable cellular responses. Several types of surfactants are used to stabilize NP dispersions and obtain homogenous dispersions. However, the effects of these surfactants, per se, on cellular responses are not completely known. The present study investigated the application of Pluronic F68 (PF68) for obtaining stable dispersion of NPs using carbon nanotubes as model NPs. PF68-stabilized NP suspensions are stable for long durations and do not show signs of aggregation or settling during storage or after autoclaving. The polyethylene oxide blocks in PF68 provide steric hindrance between adjacent NPs leading to stable NP dispersions. Further, PF68 is biocompatible in nature and does not affect integrity of mitochondria, lysosomes, DNA, and nuclei. Also, PF68 neither induce free radical or cytokine production nor does it interfere with cellular uptake mechanisms. The results of the present study suggest that PF68-assisted dispersion of NPs produced suspensions, which are stable after autoclaving. Further, PF68 does not interfere with normal physiological functions suggesting its application in nanomedicine and nanotoxicity evaluation.

  2. Reduction of {sup 68}Ga-PSMA renal uptake with mannitol infusion. Preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Matteucci, Federica; Caroli, Paola; Celli, Monica; Fantini, Lorenzo; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine Unit, Meldola (Italy); Mezzenga, Emilio; Sarnelli, Anna [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy, Meldola (Italy); Moretti, Andrea; Galassi, Riccardo [AUSL Romagna, Nuclear Medicine Unit, Forli (Italy); De Giorgi, Ugo [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology, Meldola (Italy)

    2017-12-15

    Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with {sup 68}Ga or {sup 177}Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of {sup 68}Ga-PSMA. Kidney uptake (SUVmax) was calculated in nine patients undergoing {sup 68}Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after {sup 68}Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after {sup 68}Ga-PSMA administration (B-infusion). In patients receiving the A-infusion, mean SUV{sub max} increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUV{sub max} decreased by 24.3% and 22.4% in the right and left kidney, respectively. Our preliminary findings indicate that mannitol may play a role in reducing off-target {sup 68}Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before {sup 68}Ga-PSMA injection. These results warrant dosimetric studies in patients treated with {sup 177}Lu-PSMA to find the best scheme for mannitol administration. (orig.)

  3. Development and Evaluation of User-Friendly Single Vial DOTA-Peptide Kit Formulations, Specifically Designed for Radiolabelling with 68Ga from a Tin Dioxide 68Ge/68Ga Generator.

    Science.gov (United States)

    Prince, Deidré; Rossouw, Daniel; Davids, Claudia; Rubow, Sietske

    2017-12-01

    This study was aimed to develop single vial 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-peptide kits to be used with fractionated eluates from a SnO 2 -based 68 Ge/ 68 Ga generator. Kits were formulated with 35 μg DOTA-Tyr 3 -Thre 8 -octreotide, DOTA-[Tyr 3 ]-octreotide and DOTA-[NaI 3 ]-octreotide (DOTATATE, DOTATOC and DOTANOC) and sodium acetate powder, vacuum-dried and stored at -20 °C for up to 12 months. Labelling of the kits was carried out with 2 ml 68 Ga eluate. Comparative labelling was carried out using aqueous DOTA-peptide stock solutions kept frozen at -20 °C for up to 12 months. The quality of the kits was found to be suitable over a 1-year storage period (pH, sterility, endotoxin content, radiolabelling efficiency and radiochemical yields of 68 Ga-labelled DOTA-peptides). Radiochemical yields ranged from 73 to 83 %, while those obtained from stock solutions from 64 to 79 %. No significant decline in kit labelling yields was observed over a 12-month storage period. The single vial kit formulations met the quality release specifications for human administration and appear to be highly advantageous over using peptide stock solutions in terms of stability and user-friendliness.

  4. Molecular and epidemiological study of enterovirus D68 in Taiwan.

    Science.gov (United States)

    Huang, Yuan-Pin; Lin, Tsuey-Li; Lin, Ting-Han; Wu, Ho-Sheng

    2017-08-01

    As an immunofluorescence assay for enterovirus D68 (EV-D68) is not available in the enteroviruses surveillance network in Taiwan, EV-D68 may be the actual pathogen of untypeable enterovirus-suspected isolates. The untypeable isolates collected from 2007 through 2014 were identified by nucleic acid amplification-based methods and sequencing of the VP1 region to analyze the phylogeny and epidemiology of EV-D68 in Taiwan. Twenty-nine EV-D68 isolates were sequenced, including 15 Cluster 3 and 14 Cluster 1 viruses. Approximately 41% of the patients were children under 5 years of age and their infections peaked in August. The ratio of male to female patients was 1.5 and 3.67 for Cluster 3 and Cluster 1, respectively. Fever and respiratory symptoms were commonly reported in EV-D68-infected patients. The results of phylogenetic analyses showed that EV-D68 isolates between 2007 and 2014 belonged to different clusters and existed for years, indicating that endemic circulation of EV-D68 existed in Taiwan. This study showed that EV-D68 has been endemic in Taiwan for some years despite a small number of positive cases. The continuous monitoring and efforts towards the improvement of diagnostic techniques are required to complete the surveillance system. This study provided the genetic and epidemiological information which could contribute to understanding the etiology and epidemiology of EV-D68. Copyright © 2015. Published by Elsevier B.V.

  5. Enantioselectivity and Thermostability of a Novel Hyperhermotolerant Lipase from Geobacillus Thermodenitrificans nr68 (Lip.nr-68) on Secondary Racemic Alcohols Acetylation

    Science.gov (United States)

    Nik Him, N. R.; Ibrahim, D.

    2018-05-01

    In our previous work, a new lipase enzyme has been purified from a species identified as a Gram negative Geobacillus thermodenitrificans nr68, isolated from a hot spring in Malaysia with growth temperature of 48°C. This new lipase, called Lip.nr-68 has been characterized as a hyperthermotolerant protein with high stability at 65°C and has been showing excellent characteristics that are very much comparable yet better than some of those of well-known industrially-used lipases. It shows high activity against long-chain triglycerides with molecular weight of the purified enzyme estimated to be 33.5 kDa using SDS-PAGE analysis. This paper is focusing on hyperthermotolerant Lip.nr-68 performance in promoting for enantioselectivity activities towards three secondary racemic alcohols namely 1-phenylethanol, 1-cyclohexilethanol and 1-(naft-2-il) ethanol by acetylation with vinyl acetate. Lip.nr-68 has been confirmed to show high and usual enantioselectivitiy according to the Kazlauskas Rule towards all secondary racemic alcohols and has significantly approved as an enantiomer selective biocatalyst towards 1-phenylethanol and 1-cyclohexylethanol at 65°C. Lip.nr-68 has showed a reduction of (R) and (S) enantiomers as well as the production of 68-98% ee and almost 94% yield of 3-4 mg/ml for 1-cyclohexilethanol.

  6. 46 CFR 68.7 - Qualification as an 883-1 corporation.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Qualification as an 883-1 corporation. 68.7 Section 68.7... Trade § 68.7 Qualification as an 883-1 corporation. (a) To be formally qualified as an 883-1 corporation for all purposes under the Act, a corporation which meets the requirements of § 68.5 must file with...

  7. Guideline for PET/CT imaging of neuroendocrine neoplasms with {sup 68}Ga-DOTA-conjugated somatostatin receptor targeting peptides and {sup 18}F-DOPA

    Energy Technology Data Exchange (ETDEWEB)

    Bozkurt, Murat Fani [Hacettepe University Faculty of Medicine Department of Nuclear Medicine, Ankara (Turkey); Virgolini, Irene; Decristoforo, Clemens [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Balogova, Sona [Comenius University and St. Elisabeth Oncology Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Tenon Hospital AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Beheshti, Mohsen [St. Vincent' s Hospital, PET-CT Center, Department of Nuclear Medicine and Endocrinology, Linz (Austria); Paracelsus Medical University, Department of Nuclear Medicine, Salzburg (Austria); Rubello, Domenico [Santa Maria della Misericordia Hospital, Department of Nuclear Medicine, PET Center and Medical Physics and Radiology, Rovigo (Italy); Ambrosini, Valentina; Fanti, Stefano [University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna (Italy); Kjaer, Andreas [National University Hospital and University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Delgado-Bolton, Roberto [San Pedro Hospital and Centre for Biomedical Research of La Rioja (CIBIR), Department of Diagnostic Imaging (Radiology) and Nuclear Medicine, Logrono (Spain); Kunikowska, Jolanta [Medical University of Warsaw, Nuclear Medicine, Warsaw (Poland); Oyen, Wim J.G. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London (United Kingdom); Chiti, Arturo [Humanitas University, Nuclear Medicine Department, Rozzano, MI (Italy); Giammarile, Francesco [University of Lyon, Nuclear Medicine, Lyon (France)

    2017-08-15

    Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using {sup 68}Ga-DOTA-conjugated peptides, as well as {sup 18}F-DOPA imaging for various neuroendocrine neoplasms. The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with {sup 68}Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts. (orig.)

  8. A new automated NaCl based robust method for routine production of gallium-68 labeled peptides

    Science.gov (United States)

    Schultz, Michael K.; Mueller, Dirk; Baum, Richard P.; Watkins, G. Leonard; Breeman, Wouter A. P.

    2017-01-01

    A new NaCl based method for preparation of gallium-68 labeled radiopharmaceuticals has been adapted for use with an automated gallium-68 generator system. The method was evaluated based on 56 preparations of [68Ga]DOTATOC and compared to a similar acetone-based approach. Advantages of the new NaCl approach include reduced preparation time ( 97%), and specific activity (> 40 MBq nmole−1 [68Ga]DOTATOC) and is well-suited for clinical production of radiopharmaceuticals. PMID:23026223

  9. 19 CFR 210.68 - Complainant's temporary relief bond.

    Science.gov (United States)

    2010-04-01

    ... Section 210.68 Customs Duties UNITED STATES INTERNATIONAL TRADE COMMISSION INVESTIGATIONS OF UNFAIR PRACTICES IN IMPORT TRADE ADJUDICATION AND ENFORCEMENT Temporary Relief § 210.68 Complainant's temporary... by Individual Surety United States International Trade Commission Affidavit by Individual Surety 19...

  10. Radiation protection requirements necessary for the introduction of the Ga-68 in a Nuclear Medicine Service; Requisitos de protección radiológica necesarios para la introducción del Ga-68 en un Servicio de Medicina Nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Campayo, G.; Ibáñez-Roselló, B.; Reinado, D.; Verdú, G.

    2016-07-01

    The new diagnostic technique that use Ga-68 entail a radiation safety review in nuclear medicine service. It will be evaluate the exposure risk of the workers, who actually are exposed to dose associated to labeled radiopharmaceuticals with F-18, and are estimated the risks due to radiopharmaceuticals with Ga-68. A barrier check-up is made in the current location and an increase of dose rate is estimated with the introduction of Ga-68. Two studies have been done, exposure risk and barrier check-up, in a particular installation. The results obtained conclude that the introduction of Ga-68 in a nuclear medicine service is possible taking into account the minimal modifications in the installation. However, the related modifications have to be studied for each different installation. [Spanish] Las nuevas técnicas diagnósticas que hacen uso del Ga-68 implica la revisión de aspectos de protección radiológica en un servicio de medicina nuclear. Se evalúa el riesgo de exposición de los trabajadores, que en la actualidad están expuestos a los riesgos asociados a los radiofármacos marcados con F-18, y se estiman los debidos a radiofármacos con Ga-68. Se realiza una verificación de barreras en la situación actual y se estima el aumento de la tasa de dosis con la introducción del Ga-68. Se han aplicado ambos estudios, de riesgo de exposición y de verificación de barreras, a una instalación concreta. Los resultados obtenidos concluyen que la introducción del Ga-68 en un servicio de medicina nuclear es posible teniendo en cuenta unas modificaciones mínimas de la instalación. No obstante, las modificaciones aplicables deben ser estudiadas para cada instalación concreta.

  11. Effects of Pluronic F-68 on Tetrahymena cells: protection against chemical and physical stress and prolongation of survival under toxic conditions

    DEFF Research Database (Denmark)

    Hellung-Larsen, P; Assaad, F; Pankratova, Stanislava

    2000-01-01

    exposed to hyperthermia (43 degrees C). The cellular survival is increased at reduced temperatures (e.g. 4 degrees C instead of 36 degrees C) and at increased cellular concentrations (e.g. 100 cells ml(-1) instead of 25 or 10 cells ml(-1)). There is no effect of pre-incubation with Pluronic......The effects of the non-ionic surfactant Pluronic F-68 (0.01% w/v) on Tetrahymena cells have been studied. A marked protection against chemical and physical stress was observed. The chemical stress effects were studied in cells suspended in buffer (starvation) or in buffers with added ingredients....... The protective effect of Pluronic towards Tetrahymena is observed for concentrations in the range from 0.001 to 0.1% w/v....

  12. Semi-automated lab-on-a-chip for dispensing GA-68 radiotracers

    Energy Technology Data Exchange (ETDEWEB)

    Weinberg, Irving [Weinberg Medical Physics LLC, Bethesda, MD (United States)

    2014-03-12

    We solved a technical problem that is hindering American progress in molecular medicine, and restricting US citizens from receiving optimal diagnostic care. Specifically, the project deals with a mother/daughter generator of positron-emitting radiotracers (Ge-68/Ga-68). These generator systems are approved in Europe but cannot be used in the USA, because of safety issues related to possible breakthrough of long-lived Ge-68 (mother) atoms. Europeans have demonstrated abilities of Ga-68-labeled radiotracers to image cancer foci with high sensitivity and specificity, and to use such methods to effectively plan therapy.The USA Food and Drug Administration (FDA) and Nuclear Regulatory Commission (NRC) have taken the position that every patient administration of Ga-68 should be preceded by an assay demonstrated that Ge-68 breakthrough is within acceptable limits. Breakthrough of parent elements is a sensitive subject at the FDA, as evidenced by the recent recall of Rb-82 generators due to inadvertent administrations of Sr-82. Commercially, there is no acceptable rapid method for assaying breakthrough of Ge-68 prior to each human administration. The gamma emissions of daughter Ga-68 have higher energies than the parent Ge-68, so that the shielding assays typically employed for Mo-99/Tc-99m generators cannot be applied to Ga-68 generators. The half-life of Ga-68 is 68 minutes, so that the standard 10-half-life delay (used to assess breakthrough in Sr-82/Rb-82 generators) cannot be applied to Ga-68 generators. As a result of the aforementioned regulatory requirements, Ga-68 generators are sold in the USA for animal use only.The American clinical community’s inability to utilize Ga-68 generators impairs abilities to treat patients domestically, and puts the USA at a disadvantage in developing exportable products. The proposed DOE project aimed to take advantage of recent technological advances developed for lab-on-a-chip (LOC) applications. Based on our experiences

  13. Pathogen-induced ERF68 regulates hypersensitive cell death in tomato.

    Science.gov (United States)

    Liu, An-Chi; Cheng, Chiu-Ping

    2017-10-01

    Ethylene response factors (ERFs) are a large plant-specific transcription factor family and play diverse important roles in various plant functions. However, most tomato ERFs have not been characterized. In this study, we showed that the expression of an uncharacterized member of the tomato ERF-IX subgroup, ERF68, was significantly induced by treatments with different bacterial pathogens, ethylene (ET) and salicylic acid (SA), but only slightly induced by bacterial mutants defective in the type III secretion system (T3SS) or non-host pathogens. The ERF68-green fluorescent protein (ERF68-GFP) fusion protein was localized in the nucleus. Transactivation and electrophoretic mobility shift assays (EMSAs) further showed that ERF68 was a functional transcriptional activator and was bound to the GCC-box. Moreover, transient overexpression of ERF68 led to spontaneous lesions in tomato and tobacco leaves and enhanced the expression of genes involved in ET, SA, jasmonic acid (JA) and hypersensitive response (HR) pathways, whereas silencing of ERF68 increased tomato susceptibility to two incompatible Xanthomonas spp. These results reveal the involvement of ERF68 in the effector-triggered immunity (ETI) pathway. To identify ERF68 target genes, chromatin immunoprecipitation combined with high-throughput sequencing (ChIP-seq) was performed. Amongst the confirmed target genes, a few genes involved in cell death or disease defence were differentially regulated by ERF68. Our study demonstrates the function of ERF68 in the positive regulation of hypersensitive cell death and disease defence by modulation of multiple signalling pathways, and provides important new information on the complex regulatory function of ERFs. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  14. 47 CFR 68.106 - Notification to provider of wireline telecommunications.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Notification to provider of wireline telecommunications. 68.106 Section 68.106 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... of Terminal Equipment § 68.106 Notification to provider of wireline telecommunications. (a) General...

  15. 40 CFR 68.33 - Defining offsite impacts-environment.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Defining offsite impacts-environment. 68.33 Section 68.33 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... impacts—environment. (a) The owner or operator shall list in the RMP environmental receptors within a...

  16. 47 CFR 68.320 - Supplier's Declaration of Conformity.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Supplier's Declaration of Conformity. 68.320... Approval § 68.320 Supplier's Declaration of Conformity. (a) Supplier's Declaration of Conformity is a... Supplier's Declaration of Conformity attaches to all items subsequently marketed by the responsible party...

  17. New 68Ga-PhenA bisphosphonates as potential bone imaging agents

    International Nuclear Information System (INIS)

    Wu, Zehui; Zha, Zhihao; Choi, Seok Rye; Plössl, Karl; Zhu, Lin; Kung, Hank F.

    2016-01-01

    Introduction: In vivo positron emission tomography (PET) imaging of the bone using [ 68 Ga]bisphosphonates may be a valuable tool for cancer diagnosis and monitoring therapeutic treatment. We have developed new [ 68 Ga]bisphosphonates based on the chelating group, AAZTA (6-[bis(hydroxycarbonyl-methyl)amino]-1,4-bis(hydroxycarbonyl methyl)-6-methylperhydro-1,4-diazepine). Method: Phenoxy derivative of AAZTA (2,2′-(6-(bis(carboxymethyl)amino)-6-((4-(2-carboxyethyl)phenoxy) methyl)-1,4-diazepane-1,4-diyl)diacetic acid), PhenA, 2, containing a bisphosphonate group (PhenA-BPAMD, 3, and PhenA-HBP, 4) was prepared. Labeling of these chelating agents with 68 Ga was evaluated. Results: The ligands reacted rapidly in a sodium acetate buffer with [ 68 Ga]GaCl 3 eluted from a commercially available 68 Ge/ 68 Ga generator (pH 4, > 95% labeling at room temperature in 5 min) to form [ 68 Ga]PhenA-BPAMD, 3, and [ 68 Ga]PhenA-HBP, 4. The improved labeling condition negates the need for further purification. The 68 Ga bisphosphonate biodistribution and autoradiography of bone sections in normal mice after an iv injection showed excellent bone uptake. Conclusion: New 68 Ga labeled bisphosphonates may be useful as in vivo bone imaging agents in conjunction with positron emission tomography (PET).

  18. The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells

    International Nuclear Information System (INIS)

    Lawrence, Paul; Schafer, Elizabeth A.; Rieder, Elizabeth

    2012-01-01

    Picornavirus infection can lead to disruption of nuclear pore traffic, shut-off of cell translation machinery, and cleavage of proteins involved in cellular signal transduction and the innate response to infection. Here, we demonstrated that the FMDV 3C pro induced the cleavage of nuclear RNA-binding protein Sam68 C-terminus containing the nuclear localization sequence (NLS). Consequently, it stimulated the redistribution of Sam68 to the cytoplasm. The siRNA knockdown of Sam68 resulted in a 1000-fold reduction in viral titers, which prompted us to study the effect of Sam68 on FMDV post-entry events. Interestingly, Sam68 interacts with the internal ribosomal entry site within the 5′ non-translated region of the FMDV genome, and Sam68 knockdown decreased FMDV IRES-driven activity in vitro suggesting that it could modulate translation of the viral genome. The results uncover a novel role for Sam68 in the context of picornaviruses and the proteolysis of a new cellular target of the FMDV 3C pro .

  19. 47 CFR 68.350 - Revocation of Supplier's Declaration of Conformity.

    Science.gov (United States)

    2010-10-01

    ... Conformity. 68.350 Section 68.350 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... Terminal Equipment Approval § 68.350 Revocation of Supplier's Declaration of Conformity. (a) The Commission may revoke any Supplier's Declaration of Conformity for cause in accordance with the provisions of...

  20. 40 CFR 68.30 - Defining offsite impacts-population.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Defining offsite impacts-population. 68.30 Section 68.30 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... impacts—population. (a) The owner or operator shall estimate in the RMP the population within a circle...

  1. Human enterovirus D68 in clinical and sewage samples in Israel.

    Science.gov (United States)

    Weil, Merav; Mandelboim, Michal; Mendelson, Ella; Manor, Yossi; Shulman, Lester; Ram, Daniela; Barkai, Galia; Shemer, Yonat; Wolf, Dana; Kra-Oz, Zipi; Weiss, Leah; Pando, Rakefet; Hindiyeh, Musa; Sofer, Danit

    2017-01-01

    Since mid-August 2014, North America experienced a wide outbreak of Enterovirus D68 (EV-D68) associated with severe respiratory illness in children. Several other countries also reported cases of EV-D68 in 2014. The aim of this study was to determine whether EV-D68 circulated in Israel in 2014, caused severe respiratory illness in children and was the causative agent of Acute Flaccid Paralysis. Archived clinical respiratory samples from a cohort of 710 hospitalized pediatric patient's (<10years old) with respiratory illness were screened for clade B specific EV-D68 by real-time PCR. The patients were seen at four medical centers covering the entire country between August and November 2014. We also evaluated 49 patient stool samples from 26 AFP cases during 2014 for presence of EV-D68. In addition, RNA from sewage samples collected throughout Israel during the same study period was also tested for EV-D68. Partial VP1 sequencing was performed on all positive samples. Of the 710 clinical samples evaluated, 7 (1%) were positive for EV-D68. Two patients were from the central part of Israel, while the rest was from the southern part. The majority of the patients did not have any underlying disease. Not only that, but, none of the 26 suspected AFP cases had EV-D68 nucleic acid in their stool samples. EV-D68 RNA was detected in 9 out of 93 sewage samples, mainly from Southern Israel. Sequence analysis of EV-D68 VP1 gene from both sewage and clinical samples indicated that the Israeli EV-D68 RNA belonged to Clade B which was genetically similar to 2014 circulating European and North American EV-D68 virus. EV-D68 circulated in Israel during the 2014 summer-fall season and caused hospitalization of a small percent of the patients with respiratory illness. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. (68)Ga-DOTA-peptide: A novel molecular biomarker for nasopharyngeal carcinoma.

    Science.gov (United States)

    Khor, Lih Kin; Loi, Hoi Yin; Sinha, Arvind Kumar; Tong, Kian Ti; Goh, Boon Cher; Loh, Kwok Seng; Lu, Suat-Jin

    2016-04-01

    Increased somatostatin receptor (SSTR) expression in patients with undifferentiated nasopharyngeal carcinoma (NPC) has been demonstrated with receptor autoradiography, (111) In-Octreotide scintigraphy, and (68) Ga-DOTA-TOC positron emission tomography (PET)/CT imaging. We sought to compare and correlate the uptake of fluorodeoxyglucose (FDG) and DOTA-NOC in undifferentiated NPC to ascertain the possible role of (68) Ga-DOTA-NOC PET/CT as a new imaging biomarker and to assess whether targeted peptide receptor radionuclide therapy is a feasible treatment option. After obtaining approval from our institutional review board, 4 patients with biopsy proven nonkeratinizing undifferentiated NPC who had just undergone routine staging/restaging (18) F-FDG PET/CT imaging were prospectively and consecutively recruited for (68) Ga-DOTA-NOC PET/CT imaging. Of these 4 patients, 3 were newly diagnosed with untreated NPC, whereas 1 patient was diagnosed with a case of recurrent NPC with previous treatment. These patients subsequently underwent (68) Ga-DOTA-NOC PET/CT within 10 days from the (18) F-FDG PET/CT to ensure lesion comparability. Tracer uptake in tumor lesions were assessed visually and semiquantitatively by measuring maximum standardized uptake values (SUVmax). There were 12 FDG-avid lesions of which 7 showed avid uptake of DOTA-NOC greater than liver uptake, whereas 5 showed low uptake of DOTA-NOC less than liver uptake. Subset analysis of the FDG-avid lesions at the primary and recurrent sites showed that all the FDG-avid primary tumors in the nasopharynx showed avid uptake of DOTA-NOC. On the contrary, the case of recurrent NPC showed avid FDG uptake but low DOTA-NOC uptake. Subset analysis of the suspicious FDG-avid cervical lymph nodes showed that 50% of them demonstrated avid DOTA-NOC uptake greater than liver uptake, whereas the remaining demonstrated low-grade DOTA-NOC uptake less than liver uptake. The 2 subcentimeter cervical lymph nodes that showed low

  3. Development of 68Ga ethyl cysteinate dimer for PET studies

    International Nuclear Information System (INIS)

    Alireza Mirzaei; Jalilian, A.R.; Gholamali Shabani; Ashraf Fakhari; Mehdi Akhlaghi; Davood Beiki

    2016-01-01

    In this work development of 68 Ga-ethyl cysteinate dimer ( 68 Ga-ECD) a 68 Ga tracer for possible cerebral blood flow based on 99m Tc ECD homolog is reported. 68 Ga-ECD was prepared using generator-based 68 GaCl 3 and ECD at optimized conditions. Quality control, stability, partition co-efficient and the biodistribution of the tracer (by tissue counting and PET/CT in rats) was studied. Significant metabolism of the lipophilic tracer into water soluble metabolite(s) led to urinary excretion of the tracer, un-comparable to that of homologous 99m Tc-compound. Cardiac uptake of the complex suggests formation of a possible lipophil cationic complex and/or metabolite. (author)

  4. Human Rhinovirus 87 and Enterovirus 68 Represent a Unique Serotype with Rhinovirus and Enterovirus Features

    Science.gov (United States)

    Blomqvist, Soile; Savolainen, Carita; Råman, Laura; Roivainen, Merja; Hovi, Tapani

    2002-01-01

    It has recently been reported that all but one of the 102 known serotypes of the genus Rhinovirus segregate into two genetic clusters (C. Savolainen, S. Blomqvist, M. N. Mulders, and T. Hovi, J. Gen. Virol. 83:333-340, 2002). The only exception is human rhinovirus 87 (HRV87). Here we demonstrate that HRV87 is genetically and antigenically highly similar to enterovirus 68 (EV68) and is related to EV70, the other member of human enterovirus group D. The partial nucleotide sequences of the 5′ untranslated region, capsid regions VP4/VP2 and VP1, and the 3D RNA polymerase gene of the HRV87 prototype strain F02-3607 Corn showed 97.3, 97.8, 95.2, and 95.9% identity to the corresponding regions of EV68 prototype strain Fermon. The amino acid identities were 100 and 98.1% for the products of the two capsid regions and 97.9% for 3D RNA polymerase. Antigenic cross-reaction between HRV87 and EV68 was indicated by microneutralization with monotypic antisera. Phylogenetic analysis showed definite clustering of HRV87 and EV68 with EV70 for all sequences examined. Both HRV87 and EV68 were shown to be acid sensitive by two different assays, while EV70 was acid resistant, which is typical of enteroviruses. The cytopathic effect induced by HRV87 or EV68 was inhibited by monoclonal antibodies to the decay-accelerating factor known to be the receptor of EV70. We conclude that HRV87 and EV68 are strains of the same picornavirus serotype presenting features of both rhinoviruses and enteroviruses. PMID:12409401

  5. Molecular evolution of enterovirus 68 detected in the Philippines.

    Directory of Open Access Journals (Sweden)

    Tadatsugu Imamura

    Full Text Available BACKGROUND: Detection of Enterovirus 68 (EV68 has recently been increased. However, underlying evolutionary mechanism of this increasing trend is not fully understood. METHODS: Nasopharyngeal swabs were collected from 5,240 patients with acute respiratory infections in the Philippines from June 2009 to December 2011. EV68 was detected by polymerase chain reaction (PCR targeting for 5' untranslated region (5'UTR, viral protein 1 (VP1, and VP4/VP2. Phylogenetic trees were generated using the obtained sequences. RESULTS: Of the 5,240 tested samples, 12 EV68 positive cases were detected between August and December in 2011 (detection rate, 0.23%. The detection rate was higher among inpatients than outpatients (p<0.0001. Among VP1 sequences detected from 7 patients in 2011, 5 in lineage 2 were diverged from those detected in the Philippines in 2008, however, 2 in lineage 3 were not diverged from strains detected in the Philippines in 2008 but closely associated with strains detected in the United States. Combined with our previous report, EV68 occurrences were observed twice in the Philippines within the last four years. CONCLUSIONS: EV68 detections might be occurring in cyclic patterns, and viruses might have been maintained in the community while some strains might have been newly introduced.

  6. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load.

    Science.gov (United States)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P; Holst, Peter J

    2009-11-12

    Gammaherpesviruses establish life-long latent infections in their hosts. If the host becomes immunosuppressed, these viruses may reactivate and cause severe disease, and even in immunocompetent individuals the gammaherpesviruses are presumed to have an oncogenic potential. Murine gammaherpesvirus-68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral vectors encoding both M2 and M3. Additionally we show that M3 immunization prevented the usual development of virus-induced splenomegaly at 2-3 weeks post-infection. This is the first time that immunization with a non-replicating vaccine has lead to a significantly reduced viral load at time points beyond 14 days post-infection, and thus demonstrates that a non-replicating vaccine may successfully be employed to reduce the viral burden during chronic gammaherpesvirus infection.

  7. 68Ga- and 111In-labelled DOTA-RGD peptides for imaging of αvβ3 integrin expression

    International Nuclear Information System (INIS)

    Decristoforo, Clemens; Hernandez Gonzalez, Ignacio; Rupprich, Marco; Virgolini, Irene; Carlsen, Janette; Huisman, Marc; Wester, Hans-Juergen; Haubner, Roland

    2008-01-01

    αvβ3 integrins are important cell adhesion receptors involved in angiogenic processes. Recently, we demonstrated using [ 18 F]Galacto-RGD that monitoring of αvβ3 expression is feasible. Here, we introduce 68 Ga- and 111 In-labelled derivatives and compare them with [ 18 F]Galacto-RGD. For radiolabelling, cyclo(RGDfK(DOTA)) was synthesised using SPPS. For in vitro characterisation determination of partition coefficients, protein binding, metabolic stability, αvβ3 affinity and cell uptake and for in vivo characterization, biodistribution studies and micro positron emission tomography (PET) imaging were carried out. For in vivo and in vitro studies, human melanoma M21 (αvβ3 positive) and M21-L (αvβ3 negative) cells were used. Both tracers can be synthesised straightforward. The compounds showed hydrophilic properties and high metabolic stability. Up to 23% protein-bound activity for [ 68 Ga]DOTA-RGD and only up to 1.4% for [ 111 In]DOTA-RGD was found. Cell uptake studies indicate receptor-specific accumulation. This is confirmed by the biodistribution data. One hour p.i. accumulation in αvβ3-positive tumours was 2.9 ± 0.3%ID/g and in αvβ3-negative tumours 0.8 ± 0.1%ID/g for [ 68 Ga]DOTA-RGD ([ 111 In]DOTA-RGD: 1.9 ± 0.3%ID/g and 0.5 ± 0.2%ID/g; [ 18 F]Galacto-RGD: 1.6 ± 0.2%ID/g and 0.4 ± 0.1%ID/g). Thus, tumour uptake ratios were comparable. Due to approx. 3-fold higher blood pool activities for [ 68 Ga]DOTA-RGD, tumour/blood ratios were higher for [ 111 In]DOTA-RGD and [ 18 F]Galacto-RGD. However, microPET studies demonstrated that visualisation of αvβ3-positive tumours using [ 68 Ga]DOTA-RGD is possible. Our data indicate that [ 68 Ga]DOTA-RGD allows monitoring of αvβ3 expression. Especially, the much easier radiosynthesis compared to [ 18 F]Galacto-RGD would make it an attractive alternative. However, due to higher blood pool activity, [ 18 F]Galacto-RGD remains superior for imaging αvβ3 expression. Introduction of alternative chelator

  8. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Pasteurella Haemolytica Vaccine, Bovine. 113.68 Section 113.68 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... Service. (4) A satisfactory challenge shall be evidenced in the controls by progression of clinical signs...

  9. 40 CFR 68.42 - Five-year accident history.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Five-year accident history. 68.42... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.42 Five-year accident history. (a) The owner or operator shall include in the five-year accident history all accidental releases from...

  10. 47 CFR 68.608 - Publication of technical criteria.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Publication of technical criteria. 68.608... Attachments § 68.608 Publication of technical criteria. The Administrative Council for Terminal Attachments shall place technical criteria proposed for publication on public notice for 30 days. At the end of the...

  11. Positron Tomographic Imaging Of The Liver With Ga-68 Iron Hydroxide Colloid

    Science.gov (United States)

    Kumar, Bharath; Miller, Tom R.; Siegel, Barry A.; Mathias, Carla J.; Markham, Joanne; Ehrhardt, Gary J.; Welch, Michael J.

    1980-08-01

    A new radiopharmaceutical, 68Ga-iron hydroxide colloid, for hepatic imaging by positron emission tomography (PET) was prepared from the eluate of a "Ge-68Ga solvent extraction generator. In rats, 84% of the administered dose of colloid localized in the liver and 4.6% accumulated in the spleen. Initial imaging studies in normal dogs showed close correspondence of the findings by PET and transmission computed tomography (CT). PET with 68Ga-colloid was performed in 10 patients with hepatic metastases demonstrated by conventional scintigraphy with 99mTc-sulfur colloid. All focal defects noted on the conventional scintigrams were easily identified and generally seen more clearly by PET. In one patient, lesions not identified on the initial 99mTc-sulfur colloid images were demonstrated by PET. The positron tomographic images were compared with those obtained by CT in 7 patients; the two studies showed comparable findings in 5 patients, whereas PET more clearly showed multiple lesions in 2. Our results suggest that PET is a suitable technique for obtaining high-contrast, cross-sectional images of large abdominal organs. Emission computed tomography with positron-emitting radionuclides shows promise as an important new tool for clinical research (1-4). Unfortunately, wide clinical application of positron-emission tomography (PET) is presently limited by the need for an expensive, hospital-based cyclotron facility and highly trained professional and technical personnel to synthesize the radiopharmaceuticals labeled with the very short-lived radionuclides 11c, 13N, 150 and 18 F that are employed most commonly in such studies. These difficulties may be circumvented in part by the use of a simple generator system that produces the positron-emitting radionuclide 68Ga (T1/2 = 68 min) from the long-lived parent 68Ge (T1/2 = 275 days) (5-7). A large number of radiopharmaceuticals of potential clinical interest may be prepared readily from the eluate of such a generator (6

  12. 45 CFR 5.68 - Exemption seven: Law enforcement.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Exemption seven: Law enforcement. 5.68 Section 5... INFORMATION REGULATIONS Reasons for Withholding Some Records § 5.68 Exemption seven: Law enforcement. We are not required to disclose information or records that the government has compiled for law enforcement...

  13. A new automated NaCl based robust method for routine production of gallium-68 labeled peptides

    International Nuclear Information System (INIS)

    Schultz, Michael K.; Mueller, Dirk; Baum, Richard P.; Leonard Watkins, G.; Breeman, Wouter A.P.

    2013-01-01

    A new NaCl based method for preparation of gallium-68 labeled radiopharmaceuticals has been adapted for use with an automated gallium-68 generator system. The method was evaluated based on 56 preparations of [ 68 Ga]DOTATOC and compared to a similar acetone-based approach. Advantages of the new NaCl approach include reduced preparation time ( 97%), and specific activity (>40 MBq nmole −1 [ 68 Ga]DOTATOC) and is well-suited for clinical production of radiopharmaceuticals. - Highlights: ► A NaCl based automated production of Ga-68-radiopharmaceuticals is described. ► Using 5 M NaCl for pre-purification of 68Ga eliminates the need for organic solvents. ► The method provides for high efficiency, specific activity, and radiochemical purity. ► The new method eliminates the need for the quality control by gas chromatography

  14. 40 CFR 68.151 - Assertion of claims of confidential business information.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.151...)(8), (b)(10) through (b)(13) and NAICS code and Program level of the process set forth in § 68.160(b... (b)(12). (3) Accident history data required by § 68.168; (4) Prevention program data required by § 68...

  15. Evaluation of 68Ga-DOTATOC PET/MRI for whole-body staging of neuroendocrine tumours in comparison with 68Ga-DOTATOC PET/CT.

    Science.gov (United States)

    Sawicki, Lino M; Deuschl, Cornelius; Beiderwellen, Karsten; Ruhlmann, Verena; Poeppel, Thorsten D; Heusch, Philipp; Lahner, Harald; Führer, Dagmar; Bockisch, Andreas; Herrmann, Ken; Forsting, Michael; Antoch, Gerald; Umutlu, Lale

    2017-10-01

    To compare the diagnostic performance of 68 Ga-DOTATOC PET/MRI and 68 Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET). Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar's chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson's correlation coefficient (r). According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p = 0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p = 0.031). SUVmax was strongly correlated (r = 0.86; p PET/MRI (both p PET/MRI yielded a higher proportion of correctly rated NET lesions and should be regarded as a valuable alternative to 68 Ga-DOTATOC PET/CT in whole-body staging of NET patients. • 68 Ga-DOTATOC PET/MRI correctly identified more NET lesions than 68 Ga-DOTATOC PET/CT. • 68 Ga-DOTATOC PET/MRI provides better NET lesion conspicuity than 68 Ga-DOTATOC PET/CT. • SUVmax values from the two modalities are strongly correlated and do not differ significantly.

  16. Detection of Enterovirus D68 in Canadian Laboratories

    Science.gov (United States)

    Hatchette, Todd F.; Drews, Steven J.; Grudeski, Elsie; Booth, Tim; Martineau, Christine; Dust, Kerry; Garceau, Richard; Gubbay, Jonathan; Karnauchow, Tim; Krajden, Mel; Levett, Paul N.; Mazzulli, Tony; McDonald, Ryan R.; McNabb, Alan; Mubareka, Samira; Needle, Robert; Petrich, Astrid; Richardson, Susan; Rutherford, Candy; Smieja, Marek; Tellier, Raymond; Tipples, Graham

    2015-01-01

    The recent emergence of a severe respiratory disease caused by enterovirus D68 prompted investigation into whether Canadian hospital and provincial laboratories can detect this virus using commercial and laboratory-developed assays. This study demonstrated analytical sensitivity differences between commercial and laboratory-developed assays for the detection of enterovirus D68. PMID:25740765

  17. 40 CFR 68.160 - Registration.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.160 Registration. (a) The owner or operator shall... substances handled in covered processes. (b) The registration shall include the following data: (1...

  18. Memory and History of Mexico ’68

    Directory of Open Access Journals (Sweden)

    Eugenia Allier Montaño

    2016-10-01

    Full Text Available The student movement Mexico ’68 (Sesenta-y-ocho that was active between July and December of 1968 has come to be seen as one of the most important events of the second half of the twentieth century in Mexico, in both public memory and national history. However as this was not always the case, the aim of this article is to analyse the transformations and permanencies in the many accounts that have formed over the last four decades concerning the Mexican summer of 1968, giving attention to four types of narrative: public debates, the specialized historiography on the student movement, books dealing with national history, and the official history. This analysis is intended to show how the ‘historical centrality’ of 1968 was progressively formed in the national public space and in historiographic discourse. Resumen: Memorias e historias de México 68 El movimiento estudiantil de México 68 (Sesenta-y-ocho que tuvo lugar entre julio y diciembre de 1968 se considera como uno de los acontecimientos más importantes de México en la segunda mitad del siglo XX, tanto desde la memoria pública como desde la historiografía nacional. Sin embargo, como esto no siempre fue así, el objetivo del artículo es analizar las transformaciones y permanencias en las múltiples narraciones que se han creado a lo largo de las últimas cuatro décadas acerca del verano mexicano del 68, dando preeminencia a cuatro narrativas: los debates públicos, la historiografía especializada sobre el movimiento estudiantil, los libros abocados a la historia nacional y la historia oficial. Este análisis busca mostrar cómo se fue conformando la ‘centralidad histórica’ del 68 en el espacio público nacional y en los discursos historiográficos.

  19. Anisotropic p-f mixing mechanism explaining anomalous magnetic properties in Ce monopnictides

    International Nuclear Information System (INIS)

    Takahashi, H.; Kasuya, T.

    1985-01-01

    The crystal-field splittings in CeP, PrP and NdP are calculated by considering the point-charge Coulomb interaction, the intra-atomic d-f Coulomb interaction, and the p-f and d-f mixings. The p-f mixing mechanisms, not only between the occupied 4f states and the conduction bands, but also between the unoccupied 4f states and the valence bands make an important contribution to the crystal-field splitting. The fact that the crystal-field potential in CeP is smaller than those in PrP and NdP is due to the occupied 4f level in CeP being shallower. The values of the Slater-Koster integrals, (pfσ) and (pfπ), are determined uniquely from the crystal-field fitting for PrP and NdP. (author)

  20. High-Performance, 0.6-eV, GA0.32In0.68As/In0.32P0.68 Thermophotovoltaic Converters and Monolithically Interconnected Modules

    International Nuclear Information System (INIS)

    Duda, A.; Murray, C.S.

    1998-01-01

    Recent progress in the development of high-performance, 0.6-eV Ga0.32In0.68As/InAs0.32P0.68 thermophotovoltaic (TPV) converters and monolithically interconnected modules (MIMs) is described. The converter structure design is based on using a lattice-matched InAs0.32P0.68/Ga0.32In0.68As/InAs0.32P0.68 double-heterostructure (DH) device, which is grown lattice-mismatched on an InP substrate, with an intervening compositionally step-graded region of InAsyP1-y. The Ga0.32In0.68As alloy has a room-temperature band gap of 0.6 eV and contains a p/n junction. The InAs0.32P0.68 layers have a room-temperature band gap of 0.96 eV and serve as passivation/confinement layers for the Ga0.32In0.68As p/n junction. InAsyP1-y step grades have yielded DH converters with superior electronic quality and performance characteristics. Details of the microstructure of the converters are presented. Converters prepared for this work were grown by atmospheric-pressure metalorganic vapor-phase epitaxy (APMOVPE) and were processed using a combination of photolithography, wet-chemical etching, and conventional metal and insulator deposition techniques. Excellent performance characteristics have been demonstrated for the 0.6-eV TPV converters. Additionally, the implementation of MIM technology in these converters has been highly successful

  1. Evaluation of 68Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1

    International Nuclear Information System (INIS)

    Morgat, Clement; Mazere, Joachim; Hindie, Elif; Fernandez, Philippe; Velayoudom-Cephise, Fritz-Line; Nunes, Marie-Laure; Tabarin, Antoine; Schwartz, Paul; Guyot, Martine; Gaye, Delphine; Vimont, Delphine; Schulz, Juergen; Smith, Denis

    2016-01-01

    Somatostatin receptor scintigraphy with 111 In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with 68 Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1. To compare the performances of 68 Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1. Single-institution prospective comparative study Nineteen consecutive MEN1 patients (aged 47 ± 13 years) underwent 68 Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, 18 F-2-fluoro-deoxy-d-glucose ( 18 F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis. The sensitivity of 68 Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p < 0.0001). All the true-positive lesions detected by SRS were also depicted on 68 Ga-DOTA-TOC PET/CT. 68 Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 ± 7.6 and 15.2 ± 5.9 mm, respectively, p < 0.03). False negatives of 68 Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and 18 F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with 68 Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS. Owing to higher diagnostic performance, 68 Ga-DOTA-TOC PET/CT (or alternative 68 Ga-labeled somatostatin analogues) should replace 111 In-pentetreotide in the investigation of MEN1

  2. 40 CFR 68.56 - Maintenance.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.56 Maintenance. (a) The owner or operator shall prepare and implement procedures to maintain the on-going mechanical integrity of the process...

  3. 40 CFR 68.87 - Contractors.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.87 Contractors. (a) Application. This... specialty work on or adjacent to a covered process. It does not apply to contractors providing incidental...

  4. Ventilation-perfusion-lungscintigraphy using PET and {sup 68}Ga-labeled radiopharmaceuticals; Ventilations-Perfusions-Lungenszintigraphie mit der PET und {sup 68}Ga-markierten Radiopharmaka

    Energy Technology Data Exchange (ETDEWEB)

    Kotzerke, J. [Technische Univ. Dresden (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Technische Univ. Dresden (Germany). OncoRay - Zentrum fuer Innovationskompetenz Strahlenforschung in der Onkologie; Forschungszentrum Dresden-Rossendorf e.V. (FZR) (Germany). PET-Zentrum; Andreeff, M.; Wunderlich, G.; Zoephel, K. [Technische Univ. Dresden (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Wiggermann, P. [Technische Univ. Dresden (Germany). Inst. und Poliklinik fuer Diagnostische Radiologie

    2010-07-01

    Aim: Imaging of lung perfusion with positron emission tomography (PET) is already possible with {sup 68}Ga labeled denaturized albumin. The purpose of our study was to produce and test a {sup 68}Ga labeled aerosol (Galligas {sup registered}) for ventilation and {sup 68}Ga labeled albumin particles (microspheres) for perfusion imaging with PET. Patients, methods: Galligas was produced by simmering and burning generator eluted {sup 68}Ga solution (100 MBq/0.1ml) in an ordinary technegas generator. Fifteen patients with suspicion on pulmonary embolism underwent PET/CT (Biograph 16) after inhalation of Galligas and application of {sup 68}Ga labeled microspheres. A low dose CT was acquired for attenuation correction (AC). Images were reconstructed with and without AC. The inhaled activity was calculated compared to the activity injected. Results: Inhaled radioaerosol Galligas demonstrated typical distribution as known from {sup 99m}Tc-labeled technegas with homogeneous distribution in lung without hilar deposits. Attenuation corrected images resulted in artefacts in the lung base. Therefore, non-corrected images were used for making the results. Three out of fifteen patients showed a deficient perfusion whereas ventilation was normal corresponding to pulmonary embolism. Conclusion: Lung scintigraphy with PET is feasible. Galligas is simple to produce (analogously to technegas). {sup 68}Ga labeled microspheres are available. The method is applicable to daily routine and rendered clinically relevant informations. (orig.)

  5. Radio-synthesis and mass spectrometry analysis of 68Ga-DKFZ-PSMA-617 for non-invasive prostate cancer PET imaging

    International Nuclear Information System (INIS)

    Hua Zhu; Qing Xie; Nan Li; Fei Liu; Huifang Tian; Zhi Yang

    2016-01-01

    The focus of this paper in on quality control and decay property analysis of 68 Ga-DKFZ-PSMA-617 for positron emission tomography (PET) imaging of prostate cancer. 68 Ga-DKFZ-PSMA-617 was synthesized in high radiochemical yield and specific activity (77 GBq/µmol) under optimized conditions. The decayed tracer was characterized by MADLI-TOF to support its decay and coordination characterization. Contrast PET imaging studies were performed using normal nude mice after intravenous injection of 18.5 MBq of 68 Ga-DKFZ-PSMA-617 and 18 F-FDG respectively. These results warrant the further clinical application of 68 Ga-DKFZ-PSMA-617 in prostate cancer PET imaging. (author)

  6. Development of a production scale purification of Ge-68 from irradiated gallium metal

    Energy Technology Data Exchange (ETDEWEB)

    Fitzsimmons, Jonathan M.; Mausner, Leonard [Brookhaven National Laboratory, Upton, NY (United States)

    2015-05-01

    Germanium-68 (Ge-68) is produced by proton irradiation of a gallium metal target and purified by organic extraction. The Ge-68 can be used in a medical isotope generator to produce Gallium-68 (Ga-68) which can be used to radiolabel PET imaging agents. The emerging use of Ge-68 in the Ga-68 medical isotope generator has caused us to develop a new purification method for Ge-68 that does not use toxic solvents. The purpose of this work was to develop a production scale separation of Ge-68 that utilizes a leaching step to remove a bulk of the gallium metal, followed by purification with Sephadex {sup copyright} G25. Production scale (300 mCi) purification was performed with the new method. The purified Ge-68 contained the highest radioactivity concentration of Ge-68 produced at BNL; the sample meet Department of Energy specifications and the method had an excellent recovery of Ge-68.

  7. Evaluation of bone-seeking novel radiotracer {sup 68}Ga-NO2AP-Bisphosphonate for the detection of skeletal metastases in carcinoma breast

    Energy Technology Data Exchange (ETDEWEB)

    Passah, Averilicia; Tripathi, Madhavi; Ballal, Sanjana; Yadav, Madhav Prasad; Kumar, Rajeev; Chakraborty, Partha Sarathi; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Roesch, Frank; Meckel, Marian [Johannes-Gutenberg-University, Nuclear Chemistry, Mainz (Germany)

    2017-01-15

    The successful labelling of bisphosphonates (BP) with {sup 68}Ga using macrocyclic chelators such as the based triazacyclononane (NO2AP) is a step forward in the in-house availability of a novel bone-seeking PET radiopharmaceutical with dual advantage of PET/CT imaging and generator production. In this study, we compared the novel generator-based skeletal radiotracer {sup 68}Ga-1,4,7-triazacyclonone-1,4-diacetic acid ({sup 68}Ga-NO2AP-BP) with sodium fluoride ({sup 18}F-NaF) for the detection of skeletal metastases in breast cancer patients. In addition, dosimetric analysis of {sup 68}Ga-NO2AP-BP was performed in a subset of patients. This was a prospective study of histopathologically proven cases of breast cancer patients who were referred for bone scintigraphy and underwent positron emission tomography/computed tomography (PET/CT) with {sup 18}F-NaF and {sup 68}Ga-NO2AP-BP within a week in random order. The scans of each patient were compared both qualitatively for image quality and quantitatively for number of lesions and SUVmax of lesions. Dosimetric analysis was performed in five patients. Their PET/CT scans were acquired at multiple time points and urine and blood samples were collected. Dosimetric calculations were performed using OLINDA/EXM 1.1 software. Statistical analysis was done using Stata 13 (StataCorp) software package. An agreement analysis regarding number of lesions detected with the two skeletal radiotracers was carried out. The image quality of {sup 68}Ga-NO2AP-BP PET/CT scans were comparable to that of {sup 18}F-NaF. There was no statistically significant difference in the SUVmax of lesions, normal bone and lesion to background ratio between the two skeletal radiotracers. There was good agreement in the number of lesions detected by both skeletal radiotracers. The mean whole body effective dose for {sup 68}Ga-NO2AP-BP was 0.00583 mSv/MBq and the effective dose equivalent was 0.0086 mSv/MBq. The excellent lesion detection agreement between

  8. 28 CFR 68.25 - Subpoenas.

    Science.gov (United States)

    2010-07-01

    ... BEFORE ADMINISTRATIVE LAW JUDGES IN CASES INVOLVING ALLEGATIONS OF UNLAWFUL EMPLOYMENT OF ALIENS, UNFAIR IMMIGRATION-RELATED EMPLOYMENT PRACTICES, AND DOCUMENT FRAUD § 68.25 Subpoenas. (a) An Administrative Law... testimony of witnesses and production of things including, but not limited to, papers, books, documents...

  9. 40 CFR 68.10 - Applicability.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS General § 68.10 Applicability. (a) An owner or operator of a stationary source that has more than a threshold quantity of a regulated substance in a process, as determined under...

  10. 40 CFR 68.190 - Updates.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.190 Updates. (a) The owner or operator shall... later than the date on which a new regulated substance is first present in an already covered process...

  11. Synthesis and evaluation of 68Ga-labeled DOTA-2-deoxy-D-glucosamine as a potential radiotracer in μPET imaging

    Science.gov (United States)

    Yang, Zhi; Xiong, Chiyi; Zhang, Rui; Zhu, Hua; Li, Chun

    2012-01-01

    The purposes of this study were to develop an efficient method of labeling D-glucosamine hydrochloride with gallium 68 (68Ga) and investigate the imaging properties of the resulting radiotracer in a human tumor xenograft model using micro-positron emission tomography (μPET). The precursor compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-2-deoxy-D-glucosamine (DOTA-DG) was synthesized from D-glucosamine hydrochloride and 2-(4-isothiocyanatobenzyl)-DOTA. Radiolabeling of DOTA-DG with 68Ga was achieved in 10 minutes using microwave heating. The labeling efficiency a nd radiochemical purity after purification of 68Ga-DOTA-DG were ~85% and greater than 98%, respectively. In A431 cells, the percentages of 68Ga-DOTA-DG and 18F-FDG uptakes after 60 min incubation were 15.7% and 16.2%, respectively. In vivo, the mean ± standard deviation of 68Ga-DOTADG uptake values in A431 tumors were 2.38±0.30, 0.75±0.13, and 0.39±0.04 percent of the injected dose per gram of tissue at 10, 30, and 60 minutes after intravenous injection, respectively. μPET imaging of A431-bearing mice clearly delineated tumors at 60 minutes after injection of 68Ga-DOTA-DG at a dose of 3.7 MBq. 68Ga-DOTA-DG displayed significantly higher tumor-to-heart, tumor-to-brain, and tumor-to-muscle ratios than 18F-FDG did. Further studies are needed to identify the mechanism of tumor uptake of this new glucosamine-based PET imaging tracer. PMID:23145365

  12. 41 CFR 105-68.510 - Who maintains the EPLS?

    Science.gov (United States)

    2010-07-01

    ... Regulations System (Continued) GENERAL SERVICES ADMINISTRATION Regional Offices-General Services Administration 68-GOVERNMENTWIDE DEBARMENT AND SUSPENSION (NONPROCUREMENT) Excluded Parties List System § 105-68... nonprocurement or procurement debarment and suspension system, the agency enters the information about the...

  13. Characterization of Bombyx mori nucleopolyhedrovirus orf68 gene that encodes a novel structural protein of budded virus.

    Science.gov (United States)

    Iwanaga, Masashi; Kurihara, Masaaki; Kobayashi, Masahiko; Kang, WonKyung

    2002-05-25

    All lepidopteran baculovirus genomes sequenced to date encode a homolog of the Bombyx mori nucleopolyhedrovirus (BmNPV) orf68 gene, suggesting that it performs an important role in the virus life cycle. In this article we describe the characterization of BmNPV orf68 gene. Northern and Western analyses demonstrated that orf68 gene was expressed as a late gene and encoded a structural protein of budded virus (BV). Immunohistochemical analysis by confocal microscopy showed that ORF68 protein was localized mainly in the nucleus of infected cells. To examine the function of orf68 gene, we constructed orf68 deletion mutant (BmD68) and characterized it in BmN cells and larvae of B. mori. BV production was delayed in BmD68-infected cells. The larval bioassays also demonstrated that deletion of orf68 did not reduce the infectivity, but mutant virus took 70 h longer to kill the host than wild-type BmNPV. In addition, dot-blot analysis showed viral DNA accumulated more slowly in mutant infected cells. Further examination suggested that BmD68 was less efficient in entry and budding from cells, although it seemed to possess normal attachment ability. These results suggest that ORF68 is a BV-associated protein involved in secondary infection from cell-to-cell. (c) 2002 Elsevier Science (USA).

  14. Enterovirus D68 detection in respiratory specimens: Association with severe disease.

    Science.gov (United States)

    Engelmann, Ilka; Fatoux, Marie; Lazrek, Mouna; Alidjinou, Enagnon K; Mirand, Audrey; Henquell, Cécile; Dewilde, Anny; Hober, Didier

    2017-07-01

    Molecular techniques increased the number of documented respiratory infections. In a substantial number of cases the causative agent remains undetected. Since August 2014, an increase in Enterovirus(EV)-D68 infections was reported. We aimed to investigate epidemiology and clinical relevance of EV-D68. From June to December 2014 and from September to December 2015, 803 and 847 respiratory specimens, respectively, were tested for respiratory viruses with a multiplex RT-PCR. This multiplex RT-PCR does not detect EV-D68. Therefore, 457 (2014) and 343 (2015) specimens with negative results were submitted to an EV-specific-RT-PCR. EV-positive specimens were tested with an EV-D68-specific-RT-PCR and genotyped. Eleven specimens of 2014 tested positive in the EV-specific-RT-PCR and of these seven were positive in the EV-D68-specific-RT-PCR. Typing confirmed these as EV-D68. Median age of EV-D68-positive patients was 3 years (1 month-91 years). Common symptoms included fever (n = 6, 86%), respiratory distress (n = 5, 71%), and cough (n = 4, 57%). All EV-D68-positive patients were admitted to hospital, 4 (57%) were admitted to intensive care units and 6 (86%) received oxygen. One patient suffered from acute flaccid paralysis. Seven specimens of 2015 were positive in the EV-specific-RT-PCR but negative in the EV-D68-specific-RT-PCR. In conclusion, use of an EV-specific-RT-PCR allowed us to detect EV-D68 circulation in autumn 2014 that was not detected by the multiplex RT-PCR and was associated with severe disease. © 2017 Wiley Periodicals, Inc.

  15. 40 CFR 68.150 - Submission.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.150 Submission. (a) The owner or operator shall... processes. The RMP shall be submitted in the method and format to the central point specified by EPA as of...

  16. Determination of 68Ga production parameters by different reactions ...

    Indian Academy of Sciences (India)

    function of 68Zn(p, n)68Ga reaction was compared with the reported ... 2.1.1 Brief description of nuclear models applied for cross-section calculations ... tion of isotope impurities is not possible by chemical methods, so this reaction is.

  17. 41 CFR 105-68.950 - Excluded Parties List System

    Science.gov (United States)

    2010-07-01

    ... System 105-68.950 Section 105-68.950 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION Regional Offices-General Services... General Services Administration (GSA) containing the names and other information about persons who are...

  18. Ga2O for target, solvent extraction for radiochemical separation and SnO2 for the preparation of a 68Ge/68Ga generator

    International Nuclear Information System (INIS)

    Aardaneh, K.; Walt, T.N. van der

    2006-01-01

    The target for the production of 68 Ge consists of a disc of gallium suboxide, Ga 2 O, with a 19 mm diameter. The suboxide was primarily prepared by repeatedly mixing metallic Ga and Ga 2 O 3 at 700 deg C. The target (2.4 g) was quite stable under a long-time irradiation with a 34 MeV proton beam at a current of ∼80 μA. The dissolution of the target was performed using 12M sulphuric acid solution, assisted with the dropwise addition of 30% H 2 O 2 solution, and took less than 4 hours. A solvent extraction method, using a 9M H 2 SO 4 - 0.3M HCl/CCl 4 system, was employed for the radiochemical separation of 68 Ge from Ga and Zn radionuclides, while 0.05M HCl was used for the back extraction of 68 Ge from the organic phase. The 68 Ge obtained in the dilute HCl was directly loaded onto a column containing either a hydrous tin dioxide or a crystalline tin dioxide, obtained by calcinations of the hydrous oxide at 450, 700, and 900 deg C. The calcinated hydrous tin dioxide at 900 deg C showed the highest crystallinity and highest 68 Ga elution yield and was selected for use in the generator. The 68 Ga elution from the column generator packed with 2 g of tin dioxide, using 3 ml of 1M HCl, and yielded an average of 65%. The breakthrough of 68 Ge was 6.1 x 10 -4 %. (author)

  19. 16 CFR 5.68 - Judicial review.

    Science.gov (United States)

    2010-01-01

    ... CONDUCT Disciplinary Actions Concerning Postemployment Conflict of Interest § 5.68 Judicial review. A respondent against whom the Commission has issued an order imposing disciplinary action under this part may...

  20. A mouse model of paralytic myelitis caused by enterovirus D68.

    Directory of Open Access Journals (Sweden)

    Alison M Hixon

    2017-02-01

    Full Text Available In 2014, the United States experienced an epidemic of acute flaccid myelitis (AFM cases in children coincident with a nationwide outbreak of enterovirus D68 (EV-D68 respiratory disease. Up to half of the 2014 AFM patients had EV-D68 RNA detected by RT-PCR in their respiratory secretions, although EV-D68 was only detected in cerebrospinal fluid (CSF from one 2014 AFM patient. Given previously described molecular and epidemiologic associations between EV-D68 and AFM, we sought to develop an animal model by screening seven EV-D68 strains for the ability to induce neurological disease in neonatal mice. We found that four EV-D68 strains from the 2014 outbreak (out of five tested produced a paralytic disease in mice resembling human AFM. The remaining 2014 strain, as well as 1962 prototype EV-D68 strains Fermon and Rhyne, did not produce, or rarely produced, paralysis in mice. In-depth examination of the paralysis caused by a representative 2014 strain, MO/14-18947, revealed infectious virus, virion particles, and viral genome in the spinal cords of paralyzed mice. Paralysis was elicited in mice following intramuscular, intracerebral, intraperitoneal, and intranasal infection, in descending frequency, and was associated with infection and loss of motor neurons in the anterior horns of spinal cord segments corresponding to paralyzed limbs. Virus isolated from spinal cords of infected mice transmitted disease when injected into naïve mice, fulfilling Koch's postulates in this model. Finally, we found that EV-D68 immune sera, but not normal mouse sera, protected mice from development of paralysis and death when administered prior to viral challenge. These studies establish an experimental model to study EV-D68-induced myelitis and to better understand disease pathogenesis and develop potential therapies.

  1. Evaluation of {sup 68}Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1

    Energy Technology Data Exchange (ETDEWEB)

    Morgat, Clement; Mazere, Joachim; Hindie, Elif; Fernandez, Philippe [CNRS, INCIA, Bordeaux (France); University of Bordeaux, INCIA, Bordeaux (France); University Hospital of Bordeaux, Department of Nuclear Medicine, Bordeaux (France); Velayoudom-Cephise, Fritz-Line; Nunes, Marie-Laure; Tabarin, Antoine [USN Haut-Leveque, Department of Endocrinology, Pessac (France); Schwartz, Paul; Guyot, Martine [University Hospital of Bordeaux, Department of Nuclear Medicine, Bordeaux (France); Gaye, Delphine [University Hospital of Bordeaux, Department of Radiology, Pessac (France); Vimont, Delphine; Schulz, Juergen [CNRS, INCIA, Bordeaux (France); University of Bordeaux, INCIA, Bordeaux (France); Smith, Denis [University Hospital of Bordeaux, Department of Oncology, Bordeaux (France)

    2016-07-15

    Somatostatin receptor scintigraphy with {sup 111}In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with {sup 68}Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1. To compare the performances of {sup 68}Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1. Single-institution prospective comparative study Nineteen consecutive MEN1 patients (aged 47 ± 13 years) underwent {sup 68}Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, {sup 18}F-2-fluoro-deoxy-d-glucose ({sup 18}F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis. The sensitivity of {sup 68}Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p < 0.0001). All the true-positive lesions detected by SRS were also depicted on {sup 68}Ga-DOTA-TOC PET/CT. {sup 68}Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 ± 7.6 and 15.2 ± 5.9 mm, respectively, p < 0.03). False negatives of {sup 68}Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and {sup 18}F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with {sup 68}Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS. Owing to higher diagnostic performance, {sup 68}Ga-DOTA-TOC PET/CT (or alternative {sup 68}Ga-labeled somatostatin analogues

  2. 28 CFR 68.28 - Authority of Administrative Law Judge.

    Science.gov (United States)

    2010-07-01

    ....28 Section 68.28 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RULES OF PRACTICE AND... UNLAWFUL EMPLOYMENT OF ALIENS, UNFAIR IMMIGRATION-RELATED EMPLOYMENT PRACTICES, AND DOCUMENT FRAUD § 68.28... so, any pertinent book, paper, or document, or refuses to appear after having been subpoenaed, or...

  3. Studies of the chemical behavior of carrier-free 68Ge. Pt. 1

    International Nuclear Information System (INIS)

    Mirzadeh, S.; Kahn, M.; Grant, P.M.; O'Brien, H.A. Jr.

    1981-01-01

    The diagnostic utilization of the 68 Ge- 68 Ga system in nuclear medicine stimulated the development of a rapid and efficient method for the purification of carrier-free 68 Ge. A standard procedure for the separation of macroscopic quantities for germanium from numerous other elements involves the distillation of Ge(IV) from HCl solution. The applicability of this method for the purification of carrier-free 68 Ge was studied, and it was found that 68 Ge quantitatively and conveniently distills from azetropic HCl. The distillation of 68 Ge from LiCl-HClO 4 , HCl-LiCl, and HCl-HClO 4 systems was also investigated. (orig.) [de

  4. 28 CFR 68.15 - Intervenor in unfair immigration-related employment cases.

    Science.gov (United States)

    2010-07-01

    ... employment cases. 68.15 Section 68.15 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RULES OF PRACTICE AND PROCEDURE FOR ADMINISTRATIVE HEARINGS BEFORE ADMINISTRATIVE LAW JUDGES IN CASES INVOLVING... FRAUD § 68.15 Intervenor in unfair immigration-related employment cases. The Special Counsel, or any...

  5. (68)Ga-DOTATATE PET in juvenile angiofibroma.

    Science.gov (United States)

    Gronkiewicz, Zuzanna; Kukwa, Wojciech; Krolicki, Leszek; Cyran-Chlebicka, Agata; Pawlak, Dariusz; Stankiewicz, Czeslaw; Krzeski, Antoni; Górnicka, Barbara; Wolosz, Dominika; Kunikowska, Jolanta

    2016-06-01

    As somatostatin receptors (SSTRs) may be overexpressed in rapidly growing vessels, the aim of this study was the analysis of in vivo and in vitro SSTR2A expression in juvenile angiofibroma (JA). A group of six male adolescents with a diagnosis of primary, recurrent/residual JA was enrolled in the study. All patients underwent (68)Ga-DOTATATE PET/computed tomography (CT) followed by immunohistochemical staining for SSTR expression. (68)Ga-DOTATATE PET/CT showed accumulation in areas matching the pathologic tissue in the nasopharynx of all patients studied with SUVmax of 5.1 ± 0.9 (ranging from 3.6 to 6.4). In all cases, the immunohistochemical examination showed a presence of SSTR2A with a high staining index. In vitro SSTR2A cytoplasm expression was found to be high in all tumor specimens. However, the uptake of (68)Ga-DOTATATE was weak in the PET/CT studies. We postulate that the intracellular localization of the SSTR2A in JA may cause this discrepancy.

  6. 28 CFR 68.41 - Official notice.

    Science.gov (United States)

    2010-07-01

    ... ALIENS, UNFAIR IMMIGRATION-RELATED EMPLOYMENT PRACTICES, AND DOCUMENT FRAUD § 68.41 Official notice... so noticed, and shall be given adequate opportunity to show the contrary. [54 FR 48596, Nov. 24, 1989...

  7. Emergence of enterovirus D68 in Denmark, June 2014 to February 2015

    DEFF Research Database (Denmark)

    Midgley, S E; Christiansen, C B; Poulsen, M W

    2015-01-01

    From June 2014 through February 2015, respiratory samples from 130 Danish patients were screened for enterovirus D68 (EV-D68). Fourteen EV-D68 cases were detected, of which 12 presented with respiratory symptoms, and eight had known underlying disease. The median age of EV-D68 cases was three years...

  8. 45 CFR 400.68 - Notification to local resettlement agency.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 2 2010-10-01 2010-10-01 false Notification to local resettlement agency. 400.68 Section 400.68 Public Welfare Regulations Relating to Public Welfare OFFICE OF REFUGEE RESETTLEMENT, ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES REFUGEE RESETTLEMENT PROGRAM...

  9. Positron scintigraphy of liver and kidneys with Ga-68-labelled dihydroxyanthraquinones

    International Nuclear Information System (INIS)

    Schuhmacher, J.; Maier-Borst, W.; Wellmann, H.N.

    1980-01-01

    The preparation of alizarin (1.2 dihydroxyanthraquinone) and alizarin red S (sodium 1.2 dihydroxyanthraquinone 3 sulfonate) labelled with Ga-68, which is obtained from a new high yield Ge-68/Ga-68 generator, is described. The uptake of Ga-68 alizarin by liver and spleen RES was studied in rats, dogs and humans, and amounted to 80 - 86 % of the administered dose within 5 min after i.v. injection. Ga-68 alizarin red S was preferentially accumulated in the renal parenchyma to an extent of 80 % within 90 min after i.v. administration. Both substances combine simple and fast preparation with the potential advantages of positron scintigraphy. Complete labelling of 1 mCi Ga-68 was achieved by 100 μg of each compound; an amount of substance which is without any known measurable harm to humans. Lsub(D)50 alizarin red S for i.v. injected mice: 70 mg/kg. (author)

  10. Determination of HEPES in 68Ga-labeled peptide solutions

    International Nuclear Information System (INIS)

    Revital Sasson; Dan Vaknin; Avihai Bross; Efraim Lavie

    2010-01-01

    A practical and reliable HPLC method was used for the determination of 2-[4-N-(2-hydroxyethyl)-1-piperazinyl]-N'-ethanesulfonic acid (HEPES) content in the 68 Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-octreotide (DOTANOC). Linearity of this method was observed in a concentration range of 0.01-10 mg mL -1 and the quantitative limit (signal to noise = 11) was determined as 10 μg mL -1 . The HEPES concentration in the final products of 68 Ga-DOTANOC was typically lower than the detection limit. Pure water and HEPES buffer as reaction medium were investigated using various activities of gallium-68. It was demonstrated that the presence of HEPES buffer consistently furnished very high radiochemical purity of 68 Ga-DOTANOC, which remained stable for several hours post-labeling. Evidence is provided that in addition to its role as a buffer, HEPES also functions as a radioprotectant agent. (author)

  11. Probing the semi-magicity of $^{68}$Ni via the $^{3}$H($^{66}$Ni,$^{68}$Ni)p two-neutron transfer reaction in inverse kinematics

    CERN Multimedia

    Reiter, P; Blazhev, A A; Kruecken, R; Franchoo, S; Mertzimekis, T; Darby, I G; Van de walle, J; Raabe, R; Elseviers, J; Gernhaeuser, R A; Sorlin, O H; Georgiev, G P; Bree, N C F; Habs, D; Chapman, R; Gaudefroy, L; Diriken, J V J; Jenkins, D G; Kroell, T; Axiotis, M; Huyse, M L; Patronis, N

    We propose to perform the two-neutron transfer reaction $^{3}$H($^{66}$Ni, $^{68}$Ni)$p$ using the ISOLDE radioactive ion beam at 2.7 $A$ MeV and the MINIBALL + T-REX setup to characterize the 0$^{+}$ and 2$^{+}$ states in $^{68}$Ni.

  12. 40 CFR 68.126 - Exclusion.

    Science.gov (United States)

    2010-07-01

    ... ACCIDENT PREVENTION PROVISIONS Regulated Substances for Accidental Release Prevention § 68.126 Exclusion. Flammable Substances Used as Fuel or Held for Sale as Fuel at Retail Facilities. A flammable substance... substance is used as a fuel or held for sale as a fuel at a retail facility. [65 FR 13250, Mar. 13, 2000] ...

  13. 40 CFR 68.25 - Worst-case release scenario analysis.

    Science.gov (United States)

    2010-07-01

    ... PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.25 Worst-case release... processes, one worst-case release scenario for each Program 1 process; (2) For Program 2 and 3 processes: (i... toxic substances from covered processes under worst-case conditions defined in § 68.22; (ii) One worst...

  14. Tumor Targeting via Sialic Acid: [68Ga]DOTA-en-pba as a New Tool for Molecular Imaging of Cancer with PET.

    Science.gov (United States)

    Tsoukalas, Charalambos; Geninatti-Crich, Simonetta; Gaitanis, Anastasios; Tsotakos, Theodoros; Paravatou-Petsotas, Maria; Aime, Silvio; Jiménez-Juárez, Rogelio; Anagnostopoulos, Constantinos D; Djanashvili, Kristina; Bouziotis, Penelope

    2018-02-20

    The aim of this study was to demonstrate the potential of Ga-68-labeled macrocycle (DOTA-en-pba) conjugated with phenylboronic vector for tumor recognition by positron emission tomography (PET), based on targeting of the overexpressed sialic acid (Sia). The imaging reporter DOTA-en-pba was synthesized and labeled with Ga-68 at high efficiency. Cell binding assay on Mel-C and B16-F10 melanoma cells was used to evaluate melanin production and Sia overexpression to determine the best model for demonstrating the capability of [ 68 Ga]DOTA-en-pba to recognize tumors. The in vivo PET imaging was done with B16-F10 tumor-bearing SCID mice injected with [ 68 Ga]DOTA-en-pba intravenously. Tumor, blood, and urine metabolites were assessed to evaluate the presence of a targeting agent. The affinity of [ 68 Ga]DOTA-en-pba to Sia was demonstrated on B16-F10 melanoma cells, after the production of melanin as well as Sia overexpression was proved to be up to four times higher in this cell line compared to that in Mel-C cells. Biodistribution studies in B16-F10 tumor-bearing SCID mice showed blood clearance at the time points studied, while uptake in the tumor peaked at 60 min post-injection (6.36 ± 2.41 % ID/g). The acquired PET images were in accordance with the ex vivo biodistribution results. Metabolite assessment on tumor, blood, and urine samples showed that [ 68 Ga]DOTA-en-pba remains unmetabolized up to at least 60 min post-injection. Our work is the first attempt for in vivo imaging of cancer by targeting overexpression of sialic acid on cancer cells with a radiotracer in PET.

  15. STS-68 Mission Insignia

    Science.gov (United States)

    1994-01-01

    This STS-68 patch was designed by artist Sean Collins. Exploration of Earth from space is the focus of the design of the insignia, the second flight of the Space Radar Laboratory (SRL-2). SRL-2 was part of NASA's Mission to Planet Earth (MTPE) project. The world's land masses and oceans dominate the center field, with the Space Shuttle Endeavour circling the globe. The SRL-2 letters span the width and breadth of planet Earth, symbolizing worldwide coverage of the two prime experiments of STS-68: The Shuttle Imaging Radar-C and X-Band Synthetic Aperture Radar (SIR-C/X-SAR) instruments; and the Measurement of Air Pollution from Satellites (MAPS) sensor. The red, blue, and black colors of the insignia represent the three operating wavelengths of SIR-C/X-SAR, and the gold band surrounding the globe symbolizes the atmospheric envelope examined by MAPS. The flags of international partners Germany and Italy are shown opposite Endeavour. The relationship of the Orbiter to Earth highlights the usefulness of human space flights in understanding Earth's environment, and the monitoring of its changing surface and atmosphere. In the words of the crew members, the soaring Orbiter also typifies the excellence of the NASA team in exploring our own world, using the tools which the Space Program developed to explore the other planets in the solar system.

  16. Pea p68, a DEAD-box helicase, provides salinity stress tolerance in transgenic tobacco by reducing oxidative stress and improving photosynthesis machinery.

    Science.gov (United States)

    Tuteja, Narendra; Banu, Mst Sufara Akhter; Huda, Kazi Md Kamrul; Gill, Sarvajeet Singh; Jain, Parul; Pham, Xuan Hoi; Tuteja, Renu

    2014-01-01

    The DEAD-box helicases are required mostly in all aspects of RNA and DNA metabolism and they play a significant role in various abiotic stresses, including salinity. The p68 is an important member of the DEAD-box proteins family and, in animal system, it is involved in RNA metabolism including pre-RNA processing and splicing. In plant system, it has not been well characterized. Here we report the cloning and characterization of p68 from pea (Pisum sativum) and its novel function in salinity stress tolerance in plant. The pea p68 protein self-interacts and is localized in the cytosol as well as the surrounding of cell nucleus. The transcript of pea p68 is upregulated in response to high salinity stress in pea. Overexpression of p68 driven by constitutive cauliflower mosaic virus-35S promoter in tobacco transgenic plants confers enhanced tolerances to salinity stress by improving the growth, photosynthesis and antioxidant machinery. Under stress treatment, pea p68 overexpressing tobacco accumulated higher K+ and lower Na+ level than the wild-type plants. Reactive oxygen species (ROS) accumulation was remarkably regulated by the overexpression of pea p68 under salinity stress conditions, as shown from TBARS content, electrolyte leakage, hydrogen peroxide accumulation and 8-OHdG content and antioxidant enzyme activities. To the best of our knowledge this is the first direct report, which provides the novel function of pea p68 helicase in salinity stress tolerance. The results suggest that p68 can also be exploited for engineering abiotic stress tolerance in crop plants of economic importance.

  17. Synthesis of 2-nitroimidazole-glycopeptide 68Ga-labeled for identification of areas of hypoxia in the tumor microenvironment

    International Nuclear Information System (INIS)

    Pérez Nario, Arian; Leiria Campo, Vanessa; Soares Bernardes, Emerson

    2016-01-01

    Introduction: Hypoxia is a pathological condition characterized by a reduction in oxygen delivery to a tissue or cell specific. It is estimated that 60% of solid tumors in advanced stages have areas of hypoxia and anoxia (almost complete absence of oxygen). It is now known that hypoxia in the tumor microenvironment is closely related to: 1) increased tumor aggressiveness; 2) increased relapse rate; 3) increased resistance to chemotherapy and radiotherapy; 4) poor prognosis of the disease. Therefore the use of non-invasive methods for the identification and quantification of areas of hypoxia in the tumor are extremely important for treating various types of cancers, allowing the use of individualized treatment strategies. Gallium-68 is a radionuclide widely used for positron emission tomography due to the availability of the generator 68 Ge / 68 Ga. With the aim of developing a new potential radiopharmaceutical 68 Ga-labeled for imaging hypoxia, it has been synthesized a new derivative of 2-nitroimidazole. Methods: The new glycopeptide derivative of 2-nitroimidazole was obtained by coupling the derivative of acetic acid 2-nitroimidazole with a glycopeptide obtained by solid phase synthesis, was subsequently conjugated with the chelating agent DOTA-NHS for labeling with the radionuclide 68 Ga . preparation and 68 Ga-labeled glycopeptide optimization marking with respect to solvent, time and temperature was made; also the radiochemical purity was assessed by reversed phase HPLC. Comparison with 18 F-FAZA, radiopharmaceutical used worldwide is also presented. Results: The new glycopeptide conjugate DOTA was conducted successfully synthesized and analyzed by mass spectrometry. Labeling with 68 Ga reached a maximum radiochemical purity of 96.6 ± 0.4% when 15μg glycopeptide was dissolved in 0.2 mL of acetonitrile, chloride 68Ga (5mCi) was evaporated to dryness and reconstituted in 0.1 mL of sterile water at room temperature, followed by heating to 95 ° C for 15 min. In

  18. Formulation of DOTATATE Cold Kit for Preparation of Ga-68 Radiopharmaceutical

    International Nuclear Information System (INIS)

    Sriwiang, W.; Duangta, T.; Kaeopookum, P.; Wongsanit, S.

    2014-01-01

    Radiolabeled somatostatin analogs of peptide receptors targeting tumor cells have become a common practice in the diagnosis and treatment of certain types of cancer. The aim of this research was to develop the cold kit to be label with Ga-68 radionuclide for neuroendocrine tumor imaging. DOTATATE peptide for somatostatin receptor was formulated with NaOAc and ascorbic acid into lyophilized form. Radiochemical purity (RCP) of 68 Ga-DOTATATE labeled complex prepared from the cold kit was determined during storage period of 5 months and evaluated before clinical application to EANM guideline. The %RCP of the labeled peptide was more than 95% throughout period of storage with Ge-68 breakthrough less than 0.001%. The peptide content calculated from peak area of standard DOTATATE calibration curve using HPLC at uv 220 nm was found to be 15.3±4.62 μg. The specific activity of 68 Ga-DOTATATE, which depended on activities eluted from generator, was 34.7 - 52 MBq/nmol-peptide. The pH of the Ga-68 radiopharmaceutical kit after dilution with phosphate-buffered saline was 5.0 - 5.3. These results demonstrated that preparing of 68 Ga-DOTATATE radiopharmaceutical from lyophilized kit presented in this study was suitable and convenient method obtaining high radiochemical purity of short half-life Ga-68 radionuclide.

  19. 41 CFR 105-68.350 - What must I do if I learn of information required under § 105-68.335 after entering into a...

    Science.gov (United States)

    2010-07-01

    ... General Services Administration? 105-68.350 Section 105-68.350 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION Regional... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What must I do if I...

  20. Pea p68, a DEAD-box helicase, provides salinity stress tolerance in transgenic tobacco by reducing oxidative stress and improving photosynthesis machinery.

    Directory of Open Access Journals (Sweden)

    Narendra Tuteja

    Full Text Available The DEAD-box helicases are required mostly in all aspects of RNA and DNA metabolism and they play a significant role in various abiotic stresses, including salinity. The p68 is an important member of the DEAD-box proteins family and, in animal system, it is involved in RNA metabolism including pre-RNA processing and splicing. In plant system, it has not been well characterized. Here we report the cloning and characterization of p68 from pea (Pisum sativum and its novel function in salinity stress tolerance in plant.The pea p68 protein self-interacts and is localized in the cytosol as well as the surrounding of cell nucleus. The transcript of pea p68 is upregulated in response to high salinity stress in pea. Overexpression of p68 driven by constitutive cauliflower mosaic virus-35S promoter in tobacco transgenic plants confers enhanced tolerances to salinity stress by improving the growth, photosynthesis and antioxidant machinery. Under stress treatment, pea p68 overexpressing tobacco accumulated higher K+ and lower Na+ level than the wild-type plants. Reactive oxygen species (ROS accumulation was remarkably regulated by the overexpression of pea p68 under salinity stress conditions, as shown from TBARS content, electrolyte leakage, hydrogen peroxide accumulation and 8-OHdG content and antioxidant enzyme activities.To the best of our knowledge this is the first direct report, which provides the novel function of pea p68 helicase in salinity stress tolerance. The results suggest that p68 can also be exploited for engineering abiotic stress tolerance in crop plants of economic importance.

  1. Organ biodistribution of Germanium-68 in rat in the presence and absence of [68Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body radiation dosimetry

    Science.gov (United States)

    Velikyan, Irina; Antoni, Gunnar; Sörensen, Jens; Estrada, Sergio

    2013-01-01

    Positron Emission Tomography (PET) and in particular gallium-68 (68Ga) applications are growing exponentially worldwide contributing to the expansion of nuclear medicine and personalized management of patients. The significance of 68Ga utility is reflected in the implementation of European Pharmacopoeia monographs. However, there is one crucial point in the monographs that might limit the use of the generators and consequently expansion of 68Ga applications and that is the limit of 0.001% of Germanium-68 (68Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of 68Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and justification of the 68Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [68Ge]GeCl4 in the absence or presence of [68Ga]Ga-DOTA-TOC. The tissue radioactivity distribution data was extrapolated for the estimation of human organ equivalent doses and total effective dose using Organ Level Internal Dose Assessment Code software (OLINDA/EXM). 68Ge(IV) was evenly distributed among the rat organs and fast renal excretion prevailed. Human organ equivalent dose and total effective dose estimates indicated that the kidneys were the dose-limiting organs (185±54 μSv/MBq for female and 171±38 μSv/MBq for male) and the total effective dose was 15.5±0.1 and 10.7±1.2 μSv/MBq, respectively for female and male. The results of this dosimetry study conclude that the 68Ge(IV) limit currently recommended by monographs could be increased considerably (>100 times) without exposing the patient to harm given the small absorbed doses to normal organs and fast excretion. PMID:23526484

  2. 40 CFR 68.52 - Operating procedures.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.52 Operating procedures. (a) The... for safely conducting activities associated with each covered process consistent with the safety information for that process. Operating procedures or instructions provided by equipment manufacturers or...

  3. PET/CT comparing 68Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

    International Nuclear Information System (INIS)

    Janssen, Ingo; Chen, Clara C.; Millo, Corina M.; Herscovitch, Peter; Ling, Alexander; Taieb, David; Lin, Frank I.; Adams, Karen T.; Wolf, Katherine I.; Pacak, Karel; Fojo, Antonio T.; Buchmann, Inga; Kebebew, Electron

    2016-01-01

    Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). 68 Ga-DOTA(0)-Tyr(3)-octreotate ( 68 Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of 68 Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. This prospective study included 22 patients (15 men, 7 women; aged 50.0 ± 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent 68 Ga-DOTATATE, 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) PET/CT scan and only 11 patients underwent an additional 18 F-fluorodopamine ( 18 F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. 68 Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). 18 F-FDG PET/CT, 18 F-FDOPA PET/CT, 18 F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p < 0.01), 74.8 % (CI 69.0 - 79.9 %; p < 0.01), 77.7 % (CI 71.5 - 82.8 %; p < 0.01), and 81.6 % (CI 77.8 - 84.8 %; p < 0.01), respectively. The results of this study demonstrate the superiority of 68 Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality. (orig.)

  4. 40 CFR 68.50 - Hazard review.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.50 Hazard review. (a) The owner or operator shall conduct a review of the hazards associated with the regulated substances, process, and...

  5. Single vial kit formulation for preparation of PET radiopharmaceutical. 68Ga-DOTA-TOC

    International Nuclear Information System (INIS)

    Archana Mukherjee; Usha Pandey; Rubel Chakravarty; Ashutosh Dash; Haladhar Dev Sarma

    2014-01-01

    This paper describes the development of a lyophilized cold kit of DOTA-[Tyr 3 ]-Octreotide (DOTA-TOC) for instant compounding of 68 Ga-DOTA-TOC, suitable for diagnosis of neuroendocrine tumors. The work involved formulation of DOTA-TOC kits, optimization of radiolabeling, quality control of 68 Ga-DOTA-TOC and animal biodistribution studies. The prepared kits enable a reliable method for preparation of 68 Ga-DOTA-TOC of high radiochemical purity and excellent stability. Availability of such kits along with 68 Ge/ 68 Ga generators is expected to stimulate the widespread use of 68 Ga-DOTA-TOC in nuclear medicine practice in developing countries. (author)

  6. Preparation and biological studies of 68Ga-DOTA-alendronate

    Directory of Open Access Journals (Sweden)

    Ashraf Fakhari

    2016-07-01

    Full Text Available Objective(s: In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA conjugated alendronate (DOTA-ALN was synthesized and evaluated after labeling with gallium-68 (68Ga.Methods: DOTA-ALN was synthesized and characterized, followed by 68Ga-DOTA-ALN preparation, using DOTA-ALN and 68GaCl3 (pH: 4-5 at 92-95°C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation,biodistribution studies, and imaging were performed on the developed agent in normal rats.Results: The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320GBq/mmol after solid phase purification and was stabilized for up to 90 min with a logP value of -2.91. Maximum ligand binding (65% was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low (

  7. Preclinical evaluation of potential infection-imaging probe [68 Ga]Ga-DOTA-K-A9 in sterile and infectious inflammation.

    Science.gov (United States)

    Nielsen, Karin M; Jørgensen, Nis P; Kyneb, Majbritt H; Borghammer, Per; Meyer, Rikke L; Thomsen, Trine R; Bender, Dirk; Jensen, Svend B; Nielsen, Ole L; Alstrup, Aage K O

    2018-05-23

    The development of bacteria-specific infection radiotracers is of considerable interest to improve diagnostic accuracy and enabling therapy monitoring. The aim of this study was to determine if the previously reported radiolabelled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA) conjugated peptide, [ 68 Ga]Ga-DOTA-K-A9 could detect a staphylococcal infection in vivo, and distinguish it from aseptic inflammation. An optimised [ 68 Ga]Ga-DOTA-K-A9 synthesis omitting the use of acetone was developed, yielding 93% ± 0.9% radiochemical purity. The in vivo infection binding specificity of [ 68 Ga]Ga-DOTA-K-A9 was evaluated by micro positron emission tomography/magnetic resonance imaging (μPET/MRI) of 15 mice with either subcutaneous S. aureus infection or turpentine induced inflammation and compared with 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG). The scans showed that [ 68 Ga]Ga-DOTA-K-A9 accumulated in all the infected mice at injected doses ≥3.6 MBq. However, the tracer was not found to be selective towards infection, since the [ 68 Ga]Ga-DOTA-K-A9 also accumulated in mice with inflammation. In a concurrent in vitro binding evaluation performed with a 5-Carboxytetramethylrhodamine (TAMRA) fluorescence analogue of the peptide, TAMRA-K-A9, the microscopy results suggested that TAMRA-K-A9 bound to an intracellular epitope and therefore preferentially targeted dead bacteria. Thus, the [ 68 Ga]Ga-DOTA-K-A9 uptake observed in vivo is presumably a combination of local hyperaemia, vascular leakiness and/or binding to an epitope present in dead bacteria. This article is protected by copyright. All rights reserved.

  8. {sup 68}Ga-PSMA-HBED-CC PET imaging in breast carcinoma patients

    Energy Technology Data Exchange (ETDEWEB)

    Sathekge, Mike; Lengana, Thabo; Modiselle, Moshe; Vorster, Mariza; Zeevaart, JanRijn; Ebenhan, Thomas [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine, Pretoria (South Africa); Maes, Alex [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine, Pretoria (South Africa); AZ Groeninge, Department of Nuclear Medicine, Kortrijk (Belgium); Wiele, Christophe van de [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine, Pretoria (South Africa); University Ghent, Department of Radiology and Nuclear Medicine, Ghent (Belgium)

    2017-04-15

    To report on imaging findings using {sup 68}Ga-PSMA-HBED-CC PET in a series of 19 breast carcinoma patients. {sup 68}Ga-PSMA-HBED-CC PET imaging results obtained were compared to routinely performed staging examinations and analyzed as to lesion location and progesterone receptor status. Out of 81 tumor lesions identified, 84% were identified on {sup 68}Ga-PSMA-HBED-CC PET. {sup 68}Ga-PSMA-HBED-CC SUVmean values of distant metastases proved significantly higher (mean, 6.86, SD, 5.68) when compared to those of primary or local recurrences (mean, 2.45, SD, 2.55, p = 0.04) or involved lymph nodes (mean, 3.18, SD, 1.79, p = 0.011). SUVmean values of progesterone receptor-positive lesions proved not significantly different from progesterone receptor-negative lesions. SUV values derived from FDG PET/CT, available in seven patients, and {sup 68}Ga-PSMA-HBED-CC PET/CT imaging proved weakly correlated (r = 0.407, p = 0.015). {sup 68}Ga-PSMA-HBED-CC PET/CT imaging in breast carcinoma confirms the reported considerable variation of PSMA expression on human solid tumors using immunohistochemistry. (orig.)

  9. Clinical cases with Gallium Dotatate 68

    International Nuclear Information System (INIS)

    Castro, R.

    2012-01-01

    This presentation is about the benefit's of PET - CT with 68 Ga Dotatate for the diagnosis and treatment. This technique is used for the staging, re staging, detection of primitive unknown tumors, selection of candidates for metabolic radium therapy and evaluation of treatment response

  10. 40 CFR 68.48 - Safety information.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.48 Safety information. (a) The... regulated substances, processes, and equipment: (1) Material Safety Data Sheets that meet the requirements...) Equipment specifications; and (5) Codes and standards used to design, build, and operate the process. (b...

  11. 40 CFR 68.69 - Operating procedures.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.69 Operating procedures. (a) The... presented by, the chemicals used in the process; (ii) Precautions necessary to prevent exposure, including... instructions for safely conducting activities involved in each covered process consistent with the process...

  12. May ’68: Jupiter days

    Directory of Open Access Journals (Sweden)

    Higinio Marín Pedreño

    2018-04-01

    Full Text Available The anthropological understanding of the events that took place during May’68, in the context of the historical changes of the second half of the twentieth century, requires, on the one hand, an archaeological study of the emergence of a new historical and metaphysical subject, youth, and, on the other hand, a study of the appearance of a new morphology of the conscience, joviality.

  13. Promising semi-dwarf mutant in wheat variety K68

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, D [Banaras Hindu Univ. (India). Dept. of Genetics and Plant Breeding

    1977-04-01

    A semi-dwarf mutant (HUW-SDf 1) was induced from common wheat Var. K68 through the exposure of /sup 60/Co ..gamma..-rays at 15 kR. This mutant along with other induced mutants and control was assessed for yield components, yield and grain quality (M/sub 4/ generation); internode length reduction pattern and the yielding ability at three levels of nitrogen (M/sub 5/ generation). The mutant was significantly shorter in height and almost equal in tillers per plant and grains per spike to K68. However, it showed marked reduction in spike length and spikelets per spike. On the other hand, it possessed significantly higher (50.04 g) 1000-grain weight against control (41.15 g). The mutant gave 56.0% higher yield than the control. Grain quality studies indicated that the mutant possessed significantly higher (14.15%) total protein than K68. It was equally as good as K68 in lysine content. Pelshenke value (62.5 min) of the mutant indicated medium hard nature of gluten as compared to hard nature (198.0) of the control. The mutant showed 24.0% reduction in total culm length compared to K68. Reduction occurred due to maximum and almost equal reduction in 5th and 4th internodes (ca 34.0%) followed by 3rd, 2nd and 1st. The mutant showed similar yield and yield response to increasing nitrogen levels (80 to 160 kg per ha.) as for current commercial semi-dwarf varieties.

  14. Variational approach to 68 Se

    International Nuclear Information System (INIS)

    Petrovici, A.; Schmid, K.W.; Faessler, A.; Baktash, C.; Shashi, P.

    1999-01-01

    For a unified description of the structure of medium mass proton-rich nuclei at low as well as high angular momenta we used the complex version of the Excited Vampir approach. We employed chains of variational calculations based on symmetry-projected essentially complex Hartree-Fock-Bogoliubov (HFB) vacua which include neutron-proton pairing and unnatural-parity correlations. Since the Vampir approaches allow the use of rather large model spaces and of general two-body interactions, large-scale nuclear structure studies going far beyond the abilities of the conventional shell-model configuration-mixing approach are possible. Furthermore, since these approaches provide detailed spectroscopic information for the lowest few states for each spin and parity, they also have considerable advantages with respect to the shell-model Monte Carlo method in which only expectation values of operators in the thermodynamic ensembles or the ground state can be calculated. Our previous investigations on microscopic aspects of shape coexistence in N∼Z nuclei in the A∼70 mass region indicated the presence of a strong competition between particular configurations based on large and small oblate and prolate quadrupole deformations. Furthermore, since in N = Z nuclei neutrons and protons fill the same single particle orbits, the isovector neutron-proton and the like-nucleon pairing correlations were found to be strongly competitive in even-even systems. In addition, the neutron and proton alignments with increasing angular momentum occur simultaneously in these nuclei. On the other hand the theoretical results suggest that certain properties of these nuclei are extremely sensitive to small variations of particular parts of the effective Hamiltonian. Thus, our results indicate that the oblate-prolate coexistence and mixing at low spins depend on the strengths of the neutron-proton T = 0 matrix elements involving nucleons occupying f 5/2 (f 7/2 ) and g 9/2 single particle orbits

  15. Continued seasonal circulation of enterovirus D68 in the Netherlands, 2011-2014.

    NARCIS (Netherlands)

    Meijer, A.; Benschop, K.S.; Donker, G.A.; Avoort, H.G. van der

    2014-01-01

    Enterovirus D68 (EV-D68) continued to circulate in a seasonal pattern in the Netherlands, after the outbreak in 2010. Outpatient EV-D68 cases, mainly in the under 20 and 50–59 years age groups, presented with relatively mild respiratory disease. Hospital-based enterovirus surveillance identified

  16. Genetic ablation of CD68 results in mice with increased bone and dysfunctional osteoclasts.

    Directory of Open Access Journals (Sweden)

    Jason W Ashley

    Full Text Available CD68 is a member of the lysosome associated membrane protein (LAMP family that is restricted in its expression to cells of the monocyte/macrophage lineage. This lineage restriction includes osteoclasts, and, while previous studies of CD68 in macrophages and dendritic cells have proposed roles in lipid metabolism, phagocytosis, and antigen presentation, the expression and function of CD68 in osteoclasts have not been explored. In this study, we investigated the expression and localization of CD68 in macrophages and osteoclasts in response to the monocyte/macrophage-colony stimulating factor (M-CSF and the receptor activator of NF-κB ligand (RANKL. We found that M-CSF stimulates CD68 expression and RANKL alters the apparent molecular weight of CD68 as measured by Western immunoblotting. In addition, we explored the significance of CD68 expression in osteoclasts by generating mice that lack expression of CD68. These mice have increased trabecular bone, and in vitro assessment of CD68(-/- osteoclasts revealed that, in the absence of CD68, osteoclasts demonstrate an accumulation of intracellular vesicle-like structures, and do not efficiently resorb bone. These findings demonstrate a role for CD68 in the function of osteoclasts, and future studies will determine the mechanistic nature of the defects seen in CD68(-/- osteoclasts.

  17. 28 CFR 68.18 - Discovery-general provisions.

    Science.gov (United States)

    2010-07-01

    ... UNLAWFUL EMPLOYMENT OF ALIENS, UNFAIR IMMIGRATION-RELATED EMPLOYMENT PRACTICES, AND DOCUMENT FRAUD § 68.18..., including the existence, description, nature, custody, condition, and location of any books, documents, or...

  18. Evaluation of (68)Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1.

    Science.gov (United States)

    Morgat, Clément; Vélayoudom-Céphise, Fritz-Line; Schwartz, Paul; Guyot, Martine; Gaye, Delphine; Vimont, Delphine; Schulz, Jürgen; Mazère, Joachim; Nunes, Marie-Laure; Smith, Denis; Hindié, Elif; Fernandez, Philippe; Tabarin, Antoine

    2016-07-01

    Somatostatin receptor scintigraphy with (111)In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with (68)Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1. To compare the performances of (68)Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1. Single-institution prospective comparative study Nineteen consecutive MEN1 patients (aged 47 ± 13 years) underwent (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, (18)F-2-fluoro-deoxy-D-glucose ((18)F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis. The sensitivity of (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p TOC PET/CT. (68)Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 ± 7.6 and 15.2 ± 5.9 mm, respectively, p TOC PET/CT included small dpNETs (TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS. Owing to higher diagnostic performance, (68)Ga-DOTA-TOC PET/CT (or alternative (68)Ga-labeled somatostatin analogues) should replace (111)In-pentetreotide in the investigation of MEN1 patients.

  19. 40 CFR 68.58 - Compliance audits.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 2 Prevention Program § 68.58 Compliance audits. (a) The owner or... in the process. (c) The owner or operator shall develop a report of the audit findings. (d) The owner...

  20. 40 CFR 68.83 - Employee participation.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.83 Employee participation. (a... their representatives on the conduct and development of process hazards analyses and on the development of the other elements of process safety management in this rule. (c) The owner or operator shall...

  1. 40 CFR 68.79 - Compliance audits.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.79 Compliance audits. (a) The owner or... in the process. (c) A report of the findings of the audit shall be developed. (d) The owner or...

  2. 41 CFR 105-68.600 - How do suspension and debarment actions start?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false How do suspension and debarment actions start? 105-68.600 Section 105-68.600 Public Contracts and Property Management Federal... Relating to Suspension and Debarment Actions § 105-68.600 How do suspension and debarment actions start...

  3. Radial Color Gradient in a Globular Cluster 1. M68

    Directory of Open Access Journals (Sweden)

    Sukyoung Yi

    1990-12-01

    Full Text Available Stars in M68 from the observed color-magnitude diagrams with CCD were integrated to find any radial gradient. The result shows that M68 has a slightly bluer core. The main cause of these calculated radial color variations seems to come from the random distribution of giants.

  4. DNA structure modulates the oligomerization properties of the AAV initiator protein Rep68.

    Directory of Open Access Journals (Sweden)

    Jorge Mansilla-Soto

    2009-07-01

    Full Text Available Rep68 is a multifunctional protein of the adeno-associated virus (AAV, a parvovirus that is mostly known for its promise as a gene therapy vector. In addition to its role as initiator in viral DNA replication, Rep68 is essential for site-specific integration of the AAV genome into human chromosome 19. Rep68 is a member of the superfamily 3 (SF3 helicases, along with the well-studied initiator proteins simian virus 40 large T antigen (SV40-LTag and bovine papillomavirus (BPV E1. Structurally, SF3 helicases share two domains, a DNA origin interaction domain (OID and an AAA(+ motor domain. The AAA(+ motor domain is also a structural feature of cellular initiators and it functions as a platform for initiator oligomerization. Here, we studied Rep68 oligomerization in vitro in the presence of different DNA substrates using a variety of biophysical techniques and cryo-EM. We found that a dsDNA region of the AAV origin promotes the formation of a complex containing five Rep68 subunits. Interestingly, non-specific ssDNA promotes the formation of a double-ring Rep68, a known structure formed by the LTag and E1 initiator proteins. The Rep68 ring symmetry is 8-fold, thus differing from the hexameric rings formed by the other SF3 helicases. However, similiar to LTag and E1, Rep68 rings are oriented head-to-head, suggesting that DNA unwinding by the complex proceeds bidirectionally. This novel Rep68 quaternary structure requires both the DNA binding and AAA(+ domains, indicating cooperativity between these regions during oligomerization in vitro. Our study clearly demonstrates that Rep68 can oligomerize through two distinct oligomerization pathways, which depend on both the DNA structure and cooperativity of Rep68 domains. These findings provide insight into the dynamics and oligomeric adaptability of Rep68 and serve as a step towards understanding the role of this multifunctional protein during AAV DNA replication and site-specific integration.

  5. 28 CFR 68.11 - Motions and requests.

    Science.gov (United States)

    2010-07-01

    ... ALIENS, UNFAIR IMMIGRATION-RELATED EMPLOYMENT PRACTICES, AND DOCUMENT FRAUD § 68.11 Motions and requests... be given reasonable opportunity to respond or to object to the motion or request. (b) Responses to...

  6. Retinoic acid reduces human neuroblastoma cell migration and invasiveness: effects on DCX, LIS1, neurofilaments-68 and vimentin expression

    International Nuclear Information System (INIS)

    Messi, Elio; Florian, Maria C; Caccia, Claudio; Zanisi, Mariarosa; Maggi, Roberto

    2008-01-01

    Neuroblastoma is a severe pediatric tumor, histologically characterised by a variety of cellular phenotypes. One of the pharmacological approaches to neuroblastoma is the treatment with retinoic acid. The mechanism of action of retinoic acid is still unclear, and the development of resistance to this differentiating agent is a great therapy problem. Doublecortin, a microtubule-associated protein involved in neuronal migration, has recently been proposed as a molecular marker for the detection of minimal residual disease in human neuroblastoma. Nevertheless, no information is available on the expression of doublecortin in the different cell-types composing human neuroblastoma, its correlation with neuroblastoma cell motility and invasiveness, and the possible modulations exerted by retinoic acid treatment. We analysed by immunofluorescence and by Western blot analysis the presence of doublecortin, lissencephaly-1 (another protein involved in neuronal migration) and of two intermediate filaments proteins, vimentin and neurofilament-68, in SK-N-SH human neuroblastoma cell line both in control conditions and under retinoic acid treatment. Migration and cell invasiveness studies were performed by wound scratch test and a modified microchemotaxis assay, respectively. Doublecortin is expressed in two cell subtypes considered to be the more aggressive and that show high migration capability and invasiveness. Vimentin expression is excluded by these cells, while lissencephaly-1 and neurofilaments-68 are immunodetected in all the cell subtypes of the SK-N-SH cell line. Treatment with retinoic acid reduces cell migration and invasiveness, down regulates doublecortin and lissencephaly-1 expression and up regulates neurofilament-68 expression. However, some cells that escape from retinoic acid action maintain migration capability and invasiveness and express doublecortin. a) Doublecortin is expressed in human neuroblastoma cells that show high motility and invasiveness; b

  7. Motor coordination defects in mice deficient for the Sam68 RNA-binding protein.

    Science.gov (United States)

    Lukong, Kiven E; Richard, Stéphane

    2008-06-03

    The role of RNA-binding proteins in the central nervous system and more specifically their role in motor coordination and learning are poorly understood. We previously reported that ablation of RNA-binding protein Sam68 in mice results in male sterility and delayed mammary gland development and protection against osteoporosis in females. Sam68 however is highly expressed in most regions of the brain especially the cerebellum and thus we investigated the cerebellar-related manifestations in Sam68-null mice. We analyzed the mice for motor function, sensory function, and learning and memory abilities. Herein, we report that Sam68-null mice have motor coordination defects as assessed by beam walking and rotorod performance. Forty-week-old Sam68-null mice (n=12) were compared to their wild-type littermates (n=12). The Sam68-null mice exhibited more hindpaw faults in beam walking tests and fell from the rotating drum at lower speeds and prematurely compared to the wild-type controls. The Sam68-null mice were, however, normal for forelimb strength, tail-hang reflex, balance test, grid walking, the Morris water task, recognition memory, visual discrimination, auditory stimulation and conditional taste aversion. Our findings support a role for Sam68 in the central nervous system in the regulation of motor coordination.

  8. Calibration of Ga-68 activity for PET applications in Cuba

    International Nuclear Information System (INIS)

    García Rodríguez, Lourdes; Oropesa Verdecia, Pilar; Serra Águila, Rolando A.; Moreno León, Yecenia; Jénez Magaña, Yoel; Pérez LoretdeMola, Nayla; Bell Hechavarría, Ailec; Mas Ruiz, Javier; Cassette, Philippe

    2016-01-01

    A Ga-68 solution was used to calibrate the activity concentration using the double-triple coincidence ratio (TDCR) method of liquid scintillation for the first time in the country. The expanded uncertainty (k = 2) of the concentration of Ga-68 activity in the calibrated solution was equal to 2%. For measurements, the commercial liquid scintillation counter HIDEXTM was used. Samples were prepared by adding between 40 and 50 mg of the radioactive solution to 15 mL of ULTIMAGOLD ™ scintillating cocktail. For the estimation of Ga-68 counting efficiencies in the samples used for the calibration, a FORTRAN program developed by the National Institute of Metrology of France for the magnitudes of ionizing radiation, LNHB, was used. The validation of the method was carried out by the calibration of a standard solution of Na-22, also positronic emitter with similar disintegration scheme to Ga-68. The difference between the concentration of Na-22 activity measured using the TDCR method and the certified reference value traceable to the National Institute of Metrology of the United States (NIST) was 0.15%. With the solution of Ga-68 standardized by the TDCR method the calibration of the secondary standard activity meter, model CAPINTEC CRCTM 15R, was carried out for a geometry of 2R flask with 1mL of radioactive solution. Afterwards, this standard activity meter was calibrated for the measurement of Ga-68 in the geometries of interest in nuclear medicine: Flask 15R with 6 mL of radioactive solution, 2.5 mL syringe with 2 mL of radioactive solution and 5 mL syringe with 2 mL of radioactive solution. The results presented in this paper constitute the necessary metrological support for the introduction of new PET and PET / CT technologies into medical practice in Cuba.

  9. GPR68 Senses Flow and Is Essential for Vascular Physiology.

    Science.gov (United States)

    Xu, Jie; Mathur, Jayanti; Vessières, Emilie; Hammack, Scott; Nonomura, Keiko; Favre, Julie; Grimaud, Linda; Petrus, Matt; Francisco, Allain; Li, Jingyuan; Lee, Van; Xiang, Fu-Li; Mainquist, James K; Cahalan, Stuart M; Orth, Anthony P; Walker, John R; Ma, Shang; Lukacs, Viktor; Bordone, Laura; Bandell, Michael; Laffitte, Bryan; Xu, Yan; Chien, Shu; Henrion, Daniel; Patapoutian, Ardem

    2018-04-19

    Mechanotransduction plays a crucial role in vascular biology. One example of this is the local regulation of vascular resistance via flow-mediated dilation (FMD). Impairment of this process is a hallmark of endothelial dysfunction and a precursor to a wide array of vascular diseases, such as hypertension and atherosclerosis. Yet the molecules responsible for sensing flow (shear stress) within endothelial cells remain largely unknown. We designed a 384-well screening system that applies shear stress on cultured cells. We identified a mechanosensitive cell line that exhibits shear stress-activated calcium transients, screened a focused RNAi library, and identified GPR68 as necessary and sufficient for shear stress responses. GPR68 is expressed in endothelial cells of small-diameter (resistance) arteries. Importantly, Gpr68-deficient mice display markedly impaired acute FMD and chronic flow-mediated outward remodeling in mesenteric arterioles. Therefore, GPR68 is an essential flow sensor in arteriolar endothelium and is a critical signaling component in cardiovascular pathophysiology. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Mucosal immunization with recombinant adenoviral vectors expressing murine gammaherpesvirus-68 genes M2 and M3 can reduce latent viral load

    DEFF Research Database (Denmark)

    Hoegh-Petersen, Mette; Thomsen, Allan R; Christensen, Jan P

    2009-01-01

    -68 (MHV-68) is a member of the Gammaherpesvirinae subfamily and represents a useful murine model for this category of infections, in which new vaccination strategies may initially be evaluated. Two attenuated variants of MHV-68 have successfully been used as vaccines, but the oncogenic potential...... of the gammaherpesvirinae speaks against using a similar approach in humans. DNA immunization with plasmids encoding the MHV-68 genes M2 or M3 caused a reduction in either acute or early latent viral load, respectively, but neither immunization had an effect at times later than 14 days post-infection. Adenovirus......-based vaccines are substantially more immunogenic than DNA vaccines and can be applied to induce mucosal immunity. Here we show that a significant reduction of the late viral load in the spleens, at 60 days post-infection, was achieved when immunizing mice both intranasally and subcutaneously with adenoviral...

  11. Kinetic Modelling of Infection Tracers [18F]FDG, [68Ga]Ga-Citrate, [11C]Methionine, and [11C]Donepezil in a Porcine Osteomyelitis Model

    DEFF Research Database (Denmark)

    Jødal, Lars; Jensen, Svend Borup; Nielsen, Ole Lerberg

    2017-01-01

    Introduction. Positron emission tomography (PET) is increasingly applied for infection imaging using [18F]FDG as tracer, but uptake is unspecific. The present study compares the kinetics of [18F]FDG and three other PET tracers with relevance for infection imaging. Methods. A juvenile porcine...... osteomyelitis model was used. Eleven pigs underwent PET/CT with 60-minute dynamic PET imaging of [18F]FDG, [68Ga]Ga-citrate, [11C]methionine, and/or [11C]donepezil, along with blood sampling. For infectious lesions, kinetic modelling with one- and two-tissue-compartment models was conducted for each tracer...... for the analysis. Conclusions. The kinetics of the four studied tracers in infection was characterized. For clinical applications, [18F]FDG remains the first-choice PET tracer. [11C]methionine may have a potential for detecting soft tissue infections. [68Ga]Ga-citrate and [11C]donepezil were not found useful...

  12. Preparation and Biological Study of (68)Ga-DOTA-alendronate.

    Science.gov (United States)

    Fakhari, Ashraf; Jalilian, Amir R; Johari-Daha, Fariba; Shafiee-Ardestani, Mehdi; Khalaj, Ali

    2016-01-01

    In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA-conjugated alendronate (DOTA-ALN) was synthesized and evaluated after labeling with gallium-68 ((68)Ga). DOTA-ALN was synthesized and characterized, followed by (68)Ga-DOTA-ALN preparation, using DOTA-ALN and (68)GaCl3 (pH: 4-5) at 92-95° C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation, biodistribution studies, and imaging were performed on the developed agent in normal rats. The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320 GBq/mmol) after solid phase purification and was stabilized for up to 90 min with a log P value of -2.91. Maximum ligand binding (65%) was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low (<1%) at 30 min after the injection. The data were also confirmed by sequential imaging at 30-90 min following the intravenous injection. The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors.

  13. Synthesis and biodistribution of lipophilic and monocationic gallium radiopharmaceuticals derived from N,N'-bis(3-aminopropyl)-N,N'-dimethylethylenediamine: potential agents for PET myocardial imaging with 68Ga

    International Nuclear Information System (INIS)

    Hsiao, Y.-M.; Mathias, Carla J.; Wey, S.-P.; Fanwick, Phillip E.; Green, Mark A.

    2009-01-01

    Introduction: In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68 Ga radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiological processes. Methods: The lipophilic and monocationic 67 Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-meth,oxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N'-bis(3-aminopropyl)-N,N'-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal) 2 BAPDMEN] + PF 6 - salt was determined by X-ray crystallography, and the biodistribution of each of the 67 Ga-labeled gallium chelates was determined in rats following intravenous administration and compared with the biodistribution of [ 86 Rb]rubidium chloride. Results: The [Ga(4-MeOsal) 2 BAPDMEN] + PF 6 - complex exhibited the expected pseudo-octahedral N 4 O 2 2- coordination sphere about the Ga 3+ center with a trans disposition of the phenolate oxygen atoms. All five 67 Ga radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [ 67/68 Ga][Ga(3-MeOsal) 2 BAPDMEN] 1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart 1 min and 2 h postinjection and very high heart/nontarget ratios (heart/blood ratios of 7.6±1.0 and 54±10 at 1 and 120 min, respectively; heart/liver ratios of 1.8±0.4 and 39±3 at 1 and 120 min, respectively). Conclusions: Most of these new agents, particularly [ 67/68 Ga][Ga(3-MeOsal) 2 BAPDMEN] 1+ , would appear superior to previously reported bis(salicylaldimine) ligands of N,N'-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68 Ga

  14. Anisotropic p-f mixing mechanism explaining anomalous magnetic properties in Ce monopnictides

    International Nuclear Information System (INIS)

    Takahashi, H.; Kasuya, T.

    1985-01-01

    The indirect f-f-interaction derived from fourth-order perturbation theory with respect to the p-f mixing is calculated using the valence bands obtained by the APW band calculations. The type of the f-f-interactions is described as the coupling through the symmetry exchange under the cubic crystal field, which cannot be written as a simple bilinear type of 4f spin operator. It is necessary to consider the short-range-ordering effect as well as the non-linear effect of the p-f mixing to explain the fact that a type-I antiferromagnetic ordering is established by the second-order transition in CeBi. (author)

  15. 22 CFR 40.68 - Aliens subject to INA 222(g).

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Aliens subject to INA 222(g). 40.68 Section 40... § 40.68 Aliens subject to INA 222(g). An alien who, under the provisions of INA 222(g), has voided a... new nonimmigrant visa unless the alien complies with the requirements in 22 CFR 41.101 (b) or (c...

  16. Full genome analysis of enterovirus D-68 strains circulating in Alberta, Canada.

    Science.gov (United States)

    Pabbaraju, Kanti; Wong, Sallene; Drews, Steven J; Tipples, Graham; Tellier, Raymond

    2016-07-01

    A widespread outbreak of enterovirus (EV)-D68 that started in the summer of 2014 has been reported in the USA and Canada. During the course of this outbreak, EV-D68 was identified as a possible cause of acute, unexplained severe respiratory illness and a temporal association was observed between acute flaccid paralysis with anterior myelitis and EV-D68 detection in the upper respiratory tract. In this study, four nasopharyngeal samples collected from patients in Alberta, Canada with a laboratory diagnosis of EV-D68 were used to determine the near full-length genome sequence directly from the specimens. Phylogenetic analysis was performed to study the genotypes and pathogenesis of the circulating strains. Our results support the contention that mutations in the VP1 gene and other regions of the genome causing altered antigenicity, as well as lack of immunity in the younger population, may be responsible for the increased severe respiratory disease outbreaks of EV-D68 worldwide. © 2015 Wiley Periodicals, Inc.

  17. Radiolabeling of NOTA and DOTA with Positron Emitting {sup 68}Ga and Investigation of In Vitro Properties

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min; Kim, Young Ju; Lee, Yun Sang; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2009-08-15

    We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide {sup 68}Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. Various concentrations of NOTA{center_dot}3HCl and DOTA{center_dot}4HCl were labeled with 1 mL {sup 68}GaCl{sub 3} (0.18{approx}5.75 mCi in 0.1 M HCl) in various pH. NOTA{center_dot}3HCl (0.373 mM) was labeled with {sup 68}GaCl{sub 3} (0.183{approx}0.232 mCi/0.1 M HCl 1.0 mL) in the presence of CuCl{sub 2}, FeCl{sub 2}, InCl{sub 3}, FeCl{sub 3}, GaCl{sub 3}, MgCl{sub 2} or CaCl{sub 2} (0{approx}6.07 mM) at room temperature. The labeling efficiencies of {sup 68}Ga-NOTA and {sup 68}Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. {sup 68}Ga-NOTA and {sup 68}Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37 .deg. C. NOTA was labeled at room temperature while DOTA required heating for labeling. {sup 68}Ga-NOTA labeling efficiency was reduced by CuCl{sub 2}, FeCl{sub 2}, InCl{sub 2}, FeCl{sub 3} or GaCl{sub 3}, however, was not influenced by MgCl{sub 2} or CaCl{sub 2}. The protein binding was low (2.04{approx}3.32%). Log P value of {sup 68}Ga-NOTA was -3.07 indicating high hydrophilicity. We found that NOTA is a better bifunctional chelating agent than DOTA for {sup 68}Ga labeling. Although, {sup 68}Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.

  18. Measurement of the half-life of 68Ga

    International Nuclear Information System (INIS)

    García-Toraño, Eduardo; Peyrés Medina, Virginia; Romero, Eduardo; Roteta, Miguel

    2014-01-01

    The half-life of the positron-emitter 68 Ga has been measured by following the decay rate with two systems based on ionization chamber and Ge detectors. The decay rate was measured for periods of time up to 10 half-lives. The combination of the 6 results obtained with both systems gives a value of T 1/2 =67.845(18) min, in good agreement with recommended data and with an uncertainty lower than any other previously reported value. - Highlights: • The half-life of the positron-emitter radionuclide 68 Ga was measured. • Two measurement setups (ionization chamber and Ge detector) were used. • Results agree with evaluated data but exhibit lower uncertainty

  19. 37 CFR 10.68 - Avoiding influence by others than the client.

    Science.gov (United States)

    2010-07-01

    ... than the client. 10.68 Section 10.68 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND... the client. (a) Except with the consent of the practitioner's client after full disclosure, a practitioner shall not: (1) Accept compensation from one other than the practitioner's client for the...

  20. Production, radiochemical processing and quality evaluation of 68Ge. Chapter 2

    International Nuclear Information System (INIS)

    Roesch, F.; Filosofov, D.V.

    2010-01-01

    In this chapter, the optimum chemical forms of the target material for the most relevant 68 Ge production routes are discussed. The principal methods for separation of 68 Ge (ion exchange, extraction, volatilization, precipitation, etc.) allowing high chemical separation yields of the parent radionuclide are also discussed

  1. A zebrafish screen for craniofacial mutants identifies wdr68 as a highly conserved gene required for endothelin-1 expression

    Directory of Open Access Journals (Sweden)

    Amsterdam Adam

    2006-06-01

    Full Text Available Abstract Background Craniofacial birth defects result from defects in cranial neural crest (NC patterning and morphogenesis. The vertebrate craniofacial skeleton is derived from cranial NC cells and the patterning of these cells occurs within the pharyngeal arches. Substantial efforts have led to the identification of several genes required for craniofacial skeletal development such as the endothelin-1 (edn1 signaling pathway that is required for lower jaw formation. However, many essential genes required for craniofacial development remain to be identified. Results Through screening a collection of insertional zebrafish mutants containing approximately 25% of the genes essential for embryonic development, we present the identification of 15 essential genes that are required for craniofacial development. We identified 3 genes required for hyomandibular development. We also identified zebrafish models for Campomelic Dysplasia and Ehlers-Danlos syndrome. To further demonstrate the utility of this method, we include a characterization of the wdr68 gene. We show that wdr68 acts upstream of the edn1 pathway and is also required for formation of the upper jaw equivalent, the palatoquadrate. We also present evidence that the level of wdr68 activity required for edn1 pathway function differs between the 1st and 2nd arches. Wdr68 interacts with two minibrain-related kinases, Dyrk1a and Dyrk1b, required for embryonic growth and myotube differentiation, respectively. We show that a GFP-Wdr68 fusion protein localizes to the nucleus with Dyrk1a in contrast to an engineered loss of function mutation Wdr68-T284F that no longer accumulated in the cell nucleus and failed to rescue wdr68 mutant animals. Wdr68 homologs appear to exist in all eukaryotic genomes. Notably, we found that the Drosophila wdr68 homolog CG14614 could substitute for the vertebrate wdr68 gene even though insects lack the NC cell lineage. Conclusion This work represents a systematic

  2. The human chorionic gonadotropin-beta arginine68 to glutamic acid substitution fixes the conformation of the C-terminal peptide

    DEFF Research Database (Denmark)

    Charrel-Dennis, Marie; Terrazzini, Nadia; McBride, Jeffrey D

    2005-01-01

    Wild-type human chorionic gonadotropin (hCG) has been used as a contraceptive vaccine. However, extensive sequence homology with LH elicits production of cross-reactive antibodies. Substitution of arginine(68) of the beta-subunit (hCG(beta)) with glutamic acid (R68E) profoundly reduces the cross...

  3. Potential impact of 68Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas

    International Nuclear Information System (INIS)

    Nyuyki, Fonyuy; Plotkin, Michail; Michel, Roger; Steffen, Ingo; Fahdt, Daniel; Brenner, Winfried; Graf, Reinhold; Denecke, Timm; Geworski, Lilli; Wurm, Reinhard

    2010-01-01

    Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with 68 Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of 68 Ga-DOTATOC-PET/CT on the definition of the ''gross tumour volume'' (GTV) in meningiomas, in order to assess the potential value of this method. Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and 68 Ga-DOTATOC-PET/CT examinations. History: operated n = 24, radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT and MRI data were co-registered using a BrainLAB workstation. For comparison, the GTV was defined first under consideration of CT and MRI data, then using PET data. 3/42 patients were excluded from the analysis (two with negative PET results, one with an extensive tumour, not precisely delineable by MRI or PET/CT). The average GTV CT/MRI was 22(±19)cm 3 ; GTV PET was 23(±20)cm 3 . Additional GTV, obtained as a result of PET was 9(±10)cm 3 and was observed in patients with osseous infiltration. In some pre-treated patients there were intratumoural areas (as identified in CT/MRI) without SR-expression (7(±11)cm 3 ). Common GTV as obtained by both CT/MRI and PET was 15(±14)cm 3 . The mean bi-directional difference between the GTV CT/MRI and GTV PET accounted to 16(±15)cm 3 (93%, p 68 Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration. 68 Ga-DOTATOC-PET also allows detection of additional lesions in patients with multiple meningiomas. (orig.)

  4. 40 CFR 68.36 - Review and update.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.36 Review and update. (a) The owner or operator shall... processes, quantities stored or handled, or any other aspect of the stationary source might reasonably be...

  5. Development of methods for the purification of 67Ga and 68Ga for biomolecules labeling

    International Nuclear Information System (INIS)

    Costa, Renata Ferreira

    2012-01-01

    For more than fifty years, the long-lived 68 Ge/ 68 Ga generators have been in development, obtaining 68 Ga without the need of having in house cyclotron, which is a considerable convenience for PET centers that have no nearby cyclotrons. 68 Ga decays 89% by positron emission and low photon emission (1077 keV) and the physical half life of 67.7 minutes is compatible with the pharmacokinetics of low biomolecular weight substances like peptides and antibody fragments. Moreover, its established metallic chemistry allows it to be stably bound to the carrier peptide sequence via a suitable bifunctional chelator, such as DOTA. All these reasons together with the technology of PET/CT allowed advances in molecular imaging, in particular in the diagnosis of neuroendocrine diseases. However, the eluate from the commercial 68 Ge/ 68 Ga generators still contains high levels of long lived 68 Ge, besides other metallic impurities, which competes with 68 Ga with a consequent reduction of the labeling yield of biomolecules, such as Fe 3+ and Zn 2+ . Thus, the lower the amount of impurities in the eluate, the competition between the radiolabeled and unlabeled peptide by the receptor will be smaller and the quality of imaging will be better, a subsequent purification step is needed after the generator elution. The aim of this work is to evaluate different purifications methods of 68 Ga to label biomolecules, with emphasis on the study of the chemical impurities contained in the eluate and to develop a new purification method. Several purification methods were studied. Many cationic resin were tested simulating the commercial process. 68 Ga is adsorbed in cationic resin, which is not commercial available and eluted in acid/acetone solution. The use of minor particles of cationic resin AG50W-X4 (200-400 mesh) showed the best results. An innovate method was the extraction chromatography, which is based on the absorption of diisopropyl ether in XAD 16 and 68 Ga recovery in deionized

  6. Extended study on oxidation behaviors of UN0.68 and UN1.66 by XPS

    Science.gov (United States)

    Luo, Lizhu; Hu, Yin; Pan, Qifa; Long, Zhong; Lu, Lei; Liu, Kezhao; Wang, Xiaolin

    2018-04-01

    The surface oxidation behaviors of UN0.68 and UN1.66 thin films are investigated by X-ray photoelectron spectroscopy (XPS), and the traditional U4f/N1s, O1s, valence band spectra as well as the unconventional U4d and U5d spectra are collected for the understanding of their oxidation behavior in-depth. Similar asymmetrical peak shape of the U4f spectra to uranium is observed for both uranium nitrides, despite of a slight shift to higher energy side for UN1.66 clean surface. However, significant difference among the corresponding spectra of UN0.68 and UN1.66 during oxidation reveals the distinctive properties of each own. The coexistence of UO2-x, UO2 and UO2-x.Ny on UN0.68 surface results in the peculiar features of U4f spectra as well as the others within the XPS energy scale, where peaks of the oxidized species firstly shift to higher energy side compared to the clean surface, and then return closely towards those of stoichiometric UO2. For UN1.66, the generation of U-N-O ternary compounds on the surface is identified with the symmetrical U4f peaks at 379.9eV and 390.8 eV, which locate intermediate between UO2 and UN1.66, and gradually expanding to higher energy side during the progressive oxidation. Furthermore, the formation of N-O species on UN1.66 surface is also detected as an oxidation product. The metallic character of UN1.66 is identified by the intense signal at Fermi level, which is greatly suppressed by the increasing oxygen exposure and implies the weakening metallic properties of the as-generated U-N-O compounds. Higher uranium oxides, such as UO3 and U4O9, are deduced to be the final oxidation products, and a multistage mechanism for UN1.66 following the exposure to oxygen is discussed.

  7. Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.

    Science.gov (United States)

    Kagna, Olga; Pirmisashvili, Natalia; Tshori, Sagi; Freedman, Nanette; Israel, Ora; Krausz, Yodphat

    2014-12-01

    Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.

  8. Beyond 18F-FDG: Characterization of PET/CT and PET/MR Scanners for a Comprehensive Set of Positron Emitters of Growing Application--18F, 11C, 89Zr, 124I, 68Ga, and 90Y.

    Science.gov (United States)

    Soderlund, A Therese; Chaal, Jasper; Tjio, Gabriel; Totman, John J; Conti, Maurizio; Townsend, David W

    2015-08-01

    This study aimed to investigate image quality for a comprehensive set of isotopes ((18)F, (11)C, (89)Zr, (124)I, (68)Ga, and (90)Y) on 2 clinical scanners: a PET/CT scanner and a PET/MR scanner. Image quality and spatial resolution were tested according to NU 2-2007 of the National Electrical Manufacturers Association. An image-quality phantom was used to measure contrast recovery, residual bias in a cold area, and background variability. Reconstruction methods available on the 2 scanners were compared, including point-spread-function correction for both scanners and time of flight for the PET/CT scanner. Spatial resolution was measured using point sources and filtered backprojection reconstruction. With the exception of (90)Y, small differences were seen in the hot-sphere contrast recovery of the different isotopes. Cold-sphere contrast recovery was similar across isotopes for all reconstructions, with an improvement seen with time of flight on the PET/CT scanner. The lower-statistic (90)Y scans yielded substantially lower contrast recovery than the other isotopes. When isotopes were compared, there was no difference in measured spatial resolution except for PET/MR axial spatial resolution, which was significantly higher for (124)I and (68)Ga. Overall, both scanners produced good images with (18)F, (11)C, (89)Zr, (124)I, (68)Ga, and (90)Y. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  9. 40 CFR 68.85 - Hot work permit.

    Science.gov (United States)

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.85 Hot work permit. (a) The owner or operator shall issue a hot work permit for hot work operations conducted on or near a covered process. (b...

  10. 40 CFR 68.77 - Pre-startup review.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.77 Pre-startup review. (a) The... stationary sources when the modification is significant enough to require a change in the process safety... substances to a process: (1) Construction and equipment is in accordance with design specifications; (2...

  11. 40 CFR 68.75 - Management of change.

    Science.gov (United States)

    2010-07-01

    ...) CHEMICAL ACCIDENT PREVENTION PROVISIONS Program 3 Prevention Program § 68.75 Management of change. (a) The... “replacements in kind”) to process chemicals, technology, equipment, and procedures; and, changes to stationary sources that affect a covered process. (b) The procedures shall assure that the following considerations...

  12. NAA analysis of enriched Zn-68 by

    International Nuclear Information System (INIS)

    Rafii, H.; Mirzaei, M.; Mirzajani, N.; Sardari, D.; Shahabi, I.; Majedi, F.

    2002-01-01

    Excessive application of enriched isotopes in various fields of sciences and industry necessitates measuring their abundant by a precise and rapid methos. Beside the inductively coupled plasma mass spectrometry, the thermal neutron activation analysis, NAA, is an alternative method, which is capable to determine trace amounts of elements as well as the elemental abundance. In this article the enrichment of Zn-68 in two different samples has been studied by mean of NAA. One sample was separated by an electromagnetic system in our center and the other was purchased from a French company, Cortecnet. The neutron irradiation was took place in MNSR reactor by flux 10 1 1n/cm 2 sec. for 30 min. and the produced radioactivity from Zn-69 m was measured one day after irradiation by HPGe detector. The results shows a good agreement with the reported ones and its low derivation of about ±3.05 indicates that the NAA is a precise, rapid, and supplemental method for analyzing enriched Zn-68

  13. Emergence and epidemic occurrence of enterovirus 68 respiratory infections in The Netherlands in 2010.

    NARCIS (Netherlands)

    Meijer, A.; Sanden, S. van der; Snijders, B.E.P.; Jaramillo-Gutierrez, G.; Bont, L.; Ent, C.K. van der; Overduin, P.; Jenny, S.L.; Jusic, E.; Avoort, H.G.A.M. van der; Smith, G.J.D.; Donker, G.A.; Koopmans, M.P.G.

    2012-01-01

    Following an increase in detection of enterovirus 68 (EV68) in community surveillance of respiratory infections in The Netherlands in 2010, epidemiological and virological analyses were performed to investigate the possible public health impact of EV68 infections. We retrospectively tested specimens

  14. Synthesis and Biodistribution of Lipophilic Monocationic Gallium Radiopharmaceuticals Derived from N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine: Potential Agents for PET Myocardial Imaging with 68Ga

    Science.gov (United States)

    Hsiao, Yui-May; Mathias, Carla J.; Wey, Shiaw-Pyng; Fanwick, Phillip E.; Green, Mark A.

    2009-01-01

    Introduction In locations that lack nearby cyclotron facilities for radionuclide production, generator-based 68Ga-radiopharmaceuticals might have clinical utility for positron emission tomography (PET) studies of myocardial perfusion and other physiologic processes. Methods The lipophilic, monocationic 67Ga-labeled gallium chelates of five novel hexadentate bis(salicylaldimine) ligands, the bis(salicylaldimine), bis(3-methoxysalicylaldimine), bis(4-methoxysalicylaldimine), bis(6-methoxysalicylaldimine), and bis(4,6-dimethoxysalicylaldimine) of N,N′-bis(3-aminopropyl)-N,N′-dimethylethylenediamine (BAPDMEN), were prepared. The structure of the unlabeled [Ga(4-MeOsal)2BAPDMEN]+PF6− salt was determined by X-ray crystallography, and the biodistribution of each of the 67Ga-labeled gallium chelates determined in rats following i.v. administration and compared to the biodistribution of [86Rb]rubidium chloride. Results The [Ga(4-MeOsal)2BAPDMEN]+PF6− complex exhibits the expected pseudo-octahedral N4O22− coordination sphere about the Ga3+ center with a trans-disposition of the phenolate oxygen atoms. All five of the 67Ga-radiopharmaceuticals were found to afford the desired myocardial retention of the radiogallium. The [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+ radiopharmaceutical appears to have the best properties for myocardial imaging, exhibiting 2% of the injected dose in the heart at both 1-minute and 2-hours post-injection and very high heart/non-target ratios (heart/blood ratios of 7.6 ± 1.0 and 54 ± 10 at 1-min and 120-min, respectively; heart/liver ratios of 1.8 ± 0.4 and 39 ± 3 at 1-min and 120-min, respectively). Conclusions Most of these new agents, particularly [67/68Ga][Ga(3-MeOsal)2BAPDMEN]1+, would appear superior to previously reported bis(salicyaldimines) of N,N′-bis(3-aminopropyl)ethylenediamine as candidates for PET imaging of the heart with 68Ga. PMID:19181267

  15. Ameloblastoma: Our clinical experience with 68 cases

    Directory of Open Access Journals (Sweden)

    Benjamin Fomete

    2014-01-01

    Full Text Available Introduction: In this environment, previous workers have reported on the challenges of managing large sized ameloblastoma of the jaws with less than adequate facilities. The aim of this review is to present the management of 68 cases of ameloblastoma with emphasis on surgical care. Materials and Methods: Retrospective survey of case notes of patients with histopathologic diagnosis of ameloblastoma (using the criteria of Barnes et al., 2005 seen between January 2006 and August 2010 at the Maxillofacial Unit, Ahmadu Bello University Teaching Hospital, Shika-Zaria, Nigeria was undertaken. Data collected includes histopathological diagnosis, age, gender, clinical information on site of lesion, form of intubation and surgical procedure performed. Results: Out of 94 patients, 68 with histological diagnosis of ameloblastoma (59 mandibular and 9 maxillary were operated within the study period. The remainder (26 was not treated in hospital. Among 68 patients treated, more were males (38 than females (30, giving a male to female ratio of 1.3:1. The age range was between 14 and 74 years (mean-standard deviation. The duration of the symptoms ranged from 7 months to 24 years, most were follicular ameloblastoma (n = 13 followed by acanthomatous type (n = 7. Endotracheal intubation was the most common (n = 55 followed by fiber optic laryngoscopy (n = 8. The surgical approach most used was extended Risdon with intraoral (n = 24 followed by extended Risdon with lip split and intraoral (n = 17. Segmental resection (en block formed the bulk of our procedures (n = 22 followed by subtotal mandibulectomy (n = 16. Conclusion: The treatment of ameloblastoma remains controversial. Its destructive nature has left patients with wide defects difficult to reconstruct.

  16. Development of methods for the purification of {sup 67}Ga and {sup 68}Ga for biomolecules labeling; Desenvolvimento de metodos de purificacao do {sup 67}Ga e {sup 68}Ga para a marcacao de biomoleculas

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Renata Ferreira

    2012-07-01

    For more than fifty years, the long-lived {sup 68}Ge/{sup 68}Ga generators have been in development, obtaining {sup 68}Ga without the need of having in house cyclotron, which is a considerable convenience for PET centers that have no nearby cyclotrons. {sup 68}Ga decays 89% by positron emission and low photon emission (1077 keV) and the physical half life of 67.7 minutes is compatible with the pharmacokinetics of low biomolecular weight substances like peptides and antibody fragments. Moreover, its established metallic chemistry allows it to be stably bound to the carrier peptide sequence via a suitable bifunctional chelator, such as DOTA. All these reasons together with the technology of PET/CT allowed advances in molecular imaging, in particular in the diagnosis of neuroendocrine diseases. However, the eluate from the commercial {sup 68}Ge/{sup 68}Ga generators still contains high levels of long lived {sup 68}Ge, besides other metallic impurities, which competes with {sup 68}Ga with a consequent reduction of the labeling yield of biomolecules, such as Fe{sup 3+} and Zn{sup 2+}. Thus, the lower the amount of impurities in the eluate, the competition between the radiolabeled and unlabeled peptide by the receptor will be smaller and the quality of imaging will be better, a subsequent purification step is needed after the generator elution. The aim of this work is to evaluate different purifications methods of {sup 68}Ga to label biomolecules, with emphasis on the study of the chemical impurities contained in the eluate and to develop a new purification method. Several purification methods were studied. Many cationic resin were tested simulating the commercial process. {sup 68}Ga is adsorbed in cationic resin, which is not commercial available and eluted in acid/acetone solution. The use of minor particles of cationic resin AG50W-X4 (200-400 mesh) showed the best results. An innovate method was the extraction chromatography, which is based on the absorption of

  17. Analysis of the synonymous codon usage bias in recently emerged enterovirus D68 strains.

    Science.gov (United States)

    Karniychuk, Uladzimir U

    2016-09-02

    Understanding the codon usage pattern of a pathogen and relationship between pathogen and host's codon usage patterns has fundamental and applied interests. Enterovirus D68 (EV-D68) is an emerging pathogen with a potentially high public health significance. In the present study, the synonymous codon usage bias of 27 recently emerged, and historical EV-D68 strains was analyzed. In contrast to previously studied enteroviruses (enterovirus 71 and poliovirus), EV-D68 and human host have a high discrepancy between favored codons. Analysis of viral synonymous codon usage bias metrics, viral nucleotide/dinucleotide compositional parameters, and viral protein properties showed that mutational pressure is more involved in shaping the synonymous codon usage bias of EV-D68 than translation selection. Computation of codon adaptation indices allowed to estimate expression potential of the EV-D68 genome in several commonly used laboratory animals. This approach requires experimental validation and may provide an auxiliary tool for the rational selection of laboratory animals to model emerging viral diseases. Enterovirus D68 genome compositional and codon usage data can be useful for further pathogenesis, animal model, and vaccine design studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Development of new folate-based PET radiotracers: preclinical evaluation of 68Ga-DOTA-folate conjugates

    International Nuclear Information System (INIS)

    Fani, Melpomeni; Maecke, Helmut R.; Wang, Xuejuan; Nicolas, Guillaume; Medina, Christelle; Raynal, Isabelle; Port, Marc

    2011-01-01

    A number of 111 In- and 99m Tc-folate-based tracers have been evaluated as diagnostic agents for imaging folate receptor (FR)-positive tumours. A 68 Ga-folate-based radiopharmaceutical would be of great interest, combining the advantages of PET technology and the availability of 68 Ga from a generator. The aim of the study was to develop a new 68 Ga-folate-based PET radiotracer. Two new DOTA-folate conjugates, named P3026 and P1254, were synthesized using the 1,2-diaminoethane and 3-{2-[2-(3-amino-propoxy)-ethoxy]-ethoxy}-propylamine as a spacer, respectively. Both conjugates were labelled with 67/68 Ga. Binding affinity, internalization and externalization studies were performed using the FR-positive KB cell line. Biodistribution and PET/CT imaging studies were performed in nude mice, on a folate-deficient diet, bearing KB and HT1080 (FR-negative) tumours, concurrently. The new radiotracers were evaluated comparatively to the reference molecule 111 In-DTPA-folate ( 111 In-P3139). The K d values of 67/68 Ga-P3026 (4.65 ± 0.82 nM) and 67/68 Ga-P1254 (4.27 ± 0.42 nM) showed high affinity for the FR. The internalization rate followed the order 67/68 Ga-P3026 > 67/68 Ga-P1254 > 111 In-P3139, while almost double cellular retention was found for 67/68 Ga-P3026 and 67/68 Ga-P1254, compared to 111 In-P3139. The biodistribution data of 67/68 Ga-DOTA-folates showed high and receptor-mediated uptake on the FR-positive tumours and kidneys, with no significant differences compared to 111 In-P3139. PET/CT images, performed with 68 Ga-P3026, showed high uptake in the kidneys and clear visualization of the FR-positive tumours. The DOTA-folate conjugates can be efficiently labelled with 68 Ga in labelling yields and specific activities which allow clinical application. The characteristics of the 67/68 Ga-DOTA-folates are comparable to 111 In-DTPA-folate, which has already been used in clinical trials, showing that the new conjugates are promising candidates as PET radiotracers

  19. 24 CFR 242.68 - Disclosure and verification of Social Security and Employer Identification Numbers.

    Science.gov (United States)

    2010-04-01

    ... Social Security and Employer Identification Numbers. 242.68 Section 242.68 Housing and Urban Development... Requirements § 242.68 Disclosure and verification of Social Security and Employer Identification Numbers. The requirements set forth in 24 CFR part 5, regarding the disclosure and verification of Social Security Numbers...

  20. 47 CFR 68.602 - Sponsor of the Administrative Council for Terminal Attachments.

    Science.gov (United States)

    2010-10-01

    ... Attachments. (a) The Telecommunications Industry Association (TIA) and the Alliance for Telecommunications... 47 Telecommunication 3 2010-10-01 2010-10-01 false Sponsor of the Administrative Council for Terminal Attachments. 68.602 Section 68.602 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED...

  1. 32 CFR 776.68 - Reporting professional misconduct.

    Science.gov (United States)

    2010-07-01

    ... professional misconduct: (1) A covered attorney having knowledge that another covered attorney has committed a... with the procedures set forth in subpart C of this part. (2) A covered attorney having knowledge that a... 32 National Defense 5 2010-07-01 2010-07-01 false Reporting professional misconduct. 776.68...

  2. Preparation of carrier-free 67Cu by the 68Zn(γ,p) reaction

    International Nuclear Information System (INIS)

    Yagi, M.; Kondo, K.

    1978-01-01

    The preparation of pure, carrier-free 67 Cu using the 68 Zn(γ, p) reaction with an isotopically enriched 68 Zn(98.97%) target is described. The production rates of 67 Cu and contaminants were determined as a function of the maximum bremsstrahlung energies between 30 and 60 MeV. The chemical separation of the carrier-free 67 Cu and the recovery of the 68 Zn target were also studied. (author)

  3. Mayo del 68, cuarenta años después. Entre herencias y controversias.

    Directory of Open Access Journals (Sweden)

    Virginie Laurent.

    2009-08-01

    Full Text Available Was May of ´68 a revolt or revolution? Was it a student movement or a working-class one? Was May of ´68 French or global in character? May of ´68, which combined unprecedented student protests with a massive general strike, left a strong imprint on the political, social, and cultural development of French society. Starting with a contextualization of the “facts,” this article reflects on the direct and indirect effects, as well as controversies, that May of ´68 still generates forty years later. It emphasizes the way that young people today perceive the events of period and how May of ´68 was at the center of the 2007 French presidential campaign.

  4. 40 CFR 156.68 - First aid statement.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false First aid statement. 156.68 Section... aid statement. (a) Product as sold and distributed. Each product must bear a first aid statement if... with water prior to use, the label may also include a statement describing how the first aid measures...

  5. MIL-68 (In) nano-rods for the removal of Congo red dye from aqueous solution.

    Science.gov (United States)

    Jin, Li-Na; Qian, Xin-Ye; Wang, Jian-Guo; Aslan, Hüsnü; Dong, Mingdong

    2015-09-01

    MIL-68 (In) nano-rods were prepared by a facile solvothermal synthesis using NaOAc as modulator agent at 100°C for 30 min. The BET test showed that the specific surface area and pore volume of MIL-68 (In) nanorods were 1252 m(2) g(-1) and 0.80 cm(3) g(-1), respectively. The as-prepared MIL-68 (In) nanorods showed excellent adsorption capacity and rapid adsorption rate for removal of Congo red (CR) dye from water. The maximum adsorption capacity of MIL-68 (In) nanorods toward CR reached 1204 mg g(-1), much higher than MIL-68 (In) microrods and most of the previously reported adsorbents. The adsorption process of CR by MIL-68 (In) nano-rods was investigated and found to be obeying the Langmuir adsorption model in addition to pseudo-second-order rate equation. Moreover, the MIL-68 (In) nanorods showed an acceptable reusability after regeneration with ethanol. All information gives an indication that the as-prepared MIL-68 (In) nanorods show their potential as the adsorbent for highly efficient removal of CR in wastewater. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1980-December 31, 1981

    International Nuclear Information System (INIS)

    Welch, M.J.

    1981-06-01

    Although the germanium-68 → gallium-68 generator is probably the only source of positron-emitting radionuclides that could enable the widespread application of positron tomography, the commercially available 68 Ga/ 68 Ge generator system suffers from several major disadvantages. The most important of these is that the generator is eluted with EDTA, which forms a very strong chelate with gallium. In order to produce radiopharmaceuticals other than 68 Ga-EDTA, it is first necessary to break the stable EDTA complex and remove all traces of EDTA. This procedure adds several steps and a significant amount of time to procedures for preparing 68 Ga-radiopharmaceuticals. Several years ago, we developed a new generator using a solvent extraction system which produces 68 Ga-oxine (8-hydroxyquinoline), a weak chelate. We have also carried out studies to compare generator systems which produce 68 Ga in an ionic form. Using the gallium-68 eluted from these various generator systems, several 68 Ga-labeled radiopharmaceuticals have been synthesized and tested in vitro and in vivo. In addition, attempts have been made to design and synthesize a lipophilic ligand for gallium-68. The stability of radiogallium complexed with a series of potentially lipophilic complexing agents has been studied using chromatographic techniques and in vivo distribution data. The potential of these complexing agents for altering the biodistribution of gallium radiopharmaceuticals has also been investigated

  7. Measurements of some basic constants of 68Ga(BAT-TECH) as an imaging agent

    International Nuclear Information System (INIS)

    Chen Huawei; Liu Boli

    1994-01-01

    The kinetic properties of a new myocardial imaging agent 68 Ga(BAT-TECH) are investigated and its thermodynamic constants are measured. The results are as follows: Citrate→BAT-TECH exchange reaction order is second-order; reaction rate k = 0.50 l/mol·s; activation energy E a = 56.6 kJ/mol; the stability constant of 68 Ga(BAT-TECH) lgβ = 14.9; the acid dissociation constants of BAT-TECH pK 1 = 4.62, pK 2 = 7.68, pK-3 = 8.68, pK 4 = 11.2

  8. Positron tomographic imaging of the liver: 68Ga iron hydroxide colloid

    International Nuclear Information System (INIS)

    Kumar, B.; Miller, T.R.; Siegel, B.A.; Mathias, C.J.; Markham, J.; Ehrhardt, G.J.; Welch, M.J.

    1981-01-01

    A new radiopharmaceutical, 68 Ga iron hydroxide colloid, for hepatic imaging by positron emission tomography was prepared from the eluate of a 68 Ge- 68 Ga solvent extraction generator. In rats, 84% of the administered dose of colloid localized in the liver and 4.6% accumulated in the spleen. Initial imaging studies in normal dogs showed close correspondence of the findings by positron tomography and transmission computed tomography. Emission tomography with 68 Ga-colloid was performed in 10 patients with hepatic metastases demonstrated by conventional /sup 99m/Tc-sulfur colloid scintigraphy. All focal defects noted on the conventional scintigrams were easily identified and generally were seen more clearly by positron tomography. In one patient, additional lesions not identified on the initial /sup 99m/Tc-sulfur colloid images were demonstrated. The positron tomographic images were compared with those obtained by transmission computed tomography in seven patients; the two studies showed comparable findings in five patients, whereas positron tomography more clearly showed multiple lesions in two. Our results suggest that positron emission tomography is a suitable technique for obtaining high contrast, cross-sectional images of large abdominal organs

  9. Positron tomographic imaging of the liver: 68Ga iron hydroxide colloid

    International Nuclear Information System (INIS)

    Kumar, B.; Miller, T.R.; Siegel, B.A.; Mathias, C.J.; Markham, J.; Ehrhardt, G.J.; Welch, M.J.

    1981-01-01

    A new radiopharmaceutical, 68 Ga ion hydroxide colloid, for hepatic imaging by positron emission tomography was prepared from the eluate of a 68 Ge- 68 Ga solvent extraction generator. In rats, 84% of the administered dose of colloid localized in the liver and 4.6% accumulated in the spleen. Initial imaging studies in normal dogs showed close correspondence of the findings by positron tomography and transmission computed tomography. Emission tomography with 68 Ga-colloid was performed in 10 patients with hepatic metastases demonstrated by conventional 99mTc sulfur colloid scintigraphy. All focal defects noted on the conventional scintigrams were easily identified and generally were seen more clearly by positron tomography. In one patient, additional lesions not identified on the initial 99mTc sulfur colloid images were demonstrated. The positron tomographic images were compared with those obtained by transmission computed tomography in seven patients; the two studies showed comparable findings in five patients, whereas positron tomography more clearly showed multiple lesions in two. Our results suggest that positron emission tomography is a suitable technique for obtaining high contrast, cross-sectional images of large abdominal organs

  10. 68Ga-PSMA PET/CT in the evaluation of bone metastases in prostate cancer.

    Science.gov (United States)

    Sachpekidis, Christos; Bäumer, P; Kopka, K; Hadaschik, B A; Hohenfellner, M; Kopp-Schneider, A; Haberkorn, U; Dimitrakopoulou-Strauss, A

    2018-06-01

    The aims of this retrospective analysis were to compare 68 Ga-PSMA PET findings and low-dose CT findings (120 kV, 30 mA), and to obtain semiquantitative and quantitative 68 Ga-PSMA PET data in patients with prostate cancer (PC) bone metastases. In total, 152 PET/CT scans from 140 patients were evaluated. Of these patients, 30 had previously untreated primary PC, and 110 had biochemical relapse after treatment of primary PC. All patients underwent dynamic PET/CT scanning of the pelvis and lower abdomen as well as whole-body PET/CT with 68 Ga-PSMA-11. The PET/CT scans were analysed qualitatively (visually), semiquantitatively (SUV), and quantitatively based on a two-tissue compartment model and a noncompartmental approach leading to the extraction of the fractal dimension. Differences were considered significant for p values PET-positive and CT-positive, 65 were only 68 Ga-PSMA-positive, and 10 were only CT-positive. The Yang test showed that there were significantly more 68 Ga-PSMA PET-positive lesions than CT-positive lesions. Association analysis showed that PSA plasma levels were significantly correlated with several 68 Ga-PSMA-11-associated parameters in bone metastases, including the degree of tracer uptake (SUV average and SUV max ), its transport rate from plasma to the interstitial/intracellular compartment (K 1 ), its rate of binding to the PSMA receptor and its internalization (k 3 ), its influx rate (K i ), and its distribution heterogeneity. 68 Ga-PSMA PET/CT is a useful diagnostic tool in the detection of bone metastases in PC. 68 Ga-PSMA PET visualizes more bone metastases than low-dose CT. PSA plasma levels are significantly correlated with several 68 Ga-PSMA PET parameters.

  11. Studies of the chemical behavior of carrier-free 68Ge. Pt. 2

    International Nuclear Information System (INIS)

    Mirzadeh, S.; Kahn, M.

    1986-01-01

    A determination of the 68 Ge distribution constant from the distillation of the azeotropic HCl was made. A simple correlation between the distribution constants of the 68 Ge and HCl was observed which can be expressed as D'sub(Ge)=k[D'sub(HCl)]sup(n). (orig.)

  12. A Mouse Model of Enterovirus D68 Infection for Assessment of the Efficacy of Inactivated Vaccine

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2018-01-01

    Full Text Available In recent years, enterovirus D68 (EVD68 has been reported increasingly to be associated with severe respiratory tract infections and acute flaccid myelitis (AFM in children all over the world. Yet, no effective vaccines or antiviral drugs are currently available for EVD68. Although several experimental animal models have been developed, immunogenicity and protective efficacy of inactivated EVD68 vaccines has not been fully evaluated. To promote the development of vaccines, we established an Institute of Cancer Research (ICR suckling mouse model of EVD68 infection in this study. The results showed that ICR neonatal mice up to about nine days of age were susceptible to infection with EVD68 clinical strain US/MO/14-18947 by intraperitoneal injection. The infected mice exhibited progressive limb paralysis prior to death and the mortality of mice was age- and virus dose-dependent. Tissue viral load analysis showed that limb muscle and spinal cord were the major sites of viral replication. Moreover, histopathologic examination revealed the severe necrosis of the limb and juxtaspinal muscles, suggesting that US/MO/14-18947 has a strong tropism toward muscle tissues. Additionally, β-propiolactone-inactivated EVD68 vaccine showed high purity and quality and induced robust EVD68-specific neutralizing antibody responses in adult mice. Importantly, results from both antisera transfer and maternal immunization experiments clearly showed that inactivated EVD68 vaccine was able to protect against lethal viral infection in the mouse model. In short, these results demonstrate the successful establishment of the mouse model of EVD68 infection for evaluating candidate vaccines against EVD68 and also provide important information for the development of inactivated virus-based EVD68 vaccines.

  13. Preclinical evaluation of melanocortin-1 receptor (MC1-R) specific 68Ga- and 44Sc-labeled DOTA-NAPamide in melanoma imaging.

    Science.gov (United States)

    Nagy, Gábor; Dénes, Noémi; Kis, Adrienn; Szabó, Judit P; Berényi, Ervin; Garai, Ildikó; Bai, Péter; Hajdu, István; Szikra, Dezső; Trencsényi, György

    2017-08-30

    Alpha melanocyte stimulating hormone (α-MSH) enhances melanogenesis in melanoma malignum by binding to melanocortin-1 receptors (MC1-R). Earlier studies demonstrated that alpha-MSH analog NAPamide molecule specifically binds to MC1-R receptor. Radiolabeled NAPamide is a promising radiotracer for the non-invasive detection of melanin producing melanoma tumors by Positron Emission Tomography (PET). In this present study the MC1-R selectivity of the newly developed Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using melanoma tumors. DOTA-NAPamide was labeled with Ga-68 and Sc-44 radionuclides. The MC1-R specificity of Ga-68- and Sc-44-labeled DOTA-NAPamide was investigated in vitro and in vivo using MC1-R positive (B16-F10) and negative (A375) melanoma cell lines. For in vivo imaging studies B16-F10 and A375 tumor-bearing mice were injected with 44 Sc/ 68 Ga-DOTA-NAPamide (in blocking studies with α-MSH) and whole body PET/MRI scans were acquired. Radiotracer uptake was expressed in terms of standardized uptake values (SUVs). 44 Sc/ 68 Ga-labeled DOTA-NAPamide were produced with high specific activity (approx. 19 GBq/μmol) and with excellent radiochemical purity (99%DOTA-NAPamide (SUVmean: 0.38±0.02), and Sc-44-DOTA-NAPamide (SUVmean: 0.52±0.13) uptake was observed in subcutaneously growing B16-F10 tumors, than in receptor negative A375 tumors, where the SUVmean values of Ga-68-DOTA-NAPamide and Sc-44-DOTA-NAPamide were 0.04±0.01 and 0.07±0.01, respectively. Tumor-to-muscle (T/M SUVmean) ratios were approximately 15-fold higher in B16-F10 tumor-bearing mice, than that of A375 tumors, and this difference was also significant (p≤0.01) using both radiotracers after 60 min incubation time. Our newly synthesized 44 Sc-labeled DOTA-NAPamide probe showed excellent binding properties to melanocortin-1 receptor (MC1-R) positive melanoma cell and tumors. Due to its high specificity and sensitivity 44 Sc-DOTA-NAPamide is a promising radiotracer in

  14. 47 CFR 68.610 - Database of terminal equipment.

    Science.gov (United States)

    2010-10-01

    ... permit any entity or segment of the industry to gain a competitive advantage. (d) The Administrative... 68.610 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES... requirements of the Federal Communications Commission and the U.S. Customs Service for enforcement purposes...

  15. A thermostable Salmonella phage endolysin, Lys68, with broad bactericidal properties against gram-negative pathogens in presence of weak acids.

    Directory of Open Access Journals (Sweden)

    Hugo Oliveira

    Full Text Available Resistance rates are increasing among several problematic Gram-negative pathogens, a fact that has encouraged the development of new antimicrobial agents. This paper characterizes a Salmonella phage endolysin (Lys68 and demonstrates its potential antimicrobial effectiveness when combined with organic acids towards Gram-negative pathogens. Biochemical characterization reveals that Lys68 is more active at pH 7.0, maintaining 76.7% of its activity when stored at 4°C for two months. Thermostability tests showed that Lys68 is only completely inactivated upon exposure to 100°C for 30 min, and circular dichroism analysis demonstrated the ability to refold into its original conformation upon thermal denaturation. It was shown that Lys68 is able to lyse a wide panel of Gram-negative bacteria (13 different species in combination with the outer membrane permeabilizers EDTA, citric and malic acid. While the EDTA/Lys68 combination only inactivated Pseudomonas strains, the use of citric or malic acid broadened Lys68 antibacterial effect to other Gram-negative pathogens (lytic activity against 9 and 11 species, respectively. Particularly against Salmonella Typhimurium LT2, the combinatory effect of malic or citric acid with Lys68 led to approximately 3 to 5 log reductions in bacterial load/CFUs after 2 hours, respectively, and was also able to reduce stationary-phase cells and bacterial biofilms by approximately 1 log. The broad killing capacity of malic/citric acid-Lys68 is explained by the destabilization and major disruptions of the cell outer membrane integrity due to the acidity caused by the organic acids and a relatively high muralytic activity of Lys68 at low pH. Lys68 demonstrates good (thermostability properties that combined with different outer membrane permeabilizers, could become useful to combat Gram-negative pathogens in agricultural, food and medical industry.

  16. Enterovirus D68-associated community-acquired pneumonia in children living in Milan, Italy.

    Science.gov (United States)

    Esposito, Susanna; Zampiero, Alberto; Ruggiero, Luca; Madini, Barbara; Niesters, Hubert; Principi, Nicola

    2015-07-01

    An increasing number of children infected by enterovirus D68 (EV-D68) and affected by severe respiratory illness, muscle weakness and paralysis were described in the USA and Canada in 2014 OBJECTIVES: To investigate the potential involvement of EV-D68 in determining community-acquired pneumonia (CAP) in hospitalised children in order to acquire information concerning the clinical problems associated with EV-D68 in Italy. This prospective study of children hospitalised for CAP in the largest Pediatric Department in Milan, Italy, was carried out between 1 June and 31 December 2014. All of the children's admission nasopharyngeal swabs were investigated for the presence of EV-D68. One hundred and seventy-six children with radiographically confirmed CAP were hospitalised during the 7-month study period: 97 (55.1%) had enterovirus/rhinovirus-positive nasopharyngeal samples, including four (2.3%) positive for EV-D68. These four samples were collected between 9 and 21 October, a month in which 21 cases of CAP were recorded. Phylogenetic analysis showed that all of the sequences fell into clade B. The most severe case was diagnosed in a 14-year-old girl with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS syndrome), who died after 12 days of hospitalisation. EV-D68 was detected in few children with usually mild-to-moderate lower respiratory tract infection, although the disease lead to the death of a girl with a severe chronic underlying disease. Further studies capable of better defining the epidemiological, genetic and pathogenetic characteristics of the virus are required in order to be able to prepare appropriate preventive and therapeutic measures. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    International Nuclear Information System (INIS)

    Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani; Iveson, Peter; Wilson, Ian; Karlsen, Hege; Cuthbertson, Alan; Laine, Jukka; Leppaenen, Pia; Ylae-Herttula, Seppo; Roivainen, Anne

    2009-01-01

    Increased expression of αvβ3/αvβ5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel 68 Ga-DOTA-RGD peptide binds with high affinity to αvβ3/αvβ5 integrin. The aim of this study was to investigate the uptake of the 68 Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered 68 Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR -/- ApoB 100/100 atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced 68 Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68 Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of 68 Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio ± SD 1.4 ± 0.1, p = 0.0004). We observed that 68 Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  18. Preclinical evaluation of two 68Ga-siderophores as potential radiopharmaceuticals for Aspergillus fumigatus infection imaging

    International Nuclear Information System (INIS)

    Petrik, Milos; Franssen, Gerben M.; Laverman, Peter; Haas, Hubertus; Schrettl, Markus; Hoertnagl, Caroline; Lass-Floerl, Cornelia; Helbok, Anna; Decristoforo, Clemens

    2012-01-01

    Invasive pulmonary aspergillosis is mainly caused by Aspergillus fumigatus, and is one of the major causes of morbidity and mortality in immunocompromised patients. The mortality associated with invasive pulmonary aspergillosis remains high, mainly due to the difficulties and limitations in diagnosis. We have shown that siderophores can be labelled with 68 Ga and can be used for PET imaging of A. fumigatus infection in rats. Here we report on the further evaluation of the most promising 68 Ga-siderophore candidates, triacetylfusarinine (TAFC) and ferrioxamine E (FOXE). Siderophores were labelled with 68 Ga using acetate buffer. Log P, protein binding and stability values were determined. Uptake by A. fumigatus was studied in vitro in cultures with high and low iron loads. In vivo biodistribution was determined in normal mice and an infection model was established using neutropenic rats inoculated with A. fumigatus. Static and dynamic μPET imaging was performed and correlated with CT images, and lung infection was evaluated ex vivo. 68 Ga-siderophores were labelled with high radiochemical purity and specific activity. 68 Ga-TAFC and 68 Ga-FOXE showed high uptake by A. fumigatus in iron-deficient cultures. In normal mice, 68 Ga-TAFC and 68 Ga-FOXE showed rapid renal excretion with high metabolic stability. In the rat infection model focal lung uptake was detected by μPET with both compounds and increased with severity of the infection, correlating with abnormal CT images. 68 Ga-TAFC and 68 Ga-FOXE displayed excellent in vitro stability and high uptake by A. fumigatus. Both compounds showed excellent pharmacokinetics, highly selective accumulation in infected lung tissue and good correlation with severity of disease in a rat infection model, which makes them promising agents for A. fumigatus infection imaging. (orig.)

  19. 40 CFR 68.22 - Offsite consequence analysis parameters.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 15 2010-07-01 2010-07-01 false Offsite consequence analysis... PROGRAMS (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Hazard Assessment § 68.22 Offsite consequence analysis parameters. (a) Endpoints. For analyses of offsite consequences, the following endpoints shall be...

  20. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1977-October 31, 1980

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1980-06-01

    Although the germanium-68 ..-->.. gallium-68 generator is probably the only source of positron-emitting radionuclides that could enable the widespread application of positron tomography, the commercially available /sup 68/Ga//sup 68/Ge generator system suffers from several major disadvantages. The most important of these is that the generator is eluted with EDTA, which forms a very strong chelate with gallium. In order to produce radiopharmaceuticals other than /sup 68/Ga-EDTA, it is first necessary to break the stable EDTA complex and remove all traces of EDTA. This procedure adds several steps and a significant amount of time to procedures for preparing /sup 68/Ga-radiopharmaceuticals. We have developed a new generator using a solvent extraction system which will produce /sup 68/Ga-oxine (8-hydroxyquinoline), a weak chelate. Using this agent we have synthesized several /sup 68/Ga-radiopharmaceuticals and tested them in vitro and in vivo. We have also carried out some preliminary studies to compare generator systems which produce /sup 68/Ga in an ionic form. Attempts have been made using polarographic and chromatographic techniques, and in vivo distribution data to investigate the stability of radiogallium complexes with a series of potentially lipophilic complexing agents.

  1. PSA-stratified detection rates for [68Ga]THP-PSMA, a novel probe for rapid kit-based 68Ga-labeling and PET imaging, in patients with biochemical recurrence after primary therapy for prostate cancer.

    Science.gov (United States)

    Derlin, Thorsten; Schmuck, Sebastian; Juhl, Cathleen; Zörgiebel, Johanna; Schneefeld, Sophie M; Walte, Almut C A; Hueper, Katja; von Klot, Christoph A; Henkenberens, Christoph; Christiansen, Hans; Thackeray, James T; Ross, Tobias L; Bengel, Frank M

    2018-06-01

    [ 68 Ga]Tris(hydroxypyridinone)(THP)-PSMA is a novel radiopharmaceutical for one-step kit-based radiolabelling, based on direct chelation of 68 Ga 3+ at low concentration, room temperature and over a wide pH range, using direct elution from a 68 Ge/ 68 Ga-generator. We evaluated the clinical detection rates of [ 68 Ga]THP-PSMA PET/CT in patients with biochemically recurrent prostate cancer after prostatectomy. Consecutive patients (n=99) referred for evaluation of biochemical relapse of prostate cancer by [ 68 Ga]THP-PSMA PET/CT were analyzed retrospectively. Patients underwent a standard whole-body PET/CT (1 h p.i.), followed by delayed (3 h p.i.) imaging of the abdomen. PSA-stratified cohorts of positive PET/CT results, standardized uptake values (SUVs) and target-to-background ratios (TBRs) were analyzed, and compared between standard and delayed imaging. At least one lesion suggestive of recurrent or metastatic prostate cancer was identified on PET images in 52 patients (52.5%). Detection rates of [ 68 Ga]THP-PSMA PET/CT increased with increasing PSA level: 94.1% for a PSA value of ≥10 ng/mL, 77.3% for a PSA value of 2 to PSA value of 1 to PSA value of 0.5 to PSA value of >0.2 to PSA value of 0.01 to 0.2 ng/mL. [ 68 Ga]THP-PSMA uptake (SUVs) in metastases decreased over time, whereas TBRs improved. Delayed imaging at 3 h p.i. exclusively identified pathologic findings in 2% of [ 68 Ga]THP-PSMA PET/CT scans. Detection rate was higher in patients with a Gleason score ≥8 (P=0.02) and in patients receiving androgen deprivation therapy (P=0.003). In this study, [ 68 Ga]THP-PSMA PET/CT showed suitable detection rates in patients with biochemical recurrence of prostate cancer and PSA levels ≥ 2 ng /mL. Detections rates were lower than in previous studies evaluating other PSMA ligands, though prospective direct radiotracer comparison studies are mandatory particularly in patients with low PSA levels to evaluate the relative performance of different PSMA ligands.

  2. Detection rate of PET/CT in patients with biochemical relapse of prostate cancer using [{sup 68}Ga]PSMA I and T and comparison with published data of [{sup 68}Ga]PSMA HBED-CC

    Energy Technology Data Exchange (ETDEWEB)

    Berliner, Christoph; Tienken, Milena; Kobayashi, Yuske; Helberg, Annabelle; Kirchner, Uve; Klutmann, Susanne; Mester, Janos; Bannas, Peter [University Medical Center Hamburg-Eppendorf, Diagnostic and Interventional Radiology and Nuclear Medicine, Hamburg (Germany); Frenzel, Thorsten [University Medical Center Hamburg-Eppendorf, Ambulatory Center, Department for Radiation Oncology, Hamburg (Germany); Beyersdorff, Dirk [University Medical Center Hamburg-Eppendorf, Diagnostic and Interventional Radiology and Nuclear Medicine, Hamburg (Germany); University Medical Center Hamburg-Eppendorf, Martini-Klinik, Hamburg (Germany); Budaeus, Lars [University Medical Center Hamburg-Eppendorf, Martini-Klinik, Hamburg (Germany); Wester, Hans-Juergen [Technical University Munich, Pharmaceutical Radiochemistry, Garching (Germany)

    2017-04-15

    To determine the detection rate of PET/CT in biochemical relapse of prostate cancer using [{sup 68}Ga]PSMA I and T and to compare it with published detection rates of [{sup 68}Ga]PSMA HBED-CC. We performed a retrospective analysis in 83 consecutive patients with documented biochemical relapse after prostatectomy. All patients underwent whole body [{sup 68}Ga]PSMA I and T PET/CT. PET/CT images were evaluated for presence of local recurrence, lymph node metastases, and distant metastases. Proportions of positive PET/CT results were calculated for six subgroups with increasing prostate specific antigen (PSA) levels (<0.5 ng/mL, 0.5 to <1.0 ng/mL, 1.0 to <2.0 ng/mL, 2.0 to <5.0 ng/mL, 5.0 to <10.0, ≥10.0 ng/mL). Detection rates of [{sup 68}Ga]PSMA I and T were statistically compared with published detection rates of [{sup 68}Ga]PSMA HBED-CC using exact Fisher's test. Median PSA was 0.81 (range: 0.01 - 128) ng/mL. In 58/83 patients (70 %) at least one [{sup 68}Ga]PSMA I and T positive lesion was detected. Local recurrent cancer was present in 18 patients (22 %), lymph node metastases in 29 patients (35 %), and distant metastases in 15 patients (18 %). The tumor detection rate was positively correlated with PSA levels, resulting in detection rates of 52 % (<0.5 ng/mL), 55 % (0.5 to <1.0 ng/mL), 70 % (1.0 to <2.0 ng/mL), 93 % (2.0 to <5.0 ng/mL), 100 % (5.0 to <10.0 ng/mL), and 100 % (≥10.0 ng/mL). There was no significant difference between the detection rate of [{sup 68}Ga]PSMA I and T and published detection rates of [{sup 68}Ga]PSMA HBED-CC (all p>0.05). [{sup 68}Ga]PSMA I and T PET/CT has high detection rates of recurrent prostate cancer that are comparable to [{sup 68}Ga]PSMA HBED-CC. (orig.)

  3. Study on the pyrolysis of phenol-formaldehyde (PF) resin and modified PF resin

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jigang, E-mail: wangjigang@seu.edu.cn [Jiangsu Key Laboratory of Advanced Metallic Materials, School of Materials Science and Engineering, Southeast University, Nanjing 211189 (China); Jiang, Haiyun [Jiangsu Key Laboratory of Advanced Metallic Materials, School of Materials Science and Engineering, Southeast University, Nanjing 211189 (China); School of Materials Science and Engineering, Southeast University, Nanjing Institute of Technology, Nanjing 210013 (China); Jiang, Nan [Institute of Theoretical and Computational Chemistry, Nanjing University, Nanjing 210093 (China)

    2009-12-10

    The pyrolysis of pure phenol-formaldehyde (PF) resin and boron carbide (B{sub 4}C) modified PF resin was investigated by using thermogravimetry (TG) and pyrolysis gas-chromatography-mass-spectrometry (PY-GC/MS). Scanning electron microscope (SEM) and Fourier transform infrared (FT-IR) spectroscopy were also employed to investigate the micro-structural evolution. It was shown from the TG analysis that the char residues of pure PF resin were 62.9 and 60.5% after being pyrolyzed at 700 and 1000 {sup o}C, respectively. The degradation and failure of the resin matrix were mainly resulted from the release of volatiles. The phenol and its methyl derivates took a large proportion in the amount of volatiles. In comparison with the pure PF resin, the char residues of B{sub 4}C modified PF resin were obviously higher, with the values of 71.9 and 68.4% at 700 and 1000 {sup o}C, respectively. Due to the oxidation-reduction reactions between B{sub 4}C additive and oxygen-containing volatiles including CO and H{sub 2}O, partial carbon and oxygen elements in the volatiles remained in the resin matrix in the forms of amorphous carbon and B{sub 2}O{sub 3}, respectively. The results of SEM and FT-IR characterization demonstrated the occurrence of the modification, and the amorphous carbon existed in the form of reticular substance. In addition, the amount of the released phenol and its methyl derivates was also decreased drastically due to the formation of borate.

  4. Clinical severity of pediatric respiratory illness with enterovirus D68 compared with rhinovirus or other enterovirus genotypes.

    Science.gov (United States)

    Mertz, Dominik; Alawfi, Abdulsalam; Pernica, Jeffrey M; Rutherford, Candy; Luinstra, Kathy; Smieja, Marek

    2015-11-17

    Enterovirus D68 (EV-D68) resulted in a reported increase in the number of children needing hospital or critical care admission because of respiratory insufficiency during 2014. It remains unclear, however, whether EV-D68 infections were more severe than rhinovirus or non-EV-D68 enterovirus infections. We evaluated consecutive children presenting to a pediatric hospital between Aug. 1 and Oct. 31, 2014, with positive nasopharyngeal swabs for rhinovirus or enterovirus that were sent automatically for EV-D68 testing. We compared characteristics and outcomes of patients with EV-D68 with those with rhinovirus or non-EV-D68 enterovirus in a matched cohort study. A total of 93/297 (31.3%) of rhinovirus or enterovirus samples tested positive for EV-D68, and it was possible to compare 87 matched pairs. Children with EV-D68 infection were more likely to have difficulty breathing (odds ratio [OR] 3.00, 95% confidence interval [CI] 1.47-6.14). There was no significant difference in admission to the critical care unit or death among children with EV-D68 infection compared with those with other rhinovirus or enterovirus infections (adjusted OR 1.47, 95% CI 0.61-3.52). Children with EV-D68 infection were more often admitted to hospital, but not significantly so (adjusted OR 2.29, 95% CI 0.96-5.46). Enterovirus D68 seems to be a more virulent pulmonary pathogen than rhinovirus or non-EV-D68 enterovirus, but we did not find a significant difference in death or need for critical care. © 2015 Canadian Medical Association or its licensors.

  5. Development of {sup 68}Ga-labelled DTPA galactosyl human serum albumin for liver function imaging

    Energy Technology Data Exchange (ETDEWEB)

    Haubner, Roland [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Nuklearmedizin, Innsbruck (Austria); Vera, David R.; Farshchi-Heydari, Salman [University of California, Department of Radiology, School of Medicine, and the UCSD Molecular Imaging Program, San Diego, CA (United States); Helbok, Anna; Rangger, Christine; Putzer, Daniel; Virgolini, Irene J. [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria)

    2013-08-15

    The hepatic asialoglycoprotein receptor is responsible for degradation of desialylated glycoproteins through receptor-mediated endocytosis. It has been shown that imaging of the receptor density using [{sup 99m}Tc]diethylenetriamine pentaacetic acid (DTPA) galactosyl human serum albumin ([{sup 99m}Tc]GSA) allows non-invasive determination of functional hepatocellular mass. Here we present the synthesis and evaluation of [{sup 68}Ga]GSA for the potential use with positron emission tomography (PET). Labelling of GSA with {sup 68}Ga was carried out using a fractionated elution protocol. For quality control thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and size exclusion chromatography (SEC) techniques were evaluated. Stability of [{sup 68}Ga]GSA was studied in phosphate-buffered saline (PBS) and human serum. For in vivo evaluation [{sup 68}Ga]GSA distribution in Lewis rats was compared with [{sup 99m}Tc]GSA by using a dual isotope protocol. PET and planar imaging studies were performed using the same scaled molar dose of [{sup 68}Ga]GSA and [{sup 99m}Tc]GSA. Time-activity curves (TAC) for heart and liver were generated and corresponding parameters calculated (t50, t90). [{sup 68}Ga]GSA can be produced with high radiochemical purity. The best TLC methods for determining potential free {sup 68}Ga include 0.1 M sodium citrate as eluent. None of the TLC methods tested were able to determine potential colloids. This can be achieved by SEC. HPLC confirmed high radiochemical purity (>98 %). Stability after 120 min incubation at 37 C was high in PBS (>95 % intact tracer) and low in human serum ({proportional_to}27 % intact tracer). Biodistribution studies simultaneously injecting both tracers showed comparable liver uptake, whereas activity concentration in blood was higher for [{sup 68}Ga]GSA compared to [{sup 99m}Tc]GSA. The [{sup 99m}Tc]GSA TACs exhibited a small degree of hepatic metabolism compared to the [{sup 68}Ga]GSA curves. The mean

  6. Preparation of Ga-68-NOTA as a renal PET agent and feasibility tests in mice

    International Nuclear Information System (INIS)

    Lee, Ji Youn; Jeong, Jae Min; Kim, Young Ju; Jeong, Hyuk-Jin; Lee, Yun-Sang; Lee, Dong Soo

    2014-01-01

    Introduction: Positron emission tomography (PET) may provide more accurate quantification of kidney function such as glomerular filtration rate (GFR) than gamma imaging. The purpose of these experiments was to prepare and evaluate Ga-68 complexes as potential PET agents for measurement of GFR. Methods: We labeled EDTA, DTPA, DOTA, and NOTA with Ga-68 obtained from a Ge-68/Ga-68-generator and measured the binding to serum and red blood cells. Biodistribution study was performed in male BALB/c mice after intravenous injection together with Cr-51-EDTA as the standard for glomerular filtration rate (GFR) measurement. Animal-PET study was performed using BALB/c mice. Results: All the tested chelating agents except DTPA showed quantitative labeling yields (> 99%). Among them, Ga-68-NOTA showed consistently low binding to both human and mouse RBC and serum protein. Biodistribution study showed no significant difference between Ga-68-NOTA and Cr-51-EDTA groups by one-way analysis of variance (ANOVA) (p > 0.05). Furthermore, the GFR values obtained by Ga-68-NOTA and Cr-51-EDTA were almost same (0.26 ± 0.04 and 0.25 ± 0.04 mL/min, respectively). Animal-PET study showed almost the same GFR (0.25 mL/min) with the values obtained by biodistribution study. Conclusion: We proved that an easy-to-prepare agent Ga-68-NOTA is ideal for renal PET as well as for GFR measurement

  7. 41 CFR 105-68.340 - If I disclose unfavorable information required under § 105-68.335, will I be prevented from...

    Science.gov (United States)

    2010-07-01

    ... Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION Regional Offices-General Services... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false If I disclose unfavorable information required under § 105-68.335, will I be prevented from participating in the...

  8. 68Ga-PSMA PET/CT for the detection of bone metastasis in recurrent prostate cancer and a PSA level <2 ng/ml

    DEFF Research Database (Denmark)

    Petersen, Lars J; Nielsen, Julie B; Dettmann, Katja

    2017-01-01

    /computed tomography ((68)Ga-PSMA PET/CT) is a novel and promising method for imaging in prostate cancer. The present study reports two cases of patients with prostate cancer with biochemical recurrence, with evidence of bone metastases on (68)Ga-PSMA PET/CT images and low prostate specific antigen PSA levels (.../ml) and PSA doubling time >6 months. The bone metastases were verified by supplementary imaging with (18)F-sodium fluoride PET/CT and magnetic resonance imaging as well as biochemical responses to androgen deprivation therapy. Therefore, (68)Ga-PSMA PET/CT is promising for the restaging of patients...... with prostate cancer with biochemical recurrence, including patients with low PSA levels and low PSA kinetics....

  9. Decay properties of 68,69,70Mn: Probing collectivity up to N=44 in Fe isotopic chain

    Directory of Open Access Journals (Sweden)

    G. Benzoni

    2015-12-01

    Full Text Available The β decays Mn68→Fe68, Mn69→Fe69 and Mn70→Fe70 have been measured at the RIBF facility at RIKEN using the EURICA γ spectrometer combined with an active stopper consisting of a stack of Si detectors. The nuclei were produced as fission fragments from a beam of 238U at a bombarding energy of 345 MeV/nucleon impinging on a Be target and selected using the BigRIPS separator. Half-lives and β-delayed neutron emission probabilities have been extracted for these decays, together with first experimental information on excited states populated in 69,70Fe. The data indicate a continuously increasing deformation for Fe isotopes up to A=70. This is interpreted, as for Cr isotopes, in terms of the interplay between the quadrupole correlations of the ν1d5/2 and ν0g9/2 orbitals and the monopole component of the π0f7/2–ν0f5/2 interaction.

  10. 28 CFR 68.42 - In camera and protective orders.

    Science.gov (United States)

    2010-07-01

    ... UNLAWFUL EMPLOYMENT OF ALIENS, UNFAIR IMMIGRATION-RELATED EMPLOYMENT PRACTICES, AND DOCUMENT FRAUD § 68.42... an opportunity for arrangements to permit a party or a representative to have access to such matter...

  11. 28 CFR 68.45 - Designation of parts of documents.

    Science.gov (United States)

    2010-07-01

    ... UNLAWFUL EMPLOYMENT OF ALIENS, UNFAIR IMMIGRATION-RELATED EMPLOYMENT PRACTICES, AND DOCUMENT FRAUD § 68.45... afforded an opportunity to examine the entire document and to offer in evidence in like manner other...

  12. Gallium‐68 DOTATATE Production with Automated PET Radiopharmaceutical Synthesis System: A Three Year Experience

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2014-10-01

    Full Text Available Objective(s: Gallium‐68 (Ga‐68 is an ideal research and hospital‐based PET radioisotope. Currently, the main form of Ga‐68 radiopharmaceutical that is being synthesised in‐house is Ga‐68 conjugated with DOTA based derivatives. The development of automated synthesis systems has increased the reliability, reproducibility and safety of radiopharmaceutical productions. Here we report on our three year, 500 syntheses experience with an automated system for Ga‐68 DOTATATE. Methods: The automated synthesis system we use is divided into three parts of a servomotor modules, b single use sterile synthesis cassettes and, c a computerized system that runs the modules. An audit trail is produced by the system as a requirement for GMP production. The required reagents and chemicals are made in‐. The Germanium breakthrough is determined on a weekly basis. Production yields for each synthesis are calculated to monitor the performance and efficiency of the synthesis. The quality of the final product is assessed after each synthesis by ITLC‐SG and HPLC methods. Results: A total of 500 Ga‐68 DOTATATE syntheses (>800 patient doses were performed between March 2011 and February 2014. The average generator yield was 81.3±0.2% for 2011, 76.7±0.4% for 2012 and 75.0±0.3% for 2013. Ga‐68 DOTATATE yields for 2011, 2012, and 2013 were 81.8±0.4%, 82.2±0.4% and 87.9±0.4%, respectively. These exceed the manufacturer’s expected value of approximately 70%. Germanium breakthrough averaged 8.6×10‐6% of total activity which is well below the recommended level of 0.001%. The average ITLC‐measured radiochemical purity was above 98.5% and the average HPLC‐measured radiochemical purity was above 99.5%. Although there were some system failures during synthesis, there were only eight occasions where the patient scans needed to be rescheduled. Conclusion: In our experience the automated synthesis system performs reliably with a relatively low incident

  13. Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist {sup 68}Ga-RM2: Preliminary results in patients with negative or inconclusive [{sup 18}F]Fluoroethylcholine-PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Wieser, Gesche; Bartholomae, Mark [University of Freiburg, Department of Nuclear Medicine, Medical Center -Faculty of Medicine, Freiburg (Germany); Popp, Ilinca; Grosu, Anca-Ligia [University of Freiburg, Department of Radiation Oncology, Medical Center - Faculty of Medicine, Freiburg (Germany); Christian Rischke, H. [University of Freiburg, Department of Nuclear Medicine, Medical Center -Faculty of Medicine, Freiburg (Germany); University of Freiburg, Department of Radiation Oncology, Medical Center - Faculty of Medicine, Freiburg (Germany); Drendel, Vanessa [University of Freiburg, Institute for Pathology, Faculty of Medicine, Freiburg (Germany); Weber, Wolfgang A. [Memorial Sloan Kettering Cancer Center, Molecular Imaging and Therapy Service, New York, NY (United States); Mansi, Rosalba [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Wetterauer, Ulrich; Schultze-Seemann, Wolfgang; Jilg, Cordula Annette [University of Freiburg, Department of Urology, Medical Center -Faculty of Medicine, Freiburg (Germany); Meyer, Philipp T. [University of Freiburg, Department of Nuclear Medicine, Medical Center -Faculty of Medicine, Freiburg (Germany); Partner Site Freiburg, German Cancer Consortium (DKTK), Freiburg (Germany)

    2017-08-15

    [{sup 18}F]fluoroethylcholine ({sup 18}FECH) has been shown to be a valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT is a promising technique for staging and restaging of PCa. We explore the value of GRPr-PET using the {sup 68}Ga-labeled GRPr antagonist RM2 in a selected population of patients with biochemically recurrent PCa and a negative/inconclusive {sup 18}FECH-PET/CT. In this retrospective study 16 men with biochemical PCa relapse and negative (n = 14) or inconclusive (n = 2) {sup 18}FECH-PET/CT underwent whole-body {sup 68}Ga-RM2-PET/CT. Mean time from {sup 18}FECH-PET/CT to {sup 68}Ga-RM2-PET/CT was 6.1 ± 6.8 months. Primary therapies in these patients were radical prostatectomy (n = 13; 81.3%) or radiotherapy (n = 3; 18.7%). 14/16 patients (87.5%) had already undergone salvage therapies because of biochemical relapse prior to {sup 68}Ga-RM2-PET/CT imaging. Mean ± SD PSA at {sup 68}Ga-RM2-PET/CT was 19.4 ± 53.5 ng/ml (range 1.06-226.4 ng/ml). {sup 68}Ga-RM2-PET/CT showed at least one region with focal pathological uptake in 10/16 patients (62.5%), being suggestive of local relapse (n = 4), lymph node metastases (LNM; n = 4), bone metastases (n = 1) and lung metastasis with hilar LNM (n = 1). Seven of ten positive {sup 68}Ga-RM2 scans were positively confirmed by surgical resection and histology of the lesions (n = 2), by response to site-directed therapies (n = 2) or by further imaging (n = 3). Patients with a positive {sup 68}Ga-RM2-scan showed a significantly higher median PSA (6.8 ng/ml, IQR 10.2 ng/ml) value than those with a negative scan (1.5 ng/ml, IQR 3.1 ng/ml; p = 0.016). Gleason scores or concomitant antihormonal therapy had no apparent impact on the detection of recurrent disease. Even in this highly selected population of patients with known biochemical

  14. Integration of replication-defective R68.45-like plasmids into the Pseudomonas aeruginosa chromosome.

    Science.gov (United States)

    Reimmann, C; Rella, M; Haas, D

    1988-06-01

    R68.45 and other similar broad-host-range (IncP) plasmids carrying a tandem repeat of the 2.1 kb insertion element IS21 mobilize the chromosome of many different Gram-negative bacteria. To analyse the structure of R68.45-chromosome cointegrates, whose involvement in the mobilization process had been postulated previously, we selected for the stable integration of R68.45-like plasmids into the Pseudomonas aeruginosa chromosome. Two plasmids were chosen: pME28, a transfer-deficient, mobilizable RP1 derivative with an inactive replication control (trfA) gene, and pME487, an R68.45 derivative with a trfA(ts) mutation causing temperature-sensitive replication. Chromosomally integrated pME28 and pME487 were found to be flanked by single IS21 elements. This structure is in agreement with a 'cut-and-paste' mode of R68.45 transposition. pME28 and pME487 showed a low specificity of insertion but rarely (less than 0.1%) induced auxotrophic mutations. Hfr (high-frequency-of-recombination) donors of P. aeruginosa could be obtained by chromosomal integration of pME487 or pME28; in the latter case, the transfer functions lacking from pME28 had to be provided in trans on an autonomous plasmid. Hfr donors gave higher conjugational linkage and transferred longer stretches of the P. aeruginosa chromosome than did R68.45 donors. This suggests that the integration of R68.45 into the donor chromosome is short-lived in P. aeruginosa.

  15. 28 CFR 68.50 - Receipt of documents after hearing.

    Science.gov (United States)

    2010-07-01

    ... UNLAWFUL EMPLOYMENT OF ALIENS, UNFAIR IMMIGRATION-RELATED EMPLOYMENT PRACTICES, AND DOCUMENT FRAUD § 68.50... opportunity to comment thereon. Copies shall be received not later than twenty (20) days after the close of...

  16. 40 CFR 68.175 - Prevention program/Program 3.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.175 Prevention program/Program 3. (a) For each Program 3 process, the owner or operator shall provide the information indicated in paragraphs (b) through (p) of this section. If the same information applies to more than one covered process...

  17. Susceptibilities of enterovirus D68, enterovirus 71, and rhinovirus 87 strains to various antiviral compounds.

    Science.gov (United States)

    Smee, Donald F; Evans, W Joseph; Nicolaou, K C; Tarbet, E Bart; Day, Craig W

    2016-07-01

    Compounds were evaluated for antiviral activity in rhabdomyosarcoma (RD) cells against a recent 2014 clinical isolate of enterovirus D68 (EV-D68), a 1962 strain of EV-68D, rhinovirus 87 (RV-87, serologically the same as EV-D68), and enterovirus 71 (EV-71). Test substances included known-active antipicornavirus agents (enviroxime, guanidine HCl, pirodavir, pleconaril, and rupintrivir), nucleobase/nucleoside analogs (3-deazaguanine and ribavirin), and three novel epidithiodiketopiperazines (KCN-2,2'-epi-19, KCN-19, and KCN-21). Of these, rupintrivir was the most potent, with 50% inhibition of viral cytopathic effect (EC50) and 90% inhibition (EC90) of virus yield at 0.0022-0.0053 μM against EV-D68. Enviroxime, pleconaril and the KCN compounds showed efficacy at 0.01-0.3 μM; 3-deazaguanine and pirodavir inhibited EV-D68 at 7-13 μM, and guanidine HCl and ribavirin were inhibitory at 80-135 μM. Pirodavir was active against EV-71 (EC50 of 0.78 μM) but not against RV-87 or EV-D68, and all other compounds were less effective against EV-71 than against RV-87 and EV-D68. The most promising compound inhibiting both virus infections at low concentrations was rupintrivir. Antiviral activity was confirmed for the ten compounds in virus yield reduction (VYR) assays in RD cells, and for enviroxime, guanidine HCl, and pirodavir by cytopathic effect (CPE) assays in A549, HeLa-Ohio-1, and RD cells. These studies may serve as a basis for further pre-clinical discovery of anti-enterovirus inhibitors. Furthermore, the antiviral profiles and growth characteristics observed herein support the assertion that EV-D68 should be classified together with RV-87. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Potential impact of {sup 68}Ga-DOTATOC PET/CT on stereotactic radiotherapy planning of meningiomas

    Energy Technology Data Exchange (ETDEWEB)

    Nyuyki, Fonyuy; Plotkin, Michail; Michel, Roger; Steffen, Ingo; Fahdt, Daniel; Brenner, Winfried [Charite-Universitaetsmedizin Berlin, Department for Nuclear Medicine, Berlin (Germany); Graf, Reinhold [Charite-Universitaetsmedizin Berlin, Department for Radiation Therapy, Campus Virchow, Berlin (Germany); Denecke, Timm [Charite-Universitaetsmedizin Berlin, Department for Radiology, Campus Virchow, Berlin (Germany); Geworski, Lilli [Charite-Universitaetsmedizin Berlin, Department for Nuclear Medicine, Berlin (Germany); Medizinische Hochschule Hannover, Department for Radiation Safety and Medical Physics, Hannover (Germany); Wurm, Reinhard [Charite-Universitaetsmedizin Berlin, Department for Radiation Therapy, Campus Virchow, Berlin (Germany); Klinikum Frankfurt (Oder), Department for Radiation Therapy and Radiooncology, Frankfurt (Germany)

    2010-02-15

    Since meningiomas show a high expression of somatostatin receptor subtype 2, PET with {sup 68}Ga-DOTATOC was proposed as an additional imaging modality beside CT and MRI for planning radiotherapy. We investigated the input of {sup 68}Ga-DOTATOC-PET/CT on the definition of the ''gross tumour volume'' (GTV) in meningiomas, in order to assess the potential value of this method. Prior to radiotherapy, 42 patients with meningiomas (26 f, 16 m, mean age 55) underwent MRI and {sup 68}Ga-DOTATOC-PET/CT examinations. History: operated n = 24, radiotherapy n = 1, operation and radiotherapy n = 8, no treatment n = 9. PET/CT and MRI data were co-registered using a BrainLAB workstation. For comparison, the GTV was defined first under consideration of CT and MRI data, then using PET data. 3/42 patients were excluded from the analysis (two with negative PET results, one with an extensive tumour, not precisely delineable by MRI or PET/CT). The average GTV{sub CT/MRI} was 22({+-}19)cm{sup 3}; GTV{sub PET} was 23({+-}20)cm{sup 3}. Additional GTV, obtained as a result of PET was 9({+-}10)cm{sup 3} and was observed in patients with osseous infiltration. In some pre-treated patients there were intratumoural areas (as identified in CT/MRI) without SR-expression (7({+-}11)cm{sup 3}). Common GTV as obtained by both CT/MRI and PET was 15({+-}14)cm{sup 3}. The mean bi-directional difference between the GTV{sub CT/MRI} and GTV{sub PET} accounted to 16({+-}15)cm{sup 3} (93%, p < 0.001). In a subgroup of seven patients with multiple meningiomas, PET showed a total of 19 lesions; nine of them were not recognizable by CT or MRI. {sup 68}Ga-DOTATOC-PET enables delineation of SR-positive meningiomas and delivers additional information to both CT and MRI regarding the planning of stereotactic radiotherapy. The acquisition on a PET/CT scanner helps to estimate the relation of PET findings to anatomical structures and is especially useful for detection of osseous infiltration

  19. Dipole polarizability and neutron skin in {sup 68}Ni

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, Dominic [GSI Darmstadt (Germany); Univ. Mainz (Germany); NSCL, MSU (United States); Aumann, Thomas [TU Darmstadt (Germany); Boretzky, Konstanze [GSI Darmstadt (Germany); Collaboration: R3B-Collaboration

    2014-07-01

    The symmetry energy term E{sub sym} of the nuclear equation-of-state describes fundamental phenomena both in nuclear physics and in astrophysics. The electric dipole (E1) response of nuclei as a function of the isospin asymmetry is driven by E{sub sym} and in particular by its density dependence. Studies of the Pygmy Dipole Resonance (PDR) in exotic nuclei have been used to constrain E{sub sym} or the neutron skin thickness ΔR{sub n,p}. The electric dipole polarizability α{sub D}, being very sensitive to the low-lying E1 strength, is correlated to ΔR{sub n,p} in a robust and only moderately less model-dependent manner [PRC 81, 051303 (2010)]. Recently, for the stable nucleus, 208Pb the neutron skin thickness was extracted from the measured αD. Here, a first experimental determination of α{sub D} in an unstable nucleus and the derivation of its ΔR{sub n,p} will be reported. Coulomb excitation in inverse kinematics at the R3B-LAND setup at GSI allows for the investigation of the dipole strength distribution in the neutron-rich {sup 68}Ni covering the pygmy (PDR) and giant dipole resonance (GDR). The E1 strength distribution in the neutron-rich {sup 68}Ni covering the pygmy (PDR) and giant dipole resonance (GDR) s investigated using the R3B-LAND setup at GSI. From the E1 strength distribution in {sup 68}Ni measured using the R3B-LAND setup at GSI, the resonance parameters for the observed PDR at 9.55(17) MeV and the giant dipole resonance at 17.1(2) MeV are determined. In combination with results from Wieland et al. [PRL 102, 092502 (2009)] an unexpectedly large direct photon-decay branching ratio of 7(2) is observed for the PDR. The measured α{sub D} of 3.40(23) fm{sup 3} is compared to relativistic RPA calculations yielding ΔR{sub n,p} of 0.17(2) fm for {sup 68}Ni.

  20. 68Ga-DOTA0-Tyr3-octreotide positron emission tomography in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Schartinger, Volker H.; Dudas, Jozsef; Url, Christoph; Riechelmann, Herbert; Reinold, Susanne; Virgolini, Irene J.; Kroiss, Alexander; Uprimny, Christian

    2015-01-01

    PET/CT with 68 Ga-labelled [DOTA 0 ,Tyr 3 ]-octreotide ( 68 Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased 68 Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for 68 Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios. Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases. 68 Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC. (orig.)

  1. (68)Ga-DOTA (0)-Tyr (3)-octreotide positron emission tomography in nasopharyngeal carcinoma.

    Science.gov (United States)

    Schartinger, Volker H; Dudás, József; Url, Christoph; Reinold, Susanne; Virgolini, Irene J; Kroiss, Alexander; Riechelmann, Herbert; Uprimny, Christian

    2015-01-01

    PET/CT with (68)Ga-labelled [DOTA(0),Tyr(3)]-octreotide ((68)Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased (68)Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for (68)Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios. Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases. (68)Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC.

  2. A case of positive 68Ga-DOTATOC-PET/CT pancreatic heterotopia mimicking an intestinal neuroendocrine tumor.

    Science.gov (United States)

    Zilli, Alessandra; Fanetti, Ilaria; Conte, Dario; Massironi, Sara

    Gallium-68 DOTA-peptide positron emission tomography/computed tomography ( 68 Ga-PET/CT) has emerged as a promising tool for the diagnosis and staging of gastro-entero-pancreatic neoplasms, thanks to its high sensitivity and specificity. Heterotopic pancreas, which is relatively rare, has never been reported as a possible cause of false positives of 68 Ga-PET/CT. We report on the first case of a heterotopic pancreas showing pathological uptake at 68 Ga-PET/CT, thus mimicking an intestinal neuroendocrine tumor. The present case suggests that heterotopic pancreas should be included among the possible causes of false positives at 68 Ga PET. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Geometry task & drill sheets : grades 6-8

    CERN Document Server

    Rosenberg, Mary

    2011-01-01

    For grades 6-8, our Common Core State Standards-based combined resource meets the geometry concepts addressed by the NCTM standards and encourages the students to review the concepts in unique ways. The task sheets introduce the mathematical concepts to the students around a central problem taken from real-life experiences, while the drill sheets provide warm-up and timed practice questions for the students to strengthen their procedural proficiency skills.

  4. 68Ga-autoclabeling of DOTA-TATE and DOTA-NOC

    DEFF Research Database (Denmark)

    Blom, Elisabeth; Koziorowski, Jacek

    2012-01-01

    A new method combining (68)Ga-labeling and steam sterilization, here called autoclabeling, has been evaluated for two somatostatin receptor binding tracers used for positron emission tomography (PET) imaging of neuroendocrine tumors; DOTA-TATE and -NOC....

  5. Spatial and temporal activity of the foxtail millet (Setaria italica) seed-specific promoter pF128.

    Science.gov (United States)

    Pan, Yanlin; Ma, Xin; Liang, Hanwen; Zhao, Qian; Zhu, Dengyun; Yu, Jingjuan

    2015-01-01

    pF128 drives GUS specifically expressed in transgenic seeds of foxtail millet and Zea mays with higher activity than the constitutive CaMV35S promoter and the maize seed-specific 19Z promoter. Foxtail millet (Setaria italica), a member of the Poaceae family, is an important food and fodder crop in arid regions. Foxtail millet is an excellent C4 crop model owing to its small genome (~490 Mb), self-pollination and availability of a complete genome sequence. F128 was isolated from a cDNA library of foxtail millet immature seeds. Real-time PCR analysis revealed that F128 mRNA was specifically expressed in immature and mature seeds. The highest F128 mRNA level was observed 5 days after pollination and gradually decreased as the seed matured. Sequence analysis suggested that the protein encoded by F128 is likely a protease inhibitor/seed storage protein/lipid-transfer protein. The 1,053 bp 5' flanking sequence of F128 (pF128) was isolated and fused to the GUS reporter gene. The corresponding vector was then transformed into Arabidopsis thaliana, foxtail millet and Zea mays. GUS analysis revealed that pF128 drove GUS expression efficiently and specifically in the seeds of transgenic Arabidopsis, foxtail millet and Zea mays. GUS activity was also detected in Arabidopsis cotyledons. Activity of pF128 was higher than that observed for the constitutive CaMV35S promoter and the maize seed-specific 19 Zein (19Z) promoter. These results indicate that pF128 is a seed-specific promoter. Its application is expected to be of considerable value in plant genetic engineering.

  6. {sup 68}Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    Energy Technology Data Exchange (ETDEWEB)

    Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Iveson, Peter; Wilson, Ian [Medical Diagnostics, GE Healthcare Biosciences, London (United Kingdom); Karlsen, Hege; Cuthbertson, Alan [GE Healthcare MDx Research, Oslo (Norway); Laine, Jukka [Turku University Hospital, Department of Pathology, Turku (Finland); Leppaenen, Pia; Ylae-Herttula, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland); Roivainen, Anne [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Turku Centre for Disease Modelling, Turku (Finland)

    2009-12-15

    Increased expression of {alpha}v{beta}3/{alpha}v{beta}5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel {sup 68}Ga-DOTA-RGD peptide binds with high affinity to {alpha}v{beta}3/{alpha}v{beta}5 integrin. The aim of this study was to investigate the uptake of the {sup 68}Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered {sup 68}Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR{sup -/-}ApoB{sup 100/100} atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced {sup 68}Ga. The tracer had reasonably good specific radioactivity (8.7 {+-} 1.1 GBq/{mu}mol) and was quite stable in vivo. According to ex vivo biodistribution results, {sup 68}Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of {sup 68}Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio {+-} SD 1.4 {+-} 0.1, p = 0.0004). We observed that {sup 68}Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  7. Data analysis & probability drill sheets : grades 6-8

    CERN Document Server

    Forest, Chris

    2011-01-01

    For grades 6-8, our Common Core State Standards-based resource meets the data analysis & probability concepts addressed by the NCTM standards and encourages your students to review the concepts in unique ways. Each drill sheet contains warm-up and timed drill activities for the student to practice data analysis & probability concepts.

  8. 40 CFR 68.170 - Prevention program/Program 2.

    Science.gov (United States)

    2010-07-01

    ... (CONTINUED) CHEMICAL ACCIDENT PREVENTION PROVISIONS Risk Management Plan § 68.170 Prevention program/Program 2. (a) For each Program 2 process, the owner or operator shall provide in the RMP the information... the process. (c) The name(s) of the chemical(s) covered. (d) The date of the most recent review or...

  9. 68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

    Science.gov (United States)

    Liu, Fei; Zhu, Hua; Yu, Jiangyuan; Han, Xuedi; Xie, Qinghua; Liu, Teli; Xia, Chuanqin; Li, Nan; Yang, Zhi

    2017-06-01

    Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

  10. European surveillance for enterovirus D68 during the emerging North-American outbreak in 2014

    DEFF Research Database (Denmark)

    Poelman, Randy; Schuffenecker, Isabelle; Van Leer-Buter, Coretta

    2015-01-01

    BACKGROUND: In August and September 2014, unexpected clusters of enterovirus-D68 (EV-D68) infections associated with severe respiratory disease emerged from North-America. In September, the European Centre for Disease Prevention and Control (ECDC) asked European countries to strengthen respiratory...... sample screening for enterovirus detection and typing in cases with severe respiratory presentations. OBJECTIVES: To provide a detailed picture of EV-D68 epidemiology in Europe by conducting a retrospective and prospective laboratory analysis of clinical specimens. STUDY DESIGN: An initiative supported...

  11. Cyclotron production of 68Ge with a Ga2O target

    International Nuclear Information System (INIS)

    Naidoo, C.; Walt, T.N. van der; Raubenheimer, H.G.

    2002-01-01

    Systematic information of exchange behavior of Ge(IV) and Ga(III) in varying oxalic acid (0.05M and 0.25M) and sulphuric acid (0.005M-2M range) mixtures is presented. These findings were used to develop a separation involving 68 Ge from a Ga 2 O target material. A method based on acid dissolution of the target and chromatography on an anion exchange resin (Bio-Rad R AG1-X8) was developed. The separated 68 Ge has high radionuclidic purity and an acceptable chemical purity. (author)

  12. Molecular imaging of neuroendocrine tumors using {sup 68}Ga-labeled peptides (Somatostatin receptor PET/CT); Molekulare Bildgebung neuroendokriner Tumoren mit {sup 68}Ga-markierten Peptiden (Somatostatinrezeptor-PET/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Baum, R.P.; Prasad, V. [Zentralklinik Bad Berka GmbH (Germany). Klinik fuer Nuklearmedizin/PET-Zentrum; Hoersch, D. [Zentralklinik Bad Berka GmbH (Germany). Klinik fuer Innere Medizin, Gastroenterologie, Onkologie, Endokrionologie

    2009-06-15

    Receptor PET/CT using {sup 68}Ga-labeled somatostatin analogues (DOTA-NOC, DOTA-TOC or DOTA-TATE) enables the highly sensitive molecular imaging of neuroendocrine tumors (NETs) based on the expression of somatostatin receptors and even the detection of receptor subtypes. Our experience after more than 3000 studies shows that receptor PET/CT has a significantly higher tumor detection rate than conventional scintigraphy (even in SPECT/CT technique), and that tumor lesions can be very accurately localized. By calculating standardized uptake values (SUV) - which are reproducible and investigator-independent - patients can be selected for peptide receptor radiotherapy and also the course after therapy can be controlled. Receptor-PET/CT is the most sensitive imaging modality for the detection of unknown primary tumors (CUP syndrome), which is especially true for the detection of neuroendocrine tumors of the pancreas and small bowel; whole-body staging (''one stop shop'') as well as restaging and selection of patients for peptide receptor radiotherapy can be performed using a patient-friendly procedure (examination finished within one hour) exposing the patient to less radiation than whole-body CT scanning. The {sup 68}Ge/{sup 68}Ga generator has proved very reliable over the years - even in a hospital environment. The effective costs for {sup 68}Ga labeled somatostatin analogues might be less than for scintigraphic agents, provided a certain number of studies per year are performed. The development of new tumor-specific peptides as well as of other DOTA- or NOTA-coupled radiopharmaceuticals opens a new avenue into the future: finally, the {sup 68}Ga generator could play a similar important role for PET/CT as did the {sup 99m}Tc-Generator for conventional gamma camera imaging over the last decades. (orig.)

  13. Gallium-68-DOTA-albumin as a PET blood-pool marker: experimental evaluation in vivo

    International Nuclear Information System (INIS)

    Hoffend, Johannes; Mier, Walter; Schuhmacher, Jochen; Schmidt, Kerstin; Dimitrakopoulou-Strauss, Antonia; Strauss, Ludwig G.; Eisenhut, Michael; Kinscherf, Ralf; Haberkorn, Uwe

    2005-01-01

    Investigations into tumor angiogenesis and antiangiogenic treatment have renewed interest in tumor perfusion. To image tumor blood-pool by PET, suitable tracers are not generally available. In this experimental study, we characterized a 68 Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) conjugate of rat serum albumin ( 68 Ga-DOTA-RSA) in vivo using a generator-produced isotope. Biodistribution was determined in ACI rats after intravenous administration of 3-6 MBq of 68 Ga-DOTA-RSA. Three ACI rats were imaged over 1 h by dynamic PET after intravenous administration of 15-25 MBq of 68 Ga-DOTA-RSA while the blood-pool activity was recorded simultaneously in a closed extracorporeal loop (ECL) between the carotid artery and the jugular vein. Time-activity curves (TACs) were obtained from volume of interest (VOI) analysis and from the ECL data. Stability and metabolites in plasma and urine were analyzed by size exclusion HPLC (SE-HPLC) 1 h after intravenous injection of 67 Ga-DOTA-RSA. Blood radioactivity decreased by 10% and 18% from 10 to 60 min p.i. by biodistribution and PET or ECL, respectively. Tissue sampling between 10 and 60 min p.i. showed slight increases in the uptake of spleen, myocardium, kidney and skeletal muscle while hepatic accretion remained unchanged. Total urinary excretion after 60 min amounted to 9% of the injected dose. HPLC demonstrated a single urinary metabolite corresponding in size to gallium-labeled DOTA. 68 Ga-DOTA-RSA is a blood-pool tracer whose physical and biological half-life is well suited for PET. Our findings support clinical imaging using 68 Ga-DOTA-labeled human serum albumin (HSA). The generator-produced label makes 68 Ga-DOTA-labeled albumin continuously available even to centers lacking an in-house cyclotron

  14. Exploring the radiosynthesis and in vitro characteristics of [68 Ga]Ga-DOTA-Siglec-9.

    Science.gov (United States)

    Jensen, Svend B; Käkelä, Meeri; Jødal, Lars; Moisio, Olli; Alstrup, Aage K O; Jalkanen, Sirpa; Roivainen, Anne

    2017-07-01

    Vascular adhesion protein 1 is a leukocyte homing-associated glycoprotein, which upon inflammation rapidly translocates from intracellular sources to the endothelial cell surface. It has been discovered that the cyclic peptide residues 283-297 of sialic acid-binding IgG-like lectin 9 (Siglec-9) "CARLSLSWRGLTLCPSK" bind to vascular adhesion protein 1 and hence makes the radioactive analogues of this compound ([ 68 Ga]Ga-DOTA-Siglec-9) interesting as a noninvasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [ 68 Ga]Ga-DOTA-Siglec-9 are presented and compared with previously published methods. A simple, robust radiosynthesis of [ 68 Ga]Ga-DOTA-Siglec-9 with a yield of 62% (non decay-corrected) was identified, and it had a radiochemical purity >98% and a specific radioactivity of 35 MBq/nmol. Furthermore, the protein binding and stability of [ 68 Ga]Ga-DOTA-Siglec-9 were analyzed in vitro in mouse, rat, rabbit, pig, and human plasma and compared with in vivo pig results. The plasma in vitro protein binding of [ 68 Ga]Ga-DOTA-Siglec-9 was the lowest in the pig followed by rabbit, human, rat, and mouse. It was considerably higher in the in vivo pig experiments. The in vivo stability in pigs was lower than the in vitro stability. Despite considerable species differences, the observed characteristics of [ 68 Ga]Ga-DOTA-Siglec-9 are suitable as a positron emission tomography tracer. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Study of the 16O+64,66,68Zn reactions

    International Nuclear Information System (INIS)

    Tenreiro, Claudio; Acquadro, J.C.; Liguori Neto, R.; Freitas, P.A.B.

    1989-01-01

    Excitation functions for the fusion of 16 O with 64,66 Zn in the energy range of 0.8-1.7 times the Coulomb barrier were measured. Reduced fusion excitation functions, scaled to remove the geometrical effects shown and isotopic effect in the excitation functions for the sub-barrier energies. Furthermore, angular distributions for the elastic scattering were measured for the 16 O+ 64,68 Zn systems in the energy range from 43 MeV to 56 MeV for the 16 O. An anomalous back-angle elastic scattering was observed for the 16 O+ 64 Zn system and for energies around the Coulomb barrier. (Author) [es

  16. Expression of the 68-kilodalton neurofilament gene in aluminum intoxication

    International Nuclear Information System (INIS)

    Muma, N.A.; Troncoso, J.C.; Hoffman, P.N.; Price, D.L.

    1986-01-01

    Intrathecal administration of aluminum salts induces accumulation of neurofilaments (NFs) in cell bodies and proximal axons of rabbit spinal motor neurons. Mechanisms leading to this pathological change are not well understood. Although impairments of NF transport have been demonstrated in this model, the hypothesis that NF accumulations are the result of an increase in NF synthesis needs to be explored. In rabbits, a large percentage of neurons develop accumulations of NFs following injections of aluminum lactate directly into the cisterna magna or into a reservoir placed in the lateral ventricle. To study levels of mRNA encoding cytoskeletal proteins, spinal cord RNA was extracted, separated on a denaturing agarose gel, transferred to nitrocellulose paper, and hybridized to [ 32 P]-labeled cDNA clones encoding the mouse 68-kilodalton (kd) NF subunit and tubulin. Examining a constant amount of RNA, the radioactivity of labeled mRNA bands for the 68-kd NF subunit and for tubulin was decreased in spinal cords of aluminum-treated rabbits. These preliminary results will be followed up by in situ hybridization to determine levels of mRNA for tubulin and 68-kd NF subunit in affected and in normal spinal neurons. In conclusion, administration of aluminum decreased mRNA for the 608-kd NF protein in spinal neurons

  17. 27 CFR 26.68 - Bond, Form 2898-Beer.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Bond, Form 2898-Beer. 26... Liquors and Articles in Puerto Rico Bonds § 26.68 Bond, Form 2898—Beer. Where a brewer intends to withdraw, for purpose of shipment to the United States, beer of Puerto Rican manufacture from bonded storage in...

  18. 68Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room-Temperature, 1-Step Kit-Based Radiolabeling.

    Science.gov (United States)

    Young, Jennifer D; Abbate, Vincenzo; Imberti, Cinzia; Meszaros, Levente K; Ma, Michelle T; Terry, Samantha Y A; Hider, Robert C; Mullen, Greg E; Blower, Philip J

    2017-08-01

    -HBED-CC-PSMA except for reduced uptake in the spleen. Conclusion: 68 Ga-THP-PSMA has equivalent imaging properties but greatly simplified radiolabeling compared with other 68 Ga-PSMA conjugates. THP offers the prospect of rapid, simple, 1-step, room-temperature syringe-and-vial radiolabeling of 68 Ga radiopharmaceuticals. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  19. Epidemic 2014 enterovirus D68 cross-reacts with human rhinovirus on a respiratory molecular diagnostic platform.

    Science.gov (United States)

    McAllister, Shane C; Schleiss, Mark R; Arbefeville, Sophie; Steiner, Marie E; Hanson, Ryan S; Pollock, Catherine; Ferrieri, Patricia

    2015-01-01

    Enterovirus D68 (EV-D68) is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of "low-positive" results for human rhinovirus (HRV) detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these "low-positive" RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5' untranslated region (5'-UTR) of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3%) were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA) compared to HRV (129.7 nA). Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.

  20. Quantitative Evaluation of Macrophage Expression Using CD68 in ...

    African Journals Online (AJOL)

    Submucous fibrosis is an insidious, chronic disease affecting any part of ... study suggest that CD68 plays a vital role in the pathogenesis of OSMF and can be regarded as a useful .... in lysosomes and to a lesser extent on surface membranes,.

  1. 21 CFR 211.68 - Automatic, mechanical, and electronic equipment.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Equipment § 211.68 Automatic, mechanical, and electronic equipment. (a) Automatic, mechanical, or electronic... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Automatic, mechanical, and electronic equipment...

  2. Synthesis of generator based 68Ga-labeled biphosphonates by an automated module: Indian experience

    International Nuclear Information System (INIS)

    Kumar, Rajeev; Sharma, P.; Medhavi, S.; Pandey, A.K.; Tripathy, M.; Kumar, Rakesh; Bal, C.; Malhotra, A.; Meckel, M.; Rosch, F.

    2015-01-01

    Full text of publication follows. Aim of the study: to share our experience regarding the synthesis and quality control of generator based 68 Ga-NOTA biphosphonates for bone PET imaging using an automated module. Material and methods: the eluate of a 68 Ge/ 68 Ga generator was passed through a cation exchange resin (strata X-C). 68 Ga was adsorbed on the cartridge and rest of the solvent was passed into the waste. A solution conventionally called N2 (mixture of Acetone, metal free water and HCl), was used to release concentrated and purified 68 Ga from the strata X-C to release it to the 10 ml reaction vial. The reaction vial contained 20 μg of the precursor NOTA-biphosphonate dissolved in 1.5 ml 0.25 M sodium acetate at pH of 4. Now the reaction vessel was heated at a temperature of 95 Celsius degrees for 15 minutes. After cooling the solution was diluted by adding 3 ml metal free water. The product was transferred to product vial through 0.22 μm sterile filter. All the synthesis steps were carried out in automated module (Modular lab, Eckert and Ziegler, Germany). The total synthesis time was 18 minutes. During the whole procedure radiation level was monitored around the Hot cell at all four side walls at every 3 minutes. Routine quality control test was performed with the help of Radio-TLC, Ph paper and dose calibrator respectively (For its radiochemical binding, Rf, Ph value and its half life). Results: 68 Ga-NOTA-biphosphonate yield ranged between 333 to 370 MBq from five months 1850 MBq old generator. 68 Ga-NOTA-biphosphonate conjugate was prepared with very high radio chemical yield and purity (>99 %). The product was stable up to four hours at room temperature (checked by Radio-TLC). During synthesis the radiation level around the hot cell was near to background level (∼ 3 μSv/hr). Summary: generator based PET radiotracer 68 Ga-NOTA-biphosphonate can be synthesized with high radiochemical purity and good stability, using an automated module. (authors)

  3. Preparation and evaluation of 68Ga-ECC as a PET renal imaging agent

    International Nuclear Information System (INIS)

    Mizaei, Alireza; Jaililan, Amir Reza; Mazidi, Mohammad; Aghanejad, Ayuob; Yousefnia, Hassan; Shabani, Gholamli; Ardaneh, Khosro; Geramifar, Patham; Beiki, Davood

    2015-01-01

    Development of a gallium-68-labeled renal tracer can be a good substitute for Tc-99m, a known SPECT tracer. In this study, effort was made to develop 68 Ga-ethylenecysteamine cysteine ( 68 Ga-ECC). Ga-ECC was prepared using generator-based 68 GaCl3 and ethylenecysteamine cysteine (ECC) at optimized conditions. Stability of the complex was checked in human serum followed by partition coefficient determination of the tracer. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. Ga-ECC was prepared at optimized conditions in 15 min at 90 °C (radiochemical purity ≈97 ± 0.88 % ITLC, >99 % HPLC, specific activity: 210 ± 5 GBq/mM). 68 Ga-ECC was a water-soluble complex based on partition coefficient data (log P; −1.378) and was stable in the presence of human serum for 2 h at 37 °C. The biodistribution of the tracer demonstrated high kidney excretion of the tracer in 10–20 min. The SUV max ratios of the liver to left kidney were 0.38 and 0.39 for 30 and 90 min, respectively, indicating high kidney uptake. Initial biodistribution results showed significant kidney and urinary excretion of the tracer comparable to that of the homologous 99m Tc compound. The complex could be a possible PET kidney imaging agent with a fast imaging time

  4. 47 CFR 68.110 - Compatibility of the public switched telephone network and terminal equipment.

    Science.gov (United States)

    2010-10-01

    ... changes in its communications facilities, equipment, operations or procedures, where such action is... in this part. If such changes can be reasonably expected to render any customer's terminal equipment... network and terminal equipment. 68.110 Section 68.110 Telecommunication FEDERAL COMMUNICATIONS COMMISSION...

  5. Evaluation of 68Ga-DOTATOC PET/MRI for whole-body staging of neuroendocrine tumours in comparison with 68Ga-DOTATOC PET/CT

    International Nuclear Information System (INIS)

    Sawicki, Lino M.; Deuschl, Cornelius; Beiderwellen, Karsten; Forsting, Michael; Umutlu, Lale; Ruhlmann, Verena; Poeppel, Thorsten D.; Bockisch, Andreas; Herrmann, Ken; Heusch, Philipp; Antoch, Gerald; Lahner, Harald; Fuehrer, Dagmar

    2017-01-01

    To compare the diagnostic performance of 68 Ga-DOTATOC PET/MRI and 68 Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET). Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar's chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson's correlation coefficient (r). According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p = 0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p = 0.031). SUVmax was strongly correlated (r = 0.86; p < 0.001) and did not differ significantly (p = 0.35) between the modalities. Overall conspicuity and NET lesion conspicuity were higher on PET/MRI (both p < 0.01). Ga-DOTATOC PET/MRI yielded a higher proportion of correctly rated NET lesions and should be regarded as a valuable alternative to 68 Ga-DOTATOC PET/CT in whole-body staging of NET patients. (orig.)

  6. 32 CFR 516.68 - Program Fraud Civil Remedies Act (PFCRA).

    Science.gov (United States)

    2010-07-01

    ... AUTHORITIES AND PUBLIC RELATIONS LITIGATION Remedies in Procurement Fraud and Corruption § 516.68 Program... the capability of the government to deter and recover losses from false, fictitious or fraudulent...

  7. Optimal time-point for 68Ga-PSMA-11 PET/CT imaging in assessment of prostate cancer: feasibility of sterile cold-kit tracer preparation?

    Science.gov (United States)

    Beheshti, Mohsen; Paymani, Zeinab; Brilhante, Joana; Geinitz, Hans; Gehring, Daniela; Leopoldseder, Thomas; Wouters, Ludovic; Pirich, Christian; Loidl, Wolfgang; Langsteger, Werner

    2018-07-01

    In this prospective study, we evaluated the optimal time-point for 68 Ga-PSMA-11 PET/CT acquisition in the assessment of prostate cancer. We also examined, for the first time the feasibility of tracer production using a PSMA-11 sterile cold-kit in the clinical workflow of PET/CT centres. Fifty prostate cancer patients (25 staging, 25 biochemical recurrence) were enrolled in this study. All patients received an intravenous dose of 2.0 MBq/kg body weight 68 Ga-PSMA-11 prepared using a sterile cold kit (ANMI SA, Liege, Belgium), followed by an early (20 min after injection) semi-whole-body PET/CT scan and a standard-delay (100 min after injection) abdominopelvic PET/CT scan. The detection rates with 68 Ga-PSMA-11 were compared between the two acquisitions. The pattern of physiological background activity and tumour to background ratio were also analysed. The total preparation time was reduced to 5 min using the PSMA-11 sterile cold kit, which improved the final radionuclide activity by about 30% per single 68 Ge/ 68 Ga generator elution. Overall, 158 pathological lesions were analysed in 45 patients (90%) suggestive of malignancy on both (early and standard-delay) 68 Ga-PSMA PET/CT images. There was a significant (p PET/CT imaging seems to provide a detection rate comparable with that of standard-delay imaging. Furthermore, the shorter preparation time using the 68 Ga-PSMA-11 sterile cold kit and promising value of early PET/CT scanning could allow tailoring of imaging protocols which may reduce the costs and improve the time efficiency in PET/CT centres.

  8. 68Ga-DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumors

    International Nuclear Information System (INIS)

    Pettinato, C.; Sarnelli, A.; Di Donna, M.; Civollani, S.; Marengo, M.; Bergamini, C.; Nanni, C.; Montini, G.; Di Pierro, D.; Ferrari, M.

    2008-01-01

    The aim of this work was the evaluation of biodistribution and radiation dosimetry of 68 Ga-DOTANOC in patients affected by neuroendocrine tumors. We enrolled nine patients (six male and three female) affected by different types of neuroendocrine tumors (NETs). Each patient underwent four whole body positron emission tomography (PET) scans, respectively, at 5, 20, 60, and 120 min after the intravenous injection of about 185 MBq of 68 Ga-DOTANOC. Blood and urine samples were taken at different time points post injection: respectively, at about 5, 18, 40, 60, and 120 min for blood and every 40-50 min from injection time up to 4 h for urine. The organs involved in the dosimetric evaluations were liver, heart, spleen, kidneys, lungs, pituitary gland, and urinary bladder. Dosimetric evaluations were done using the OLINDA/EXM 1.0 software. A physiological uptake of 68 Ga-DOTANOC was seen in all patients in the pituitary gland, the spleen, the liver, and the urinary tract (kidneys and urinary bladder). Organs with the highest absorbed doses were kidneys (9.0 E-02±3.2 E-02 mSv/Mq). The mean effective dose equivalent (EDE) was 2.5 E-02±4.6 E-03 mSv/MBq. The excretion of the compound was principally via urine, giving dose to the kidney and the urinary bladder wall. As SSTR2 is the most frequently expressed somatostatin receptor and 68 Ga-DOTANOC has high affinity to it, this compound might play an important role in PET oncology in the future. The dosimetric evaluation carried out by our team demonstrated that 68 Ga-DOTANOC delivers a dose to organs comparable to, and even lower than, analogous diagnostic compounds. (orig.)

  9. The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation.

    Directory of Open Access Journals (Sweden)

    Andrea M Siegel

    2008-04-01

    Full Text Available Murine gammaherpesvirus 68 (MHV68 establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV. EBV encodes an interleukin-10 (IL-10 homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25 and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis

  10. The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation.

    Science.gov (United States)

    Siegel, Andrea M; Herskowitz, Jeremy H; Speck, Samuel H

    2008-04-04

    Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis-identifying a

  11. Synthesis of a Fluorescently Labeled 68Ga-DOTA-TOC Analog for Somatostatin Receptor Targeting.

    Science.gov (United States)

    Ghosh, Sukhen C; Hernandez Vargas, Servando; Rodriguez, Melissa; Kossatz, Susanne; Voss, Julie; Carmon, Kendra S; Reiner, Thomas; Schonbrunn, Agnes; Azhdarinia, Ali

    2017-07-13

    Fluorescently labeled imaging agents can identify surgical margins in real-time to help achieve complete resections and minimize the likelihood of local recurrence. However, photon attenuation limits fluorescence-based imaging to superficial lesions or lesions that are a few millimeters beneath the tissue surface. Contrast agents that are dual-labeled with a radionuclide and fluorescent dye can overcome this limitation and combine quantitative, whole-body nuclear imaging with intraoperative fluorescence imaging. Using a multimodality chelation (MMC) scaffold, IRDye 800CW was conjugated to the clinically used somatostatin analog, 68 Ga-DOTA-TOC, to produce the dual-labeled analog, 68 Ga-MMC(IRDye 800CW)-TOC, with high yield and specific activity. In vitro pharmacological assays demonstrated retention of receptor-targeting properties for the dual-labeled compound with robust internalization that was somatostatin receptor (SSTR) 2-mediated. Biodistribution studies in mice identified the kidneys as the primary excretion route for 68 Ga-MMC(IRDye 800CW)-TOC, along with clearance via the reticuloendothelial system. Higher uptake was observed in most tissues compared to 68 Ga-DOTA-TOC but decreased as a function of time. The combination of excellent specificity for SSTR2-expressing cells and suitable biodistribution indicate potential application of 68 Ga-MMC(IRDye 800CW)-TOC for intraoperative detection of SSTR2-expressing tumors.

  12. Fast and simple one-step preparation of Ga-68 citrate for routine clinical PET

    DEFF Research Database (Denmark)

    Jensen, Svend B.; Nielsen, Karin M.; Mewis, Dennis

    2013-01-01

    The imaging of infectious and inflammatory diseases using gallium-67 (Ga-67) citrate scintigraphy has been a well-established diagnostic tool for decades. In recent times, interest has focused on PET using the short-lived positron emitting radioisotope Ga-68. Ga-68 is not only more readily...

  13. Acute flaccid myelitis associated with enterovirus-D68 infection in an otherwise healthy child

    NARCIS (Netherlands)

    Esposito, Susanna; Chidini, Giovanna; Cinnante, Claudia; Napolitano, Luisa; Giannini, Alberto; Terranova, Leonardo; Niesters, Hubert; Principi, Nicola; Calderini, Edoardo

    2017-01-01

    Background: Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. Case presentation: A previously healthy 4-year-old boy presented with sudden

  14. Formulation of 68Ga BAPEN kit for myocardial positron emission tomography imaging and biodistribution study

    International Nuclear Information System (INIS)

    Yang, Bo Yeun; Jeong, Jae Min; Kim, Young Joo; Choi, Jae Yeon; Lee, Yun-Sang; Lee, Dong Soo

    2010-01-01

    Introduction: Tris(4,6-dimethoxysalicylaldimine)-N,N'-bis(3-aminopropyl) -N,N'-ethylenediamine (BAPEN), a tris(salicylaldimine) derivative, is a heart positron emission tomography (PET) agent when labeled with 68 Ga. However, its labeling requires complicated and time-consuming procedures. In this study, the authors formulated a new BAPEN kit for convenient 68 Ga labeling. Methods: BAPEN (0.25 mg) kits were prepared by dispensing its solution in 1 M sodium acetate buffer (pH 5.5) into sterile vials and lyophilization. The prepared kits were labeled with generator-eluted 68 Ga in 0.1 N HCl. Stability in human serum was tested. Expiration date was determined by accelerated testing according to US Food and Drug Administration guidelines. A Biodistribution study was performed in normal mice after injection via tail vein. Results: The prepared kits achieved radiolabeling efficiencies in excess of 95% and showed a shelf-life of 98 days at 25 deg. C and 64.3 months at 4 deg. C. 68 Ga-BAPEN was found to be stable in human serum at 37 deg. C for at least 1 h. Furthermore, a biodistribution study revealed high heart uptake (10.8% ID/g, 1 h). Conclusions: The authors developed a BAPEN kit for convenient labeling with 68 Ga. The 68 Ga-BAPEN showed high stability and excellent biodistribution results in normal mice, which is required for myocardial PET imaging.

  15. Re-Analysis of Metagenomic Sequences from Acute Flaccidmyelitis Patients Reveals Alternatives to Enterovirus D68 Infection

    Science.gov (United States)

    2015-07-13

    caused in some cases by infection with enterovirus D68. We found that among the patients whose symptoms were previously attributed to enterovirus D68...distribution is unlimited. Re-analysis of metagenomic sequences from acute flaccidmyelitis patients reveals alternatives to enterovirus D68...Street Baltimore, MD 21218 -2685 ABSTRACT Re-analysis of metagenomic sequences from acute flaccidmyelitis patients reveals alternatives to enterovirus

  16. Radiolabeling of DOTA-like conjugated peptides with generator-produced 68Ga and using NaCl-based cationic elution method

    Science.gov (United States)

    Mueller, Dirk; Breeman, Wouter A P; Klette, Ingo; Gottschaldt, Michael; Odparlik, Andreas; Baehre, Manfred; Tworowska, Izabela; Schultz, Michael K

    2017-01-01

    Gallium-68 (68Ga) is a generator-produced radionuclide with a short half-life (t½ = 68 min) that is particularly well suited for molecular imaging by positron emission tomography (PET). Methods have been developed to synthesize 68Ga-labeled imaging agents possessing certain drawbacks, such as longer synthesis time because of a required final purification step, the use of organic solvents or concentrated hydrochloric acid (HCl). In our manuscript, we provide a detailed protocol for the use of an advantageous sodium chloride (NaCl)-based method for radiolabeling of chelator-modified peptides for molecular imaging. By working in a lead-shielded hot-cell system, 68Ga3+ of the generator eluate is trapped on a cation exchanger cartridge (100 mg, ∼8 mm long and 5 mm diameter) and then eluted with acidified 5 M NaCl solution directly into a sodium acetate-buffered solution containing a DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or DOTA-like chelator-modified peptide. The main advantages of this procedure are the high efficiency and the absence of organic solvents. It can be applied to a variety of peptides, which are stable in 1 M NaCl solution at a pH value of 3–4 during reaction. After labeling, neutralization, sterile filtration and quality control (instant thin-layer chromatography (iTLC), HPLC and pH), the radiopharmaceutical can be directly administered to patients, without determination of organic solvents, which reduces the overall synthesis-to-release time. This procedure has been adapted easily to automated synthesis modules, which leads to a rapid preparation of 68Ga radiopharmaceuticals (12–16 min). PMID:27172166

  17. Shape coexistence from lifetime and branching-ratio measurements in 68,70Ni

    Directory of Open Access Journals (Sweden)

    B.P. Crider

    2016-12-01

    Full Text Available Shape coexistence near closed-shell nuclei, whereby states associated with deformed shapes appear at relatively low excitation energy alongside spherical ones, is indicative of the rapid change in structure that can occur with the addition or removal of a few protons or neutrons. Near 68Ni (Z=28, N=40, the identification of shape coexistence hinges on hitherto undetermined transition rates to and from low-energy 0+ states. In 68,70Ni, new lifetimes and branching ratios have been measured. These data enable quantitative descriptions of the 0+ states through the deduced transition rates and serve as sensitive probes for characterizing their nuclear wave functions. The results are compared to, and consistent with, large-scale shell-model calculations which predict shape coexistence. With the firm identification of this phenomenon near 68Ni, shape coexistence is now observed in all currently accessible regions of the nuclear chart with closed proton shells and mid-shell neutrons.

  18. Exploring the radiosynthesis and in vitro characteristics of [68Ga]Ga-DOTA-Siglec-9

    DEFF Research Database (Denmark)

    Jensen, Svend Borup; Käkelä, Meeri; Jødal, Lars

    2017-01-01

    (Siglec-9) "CARLSLSWRGLTLCPSK" bind to VAP-1 and hence makes the radioactive analogues of this compound ([68 Ga]Ga-DOTA-Siglec-9) interesting as a non-invasive visualizing marker of inflammation. Three different approaches to the radiosynthesis of [68 Ga]Ga-DOTA-Siglec-9 are presented and compared...

  19. Ga-68-DOTA-TATE PET/CT for discrimination of tumors of the optic pathway.

    Science.gov (United States)

    Klingenstein, Annemarie; Haug, Alexander R; Miller, Christina; Hintschich, Christoph

    2015-02-01

    Symptomatic tumors of the optic nerve pathway may endanger vision. They are difficult to classify by imaging alone and biopsy may damage visual function. Tumor pathology influences treatment decision and a diagnostic tool with a high sensitivity and specificity would therefore be invaluable. We hypothesized that Ga-68-DOTA-TATE PET/CT may help in discriminating optic nerve tumors as uptake of somatostatin is elevated in meningiomas. Ga-68-DOTA-TATE PET/CT was used to examine 13 patients with ambiguous, symptomatic lesions of the optic pathway for treatment planning. The presence or absence of meningioma was validated by histopathology or supplementary diagnostic work-up. Ga-68-DOTA-TATE PET/CT identified 10 meningiomas (en plaque = 1, optic nerve sheath = 4, sphenoidal = 5) correctly via increased SSTR (somatostatin receptor) expression (mean SUVmax (maximum standardized uptake value) = 14.3 ± 15.4). 3 tumors did not show elevated Ga-68-DOTA-TATE uptake (SUVmax = 2.1 ± 1.0). Subsumizing all clinical-radiological follow-up tools available, these lesions were classified as an intracerebral metastasis of an advanced gastric carcinoma, histologically proven inflammatory collagenous connective tissue and presumed leukemic infiltration of a newly diagnosed chronic lymphocytic leukemia. In this case series, Ga-68-DOTA-TATE PET/CT demonstrated both a sensitivity and specificity of 100%. Yet, the golden standard of histopathology was only available in a subset of patients included. Ga-68-DOTA-TATE PET/CT proved to be a valuable diagnostic tool for the correct classification of equivocal, symptomatic tumors of the anterior optic pathway requiring therapy. PET/CT results influenced therapy decision essentially in all cases.

  20. Measurements of pulmonary vascular permeability with PET and gallium-68 transferrin

    International Nuclear Information System (INIS)

    Mintun, M.A.; Dennis, D.R.; Welch, M.J.; Mathias, C.J.; Schuster, D.P.

    1987-01-01

    We quantified pulmonary vascular permeability with positron emission tomography (PET) and gallium-68-( 68 Ga) labeled transferrin. Six dogs with oleic acid-induced lung injury confined to the left lower lobe, two normal human volunteers, and two patients with the adult respiratory distress syndrome (ARDS) were evaluated. Lung tissue-activity measurements were obtained from sequential 1-5 min PET scans collected over 60 min, after in vivo labeling of transferrin through intravenous administration of [ 68 Ga]citrate. Blood-activity measurements were measured from simultaneously obtained peripheral blood samples. A forward rate constant describing the movement of transferrin from pulmonary vascular to extravascular compartments, the pulmonary transcapillary escape rate (PTCER), was then calculated from these data using a two-compartment model. In dogs, PTCER was 49 +/- 18 in normal lung tissue and 485 +/- 114 10(-4) min-1 in injured lung. A repeat study in these dogs 4 hr later showed no significant change. Values in the human subjects showed similarly marked differences between normal and abnormal lung tissue. We conclude that PET will be a useful method of evaluating vascular permeability changes after acute lung injury

  1. Radiochemical studies relevant to cyclotron production of the radionuclides 71,72As, 68Ge/68Ga and 76,77,80mBr

    International Nuclear Information System (INIS)

    Shehata, Mohamed Mostafa Mostafa

    2011-01-01

    The radionuclides 71,72,73,74 As, 68 Ge/ 68 Ga and 76,77,80m Br are gaining considerable interest in nuclear medicine. A method for the separation of no-carrier-added arsenic radionuclides from the bulk amount of proton-irradiated GeO 2 target as well as from coproduced radiogallium was developed. The extraction of radioarsenic by different organic solvents from acid solutions containing alkali iodide was studied and optimized. The influence of the concentration of various acids (HCl, HClO 4 , HNO 3 , HBr, H 2 SO 4 ) as well as of KI was studied using cyclohexane. The practical application of the optimized procedure in the production of 71 As and 72 As is demonstrated. The batch yields achieved were in the range of 75-84% of the theoretical values. The radiochemical separation of radiogallium from radiogermanium was studied using ion exchange chromatography (Amberlite IR-120) and solvent extraction (Aliquat 336 in o-xylene). At first optimized methods for the separation of no-carrier-added 68 Ge/ 69 Ge formed via the nat Ga(p,xn) 69 Ge process in a Ga 2 O 3 target and for n.c.a. 67 Ga formed via the nat Zn(p,xn) 67 Ga reaction in a Zn target were developed. Using those radionuclides as tracers several factors affecting the separation of radiogallium from radiogermanium were studied and for each procedure the optimum conditions were determined. The solvent extraction using Aliquat 336 was found to be more suitable and was adapted to the separation of n.c.a. 68 Ga from its parent n.c.a. 68 Ge. The quality of the product thus obtained is discussed. The separation of no-carrier-added radiobromine and no-carrier-added radiogallium from proton irradiated ZnSe target was studied in detail. The adsorption behaviour of n.c.a. radiobromine, n.c.a. radiogallium, zinc and selenium towards the cation-exchange resin Amberlyst 15, in H + form, and towards the anion-exchange resin Dowex 1X10 in Cl - and OH - forms, was investigated. The elution of n.c.a. radiobromine and n

  2. Breast fibroadenoma with increased activity on 68Ga-DOTATATE PET/CT

    Science.gov (United States)

    Papadakis, Georgios Z.; Millo, Corina; Sadowski, Samira M.; Karantanas, Apostolos H.; Bagci, Ulas; Patronas, Nicholas J.

    2016-01-01

    Fibroadenoma is the most common benign breast tumor in women of reproductive age, carrying little to no risk of breast cancer development. We report on a case of a woman with history of neuroendocrine tumor (NET), who on follow-up imaging tests underwent whole-body PET/CT study using 68Ga-DOTATATE. The scan showed increased focal activity in the right breast, which was biopsied revealing a fibroadenoma. The presented data suggests cell surface over-expression of somatostatin receptors (SSTRs) by this benign breast tumor. Moreover, this finding emphasizes the need for cautious interpretation of 68Ga-DOTATATE avid breast lesions which could mimic malignancy in NET patients. PMID:27879489

  3. 28 CFR 68.3 - Service of complaint, notice of hearing, written orders, and decisions.

    Science.gov (United States)

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Service of complaint, notice of hearing, written orders, and decisions. 68.3 Section 68.3 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED..., registered agent for service of process of a corporate party, or attorney or representative of record of a...

  4. Monte Carlo FLUKA code simulation for study of {sup 68}Ga production by direct proton-induced reaction

    Energy Technology Data Exchange (ETDEWEB)

    Mokhtari Oranj, Leila; Kakavand, Tayeb [Physics Faculty, Zanjan University, P.O. Box 451-313, Zanjan (Iran, Islamic Republic of); Sadeghi, Mahdi, E-mail: msadeghi@nrcam.org [Agricultural, Medical and Industrial Research School, Nuclear Science and Technology Research Institute, P.O. Box 31485-498, Karaj (Iran, Islamic Republic of); Aboudzadeh Rovias, Mohammadreza [Agricultural, Medical and Industrial Research School, Nuclear Science and Technology Research Institute, P.O. Box 31485-498, Karaj (Iran, Islamic Republic of)

    2012-06-11

    {sup 68}Ga is an important radionuclide for positron emission tomography. {sup 68}Ga can be produced by the {sup 68}Zn(p,n){sup 68}Ga reaction in a common biomedical cyclotrons. To facilitate optimization of target design and study activation of materials, Monte Carlo code can be used to simulate the irradiation of the target materials with charged hadrons. In this paper, FLUKA code simulation was employed to prototype a Zn target for the production of {sup 68}Ga by proton irradiation. Furthermore, the experimental data were compared with the estimated values for the thick target yield produced in the irradiation time according to FLUKA code. In conclusion, FLUKA code can be used for estimation of the production yield.

  5. Outbreak of enterovirus D68 of the new B3 lineage in Stockholm, Sweden, August to September 2016.

    Science.gov (United States)

    Dyrdak, Robert; Grabbe, Malin; Hammas, Berit; Ekwall, Jonas; Hansson, Karin E; Luthander, Joachim; Naucler, Pontus; Reinius, Henrik; Rotzén-Östlund, Maria; Albert, Jan

    2016-11-17

    We report an enterovirus D68 (EV-D68) outbreak in Stockholm Sweden in 2016. Between 22 August and 25 September EV-D68 was detected in 74/495 respiratory samples analysed at the Karolinska University Hospital. During the peak week, 30/91 (33%) samples were EV-D68 positive. Viral protein (VP)P4/VP2 sequencing revealed that cases were caused by B3 lineage strains. Forty-four (59%) EV-D68-positive patients were children aged ≤ 5 years. Ten patients had severe respiratory or neurological symptoms and one died. This article is copyright of The Authors, 2016.

  6. KEPLER-68: THREE PLANETS, ONE WITH A DENSITY BETWEEN THAT OF EARTH AND ICE GIANTS

    Energy Technology Data Exchange (ETDEWEB)

    Gilliland, Ronald L. [Department of Astronomy, and Center for Exoplanets and Habitable Worlds, The Pennsylvania State University, 525 Davey Lab, University Park, PA 16802 (United States); Marcy, Geoffrey W.; Isaacson, Howard [Department of Astronomy, University of California, Berkeley, CA 94720 (United States); Rowe, Jason F.; Henze, Christopher E.; Lissauer, Jack J. [NASA Ames Research Center, Moffett Field, CA 94035 (United States); Rogers, Leslie [California Institute of Technology, Pasadena, CA 91125 (United States); Torres, Guillermo; Fressin, Francois; Desert, Jean-Michel [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Lopez, Eric D. [University of California, Santa Cruz, CA 95064 (United States); Buchhave, Lars A. [Niels Bohr Institute, Copenhagen University (Denmark); Christensen-Dalsgaard, Jorgen; Handberg, Rasmus [Stellar Astrophysics Centre, Department of Physics and Astronomy, DK-8000 Aarhus C (Denmark); Jenkins, Jon M. [SETI Institute/NASA Ames Research Center, Moffett Field, CA 94035 (United States); Chaplin, William J.; Elsworth, Yvonne [School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom); Basu, Sarbani [Department of Astronomy, Yale University, 260 Whitney Ave., New Haven, CT 06511 (United States); Metcalfe, Travis S. [White Dwarf Research Corporation, Boulder, CO 80301 (United States); Hekker, Saskia, E-mail: gillil@stsci.edu [Astronomical Institute Anton Pannekoek, University of Amsterdam, 1098 XH Amsterdam, Science Park 904 (Netherlands); and others

    2013-03-20

    NASA's Kepler Mission has revealed two transiting planets orbiting Kepler-68. Follow-up Doppler measurements have established the mass of the innermost planet and revealed a third Jovian-mass planet orbiting beyond the two transiting planets. Kepler-68b, in a 5.4 day orbit, has M{sub P}=8.3{sup +2.2}{sub -2.4} M{sub Circled-Plus }, R{sub P}=2.31{sup +0.06}{sub -0.09} R{sub Circled-Plus }, and {rho}{sub P}=3.32{sup +0.86}{sub -0.98} g cm{sup -3}, giving Kepler-68b a density intermediate between that of the ice giants and Earth. Kepler-68c is Earth-sized, with a radius R{sub P}=0.953{sup +0.037}{sub -0.042} R{sub Circled-Plus} and transits on a 9.6 day orbit; validation of Kepler-68c posed unique challenges. Kepler-68d has an orbital period of 580 {+-} 15 days and a minimum mass of M{sub P}sin i = 0.947 {+-} 0.035M{sub J} . Power spectra of the Kepler photometry at one minute cadence exhibit a rich and strong set of asteroseismic pulsation modes enabling detailed analysis of the stellar interior. Spectroscopy of the star coupled with asteroseismic modeling of the multiple pulsation modes yield precise measurements of stellar properties, notably T{sub eff} = 5793 {+-} 74 K, M{sub *} = 1.079 {+-} 0.051 M{sub Sun }, R{sub *} = 1.243 {+-} 0.019 R{sub Sun }, and {rho}{sub *} = 0.7903 {+-} 0.0054 g cm{sup -3}, all measured with fractional uncertainties of only a few percent. Models of Kepler-68b suggest that it is likely composed of rock and water, or has a H and He envelope to yield its density {approx}3 g cm{sup -3}.

  7. [68Ga]Pentixafor-PET/MRI for the detection of Chemokine receptor 4 expression in atherosclerotic plaques

    International Nuclear Information System (INIS)

    Li, Xiang; Heber, Daniel; Leike, Tatjana; Hacker, Marcus; Haug, Alexander R.; Beitzke, Dietrich; Loewe, Christian; Lu, Xia; Zhang, Xiaoli; Wei, Yongxiang; Mitterhauser, Markus; Wadsak, Wolfgang; Kropf, Saskia; Wester, Hans J.

    2018-01-01

    The expression of chemokine receptor type 4 (CXCR4) was found co-localized with macrophages on the atherosclerotic vessel wall and participated in the initial emigration of leukocytes. Gallium-68 [ 68 Ga]Pentixafor has recently been introduced for the imaging of atherosclerosis by targeting CXCR4. We sought to evaluate human atherosclerotic lesions using [ 68 Ga]Pentixafor PET/MRI. Thirty-eight oncology patients underwent [ 68 Ga]Pentixafor PET/MR imaging at baseline. Maximum standardized uptake values (SUV max ) were derived from hot lesions in seven arterial segments and target-to-blood ratios (TBR) were calculated. ANOVA post-hoc and paired t test were performed for statistical comparison, Spearman's correlation coefficient between uptake ratios and cardiovascular risk factors were assessed. The reproducibility of [ 68 Ga]Pentixafor PET/MRI was assessed in seven patients with a follow-up examination by Pearson's regression and Bland-Altman plots analysis. Thirty-four of 38 patients showed 611 focal [ 68 Ga]Pentixafor uptake that followed the contours of the large arteries. Both prevalence and mean TBR max were highest in the descending aorta. There were significantly higher TBR values found in men (1.9 ± 0.3) as compared to women (1.7 ± 0.2; p < 0.05). Patients with mean TBR max > 1.7 showed a significantly higher incidence of diabetes, hypertension hypercholesterolemia and history of cardiovascular disease than patients with mean TBR max ≤ 1.7. [ 68 Ga]Pentixafor uptake showed a good reproducibility (r = 0.6, p < 0.01), and there was no difference between the mean TBR max values of plaque lesions (TBR baseline 1.8 ± 0.3 vs TBR follow-up 1.8 ± 0.3) (p = 0.9). Patients with high arterial uptake showed increased incidence of cardiovascular risk factors, suggesting a potential role of [ 68 Ga]Pentixafor in characterization of atherosclerosis. (orig.)

  8. 31 CFR 351.68 - Are taxpayer identification numbers (TINs) required for registration of book-entry Series EE...

    Science.gov (United States)

    2010-07-01

    ... (TINs) required for registration of book-entry Series EE savings bonds? 351.68 Section 351.68 Money and... TREASURY BUREAU OF THE PUBLIC DEBT OFFERING OF UNITED STATES SAVINGS BONDS, SERIES EE Book-Entry Series EE Savings Bonds § 351.68 Are taxpayer identification numbers (TINs) required for registration of book-entry...

  9. Enterovirus D68 in Viet Nam (2009-2015 [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Nguyen Thi Han Ny

    2017-06-01

    Full Text Available Background: Since 1962, enterovirus D68 (EV-D68 has been implicated in multiple outbreaks and sporadic cases of respiratory infection worldwide, but especially in the USA and Europe with an increasing frequency between 2010 and 2014. We describe the detection, associated clinical features and molecular characterization of EV-D68 in central and southern Viet Nam between 2009 and 2015. Methods: Enterovirus/rhinovirus PCR positive respiratory or CSF samples taken from children and adults with respiratory/central nervous system infections in Viet Nam were tested by an EV-D68 specific PCR. The included samples were derived from 3 different observational studies conducted at referral hospitals across central and southern Viet Nam between 2009 and 2015. Whole-genome sequencing was carried out using a MiSeq based approach. Phylogenetic reconstruction and estimation of evolutionary rate and recombination were carried out in BEAST and Recombination Detection Program, respectively. Results: EV-D68 was detected in 21/625 (3.4% enterovirus/rhinovirus PCR positive respiratory samples but in none of the 15 CSF. All the EV-D68 patients were young children (age range: 11.8 – 24.5 months and had moderate respiratory infections. Phylogenetic analysis suggested that the Vietnamese sequences clustered with those from Asian countries, of which 9 fell in the B1 clade, and the remaining sequence was identified within the A2 clade. One intra sub-clade recombination event was detected, representing the second reported recombination within EV-D68. The evolutionary rate of EV-D68 was estimated to be 5.12E-3 substitutions/site/year. Phylogenetic analysis indicated that the virus was imported into Viet Nam in 2008. Conclusions: We have demonstrated for the first time EV-D68 has been circulating at low levels in Viet Nam since 2008, associated with moderate acute respiratory infection in children. EV-D68 in Viet Nam is most closely related to Asian viruses, and clusters

  10. DISCOVERY OF A GAS-RICH COMPANION TO THE EXTREMELY METAL-POOR GALAXY DDO 68

    Energy Technology Data Exchange (ETDEWEB)

    Cannon, John M.; Alfvin, Erik D. [Department of Physics and Astronomy, Macalester College, 1600 Grand Avenue, Saint Paul, MN 55105 (United States); Johnson, Megan; Koribalski, Baerbel [Australia Telescope National Facility, CSIRO Astronomy and Space Science, P.O. Box 76, NSW 1710, Epping (Australia); McQuinn, Kristen B. W.; Skillman, Evan D. [Minnesota Institute for Astrophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Bailin, Jeremy [Department of Physics and Astronomy, University of Alabama, P.O. Box 870324, Tuscaloosa, AL 35487-0324 (United States); Ford, H. Alyson [National Radio Astronomy Observatory, P.O. Box 2, Green Bank, WV 24944 (United States); Girardi, Léo [Osservatorio Astronomico di Padova—INAF, Vicolo dell' Osservatorio 5, I-35122 Padova (Italy); Hirschauer, Alec S.; Janowiecki, Steven; Salzer, John J.; Van Sistine, Angela [Department of Astronomy, Indiana University, 727 East Third Street, Bloomington, IN 47405 (United States); Dolphin, Andrew [Raytheon Company, 1151 E. Hermans Road, Tucson, AZ 85756 (United States); Elson, E. C. [Astrophysics, Cosmology and Gravity Centre (ACGC), Department of Astronomy, University of Cape Town, Private Bag X3, Rondebosch 7701 (South Africa); Marigo, Paola; Rosenfield, Philip [Dipartimento di Fisica e Astronomia Galileo Galilei, Universitá degli Studi di Padova, Vicolo dell' Osservatorio 3, I-35122 Padova (Italy); Rosenberg, Jessica L. [School of Physics, Astronomy, and Computational Science, George Mason University, Fairfax, VA 22030 (United States); Venkatesan, Aparna [Department of Physics and Astronomy, University of San Francisco, 2130 Fulton Street, San Francisco, CA 94117 (United States); Warren, Steven R., E-mail: jcannon@macalester.edu [Department of Astronomy, University of Maryland, CSS Bldg., Rm. 1024, Stadium Drive, College Park, MD 20742-2421 (United States)

    2014-05-20

    We present H I spectral-line imaging of the extremely metal-poor galaxy DDO 68. This system has a nebular oxygen abundance of only ∼3% Z {sub ☉}, making it one of the most metal-deficient galaxies known in the local volume. Surprisingly, DDO 68 is a relatively massive and luminous galaxy for its metal content, making it a significant outlier in the mass-metallicity and luminosity-metallicity relationships. The origin of such a low oxygen abundance in DDO 68 presents a challenge for models of the chemical evolution of galaxies. One possible solution to this problem is the infall of pristine neutral gas, potentially initiated during a gravitational interaction. Using archival H I spectral-line imaging obtained with the Karl G. Jansky Very Large Array, we have discovered a previously unknown companion of DDO 68. This low-mass (M{sub H} {sub I} = 2.8 × 10{sup 7} M {sub ☉}), recently star-forming (SFR{sub FUV} = 1.4 × 10{sup –3} M {sub ☉} yr{sup –1}, SFR{sub Hα} < 7 × 10{sup –5} M {sub ☉} yr{sup –1}) companion has the same systemic velocity as DDO 68 (V {sub sys} = 506 km s{sup –1}; D = 12.74 ± 0.27 Mpc) and is located at a projected distance of ∼42 kpc. New H I maps obtained with the 100 m Robert C. Byrd Green Bank Telescope provide evidence that DDO 68 and this companion are gravitationally interacting at the present time. Low surface brightness H I gas forms a bridge between these objects.

  11. SON68 glass alteration enhanced by magnetite

    Energy Technology Data Exchange (ETDEWEB)

    Godon, Nicole; Gin, Stephane; Rebiscoul, Diane; Frugier, Pierre [CEA, DEN-Marcoule, F30207, Bagnols-sur-Ceze (France)

    2013-07-01

    This paper reports experimental and modeling results of SON68 glass / magnetite interactions while in contact with synthetic groundwater from a clay environment. It is shown that magnetite enhances glass alteration, first by the sorption of Si released from the glass onto magnetite surfaces, then by a second process that could be the precipitation of an iron silicate mineral or the transformation of magnetite into a more reactive phase like hematite or goethite. This study globally suggests a detrimental effect of magnetite on the long-term durability of nuclear glass in geological disposal conditions. (authors)

  12. Comparison of autologous 111In-leukocytes, 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga-citrate for diagnostic nuclear imaging in a juvenile porcine haematogenous Staphylococcus aureus osteomyelitis model

    DEFF Research Database (Denmark)

    Nielsen, Ole L.; Afzelius, Pia; Bender, Dirk

    characterized as abscesses/cellulitis, arthritis in three joints and five enlarged lymph nodes. None of the tracers accumulated in joints with arthritis. By comparing the 10 infectious lesions, 18F-FDG accumulated in nine, 111In-leukocytes in eight, 11C-methionine in six, 68Ga-citrate in four and 11C-PK11195...

  13. Development of a Ga-68 labeled triptorelin analog for GnRH receptor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Zoghi, Masoumeh; Niazi, Ali [Islamic Azad Univ., Arak (Iran, Islamic Republic of). Dept. of Chemistry; Jalilian, Amir R.; Johari-daha, Fariba; Alirezapour, Behrouz [Nuclear Science and Technology Research Institute (NSTRI) (Iran, Islamic Republic of). Radiation Application Research School; Ramezanpour, Sorour [K.N. Toosi Univ. of Technology, Tehran (Iran, Islamic Republic of). Peptide Chemistry Research Center

    2016-08-01

    Optimized total synthesis, radiolabeling and quality control of [{sup 68}Ga]-DOTA-Hyd-TRP as an efficient and possible PET radiotracer for GnRH receptor imaging in various tumors is of great interest. DOTA-Hyd-TRP was synthesized using solid phase peptide synthesis followed by conjugation to DOTA using pSCN-Bn-DOTA. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared using generator-based [{sup 68}Ga]GaCl{sub 3} and DOTA-Hyd-TRP under optimized conditions for time, temperature, ligand amount, gallium content and column cartridge purification followed by proper formulation. The biodistribution of the tracer in rats was studied using tissue counting up to 120 min. [{sup 68}Ga]-DOTA-Hyd-TRP was prepared at optimized conditions in 5-7 min at 95 C followed by separation using C{sub 18} cartridge (radiochemical purity ∼99 ± 0.88% ITLC, > 99% HPLC, specific activity: 300 ± 15 MBq/nM). The biodistribution of the tracer demonstrated high kidney uptake of the tracer in 10-20 min as well as significant testicular uptake consistent with reported GnRH receptor mappings. Block test studies by triptorelin pretreatment of the animals prior to tracer administration demonstrated significant specific uptake in receptor rich organs including testes and stomach.

  14. Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    Schreiter, Nils F.; Brenner, Winfried; Buchert, Ralph; Prasad, Vikas; Nogami, Munenobu; Huppertz, Alexander; Pape, Ulrich-Frank; Hamm, Bernd; Maurer, Martin H.

    2012-01-01

    Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies, 111 In-diethylenetriaminepentaacetic acid (DTPA)-octreotide is still the current standard for diagnosis of neuroendocrine tumours (NET). The aim of this study was to compare the costs for the two diagnostic tests and the respective consequential costs. From January 2009 to July 2009, 51 consecutive patients with enteropancreatic NET who underwent contrast-enhanced 68 Ga-DOTATOC PET/CT (n = 29) or 111 In-DTPA-octreotide (mean 3 whole-body scans plus 1.6 low-dose single photon emission computed tomography/CT; n = 22) were included. For cost analysis, direct costs (equipment) and variable costs (material, labour) per examination were calculated. Additionally required CT and/or MRI examinations within the staging process were assessed as consequential costs. An additional deterministic sensitivity analysis was performed. A 68 Ga-DOTATOC PET/CT examination yielded total costs (equipment, personnel and material costs) of 548 EUR. On the other hand, an 111 In-DTPA-octreotide examination resulted in 827 EUR total costs. Costs for equipment and material had a share of 460 EUR/720 EUR for 68 Ga-DOTATOC/ 111 In-DTPA-octreotide and labour costs of 89 EUR/106 EUR. With 68 Ga-DOTATOC additional MRI had to be performed in 7% of the patients resulting in a mean of 20 EUR for supplementary imaging per patient; 82% of patients with 111 In-DTPA-octreotide needed additional MRI and/or CT resulting in mean additional costs of 161 EUR per patient. 68 Ga-DOTATOC PET/CT was considerably cheaper than 111 In-DTPA-octreotide with respect to both material and personnel costs. Furthermore, by using 68 Ga-DOTATOC PET/CT considerably fewer additional examinations were needed reducing the consequential costs significantly. (orig.)

  15. 47 CFR 68.316 - Hearing aid compatibility: Technical requirements.

    Science.gov (United States)

    2010-10-01

    ... network and terminal equipment technology and changes in the FCC Rules and Regulations. 2Scope 2.1The... standard is intended to be in conformance with part 68 of the FCC Rules and Regulations, but it is not... standard have been chosen to ensure reproducible results and permit comparison of evaluations. The measured...

  16. 44 CFR 6.8 - Subpoena and other legal demands.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Subpoena and other legal..., DEPARTMENT OF HOMELAND SECURITY GENERAL IMPLEMENTATION OF THE PRIVACY ACT OF 1974 General § 6.8 Subpoena and other legal demands. Access to records in systems of records by subpoena or other legal process shall be...

  17. Enterovirus D68 Infection Among Children With Medically Attended Acute Respiratory Illness, Cincinnati, Ohio, July-October 2014.

    Science.gov (United States)

    Biggs, Holly M; McNeal, Monica; Nix, W Allan; Kercsmar, Carolyn; Curns, Aaron T; Connelly, Beverly; Rice, Marilyn; Chern, Shur-Wern Wang; Prill, Mila M; Back, Nancy; Oberste, M Steven; Gerber, Susan I; Staat, Mary A

    2017-07-15

    Enterovirus D68 (EV-D68) caused a widespread outbreak of respiratory illness in the United States in 2014, predominantly affecting children. We describe EV-D68 rates, spectrum of illness, and risk factors from prospective, population-based acute respiratory illness (ARI) surveillance at a large US pediatric hospital. Children infection was detected in 51 of 207 (25%) inpatients and 58 of 505 (11%) ED patients. Rates of EV-D68 hospitalization and ED visit were 1.3 (95% confidence interval [CI], 1.0-1.6) and 8.4 per 1000 children infection (adjusted odds ratio, 3.2; 95% CI, 2.0-5.1). Compared with other ARI, children with EV-D68 were more likely to be admitted from the ED (P ≤ .001), receive supplemental oxygen (P = .001), and require intensive care unit admission (P = .04); however, mechanical ventilation was uncommon (2/51 inpatients; P = .64), and no deaths occurred. During the 2014 EV-D68 epidemic, high rates of pediatric hospitalizations and ED visits were observed. Children with asthma were at increased risk for medically attended EV-D68 illness. Preparedness planning for a high-activity EV-D68 season in the United States should take into account increased healthcare utilization, particularly among children with asthma, during the late summer and early fall. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  18. Coexistence of two clades of enterovirus D68 in pediatric Swedish patients in the summer and fall of 2014.

    Science.gov (United States)

    Dyrdak, Robert; Rotzén-Östlund, Maria; Samuelson, Agneta; Eriksson, Margareta; Albert, Jan

    2015-01-01

    In 2014, an outbreak of enterovirus D68 (EV-D68) was observed in North America, with cases of severe respiratory illness and a possible etiological link to cases of acute flaccid paralysis. EV-D68 has also been reported from European countries, but no data from Sweden are available. This study investigated respiratory specimens collected during July-October 2014 from 30 Swedish children aged 0-9 years who were positive for enterovirus and/or rhinovirus in routine clinical PCR. Seven samples were typed as EV-D68 by VP4/VP2 sequencing. Two genetically distinct EV-D68 variants coexisted. Six viruses belonged to clade B, the variant involved in the North American outbreak, and one virus belonged to clade A. Respiratory illness was the major symptom among EV-D68 infected patients and all fully recovered. This is the first report of EV-D68 in Sweden. Considering the current epidemiological situation, genotyping and specific EV-D68 testing should be considered in patients with severe respiratory illness who test positive for enterovirus or rhinovirus in routine diagnostics.

  19. Preparation and evaluation of {sup 68}Ga-ECC as a PET renal imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Mizaei, Alireza; Jaililan, Amir Reza; Mazidi, Mohammad; Aghanejad, Ayuob; Yousefnia, Hassan; Shabani, Gholamli; Ardaneh, Khosro [Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of); Geramifar, Patham; Beiki, Davood [Research Center for Nuclear Medicine, Shariati Hospital, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2015-09-15

    Development of a gallium-68-labeled renal tracer can be a good substitute for Tc-99m, a known SPECT tracer. In this study, effort was made to develop {sup 68}Ga-ethylenecysteamine cysteine ({sup 68}Ga-ECC). Ga-ECC was prepared using generator-based {sup 68}GaCl3 and ethylenecysteamine cysteine (ECC) at optimized conditions. Stability of the complex was checked in human serum followed by partition coefficient determination of the tracer. The biodistribution of the tracer in rats was studied using tissue counting and PET/CT imaging up to 120 min. Ga-ECC was prepared at optimized conditions in 15 min at 90 °C (radiochemical purity ≈97 ± 0.88 % ITLC, >99 % HPLC, specific activity: 210 ± 5 GBq/mM). {sup 68}Ga-ECC was a water-soluble complex based on partition coefficient data (log P; −1.378) and was stable in the presence of human serum for 2 h at 37 °C. The biodistribution of the tracer demonstrated high kidney excretion of the tracer in 10–20 min. The SUV{sub max} ratios of the liver to left kidney were 0.38 and 0.39 for 30 and 90 min, respectively, indicating high kidney uptake. Initial biodistribution results showed significant kidney and urinary excretion of the tracer comparable to that of the homologous {sup 99m}Tc compound. The complex could be a possible PET kidney imaging agent with a fast imaging time.

  20. Utility of Gallium-68 DOTANOC PET/CT in the localization of Tumour-induced osteomalacia.

    Science.gov (United States)

    Bhavani, Nisha; Reena Asirvatham, Adlyne; Kallur, Kumar; Menon, Arun S; Pavithran, Praveen V; Nair, Vasantha; Vasukutty, Jayakumar R; Menon, Usha; Kumar, Harish

    2016-01-01

    Tumour-induced osteomalacia (TIO) is a rare disorder characterized by hypophosphataemic osteomalacia caused by small mesenchymal tumours secreting fibroblast growth factor 23 (FGF 23). The most difficult part in the management of these patients is the localization of tumours causing TIO. We describe the utility of Gallium (Ga)-68 DOTANOC PET/CT in the localization of tumours causing TIO. The study was conducted in a single tertiary referral university teaching hospital in India. Ten patients with TIO who underwent Ga-68 DOTANOC PET/CT from the time period 2009 to 2014 were included in this study. Their detailed clinical history, biochemical parameters, imaging modalities, surgical interventions, histopathology and outcomes were reviewed. Ga-68 DOTANOC PET/CT could correctly localize the tumours in TIO in 9 of the 10 cases in which it was performed. Complete resection of the tumour led to full clinical recovery in six of the ten patients; two patients who had partial resection and one patient who underwent radiofrequency ablation showed partial remission. One patient in whom Ga-68 DOTANOC PET/CT was positive in vertebral body with a low standardized uptake value (SUV) did not show up the tumour on surgery. We conclude that Ga-68 DOTANOC PET/CT can be used as the first imaging modality in patients diagnosed with TIO. The extremely good outcome following the resection of these small otherwise undiagnosed tumours far outweighs its cost even in resource limited settings. © 2015 John Wiley & Sons Ltd.

  1. Characterization of the low-lying 0$^{+}$ and 2$^{+}$ states of $^{68}$ Ni

    CERN Multimedia

    Recently, a number of low-lying low-spin states have been firmly identified in $^{68}$Ni; the position of the first excited state (which is a 0$^{+}$ state), the spin and parity of the second excited 0$^{+}$ state and the spin and parity of the second and third 2$^+$ states have been fixed. The identification of these three pairs of 0$^+$ and 2$^+$ states in $^{68}$Ni (Z=28 and N=40) forms ideal tests to validate shell-model calculations and the effective interactions developed for the nickel region but also hints to triple shape coexistence including even strongly deformed structures. The aim of this proposal is to collect detailed spectroscopic data of the low-spin states of $^{68}$Ni (Z=28, N=40) in order to characterize these triple pairs of 0$^+$ and 2$^+$ states. $\\gamma$-branching ratios of the 0$^+$ and 2$^+$ states and the E0 transition strengths as well as the E2 transition rate of the 0$_3^+$ will be obtained using the new ISOLDE decay station that is constructed from an efficient array of germaniu...

  2. Enterovirus D-68 Infection, Prophylaxis, and Vaccination in a Novel Permissive Animal Model, the Cotton Rat (Sigmodon hispidus.

    Directory of Open Access Journals (Sweden)

    Mira C Patel

    Full Text Available In recent years, there has been a significant increase in detection of Enterovirus D-68 (EV-D68 among patients with severe respiratory infections worldwide. EV-D68 is now recognized as a re-emerging pathogen; however, due to lack of a permissive animal model for EV-D68, a comprehensive understanding of the pathogenesis and immune response against EV-D68 has been hampered. Recently, it was shown that EV-D68 has a strong affinity for α2,6-linked sialic acids (SAs and we have shown previously that α2,6-linked SAs are abundantly present in the respiratory tract of cotton rats (Sigmodon hispidus. Thus, we hypothesized that cotton rats could be a potential model for EV-D68 infection. Here, we evaluated the ability of two recently isolated EV-D68 strains (VANBT/1 and MO/14/49, along with the historical prototype Fermon strain (ATCC, to infect cotton rats. We found that cotton rats are permissive to EV-D68 infection without virus adaptation. The different strains of EV-D68 showed variable infection profiles and the ability to produce neutralizing antibody (NA upon intranasal infection or intramuscular immunization. Infection with the VANBT/1 resulted in significant induction of pulmonary cytokine gene expression and lung pathology. Intramuscular immunization with live VANBT/1 or MO/14/49 induced strong homologous antibody responses, but a moderate heterologous NA response. We showed that passive prophylactic administration of serum with high content of NA against VANBT/1 resulted in an efficient antiviral therapy. VANBT/1-immunized animals showed complete protection from VANBT/1 challenge, but induced strong pulmonary Th1 and Th2 cytokine responses and enhanced lung pathology, indicating the generation of exacerbated immune response by immunization. In conclusion, our data illustrate that the cotton rat is a powerful animal model that provides an experimental platform to investigate pathogenesis, immune response, anti-viral therapies and vaccines

  3. (68)Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer.

    Science.gov (United States)

    Sachpekidis, C; Eder, M; Kopka, K; Mier, W; Hadaschik, B A; Haberkorn, U; Dimitrakopoulou-Strauss, A

    2016-07-01

    We aim to investigate the pharmacokinetics and distribution of the recently clinically introduced radioligand (68)Ga-PSMA-11 in men with recurrent prostate cancer (PC) by means of dynamic and whole-body PET/CT. The correlation between PSA levels and (68)Ga-PSMA-11 PET parameters is also investigated. 31 patients with biochemical failure after primary PC treatment with curative intent (median age 71.0 years) were enrolled in the analysis. The median PSA value was 2.0 ng/mL (range = 0.1 - 130.0 ng/mL) and the median Gleason score was 7 (range = 5 - 9). 8/31 (25.8 %) of the included patients had a PSA value dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with (68)Ga-PSMA-11. dPET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). 22/31 patients (71.0 %) were (68)Ga-PSMA-11-positive, while 9/31 (29.0 %) patients were (68)Ga-PSMA-11-negative. The median PSA value in the (68)Ga-PSMA-11-positive group was significantly higher (median = 2.35 ng/mL; range = 0.19 - 130.0 ng/mL) than in the (68)Ga-PSMA-11-negative group (median value: 0.34 ng/mL; range = 0.10 - 4.20 ng/mL). A total of 76 lesions were semi-quantitatively evaluated. PC recurrence-associated lesions demonstrated a mean SUVaverage = 12.4 (median = 9.0; range = 2.2 - 84.5) and mean SUVmax = 18.8 (median = 14.1; range = 3.1 - 120.3). Dynamic PET/CT studies of the pelvis revealed the following mean values for the PC recurrence-suspicious lesions: K1 = 0.26, k3 = 0.30, influx = 0.14 and FD = 1.24. Time-activity curves derived from PC-recurrence indicative lesions revealed an increasing (68)Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate, but significant, correlation between PSA

  4. Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo.

    Science.gov (United States)

    Iqbal, Asif J; McNeill, Eileen; Kapellos, Theodore S; Regan-Komito, Daniel; Norman, Sophie; Burd, Sarah; Smart, Nicola; Machemer, Daniel E W; Stylianou, Elena; McShane, Helen; Channon, Keith M; Chawla, Ajay; Greaves, David R

    2014-10-09

    The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115(+) monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow-derived CD68-GFP monocytes to that of CX3CR1(GFP) monocytes in vivo using a sterile zymosan peritonitis model. Unlike CX3CR1(GFP) monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation. © 2014 by The American Society of Hematology.

  5. Turnover of T cells in murine gammaherpesvirus 68-infected mice

    DEFF Research Database (Denmark)

    Hamilton-Easton, A M; Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    Respiratory challenge of C57BL/6 mice with murine gammaherpesvirus 68 induces proliferation of T lymphocytes early after infection, as evidenced by incorporation of the DNA precursor bromodeoxyuridine. Using pulse-chase analysis, splenic and peripheral blood activated T lymphocytes were found...

  6. Potential use of 68Ga-apo-transferrin as a PET imaging agent for detecting Staphylococcus aureus infection

    International Nuclear Information System (INIS)

    Kumar, Vijay; Boddeti, Dilip K.; Evans, Scott G.; Roesch, Frank; Howman-Giles, Robert

    2011-01-01

    Introduction: 67 Ga citrate has been extensively used to detect infection and inflammation since 1971. However, its clinical utility is compromised due to several limitations. The present project explored whether 68 Ga-apo-transferrin ( 68 Ga-TF), when prepared in vitro, is a useful agent for positron emission tomography (PET) imaging of bacterial infection. Methods: An infection was induced in male Wistar rats by injecting 5x10 5 CFU units of Staphyococcus aureus in the right thigh muscle. 68 Ga-TF was synthesized by mixing 68 GaCl 3 with apo-transferrin (TF, 2 mg) in sodium carbonate (0.1 M, pH 7.0) and incubating at 40 o C for 1 h. Animals were injected with 10-15 MBq of 68 Ga-TF containing approximately 0.2 mg TF and imaged at different time intervals using Siemens Biograph PET-CT. Results: When 68 Ga-TF were injected in the infected rats, the infection lesion was detectable within 20 min post injection. The biodistribution showed the uptake at the lesion increased with time as shown by significantly increased standard uptake values for up to 4 h post injection. There was a considerable decrease in the background activity during the same period of study, giving higher target-to-muscle ratios. Blood pool activity at 3 h post injection was insignificant. 68 GaCl 3 (when not conjugated to TF) did not localize at the infection lesion up to 120 min post injection. Conclusion: The preliminary results suggest that 68 Ga-TF is capable of detecting S. aureus infection in the rat model, within an hour after intravenous injection.

  7. [68Ga]Pentixafor-PET/MRI for the detection of Chemokine receptor 4 expression in atherosclerotic plaques

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiang; Heber, Daniel; Leike, Tatjana; Hacker, Marcus; Haug, Alexander R. [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Beitzke, Dietrich; Loewe, Christian [Medical University of Vienna, Division of Cardiovascular and Interventional Radiology, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Lu, Xia; Zhang, Xiaoli; Wei, Yongxiang [Capital Medical University, Department of Nuclear Medicine, Beijing Anzhen Hospital, Beijing (China); Mitterhauser, Markus [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Ludwig Boltzmann Institute Applied Diagnostics, Vienna (Austria); Wadsak, Wolfgang [Medical University of Vienna, Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); CBmed, Center for Biomarker Research in Medicine, Graz (Austria); Kropf, Saskia [Scintomics GmbH, Fuerstenfeldbruck (Germany); Wester, Hans J. [Technische Universitaet Muenchen, Department of Radiopharmaceutical Chemistry, Garching (Germany)

    2018-04-15

    The expression of chemokine receptor type 4 (CXCR4) was found co-localized with macrophages on the atherosclerotic vessel wall and participated in the initial emigration of leukocytes. Gallium-68 [{sup 68}Ga]Pentixafor has recently been introduced for the imaging of atherosclerosis by targeting CXCR4. We sought to evaluate human atherosclerotic lesions using [{sup 68}Ga]Pentixafor PET/MRI. Thirty-eight oncology patients underwent [{sup 68}Ga]Pentixafor PET/MR imaging at baseline. Maximum standardized uptake values (SUV{sub max}) were derived from hot lesions in seven arterial segments and target-to-blood ratios (TBR) were calculated. ANOVA post-hoc and paired t test were performed for statistical comparison, Spearman's correlation coefficient between uptake ratios and cardiovascular risk factors were assessed. The reproducibility of [{sup 68}Ga]Pentixafor PET/MRI was assessed in seven patients with a follow-up examination by Pearson's regression and Bland-Altman plots analysis. Thirty-four of 38 patients showed 611 focal [{sup 68}Ga]Pentixafor uptake that followed the contours of the large arteries. Both prevalence and mean TBR{sub max} were highest in the descending aorta. There were significantly higher TBR values found in men (1.9 ± 0.3) as compared to women (1.7 ± 0.2; p < 0.05). Patients with mean TBR{sub max} > 1.7 showed a significantly higher incidence of diabetes, hypertension hypercholesterolemia and history of cardiovascular disease than patients with mean TBR{sub max} ≤ 1.7. [{sup 68}Ga]Pentixafor uptake showed a good reproducibility (r = 0.6, p < 0.01), and there was no difference between the mean TBR{sub max} values of plaque lesions (TBR{sub baseline}1.8 ± 0.3 vs TBR{sub follow-up}1.8 ± 0.3) (p = 0.9). Patients with high arterial uptake showed increased incidence of cardiovascular risk factors, suggesting a potential role of [{sup 68}Ga]Pentixafor in characterization of atherosclerosis. (orig.)

  8. CD68+ cell count, early evaluation with PET and plasma TARC levels predict response in Hodgkin lymphoma.

    Science.gov (United States)

    Cuccaro, Annarosa; Annunziata, Salvatore; Cupelli, Elisa; Martini, Maurizio; Calcagni, Maria L; Rufini, Vittoria; Giachelia, Manuela; Bartolomei, Francesca; Galli, Eugenio; D'Alò, Francesco; Voso, Maria T; Leone, Giuseppe; Giordano, Alessandro; Larocca, Luigi M; Hohaus, Stefan

    2016-03-01

    Early response evaluation with [(18) F]fluordeoxyglucose (FDG) positron emission tomography after 2 cycles of chemotherapy (interim PET) has been indicated as the strongest predictor for outcome in classical Hodgkin lymphoma (HL). We studied the prognostic role of the number of tumor-infiltrating CD68+ cells and of the plasma levels of TARC (thymus and activation-regulated chemokine) in the context of interim PET in 102 patients with classical HL treated with Adriamycin, Bleomycin, Vinblastine, Dacarbazine (ABVD). After 2 ABVD cycles, interim PET according to Deauville criteria was negative (score 0-3) in 85 patients and positive (score 4-5) in 15 patients (2 patients technically not evaluable). TARC levels were elevated in 89% of patients at diagnosis, and decreased after 2 cycles in 82% of patients. Persistently elevated TARC levels in 18% of patients were significantly associated with a positive PET result (P = 0.007). Strong predictors for progression-free survival (PFS) were a negative interim PET (85% vs. 28%, P evaluation had no prognostic role. In multivariate analysis, interim PET, CD68+ cell counts and presence of B-symptoms were independently associated with PFS. We conclude that although TARC levels are a biomarker for early response evaluation, they cannot substitute for interim PET as outcome predictor in HL. The evaluation of CD68 counts and B-symptoms at diagnosis may help to identify low-risk patients regardless positive interim PET. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  9. 41 CFR 105-68.365 - What must I do if I learn of information required under § 105-68.355 after entering into a...

    Science.gov (United States)

    2010-07-01

    ... Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION Regional Offices-General... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What must I do if I learn of information required under § 105-68.355 after entering into a covered transaction with a...

  10. Ionization ratios and elemental abundances in the atmosphere of 68 Tauri

    Science.gov (United States)

    Aouina, A.; Monier, R.

    2017-12-01

    We have derived the ionization ratios of twelve elements in the atmosphere of the star 68 Tauri (HD 27962) using an ATLAS9 model atmosphere with 72 layers computed for the effective temperature and surface gravity of the star. We then computed a grid of synthetic spectra generated by SYNSPEC49 based on an ATLAS9 model atmosphere in order to model one high resolution spectrum secured by one of us (RM) with the échelle spectrograph SOPHIE at Observatoire de Haute Provence. We could determine the abundances of several elements in their dominant ionization stage, including those defining the Am phenomenon. We thus provide new abundance determinations for 68 Tauri using updated accurate atomic data retrieved from the NIST database which extend previous abundance works.

  11. Kepler-68: Three Planets, One with a Density between that of Earth and Ice Giants

    NARCIS (Netherlands)

    Gilliland, R.L.; Marcy, G.W.; Rowe, J.F.; Rogers, L.; Torres, G.; Fressin, F.; Lopez, E.D.; Buchhave, L.A.; Christensen-Dalsgaard, J.; Désert, J.M.; Henze, C.E.; Isaacson, H.; Jenkins, J.M.; Lissauer, J.J.; Chaplin, W.J.; Basu, S.; Metcalfe, T.S.; Elsworth, Y.; Handberg, R.; Hekker, S.; Huber, D.; Karoff, C.; Kjeldsen, H.; Lund, M.N.; Lundkvist, M.; Miglio, A.; Charbonneau, D.; Ford, E.B.; Fortney, J.J.; Haas, M.R.; Howard, A.W.; Howell, S.B.; Ragozzine, D.; Thompson, S.E.

    2013-01-01

    NASA's Kepler Mission has revealed two transiting planets orbiting Kepler-68. Follow-up Doppler measurements have established the mass of the innermost planet and revealed a third Jovian-mass planet orbiting beyond the two transiting planets. Kepler-68b, in a 5.4 day orbit, has Mp_{\\rm

  12. Evaluation of {sup 68}Ga-DOTATOC PET/MRI for whole-body staging of neuroendocrine tumours in comparison with {sup 68}Ga-DOTATOC PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Sawicki, Lino M. [University Dusseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Dusseldorf (Germany); University Duisburg-Essen, Department of Nuclear Medicine, Medical Faculty, Essen (Germany); Deuschl, Cornelius; Beiderwellen, Karsten; Forsting, Michael; Umutlu, Lale [University Duisburg-Essen, Department of Diagnostic and Interventional Radiology and Neuroradiology, Medical Faculty, Essen (Germany); Ruhlmann, Verena; Poeppel, Thorsten D.; Bockisch, Andreas; Herrmann, Ken [University Duisburg-Essen, Department of Nuclear Medicine, Medical Faculty, Essen (Germany); Heusch, Philipp; Antoch, Gerald [University Dusseldorf, Department of Diagnostic and Interventional Radiology, Medical Faculty, Dusseldorf (Germany); Lahner, Harald; Fuehrer, Dagmar [University Duisburg-Essen, Department of Endocrinology and Metabolism, Endocrine Tumour Center at WTZ and ENETS Center of Excellence, Medical Faculty, Essen (Germany); Endocrine Tumour Center at WTZ and ENETS Center of Excellence, Essen (Germany)

    2017-10-15

    To compare the diagnostic performance of {sup 68}Ga-DOTATOC PET/MRI and {sup 68}Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET). Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar's chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson's correlation coefficient (r). According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p = 0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p = 0.031). SUVmax was strongly correlated (r = 0.86; p < 0.001) and did not differ significantly (p = 0.35) between the modalities. Overall conspicuity and NET lesion conspicuity were higher on PET/MRI (both p < 0.01). Ga-DOTATOC PET/MRI yielded a higher proportion of correctly rated NET lesions and should be regarded as a valuable alternative to {sup 68}Ga-DOTATOC PET/CT in whole-body staging of NET patients. (orig.)

  13. {sup 68}Ga-labelled recombinant antibody variants for immuno-PET imaging of solid tumours

    Energy Technology Data Exchange (ETDEWEB)

    Eder, Matthias; Eisenhut, Michael [German Cancer Research Center, Radiopharmaceutical Chemistry, Heidelberg (Germany); Knackmuss, Stefan; Gall, Fabrice Le; Reusch, Uwe; Little, Melvyn [Affimed Therapeutics AG, Heidelberg (Germany); Rybin, Vladimir [European Molecular Biology Laboratory, Heidelberg (Germany); Haberkorn, Uwe; Mier, Walter [University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany)

    2010-07-15

    Recombinant antibodies isolated from human antibody libraries have excellent affinities and high target specificity. As full-length IgGs are cleared inadequately slowly from the circulation, the aim of this work was to figure out which kind of recombinant antibody fragment proves to be appropriate for imaging epithelial cell adhesion molecule (EpCAM)-expressing tumours with the short-living radioisotope {sup 68}Ga. In order to combine the promising tumour targeting properties of antibodies with {sup 68}Ga, four antibody variants with the same specificity and origin only differing in molecular weight were constructed for comparison. Therefore, the binding domains of a single-chain fragment variable (scFv) isolated from a human naive antibody library were modified genetically to construct the respective full-length IgG, the tria- and diabody variants. These molecules were conjugated with the bifunctional chelating agent N,N{sup '}-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N{sup '}-diacetic acid (HBED-CC) to enable {sup 68}Ga labelling at ambient temperature and compared in biodistribution and immuno-PET imaging experiments. The antibody variants with identical specificity proved to have the correct molecular weight, high binding affinity and specificity to their antigen, EpCAM. Radiometal complexation was efficiently performed at room temperature leading to {sup 68}Ga-labelled antibodies with unchanged binding properties compared to the original antibody variants. The best targeting properties were obtained with the scFv and especially with the diabody. The triabody showed higher absolute tumour uptake but only moderate clearance from circulation. The antibody variants differed considerably in normal organ uptake, clearance from circulation and tumour accumulation. The data demonstrate the feasibility of imaging solid tumours with the {sup 68}Ga-labelled diabody format. This type of recombinant protein might be a promising carrier even for the

  14. DATATOC: a novel conjugate for kit-type 68Ga labelling of TOC at ambient temperature.

    Science.gov (United States)

    Seemann, Johanna; Waldron, Bradley; Parker, David; Roesch, Frank

    2017-01-01

    The widespread acceptance and application of 68 Ga-PET depends on our ability to develop radiopharmaceuticals that can be prepared in a convenient and suitable manner. A kit-type labelling protocol provides such characteristics and requires chelators that can be radiolabelled under exceptionally mild conditions. Recently the DATA chelators have been introduced that fulfil these requirements. In continuing their development, the synthesis and radiolabelling of the first DATA bifunctional chelator (BFC) and peptide conjugate are described. A BFC derived from the DATA ligand (2,2'-(6-((carboxymethyl)amino)-1,4-diazepane-1,4-diyl)diacetic acid) has been synthesised in five steps from simple building blocks, with an overall yield of 8 %. DATA M5 -3 t Bu (5-[1,4-Bis-tert-butoxycarbonylmethyl-6-(tert-butoxycarbonylmethyl-methyl-amino)-[1, 4]diazepan-6-yl]-pentanoic acid) has been coupled to [DPhe 1 ][Tyr 3 ]-octreotide (TOC) and the resulting peptide conjugate (DATATOC) radiolabelled with purified 68 Ga derived via four different 68 Ge/ 68 Ga generator post-processing (PP) methods. The stability and lipophilicity of the radiotracer have been assessed and a kit-type formulation for radiolabelling evaluated. 68 Ga-DATATOC has been prepared with a > 95 % radiochemical yield (RCY) within 1 (fractionated and acetone-PP) and 10 min (ethanol- and NaCl-PP) at 23 °C (pH 4.2-4.9, 13 nmol). The radiolabelled peptide is stable in the presence of human serum. Lipophilicity of 68 Ga-DATATOC was calculated as logP = -3.2 ± 0.3, with a HPLC retention time ( t R  = 10.4 min) similar to 68 Ga-DOTATOC (logP = -2.9 ± 0.4, t R  = 10.3 min). Kit-type labelling from a lyophilised solid using acetone-PP based labelling achieves > 95 % RCY in 10 min at 23 °C. The favourable labelling properties of the DATA chelators have been retained for DATATOC. High radiochemical purity can be achieved at 23 °C in less than 1 min and from a kit formulation. The

  15. PSA levels as a predictor of 68Ga PSMA PET/CT positivity in patients with prostate cancer?

    Science.gov (United States)

    Soydal, Cigdem; Urun, Yuksel; Suer, Evren; Nak, Demet; Ozkan, Elgin; Kucuk, Ozlem N

    2018-05-10

    The aim of this study is to evaluate predictive factors of 68Gallium (68Ga) Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET)/Computed Tomography (CT) positivity. Relationships between serum Prostate Specific Antigen (PSA), Lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) levels, Gleason Score (GS) and positivity of 68Ga PSMA PET in patients who underwent 68Ga PSMA PET/CT for restaging for PCa were evaluated retrospectively. One hundred and four (median age: 67; range: 51-88) patients were included in this study. Of these patients, PSMA PET was positive in 75 (72%) patients. Mean serum PSA levels for PET negative and positive groups were 0.76±1.00 and 180.85±324.93 ng/ml (pPSA cut-off and 92% and 90%, respectively, for the 2 ng/ml PSA cut-off values. The positivity rates for patients with PSA levels PSA recurrence. Patients with higher GS and early PSA recurrence could benefit from 68Ga PSMA PET/CT.

  16. A viable fetus presenting 68,XX[73]/69,XXX[27] triploid mosaicism

    Directory of Open Access Journals (Sweden)

    A.X. Acosta

    1998-09-01

    Full Text Available Triploidy is common in human pregnancies. It is detected in 1 to 2% of clinically recognized pregnancies and in approximately 15 to 20% of spontaneous abortions produced by chromosome anomalies. We report a premature liveborn girl (30 weeks of gestation with microcephaly, facial dysmorphism and skeletal abnormalities who died at one day of age due to respiratory failure. The placenta showed partial hydatiform mole. Autopsy revealed no internal malformations. Cytogenetic analysis of 100 metaphases obtained from renal tissue culture revealed a 68,XX[73]/69,XXX[27] karyotype. To our knowledge this is the first report in the literature of 68,XX[73]/69,XXX[27] mosaicism in a liveborn infant.A triploidia é uma anomalia cromossômica comum encontrada em 1 a 2% das gestações clinicamente reconhecidas e em cerca de 15 a 20% dos abortos espontâneos de causa cromossômica. Em aproximadamente 5% dos casos, uma aneuploidia pode estar também associada (Boué et al., 1985. Descrevemos um recém-nascido do sexo feminino, prematuro (30 semanas de idade gestacional, com microcefalia, dismorfias faciais e alterações de membros, que foi a óbito com 1 dia de vida por insuficiência respiratória. O exame anátomo-patológico da placenta revelou alterações compatíveis com degeneração molar. A necrópsia da criança não evidenciou malformações internas. A análise citogenética de 100 metáfases, obtidas a partir de cultura de tecido renal, evidenciou cariótipo 68,XX[73]/69,XXX[27]. Apenas 9 casos de triploidia 68,XX foram descritos anteriormente, sendo 7 em abortos, 1 em feto de 21 semanas e 1 em recém-nascido a termo. Consideramos que este estudo seja o primeiro da literatura relatando a ocorrência de mosaicismo 69,XXX/68,XX em um recém-nascido vivo. Os autores discutem os achados clínicos e os possíveis mecanismos envolvidos nesta aberração cromossômica.

  17. 76 FR 2917 - Agency Information Collection Activities: Canadian Border Boat Landing Permit (CBP Form I-68)

    Science.gov (United States)

    2011-01-18

    ... 235.1(e) and Section 235 of Immigration and Nationality Act. CBP Form I-68 is accessible at http://forms.cbp.gov/pdf/CBP_Form_I68.pdf Current Actions: This submission is being made to extend the...

  18. Synthesis and evaluation of a "6"8Ga labeled folic acid derivative for targeting folate receptors

    International Nuclear Information System (INIS)

    Jain, Akanksha; Mathur, Anupam; Pandey, Usha; Bhatt, Jyotsna; Mukherjee, Archana; Ram, Ramu; Sarma, Haladhar Dev; Dash, Ashutosh

    2016-01-01

    Present work evaluates the potential of a newly synthesized "6"8Ga-NOTA-folic acid conjugate for PET imaging of tumors over-expressing folate receptors (FRs). NOTA-folic acid conjugate was synthesized and characterized. It was radiolabeled with "6"8Ga in ≥ 95% radiolabeling yields. In vitro cell binding studies showed a maximum cell uptake of 1.7±0.4% per million KB cells which was completely blocked on addition of cold folic acid showing specificity towards the FRs. However, further studies in tumor xenografts are warranted in order to assess the potential of "6"8Ga-folic acid complex for imaging tumors over-expressing FRs. - Highlights: • NOTA-Bn-(3-aminopropyl) folic acid conjugate was synthesized and characterized by "1H-NMR, ESI-MS and HPLC analysis. • NOTA-folic acid conjugate radiolabeled with "6"8Ga in >95% yields and high serum stability (≥95%) upto 1 h. • In vitro studies in KB cells showed specificity of NOTA-Bn-(3-aminopropyl) folic acid. • A maximum cell uptake of 1.7±0.4% per million KB cells was observed for "6"8Ga-NOTA-folic acid.

  19. Using Ga-67/68-DOTATOC for pretherapeutic dosimetry

    International Nuclear Information System (INIS)

    Hofmann, M.; Fitschen, J.; Oei, M.L.; Boerner, A.R.; Knoop, B.O.; Otto, D.; Maecke, H.; Geworski, L.; Knapp, W.H.; Kalbacher, H.

    2002-01-01

    Full text: To date, treatment of somatostatin-positive tumors using Y-90-radiopeptide therapy has gained importance. Because accurate dosimetry is a prerequisite for proper treatment the most precise determination of maximum uptake and the measurement of tracer half-life in tumors and organs is highly desirable. In 12 patients we performed Ga-68-DOTATOC PET and measured the SUVs in tumors and organs 90 min p.i. as maximum tumor uptake. One day later Ga-67-DOTATOC planar scintigraphy (and SPET) were performed 2 / 24 / 48 h p.i.. Organs and tumors were evaluated by ROI techniques yielding in the corresponding half-lives. Absorbed doses were calculated according to MIRD 3.0. SUV varied for liver tumors from 5-15 and from 3 to 9 for bone metastases. The standardized uptake values of organ were 0.8 to 2.5 for liver, 4-10 for spleen and 3-6 for kidneys. The calculated doses varied in a relative broad range (intra- and interindividually). Over all small tumors (< 3 cm) displayed the most uptake and therefore yielded in the highest doses per injected MBq. Dosimetry using 67/68-Ga-DOTATOC PET and planar scintigraphy is feasible and yields in dosimetric data, which may help to adjust injected doses for adequate tumor treatment and avoid unwanted organ toxicity in future therapeutical trials. (author)

  20. Preparation of gallium-68 radiopharmaceuticals for positron tomography. Progress report, November 1, 1978-October 31, 1979

    International Nuclear Information System (INIS)

    Welch, M.J.

    1978-06-01

    Although the germanium-gallium generator is probably the only source of positron-emitting radionuclides that would enable the wide application of positron tomography, the generator system in use suffers from several major disadvantages. The most important of these is that the generator is eluted with EDTA, and EDTA forms a very strong chelate with gallium. In order to produce radiopharmaceuticals other than gallium-68 EDTA it is necessary to break the stable EDTA complex and remove all the EDTA. A new generator system using a solvent extraction system which will produce gallium-68 8-hydroxyquinoline, a weak chelate has been developed. Using this agent, several gallium-68 radiopharmaceuticals have been synthesized and tested in vitro and in vivo. Attempts have been made using polarographic and chromatographic techniques to investigate the stability of gallium-68 complexes with a series of cryptates

  1. Microsurgery guided by sequential preoperative lymphography using {sup 68}Ga-NEB PET and MRI in patients with lower-limb lymphedema

    Energy Technology Data Exchange (ETDEWEB)

    Long, Xiao; Gao, Chao; Yang, Elan [Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Plastic Surgery, Beijing (China); Zhang, Jingjing [Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Nuclear Medicine, Beijing (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); Zhang, Daming; Xue, Huadan [Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Radiology, Beijing (China); Chi, Chongwei [Institute of Automation Chinese Academy of Sciences Beijing, Key Laboratory of Molecular Imaging of Chinese Academy of Sciences, Beijing (China); Lang, Lixin; 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); Zhu, Zhaohui; Li, Fang [Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Department of Nuclear Medicine, Beijing (China)

    2017-08-15

    The popularity of contemporary microsurgical techniques in treatment of lower-limb lymphedema calls for better visualization of the lymphatic system, both preoperatively and intra-operatively. The aim of this prospective study was to investigate the feasibility of a novel combination of {sup 68}Ga-NEB positron emission tomography (PET) with magnetic resonance lymphography (MRL) in evaluating lymphedema and guiding surgical intervention. A total of 11 patients (F 9, M 2, age range 29-69 y) with lower-limb lymphedema classified into stage I to III were recruited. PET acquisition was performed at 30, 60 and 90 min after subcutaneous injection of the albumin-binding radiotracer {sup 68}Ga-NEB into the bilateral first web spaces of the feet. All the patients were also subjected to {sup 99m}Tc-sulfur colloid (SC) lymphoscintigraphy for comparison. Gd-DTPA-enhanced magnetic resonance imaging (MRI) was performed using sequences specialized for lymphatic vessel scans. All the patients underwent surgical interventions within a week. The surgical approach includes the use of a linear marker for edema localization and indocyanine green (ICG) lymphography with a near-infrared surgical navigation system intra-operatively. Lymph transport in lymphatic channels was clearly observed by visualization of {sup 68}Ga-NEB activity in the lymphatic vessels and within lymph nodes for all 11 patients as well as the visualization of the edema section plane with dermal backflow (DB), abnormally increased and disconnected uptake along the lymphatic channels. Preoperative {sup 68}Ga-NEB PET combined with MRL provides advantageous three-dimensional images, higher temporal resolution, significantly shorter time lapse before image acquisition after tracer injection and more accurate pathological lymphatic vessel distribution than {sup 99m}Tc-SC lymphoscintigraphy combined with MRI. This study documented an effective imaging pattern to combine {sup 68}Ga-NEB PET and MRL in patients with lower

  2. Proton receptor GPR68 expression in dendritic-cell-like S100β-positive cells of rat anterior pituitary gland: GPR68 induces interleukin-6 gene expression in extracellular acidification.

    Science.gov (United States)

    Horiguchi, Kotaro; Higuchi, Masashi; Yoshida, Saishu; Nakakura, Takashi; Tateno, Kozue; Hasegawa, Rumi; Takigami, Shu; Ohsako, Shunji; Kato, Takako; Kato, Yukio

    2014-11-01

    S100β-positive cells, which do not express the classical pituitary hormones, appear to possess multifunctional properties and are assumed to be heterogeneous in the anterior pituitary gland. The presence of several protein markers has shown that S100β-positive cells are composed of populations such as stem/progenitor cells, epithelial cells, astrocytes and dendritic cells. Recently, we succeeded in separating S100β-positive cells into round-cell (dendritic-cell-like) and process-cell types. We also found the characteristic expression of anti-inflammatory factors (interleukin-6, Il-6) and membrane receptors (integrin β-6) in the round type. Here, we further investigate the function of the subpopulation of S100β-positive cells. Since IL-6 is also a paracrine factor that regulates hormone producing-cells, we examine whether a correlation exists among extracellular acid stress, IL-6 and hormone production by using primary cultures of anterior pituitary cells. Dendritic-cell-like S100β-positive cells notably expressed Gpr68 (proton receptor) and Il-6. Furthermore, the expression of Il-6 and proopiomelanocortin (Pomc) was up-regulated by extracellular acidification. The functional role of IL-6 and GPR68 in the gene expression of Pomc during extracellular acidification was also examined. Small interfering RNA for Il-6 up-regulated Pomc expression and that for Gpr68 reversed the down-regulation of Il-6 and up-regulated Pomc expression by extracellular acidification. Thus, S100β-positive dendritic-like cells can sense an increase in extracellular protons via GPR68 and respond by the production of IL-6 in order to suppress the up-regulation of Pomc expression.

  3. Femmes cinéastes en France : l'après-mai 68

    OpenAIRE

    ROLLET, Brigitte

    2006-01-01

    Agnès Varda, Coline Serreau, Nelly Kaplan, trois noms parmi des dizaines qui illustrent chacun à leur manière une nouvelle façon de faire du cinéma : même si la carrière de la première est antérieure à mai 68, son nom comme celui des autres est lié à ce qu’on appellera dans les années 1970 le « cinéma des femmes ». Cet article propose une interrogation sur ce cinéma au féminin, afin d’envisager à la fois le contexte particulier dans lequel il émerge, les problématiques qu’il soulève, et ce en...

  4. Preclinical Assessment of a 68Ga-DOTA-Functionalized Depsipeptide as a Radiodiagnostic Infection Imaging Agent.

    Science.gov (United States)

    Ebenhan, Thomas; Mokaleng, Botshelo Brenda; Venter, Jacobus Daniel; Kruger, Hendrik Gert; Zeevaart, Jan Rijn; Sathekge, Mike

    2017-08-24

    The study assessed a radiolabeled depsipeptide conjugate ( 68 Ga-DOTA-TBIA101) for its potential as an imaging agent targeting infection or infection-associated inflammation. 68 Ga-labeled DOTA-TBIA101 imaging was performed in (NZR1) healthy rabbits; (NZR2) rabbits bearing muscular sterile inflammation and Staphylococcus aureus (SA) infection; and (NZR3) rabbits infected with Mycobacterium tuberculosis (MTB) combined with a subcutaneous scruff infection of SA in the same animal. All animals were imaged using a PET/CT scanner at 5 and 60 min post injection. Images showed elevated accumulation of 68 Ga-DOTA-TBIA101 in the sterile muscular inflammation site (T/NT ratio = 2.6 ± 0.37 (5 min) and 2.8 ± 2.3 (60 min)) and muscles infected with MTB (T/NT ratio = 2.6 ± 0.35 (5 min) and 2.8 ± 0.16 (60 min)). The findings suggest that 68 Ga-DOTA-TBIA101-PET/CT may detect MTB-associated inflammation, although more foundational studies need to be performed to rationalize the diagnostic value of this technique.

  5. CT vs 68Ge attenuation correction in a combined PET/CT system: evaluation of the effect of lowering the CT tube current

    International Nuclear Information System (INIS)

    Kamel, Ehab; Hany, Thomas F.; Burger, Cyrill; Treyer, Valerie; Schulthess von, Gustav K.; Buck, Alfred; Lonn, Albert H.R.

    2002-01-01

    With the introduction of combined positron emission tomography/computed tomography (PET/CT) systems, several questions have to be answered. In this work we addressed two of these questions: (a) to what value can the CT tube current be reduced while still yielding adequate maps for the attenuation correction of PET emission scans and (b) how do quantified uptake values in tumours derived from CT and germanium-68 attenuation correction compare. In 26 tumour patients, multidetector CT scans were acquired with 10, 40, 80 and 120 mA (CT 10 , CT 40 , CT 80 and CT 120 ) and used for the attenuation correction of a single FDG PET emission scan, yielding four PET scans designated PET CT10 -PET CT120 . In 60 tumorous lesions, FDG uptake and lesion size were quantified on PET CT10 -PET CT120 . In another group of 18 patients, one CT scan acquired with 80 mA and a standard transmission scan acquired using 68 Ge sources were employed for the attenuation correction of the FDG emission scan (PET CT80 , PET 68Ge ). Uptake values and lesion size in 26 lesions were compared on PET CT80 and PET 68Ge . In the first group of patients, analysis of variance revealed no significant effect of CT current on tumour FDG uptake or lesion size. In the second group, tumour FDG uptake was slightly higher using CT compared with 68 Ge attenuation correction, especially in lesions with high FDG uptake. Lesion size was similar on PET CT80 and PET 68Ge . In conclusion, low CT currents yield adequate maps for the attenuation correction of PET emission scans. Although the discrepancy between CT- and 68 Ge-derived uptake values is probably not relevant in most cases, it should be kept in mind if standardised uptake values derived from CT and 68 Ge attenuation correction are compared. (orig.)

  6. 47 CFR 68.348 - Changes in equipment and circuitry subject to a Supplier's Declaration of Conformity.

    Science.gov (United States)

    2010-10-01

    ... Supplier's Declaration of Conformity. 68.348 Section 68.348 Telecommunication FEDERAL COMMUNICATIONS... a Supplier's Declaration of Conformity. (a) No change shall be made in terminal equipment or... Declaration of Conformity Statement furnished to users. (b) Any other changes in terminal equipment or...

  7. Rapid kit-based (68)Ga-labelling and PET imaging with THP-Tyr(3)-octreotate: a preliminary comparison with DOTA-Tyr(3)-octreotate.

    Science.gov (United States)

    Ma, Michelle T; Cullinane, Carleen; Waldeck, Kelly; Roselt, Peter; Hicks, Rodney J; Blower, Philip J

    2015-12-01

    Ge/(68)Ga generators provide an inexpensive source of a PET isotope to hospitals without cyclotron facilities. The development of new (68)Ga-based molecular imaging agents and subsequent clinical translation would be greatly facilitated by simplification of radiochemical syntheses. We report the properties of a tris(hydroxypyridinone) conjugate of the SSTR2-targeted peptide, Tyr(3)-octreotate (TATE), and compare the (68)Ga-labelling and biodistribution of [(68)Ga(THP-TATE)] with the clinical radiopharmaceutical [(68)Ga(DOTATATE)]. A tris(hydroxypyridinone) with a pendant isothiocyanate group was conjugated to the primary amine terminus of H2N-PEG2-Lys(iv-Dde)(5)-TATE, and the resulting conjugate was deprotected to provide THP-TATE. THP-TATE was radiolabelled with (68)Ga(3+) from a (68)Ge/(68)Ga generator. In vitro uptake was assessed in SSTR2-positive 427-7 cells and SSTR2-negative 427 (parental) cells. Biodistribution of [(68)Ga(THP-TATE)] was compared with that of [(68)Ga(DOTATATE)] in Balb/c nude mice bearing SSTR2-positive AR42J tumours. PET scans were obtained 1 h post-injection, after which animals were euthanised and tissues/organs harvested and counted. [(68)Ga(THP-TATE)] was radiolabelled and formulated rapidly in negative cells, and receptor binding and internalisation were specific. Animals administered [(68)Ga(THP-TATE)] demonstrated comparable SSTR2-positive tumour activity (11.5 ± 0.6 %ID g(-1)) compared to animals administered [(68)Ga(DOTATATE)] (14.4 ± 0.8 %ID g(-1)). Co-administration of unconjugated Tyr(3)-octreotate effectively blocked tumour accumulation of [(68)Ga(THP-TATE)] (2.7 ± 0.6 %ID g(-1)). Blood clearance of [(68)Ga(THP-TATE)] was rapid and excretion was predominantly renal, although compared to [(68)Ga(DOTATATE)], [(68)Ga(THP-TATE)] exhibited comparatively longer kidney retention. Radiochemical synthesis of [(68)Ga(THP-TATE)] is significantly faster, proceeds under milder conditions, and requires less manipulation

  8. Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models.

    Science.gov (United States)

    Zhang, Libo; Vines, Douglass C; Scollard, Deborah A; McKee, Trevor; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Vali, Reza; Shammas, Amer; Besanger, Travis; Baruchel, Sylvain

    2017-01-01

    Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68 Ga-DOTA-TATE uptake and 177 Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68 Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68 Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177 Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro , NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131 I-MIBG therapy, low 123 I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68 Ga-DOTA-TATE uptake and antitumor efficacy of 177 Lu-DOTA-TATE. 68 Ga-DOTA-TATE PET is superior to 123 I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177 Lu-DOTA-TATE therapy.

  9. Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

    Directory of Open Access Journals (Sweden)

    Libo Zhang

    2017-01-01

    Full Text Available Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2 expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15 compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2. Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal, tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET, a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy.

  10. 7 CFR 1956.68 - Compromise or adjustment without debtor's signature.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 14 2010-01-01 2009-01-01 true Compromise or adjustment without debtor's signature... Loan Programs and Multi-Family Housing § 1956.68 Compromise or adjustment without debtor's signature... made to obtain the debtor's signature and the date(s) of such effort. (c) The specific reasons why it...

  11. Functional interaction between Smad, CREB binding protein, and p68 RNA helicase

    International Nuclear Information System (INIS)

    Warner, Dennis R.; Bhattacherjee, Vasker; Yin, Xiaolong; Singh, Saurabh; Mukhopadhyay, Partha; Pisano, M. Michele; Greene, Robert M.

    2004-01-01

    The transforming growth factors β control a diversity of biological processes including cellular proliferation, differentiation, apoptosis, and extracellular matrix production, and are critical effectors of embryonic patterning and development, including that of the orofacial region. TGFβ superfamily members signal through specific cell surface receptors that phosphorylate the cytoplasmic Smad proteins, resulting in their translocation to the nucleus and interaction with promoters of TGFβ-responsive genes. Subsequent alterations in transcription are cell type-specific and dependent on recruitment to the Smad/transcription factor complex of coactivators, such as CBP and p300, or corepressors, such as c-ski and SnoN. Since the affinity of Smads for DNA is generally low, additional accessory proteins that facilitate Smad/DNA binding are required, and are often cell- and tissue-specific. In order to identify novel Smad 3 binding proteins in developing orofacial tissue, a yeast two hybrid assay was employed in which the MH2 domain of Smad 3 was used to screen an expression library derived from mouse embryonic orofacial tissue. The RNA helicase, p68, was identified as a unique Smad binding protein, and the specificity of the interaction was confirmed through various in vitro and in vivo assays. Co-expression of Smad 3 and a CBP-Gal4 DNA binding domain fusion protein in a Gal4-luciferase reporter assay resulted in increased TGFβ-stimulated reporter gene transcription. Moreover, co-expression of p68 RNA helicase along with Smad 3 and CBP-Gal4 resulted in synergistic activation of Gal4-luciferase reporter expression. Collectively, these data indicate that the RNA helicase, p68, can directly interact with Smad 3 resulting in formation of a transcriptionally active ternary complex containing Smad 3, p68, and CBP. This offers a means of enhancing TGFβ-mediated cellular responses in developing orofacial tissue

  12. {sup 68}Ga-DOTA{sup 0}-Tyr{sup 3}-octreotide positron emission tomography in nasopharyngeal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Schartinger, Volker H.; Dudas, Jozsef; Url, Christoph; Riechelmann, Herbert [Medical University Innsbruck, Department of Otorhinolaryngology, Innsbruck (Austria); Reinold, Susanne [Medical University Innsbruck, Institute of Pathology, Innsbruck (Austria); Virgolini, Irene J.; Kroiss, Alexander; Uprimny, Christian [Medical University Innsbruck, Department for Nuclear Medicine, Innsbruck (Austria)

    2015-01-15

    PET/CT with {sup 68}Ga-labelled [DOTA{sup 0},Tyr{sup 3}]-octreotide ({sup 68}Ga-DOTA-TOC PET/CT) is a routinely used imaging modality for neuroendocrine tumours expressing somatostatin receptors (SSTR). Recent studies have shown SSTR expression in head and neck squamous cell carcinoma, albeit lower than in highly differentiated neuroendocrine tumours. We sought to determine whether nasopharyngeal carcinoma (NPC) positive for Epstein-Barr virus (EBV), a rare subtype of head and neck cancer, shows increased {sup 68}Ga-DOTA-TOC uptake indicating expression of SSTR. Five patients with untreated, histologically proven EBV-positive NPC were referred for {sup 68}Ga-DOTA-TOC PET/CT. Tracer uptake in tumour lesions was assessed visually and semiquantitatively measuring maximum standardized uptake values (SUVmax) and tumour to background ratios. Increased tumour-specific uptake was detected in all five patients with a median SUVmax of 10.6 (range 3.6 - 17.1) in the primary tumour and 13.2 (range 6.1 - 14.5) in cervical lymph node metastases. {sup 68}Ga-DOTA-TOC PET/CT demonstrated tracer uptake in EBV-positive NPC comparable to that in highly differentiated neuroendocrine tumours. This observation is consistent with increased SSTR expression in EBV-positive NPC and may open new diagnostic and therapeutic windows in NPC. (orig.)

  13. Genome packaging in EL and Lin68, two giant phiKZ-like bacteriophages of P. aeruginosa

    International Nuclear Information System (INIS)

    Sokolova, O.S.; Shaburova, O.V.; Pechnikova, E.V.; Shaytan, A.K.; Krylov, S.V.; Kiselev, N.A.; Krylov, V.N.

    2014-01-01

    A unique feature of the Pseudomonas aeruginosa giant phage phiKZ is its way of genome packaging onto a spool-like protein structure, the inner body. Until recently, no similar structures have been detected in other phages. We have studied DNA packaging in P. aeruginosa phages EL and Lin68 using cryo-electron microscopy and revealed the presence of inner bodies. The shape and positioning of the inner body and the density of the DNA packaging in EL are different from those found in phiKZ and Lin68. This internal organization explains how the shorter EL genome is packed into a large EL capsid, which has the same external dimensions as the capsids of phiKZ and Lin68. The similarity in the structural organization in EL and other phiKZ-like phages indicates that EL is phylogenetically related to other phiKZ-like phages, and, despite the lack of detectable DNA homology, EL, phiKZ, and Lin68 descend from a common ancestor. - Highlights: • We performed a comparative structural study of giant P. aeruginosa phages: EL, Lin68 and phiKZ. • We revealed that the inner body is a common feature in giant phages. • The phage genome size correlates with the overall dimensions of the inner body

  14. Genome packaging in EL and Lin68, two giant phiKZ-like bacteriophages of P. aeruginosa

    Energy Technology Data Exchange (ETDEWEB)

    Sokolova, O.S., E-mail: sokolova@mail.bio.msu.ru [M.V. Lomonosov Moscow State University, Moscow (Russian Federation); A.V. Shoubnikov Institute of Crystallography RAS, Moscow (Russian Federation); Shaburova, O.V. [I.I. Mechnikov Research Institute of Vaccines and Sera, RAMS, Moscow (Russian Federation); Pechnikova, E.V. [A.V. Shoubnikov Institute of Crystallography RAS, Moscow (Russian Federation); Shaytan, A.K. [M.V. Lomonosov Moscow State University, Moscow (Russian Federation); Krylov, S.V. [I.I. Mechnikov Research Institute of Vaccines and Sera, RAMS, Moscow (Russian Federation); Kiselev, N.A. [A.V. Shoubnikov Institute of Crystallography RAS, Moscow (Russian Federation); Krylov, V.N. [I.I. Mechnikov Research Institute of Vaccines and Sera, RAMS, Moscow (Russian Federation)

    2014-11-15

    A unique feature of the Pseudomonas aeruginosa giant phage phiKZ is its way of genome packaging onto a spool-like protein structure, the inner body. Until recently, no similar structures have been detected in other phages. We have studied DNA packaging in P. aeruginosa phages EL and Lin68 using cryo-electron microscopy and revealed the presence of inner bodies. The shape and positioning of the inner body and the density of the DNA packaging in EL are different from those found in phiKZ and Lin68. This internal organization explains how the shorter EL genome is packed into a large EL capsid, which has the same external dimensions as the capsids of phiKZ and Lin68. The similarity in the structural organization in EL and other phiKZ-like phages indicates that EL is phylogenetically related to other phiKZ-like phages, and, despite the lack of detectable DNA homology, EL, phiKZ, and Lin68 descend from a common ancestor. - Highlights: • We performed a comparative structural study of giant P. aeruginosa phages: EL, Lin68 and phiKZ. • We revealed that the inner body is a common feature in giant phages. • The phage genome size correlates with the overall dimensions of the inner body.

  15. {sup 68}Ga-PSMA-11 dynamic PET/CT imaging in biochemical relapse of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Sachpekidis, C. [German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center, Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Eder, M. [German Cancer Research Center (DKFZ), Division of Radiopharmaceutical Chemistry, Heidelberg (Germany); Kopka, K. [German Cancer Research Center (DKFZ), Division of Radiopharmaceutical Chemistry, Heidelberg (Germany); German Cancer Consortium (DKTK), Heidelberg (Germany); Mier, W. [University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany); Hadaschik, B.A. [University Hospital Heidelberg, Department of Urology, Heidelberg (Germany); Haberkorn, U. [German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); German Cancer Consortium (DKTK), Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

    2016-07-15

    We aim to investigate the pharmacokinetics and distribution of the recently clinically introduced radioligand {sup 68}Ga-PSMA-11 in men with recurrent prostate cancer (PC) by means of dynamic and whole-body PET/CT. The correlation between PSA levels and {sup 68}Ga-PSMA-11 PET parameters is also investigated. 31 patients with biochemical failure after primary PC treatment with curative intent (median age 71.0 years) were enrolled in the analysis. The median PSA value was 2.0 ng/mL (range = 0.1 - 130.0 ng/mL) and the median Gleason score was 7 (range = 5 - 9). 8/31 (25.8 %) of the included patients had a PSA value < 0.5 ng/ml. All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with {sup 68}Ga-PSMA-11. dPET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). 22/31 patients (71.0 %) were {sup 68}Ga-PSMA-11-positive, while 9/31 (29.0 %) patients were {sup 68}Ga-PSMA-11-negative. The median PSA value in the {sup 68}Ga-PSMA-11-positive group was significantly higher (median = 2.35 ng/mL; range = 0.19 - 130.0 ng/mL) than in the {sup 68}Ga-PSMA-11-negative group (median value: 0.34 ng/mL; range = 0.10 - 4.20 ng/mL). A total of 76 lesions were semi-quantitatively evaluated. PC recurrence-associated lesions demonstrated a mean SUV{sub average} = 12.4 (median = 9.0; range = 2.2 - 84.5) and mean SUV{sub max} = 18.8 (median = 14.1; range = 3.1 - 120.3). Dynamic PET/CT studies of the pelvis revealed the following mean values for the PC recurrence-suspicious lesions: K{sub 1} = 0.26, k{sub 3} = 0.30, influx = 0.14 and FD = 1.24. Time-activity curves derived from PC-recurrence indicative lesions revealed an increasing {sup 68}Ga-PSMA-11 accumulation during dynamic PET acquisition. Correlation analysis revealed a moderate, but significant

  16. Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor–Positive Tumors

    Science.gov (United States)

    Brom, Maarten; Joosten, Lieke; Laverman, Peter; Oyen, Wim J.G.; Béhé, Martin; Gotthardt, Martin; Boerman, Otto C.

    2011-01-01

    In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0) showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET), which could improve image quality. Targeting of cholecystokinin-2 (CCK2)/gastrin receptor–positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET–computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g), indicating CCK2/gastrin receptor–mediated uptake (p = .0005). The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor–positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor–positive tumors in humans. PMID:21439259

  17. Preclinical Evaluation of 68Ga-DOTA-Minigastrin for the Detection of Cholecystokinin-2/Gastrin Receptor-Positive Tumors

    Directory of Open Access Journals (Sweden)

    Maarten Brom

    2011-03-01

    Full Text Available In comparison to somatostatin receptor scintigraphy, gastrin receptor scintigraphy using 111In-DTPA-minigastrin (MG0 showed added value in diagnosing neuroendocrine tumors. We investigated whether the 68Ga-labeled gastrin analogue DOTA-MG0 is suited for positron emission tomography (PET, which could improve image quality. Targeting of cholecystokinin-2 (CCK2/gastrin receptor-positive tumor cells with DOTA-MG0 labeled with either 111In or 68Ga in vitro was investigated using the AR42J rat tumor cell line. Biodistribution was examined in BALB/c nude mice with a subcutaneous AR42J tumor. In vivo PET imaging was performed using a preclinical PET-computed tomographic scanner. DOTA-MG0 showed high receptor affinity in vitro. Biodistribution studies revealed high tumor uptake of 68Ga-DOTA-MG0: 4.4 ± 1.3 %ID/g at 1 hour postinjection. Coadministration of an excess unlabeled peptide blocked the tumor uptake (0.7 ± 0.1 %ID/g, indicating CCK2/gastrin receptor-mediated uptake (p = .0005. The biodistribution of 68Ga-DOTA-MG0 was similar to that of 111In-DOTA-MG0. Subcutaneous and intraperitoneal tumors were clearly visualized by small-animal PET imaging with 5 MBq 68Ga-DOTA-MG0. 111In- and 68Ga-labeled DOTA-MG0 specifically accumulate in CCK2/gastrin receptor-positive AR42J tumors with similar biodistribution apart from the kidneys. AR42J tumors were clearly visualized by microPET. Therefore, 68Ga-DOTA-MG0 is a promising tracer for PET imaging of CCK2/gastrin receptor-positive tumors in humans.

  18. Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Weijie, E-mail: 459586768@qq.com; Liu, Yuxi, E-mail: 924013616@qq.com; Wang, Youhua, E-mail: wyouhua1516@163.com

    2016-05-13

    Sam68 (Src-associated in mitosis of 68 kD), a KH domain RNA-binding protein, is not only important in signaling transduction cascades, but crucial in a variety of cellular processes. Sam68 is reported to be involved in the phospoinositide3-kinase (PI3K) and nuclear factor-kappa B (NF-κB) signaling pathways, and it is closely associated with cell proliferation, RNA metabolism, and tumor progression. However, we know little about the role of Sam68 during peripheral nervous system injury and regeneration. In this study, we investigated the expression of Sam68 and its biological significances in sciatic nerve crush. Interestingly, we found Sam68 had a co-localization with S100 (Schwann cell marker). Moreover, after crush, Sam68 had a spatiotemporal protein expression, which was in parallel with proliferation cell nuclear antigen (PCNA). In vitro, we also observed increased expression of Sam68 during the process of TNF-α-induced Schwann cell proliferation model. Besides, flow cytometry analyses, CCK-8, and EDU were all performed with the purpose of investigating the role of Sam68 in the regulation of Schwann cell proliferation. Even more importantly, we discovered that Sam68 could enhance the phosphorylation of Akt while LY294002 (a PI3K inhibitor) obviously reversed Sam68-induced cell proliferation. Finally, we detected the variance during regeneration progress through the rat walk footprint test. In summary, all these evidences demonstrated that Sam68 might participate in Schwann cell proliferation partially via PI3K/Akt pathway and also regulate regeneration after sciatic nerve crush. -- Highlights: •The dynamic changes and location of Sam68 after sciatic nerve crush. •Sam68 promoted Schwann cell proliferation via PI3K/Akt pathway. •Sam68 modulated functional recovery after sciatic nerve crush.

  19. Sam68 promotes Schwann cell proliferation by enhancing the PI3K/Akt pathway and acts on regeneration after sciatic nerve crush

    International Nuclear Information System (INIS)

    Wu, Weijie; Liu, Yuxi; Wang, Youhua

    2016-01-01

    Sam68 (Src-associated in mitosis of 68 kD), a KH domain RNA-binding protein, is not only important in signaling transduction cascades, but crucial in a variety of cellular processes. Sam68 is reported to be involved in the phospoinositide3-kinase (PI3K) and nuclear factor-kappa B (NF-κB) signaling pathways, and it is closely associated with cell proliferation, RNA metabolism, and tumor progression. However, we know little about the role of Sam68 during peripheral nervous system injury and regeneration. In this study, we investigated the expression of Sam68 and its biological significances in sciatic nerve crush. Interestingly, we found Sam68 had a co-localization with S100 (Schwann cell marker). Moreover, after crush, Sam68 had a spatiotemporal protein expression, which was in parallel with proliferation cell nuclear antigen (PCNA). In vitro, we also observed increased expression of Sam68 during the process of TNF-α-induced Schwann cell proliferation model. Besides, flow cytometry analyses, CCK-8, and EDU were all performed with the purpose of investigating the role of Sam68 in the regulation of Schwann cell proliferation. Even more importantly, we discovered that Sam68 could enhance the phosphorylation of Akt while LY294002 (a PI3K inhibitor) obviously reversed Sam68-induced cell proliferation. Finally, we detected the variance during regeneration progress through the rat walk footprint test. In summary, all these evidences demonstrated that Sam68 might participate in Schwann cell proliferation partially via PI3K/Akt pathway and also regulate regeneration after sciatic nerve crush. -- Highlights: •The dynamic changes and location of Sam68 after sciatic nerve crush. •Sam68 promoted Schwann cell proliferation via PI3K/Akt pathway. •Sam68 modulated functional recovery after sciatic nerve crush.

  20. Ga-68 Somatostatin Receptor PET/CT in von Hippel-Lindau Disease

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Jong-Ryool; Min, Jung-Joon [Chonnam National Univ. Hwasun Hospital, Hwasun (Korea, Republic of); Kulkarui, Harshad; Carreras, Cecilia; Schalch, Georg; Baum, Richard P. [Nuclear Medicine and Center for PET/CT, Zentralk Bad Berka, Bad Verka (Germany)

    2012-06-15

    Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome with a variety of benign and malignant tumors such as retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renalcysts and tumors, pancreatic cysts and tumors, pheochromo-cytomas, and epididymal cystadenomas. Cross-sectional mo-dalities (computed tomography and magnetic resonance imaging) as well as ultrasound play a major role in the initial evaluation and follow-up of the various manifestations of VHL disease. Ga-68-labeled somatostatin receptor analogs already have a significant role in the diagnosis, staging, and therapy management of neuroendocrine neoplasms and neural crest tumors. Herein, we report a case presenting a variety of malignancies in VHL and showing the usefulness of Ga-68 somatostatin receptor PET/CT as a one-stop-shop imaging modality in the management of VHL disease.

  1. Ga-68 Somatostatin Receptor PET/CT in von Hippel-Lindau Disease

    International Nuclear Information System (INIS)

    Oh, Jong-Ryool; Min, Jung-Joon; Kulkarui, Harshad; Carreras, Cecilia; Schalch, Georg; Baum, Richard P.

    2012-01-01

    Von Hippel-Lindau (VHL) disease is a dominantly inherited familial cancer syndrome with a variety of benign and malignant tumors such as retinal and central nervous system hemangioblastomas, endolymphatic sac tumors, renalcysts and tumors, pancreatic cysts and tumors, pheochromo-cytomas, and epididymal cystadenomas. Cross-sectional mo-dalities (computed tomography and magnetic resonance imaging) as well as ultrasound play a major role in the initial evaluation and follow-up of the various manifestations of VHL disease. Ga-68-labeled somatostatin receptor analogs already have a significant role in the diagnosis, staging, and therapy management of neuroendocrine neoplasms and neural crest tumors. Herein, we report a case presenting a variety of malignancies in VHL and showing the usefulness of Ga-68 somatostatin receptor PET/CT as a one-stop-shop imaging modality in the management of VHL disease

  2. Single vial kit formulation for preparation of {sup 68}Ga-AMBA: a PET imaging agent for prostate cancers

    Energy Technology Data Exchange (ETDEWEB)

    Pandey, Usha; Mukherjee, Archana; Gamre, Naresh; Dash, Ashutosh [Isotope Applications and Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai (India); Sarma, Haladhar Dev [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai (India)

    2014-05-01

    This work was aimed at the kit formulation of a bombesin analog, AMBA, for potential use in imaging of prostate cancers after {sup 68}Ga labeling. Towards this aim, a kit was formulated in acetate buffer under aseptic conditions for labeling with {sup 68}Ga eluted from the nanoceria-PAN based {sup 68}Ge/{sup 68}Ga BARC generator. All the reaction parameters for optimum radiolabeling were standardized and the radiometal complexes were characterized by chromatography techniques. The kit formulations gave >95% radiolabeling yields consistently when tested up to two months. Pharmacokinetics of the radiolabeled peptide was studied in Swiss mice, which showed fast clearance of activity via renal route. (author)

  3. 36 CFR 6.8 - National Park Service solid waste responsibilities.

    Science.gov (United States)

    2010-07-01

    ..., DEPARTMENT OF THE INTERIOR SOLID WASTE DISPOSAL SITES IN UNITS OF THE NATIONAL PARK SYSTEM § 6.8 National Park Service solid waste responsibilities. (a) Beginning one year after January 23, 1995, a Superintendent will not permit or allow a person to dispose of solid waste at a National Park Service operated...

  4. Supporting English Language Learners in Math Class, Grades 6-8

    Science.gov (United States)

    Melanese, Kathy; Chung, Luz; Forbes, Cheryl

    2011-01-01

    This new addition to Math Solutions "Supporting English Language Learners in Math Class series" offers a wealth of lessons and strategies for modifying grades 6-8 instruction. Section I presents an overview of teaching math to English learners: the research, the challenges, the linguistic demands of a math lesson, and specific strategies and…

  5. Immunohistochemical Expression of TGF-Β1, SMAD4, SMAD7, TGFβRII and CD68-Positive TAM Densities in Papillary Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Koni Ivanova

    2018-03-01

    Full Text Available BACKGROUND: Papillary thyroid carcinoma (PTC accounts for 80% of the thyroid malignancies that are characterised by slow growth and an excellent prognosis. Over-expression of SMAD4 protein restores TGF-β signalling, determines a strong increase in anti-proliferative effect and reduces invasive potential of tumour cells expressing it. AIM: The study aimed to analyse the immunohistochemical expression of TGF-β1 and its downstream phosphorylated SMAD4, element and of the inhibitory SMAD7 PTC variants and their association with the localisation of TAMs within the tumour microenvironment. METHODS: For this retrospective study we investigated 69 patients immunohistochemistry with antibodies against TGF-β, TGF – β-RII, SMAD4, SMAD7, CD68+ macrophages. RESULTS: Patients with low infiltration with CD68+ cells in tumour stroma has significantly shorter survival (median of 129.267 months compared to those with high CD68+ cells infiltration (p = 0.034. From the analysis of CD68+ cells in tumour border and tumour stroma correlated with expression of TGF-β1 / SMAD proteins, we observed that the positive expression of TGF-β1 in tumour cytoplasm, significantly correlated with increased number of CD68+ cells in tumour border (X2 = 5,945; р = 0.015. CONCLUSION: TGF-β enhances motility and stimulates recruitment of monocytes, macrophages and other immune cells while directly inhibiting their anti-tumour effector functions.

  6. Functional Heterogeneity in the CD4+ T Cell Response to Murine γ-Herpesvirus 68

    Science.gov (United States)

    Hu, Zhuting; Blackman, Marcia A.; Kaye, Kenneth M.; Usherwood, Edward J.

    2015-01-01

    CD4+ T cells are critical for the control of virus infections, T cell memory and immune surveillance. Here we studied the differentiation and function of murine γ-herpesvirus 68 (MHV-68)-specific CD4+ T cells using gp150-specific TCR transgenic mice. This allowed a more detailed study of the characteristics of the CD4+ T cell response than previously available approaches for this virus. Most gp150-specific CD4+ T cells expressed T-bet and produced IFN-γ, indicating MHV-68 infection triggered differentiation of CD4+ T cells largely into the Th1 subset, whereas some became TFH and Foxp3+ regulatory T cells. These CD4+ T cells were protective against MHV-68 infection, in the absence of CD8+ T cells and B cells, and protection depended on IFN-γ secretion. Marked heterogeneity was observed in the CD4+ T cells, based on Ly6C expression. Ly6C expression positively correlated with IFN-γ, TNF-α and granzyme B production, T-bet and KLRG1 expression, proliferation and CD4+ T cell-mediated cytotoxicity. Ly6C expression inversely correlated with survival, CCR7 expression and secondary expansion potential. Ly6C+ and Ly6C− gp150-specific CD4+ T cells were able to interconvert in a bidirectional manner upon secondary antigen exposure in vivo. These results indicate that Ly6C expression is closely associated with antiviral activity in effector CD4+ T cells, but inversely correlated with memory potential. Interconversion between Ly6C+ and Ly6C− cells may maintain a balance between the two antigen-specific CD4+ T cell populations during MHV-68 infection. These findings have significant implications for Ly6C as a surface marker to distinguish functionally distinct CD4+ T cells during persistent virus infection. PMID:25662997

  7. Molecular imaging of neuroendocrine tumors using 68Ga-labeled peptides (Somatostatin receptor PET/CT)

    International Nuclear Information System (INIS)

    Baum, R.P.; Prasad, V.; Hoersch, D.

    2009-01-01

    Receptor PET/CT using 68 Ga-labeled somatostatin analogues (DOTA-NOC, DOTA-TOC or DOTA-TATE) enables the highly sensitive molecular imaging of neuroendocrine tumors (NETs) based on the expression of somatostatin receptors and even the detection of receptor subtypes. Our experience after more than 3000 studies shows that receptor PET/CT has a significantly higher tumor detection rate than conventional scintigraphy (even in SPECT/CT technique), and that tumor lesions can be very accurately localized. By calculating standardized uptake values (SUV) - which are reproducible and investigator-independent - patients can be selected for peptide receptor radiotherapy and also the course after therapy can be controlled. Receptor-PET/CT is the most sensitive imaging modality for the detection of unknown primary tumors (CUP syndrome), which is especially true for the detection of neuroendocrine tumors of the pancreas and small bowel; whole-body staging (''one stop shop'') as well as restaging and selection of patients for peptide receptor radiotherapy can be performed using a patient-friendly procedure (examination finished within one hour) exposing the patient to less radiation than whole-body CT scanning. The 68 Ge/ 68 Ga generator has proved very reliable over the years - even in a hospital environment. The effective costs for 68 Ga labeled somatostatin analogues might be less than for scintigraphic agents, provided a certain number of studies per year are performed. The development of new tumor-specific peptides as well as of other DOTA- or NOTA-coupled radiopharmaceuticals opens a new avenue into the future: finally, the 68 Ga generator could play a similar important role for PET/CT as did the 99m Tc-Generator for conventional gamma camera imaging over the last decades. (orig.)

  8. Is {sup 68}Ga-DOTA-NOC PET/CT indicated in patients with clinical, biochemical or radiological suspicion of neuroendocrine tumour?

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosini, Valentina [S. Orsola-Malpighi University Hospital, Nuclear Medicine, Bologna (Italy); Azienda Ospedaliero Universitaria di Bologna, Policlinico S. Orsola-Malpighi, Nuclear Medicine, Pad 30, Bologna (Italy); Campana, Davide; Tomassetti, Paola [S. Orsola-Malpighi University Hospital, Internal Medicine, Bologna (Italy); Nanni, Cristina; Cambioli, Silvia; Fanti, Stefano [S. Orsola-Malpighi University Hospital, Nuclear Medicine, Bologna (Italy); Rubello, Domenico [Ospedale S. Maria della Misericordia, Nuclear Medicine, Rovigo (Italy)

    2012-08-15

    In recent years, {sup 68}Ga-DOTA-peptides positron emission tomography (PET)/CT has been increasingly used to study patients with neuroendocrine tumours (NET). However, performing specialized examinations in the appropriate contest is mandatory for both medical and economic reasons. The aim of the study is to evaluate the potential usefulness of {sup 68}Ga-DOTA-NOC PET/CT in patients with suspected NET. Among the patients undergoing {sup 68}Ga-DOTA-NOC PET/CT at our centre, we reviewed those studied for suspected NET based on the presence of either clinical signs/symptoms or imaging or raised biochemical markers or a combination of these conditions. PET/CT results were compared with clinical and imaging follow-up of at least 1 year or pathology. Overall 131 suspected NET cases were included. The most common condition considered suspicious for NET was the increase of blood markers (66), followed by inconclusive findings at conventional imaging (CI, 41), clinical signs/symptoms (10), equivocal {sup 18}F-fluorodeoxyglucose (FDG) PET (7) or somatostatin receptor scintigraphy (SRS, 4), or a combination of the above (3). PET/CT results were true-positive in 17 cases, true-negative in 112 and false-negative in 2 (overall sensitivity 89.5 %, specificity 100 %). Interestingly, increased blood markers and clinical signs/symptoms were associated with the lowest frequency of true-positive findings (1/66 and 1/10, respectively), while CI findings were confirmed in one third of the cases (13/41). Overall, the incidence of NET in the studied population was 14.5 % (19/131). Our data confirm the good accuracy (98 %) of {sup 68}Ga-DOTA-NOC PET/CT in NET lesion detection. However, our results also suggest that {sup 68}Ga-DOTA-NOC PET/CT may not be routinely recommended in patients with a suspicion of NET based on the mere detection of increased blood markers or clinical symptoms. Positive CI alone or in association with clinical/biochemical findings is on the contrary associated with

  9. Automated synthesis, characterization and biological evaluation of [{sup 68}Ga]Ga-AMBA, and the synthesis and characterization of {sup nat}Ga-AMBA and [{sup 67}Ga]Ga-AMBA

    Energy Technology Data Exchange (ETDEWEB)

    Cagnolini, Aldo; Chen Jianqing; Ramos, Kimberly; Marie Skedzielewski, Tina; Lantry, Laura E.; Nunn, Adrian D.; Swenson, Rolf E. [Ernst Felder Laboratories, Bracco Research USA Inc., 305 College Road East, Princeton, NJ 08540 (United States); Linder, Karen E., E-mail: karen.e.linder@gmail.co [Ernst Felder Laboratories, Bracco Research USA Inc., 305 College Road East, Princeton, NJ 08540 (United States)

    2010-12-15

    Ga-AMBA (Ga-DO3A-CH{sub 2}CO-G-[4-aminobenzoyl]-QWAVGHLM-NH{sub 2}) is a bombesin-like agonist with high affinity for gastrin releasing peptide receptors (GRP-R). Syntheses for {sup nat}Ga-AMBA, [{sup 67}Ga]Ga-AMBA and [{sup 68}Ga]Ga-AMBA were developed. The preparation of HPLC-purified and Sep-Pak purified [{sup 68}Ga]Ga-AMBA were fully automated, using the built-in radiodetector of the Tracerlab FX F-N synthesizer to monitor fractionated {sup 68}Ge/{sup 68}Ga generator elution and purification. The total synthesis time, including the fractional elution of the generator, was 20 min for Sep-Pak purified material and 40 min for HPLC-purified [{sup 68}Ga]Ga-AMBA. Both [{sup 67}Ga]Ga-AMBA and [{sup 177}Lu]Lu-AMBA showed comparable high affinity for GRP-R in the human prostate cancer cell line PC-3 in vitro (k{sub D}=0.46{+-}0.07; 0.44{+-}0.08 nM), high internalization (78; 77%) and low efflux from cells at 2 h (2.4{+-}0.7; 2.9{+-}1.8%). Biodistribution results in PC-3 tumor-bearing male nude mice showed comparable uptake for [{sup 177}Lu]Lu-, [{sup 111}In]In-, [{sup 67}Ga]Ga- and [{sup 68}Ga]Ga-AMBA.

  10. Nuclear Protein Sam68 Interacts with the Enterovirus 71 Internal Ribosome Entry Site and Positively Regulates Viral Protein Translation.

    Science.gov (United States)

    Zhang, Hua; Song, Lei; Cong, Haolong; Tien, Po

    2015-10-01

    Enterovirus 71 (EV71) recruits various cellular factors to assist in the replication and translation of its genome. Identification of the host factors involved in the EV71 life cycle not only will enable a better understanding of the infection mechanism but also has the potential to be of use in the development of antiviral therapeutics. In this study, we demonstrated that the cellular factor 68-kDa Src-associated protein in mitosis (Sam68) acts as an internal ribosome entry site (IRES) trans-acting factor (ITAF) that binds specifically to the EV71 5' untranslated region (5'UTR). Interaction sites in both the viral IRES (stem-loops IV and V) and the heterogeneous nuclear ribonucleoprotein K homology (KH) domain of Sam68 protein were further mapped using an electrophoretic mobility shift assay (EMSA) and biotin RNA pulldown assay. More importantly, dual-luciferase (firefly) reporter analysis suggested that overexpression of Sam68 positively regulated IRES-dependent translation of virus proteins. In contrast, both IRES activity and viral protein translation significantly decreased in Sam68 knockdown cells compared with the negative-control cells treated with short hairpin RNA (shRNA). However, downregulation of Sam68 did not have a significant inhibitory effect on the accumulation of the EV71 genome. Moreover, Sam68 was redistributed from the nucleus to the cytoplasm and interacts with cellular factors, such as poly(rC)-binding protein 2 (PCBP2) and poly(A)-binding protein (PABP), during EV71 infection. The cytoplasmic relocalization of Sam68 in EV71-infected cells may be involved in the enhancement of EV71 IRES-mediated translation. Since Sam68 is known to be a RNA-binding protein, these results provide direct evidence that Sam68 is a novel ITAF that interacts with EV71 IRES and positively regulates viral protein translation. The nuclear protein Sam68 is found as an additional new host factor that interacts with the EV71 IRES during infection and could potentially

  11. of radioconjugated DOTA-1-Nal3-octreotide labeled with gallium-68 using non-aqueous solvents

    International Nuclear Information System (INIS)

    Pérez-Malo Cruz, Marylaine; Leyva Montaña, René

    2016-01-01

    Neuroendocrine tumors specifically over-expressing somatostatin receptors. Diagnosis has expanded due to radiolabelling of DOTA-peptides such as somatostatin analogue DOTA-1-Nal 3 -Octreotide (DOTA-NOC) conjugated to β+ emitting radionuclides such as 68 Ga, which has very favorable physics-nuclear properties. This paper describes the radiolabeling procedures of DOTA-NOC with 68 Ga, in pure aqueous medium and in presence of non-aqueous solvents as well as the methods used for quality control where a formulation is obtained with a radiochemical yield exceeding 95%. The addition of ethanol (30% - v / v) to reaction mixture allowed to increase the specific activity of 68 Ga-DOTA-NOC radioconjugate, reaching a value of 182 MBq / nmol, higher than reported in the literature (50 MBq / nmol ) for labeling in pure aqueous medium. Stability studies are also presented (in presence of saline solution and saline phosphate buffer, transmetallation studies in Fe 3+ , Ca 2+ , Mg 2+ and Zn 2+ solutions, challenges competition against EDTA and DTPA chelators and in vitro stability in human transferrin) performed to 68Ga-DOTA-NOC radioconjugated, showing its high stability (> 95%). (author)

  12. Mutations in the pH-Sensing G-protein-Coupled Receptor GPR68 Cause Amelogenesis Imperfecta.

    Science.gov (United States)

    Parry, David A; Smith, Claire E L; El-Sayed, Walid; Poulter, James A; Shore, Roger C; Logan, Clare V; Mogi, Chihiro; Sato, Koichi; Okajima, Fumikazu; Harada, Akihiro; Zhang, Hong; Koruyucu, Mine; Seymen, Figen; Hu, Jan C-C; Simmer, James P; Ahmed, Mushtaq; Jafri, Hussain; Johnson, Colin A; Inglehearn, Chris F; Mighell, Alan J

    2016-10-06

    Amelogenesis is the process of dental enamel formation, leading to the deposition of the hardest tissue in the human body. This process requires the intricate regulation of ion transport and controlled changes to the pH of the developing enamel matrix. The means by which the enamel organ regulates pH during amelogenesis is largely unknown. We identified rare homozygous variants in GPR68 in three families with amelogenesis imperfecta, a genetically and phenotypically heterogeneous group of inherited conditions associated with abnormal enamel formation. Each of these homozygous variants (a large in-frame deletion, a frameshift deletion, and a missense variant) were predicted to result in loss of function. GPR68 encodes a proton-sensing G-protein-coupled receptor with sensitivity in the pH range that occurs in the developing enamel matrix during amelogenesis. Immunohistochemistry of rat mandibles confirmed localization of GPR68 in the enamel organ at all stages of amelogenesis. Our data identify a role for GPR68 as a proton sensor that is required for proper enamel formation. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Diagnostic performance and impact on patient management of 68Ga-DOTA-TOC PET/CT for detecting osteomalacia-associated tumours.

    Science.gov (United States)

    Paquet, Marie; Gauthé, Mathieu; Zhang Yin, Jules; Nataf, Valérie; Bélissant, Ophélie; Orcel, Philippe; Roux, Christian; Talbot, Jean-Noël; Montravers, Françoise

    2018-03-12

    Oncogenic osteomalacia is an endocrine disorder induced by small benign tumours (TIO) producing excessive fibroblast growth factor-23 (FGF23). The only way of curing oncogenic osteomalacia is surgical resection of the culprit TIO, which is extremely difficult to detect using conventional imaging modalities due to its small size and variable location in the body. Since TIO frequently overexpress somatostatin receptors, a clinical utility of SPECT or PET with radiolabelled somatostatin analogues has been reported. Among them, 68 Ga-DOTA-TOC has recently been granted a marketing authorization, facilitating its routine application. We report here the results of the first series evaluating the diagnostic performance of 68 Ga-DOTA-TOC PET/CT in detecting TIO and its impact on patient management. 68 Ga-DOTA-TOC PET/CT and clinical and imaging data from 15 patients with clinical and biochemical signs of oncogenic osteomalacia were retrospectively reviewed. The 68 Ga-DOTA-TOC PET/CT findings were compared with the results of post-surgical pathology and clinical and biochemical follow-up. 68 Ga-DOTA-TOC PET/CT resulted in the detection of one focus suspicious for TIO in nine of 15 patients (60%), and a tumour was surgically removed in eight. Post-operative pathology confirmed a TIO in those eight patients whose symptoms diminished promptly and biochemical anomalies resolved. 68 Ga-DOTA-TOC PET/CT sensitivity, specificity and accuracy were 73%, 67% and 71%, respectively. 68 Ga-DOTA-TOC PET/CT findings affected patient management in 67% of cases. In particular, 68 Ga-DOTA-TOC PET/CT was able to detect the TIO with a negative or a false-positive result of a previous 111 In-pentetreotide SPECT/CT in 5/8 patients (63%) or a previous FDG PET/CT in 7/11 patients (64%). No close relationship was found between the positivity of 68 Ga-DOTA-TOC PET/CT and the serum level of a biochemical marker. However, a true-positive result of 68 Ga-DOTA-TOC PET/CT was obtained in only one patient

  14. 68Ga-labeled phage-display selected peptides as tracers for positron emission tomography imaging of Staphylococcus aureus biofilm-associated infections: Selection, radiolabelling and preliminary biological evaluation

    International Nuclear Information System (INIS)

    Nielsen, Karin M.; Kyneb, Majbritt H.; Alstrup, Aage K.O.; Jensen, Jakob J.; Bender, Dirk; Schønheyder, Henrik C.; Afzelius, Pia; Nielsen, Ole L.; Jensen, Svend B.

    2016-01-01

    Introduction: Staphylococcus aureus is a major cause of skin and deep-sited infections, often associated with the formation of biofilms. Early diagnosis and initiated therapy is essential to prevent disease progression and to reduce complications that can be serious. Imaging techniques are helpful combining anatomical with functional data in order to describe and characterize site, extent and activity of the disease. The purpose of the study was to identify and 68 Ga-label peptides with affinity for S. aureus biofilm and evaluate their potential as bacteria-specific positron emission tomography (PET) imaging agents. Methods: Phage-displayed dodecapeptides were selected using an in vitro grown S. aureus biofilm as target. One cyclic (A8) and two linear (A9, A11) dodecapeptides were custom synthesized with 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid (DOTA) conjugated via a lysine linker (K), and for A11 also a glycine–serine–glycine spacer (GSG). The 68 Ga-labeling of A8-K-DOTA, A9-K-DOTA, and A11-GSGK-DOTA were optimized and in vitro bacterial binding was evaluated for 68 Ga-A9-K-DOTA and 68 Ga-A11-GSGK-DOTA. Stability of 68 Ga-A9-K-DOTA was studied in vitro in human serum, while the in vivo plasma stability was analyzed in mice and pigs. Additionally, the whole-body distribution kinetics of 68 Ga-A9-K-DOTA was measured in vivo by PET imaging of pigs and ex vivo in excised mice tissues. Results: The 68 Ga-A9-K-DOTA and 68 Ga-A11-GSGK-DOTA remained stable in product formulation, whereas 68 Ga-A8-K-DOTA was unstable. The S. aureus binding of 68 Ga-A11-GSGK-DOTA and 68 Ga-A9-K-DOTA was observed in vitro, though blocking of the binding was not possible by excess of cold peptide. The 68 Ga-A9-K-DOTA was degraded slowly in vitro, while the combined in vivo evaluation in pigs and mice showed a rapid blood clearance and renal excretion of the 68 Ga-A9-K-DOTA. Conclusion: The preliminary in vitro and in vivo studies of the phage-display S. aureus

  15. Brain and liver fatty acid composition changes upon consumption of Lactobacillus rhamnosus LA68.

    Science.gov (United States)

    Ivanovic, Nevena; Minic, Rajna; Djuricic, Ivana; Dimitrijevic, Ljiljana; Sobajic, Sladjana; Zivkovic, Irena; Djordjevic, Brizita

    2015-02-01

    Recent reports suggest that the metabolic activity of the enteric microbiota may influence the fatty acid composition of the host tissue. There are many studies dealing with the influence of lactobacilli on various pathological conditions, and some of the effects are strain-specific. This study was designed to test the effects of a particular Lactobacillus strain, Lactobacillus rhamnosus LA68 on fatty acid composition of the liver and the brain of C57BL/6 mice in the absence of an underlying pathological condition. Female mice were supplemented with live L. rhamnosus LA68 bacteria for the duration of 1 month. Serum biochemistry was analyzed and liver and brain fatty acid composition was assessed by gas-liquid chromatography. Significant changes in liver and brain fatty acid composition were detected. In the liver tissue we detected an increase in palmitoleic acid (p = 0.038), while in the brain compartment we found an increase in palmitic (p = 0.042), stearic (p = 0.017), arachidonic acid (p = 0.009) and docosahexaenoic acid (p = 0.004) for control versus experimental group. These results show discrete changes caused by LA68 strain consumption. Even short duration of administration of LA68 influences the fatty acid composition of the host which adds to the existing knowledge about Lactobacillus host interaction, and adds to the growing knowledge of metabolic intervention possibilities.

  16. Ectopic ACTH and CRH co-secreting tumor localized by 68Ga-DOTA-TATE PET/CT

    Science.gov (United States)

    Papadakis, Georgios Z.; Bagci, Ulas; Sadowski, Samira M.; Patronas, Nicholas J.; Stratakis, Constantine A.

    2015-01-01

    Diagnosis of ectopic adrenocorticotropic hormone (ACTH) and corticotropin releasing hormone (CRH) co-secreting tumors causing Cushing syndrome (CS) is challenging, since these tumors are rare and their diagnosis is frequently confused with Cushing disease (CD), due to the effect of CRH on the pituitary. We report a case of a 21-year-old male who was referred to our institution with persistent hypercortisolemia and CS after undergoing unnecessary transsphenoidal surgery (TSS). 68Ga-DOTA-TATE PET/CT revealed increased tracer uptake in the thymus which was histologically proved to be neuroendocrine tumor (NET) staining positive for ACTH and CRH. Imaging with 18F-FDG PET/CT was not diagnostic. PMID:26018709

  17. Biodistribution and radiation dosimetry of {sup 68}Ga-PSMA HBED CC - a PSMA specific probe for PET imaging of prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pfob, Christian H.; Ziegler, Sibylle; Graner, Frank Philipp; Koehner, Markus; Schachoff, Sylvia; Blechert, Birgit; Scheidhauer, Klemens; Schwaiger, Markus; Eiber, Matthias [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Wester, Hans-Juergen [Technische Universitaet Muenchen, Chair of Pharmaceutical Radiochemistry, Department Chemie, Garching (Germany); Maurer, Tobias [Technische Universitaet Muenchen, Department of Urology, Munich (Germany)

    2016-10-15

    Positron emission tomography (PET) agents targeting the prostate-specific membrane antigen (PSMA) are currently under broad clinical and scientific investigation. {sup 68}Ga-PSMA HBED-CC constitutes the first {sup 68}Ga-labelled PSMA-inhibitor and has evolved as a promising agent for imaging PSMA expression in vivo. The aim of this study was to evaluate the whole-body distribution and radiation dosimetry of this new probe. Five patients with a history or high suspicion of prostate cancer were injected intravenously with a mean of 139.8 ± 13.7 MBq of {sup 68}Ga-PSMA HBED-CC (range 120-158 MBq). Four static skull to mid-thigh scans using a whole-body fully integrated PET/MR-system were performed 10 min, 60 min, 130 min, and 175 min after the tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses (ED) were calculated using OLINDA/EXM. Injection of a standard activity of 150 MBq {sup 68}Ga-PSMA HBED-CC resulted in a median effective dose of 2.37 mSv (Range 1.08E-02 - 2.46E-02 mSv/MBq). The urinary bladder wall (median absorbed dose 1.64E-01 mGv/MBq; range 8.76E-02 - 2.91E-01 mGv/MBq) was the critical organ, followed by the kidneys (median absorbed dose 1.21E-01 mGv/MBq; range 7.16E-02 - 1.75E-01), spleen (median absorbed dose 4.13E-02 mGv/MBq; range 1.57E-02 - 7.32E-02 mGv/MBq) and liver (median absorbed dose 2.07E-02 mGv/MBq; range 1.80E-02 - 2.57E-02 mGv/MBq). No drug-related pharmacological effects occurred. The use of {sup 68}Ga-PSMA HBED-CC results in a relatively low radiation exposure, delivering organ doses that are comparable to those of other {sup 68}Ga-labelled PSMA-inhibitors used for PET-imaging. Total effective dose is lower than for other PET-agents used for prostate cancer imaging (e.g. {sup 11}C- and {sup 18}F-Choline). (orig.)

  18. Illumination of murine gammaherpesvirus-68 cycle reveals a sexual transmission route from females to males in laboratory mice.

    Directory of Open Access Journals (Sweden)

    Sylvie François

    Full Text Available Transmission is a matter of life or death for pathogen lineages and can therefore be considered as the main motor of their evolution. Gammaherpesviruses are archetypal pathogenic persistent viruses which have evolved to be transmitted in presence of specific immune response. Identifying their mode of transmission and their mechanisms of immune evasion is therefore essential to develop prophylactic and therapeutic strategies against these infections. As the known human gammaherpesviruses, Epstein-Barr virus and Kaposi's Sarcoma-associated Herpesvirus are host-specific and lack a convenient in vivo infection model; related animal gammaherpesviruses, such as murine gammaherpesvirus-68 (MHV-68, are commonly used as general models of gammaherpesvirus infections in vivo. To date, it has however never been possible to monitor viral excretion or virus transmission of MHV-68 in laboratory mice population. In this study, we have used MHV-68 associated with global luciferase imaging to investigate potential excretion sites of this virus in laboratory mice. This allowed us to identify a genital excretion site of MHV-68 following intranasal infection and latency establishment in female mice. This excretion occurred at the external border of the vagina and was dependent on the presence of estrogens. However, MHV-68 vaginal excretion was not associated with vertical transmission to the litter or with horizontal transmission to female mice. In contrast, we observed efficient virus transmission to naïve males after sexual contact. In vivo imaging allowed us to show that MHV-68 firstly replicated in penis epithelium and corpus cavernosum before spreading to draining lymph nodes and spleen. All together, those results revealed the first experimental transmission model for MHV-68 in laboratory mice. In the future, this model could help us to better understand the biology of gammaherpesviruses and could also allow the development of strategies that could prevent

  19. 68Ga-DOTA-NGR as a novel molecular probe for APN-positive tumor imaging using MicroPET.

    Science.gov (United States)

    Zhang, Jun; Lu, Xiaoli; Wan, Nan; Hua, Zichun; Wang, Zizheng; Huang, Hongbo; Yang, Min; Wang, Feng

    2014-03-01

    Aminopeptidase N (APN) is selectively expressed on many tumors and the endothelium of tumor neovasculature, and may serve as a promising target for cancer diagnosis and therapy. Asparagine-glycine-arginine (NGR) peptides have been shown to bind specifically to the APN receptor and have served as vehicles for the delivery of various therapeutic drugs in previous studies. The purpose of this study was to synthesize and evaluate the efficacy of a (68)Ga-labeled NGR peptide as a new molecular probe that binds to APN. NGR peptide was conjugated with 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA) and labeled with (68)Ga at 95°C for 10 min. In vitro uptake and binding analysis was performed with A549 and MDA-MB231 cells. Biodistribution of (68)Ga-DOTA-NGR was determined in normal mice by dissection method. (68)Ga-DOTA-NGR PET was performed in A549 and MDA-MB231 xenografts, and included dynamic and static imaging. APN expression in tumors and new vasculatures was analyzed by immunohistochemistry. The radiochemical purity of (68)Ga-DOTA-NGR was 98.0% ± 1.4% with a specific activity of about 17.49 MBq/nmol. The uptake of (68)Ga-DOTA-NGR in A549 cells increased with longer incubation times, and could be blocked by cold DOTA-NGR, while no specific uptake was found in MDA-MB231 cells. In vivo biodistribution studies showed that (68)Ga-DOTA-NGR was mainly excreted from the kidney, and rapidly cleared from blood and nonspecific organs. MicroPET imaging showed that high focal accumulation had occurred in the tumor site at 1 h post-injection (pi) in A549 tumor xenografts. A significant reduction of tumor uptake was observed following coinjection with a blocking dose of DOTA-NGR, whereas only mild uptake was found in MDA-MB231 tumor xenografts. Tumor uptake, measured as the tumor/lung ratio, increased with time peaking at 12.58 ± 1.26 at 1.5 h pi. Immunohistochemical staining confirmed that APN was overexpressed on A549 cells and neovasculature. (68)Ga

  20. Preclinical Study of 68Ga-DOTATOC: Biodistribution Assessment in Syrian Rats and Evaluation of Absorbed Dose in Human Organs.

    Science.gov (United States)

    Naderi, Mojdeh; Zolghadri, Samaneh; Yousefnia, Hassan; Ramazani, Ali; Jalilian, Amir Reza

    2016-01-01

    Gallium-68 DOTA-DPhe 1 -Tyr 3 -Octreotide ( 68 Ga-DOTATOC) has been applied by several European centers for the treatment of a variety of human malignancies. Nevertheless, definitive dosimetric data are yet unavailable. According to the Society of Nuclear Medicine and Molecular Imaging, researchers are investigating the safety and efficacy of this radiotracer to meet Food and Drug Administration requirements. The aim of this study was to introduce the optimized procedure for 68 Ga-DOTATOC preparation, using a novel germanium-68 ( 68 Ge)/ 68 Ga generator in Iran and evaluate the absorbed doses in numerous organs with high accuracy. The optimized conditions for preparing the radiolabeled complex were determined via several experiments by changing the ligand concentration, pH, temperature and incubation time. Radiochemical purity of the complex was assessed, using high-performance liquid chromatography and instant thin-layer chromatography. The absorbed dose of human organs was evaluated, based on biodistribution studies on Syrian rats via Radiation Absorbed Dose Assessment Resource Method. 68 Ga-DOTATOC was prepared with radiochemical purity of >98% and specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37°C at least two hours after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreatic and adrenal tissues (12.83 %ID/g and 0.91 %ID/g, respectively). Dose estimations in human organs showed that the pancreas, kidneys and adrenal glands received the maximum absorbed doses (0.105, 0.074 and 0.010 mGy/MBq, respectively). Also, the effective absorbed dose was estimated at 0.026 mSv/MBq for 68 Ga-DOTATOC. The obtained results showed that 68 Ga-DOTATOC can be considered as an effective agent for clinical PET imaging in Iran.

  1. New results on 68Ge by means of the (p,t) reaction

    International Nuclear Information System (INIS)

    Guilbault, F.; Ardouin, D.; Tamisier, R.; Avignon, P.; Vergnes, M.; Rotbard, G.; Berrier, G.; Seltz, R.

    1976-11-01

    The 70 Ge(p,t) 68 Ge reaction has been studied at 26MeV incident energy with an overall resolution of 10keV using a split-pole spectrometer. Forty-one 68 Ge levels, among which twenty-eight are observed for the first time are populated below 5.2MeV excitation energy. Angular distributions are obtained and comparison with distorted-wave Born approximation calculations allows spin and parity assignments. Some interesting results are the discovery of the first excited 0 + level at 1.753 MeV, of the first level Jsup(π)=3 - at 2.651MeV and the observation of seven 0 + levels above 2MeV excitation energy. A level at 4.456MeV is postulated Jsup(π)=6 +

  2. Lipofection of purified adeno-associated virus Rep68 protein: toward a chromosome-targeting nonviral particle.

    Science.gov (United States)

    Lamartina, S; Roscilli, G; Rinaudo, D; Delmastro, P; Toniatti, C

    1998-09-01

    Adeno-associated virus (AAV) integrates very efficiently into a specific site (AAVS1) of human chromosome 19. Two elements of the AAV genome are sufficient: the inverted terminal repeats (ITRs) and the Rep78 or Rep68 protein. The incorporation of the AAV integration machinery in nonviral delivery systems is of great interest for gene therapy. We demonstrate that purified recombinant Rep68 protein is functionally active when directly delivered into human cells by using the polycationic liposome Lipofectamine, promoting the rescue-replication of a codelivered ITR-flanked cassette in adenovirus-infected cells and its site-specific integration in noninfected cells. The sequencing of cloned virus-host DNA junctions confirmed that lipofected Rep68 protein triggers site-specific integration at the same sites in chromosome 19 already characterized in cells latently infected with AAV.

  3. The effect of macrocyclic chelators on the targeting properties of the 68Ga-labeled gastrin releasing peptide receptor antagonist PEG2-RM26

    International Nuclear Information System (INIS)

    Varasteh, Zohreh; Mitran, Bogdan; Rosenström, Ulrika; Velikyan, Irina; Rosestedt, Maria; Lindeberg, Gunnar; Sörensen, Jens; Larhed, Mats; Tolmachev, Vladimir; Orlova, Anna

    2015-01-01

    Introduction: Overexpression of gastrin-releasing peptide receptors (GRPR) has been reported in several cancers. Bombesin (BN) analogs are short peptides with a high affinity for GRPR. Different BN analogs were evaluated for radionuclide imaging and therapy of GRPR-expressing tumors. We have previously investigated an antagonistic analog of BN (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH 2 , RM26) conjugated to NOTA via a PEG 2 spacer (NOTA-PEG 2 -RM26) labeled with 68 Ga, 111 In and Al 18 F. 68 Ga-labeled NOTA-PEG 2 -RM26 showed high tumor-to-organ ratios. Methods: The influence of different macrocyclic chelators (NOTA, NODAGA, DOTA and DOTAGA) on the targeting properties of 68 Ga-labeled PEG 2 -RM26 was studied in vitro and in vivo. Results: All conjugates were labeled with generator-produced 68 Ga with high yields and demonstrated high stability and specific binding to GRPR. The IC 50 values of nat Ga-X-PEG 2 -RM26 (X = NOTA, DOTA, NODAGA, DOTAGA) were 2.3 ± 0.2, 3.0 ± 0.3, 2.9 ± 0.3 and 10.0 ± 0.6 nM, respectively. The internalization of the conjugates by PC-3 cells was low. However, the DOTA-conjugated analog demonstrated a higher internalization rate compared to other analogs. GRPR-specific uptake was found in receptor-positive normal tissues and PC-3 xenografts for all conjugates. The biodistribution of the conjugates was influenced by the choice of the chelator moiety. Although all radiotracers cleared rapidly from the blood, [ 68 Ga]Ga-NOTA-PEG 2 -RM26 showed significantly lower uptake in lung, muscle and bone compared to the other analogs. The uptake in tumors (5.40 ± 1.04 %ID/g at 2 h p.i.) and the tumor-to-organ ratios (25 ± 3, 157 ± 23 and 39 ± 4 for blood, muscle and bone, respectively) were significantly higher for the NOTA-conjugate than the other analogs. Conclusions: Chelators had a clear influence on the biodistribution and targeting properties of 68 Ga-labeled antagonistic BN analogs. Positively charged [ 68 Ga]Ga-NOTA-PEG 2 -RM26 provided

  4. 41 CFR 105-68.325 - What happens if I do business with an excluded person in a covered transaction?

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What happens if I do business with an excluded person in a covered transaction? 105-68.325 Section 105-68.325 Public Contracts...-68.325 What happens if I do business with an excluded person in a covered transaction? If as a...

  5. Biodistribution of the radionuclides 18F-FDG, 11C-methionine, 11C-PK11195, and 68Ga-citrate in domestic juvenile female pigs and morphological and molecular imaging of the tracers in hematogenously disseminated Staphylococcus aureus lesions

    DEFF Research Database (Denmark)

    Afzelius, Pia; Nielsen, Ole Lerberg; Alstrup, Aage K. O.

    2016-01-01

    with experimental bacterial infection. Four juvenile 14-15 weeks old female domestic pigs were scanned seven days after intra-arterial inoculation in the right femoral artery with a porcine strain of S. aureus using a sequential scanning protocol with 18F-FDG, 11C-methionine, 11C-PK11195 and 68Ga...

  6. Eradication of Helicobacter pylori infection by the probiotic strains Lactobacillus johnsonii MH-68 and L. salivarius ssp. salicinius AP-32.

    Science.gov (United States)

    Hsieh, Pei-Shan; Tsai, Yi-Chun; Chen, Yi-Chun; Teh, Su-Fen; Ou, Chung-Mou; King, V An-Erl

    2012-12-01

    The current therapy for Helicobacter pylori infection includes antimicrobial agents and proton pump inhibitors. We have examined the ability of Lactobacillus spp. to inhibit H. pylori infection. Probiotic strains isolated from samples of adult feces, infant feces, breast milk, and vaginal swab collected from healthy volunteers in Taiwan and commercially available strains were screened for antagonism toward H. pylori. Inhibition liquid culture assay was used to screen potential anti-H. pylori activity. Then, we performed agar plate inhibition assay, and assays to determine the capacity of probiotics for adhesion, and inhibition and killing of H. pylori, and measured the levels of IL-8 and IL-10. Using animal models, we studied regulation of gastric acid and histopathological changes accompanying anti-H. pylori activity. We found that six of the tested strains suppressed urease activity of H. pylori: Lactobacillus acidophilus TYCA08, L. acidophilus TYCA15, L. johnsonii MH-68, and L. salivarius subsp. salicinius AP-32 were more effective than the others. In vivo, L. johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 alone or in combination, reduced the H. pylori load in the gastric mucosa, and also reduced inflammatory chemokine expression and lymphocyte infiltration. Lactobacillus johnsonii MH-68 and L. salivarius subsp. salicinius AP-32 effectively suppress H. pylori viability, and when used as probiotics, they may help decrease the occurrence of gastritis, and even reduce the risk of H. pylori infection. © 2012 Blackwell Publishing Ltd.

  7. The Drosophila melanogaster Muc68E Mucin Gene Influences Adult Size, Starvation Tolerance, and Cold Recovery.

    Science.gov (United States)

    Reis, Micael; Silva, Ana C; Vieira, Cristina P; Vieira, Jorge

    2016-07-07

    Mucins have been implicated in many different biological processes, such as protection from mechanical damage, microorganisms, and toxic molecules, as well as providing a luminal scaffold during development. Nevertheless, it is conceivable that mucins have the potential to modulate food absorption as well, and thus contribute to the definition of several important phenotypic traits. Here we show that the Drosophila melanogaster Muc68E gene is 40- to 60-million-yr old, and is present in Drosophila species of the subgenus Sophophora only. The central repeat region of this gene is fast evolving, and shows evidence for repeated expansions/contractions. This and/or frequent gene conversion events lead to the homogenization of its repeats. The amino acid pattern P[ED][ED][ST][ST][ST] is found in the repeat region of Muc68E proteins from all Drosophila species studied, and can occur multiple times within a single conserved repeat block, and thus may have functional significance. Muc68E is a nonessential gene under laboratory conditions, but Muc68E mutant flies are smaller and lighter than controls at birth. However, at 4 d of age, Muc68E mutants are heavier, recover faster from chill-coma, and are more resistant to starvation than control flies, although they have the same percentage of lipids as controls. Mutant flies have enlarged abdominal size 1 d after chill-coma recovery, which is associated with higher lipid content. These results suggest that Muc68E has a role in metabolism modulation, food absorption, and/or feeding patterns in larvae and adults, and under normal and stress conditions. Such biological function is novel for mucin genes. Copyright © 2016 Reis et al.

  8. The Compatibility of Developed Mathematics Textbooks' Content in Saudi Arabia (Grades 6-8) with NCTM Standards

    Science.gov (United States)

    Alshehri, Mohammed Ali; Ali, Hassan Shawki

    2016-01-01

    This study aimed to investigate the compatibility of developed mathematics textbooks' content (grades 6-8) in Saudi Arabia with NCTM standards in the areas of: number and operations, algebra, geometry, measurement, data analysis and probability. To achieve that goal, a list of (NCTM) standards for grades (6-8) were translated to Arabic language,…

  9. Enterovirus type D68 en acute slappe verlamming: een nieuw duo?

    NARCIS (Netherlands)

    van Dissel, J T; Meijer, A

    2017-01-01

    Following a case of acute flaccid paralysis after infection with enterovirus type D68, we highlight current understanding of the causal role of enterovirus infection in this neurological syndrome. Acute flaccid paralysis is a rare complication of enterovirus infections. Such viruses have become a

  10. Measurements of nitrous oxide emissions from P.F. fired power stations

    Science.gov (United States)

    Sloan, S. A.; Laird, C. K.

    Nitrous oxide (N 2O) was measured in the flue gas from four wall-fired and three corner-fired 500 MW boilers, fitted with either conventional or low-NO x burners, at four C.E.G.B. power stations. Measurements were made both by on-line non-dispersive infra red (NDIR) monitors and by extractive sampling for later laboratory analysis by electron capture gas chromatography (ECD GC). It was found that the on-line and laboratory methods were in good agreement for samples analyzed within 1-3 h of sampling, but that the nitrous oxide concentration in the stored samples had a tendency to increase with time, which was dependent on the concentration of water in the sample. Experiments with synthetic mixtures showed that the increase in nitrous oxide concentration was consistent with the overall reaction2NO+SO 2→N 2O+SO 3 in which nitric oxide is reduced by sulphur dioxide. The highest average N 2O concentration measured by the on-line analyzer was 16 vpm, and for most of the boilers monitored the concentration was less than 10 vpm. There was no statistically significant difference between the measured N 2O emissions from normal boilers and those fitted with low-NO x burners. It is suggested that these values are close to the true levels of N 2O emissions from p.f. fired boilers and that recent reports of high levels (up to 200 vpm) are likely to be an artefact resulting from the observed generation of N 2O in stored samples. A consequence of these measurements of N 2O is that current estimates of the contribution of emissions from p.f. fired boilers to the global N 2O budget are likely to be too high.

  11. Imaging benign pathology and variants with uptake in 68ga-Dotatate PET/CT studies

    International Nuclear Information System (INIS)

    Servente, L.; Bianco, C.; Gigirey, V.; Alonso, O.

    2017-01-01

    Purpose: To evaluate the physiological, anatomical variants and benign lesions in positron emission computed tomography (PET/CT) studies with 68Ga-DOTATATE.Materials and methods: We retrospectively reviewed PET/CT reports scanned with 68Ga-DOTATATE and selected those that contained words in the report related to anatomical, physiological variants and benign tumors. The degree of 68Ga-DOTATATE uptake was evaluated qualitatively and quantitatively by measuring the standarized uptake max value (SUVmax value). The anatomical location, SUVmax value and morphological CT image findings were recorded. All cases had clinical and imaging follow-up. Results: From a total of 772 PET/CT reports, 28 patients were obtained with 33 benign variants or tumors, 14 females and 14 males with a median age of 63 years. Uptake patterns were classified into four groups: anatomic and physiological variants (15), dependent on osteoblastic activity (4), dependent on inflammatory activity (10) and non-neuro-endocrine benign tumors (4).Discussion: Somatostatin receptors are overexpressed not only in the neuroendocrine system but also in other tissues. Physiological, anatomical variants and benign tumors expressing these receptors may be misleading. In the present work the frequency of this finding is 5.1%.Conclusion: Physiological variants and benign lesions (tumor and inflammatory) can accumulate 68Ga-DOTATATE since their tissues can express somatostatin receptors. The semiologic analysis of the tomographic component of this hybrid method enhances the diagnostic efficacy, optimizing PET/CT study performance. (authors) [es

  12. Speciation of no-carrier-added 68Ga prior to its labeling for PET imaging

    International Nuclear Information System (INIS)

    Kamalika Sen; Breeman, W.A.P.; Wolterbeek, H.Th.

    2012-01-01

    The present article describes the probable speciation of 68 Ga radionuclide just before labeling to DOTA peptides for PET imaging. The 68 Ga eluted from an anion exchange column after its purification was analyzed for its elemental composition and pH at several stages. Neutron activation analysis of the eluted fractions yields the concentrations of Na and Cl, pH measurements indicate the concentration of free H + ions in the medium and specific activity calculations indicate the concentration of 68 Ga in the solution. Using all these information we get the idea of speciation of no carrier added Ga in the eluted fractions from CHEAQS programme. The estimations indicate that Ga is mostly present as GaCl 2+ in the total MiliQ eluate. However, just before labeling of DOTA the pH of the Ga-containing eluate is adjusted to ∼3.5 using HEPES buffer and at that condition Ga remains as Ga 3+ species which is responsible for a successful and efficient labeling. The MilliQ eluate collected before actual labeling was estimated for trace elements using inductively coupled plasma atomic emission spectrometry was found to contain a few ppb of Al, Co, Pd and Pt that did not interfere in the actual labeling. A clear idea about the prerequisite of 68 Ga species before labeling to a peptide might be of special interest for its judicious application as a radiopharmaceutical. (author)

  13. Synthesis of novel 68Ga-labeled amino acid derivatives for positron emission tomography of cancer cells

    International Nuclear Information System (INIS)

    Shetty, Dinesh; Jeong, Jae Min; Ju, Chang Hwan; Lee, Yun-Sang; Jeong, Seo Young; Choi, Jae Yeon; Yang, Bo Yeun

    2010-01-01

    Objectives: We developed amino acid derivatives of 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) and 1,4,7,10-tetraazacyclododecane-1,4,7,-triacetic acid (DO3A) that can be labeled with 68 Ga, and we investigated their basic biological properties. Materials and methods: Alanine derivatives of DO2A and DO3A were synthesized by regiospecific nucleophilic attack of DO2tBu and DO3tBu on the β-position of Boc-L-serine-β-lactone, followed by acid hydrolysis. Also, homoalanine derivatives were synthesized by reacting with the protected bromo derivative of homoalanine, which was synthesized from N-Cbz-L-homoserine lactone. Further catalytic reduction and acid cleavage of protected groups resulted in the required products. All derivatives were labeled with 68 Ga. Cell uptake assays were carried out in Hep3B (human hepatoma) and U87MG (human glioma) cell lines at 37 o C. Positron emission tomography (PET) imaging studies were performed using balb/c mice xenografted with CT-26 (mouse colon cancer). Results: All compounds were labeled with >97% efficiency. According to in vitro studies, the labeled amino acid derivatives showed significantly greater uptakes than the control ( 68 Ga 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) in cancer cells. Small animal PET images for labeled compounds showed high tumor uptake, as well as kidney and bladder uptakes, at 30 min postinjection. 68 Ga-DO3A-homoalanine showed the highest standardized uptake value ratio (3.9±0.3), followed by 68 Ga-DO2A-alanine (3.1±0.2), 68 Ga-DO3A-alanine (2.8±0.2) and 68 Ga-DO2A-homoalanine (2.3±0.2). Conclusion: These derivatives were found to have high labeling efficiencies, high stabilities, high tumor cell uptakes, high tumor/nontumor xenograft uptakes and low nonspecific uptake in normal organs, except for the kidneys. However, the uptake mechanism of these derivatives remains unclear, and uptake via specific amino acid transporters needs to be demonstrated.

  14. Automated Synthesis of 68Ga-DOTA-TOC: Methodological Aspects and Suitable Technical Solutions for a Cationic Purification System.

    Science.gov (United States)

    Uccelli, Licia; Boschi, Alessandra; Cittanti, Corrado; Martini, Petra; Lodi, Luca; Zappaterra, Elisa; Romani, Simona; Zaccaria, Samanta; Cecconi, Davide; Rambaldi, Ilaria; Santi, Ivan; Panareo, Stefano; Giganti, Melchiore; Bartolomei, Mirco

    2018-05-08

    The PET Gallium-68 isotope has the advantage of being produced from a generator, so it is also available in nuclear medicine departments without a cyclotron. The preparation of Ga-68 DOTA-labelled compounds is actually performed by remotely controlled automated systems developed in order to assure production efficiency, reproducibility of the results, guarantee fast reaction time, to facilitate the synthesis and minimize the radiation exposure. Many automatic synthesis systems are available on the radiopharmaceutical market, and each of these requires the realization of some technical adaptations for routine use. We reported the Ga-68 DOTATOC production by automated cassette-based theranostic synthesizer system used in combination with a disposable GMP grade cassette system for cationic purification. The synthesizer is integrated with the 68Ge/68Ga generator systems and it allows to perform elution, eluate purification and radiolabeling in about 38 minutes. We have performed between January 2016 and January 2017 over 100 [68Ga]Ga-DOTA-TOC preparation and of these only three have failed. The average synthesis yield of radiopharmaceutical production was 54.4 ± 2.3 % and the average radiochemical purity was 96.94 ± 0.74 %. The methodology and the technical solutions adopted have allowed to obtain a high quality radiopharmaceutical product as required by the European Pharmacopoeia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. PET-CT and PET-MRI of the prostate. From {sup 18}F-FDG to {sup 68}Ga-PSMA; PET-CT/-MRT der Prostata. Von {sup 18}F-FDG zu {sup 68}Ga-PSMA

    Energy Technology Data Exchange (ETDEWEB)

    Knorr, K.; Eiber, M.; Scheidhauer, K. [Technische Universitaet Muenchen, Nuklearmedizinische Klinik und Poliklinik, Klinikum rechts der Isar, Muenchen (Germany); Maurer, T. [Technische Universitaet Muenchen, Urologische Klinik und Poliklinik, Klinikum rechts der Isar, Muenchen (Germany); Wester, H.J. [Technische Universitaet Muenchen, Pharmazeutische Radiochemie, Garching (Germany)

    2017-08-15

    In the last few years nuclear medical diagnostics have experienced a unprecedented renaissance in the diagnostics of prostate cancer, due to the availability of hybrid imaging with positron emission tomography computed tomography (PET/CT), PET magnetic resonance imaging (PET/MRI) and single photon emission computed tomography (SPECT) CT as well as the development of prostate-specific radiopharmaceuticals. The use of fluorodeoxyglucose (FDG), which has been successfully implemented for many years in PET diagnostics, is only helpful in dedifferentiated tumors due to the biological characteristics of prostate cancer. New specific radiopharmaceuticals, such as choline-derivatives, which are incorporated into the prostate cancer cell and built into the cell membrane as well as the recently developed highly specific ligands for prostate-specific membrane antigen (PSMA) are revolutionizing prostate cancer imaging and (re-) staging. The {sup 68} Ga-labeled PSMA ligands for PET-CT and PET-MRI are highly specific tracers for primary diagnostics and detection of metastases of prostate carcinoma. In risk patients, which includes patients with intermediate and high-risk tumors, they have largely replaced choline-based PET-CT, especially in the case of very low PSA values <0.5 ng/ml in the diagnostics of recurrence. The use in the primary diagnostics as PET-MRI, also in combination with multiparametric MRI (mpMRI), is promising with respect to early diagnostics and image fusion-assisted biopsy as well as surgery and irradiation planning. (orig.) [German] Die nuklearmedizinische Diagnostik hat in den letzten Jahren bei der Bildgebung des Prostatakarzinoms eine rasante Entwicklung erlebt, sowohl aufgrund der verfuegbaren Hybridbildgebung mit der Positronenemissionstomographie(PET)-CT, PET-MRT sowie der Single-photon-emission-computed-tomography(SPECT)-CT als auch durch die Entwicklung prostataspezifischer Radiopharmaka. Die in der PET-Diagnostik seit Jahren erfolgreich eingesetzte

  16. Response assessment with the CXCR4-directed positron emission tomography tracer [68Ga]Pentixafor in a patient with extranodal marginal zone lymphoma of the orbital cavities.

    Science.gov (United States)

    Herhaus, Peter; Habringer, Stefan; Vag, Tibor; Steiger, Katja; Slotta-Huspenina, Julia; Gerngroß, Carlos; Wiestler, Benedikt; Wester, Hans-Jürgen; Schwaiger, Markus; Keller, Ulrich

    2017-12-01

    CXCR4 belongs to the family of chemokine receptors. Together with its sole known ligand CXCL12 (SDF-1alpha), it has a pivotal role during organogenesis and for homing of hematopoietic stem cells. CXCR4 is overexpressed in various malignancies, and this is often associated with poor prognosis. Therefore, molecular imaging of CXCR4 bears a great potential for diagnostics and selecting patients for CXCR4-directed therapies. The CXCR4-directed positron emission tomography (PET) tracer [ 68 Ga]Pentixafor has been shown to visualize CXCR4 expression in various malignancies in vivo. Whereas this tracer has limitations compared to 18 F-Fluorodeoxyglucose ([ 18 F]FDG) in diagnostic PET imaging in peripheral tumour lesions, it might add valuable information in routine diagnostics and response assessment of tumours in close proximity to the central nervous system (CNS) and malignancies within this organ. As a proof-of-concept, we performed [ 68 Ga]Pentixafor PET imaging in a patient with extranodal marginal zone lymphoma (MZL) of the orbital cavities at diagnosis and for post-therapy response assessment. Compared to routinely conducted [ 18 F]FDG PET, the lymphoma lesions determined by magnetic resonance imaging (MRI) showed high tracer accumulation at diagnosis, which decreased upon treatment. We therefore propose that imaging of CXCR4 with [ 68 Ga]Pentixafor is a potential diagnostic tool for tumours close to or within the CNS and suggest this being studied in clinical trials.

  17. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Science.gov (United States)

    2010-04-01

    ... requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and... requirements for biological products held by the Strategic National Stockpile. (a) The appropriate FDA Center... Strategic National Stockpile. (b)(1)(i) A Strategic National Stockpile official or any entity that...

  18. In vivo binding of [68Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours - impact of peptide mass

    International Nuclear Information System (INIS)

    Velikyan, Irina; Sundin, Anders; Eriksson, Barbro; Lundqvist, Hans; Soerensen, Jens; Bergstroem, Mats; Langstroem, Bengt

    2010-01-01

    Objectives: The aim of this pilot study was to explore the impact of peptide mass on binding of [ 68 Ga]-DOTATOC to neuroendocrine tumour somatostatin receptors in vivo using a tracer of variable specific radioactivity (SRA) and to show the logistic feasibility of sequential PET scans in the same patient. Material and Methods: Nine patients with gastroenteropancreatic neuroendocrine tumours were included. Six of them underwent three sequential PET-CT examinations with intravenous injections of [ 68 Ga]-DOTATOC proceeded by 0, 50 and 250 or 500 μg of octreotide, administered 10 min before the tracer. Three patients were examined by dynamic and static PET/CT for pharmacokinetic and dosimetric calculations. The [ 68 Ga]-DOTATOC synthesis included preconcentration and purification of the generator eluate and microwave heating in a semi-automated in-house procedure. Results: [ 68 Ga]-DOTATOC synthesis and quality control were accomplished within 30 min and radiochemical purity was >95%. The tracer accumulation in the tumours varied and depended on the total amount of the administered peptide. In five of six patients, the highest tumour-to-normal tissue ratio was found when 50 μg of octreotide was preadministered. One patient showed a continuously increasing tumour uptake. Dosimetrically, a large variation in organ doses was found (kidney: 0.086-0.168 mSv/MBq; liver: 0.026-0.096 mSv/MBq; spleen: 0.046-0.226 mSv/MBq). The effective dose (0.015, 0.0067 and 0.0042 mSv/MBq) was correlated to the total amount of decays. Discussion: Three sequential PET-CT examinations using 68 Ga-based tracer was carried out in 1 day. The use of high SRA [ 68 Ga]-DOTATOC and unlabelled octreotide indicates an optimal mass leading to better image contrast. [ 68 Ga]-DOTATOC-PET-CT employing variable SRA may be utilised for accurate quantification of tumour uptake with subsequent dosimetry for personalized therapy management.

  19. Crystal structure and magnetic properties of PrCo6.8-xCuxHf0.2 compounds

    International Nuclear Information System (INIS)

    Luo, J; Liang, J K; Guo, Y Q; Liu, Q L; Liu, F S; Yang, L T; Zhang, Y; Rao, G H

    2004-01-01

    The effects of Cu substitution on the crystal structure and magnetic properties of PrCo 6.8-x Cu x Hf 0.2 (x = 0-1.0) compounds were investigated by means of x-ray powder diffraction and magnetic measurements. The as-cast PrCo 6.8-x Cu x Hf 0.2 compounds crystallize in the TbCu 7 -type structure with the space group P6/mmm. The Curie temperature and magnetic anisotropy field decrease with increasing Cu content. A spin reorientation behaviour has been observed in the PrCo 6.8-x Cu x Hf 0.2 compounds. The addition of Cu weakens the anisotropy of the Co sublattice, leading to an increase in the spin reorientation temperature with increasing content of Cu

  20. Physiological and tumoral uptake of 68Ga-DOTATATE. Standardized uptake values and challenges in interpretation

    International Nuclear Information System (INIS)

    Kuyumcu, Serkan; Oezkan, Zeynep Goezde; Sanli, Yasemin; Yilmaz, Ebru; Mudun, Ayse; Adalet, Isik; Unal, Seher

    2013-01-01

    The objective of this study is to determine the range of standardized uptake value (SUV) max of 68Ga-DOTA-tyr3-octreotate (DOTATATE) in normal organs and tumoral lesions and establish uptake unrelated to neuroendocrine tumors (NET). One hundred and twenty patients (57 men, 63 women), who underwent 68 Ga-DOTATATE positron emission tomography (PET)/CT imaging in our institution were analyzed. Patients were indicated for 68 Ga-DOTATATE PET/CT imaging to detect primary tumor or metastasis of suspected or previously known NET, to determine somatostatin receptor (SSTR) positivity and to detect occult source of ectopic Cushing syndrome. Normal range of uptake was calculated for the organs that were proven to have no pathology by either conventional radiological imaging or clinical follow-up, using SUV max as a semiquantitative measure. Uptake and tumor to background (T/B) ratios of tumoral lesions in liver, pancreas, bone, brain and lymph nodes were calculated. Uptakes due to lesions unrelated to NET were also documented. Significant uptake was found in spleen, kidneys, adrenal glands, liver and pituitary gland with mean SUV max of 24.67, 14.30, 13.73, 9.12 and 9.74 respectively. Uptake was measured separately for the pancreatic head and body separately, however, besides a slightly heterogeneous uptake; the difference was not statistically significant. Uptake in the tumoral lesions had high (T/B) ratios with mean SUV max of 28.72, 25.21, 18.28, 34.73 and 12.59 for liver, pancreas, bone, brain and lymph nodes, respectively. Incidental benign tumoral lesions were detected in 3 patients (2.5%) which were meningioma and fibrous dysplasia demonstrating significant and breast fibroadenoma demonstrating mild 68 Ga-DOTATATE uptake. Non-neoplastic processes were detected in 4 patients (14.1%), including postsurgical inflammation, reactive lymph nodes, arthritis and demonstrated faint to mild 68 Ga-DOTATATE uptake, with the exception of significant uptake in accessory spleen. 68 Ga

  1. Tetrafluorophenolate of HBED-CC: a versatile conjugation agent for 68Ga-labeled small recombinant antibodies

    International Nuclear Information System (INIS)

    Eder, Matthias; Waengler, Bjoern; Eisenhut, Michael; Knackmuss, Stefan; LeGall, Fabrice; Little, Melvyn; Haberkorn, Uwe; Mier, Walter

    2008-01-01

    The success of 68 Ga-labeled peptides for positron emission tomography of neuroendocrine tumors is mainly depending on the complex chemistry of this radioisotope. 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), the chelator of choice has however limitations if its application is expanded to heat-sensitive proteins. Recombinant antibodies like single chain Fv or diabodies belong to this class of proteins. They are suited to provide imaging contrast despite the short-lived 68 Ga because of their rapid blood clearances and nanomolar affinities. The heterobifunctional agent N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC) was chosen as an alternative ligand because this agent is complexing [ 68 Ga]Ga 3+ much faster than DOTA at ambient temperatures. A versatile technology for HBED-CC conjugation of proteins and 68 Ga-labeling has been developed. This included HBED-CC-tetrafluorophenol (TFP) ester synthesis, coupling to the antibody at various pH and complexation reactions performed in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer under different conditions. The synthesis of the monoreactive 2,3,5,6-tetrafluorophenolate of HBED-CC at a carboxyl group not participating in complex formation used [Fe(HBED-CC)] - for ester formation. The removal of Fe 3+ from purified (HBED-CC)TFP ester was achieved with RP 18 cartridge technology. The conjugation chemistry was performed with mAb425 which binds to the epidermal growth factor receptor (EGFR). This protein was used for optimizing purposes only. The influence of complexation parameters like temperature, pH, reaction time, and HBED-CC/antibody ratio on the biological activity of this model antibody was investigated. Furthermore, the outcome of this labeling procedure on the biological activity of a recombinant diabody (50 kDa) was studied. It is known that small HBED-CC/antibody ratios are prerequisites for minimal interference of labels with antigen

  2. Radiation exposure of patients during 68Ga-DOTATOC PET/CT examinations

    International Nuclear Information System (INIS)

    Hartmann, Holger; Freudenberg, R.; Oehme, L.; Andreeff, M.; Wunderlich, G.; Zoephel, K.; Eisenhofer, G.; Kotzerke, J.

    2009-01-01

    Investigation of the biodistribution and calculation of dosimetry of Ga-68-DOTATOC-for patients imaged in the routine clinical setting for diagnosis or exclusion of neuroendocrine tumours. Patients methods: Dynamic PET/CT-imaging (Biograph 16) was performed over 20 min in 14 patients (8 men, 6 women) after injection of (112 ± 22) MBq 68 Ga-DOTATOC followed by whole body 3D-acquisition (8 bed positions, 3 or 4 min each) 30 min p.i. and 120 min p.i., Urinary tracer elimination was measured and blood activity was derived non-invasively from the blood pool of the heart. The relevant organs for dosimetry were spleen, kidneys, liver, adrenals, urinary bladder and pituitary gland. Dosimetry was performed using OLINDA/EXM 1.0 software and specific organ uptake was expressed as standardized uptake values (SUVs). Results Rapid physiological uptake of the radiotracer could be demonstrated in liver, spleen and kidneys, adrenals and pituitary gland (mean SUVs were 6, 20, 16, 10, and 4, respectively). Radiotracer elimination was exclusively via urine (16% of injected dose within 2h); no redistribution could be observed. The spleen and the kidneys received the highest radiation exposure (0.24 mSv/MBq, 0.22 mSv/MBq resp.), mean effective dose yielded 0.023 mSv/MBq. Conclusion: 68 Ga-DOTATOC is used extensively for diagnosis of somatostatin receptor positive tumours because it has several advantages over the 111 In-labelled ligand. The derived dosimetric values are lower than first approximations from the biological data of OctreoScan. The use of CT for transmission correction of the PET data delivers radiation exposure up to 1 mSv (low dose). (orig.)

  3. Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine

    International Nuclear Information System (INIS)

    Kroiss, Alexander; Putzer, Daniel; Uprimny, Christian; Decristoforo, Clemens; Gabriel, Michael; Warwitz, Boris; Waitz, Dietmar; Kendler, Dorota; Virgolini, Irene Johanna; Santner, Wolfram; Kranewitter, Christof

    2011-01-01

    68 Ga-DOTA-Tyr 3 -octreotide positron emission tomography ( 68 Ga-DOTA-TOC PET) has proven to be superior to 111 In-DTPA-D-Phe 1 -octreotide ( 111 In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of 123 I-metaiodobenzylguanidine ( 123 I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard. Three male and eight female patients (age range 3 to 68 years) with biochemically and histologically proven disease were included in this study. Three male and three female patients were suffering from phaeochromocytoma, and five female patients from neuroblastoma. Comparative evaluation included morphological imaging with CT or MRI, functional imaging with 68 Ga-DOTA-TOC PET and 123 I-MIBG imaging. Imaging results were analysed on a per-patient and on a per-lesion basis. On a per-patient basis, both 68 Ga-DOTA-TOC and 123 I-MIBG showed a sensitivity of 100%, when compared with anatomical imaging. In phaeochromocytoma patients, on a per-lesion basis, the sensitivity of 68 Ga-DOTA-TOC was 91.7% and that of 123 I-MIBG was 63.3%. In neuroblastoma patients, on a per-lesion basis, the sensitivity of 68 Ga-DOTA-TOC was 97.2% and that of 123 I-MIBG was 90.7%. Overall, in this patient cohort, 68 Ga-DOTA-TOC PET identified 257 lesions, anatomical imaging identified 216 lesions, and 123 I-MIBG identified only 184 lesions. In this patient group, the overall sensitivity of 68 Ga-DOTA-TOC PET on a lesion basis was 94.4% (McNemar p 123 I-MIBG was 76.9% (McNemar p 68 Ga-DOTA-TOC PET may be superior to 123 I-MIBG gamma-scintigraphy and even to the reference CT/MRI technique in providing particularly valuable information for pretherapeutic staging of phaeochromocytoma and neuroblastoma. (orig.)

  4. Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine.

    Science.gov (United States)

    Kroiss, Alexander; Putzer, Daniel; Uprimny, Christian; Decristoforo, Clemens; Gabriel, Michael; Santner, Wolfram; Kranewitter, Christof; Warwitz, Boris; Waitz, Dietmar; Kendler, Dorota; Virgolini, Irene Johanna

    2011-05-01

    (68)Ga-DOTA-Tyr(3)-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) has proven to be superior to (111)In-DTPA-D-Phe(1)-octreotide ((111)In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard. Three male and eight female patients (age range 3 to 68 years) with biochemically and histologically proven disease were included in this study. Three male and three female patients were suffering from phaeochromocytoma, and five female patients from neuroblastoma. Comparative evaluation included morphological imaging with CT or MRI, functional imaging with (68)Ga-DOTA-TOC PET and (123)I-MIBG imaging. Imaging results were analysed on a per-patient and on a per-lesion basis. On a per-patient basis, both (68)Ga-DOTA-TOC and (123)I-MIBG showed a sensitivity of 100%, when compared with anatomical imaging. In phaeochromocytoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 91.7% and that of (123)I-MIBG was 63.3%. In neuroblastoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 97.2% and that of (123)I-MIBG was 90.7%. Overall, in this patient cohort, (68)Ga-DOTA-TOC PET identified 257 lesions, anatomical imaging identified 216 lesions, and (123)I-MIBG identified only 184 lesions. In this patient group, the overall sensitivity of (68)Ga-DOTA-TOC PET on a lesion basis was 94.4% (McNemar p<0.0001) and that of (123)I-MIBG was 76.9% (McNemar p<0.0001). Our analysis in this relatively small patient cohort indicates that (68)Ga-DOTA-TOC PET may be superior to (123)I-MIBG gamma-scintigraphy and even to the reference CT/MRI technique in providing particularly valuable information for pretherapeutic staging of phaeochromocytoma and

  5. Impact of 68Ga-PSMA PET on the Management of Patients with Prostate Cancer: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Han, Sangwon; Woo, Sungmin; Kim, Yeon Joo; Suh, Chong Hyun

    2018-04-18

    68 Gallium prostate-specific membrane antigen positron emission tomography ( 68 Ga-PSMA PET) is an emerging imaging modality for assessment of prostate cancer. Recent studies show promising results regarding its ability to detect recurrent or metastatic prostate cancer superior to that of conventional imaging modalities. However, the impact of 68 Ga-PSMA PET on management of patients with prostate cancer has not been well established. To perform a systematic review and meta-analysis to evaluate the impact of 68 Ga-PSMA PET on management of patients with prostate cancer. Pubmed and EMBASE databases were searched up to January 20, 2018. We included studies that reported proportion of management change after 68 Ga-PSMA PET in patients with prostate cancer. The quality of the studies was evaluated using the GRADE system. The proportion of management changes were pooled using random-effects model. Subgroup analyses and meta-regression analyses were performed to explore heterogeneity. Fifteen studies (1163 patients) were included. The pooled proportion of management changes was 54% (95% confidence interval 47-60%). At meta-regression analyses, PET positivity (%) was a significant factor of heterogeneity (p=0.0486). For patients with biochemical failure, the proportion of radiotherapy (from 56% to 61%), surgery (from 1% to 7%), focal therapy (from 1% to 2%), and multimodal treatment (from 2% to 6%) increased, whereas that of systemic treatment (from 26% to 12%) and no treatment (from 14% to 11%) decreased with 68 Ga-PSMA PET. 68 Ga-PSMA PET had a large impact on the management of patients with prostate cancer. Greater PET positivity was associated with higher proportion of management changes. We reviewed all previous studies assessing the impact of 68 Gallium prostate-specific membrane antigen positron emission tomography ( 68 Ga-PSMA PET) in patients with prostate cancer. We found that 68 Ga-PSMA PET altered the management in approximately half of the patients. Copyright

  6. Diagnostic Challenges in Prostate Cancer and 68Ga-PSMA PET Imaging: A Game Changer?

    Science.gov (United States)

    Zaman, Maseeh uz; Fatima, Nosheen; Zaman, Areeba; Sajid, Mahwsih; Zaman, Unaiza; Zaman, Sidra

    2017-10-26

    Prostate cancer (PC) is the most frequent solid tumor in men and the third most common cause of cancer mortality among men in developed countries. Current imaging modalities like ultrasound (US), computerized tomography (CT), magnetic resonance imaging (MRI) and choline based positron emission (PET) tracing have disappointing sensitivity for detection of nodal metastasis and small tumor recurrence. This poses a diagnostic challenge in staging of intermediate to high risk PC and restaging of patients with biochemical recurrence (PSA >0.2 ng/ml). Gallium-68 labeled prostate specific membrane antigen (68Ga-PSMA) PET imaging has now emerged with a higher diagnostic yield. 68Ga-PSMA PET/CT or PET/MRI can be expected to offer a one-stop-shop for staging and restaging of PC. PSMA ligands labeled with alpha and beta emitters have also shown promising therapeutic efficacy for nodal, bone and visceral metastasis. Therefore a PSMA based theranostics approach for detection, staging, treatment, and follow-up of PC would appear to be highly valuable to achieve personalized PC treatment. Creative Commons Attribution License

  7. (68)Ga-labeled phage-display selected peptides as tracers for positron emission tomography imaging of Staphylococcus aureus biofilm-associated infections: Selection, radiolabelling and preliminary biological evaluation

    DEFF Research Database (Denmark)

    Nielsen, Karin M; Kyneb, Majbritt H; Alstrup, Aage K O

    2016-01-01

    , while the in vivo plasma stability was analyzed in mice and pigs. Additionally, the whole-body distribution kinetics of (68)Ga-A9-K-DOTA was measured in vivo by PET imaging of pigs and ex vivo in excised mice tissues. RESULTS: The (68)Ga-A9-K-DOTA and (68)Ga-A11-GSGK-DOTA remained stable in product......INTRODUCTION: Staphylococcus aureus is a major cause of skin and deep-sited infections, often associated with the formation of biofilms. Early diagnosis and initiated therapy is essential to prevent disease progression and to reduce complications that can be serious. Imaging techniques are helpful...... combining anatomical with functional data in order to describe and characterize site, extent and activity of the disease. The purpose of the study was to identify and (68)Ga-label peptides with affinity for S. aureus biofilm and evaluate their potential as bacteria-specific positron emission tomography (PET...

  8. Positron emission tomography study on pancreatic somatostatin receptors in normal and diabetic rats with {sup 68}Ga-DOTA-octreotide: A potential PET tracer for beta cell mass measurement

    Energy Technology Data Exchange (ETDEWEB)

    Sako, Takeo [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Hasegawa, Koki; Nishimura, Mie; Kanayama, Yousuke; Wada, Yasuhiro; Hayashinaka, Emi; Cui, Yilong; Kataoka, Yosky [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Senda, Michio [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Division of Molecular Imaging, Institute of Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Watanabe, Yasuyoshi, E-mail: yywata@riken.jp [Division of Bio-function Dynamics Imaging, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan)

    2013-12-06

    Highlights: •PET images showed high uptake of {sup 68}Ga-DOTA-octreotide in the normal pancreas. •{sup 68}Ga-DOTA-octreotide specifically binds to somatostatin receptors in the pancreas. •The pancreatic uptake of {sup 68}Ga-DOTA-octreotide was decreased in the diabetic rats. •{sup 68}Ga-DOTA-octreotide could be a candidate PET probe to measure the beta cell mass. -- Abstract: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, and the loss or dysfunction of pancreatic beta cells has been reported before the appearance of clinical symptoms and hyperglycemia. To evaluate beta cell mass (BCM) for improving the detection and treatment of DM at earlier stages, we focused on somatostatin receptors that are highly expressed in the pancreatic beta cells, and developed a positron emission tomography (PET) probe derived from octreotide, a metabolically stable somatostatin analog. Octreotide was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), a chelating agent, and labeled with {sup 68}Gallium ({sup 68}Ga). After intravenous injection of {sup 68}Ga-DOTA-octreotide, a 90-min emission scan of the abdomen was performed in normal and DM model rats. The PET studies showed that {sup 68}Ga-DOTA-octreotide radioactivity was highly accumulated in the pancreas of normal rats and that the pancreatic accumulation was significantly reduced in the rats administered with an excess amount of unlabeled octreotide or after treatment with streptozotocin, which was used for the chemical induction of DM in rats. These results were in good agreement with the ex vivo biodistribution data. These results indicated that the pancreatic accumulation of {sup 68}Ga-DOTA-octreotide represented specific binding to the somatostatin receptors and reflected BCM. Therefore, PET imaging with {sup 68}Ga-DOTA-octreotide could be a potential tool for evaluating BCM.

  9. High spin levels in 66Ga, 68Ga, 70Ga and 68Ge, 70Ge, 72Ge via fusion evaporation reactions induced by α-particles

    International Nuclear Information System (INIS)

    Morand, C.

    1979-01-01

    The high spin (J 70 Ga all the members (except the 3 - one) of the (πpsub(3/2), νgsub(9/2)) configuration have been identified, in addition with the (πfsub(5/2), νgsub(9/2))sub(7 - ) and (πgsub(9/2), νgsub(9/2))sub(9 + ) states. In 66 Ga and 68 Ga most of the levels with J>7 ca be described as a result of maximum coupling of a gsub(9/2) neutron with the odd Ga core. Thus the (πgsub(9/2), νgsub(9/2))sub(9 + ) states have been safely located. In the same way the even Ge, the backbending effect at the Jsup(π)=8 + state is less and less pronouced from the 68 Ge to the 72 Ge; that can be explained by the (νgsub(9/2)) 2 sub(8 + ) configuration of this state, so that the 8 + →6 + γ-transition is more and more allowed with increasing N, i.e. as the νgsub(9/2) shell acts more and more in the lower yrast levels Jsup(π)=0 + , 2 + , 4 + , 6 + configurations [fr

  10. Influence of macrocyclic chelators on the targeting properties of (68Ga-labeled synthetic affibody molecules: comparison with (111In-labeled counterparts.

    Directory of Open Access Journals (Sweden)

    Joanna Strand

    Full Text Available Affibody molecules are a class of small (7 kDa non-immunoglobulin scaffold-based affinity proteins, which have demonstrated substantial potential as probes for radionuclide molecular imaging. The use of positron emission tomography (PET would further increase the resolution and quantification accuracy of Affibody-based imaging. The rapid in vivo kinetics of Affibody molecules permit the use of the generator-produced radionuclide (68Ga (T1/2=67.6 min. Earlier studies have demonstrated that the chemical nature of chelators has a substantial influence on the biodistribution properties of Affibody molecules. To determine an optimal labeling approach, the macrocyclic chelators 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA, 1,4,7-triazacyclononane-N,N,N-triacetic acid (NOTA and 1-(1,3-carboxypropyl-1,4,7- triazacyclononane-4,7-diacetic acid (NODAGA were conjugated to the N-terminus of the synthetic Affibody molecule ZHER2:S1 targeting HER2. Affibody molecules were labeled with (68Ga, and their binding specificity and cellular processing were evaluated. The biodistribution of (68Ga-DOTA-ZHER2:S1, (68Ga-NOTA-ZHER2:S1 and (68Ga-NODAGA-ZHER2:S1, as well as that of their (111In-labeled counterparts, was evaluated in BALB/C nu/nu mice bearing HER2-expressing SKOV3 xenografts. The tumor uptake for (68Ga-DOTA-ZHER2:S1 (17.9 ± 0.7%IA/g was significantly higher than for both (68Ga-NODAGA-ZHER2:S1 (16.13 ± 0.67%IA/g and (68Ga-NOTA-ZHER2:S1 (13 ± 3%IA/g at 2 h after injection. (68Ga-NODAGA-ZHER2:S1 had the highest tumor-to-blood ratio (60 ± 10 in comparison with both (68Ga-DOTA-ZHER2:S1 (28 ± 4 and (68Ga-NOTA-ZHER2:S1 (42 ± 11. The tumor-to-liver ratio was also higher for (68Ga-NODAGA-ZHER2:S1 (7 ± 2 than the DOTA and NOTA conjugates (5.5 ± 0.6 vs.3.3 ± 0.6. The influence of chelator on the biodistribution and targeting properties was less pronounced for (68Ga than for (111In. The results of this study demonstrate that macrocyclic

  11. HAT-P-68b: A Transiting Hot Jupiter Around a K5 Dwarf Star

    Science.gov (United States)

    Lindor, Bethlee; Hartman, Joel D.

    2018-01-01

    One of the main goals of the astrophysical society has been to detect sources of life outside of Earth. To aid this search, astronomers have spent the last 2 decades focused on the discovery and characterization of exoplanets. The most effective method for doing so has been transit photometry, wherein we measure the brightness of stars over periods of time. These measurements, or light curves, are later analyzed for dips in brightness caused by objects passing in front of the star. However, variations in these time series can also occur due to non-planetary systems and a meticulous process is needed to distinguish the planets from the various false positives that are detected. HATNet is one of many surveys involved in this endeavor, and in this work I analyze HAT-P-68. First, I model the system as a single star with a transiting planet and derive estimates of the stellar and planetary physical parameters. I also model HAT-P-68 as a number of a false positives such as a pair of stars in an eclipsing binary blended with a background star, and a planet-sized star orbiting a Sun-like star. In order to rule out the possibility that HAT-P-68 is a blend, I carried out a statistical blend analysis of the photometric data and find that all blend models tested can be ruled out. Thus, I conclude that HAT-P-68 is a system with a transiting hot jupiter and consider what future observations would be most promising to further characterize the system.

  12. Preclinical evaluation of a 68Ga-labeled biotin analogue for applications in islet transplantation

    International Nuclear Information System (INIS)

    Eriksson, Olof; Carlsson, Fredrik; Blom, Elisabeth; Sundin, Anders; Långström, Bengt; Korsgren, Olle; Velikyan, Irina

    2012-01-01

    Introduction: Islet transplantation is a promising treatment for type 1 diabetes mellitus, but the fate of the cells after intraportal infusion is unclear. It is therefore imperative to develop novel techniques for noninvasive imaging and quantification of events following islet transplantation. Methods: Small islet-like microbeads, avidin-covered agarose resins (AARs), were used as a model system for islet transplantation. Capability for specific [ 68 Ga]Ga-DOTA-(PEG) 2 -biotin uptake and retention for either AARs or human islets conjugated with avidin by means of a heparin scaffold was studied in vitro. Biodistribution of the novel positron emission tomography (PET) tracer [ 68 Ga]Ga-DOTA-(PEG) 2 -biotin was evaluated in mice treated by intraportal transplantation of AARs by μPET/computed tomography and ex vivo organ distribution and compared with control mice. Results: AARs had high capability to bind [ 68 Ga]Ga-DOTA-(PEG) 2 -biotin, close to 50% of administrated tracer/μl in vitro (>0.25 MBq/μl). Avidin-tagged human islets could bind on average 2.2% of administered tracer/μl. Specificity (>90%) and retention (>90% after 1 h) were high for both AARs and avidin-tagged islets. Hepatic tracer uptake and retention were increased in mice transplanted with AARs [standardized uptake value (SUV)=2.6] compared to the untreated group (SUV=1.4). In vivo uptake of tracer to AARs was blocked by preadministration of unlabeled biotin. Conclusions: Avidin-tagged islet-like objects can be tracked in hepatic volume after intraportal transplantation by using [ 68 Ga]Ga-DOTA-(PEG) 2 -biotin and PET.

  13. Pair phase transition and its evolution on even 64-68Ge isotopes

    International Nuclear Information System (INIS)

    Tong Hong; Shi Zhuyi

    2004-01-01

    By using a microscopic sdIBM-2+2q . p . approach which is the phenomenological core plus two-quasi-particle model and the experimental single-particle energies, the levels of the ground-band, β-band, γ-band, and partial two-quasi-particle states on 64-68 Ge isotopes are successfully reproduced. Based on the phenomenological model and microscopic approach, it has been deduced that no s-boson in the nucleus is breaking up and aligning; and that when one d-boson does, the minimum aligned energy can be calculated. This paper explicitly indicates that, with the increase of neutron number, an evolution process of PPT objects, i.e. from the two-quasi-proton states (on 64 Ge nucleus) to the two-quasi-neutron states (on 68 Ge nucleus) may take place in even Ge isotopes. (authors)

  14. MicroPET/CT imaging of {alpha}{sub v}{beta}{sub 3} integrin via a novel {sup 68}Ga-NOTA-RGD peptidomimetic conjugate in rat myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Menichetti, Luca; Kusmic, Claudia; Panetta, Daniele; Petroni, Debora; Salvadori, Piero A. [CNR-Institute of Clinical Physiology (IFC), Pisa (Italy); Arosio, Daniela; Manzoni, Leonardo [CNR-Institute of Molecular Science and Technologies (ISTM), Milan (Italy); Matteucci, Marco [Scuola Superiore Sant' Anna, Pisa (Italy); Casagrande, Cesare [University of Milan, Department of Chemistry, Milan (Italy); L' Abbate, Antonio [CNR-Institute of Clinical Physiology (IFC), Pisa (Italy); Scuola Superiore Sant' Anna, Pisa (Italy)

    2013-08-15

    The {alpha}{sub v}{beta}{sub 3} integrin is expressed in angiogenic vessels and is a potential target for molecular imaging of evolving pathological processes. Its expression is upregulated in cancer lesions and metastases as well as in acute myocardial infarction (MI) as part of the infarct healing process. The purpose of our study was to determine the feasibility of a new imaging approach with a novel {sup 68}Ga-2,2',2''-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (NOTA)-arginine-glycine-aspartic acid (RGD) construct to assess integrin expression in the evolving MI. A straightforward labelling chemistry to attach the radionuclide {sup 68}Ga to a NOTA-based chelating agent conjugated with a cyclic RGD peptidomimetic is described. Affinity for {alpha}{sub v}{beta}{sub 3} integrin was assessed by in vitro receptor binding assay. The proof-of-concept in vivo studies combined the {sup 68}Ga-NOTA-RGD with the flow tracer {sup 13}N-NH{sub 3} imaging in order to obtain positron emission tomography (PET)/CT imaging of both integrin expression and perfusion defect at 4 weeks after infarction. Hearts were then processed for immunostaining of integrin {beta}{sub 3}. NOTA-RGD conjugate displayed a binding affinity for {alpha}{sub v}{beta}{sub 3} integrin of 27.9 {+-} 6.8 nM. {sup 68}Ga-NOTA-RGD showed stability without detectable degradation or formation of by-products in urine up to 2 h following injection in the rat. MI hearts exhibited {sup 68}Ga-NOTA-RGD uptake in correspondence to infarcted and border zone regions. The tracer signal drew a parallel with vascular remodelling due to ischaemia-induced angiogenesis as assessed by immunohistochemistry. As compared to similar imaging approaches using the {sup 18}F-galacto-derivative, we documented for the first time with microPET/CT imaging the {sup 68}Ga-NOTA-RGD derivative that appears eligible for PET imaging in animal models of vascular remodelling during evolving MI. The simple chemistry employed to

  15. Assessing patient-caregiver communication in cancer--a psychometric validation of the Cancer Communication Assessment Tool (CCAT-PF) in a German sample.

    Science.gov (United States)

    Haun, Markus W; Sklenarova, Halina; Winkler, Eva C; Huber, Johannes; Thomas, Michael; Siminoff, Laura A; Woll, Michael; Brechtel, Anette; Herzog, Wolfgang; Hartmann, Mechthild

    2014-09-01

    The recently introduced Cancer Communication Assessment Tool (CCAT-PF) measures congruence in patient-caregiver communication and was initially validated in lung cancer patients. Contributing to a greater proportion of the variance in the conflict scores, primary caregivers were hypothesized to experience greater stress. For a detailed understanding of conflicting communication patterns of cancer-affected families, our study aimed for psychometric validation of the CCAT-PF in a sample covering heterogeneous tumor entities. Subsequent to a cross-sectional survey of 189 pairs of cancer patients (31 % gastrointestinal, 34 % lung, and 35 % urological) and their caregivers' exploratory factor analysis with principal component condensation and varimax rotation was conducted (response rate, 74.2 %). Reliability and construct validity were assessed calculating Cronbach's α and Pearson correlation coefficients for CCAT-P and CCAT-F scales and related constructs, respectively. Cancer-related communication according to the CCAT-PF can be subdivided into four factors including the scales Disclosure, Limitation of treatment, Family involvement in treatment decisions, and Continuing treatment. Reliability ranged from α = .51-.68. The Disclosure scale, describing poor cancer-related communication of the patient, was correlated with patient's distress (QSC-R10: r = .30, p reliable stand-alone instrument for identifying conflicting communication in patient-caregiver-dyads at risk.

  16. 12 CFR 792.68 - Use and collection of Social Security numbers.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Use and collection of Social Security numbers... Act § 792.68 Use and collection of Social Security numbers. The head of each NCUA Office shall take... furnish Social Security numbers, and that individuals who are requested to provide Social Security numbers...

  17. Coxsackievirus A21, Enterovirus 68, and Acute Respiratory Tract Infection, China

    OpenAIRE

    Xiang, Zichun; Gonzalez, Richard; Wang, Zhong; Ren, Lili; Xiao, Yan; Li, Jianguo; Li, Yongjun; Vernet, Guy; Paranhos-Baccalà, Gláucia; Jin, Qi; Wang, Jianwei

    2012-01-01

    During August 2006–April 2010, in Beijing, China, 2 rare human enterovirus serotypes, coxsackievirus A21 and enterovirus 68, were detected most frequently in human enterovirus–positive adults with acute respiratory tract infections. Thus, during some years, these 2 viruses cause a substantial proportion of enterovirus-associated adult acute respiratory tract infections.

  18. Evaluation of (68)Ga- and (177)Lu-DOTA-PEG4-LLP2A for VLA-4-Targeted PET Imaging and Treatment of Metastatic Melanoma.

    Science.gov (United States)

    Beaino, Wissam; Nedrow, Jessie R; Anderson, Carolyn J

    2015-06-01

    Malignant melanoma is a highly aggressive cancer, and the incidence of this disease is increasing worldwide at an alarming rate. Despite advances in the treatment of melanoma, patients with metastatic disease still have a poor prognosis and low survival rate. New strategies, including targeted radiotherapy, would provide options for patients who become resistant to therapies such as BRAF inhibitors. Very late antigen-4 (VLA-4) is expressed on melanoma tumor cells in higher levels in more aggressive and metastatic disease and may provide an ideal target for drug delivery and targeted radiotherapy. In this study, we evaluated (177)Lu- and (68)Ga-labeled DOTA-PEG4-LLP2A as a VLA-4-targeted radiotherapeutic with a companion PET agent for diagnosis and monitoring metastatic melanoma treatment. DOTA-PEG4-LLP2A was synthesized by solid-phase synthesis. The affinity of (177)Lu- and (68)Ga-labeled DOTA-PEG4-LLP2A to VLA-4 was determined in B16F10 melanoma cells by saturation binding and competitive binding assays, respectively. Biodistribution of the LLP2A conjugates was determined in C57BL/6 mice bearing B16F10 subcutaneous tumors, while PET/CT imaging was performed in subcutaneous and metastatic models. (177)Lu-DOTA-PEG4-LLP2A showed high affinity to VLA-4 with a Kd of 4.1 ± 1.5 nM and demonstrated significant accumulation in the B16F10 melanoma tumor after 4 h (31.5 ± 7.8%ID/g). The tumor/blood ratio of (177)Lu-DOTA-PEG4-LLP2A was highest at 24 h (185 ± 26). PET imaging of metastatic melanoma with (68)Ga-DOTA-PEG4-LLP2A showed high uptake in sites of metastases and correlated with bioluminescence imaging of the tumors. These data demonstrate that (177)Lu-DOTA-PEG4-LLP2A has potential as a targeted therapeutic for treating melanoma as well as other VLA-4-expressing tumors. In addition, (68)Ga-DOTA-PEG4-LLP2A is a readily translatable companion PET tracer for imaging of metastatic melanoma.

  19. Development of 68Ga-SCN-DOTA-Capsaicin as an Imaging Agent Targeting Apoptosis and Cell Cycle Arrest in Breast Cancer.

    Science.gov (United States)

    Lee, Jun Young; Lee, Sang-Yeun; Kim, Gun Gyun; Hur, Min Goo; Yang, Seung Dae; Park, Jeong-Hoon; Kim, Sang Wook

    2017-06-01

    68 Ga-labeled capsaicin using a DOTA (1,4,7,10-tetraazocyclododecane-N,N',N″,N'″-tetraacetic acid) derivative [ 68 Ga-SCN-Benzyl(Bn)-DOTA-capsaicin] was studied for the diagnosis of breast cancers, such as MCF-7 and SK-BR-3. The standard compound, 69 Ga-SCN-Bn-DOTA-capsaicin, was also prepared and characterized by spectroscopic analysis. The binding affinity of 68 Ga-SCN-Bn-DOTA-capsaicin was evaluated by using breast cancer cell lines (MCF-7, SK-BR-3) and colon cancer cell (CT-26); the biodistribution was carried out by using MCF-7-bearing nude mice, after which the positron emission tomography (PET) images were obtained at different time intervals (15-120 minutes). 68 Ga-SCN-Bn-DOTA-capsaicin showed a cellular uptake of 0.93% Injected Dose (ID) after 30 minutes of incubation, whereas 68 Ga-SCN-Bn-DOTA showed a lower uptake of 0.25% ID. The tumor-to-blood ID/g% ratios increased and were found to be 0.49, 0.22, and 0.77 for 15, 30, and 60 minutes, respectively. The small-animal PET study showed that the uptake of 68 Ga-SCN-Bn-DOTA-capsaicin was higher in the tumor regions even at 30 minutes after injection. These results suggest that 68 Ga-SCN-Bn-DOTA-capsaicin is a potential targeting agent for PET imaging of MCF-7.

  20. Defense Acquisition Research Journal. Volume 21, Number 1, Issue 68

    Science.gov (United States)

    2014-01-01

    Manual of the American Psychological Association ( 6th Edition ). For all other style questions, please refer to the Chicago Manual of Style (15th...language. Format Please submit your manuscript with references in APA format (author- date-page number form of citation) as outlined in the Publication ...January 2014 Vol. 21 No. 1 | ISSUE 68 Challenging Conventional Wisdom REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704-0188 Public

  1. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study.

    Science.gov (United States)

    Greninger, Alexander L; Naccache, Samia N; Messacar, Kevin; Clayton, Anna; Yu, Guixia; Somasekar, Sneha; Federman, Scot; Stryke, Doug; Anderson, Christopher; Yagi, Shigeo; Messenger, Sharon; Wadford, Debra; Xia, Dongxiang; Watt, James P; Van Haren, Keith; Dominguez, Samuel R; Glaser, Carol; Aldrovandi, Grace; Chiu, Charles Y

    2015-06-01

    Enterovirus D68 was implicated in a widespread outbreak of severe respiratory illness across the USA in 2014 and has also been reported sporadically in patients with acute flaccid myelitis. We aimed to investigate the association between enterovirus D68 infection and acute flaccid myelitis during the 2014 enterovirus D68 respiratory outbreak in the USA. Patients with acute flaccid myelitis who presented to two hospitals in Colorado and California, USA, between Nov 24, 2013, and Oct 11, 2014, were included in the study. Additional cases identified from Jan 1, 2012, to Oct 4, 2014, via statewide surveillance were provided by the California Department of Public Health. We investigated the cause of these cases by metagenomic next-generation sequencing, viral genome recovery, and enterovirus D68 phylogenetic analysis. We compared patients with acute flaccid myelitis who were positive for enterovirus D68 with those with acute flaccid myelitis but negative for enterovirus D68 using the two-tailed Fisher's exact test, two-sample unpaired t test, and Mann-Whitney U test. 48 patients were included: 25 with acute flaccid myelitis, two with enterovirus-associated encephalitis, five with enterovirus-D68-associated upper respiratory illness, and 16 with aseptic meningitis or encephalitis who tested positive for enterovirus. Enterovirus D68 was detected in respiratory secretions from seven (64%) of 11 patients comprising two temporally and geographically linked acute flaccid myelitis clusters at the height of the 2014 outbreak, and from 12 (48%) of 25 patients with acute flaccid myelitis overall. Phylogenetic analysis revealed that all enterovirus D68 sequences associated with acute flaccid myelitis grouped into a clade B1 strain that emerged in 2010. Of six coding polymorphisms in the clade B1 enterovirus D68 polyprotein, five were present in neuropathogenic poliovirus or enterovirus D70, or both. One child with acute flaccid myelitis and a sibling with only upper respiratory

  2. Synthesis of novel {sup 68}Ga-labeled amino acid derivatives for positron emission tomography of cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Shetty, Dinesh [Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Jeong, Jae Min, E-mail: jmjng@snu.ac.k [Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Ju, Chang Hwan [Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul (Korea, Republic of); Lee, Yun-Sang [Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Jeong, Seo Young [Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul (Korea, Republic of); Choi, Jae Yeon; Yang, Bo Yeun [Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Department of Radiation Applied Life Science, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of)

    2010-11-15

    Objectives: We developed amino acid derivatives of 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) and 1,4,7,10-tetraazacyclododecane-1,4,7,-triacetic acid (DO3A) that can be labeled with {sup 68}Ga, and we investigated their basic biological properties. Materials and methods: Alanine derivatives of DO2A and DO3A were synthesized by regiospecific nucleophilic attack of DO2tBu and DO3tBu on the {beta}-position of Boc-L-serine-{beta}-lactone, followed by acid hydrolysis. Also, homoalanine derivatives were synthesized by reacting with the protected bromo derivative of homoalanine, which was synthesized from N-Cbz-L-homoserine lactone. Further catalytic reduction and acid cleavage of protected groups resulted in the required products. All derivatives were labeled with {sup 68}Ga. Cell uptake assays were carried out in Hep3B (human hepatoma) and U87MG (human glioma) cell lines at 37{sup o}C. Positron emission tomography (PET) imaging studies were performed using balb/c mice xenografted with CT-26 (mouse colon cancer). Results: All compounds were labeled with >97% efficiency. According to in vitro studies, the labeled amino acid derivatives showed significantly greater uptakes than the control ({sup 68}Ga 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) in cancer cells. Small animal PET images for labeled compounds showed high tumor uptake, as well as kidney and bladder uptakes, at 30 min postinjection. {sup 68}Ga-DO3A-homoalanine showed the highest standardized uptake value ratio (3.9{+-}0.3), followed by {sup 68}Ga-DO2A-alanine (3.1{+-}0.2), {sup 68}Ga-DO3A-alanine (2.8{+-}0.2) and {sup 68}Ga-DO2A-homoalanine (2.3{+-}0.2). Conclusion: These derivatives were found to have high labeling efficiencies, high stabilities, high tumor cell uptakes, high tumor/nontumor xenograft uptakes and low nonspecific uptake in normal organs, except for the kidneys. However, the uptake mechanism of these derivatives remains unclear, and uptake via specific amino acid

  3. Development of 68Ga-labeled mannosylated human serum albumin (MSA) as a lymph node imaging agent for positron emission tomography

    International Nuclear Information System (INIS)

    Choi, Jae Yeon; Jeong, Jae Min; Yoo, Byong Chul; Kim, Kyunggon; Kim, Youngsoo; Yang, Bo Yeun; Lee, Yun-Sang; Lee, Dong Soo; Chung, June-Key; Lee, Myung Chul

    2011-01-01

    Introduction: Although many sentinel lymph node (SLN) imaging agents labeled with 99m Tc have been developed, no positron-emitting agent has been specifically designed for SLN imaging. Furthermore, the development of the beta probe and the requirement for better image resolution have increased the need for a positron-emitting SLN imaging agent. Here, we describe the development of a novel positron-emitting SLN imaging agent labeled with 68 Ga. Methods: A mannosylated human serum albumin (MSA) was synthesized by conjugating α-D-mannopyranosylphenyl isothiocyanate to human serum albumin in sodium carbonate buffer (pH 9.5), and then 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid was conjugated to synthesize NOTA-MSA. Numbers of mannose and NOTA units conjugated in NOTA-MSA were determined by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. NOTA-MSA was labeled with 68 Ga at room temperature. The stability of 68 Ga-NOTA-MSA was checked in labeling medium at room temperature and in human serum at 37 o C. Biodistribution in normal ICR mice was investigated after tail vein injection, and micro-positron emission tomography (PET) images were obtained after injecting 68 Ga-NOTA-MSA into a tail vein or a footpad. Results: The numbers of conjugated α-D-mannopyranosylphenyl isothiocyanate and 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid units in NOTA-MSA were 10.6 and 6.6, respectively. The labeling efficiency of 68 Ga-NOTA-MSA was greater than 99% at room temperature, and its stability was greater than 99% at 4 h. Biodistribution and micro-PET studies of 68 Ga-NOTA-MSA showed high liver and spleen uptakes after intravenous injection. 68 Ga-NOTA-MSA injected into a footpad rapidly migrated to the lymph node. Conclusions: 68 Ga-NOTA-MSA was successfully developed as a novel SLN imaging agent for PET. NOTA-MSA is easily labeled at high efficiency, and subcutaneously administered 68 Ga-NOTA-MSA was

  4. Five strands of math drills big book : grades 6-8

    CERN Document Server

    Reed, Nat; Forest, Chris

    2011-01-01

    For grades 6-8, our Common Core State Standards-based resource meets the five strands of math concepts addressed by the NCTM standards and encourages the students to review the concepts in unique ways. Included are warm-up and timed drill activities which will push the boundaries of critical thought and demonstrate to students the importance of mathematical problems in Number & Operations, Geometry, Measurement, Data Analysis & Probability and Algebra using real world situations.

  5. In vivo binding of [{sup 68}Ga]-DOTATOC to somatostatin receptors in neuroendocrine tumours - impact of peptide mass

    Energy Technology Data Exchange (ETDEWEB)

    Velikyan, Irina [Department of Biochemistry and Organic Chemistry, BMC, Uppsala University, Box 599, SE-751 24 Uppsala (Sweden); Uppsala Applied Science Lab, GEMS PET Systems, GE Healthcare, SE-752 28 Uppsala (Sweden); Sundin, Anders [Department of Radiology, Karolinska University Hospital, SE-171 76 Stockholm (Sweden); Eriksson, Barbro [Department of Endocrine Oncology, Uppsala University Hospital, SE-751 85 Uppsala (Sweden); Lundqvist, Hans [Department of Oncology, Radiology and Clinical Immunology, Uppsala University, SE-751 85 Uppsala (Sweden); Soerensen, Jens [Department of Medicinal Sciences, Clinical Physiology and Nuclear Medicine, Uppsala University Hospital, SE-751 85 Uppsala (Sweden); Bergstroem, Mats [Department of Pharmaceutical Biosciences, Uppsala Biomedical Centre, Uppsala University, Uppsala (Sweden); Langstroem, Bengt [Department of Biochemistry and Organic Chemistry, BMC, Uppsala University, Box 599, SE-751 24 Uppsala (Sweden)], E-mail: langstrom@biorg.uu.se

    2010-04-15

    Objectives: The aim of this pilot study was to explore the impact of peptide mass on binding of [{sup 68}Ga]-DOTATOC to neuroendocrine tumour somatostatin receptors in vivo using a tracer of variable specific radioactivity (SRA) and to show the logistic feasibility of sequential PET scans in the same patient. Material and Methods: Nine patients with gastroenteropancreatic neuroendocrine tumours were included. Six of them underwent three sequential PET-CT examinations with intravenous injections of [{sup 68}Ga]-DOTATOC proceeded by 0, 50 and 250 or 500 {mu}g of octreotide, administered 10 min before the tracer. Three patients were examined by dynamic and static PET/CT for pharmacokinetic and dosimetric calculations. The [{sup 68}Ga]-DOTATOC synthesis included preconcentration and purification of the generator eluate and microwave heating in a semi-automated in-house procedure. Results: [{sup 68}Ga]-DOTATOC synthesis and quality control were accomplished within 30 min and radiochemical purity was >95%. The tracer accumulation in the tumours varied and depended on the total amount of the administered peptide. In five of six patients, the highest tumour-to-normal tissue ratio was found when 50 {mu}g of octreotide was preadministered. One patient showed a continuously increasing tumour uptake. Dosimetrically, a large variation in organ doses was found (kidney: 0.086-0.168 mSv/MBq; liver: 0.026-0.096 mSv/MBq; spleen: 0.046-0.226 mSv/MBq). The effective dose (0.015, 0.0067 and 0.0042 mSv/MBq) was correlated to the total amount of decays. Discussion: Three sequential PET-CT examinations using {sup 68}Ga-based tracer was carried out in 1 day. The use of high SRA [{sup 68}Ga]-DOTATOC and unlabelled octreotide indicates an optimal mass leading to better image contrast. [{sup 68}Ga]-DOTATOC-PET-CT employing variable SRA may be utilised for accurate quantification of tumour uptake with subsequent dosimetry for personalized therapy management.

  6. Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?

    Science.gov (United States)

    Gauthé, Mathieu; Testart Dardel, Nathalie; Ruiz Santiago, Fernando; Ohnona, Jessica; Nataf, Valérie; Montravers, Françoise; Talbot, Jean-Noël

    2018-03-12

    To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe 1 -Tyr 3 -octreotide labelled with gallium-68 ( 68 Ga-DOTA-TOC). In 535 NET patients, 68 Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUV max ) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion. In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm 3 , SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68 Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively. The high sensitivity of 68 Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68 Ga-DOTA-TOC uptake. • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

  7. Effect of three 2-allyl-p-mentha-6,8-dien-2-ols on inhibition of mild steel corrosion in 1 M HCl

    Directory of Open Access Journals (Sweden)

    S. Kharchouf

    2014-11-01

    Full Text Available 2-Allyl-p-mentha-6,8-dien-2-ols P1−P3 synthesized from carvone P are tested as corrosion inhibitors of steel in 1 M HCl using weight loss measurements, potentiodynamic polarisation and impedance spectroscopy (EIS methods. The addition of 2-allyl-p-mentha-6,8-dien-2-ols reduced the corrosion rate. Potentiodynamic polarisation studies clearly reveal that the presence of inhibitors does not change the mechanism of hydrogen evolution and that they act essentially as cathodic inhibitors. 2-Allyl-p-mentha-6,8-dien-2-ols tested adsorb on the steel surface according to Langmuir isotherm. From the adsorption isotherm some thermodynamic data for the adsorption process are calculated and discussed. EIS measurements show the increase of the charge-transfer resistance with the inhibitor concentration. The highest inhibition efficiency (92% is obtained for P1 at 3 g/L. The corrosion rate decreases with the rise of temperature. The corresponding activation energies are determined.

  8. Comprehensive analysis of interactions between the Src-associated protein in mitosis of 68 kDa and the human Src-homology 3 proteome.

    Directory of Open Access Journals (Sweden)

    Benedikt Asbach

    Full Text Available The protein Sam68 is involved in many cellular processes such as cell-cycle regulation, RNA metabolism, or signal transduction. Sam68 comprises a central RNA-binding domain flanked by unstructured tails containing docking sites for signalling proteins including seven proline-rich sequences (denoted P0 to P6 as potential SH3-domain binding motifs. To comprehensively assess Sam68-SH3-interactions, we applied a phage-display screening of a library containing all approx. 300 human SH3 domains. Thereby we identified five new (from intersectin 2, the osteoclast stimulating factor OSF, nephrocystin, sorting nexin 9, and CIN85 and seven already known high-confidence Sam68-ligands (mainly from the Src-kinase family, as well as several lower-affinity binders. Interaction of the high-affinity Sam68-binders was confirmed in independent assays in vitro (phage-ELISA, GST-pull-down and in vivo (FACS-based FRET-analysis with CFP- and YFP-tagged proteins. Fine-mapping analyses with peptides established P0, P3, P4, and P5 as exclusive docking-sites for SH3 domains, which showed varying preferences for these motifs. Mutational analyses identified individual residues within the proline-rich motifs being crucial for the interactions. Based on these data, we generated a Sam68-mutant incapable of interacting with SH3 domains any more, as subsequently demonstrated by FRET-analyses. In conclusion, we present a thorough characterization of Sam68's interplay with the SH3 proteome. The observed interaction between Sam68 and OSF complements the known Sam68-Src and OSF-Src interactions. Thus, we propose, that Sam68 functions as a classical scaffold protein in this context, assembling components of an osteoclast-specific signalling pathway.

  9. (68)Ga-DOTA-Siglec-9 PET/CT imaging of peri-implant tissue responses and staphylococcal infections.

    Science.gov (United States)

    Ahtinen, Helena; Kulkova, Julia; Lindholm, Laura; Eerola, Erkki; Hakanen, Antti J; Moritz, Niko; Söderström, Mirva; Saanijoki, Tiina; Jalkanen, Sirpa; Roivainen, Anne; Aro, Hannu T

    2014-01-01

    Staphylococcus epidermidis (S. epidermidis) has emerged as one of the leading pathogens of biomaterial-related infections. Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial molecule controlling extravasation of leukocytes. Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a leukocyte ligand of VAP-1. We hypothesized that (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-conjugated Siglec-9 motif containing peptide ((68)Ga-DOTA-Siglec-9) could detect inflammatory response due to S. epidermidis peri-implant infection by positron emission tomography (PET). Thirty Sprague-Dawley rats were randomized into three groups. A sterile catheter was implanted into the medullary canal of the left tibia. In groups 1 and 2, the implantation was followed by peri-implant injection of S. epidermidis or Staphylococcus aureus (S. aureus) with adjunct injections of aqueous sodium morrhuate. In group 3, sterile saline was injected instead of bacteria and no aqueous sodium morrhuate was used. At 2 weeks after operation, (68)Ga-DOTA-Siglec-9 PET coupled with computed tomography (CT) was performed with the measurement of the standardized uptake value (SUV). The presence of the implant-related infection was verified by microbiological analysis, imaging with fluorescence microscope, and histology. The in vivo PET results were verified by ex vivo measurements by gamma counter. In group 3, the tibias with implanted sterile catheters showed an increased local uptake of (68)Ga-DOTA-Siglec-9 compared with the intact contralateral bones (SUVratio +29.5%). (68)Ga-DOTA-Siglec-9 PET detected inflammation induced by S. epidermidis and S. aureus catheter-related bone infections (SUVratio +58.1% and +41.7%, respectively). The tracer uptake was significantly higher in the S. epidermidis group than in group 3 without bacterial inoculation, but the difference between S. epidermidis and S. aureus groups was not statistically significant. The

  10. Identification of human genes involved in cellular responses to ionizing radiation: molecular and cellular studies of gene encoding the p68 helicase in mammalian cells

    International Nuclear Information System (INIS)

    Menaa, F.

    2003-12-01

    Cells submitted to genotoxic factors -like IR- activate several and important mechanisms such as repair, cell cycle arrest or 'apoptosis' to maintain genetic integrity. So, the damaged cells will induce many and different genes. The human transcriptome analysis by 'SSH' method in a human breast carcinoma cell line MCF7 γ-irradiated versus not irradiated, allowed to identify about one hundred genes. Among of these genes, we have focused our study on a radio-induced gene encoding the p68 helicase. In the conditions of irradiation used, our results show that the kinetic and the regulation of this gene expression differs between the nature of radiations used. Indeed, in γ-irradiated mammalian cells, ATM, a protein kinase activated by DSB and IR, is required to induce quickly P68 gene via the important transcription factor p53 stabilized by IR. In the case of UVC-irradiated cells, the P68 gene induction is late and the intracellular signalling pathway that lead to this induction is independent from the p53 protein. Finally, we show that the p68 protein under-expression is responsible for an increased radiosensitivity of MCF7 cells. Consequently, we can postulate that the p68 protein is involved in cellular responses to radiations to reduce the increased radiosensitivity of cells exposed to γ-rays. (author)

  11. Prospective of 68Ga Radionuclide Contribution to the Development of Imaging Agents for Infection and Inflammation

    Science.gov (United States)

    2018-01-01

    During the last decade, the utilization of 68Ga for the development of imaging agents has increased considerably with the leading position in the oncology. The imaging of infection and inflammation is lagging despite strong unmet medical needs. This review presents the potential routes for the development of 68Ga-based agents for the imaging and quantification of infection and inflammation in various diseases and connection of the diagnosis to the treatment for the individualized patient management. PMID:29531507

  12. Standardization of Ga-68 by coincidence measurements, liquid scintillation counting and 4πγ counting

    International Nuclear Information System (INIS)

    Roteta, Miguel; Peyres, Virginia; Rodríguez Barquero, Leonor; García-Toraño, Eduardo; Arenillas, Pablo; Balpardo, Christian; Rodrígues, Darío; Llovera, Roberto

    2012-01-01

    The radionuclide 68 Ga is one of the few positron emitters that can be prepared in-house without the use of a cyclotron. It disintegrates to the ground state of 68 Zn partially by positron emission (89.1%) with a maximum energy of 1899.1 keV, and partially by electron capture (10.9%). This nuclide has been standardized in the frame of a cooperation project between the Radionuclide Metrology laboratories from CIEMAT (Spain) and CNEA (Argentina). Measurements involved several techniques: 4πβ−γ coincidences, integral gamma counting and Liquid Scintillation Counting using the triple to double coincidence ratio and the CIEMAT/NIST methods. Given the short half-life of the radionuclide assayed, a direct comparison between results from both laboratories was excluded and a comparison of experimental efficiencies of similar NaI detectors was used instead. - Highlights: ► We standardized the positron emitter Ga-68 in a bilateral cooperation. ► We used several techniques, as coincidence, integral gamma and liquid scintillation. ► An efficiency comparison replaced a direct comparison of reference materials.

  13. Development of an injectable formulation for the preparation of radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin; Desarrollo de una formulacion inyectable para la preparacion del radiofarmaco {sup 68}Ga-DOTA-Sargastrina

    Energy Technology Data Exchange (ETDEWEB)

    Castillo P, M.

    2015-07-01

    The CCK2 receptor (cholecystokinin) is located in areas of the central and peripheral nervous system and is over expressed in several types of human cancer, as medullar thyroid, lung and ovarian carcinomas. One of the endogenous ligands for the CCK2 receptor is the gastrin, so that radiolabeled peptides analogues to gastrin as Sar gastrin (Gln-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH{sub 2}) have been proposed as potential diagnostic radiopharmaceuticals for obtaining tumors images with CCK2 receptors over expressed. The {sup 68}Ga is an ideal candidate for the peptides radiolabelled and has favorable characteristics to be used for diagnostic purposes by imaging with Positron emission tomography (PET). This work aimed to verify the technical documentation of the production process of radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin for its sanitary registration before the Comision Federal contra Riesgos Sanitarios (COFEPRIS) in Mexico. For optimization of the production process was assessed a factorial design of two variables with mixed levels (27 combinations), where the dependent variable was the radiochemical purity. The analytical method used for evaluating the content of Sar gastrin peptide in the injectable formulation was also validated by High-performance liquid chromatography. Subsequently the validation of the production process was carried out by manufacturing of lots in single-dose of the optimized injectable formulation of the radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin and the stability study was conducted at different times to determine the useful life time. The following was established as the optimal pharmaceutical formulation: 185 MBq of {sup 68}Ga, 50 μg de DOTA-Sar gastrin, 14 mg of sodium acetate and 0.5 m L of buffer acetates, 1.0 M, ph 4.22 in 2.5 m L of the vehicle. The analytical method used to determine the radiochemical purity of the formulation satisfied the requirements for the intended analytical

  14. Mechanism analysis of acid tolerance response of bifidobacterium longum subsp. longum BBMN 68 by gene expression profile using RNA-sequencing.

    Directory of Open Access Journals (Sweden)

    Junhua Jin

    Full Text Available To analyze the mechanism of the acid tolerance response (ATR in Bifidobacterium longum subsp. longum BBMN68, we optimized the acid-adaptation condition to stimulate ATR effectively and analyzed the change of gene expression profile after acid-adaptation using high-throughput RNA-Seq. After acid-adaptation at pH 4.5 for 2 hours, the survival rate of BBMN68 at lethal pH 3.5 for 120 min was increased by 70 fold and the expression of 293 genes were upregulated by more than 2 fold, and 245 genes were downregulated by more than 2 fold. Gene expression profiling of ATR in BBMN68 suggested that, when the bacteria faced acid stress, the cells strengthened the integrity of cell wall and changed the permeability of membrane to keep the H(+ from entering. Once the H(+ entered the cytoplasm, the cells showed four main responses: First, the F(0F(1-ATPase system was initiated to discharge H(+. Second, the ability to produce NH(3 by cysteine-cystathionine-cycle was strengthened to neutralize excess H(+. Third, the cells started NER-UVR and NER-VSR systems to minimize the damage to DNA and upregulated HtpX, IbpA, and γ-glutamylcysteine production to protect proteins against damage. Fourth, the cells initiated global response signals ((pppGpp, polyP, and Sec-SRP to bring the whole cell into a state of response to the stress. The cells also secreted the quorum sensing signal (AI-2 to communicate between intraspecies cells by the cellular signal system, such as two-component systems, to improve the overall survival rate. Besides, the cells varied the pathways of producing energy by shifting to BCAA metabolism and enhanced the ability to utilize sugar to supply sufficient energy for the operation of the mechanism mentioned above. Based on these reults, it was inferred that, during industrial applications, the acid resistance of bifidobacteria could be improved by adding BCAA, γ-glutamylcysteine, cysteine, and cystathionine into the acid-stress environment.

  15. TaWRKY68 responses to biotic stresses are revealed by the orthologous genes from major cereals

    Directory of Open Access Journals (Sweden)

    Bo Ding

    2014-01-01

    Full Text Available WRKY transcription factors have been extensively characterized in the past 20 years, but in wheat, studies onWRKY genes and their function are lagging behind many other species. To explore the function of wheat WRKY genes, we identified a TaWRKY68 gene from a common wheat cultivar. It encodes a protein comprising 313 amino acids which harbors 19 conserved motifs or active sites. Gene expression patterns were determined by analyzing microarray data of TaWRKY68 in wheat and of orthologous genes from maize, rice and barley using Genevestigator. TaWRKY68 orthologs were identified and clustered using DELTA-BLAST and COBALT programs available at NCBI. The results showed that these genes, which are expressed in all tissues tested, had relatively higher levels in the roots and were up-regulated in response to biotic stresses. Bioinformatics results were confirmed by RT-PCR experiments using wheat plants infected by Agrobacterium tumefaciens and Blumeria graminis, or treated with Deoxynivalenol, a Fusarium graminearum-induced mycotoxin in wheat or barley. In summary,TaWRKY68 functions differ during plant developmental stages and might be representing a hub gene function in wheat responses to various biotic stresses. It was also found that including data from major cereal genes in the bioinformatics analysis gave more accurate and comprehensive predictions of wheat gene functions.

  16. Evaluation of the Possible Utilization of 68Ga-DOTATOC in Diagnosis of Adenocarcinoma Breast Cancer.

    Science.gov (United States)

    Zolghadri, Samaneh; Naderi, Mojdeh; Yousefnia, Hassan; Alirezapour, Behrouz; Beiki, Davood

    2018-01-01

    Studies have indicated advantageous properties of [DOTA-DPhe 1 , Tyr 3 ] octreotide (DOTATOC) in tumor models and labeling with gallium. Breast cancer is the second leading cause of cancer mortality in women, and most of these cancers are often an adenocarcinoma. Due to the importance of target to non-target ratios in the efficacy of diagnosis, the pharmacokinetic of 68 Ga-DOTATOC in an adenocarcinoma breast cancer animal model was studied in this research, and the optimized time for imaging was determined. 68 Ga was obtained from 68 Ge/ 68 Ga generator. The complex was prepared at optimized conditions. Radiochemical purity of the complex was checked using both HPLC and ITLC methods. Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer. Also, PET/CT imaging was performed up to 120 min post injection. The complex was produced with radiochemical purity of greater than 98% and specific activity of about 40 GBq/mM at optimized conditions. Biodistribution of the complex was studied in BALB/c mice bearing adenocarcinoma breast cancer indicated fast blood clearance and significant uptake in the tumor. Significant tumor: blood and tumor:muscle uptake ratios were observed even at early times post-injection. PET/CT images were also confirmed the considerable accumulation of the tracer in the tumor. Generally, the results proved the possible application of the radiolabelled complex for the detection of the adenocarcinoma breast cancer and according to the pharmacokenitic data, the suitable time for imaging was determined as at least 30 min after injection.

  17. In-beam study of excited states in 68 As

    International Nuclear Information System (INIS)

    Badica, T.; Popa, G.; Popescu, I.; Scantei, N.

    1994-01-01

    As a continuation of our study of odd-odd 68 As nucleus, neutron gamma-gamma coincidence spectra were measured with two Ge(HP) γ-ray and a NE213 scintillation neutron detector. The levels were populated in the 54 Fe( 16 O, p n) reaction. On the basis of the n-γ and n-γγ coincidences a new, more complete level scheme has been established up to 3.2 MeV. Yield functions and angular distribution were used to extract information on spins and multipolarities of γ-transitions. Available level experimental parameters were compared with theoretical predictions of the parabolic rule. (Author)

  18. Laboratory Synthesized Calcium Oxide and Calcium Hydroxide Grains: A Candidate to Explain the 6.8 Micron Band

    Science.gov (United States)

    Kimura, Yuki; Nuth, Joseph A., III

    2005-01-01

    We will demonstrate that CaO and Ca(OH)2 are excellent candidates to explain the 6.8 microns feature, which is one of the most obscure features in young stellar objects. We discuss the condensation of CaO grains and the potential formation of a Ca(OH)2 surface layer. The infrared spectra of these grains are compared with the spectra of fifteen young stellar objects. We note that CaO-rich grains are seen in all meteoritic CAIs (calcium-aluminum-rich inclusions) and the 6.8 micron feature has only been observed in young stellar objects. Therefore, we consider CaO grains to be a plausible candidate to explain the 6.8 microns feature and hypothesize that they are produced in the hot interiors of young stellar environments.

  19. Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models

    OpenAIRE

    Zhang, Libo; Vines, Douglass C.; Scollard, Deborah A.; McKee, Trevor; Komal, Teesha; Ganguly, Milan; Do, Trevor; Wu, Bing; Alexander, Natasha; Vali, Reza; Shammas, Amer; Besanger, Travis; Baruchel, Sylvain

    2017-01-01

    Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imagin...

  20. 47 CFR 68.214 - Changes in other than “fully protected” premises wiring that serves fewer than four subscriber...

    Science.gov (United States)

    2010-10-01

    ... premises wiring that serves fewer than four subscriber access lines. 68.214 Section 68.214... other than “fully protected” premises wiring that serves fewer than four subscriber access lines. Operations associated with the installation, connection, reconfiguration and removal (other than final...