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Sample records for cancer tracer synthesis

  1. Microfluidics for Synthesis of Peptide-Based PET Tracers

    OpenAIRE

    Hong Zhang; Mei Tian; Yang Liu

    2013-01-01

    Positron emission tomography (PET) is a powerful noninvasive tool for acquisition of the physiological parameters in human and animals with the help of PET tracers. Among all the PET tracers, radiolabeled peptides have been widely explored for cancer-related receptor imaging due to their high affinity and specificity to receptors. But radiochemistry procedures for production of peptide-based PET tracers are usually complex, which makes large-scale clinical studies relatively challenging. New ...

  2. The role of new PET tracers for lung cancer.

    Science.gov (United States)

    Szyszko, Teresa A; Yip, Connie; Szlosarek, Peter; Goh, Vicky; Cook, Gary J R

    2016-04-01

    18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is established for characterising indeterminate pulmonary nodules and staging lung cancer where there is curative intent. Whilst a sensitive technique, specificity for characterising lung cancer is limited. There is recognition that evaluation of other aspects of abnormal cancer biology in addition to glucose metabolism may be more helpful in characterising tumours and predicting response to novel targeted cancer therapeutics. Therefore, efforts have been made to develop and evaluate new radiopharmaceuticals in order to improve the sensitivity and specificity of PET imaging in lung cancer with regards to characterisation, treatment stratification and therapeutic monitoring. 18F-fluorothymidine (18F-FLT) is a marker of cellular proliferation. It shows a lower accumulation in tumours than 18F-FDG as it only accumulates in the cells that are in the S phase of growth and demonstrates a low sensitivity for nodal staging. Its main role is in evaluating treatment response. Methionine is an essential amino acid. 11C-methionine is more specific and sensitive than 18F-FDG in differentiating benign and malignant thoracic nodules. 18Ffluoromisonidazole (18F-FMISO) is used for imaging tumour hypoxia. Tumour response to treatment is significantly related to the level of tumour oxygenation. Angiogenesis is the process by which new blood vessels are formed in tumours and is involved in tumour growth and metastatic tumour spread and is a therapeutic target. Most clinical studies have focused on targeted integrin PET imaging of which αvβ3 integrin is the most extensively investigated. It is upregulated on activated endothelial cells in association with tumour angiogenesis. Neuroendocrine tumour tracers, particularly 68Ga-DOTA-peptides, have an established role in imaging of carcinoid tumours. Whilst most of these tracers have predominantly been used in the research environment, they offer

  3. Design and synthesis of tracers labelled with a short-lived positron emitting

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) is currently used widely as a non-invasive tool for dynamic studies of regional in vivo biochemistry in biomedical research as well as in medical diagnosis. Its advance has increased the demand for labeled tracers and stimulated the search for synthetic strategies for rapid synthesis of tracer molecules labeled with short-lived radionuclides. The paper deals with various topics in this field with emphasis on the design and the synthesis of interesting radiolabeled tracer molecules. It first discusses requirements for the design of labeled tracer molecules. Important factors in selecting an appropriate tracer molecule for PET study include the type of radionuclide to be used, position for labeling, and appropriate stereochemical configuration. The report then discusses position specific labeling for studies of metabolism, kinetic isotopic effects in PET, multiple isotopic labeling for non-invasive validation of metabolism, synthetic strategies for labeling tracer molecules with short-lived radionuclides, and creation of chirality by asymmetric organic and enzyme catalyzed synthesis. (N.K.)

  4. Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

    International Nuclear Information System (INIS)

    The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are α-[11C]methyltryptophan ([11C]AMT) and 5-hydroxy-L-[β-11C]tryptophan ([11C]5-HTP). Both tracers have advantages and disadvantages. [11C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [11C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain. (orig.)

  5. Measuring serotonin synthesis: from conventional methods to PET tracers and their (pre)clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Visser, Anniek K.D.; Waarde, Aren van; Willemsen, Antoon T.M. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Bosker, Fokko J. [University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Luiten, Paul G.M. [University of Groningen, Center for Behavior and Neurosciences, Department of Molecular Neurobiology, Haren (Netherlands); Boer, Johan A. den [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, University Center of Psychiatry, Groningen (Netherlands); Kema, Ido P. [University of Groningen, University Medical Center Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Dierckx, Rudi A.J.O. [University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium)

    2011-03-15

    The serotonergic system of the brain is complex, with an extensive innervation pattern covering all brain regions and endowed with at least 15 different receptors (each with their particular distribution patterns), specific reuptake mechanisms and synthetic processes. Many aspects of the functioning of the serotonergic system are still unclear, partially because of the difficulty of measuring physiological processes in the living brain. In this review we give an overview of the conventional methods of measuring serotonin synthesis and methods using positron emission tomography (PET) tracers, more specifically with respect to serotonergic function in affective disorders. Conventional methods are invasive and do not directly measure synthesis rates. Although they may give insight into turnover rates, a more direct measurement may be preferred. PET is a noninvasive technique which can trace metabolic processes, like serotonin synthesis. Tracers developed for this purpose are {alpha}-[{sup 11}C]methyltryptophan ([{sup 11}C]AMT) and 5-hydroxy-L-[{beta}-{sup 11}C]tryptophan ([{sup 11}C]5-HTP). Both tracers have advantages and disadvantages. [{sup 11}C]AMT can enter the kynurenine pathway under inflammatory conditions (and thus provide a false signal), but this tracer has been used in many studies leading to novel insights regarding antidepressant action. [{sup 11}C]5-HTP is difficult to produce, but trapping of this compound may better represent serotonin synthesis. AMT and 5-HTP kinetics are differently affected by tryptophan depletion and changes of mood. This may indicate that both tracers are associated with different enzymatic processes. In conclusion, PET with radiolabelled substrates for the serotonergic pathway is the only direct way to detect changes of serotonin synthesis in the living brain. (orig.)

  6. Imaging of Enzymes in the Steroid Biosynthetic Pathway : Synthesis of 18F-Labelled Tracers

    OpenAIRE

    ERLANDSSON Maria

    2009-01-01

    This thesis deals with the synthesis and development of 18F-labelled alkyl etomidate and vorozole analogues, and their use as positron emission tomography (PET) tracers for the imaging of the steroid enzymes 11β-hydroxylase and aromatase. Two synthetic 18F-labelling approaches to the etomidate and vorozole analogues were developed, and the analogues were evaluated in some biological assays. The two-step labelling method was used to synthesise many compounds for biological evaluation. In the f...

  7. Synthesis and characterization of coordination polymer nanoparticles as radioisotope tracers

    International Nuclear Information System (INIS)

    Coordination polymer nanoparticles (NPs) with gamma-emitting nuclide (Au-198), 411 keV, 675 keV, 822 keV and 1087 keV were prepared by coordination polymerization of the radioisotope Au3+ ions and 1,4-bis(imidazole-1-ylmethyl)benzene in an aqueous solution at room temperature for 3 h. Here, the radioisotope Au3+ ions were prepared by dissolution of Au-198 foil, which was prepared by neutron irradiation from the HANARO reactor, in KCN aqueous solution. The successful synthesis of the radioisotope coordination polymer NPs with 5±0.5 nm was confirmed via UV–vis spectroscopy, Transmission Electron Microscopy (TEM), Energy Dispersive X-ray Spectrometry (EDXS), Thermogravimetric analysis (TGA), and Gamma spectroscopy analysis. The synthesized radioisotope coordination polymer NPs can be used as radiotracers in science, engineering, and industrial fields

  8. Analysis of plasmid DNA synthesis by double tracer method

    International Nuclear Information System (INIS)

    An Escherichia coli strain, CR34, harboring both pSC101 and ColEl-amp plasmids was exposed to media containing rifampicin (100 μg/ml) and/or chloramphenicol (180 μg/ml) and the cells were labeled for 20 min with 3H-thymine at 3,25 and 50 min after exposure to drug(s). The plasmid DNA synthesis was assayed by DNA-DNA hybridization with 14C-labeled pSC134 DNA as internal marker. In the presence of rifampicin, the replication of pSC 101 was from 57 to 104% that in its absence, and that of ColEl-amp was from 17 to 26%. The DNA replication of pSC101 after addition of chloramphenicol was reduced to 35 to 75%, and that of ColEl-amp was reduced to 39% and then restored to 92%. This restoration was not observed in the presence of rifampicin. (author)

  9. Automated synthesis of [11C]choline, a positron-emitting tracer for tumor imaging

    International Nuclear Information System (INIS)

    (β-Hydroxyethyl)tri([11C]methyl)ammonium ([11C]choline) is a tracer very effective in imaging various human tumors using positron emission tomography (PET). We have constructed a computer-controlled [11C]choline synthetic apparatus which carries out the whole process of synthesis and product purification automatically. The setup is simple and the process quick. In 20 min, 11 GBq of [11C]choline (chloride) is obtainable from 26 GBq of [11C]CO2. The final product is a sterile and pyrogen-free [11C]choline 'injection'

  10. Synthesis of [18F]fluoroetanidazole: A potential new tracer for imaging hypoxia

    International Nuclear Information System (INIS)

    A method has been developed for the synthesis of [18F]fluoroetanidazole, a potential tracer for imaging hypoxia with positron emission tomography. The compound is prepared by an active ester coupling reaction between the 2,3,5,6-tetrafluorophenyl ester of 2-nitroimidazole acetic acid and [18F]fluoroethylamine. [18F]Fluoroethylamine is prepared from N-[2-(toluene-4-sulfonyloxy)-ethyl]-phthalimide and [18F]fluoride and purified by distillation. The overall reaction takes about 90 min and gives a yield, uncorrected, of about 25%. Purification on a reversed-phase column is straightforward

  11. An efficient synthesis of dopamine transporter tracer [18F]FECNT

    International Nuclear Information System (INIS)

    A simple synthesis of the dopamine transporter ligand [18F]FECNT with high radiochemical yield and short synthesis time, suitable for routine production is reported. Reaction of 2β-carbomethoxy-3β-(4-chlorophenyl)nortropane with [18F]2-fluoroethyl triflate ([18F]FEtOTf) at room temperature for 4 min provided [18F]FECNT in 84% decay corrected radiochemical yield. Since [18F]FEtOTf was prepared from [18F]2-fluoroethyl bromide that was isolated from its starting material, formation of unwanted side products and the amount of expensive precursor used could be greatly reduced. The overall radiochemical yields of [18F]FECNT were 40% (n=29) and the total synthesis time was ca. 100 min. The average specific activity of [18F]FECNT was 377.4 GBq/μmol (10.2 Ci/μmol). - Highlights: ► An efficient synthesis of dopamine transporter tracer [18F]FECNT is presented. ► Coupling using isolated labeling synthon reduces side products formation. ► Higher radiochemical yields and mild reaction conditons achieved. ► Very low amounts of expensive precursor used reducing the cost per synthesis. ► Suitable for routine production of [18F]FECNT.

  12. Double-tracer autoradiographic study of protein synthesis and glucose consumption in rats with focal cerebral ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas; Balchen, T; Bruhn, T; Diemer, Nils Henrik

    1999-01-01

    A double-tracer autoradiographic method for simultaneous measurement of regional glucose utilization (rCMRglc) and regional protein synthesis (PS) in consecutive brain sections is described and applied to study the metabolism of the ischemic penumbra 2 h after occlusion of the middle cerebral art...

  13. Isotopic tracer studies of Fischer-Tropsch Synthesis over Ru/TiO sub 2 catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Krishna, K.R.

    1992-01-01

    Fischer-Tropsch synthesis is a process in which CO and H{sub 2} react to give predominantly liquid hydrocarbons. The reaction can be considered a special type of polymerization in which the monomer is produced in situ, and chain growth occurs by a sequence of independently repeated additions of the monomer to the growing chain. A investigation has been conducted to study the CO hydrogenation reaction in order to better understand catalyst deactivation and the elementary surface processes involved in chain growth. Isotopic tracers are used in conjunction with transient-response techniques in this study of Fischer-Tropsch synthesis over Ru/TiO{sub 2} catalysts. Experiments are conducted at a total pressure of 1 atmosphere, reaction temperatures of 453--498 K and D{sub 2}/CO (or H{sub 2}/CO) ratios of 2--5. Synthesis products are analyzed by gas chromatography or isotope-ratio gas chromatography-mass spectrometry. Rate constants for chain initiation, propagation and termination are evaluated under steady-state reaction conditions by using transients in isotopic composition. The activation energy for chain termination is much higher than that for propagation, accounting for the observed decrease in the chain growth parameter are also estimated. Coverages by reaction intermediates are also estimated. When small amounts of {sup 12}C-labelled ethylene are added to {sup 13}CO/H{sub 2} synthesis gas, ethylene acts as the sole chain initiator. Ethylene-derived carbon also accounts for 45% of the C{sub 1} monomer pool. 102 refs., 29 figs., 11 tabs.

  14. Isotopic tracer studies of Fischer-Tropsch Synthesis over Ru/TiO{sub 2} catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Krishna, K.R.

    1992-01-01

    Fischer-Tropsch synthesis is a process in which CO and H{sub 2} react to give predominantly liquid hydrocarbons. The reaction can be considered a special type of polymerization in which the monomer is produced in situ, and chain growth occurs by a sequence of independently repeated additions of the monomer to the growing chain. A investigation has been conducted to study the CO hydrogenation reaction in order to better understand catalyst deactivation and the elementary surface processes involved in chain growth. Isotopic tracers are used in conjunction with transient-response techniques in this study of Fischer-Tropsch synthesis over Ru/TiO{sub 2} catalysts. Experiments are conducted at a total pressure of 1 atmosphere, reaction temperatures of 453--498 K and D{sub 2}/CO (or H{sub 2}/CO) ratios of 2--5. Synthesis products are analyzed by gas chromatography or isotope-ratio gas chromatography-mass spectrometry. Rate constants for chain initiation, propagation and termination are evaluated under steady-state reaction conditions by using transients in isotopic composition. The activation energy for chain termination is much higher than that for propagation, accounting for the observed decrease in the chain growth parameter are also estimated. Coverages by reaction intermediates are also estimated. When small amounts of {sup 12}C-labelled ethylene are added to {sup 13}CO/H{sub 2} synthesis gas, ethylene acts as the sole chain initiator. Ethylene-derived carbon also accounts for 45% of the C{sub 1} monomer pool. 102 refs., 29 figs., 11 tabs.

  15. Fully automated synthesis of 11C-acetate as tumor PET tracer by simple modified solid-phase extraction purification

    International Nuclear Information System (INIS)

    Introduction: Automated synthesis of 11C-acetate (11C-AC) as the most commonly used radioactive fatty acid tracer is performed by a simple, rapid, and modified solid-phase extraction (SPE) purification. Methods: Automated synthesis of 11C-AC was implemented by carboxylation reaction of MeMgBr on a polyethylene Teflon loop ring with 11C-CO2, followed by acidic hydrolysis with acid and SCX cartridge, and purification on SCX, AG11A8 and C18 SPE cartridges using a commercially available 11C-tracer synthesizer. Quality control test and animals positron emission tomography (PET) imaging were also carried out. Results: A high and reproducible decay-uncorrected radiochemical yield of (41.0±4.6)% (n=10) was obtained from 11C-CO2 within the whole synthesis time about 8 min. The radiochemical purity of 11C-AC was over 95% by high-performance liquid chromatography (HPLC) analysis. Quality control test and PET imaging showed that 11C-AC injection produced by the simple SPE procedure was safe and efficient, and was in agreement with the current Chinese radiopharmaceutical quality control guidelines. Conclusion: The novel, simple, and rapid method is readily adapted to the fully automated synthesis of 11C-AC on several existing commercial synthesis module. The method can be used routinely to produce 11C-AC for preclinical and clinical studies with PET imaging. - Highlights: • A fully automated synthesis of 11C-acetate by simple modified solid-phase extraction purification has been developed. • Typical non-decay-corrected yields were (41.0±4.6)% (n=10) • Radiochemical purity was determined by radio-HPLC analysis on a C18 column using the gradient program, instead of expensive organic acid column or anion column. • QC testing (RCP>99%)

  16. Comparison of radioactive tracer tin colloid and phytate for sentinel node biopsy in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yagata, Hiroshi; Suzuki, Masato; Nagashima, Takashi; Kasagawa, Takahiro; Sakakibara, Masahiro; Oshida, Keiko; Sangai, Takafumi; Nakano, S.; Miyazaki, Masaru [Chiba Univ. (Japan). Graduate School of Medicine

    2002-10-01

    Eighty-four consecutive sentinel node biopsies were performed using dye and radioactive tracer (tin colloid for 42 tumors and phytate for 42 tumors). They had subdermal injection on the morning of surgery or the afternoon before surgery. Maximum RI count of each sentinel node was recorded and classified {<=}5 counts per second (cps), 5-20, or 20<. In injection on the afternoon before surgery, 19 tumors had {<=}5 cps and 2 had 20 cps< in 24 of tin colloid, whereas 1 had {<=}5 cps and 18 had 20 cps< in 22 of phytate. In injection on the morning of surgery, 9 had {<=}5 and 20 had 20< in 18 of tin colloid, whereas 1 had {<=}5 and 18 had 20< in 20 of phytate. The injection of phytate tended to have higher RI count than tin colloid. Phytate is superior to tin colloid for sentinel node biopsy in breast cancer. (author)

  17. Development of a New Positron Emission Tomography Tracer for Targeting Tumor Angiogenesis: Synthesis, Small Animal Imaging, and Radiation Dosimetry

    Directory of Open Access Journals (Sweden)

    David S. Lalush

    2013-05-01

    Full Text Available Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of tumor aggressiveness. In this study, we tested the ability of a phage-display-selected peptide sequence recognizing specifically bone marrow- derived pro-angiogenic tumor-homing cells, the QFP-peptide, radiolabeled with 64Cu radioisotope to selectively image tumor vasculature in vivo by positron emission tomography (PET. To prepare the targeted PET tracer we modified QFP-phage with the DOTA chelator and radiolabeled the purified QFP-phage-DOTA intermediate with 64Cu to obtain QFP-targeted radioconjugate with high radiopharmaceutical yield and specific activity. We evaluated the new PET tracer in vivo in a subcutaneous (s.c. Lewis lung carcinoma (LLC mouse model and conducted tissue distribution, small animal PET/CT imaging study, autoradiography, histology, fluorescence imaging, and dosimetry assessments. The results from this study show that, in the context of the s.c. LLC immunocompetent mouse model, the QFP-tracer can target tumor blood vessels selectively. However, further optimization of the biodistribution and dosimetry profile of the tracer is necessary to ensure efficient radiopharmaceutical applications enabled by the biological specificity of the QFP-peptide.

  18. A validation of the application of D2O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans

    OpenAIRE

    Wilkinson, Daniel J.; Franchi, Martino V.; Brook, Matthew S.; Narici, Marco V.; Williams, John P; Mitchell, William K.; Szewczyk, Nathaniel J.; Greenhaff, Paul L; Atherton, Philip J.; Smith, Kenneth

    2013-01-01

    Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control of muscle mass. Traditional [13C]amino acid tracer methodologies necessitate sustained bed rest and intravenous cannulation(s), restricting studies to ∼12 h, and thus cannot holistically inform on diurnal MPS. This limits insight into the regulation of habitual muscle metabolism in health, aging, and disease while querying the utility of tracer techniques to predict the long-term efficacy of a...

  19. Multi-contrast attenuation map synthesis for PET/MR scanners: assessment on FDG and Florbetapir PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Burgos, Ninon [University College London, Translational Imaging Group, Centre for Medical Image Computing, London (United Kingdom); Cardoso, M.J.; Modat, Marc; Ourselin, Sebastien [University College London, Translational Imaging Group, Centre for Medical Image Computing, London (United Kingdom); University College London, Dementia Research Centre, Institute of Neurology, London (United Kingdom); Thielemans, Kris; Dickson, John [University College London, Institute of Nuclear Medicine, London (United Kingdom); Schott, Jonathan M. [University College London, Dementia Research Centre, Institute of Neurology, London (United Kingdom); Atkinson, David [University College London, Centre for Medical Imaging, London (United Kingdom); Arridge, Simon R. [University College London, Centre for Medical Image Computing, London (United Kingdom); Hutton, Brian F. [University College London, Institute of Nuclear Medicine, London (United Kingdom); University of Wollongong, Centre for Medical Radiation Physics, Wollongong, NSW (Australia)

    2015-08-15

    Positron Emission Tomography/Magnetic Resonance Imaging (PET/MR) scanners are expected to offer a new range of clinical applications. Attenuation correction is an essential requirement for quantification of PET data but MRI images do not directly provide a patient-specific attenuation map. Methods We further validate and extend a Computed Tomography (CT) and attenuation map (μ-map) synthesis method based on pre-acquired MRI-CT image pairs. The validation consists of comparing the CT images synthesised with the proposed method to the original CT images. PET images were acquired using two different tracers ({sup 18}F-FDG and {sup 18}F-florbetapir). They were then reconstructed and corrected for attenuation using the synthetic μ-maps and compared to the reference PET images corrected with the CT-based μ-maps. During the validation, we observed that the CT synthesis was inaccurate in areas such as the neck and the cerebellum, and propose a refinement to mitigate these problems, as well as an extension of the method to multi-contrast MRI data. Results With the improvements proposed, a significant enhancement in CT synthesis, which results in a reduced absolute error and a decrease in the bias when reconstructing PET images, was observed. For both tracers, on average, the absolute difference between the reference PET images and the PET images corrected with the proposed method was less than 2%, with a bias inferior to 1%. Conclusion With the proposed method, attenuation information can be accurately derived from MRI images by synthesising CT using routine anatomical sequences. MRI sequences, or combination of sequences, can be used to synthesise CT images, as long as they provide sufficient anatomical information. (orig.)

  20. Multi-contrast attenuation map synthesis for PET/MR scanners: assessment on FDG and Florbetapir PET tracers

    International Nuclear Information System (INIS)

    Positron Emission Tomography/Magnetic Resonance Imaging (PET/MR) scanners are expected to offer a new range of clinical applications. Attenuation correction is an essential requirement for quantification of PET data but MRI images do not directly provide a patient-specific attenuation map. Methods We further validate and extend a Computed Tomography (CT) and attenuation map (μ-map) synthesis method based on pre-acquired MRI-CT image pairs. The validation consists of comparing the CT images synthesised with the proposed method to the original CT images. PET images were acquired using two different tracers (18F-FDG and 18F-florbetapir). They were then reconstructed and corrected for attenuation using the synthetic μ-maps and compared to the reference PET images corrected with the CT-based μ-maps. During the validation, we observed that the CT synthesis was inaccurate in areas such as the neck and the cerebellum, and propose a refinement to mitigate these problems, as well as an extension of the method to multi-contrast MRI data. Results With the improvements proposed, a significant enhancement in CT synthesis, which results in a reduced absolute error and a decrease in the bias when reconstructing PET images, was observed. For both tracers, on average, the absolute difference between the reference PET images and the PET images corrected with the proposed method was less than 2%, with a bias inferior to 1%. Conclusion With the proposed method, attenuation information can be accurately derived from MRI images by synthesising CT using routine anatomical sequences. MRI sequences, or combination of sequences, can be used to synthesise CT images, as long as they provide sufficient anatomical information. (orig.)

  1. Synthesis of isotopically modified ZnO nanoparticles and their potential as nanotoxicity tracers

    International Nuclear Information System (INIS)

    Understanding the behavior of engineered nanoparticles in the environment and within organisms is perhaps the biggest obstacle to the safe development of nanotechnologies. Reliable tracing is a particular issue for nanoparticles such as ZnO, because Zn is an essential element and a common pollutant thus present at elevated background concentrations. We synthesized isotopically enriched (89.6%) with a rare isotope of Zn (67Zn) ZnO nanoparticles and measured the uptake of 67Zn by L. stagnalis exposed to diatoms amended with the particles. Stable isotope technique is sufficiently sensitive to determine the uptake of Zn at an exposure equivalent to lower concentration range (-1). Without a tracer, detection of newly accumulated Zn is significant at Zn exposure concentration only above 5000 μg g-1 which represents some of the most contaminated Zn conditions. Only by using a tracer we can study Zn uptake at a range of environmentally realistic exposure conditions. - ZnO nanoparticles with distinct isotopic composition can be tailor synthesized to be used as tracers of environmental fate and uptake by organisms.

  2. Tracer kinetic model selection for dynamic contrast-enhanced magnetic resonance imaging of locally advanced cervical cancer

    DEFF Research Database (Denmark)

    Kallehauge, Jesper Folsted; Tanderup, Kari; Duan, Chong;

    2014-01-01

    conditions the Tofts (TM), extended Tofts (ETM), compartmental tissue uptake model (C-TU) and 2-compartment exchange model (2CXM) were the optimal tracer kinetic models (TKMs) for the analysis of DCE-MRI in patients with cervical cancer. Material and methods. Ten patients with locally advanced cervical......-treatment cervical cancers, although this model broke down in a subset of the tumour voxels where overfitting resulted in non-physiological parameter estimates. Due to the possible overfitting of the 2CXM, the C-TU was found more robust and when 2CXM was excluded from comparison the C-TU was the preferred model....... cancer (FIGO: IIA/IIB/IIIB/IVA-1/5/3/1) underwent DCE-MRI prior to radiotherapy. From the two-parameter TM it was possible to extract the forward volume transfer constant (Ktrans) and the extracellular-extravascular volume fraction (ve). From the three-parameter ETM, additionally the plasma volume...

  3. Synthesis, characterization, biodistribution and scintigraphy of 99mTc-paclitaxel. A potential tracer of paclitaxel

    International Nuclear Information System (INIS)

    99mTc-paclitaxel was synthesized by using sodium borohydride as a reducing agent. Greater than 95 % labelling efficiency was achieved. Radiochemical purity of the synthesized 99mTc-paclitaxel was validated by thin layer chromatography (TLC) scanner and high performance liquid chromatography (HPLC). 99mTc-paclitaxel passed in vitro stability tests. Biodistribution and scintigraphy studies were performed in Sprague-Dawley rats. The biodistribution study results of 99mTc-paclitaxel were related mainly to the metabolism and excretion routes followed by the parental drug, paclitaxel. Apart from that, biodistribution of 99mTc-paclitaxel was altered after pre-treatment with cold paclitaxel. Hence, 99mTc-paclitaxel may be used as a tracer for paclitaxel. (author)

  4. Radionuclides as tracers of coastal processes in Brazil: review, synthesis, and perspectives

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Isaac R.; Burnett, William C., E-mail: santos@ocean.fsu.edu [Florida State University, Tallahassee, FL (United States). Dept. of Oceanography. Environmental Radioactivity Measurement Facility; Godoy, Jose M. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2008-04-15

    We review the usefulness, limitations, significance, and coastal management implications of radionuclide measurements in Brazilian coastal environments. We focus on the use of radionuclides as tracers of sedimentary processes and submarine groundwater discharge (SGD). We also discuss artificial radionuclide contamination and high natural radioactivity areas. The interpretation of {sup 14}C-, {sup 137}Cs-, and {sup 210}Pb-derived sedimentation rates has provided evidence that inappropriate soil use by urban and agricultural activities has intensified erosion processes on land, which is reflected in depositional environments, such as coastal lagoons, estuaries and mangroves. Of the processes discussed in this paper, SGD is the one that requires the most scientific effort in the short-term. There have been only two case studies using {sup 222}Rn and radium isotopes as groundwater tracers in Brazil. These investigations showed that SGD can be a major source of nutrients and other dissolved species to the coastal ocean. Baseline {sup 137}Cs, {sup 90}Sr, {sup 239+240}Pu, and {sup 238}Pu concentrations in seawater from the whole Brazilian coastal zone are very low. Therefore, in spite of contamination problems in many ecosystems in the northern hemisphere, artificial radionuclide pollution appears to be negligible along the Brazilian coast. Phosphate fertilizer industries and petroleum processing facilities are the main economic activities producing Technologically Enhanced Naturally Occurring Radioactive Materials (TENORM). Even though a few attempts have been made to assess the radiological effects of these activities, their potential threats indicate a need for the radiological control of their wastes. This review showed that the number of studies within the field of environmental radioactivity is still small in Brazil and much more research is needed to understand processes of high interest for environmental managers. In the near future, it is likely that such studies

  5. Feasibility of Real-Time Near-Infrared Fluorescence Tracer Imaging in Sentinel Node Biopsy for Oral Cavity Cancer Patients

    DEFF Research Database (Denmark)

    Christensen, Anders; Juhl, Karina; Charabi, Birgitte; Mortensen, Jann; Kiss, Katalin; Kjær, Andreas; von Buchwald, Christian

    2016-01-01

    be identified in vivo using NIRF imaging, and the majority of those were located in level 1 close to the primary tumor. CONCLUSIONS: A combined fluorescent and radioactive tracer for SNB is feasible, and the additional use of NIRF imaging may improve the accuracy of SN identification in oral cancer......BACKGROUND: Sentinel node biopsy (SNB) is an established method in oral squamous cell carcinoma (OSCC) for staging the cN0 neck and to select patients who will benefit from a neck dissection. Near-infrared fluorescence (NIRF) imaging has the potential to improve the SNB procedure by facilitating...

  6. Methods for the Synthesis of PET Tracers and NMR Studies of Ribonuclease A

    OpenAIRE

    Samuelsson, Linda

    2005-01-01

    This thesis contains two parts. In the first part, general and versatile palladium-mediated 11C-C bond forming reactions for use in the production of radiotracers for Positron Emission Tomography (PET) were explored. Two complimentarty approaches were investigated: the coupling of [11C]methyl iodide with a vinyl stannane and the reaction of a [11C]methylated stannane with various organohalides. The former approach resulted in an improved, fully automated method for the synthesis of the potent...

  7. Guiding principles for estimation of whole-body synthesis rates by tracer experiments

    International Nuclear Information System (INIS)

    Methodical recommendations are suggested-predominantly for laboratory and small animals (rats and young chickens)-for the determination of parameters of the protein metabolism of the whole body after single dosis of a mixture of 15N-labelled amino acids by means of the determination of the temporal course of cumulative 15N excretion in urine and the assessment of the tracer kinetic data in a compartment model. These recommendations are to make it possible to carry out purposefully such experiments under comparable conditions. The advantages of this method are: (1) the non-invasive character of the method; (2) the possibility of repeating the experiment with the same animal; (3) the adaptability to other methods of investigation (e.g. measuring energy metabolism); (4) the relatively low expenditure of labour and requirement of test animals; (5) the relatively good reproducibility of the method. Thus this method is a good supplement to the flooding and permanent infusion methods and should be used wherever the determination of parameters of the protein metabolism of the total body is sufficient. (author)

  8. Synthesis of [18F]-labelled Maltose Derivatives as PET Tracers for Imaging Bacterial Infection

    Science.gov (United States)

    Namavari, Mohammad; Gowrishankar, Gayatri; Hoehne, Aileen; Jouannot, Erwan; Gambhir, Sanjiv S

    2015-01-01

    Purpose To develop novel positron emission tomography (PET) agents for visualization and therapy monitoring of bacterial infections. Procedures It is known that maltose and maltodextrins are energy sources for bacteria. Hence, 18F-labelled maltose derivatives could be a valuable tool for imaging bacterial infections. We have developed methods to synthesize 4-O-(α-D-glucopyranosyl)-6-deoxy-6-[18F]fluoro-D-glucopyranoside (6-[18F]fluoromaltose) and 4-O-(α-D-glucopyranosyl)-1-deoxy-1-[18F]fluoro-D-glucopyranoside (1-[18F]fluoromaltose) as bacterial infection PET imaging agents. 6-[18F]fluoromaltose was prepared from precursor 1,2,3-tri-O-acetyl-4-O-(2′,3′,-di-O-acetyl-4′,6′-benzylidene-α-D-glucopyranosyl)-6-deoxy-6-nosyl-D-glucopranoside (5). The synthesis involved the radio-fluorination of 5 followed by acidic and basic hydrolysis to give 6-[18F]fluoromaltose. In an analogous procedure, 1-[18F]fluoromaltose was synthesized from 2,3, 6-tri-O-acetyl-4-O-(2′,3′,4′,6-tetra-O-acetyl-α-D-glucopyranosyl)-1-deoxy-1-O-triflyl-D-glucopranoside (9). Stability of 6-[18F]fluoromaltose in phosphate-buffered saline (PBS) and human and mouse serum at 37 °C was determined. Escherichia coli uptake of 6-[18F]fluoromaltose was examined. Results A reliable synthesis of 1- and 6-[18F]fluoromaltose has been accomplished with 4–6 and 5–8 % radiochemical yields, respectively (decay-corrected with 95 % radiochemical purity). 6-[18F]fluoromaltose was sufficiently stable over the time span needed for PET studies (~96 % intact compound after 1-h and ~65 % after 2-h incubation in serum). Bacterial uptake experiments indicated that E. coli transports 6-[18F]fluoromaltose. Competition assays showed that the uptake of 6-[18F]fluoromaltose was completely blocked by co-incubation with 1 mM of the natural substrate maltose. Conclusion We have successfully synthesized 1- and 6-[18F]fluoromaltose via direct fluorination of appropriate protected maltose precursors. Bacterial uptake

  9. Criteria for the tracer kinetic measurement of cerebral protein synthesis in humans with positron emission tomography

    International Nuclear Information System (INIS)

    The principles and initial results of the use of PET to measure the local cerebral metabolic rate for protein synthesis (lCRPS) in humans are described. The labeling of leucine, phenylalanine, and methionine in the carboxyl position provides a strategy (selective position labeling) for discriminating between the incorporation of these amino acids into proteins and metabolic oxidation. In metabolic oxidation the label is removed from tissue through decarboxylation. The resulting labeled carbon dioxide is diluted by the tissue carbon dioxide pool, cleared from cerebral tissue by blood flow, and subsequently ventilated by the lungs. This approach also provides a plasma input function that is free of other labeled amino acids produced through systemic reactions, such as those that occur for methionine labeled in the methyl group. The measured lCRPS is in good agreement with values determined by Smith and Sokoloff by autoradiographic and biochemical assay techniques, as are the measured kinetic rate constants of bidirectional transport, incorporation into proteins, and metabolism, as determined in monkeys and humans using L-leucine labeled with carbon-11 in position 1 (L-[1-11C]leucine) with PET. The tissue leucine precursor pool exhibits a rapid turnover rate (1.5 to 2 minutes), while the metabolic pathway has a half-time (about 18 minutes) that is close to the radioactive half-life of carbon-11. The dietary state was found to affect the branching ratio of lCRPS /metabolism, with a fasted value of 0.4 and carbohydrate feed values ranging up to 1.7. The principle of the method appears sound, and a first-order model provides good fits to data, but much more work is required to determine and validate the model structure and to optimize the study conditions and estimation criteria

  10. Automated synthesis of novel cell death imaging tracer 18F-FPDuramycin

    International Nuclear Information System (INIS)

    Background: The noninvasive imaging of cell death plays an important role in the evaluation of degenerative diseases and detection of tumor treatments. Duramycin, a peptide with 19-amino acid, is produced by Streptoverticillium cinnamoneus. It binds specifically to phosphatidylethanolamine (PE), a novel molecular target for cell death. Purpose: The aim is to develop a synthetic method to label duramycin using 18F ion. The automated synthesis was carried out by multi-step procedure on the modified PET-MF-2V-IT-I synthesizer. Methods: Firstly, the prosthetic group of 4-nitrophenyl 2-[18F]fluoropropionate (18F-NFP) was automatically synthesized by a convenient three-step procedure. Secondly, 18F-FPDuramycin was synthesized by conjunction of 18F-NFP with duramycin, which was purified by a solid-phase extraction cartridge. Orthogonal test was performed to confirm the suitable reaction conditions (solvent, base and temperature). Results: The radiochemical yields of 18F-NFP were (25±5)% (n=10, decay-uncorrected) based on[18F]fluoride in 80 min. 18F-FPDuramycin was obtained with yield of (70±3)% (n=8, decay-uncorrected) based on 18F-NFP within 20 min. The radiochemical purity of 18F-FPDuramycin was greater than 99% and the specific activity was greater than (23.7±13.7) GBq·μmol-1 (n=10). Conclusion: 18F-FPDuramycin injection is easy to be prepared with 'two-pot reaction' and is a promising radiotracer used for the clinical and scientific study on positron emission tomography (PET) imaging. (authors)

  11. A comparative study of methylene blue dye and methylene blue with radioactive tracer in breast cancer sentinel node mapping

    International Nuclear Information System (INIS)

    Sentinel lymph node (SLN) biopsy was performed in 72 women with primary breast cancer. During the SLN biopsy, blue dye was used in 18 patients (blue dye; B group), and methylene blue associated with radioactive tracer was used with rhenium colloid in 12 patients (R group) and with phytate in 42 patients (F group). The identification rate of SLNs was 83.3% in the B group, 91.7% in the R group, and 92.9% in the F group. The frequency of SLNs was higher in the B group than in the R or the F group. Back up lymph node dissection was performed in all cases following the identification of SLNs. The rate of accurate identification was 93.3% in the B group, 90.9% in the R group, and 92.3% in the F group. In conclusion, the identification rate was lower in the B group than in the R or the F group, suggesting that methylene blue associated with radioactive tracer using rhenium colloid or phytate may improve the reliability of SLN biopsy. (author)

  12. [18F]Fluoroazabenzoxazoles as potential amyloid plaque PET tracers: synthesis and in vivo evaluation in rhesus monkey

    International Nuclear Information System (INIS)

    Introduction: An 18F-labeled positron emission tomography (PET) tracer for amyloid plaque is desirable for early diagnosis of Alzheimer's disease, particularly to enable preventative treatment once effective therapeutics are available. Similarly, such a tracer would be useful as a biomarker for enrollment of patients in clinical trials for evaluation of antiamyloid therapeutics. Furthermore, changes in the level of plaque burden as quantified by an amyloid plaque PET tracer may provide valuable insights into the effectiveness of amyloid-targeted therapeutics. This work describes our approach to evaluate and select a candidate PET tracer for in vivo quantification of human amyloid plaque. Methods: Ligands were evaluated for their in vitro binding to human amyloid plaques, lipophilicity and predicted blood–brain barrier permeability. Candidates with favorable in vitro properties were radiolabeled with 18F and evaluated in vivo. Baseline PET scans in rhesus monkey were conducted to evaluate the regional distribution and kinetics of each tracer using tracer kinetic modeling methods. High binding potential in cerebral white matter and cortical grey matter was considered an unfavorable feature of the candidate tracers. Results: [18F]MK-3328 showed the most favorable combination of low in vivo binding potential in white matter and cortical grey matter in rhesus monkeys, low lipophilicity (Log D=2.91) and high affinity for human amyloid plaques (IC50=10.5±1.3 nM). Conclusions: [18F]MK-3328 was identified as a promising PET tracer for in vivo quantification of amyloid plaques, and further evaluation in humans is warranted.

  13. Effects of 2-methoxyestradiol on proliferation, apoptosis and PET-tracer uptake in human prostate cancer cell aggregates

    Energy Technology Data Exchange (ETDEWEB)

    Davoodpour, Padideh; Bergstroem, Mats; Landstroem, Marene E-mail: Marene.Landstrom@LICR.uu.se

    2004-10-01

    The purpose of this study was to investigate the potential use of PET in vivo to record cytotoxic effects of 2-methoxyestradiol (2-ME), an endogenous metabolite of 17{beta}-estradiol. The anti-proliferative and pro-apoptotic effects of 2-ME on human prostate cancer cell (PC3) aggregates in vitro, were correlated with the uptake of fluoro-deoxy-D-glucose, FMAU and choline labelled with {sup 18}F, {sup 11}C, or {sup 3}H. 2-ME clearly reduced growth of PC3 aggregates and induced apoptosis in a dose-dependent manner. However, the uptake of the putative proliferation markers {sup 11}C-FMAU or {sup 3}H-choline failed to record the growth inhibitory effects of 2-ME on PC3 cell aggregates. The uptake of {sup 18}F-FDG was used as a marker for effects on cellular metabolism and also failed to show any dose-dependent effects in PC3 aggregates. The use of these PET-tracers in vivo is therefore not recommended in order to evaluate the cytotoxic effects of 2-ME on human prostate cancer cells.

  14. Monitoring protein synthesis in single live cancer cells.

    Science.gov (United States)

    Tu, Chengyi; Santo, Loredana; Mishima, Yuko; Raje, Noopur; Smilansky, Zeev; Zoldan, Janet

    2016-05-16

    Protein synthesis is generally under sophisticated and dynamic regulation to meet the ever-changing demands of a cell. Global up or down-regulation of protein synthesis and the shift of protein synthesis location (as shown, for example, during cellular stress or viral infection) are recognized as cellular responses to environmental changes such as nutrient/oxygen deprivation or to alterations such as pathological mutations in cancer cells. Monitoring protein synthesis in single live cells can be a powerful tool for cancer research. Here we employed a microfluidic platform to perform high throughput delivery of fluorescent labeled tRNAs into multiple myeloma cells with high transfection efficiency (∼45%) and high viability (>80%). We show that the delivered tRNAs were actively recruited to the ER for protein synthesis and that treatment with puromycin effectively disrupted this process. Interestingly, we observed the scattered distribution of tRNAs in cells undergoing mitosis, which has not been previously reported. Fluorescence lifetime analysis detected extensive FRET signals generated from tRNAs labeled as FRET pairs, further confirming that the delivered tRNAs were used by active ribosomes for protein translation. Our work demonstrates that the microfluidic delivery of FRET labeled tRNAs into living cancer cells can provide new insights into basic cancer metabolism and has the potential to serve as a platform for drug screening, diagnostics, or personalized medication. PMID:26956582

  15. Validation of a single biopsy approach and bolus protein feeding to determine myofibrillar protein synthesis in stable isotope tracer studies in humans

    Directory of Open Access Journals (Sweden)

    Baker Steven K

    2011-03-01

    Full Text Available Abstract Background Minimizing the number of muscle biopsies has important methodological implications and minimizes subject discomfort during a stable isotope amino acid infusion. We aimed to determine the reliability of obtaining a single muscle biopsy for the calculation of muscle protein fractional synthetic rate (FSR as well as the amount of incorporation time necessary to obtain that biopsy after initiating a stable isotope infusion (Study 1. The calculation of muscle protein FSR requires tracer steady-state during the stable isotope infusion. Therefore, a second aim was to examine if steady-state conditions are compromised in the precursor pools (plasma free or muscle intracellular [IC] after ingestion of a tracer enriched protein drink and after resistance exercise (Study 2. Methods Sixteen men (23 ± 3 years; BMI = 23.8 ± 2.2 kg/m2, means ± SD were randomized to perform Study 1 or Study 2 (n = 8, per study. Subjects received a primed, constant infusion of L-[ring-13C6]phenylalanine coupled with muscle biopsies of the vastus lateralis to measure rates of myofibrillar protein synthesis (MPS. Subjects in Study 2 were fed 25 g of whey protein immediately after an acute bout of unilateral resistance exercise. Results There was no difference (P = 0.3 in rates of MPS determined using the steady-state precursor-product equation and determination of tracer incorporation between sequential biopsies 150 min apart or using plasma protein as the baseline enrichment, provided the infusion length was sufficient (230 ± 0.3 min. We also found that adding a modest amount of tracer (4% enriched, calculated based on the measured phenylalanine content of the protein (3.5% in the drink, did not compromise steady-state conditions (slope of the enrichment curve not different from zero in the plasma free or, more importantly, the IC pool (both P > 0.05. Conclusions These data demonstrate that the single biopsy approach yields comparable rates of muscle

  16. Biological activity determination of I-BSP, a potent MMP 2 inhibitor, and its 123I tracer synthesis

    International Nuclear Information System (INIS)

    Aim: Matrix metalloproteinases (MMPs) are a family of at least 18 secreted and membrane-bound zinc endopeptidases. Collectively they function in the degradation of extracellular matrix proteins and play an important role in both normal and pathological tissue remodelling. Increased MMP activity is detected in a wide range of cancers and seems to be correlated to their invasive and metastatic potential. MMPs thus seem an attractive target for both diagnostic (SPECT tracer) and therapeutic purposes. Therefore, we synthesised a 123I-labelled MMP 2 inhibitor and evaluated it in vitro. Materials and methods: The 123I-labelled compound was synthesised by a Cu-assisted nucleophilic non-isotopic exchange starting from Br-BSP. After reaction, the mixture was purified by HPLC. IC50 values were obtained by in vitro enzyme assays. A 1:1 mix between non-radiolabelled inhibitor (concentration range: 300 nM - 0.05 nM) and enzymes (MMP2, cMT1-MMP, cMT3-MMP) was incubated for 15 minutes at 370C. The fluorescent substrate (Mca-Pro-Leu-Gly-Leu-Dap(Dnp)-Ala-Arg-NH2) was added and the increase of fluorescence versus time, due to the hydrolysis of substrate, was measured (GEMINI-XS, λexc = 328 nm and λem = 393nm). Initial velocities were calculated for different concentrations of inhibitor and the IC50 values were then determined. Results: Radiochemical yield was 30% ±3%. Radiochemical purity was >95%. IC50 values for inhibition of MMP2, cMT3-MMP and cMT1-MMP were 0.5 nM, 7.1 nM and 16.9 nM respectively. Conclusion: 123I-BSP was synthesised with 30% ±3% yield. After HPLC the radiochemical purity was >95%. In vitro enzyme assays of I-BSP showed an inhibition of MMP2, cMT3-MMP and cMT1-MMP in the low nM range (0.5 nM, 7.1 nM and 16.9 nM respectively). In vivo studies (biodistribution, metabolizing) in mice will be performed in the near future

  17. Synthesis and preclinical evaluation of [{sup 11}C]PAQ as a PET imaging tracer for VEGFR-2

    Energy Technology Data Exchange (ETDEWEB)

    Samen, Erik; Stone-Elander, Sharon [Karolinska University Hospital Solna, Karolinska Pharmacy, Stockholm (Sweden); Karolinska Institutet, Clinical Neurosciences, Stockholm (Sweden); Thorell, Jan-Olov [Karolinska University Hospital Solna, Karolinska Pharmacy, Stockholm (Sweden); Lu, Li [Karolinska Institutet, Clinical Neurosciences, Stockholm (Sweden); Tegnebratt, Tetyana; Holmgren, Lars [Karolinska Institutet, Cancer Center Karolinska, Oncology-Pathology, Stockholm (Sweden)

    2009-08-15

    (R,S)-N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-3-piperidinyl)methoxy)-4-quinazolinamine (PAQ) is a tyrosine kinase inhibitor with high affinity for the vascular endothelial growth factor receptor 2 (VEGFR-2), which plays an important role in tumour angiogenesis. The aim of this work was to develop and evaluate in mice the {sup 11}C-labelled analogue as an in vivo tracer for VEGFR-2 expression in solid tumours. [{sup 11}C]PAQ was synthesized by an N-methylation of desmethyl-PAQ using [{sup 11}C]methyl iodide. The tracer's pharmacokinetic properties and its distribution in both subcutaneous and intraperitoneal tumour models were evaluated with positron emission tomography (PET). [{sup 18}F]FDG was used as a reference tracer for tumour growth. PET results were corroborated by ex vivo and in vitro phosphor imaging and immunohistochemical analyses. In vitro assays and PET in healthy animals revealed low tracer metabolism, limited excretion over 60 min and a saturable and irreversible binding. Radiotracer uptake in subcutaneous tumour masses was low, while focal areas of high uptake (up to 8% ID/g) were observed in regions connecting the tumour to the host. Uptake was similarly high but more distributed in tumours growing within the peritoneum. The pattern of radiotracer uptake was generally different from that of the metabolic tracer [{sup 18}F]FDG and correlated well with variations in VEGFR-2 expression determined ex vivo by immunohistochemical analysis. These results suggest that [{sup 11}C]PAQ has potential as a noninvasive PET tracer for in vivo imaging of VEGFR-2 expression in angiogenic ''hot spots''. (orig.)

  18. Synthesis and preclinical evaluation of [11C]PAQ as a PET imaging tracer for VEGFR-2

    International Nuclear Information System (INIS)

    R,S-N-(4-Bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-3-piperidinyl)methox y)-4-quinazolinamine (PAQ) is a tyrosine kinase inhibitor with high affinity for the vascular endothelial growth factor receptor 2 (VEGFR-2), which plays an important role in tumour angiogenesis. The aim of this work was to develop and evaluate in mice the 11C-labelled analogue as an in vivo tracer for VEGFR-2 expression in solid tumours. [11C]PAQ was synthesized by an N-methylation of desmethyl-PAQ using [11C]methyl iodide. The tracer's pharmacokinetic properties and its distribution in both subcutaneous and intraperitoneal tumour models were evaluated with positron emission tomography (PET). [18F]FDG was used as a reference tracer for tumour growth. PET results were corroborated by ex vivo and in vitro phosphor imaging and immunohistochemical analyses. In vitro assays and PET in healthy animals revealed low tracer metabolism, limited excretion over 60 min and a saturable and irreversible binding. Radiotracer uptake in subcutaneous tumour masses was low, while focal areas of high uptake (up to 8% ID/g) were observed in regions connecting the tumour to the host. Uptake was similarly high but more distributed in tumours growing within the peritoneum. The pattern of radiotracer uptake was generally different from that of the metabolic tracer [18F]FDG and correlated well with variations in VEGFR-2 expression determined ex vivo by immunohistochemical analysis. These results suggest that [11C]PAQ has potential as a noninvasive PET tracer for in vivo imaging of VEGFR-2 expression in angiogenic ''hot spots''. (orig.)

  19. Screening of HER2 Overexpressed Breast Cancer Subtype In Vivo by the Validation of High-Performance, Long-Term, and Noninvasive Fluorescence Tracer.

    Science.gov (United States)

    Ding, Jie; Zhou, Ying; Li, Jingjing; Jiang, Liping; He, Zhiwei; Zhu, Jun-Jie

    2015-12-15

    The high-performance and noninvasive screening of heterogeneous tumor subtypes in vivo is particularly desirable for the diagnosis and symptomatic treatment of cancer. Therefore, we report a near-infrared (NIR) fluorescence tracer "smartly identified HER2" (SI-HER2) for rapid, accurate, and highly specific screening of HER2 overexpressed breast cancer. An antibody against HER2 protein receptor, EP1045Y, was conjugated with NIR emitting CdSeTe/CdS/ZnS QDs via polyhistidine-driven self-assembly approach. The further adsorption of black hole quencher 3 on antibody enabled a "turn on" fluorescence response of the fluorescence tracer to HER2 protein receptor. Aside from the capability of differentiating the HER2 overexpressed MCF-7 cells from its counterparts, the fluorescence tracer can also accurately and rapidly identify the HER2 overexpressed breast tumor subtype in two tumors-bearing mouse model, providing a platform for the investigation of advanced pathways to distinguish the different breast cancer subtypes. PMID:26598802

  20. Cancer Control Framework and Synthesis Rationale

    Science.gov (United States)

    Cancer control science is the conduct of basic and applied research in the behavioral, social, and population sciences to create or enhance interventions that, independently or in combination with biomedical approaches, reduce cancer risk, incidence, morbidity and mortality, and improve quality of life.

  1. Improved synthesis of 17β-hydroxy-16α-iodo-wortmannin, 17β-hydroxy-16α-iodoPX866, and the [131I] analogue as useful PET tracers for PI3-kinase

    OpenAIRE

    Sun, Duoli; Basvoju A. Bhanu Prasad; Schuber, Paul T.; Peng, Zhenghong; Maxwell, David S.; Martin, Diana V.; Guo, Liwei; Han, Dongmei; Kurihara, Hiroaki; Yang, David J.; Gelovani, Juri G.; Powis, Garth; Bornmann, William G.

    2013-01-01

    An improved method for the synthesis of 17β-hydroxy-16α-iodo-wortmannin along with the first synthesis of 17β-hydroxy-16α-iodoPX866 and [131I] radiolabeled 17β-hydroxy-16α-[131I]iodo-wortmannin, as potential PET tracers for PI3K was also described. The differences between wortmannin and its iodo analogue were compared by covalently docking each structure to L833 in PI3K.

  2. Environmental Tracers

    Directory of Open Access Journals (Sweden)

    Trevor Elliot

    2014-10-01

    Full Text Available Environmental tracers continue to provide an important tool for understanding the source, flow and mixing dynamics of water resource systems through their imprint on the system or their sensitivity to alteration within it. However, 60 years or so after the first isotopic tracer studies were applied to hydrology, the use of isotopes and other environmental tracers are still not routinely necessarily applied in hydrogeological and water resources investigations where appropriate. There is therefore a continuing need to promote their use for developing sustainable management policies for the protection of water resources and the aquatic environment. This Special Issue focuses on the robustness or fitness-for-purpose of the application and use of environmental tracers in addressing problems and opportunities scientifically, to promote their wider use and to address substantive issues of vulnerability, sustainability, and uncertainty in (groundwater resources systems and their management.

  3. Development of a new structure for in vivo tracers synthesis: application to tumor neo-angiogenesis imaging

    International Nuclear Information System (INIS)

    Molecular imaging is an essential non-invasive tool usable for diagnosis and characterisation of many diseases. Technetium-based tracers are the most popular ones due to availability, cost and radiochemical properties of 99mTc. Nevertheless, effective tracers development requires a long, expensive, and mainly empirical optimisation process. This context prompted us to carry on the development of a new technetium structure which exhibits lots of potential functionalization spots compatible with a combinatorial approach. We synthesised 12 N3X (X = N, O, S) different ligands. Each of them includes a triazole moiety, (formed via a click-chemistry reaction), which is involved in the metal complexation that implies one of its nitrogen atoms. Then we evaluated their ability to readily form oxo-technetium complexes in conditions that are compatible with medical use in hospital. One complex was formed in quantitative yields and its stability in mice plasma was investigated. A complex called TriaS-99mTc, stable to more than 90% after 6 h incubation, was selected. In vivo study of TriaS-99mTc revealed an efficient blood clearance via the urinary excretion pathway with very low degradation. As an application, we used this structure for the development of tracers that target integrin αvβ3, a known bio-marker of tumor neo-angiogenesis. First, we synthesised functionalized TriaS-based integrated complexes. Functional modification of TriaS by addition of side chains and substituents did not affect its ability to chelate oxo-technetium quantitatively. In addition, its stability in mice plasma was satisfactory. We also developed a bifunctional approach using c(RGDfK) peptide as the targeting biomolecule. In this way, a variable moiety (herein a PEG moiety) can be inserted in the structure through click-chemistry in order to modulate tracers solubility, biodistribution and excretion. (author)

  4. 6-[18F]fluoro-L-fucose: A possible tracer for assessing glycoconjugate synthesis in tumors with positron emission tomography

    International Nuclear Information System (INIS)

    The potential of 6-[18F]fluoro-L-fucose (6-[18F]FFuc) for assessing glycoconjugate synthesis in tumors with positron emission tomography (PET) was investigated. Using the tissue sampling method with five tumor models, different time-radioactivity profiles were found: a nearly constant level in Lewis lung carcinoma (3LL) and different clearance patterns in others. Rapid clearance in normal tissues resulted in preferable uptake ratios for tumor imaging of brain and pancreas. Metabolic studies and the L-fucose loading effects on the tissue uptake proved the tracer to be a biochemically active L-fucose analog. Imaging of the intracranial rat glioma and 3LL in lungs or hepatomas in mice by autoradiography (ARG) and intramuscular VX-2 carcinoma in rabbits by PET was demonstrated. Using double-radionuclide ARG, similar distribution images of 6-[18F]FFuc and 14C-L-fucose but different tumor-to-liver uptake ratios were found. A metastasis model seemed to show a higher uptake of both tracers as compared to a primary tumor model

  5. A validation of the application of D(2)O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans.

    Science.gov (United States)

    Wilkinson, Daniel J; Franchi, Martino V; Brook, Matthew S; Narici, Marco V; Williams, John P; Mitchell, William K; Szewczyk, Nathaniel J; Greenhaff, Paul L; Atherton, Philip J; Smith, Kenneth

    2014-03-01

    Quantification of muscle protein synthesis (MPS) remains a cornerstone for understanding the control of muscle mass. Traditional [(13)C]amino acid tracer methodologies necessitate sustained bed rest and intravenous cannulation(s), restricting studies to ~12 h, and thus cannot holistically inform on diurnal MPS. This limits insight into the regulation of habitual muscle metabolism in health, aging, and disease while querying the utility of tracer techniques to predict the long-term efficacy of anabolic/anticatabolic interventions. We tested the efficacy of the D2O tracer for quantifying MPS over a period not feasible with (13)C tracers and too short to quantify changes in mass. Eight men (22 ± 3.5 yr) undertook one-legged resistance exercise over an 8-day period (4 × 8-10 repetitions, 80% 1RM every 2nd day, to yield "nonexercised" vs. "exercise" leg comparisons), with vastus lateralis biopsies taken bilaterally at 0, 2, 4, and 8 days. After day 0 biopsies, participants consumed a D2O bolus (150 ml, 70 atom%); saliva was collected daily. Fractional synthetic rates (FSRs) of myofibrillar (MyoPS), sarcoplasmic (SPS), and collagen (CPS) protein fractions were measured by GC-pyrolysis-IRMS and TC/EA-IRMS. Body water initially enriched at 0.16-0.24 APE decayed at ~0.009%/day. In the nonexercised leg, MyoPS was 1.45 ± 0.10, 1.47 ± 0.06, and 1.35 ± 0.07%/day at 0-2, 0-4, and 0-8 days, respectively (~0.05-0.06%/h). MyoPS was greater in the exercised leg (0-2 days: 1.97 ± 0.13%/day; 0-4 days: 1.96 ± 0.15%/day, P < 0.01; 0-8 days: 1.79 ± 0.12%/day, P < 0.05). CPS was slower than MyoPS but followed a similar pattern, with the exercised leg tending to yield greater FSRs (0-2 days: 1.14 ± 0.13 vs. 1.45 ± 0.15%/day; 0-4 days: 1.13 ± 0.07%/day vs. 1.47 ± 0.18%/day; 0-8 days: 1.03 ± 0.09%/day vs. 1.40 ± 0.11%/day). SPS remained unchanged. Therefore, D2O has unrivaled utility to quantify day-to-day MPS in humans and inform on short-term changes in anabolism and

  6. Synthesis and biological evaluation of carbon-11 and fluorine-18 labeled tracers for in vivo visualization of PDE10A

    International Nuclear Information System (INIS)

    Introduction: In vivo visualization of PDE10A using PET provides a tool to evaluate the role of PDE10A in various neuropsychiatric diseases and can also be useful in the clinical evaluation of PDE10A inhibitor drug candidates. We evaluated several carbon-11 and fluorine-18 labeled PDE10A inhibitors as potential PDE10A PET radioligands. Materials and Methods: [11C]MP10, [11C]JNJ42071965 and four other tracers were developed. Their biodistribution was evaluated in rats. Rat plasma and brain radiometabolites were quantified. Baseline microPET imaging was performed in normal rats and PDE10A knockout (KO) and wild-type (WT) mice. Blocking and displacement studies were conducted. The selectivity of the tracer binding was further studied in an ex vivo autoradiography experiment in PDE10A KO and WT mice. Results: Biodistribution showed brain uptake for all tracers in the striatum and wash-out from the cerebellum. [11C]1 (11C-MP10) had the highest specific uptake index (striatum (S) vs. cerebellum (C) ratios (S/C)-1) at 60 min (7.4). [11C]5 ([11C]JNJ42071965) had a high index at the early time points (1.0 and 3.7 at 2 and 30 min p.i., respectively). The affinity of [11C]4, [18 F]3 and [18 F]6 was too low to visualize PDE10A using microPET. [11C] 2 showed a specific binding, while kinetics of [11C]1 were too slow. [11C]5 reached equilibrium after 10 min (uptake index = 1.2). Blocking and displacement experiments in rats and baseline imaging in PDE10A KO mice showed specific and reversible binding of [11C]5 to PDE10A. Conclusions: We successfully radiolabeled and evaluated six radiotracers for their potential to visualize PDE10A in vivo. While [11C]1 had the highest striatal specific uptake index, its slow kinetics likely compromise clinical use of this tracer. [11C]5 has a relatively high striatum-to-background ratio and fast kinetic profile, which makes it a valuable carbon-11 alternative

  7. Synthesis and evaluation of [(18)F]-fluoromethyl triphenylphosphonium cation as a novel mitochondria-specific positron emission tomography tracer.

    Science.gov (United States)

    Zeng, Huahui; Wu, Xiangxiang; Song, Fahuan; Xu, Caiyun; Liu, Hao; Liu, Wendi

    2016-08-01

    We developed a radiosynthesis of the voltage sensitive tracer [(18)F]-fluoromethyltriphenylphosphonium cation ([(18)F]-FTPMP), giving high yield (30-34%, decay-corrected), radiochemical purity (>99%) and specific activity (about 760 GBq/μmol). [(18)F]-FTPMP had suitable lipophilicity (logP = 0.91 ± 0.03) and high in vivo/vitro stability. Biodistribution studies showed that [(18)F]-FTPMP had high heart uptake (>7%ID/g from 10 min to 120 min postinjection) and rapid clearance from the background. Clear cardiac images were obtained at different time periods, and the infarction areas could be detected sensitively with small-animal PET. The autoradiography and myocardial membrane potential studies confirmed the mitochondria specific of [(18)F]-FTPMP in rat myocardia. These excellent pharmacokinetic properties suggest [(18)F]-FTPMP is a promising mitochondria-specific tracer for clinical PET imaging of myocardial diseases associated with mitochondrial dysfunction. PMID:27123902

  8. 11C-2-deoxy-D-glucose: Synthesis and preliminary comparison with 11C-D-glucose as a tracer for cerebral energy metabolism in PET studies

    International Nuclear Information System (INIS)

    11C-2-Deoxy-D-glucose has been prepared by the reaction of 11C-hydrogen cyanide with a stable precursor, 1-deoxy-2,3:4,5-di-O-isopropylidine-1-iodo-D-arabitol, thereby avoiding the synthesis of starting material immediately prior to labeling. Fast, efficient, and reproducible solvent change from dimethyl sulfoxide to ether by flash chromatography enabled the use of diisobutylaluminium hydride in the reduction of the intermediate nitrile. Hydrolysis of the imine-aluminum complex with sulfuric acid, removal of the isopropylidine protecting groups with formic acid, and HPLC purifiction with an Aminex HPX-87P column yielded 11C-2-deoxy-D-glucose in an aqueous solution, sterile, pyrogen-free, and ready for use in human studies. The radiochemical yield was proportional20% after a synthesis time of 50 min. The 11C-2-deoxy-D-glucose thus obtained is presently being compared with photosynthetically prepared 11C-D-glucose in PET studies of cerebral metabolism. A preliminary report of the regional cerebral metabolic rate of glucose obtained with the two tracers in a healthy subject with visual stimulation is presented. (orig.)

  9. A novel PET tracer for the imaging of αvβ3 and αvβ5 integrins in experimental breast cancer bone metastases.

    Science.gov (United States)

    Mühlhausen, Ute; Komljenovic, Dorde; Bretschi, Maren; Leotta, Karin; Eisenhut, Michael; Semmler, Wolfhard; Bäuerle, Tobias

    2011-01-01

    The aim of this study was the evaluation of (68)Ga-DOTA-E-[c(RGDfK)](2) as a novel PET tracer to image αvβ3 and αvβ5 integrins. For this purpose, DOTA-E-[c(RGDfK)](2) was labeled with (68)Ga, which was obtained from a (68)Ge/(68)Ga generator, purified by solid-phase extraction and the radiochemical purity analyzed by radio-RP-HPLC. (68) Ga-DOTA-E-[c(RGDfK)](2) was obtained reproducibly in radiochemical yields of 60 ± 6% and with an excellent radiochemical purity of >99%. In nude rats bearing bone metastases after injection of MDA-MB-231 human breast cancer cells, biodistribution studies were performed to evaluate the accumulation of the radiotracer in selected organs, blood and bone metastases 0.5, 1, 2 and 3 h post injection. A rapid uptake into the bone metastases and rapid blood clearance was observed, resulting in tumor-blood ratios of up to 26.6 (3 h post injection) and tumor-muscle ratios of up to 7.9 (3 h post injection). A blocking experiment with coinjected αvβ3/αvβ5 antagonist showed the tumor uptake to be receptor-specific. In an initial in vivo micro PET evaluation of the tracer using the same animal model, the bone metastasis was clearly visualized. These results suggest that (68)Ga-DOTA-E-[c(RGDfK)](2) is a promising PET tracer suitable for the imaging of αvβ3 and αvβ5 integrins in bone metastases. This novel PET tracer should be further evaluated concerning its usefulness for early detection of bone metastases and monitoring treatment response of these lesions. PMID:22162137

  10. A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination

    Science.gov (United States)

    Zlatopolskiy, Boris D; Zischler, Johannes; Urusova, Elizaveta A; Endepols, Heike; Kordys, Elena; Frauendorf, Holm; Mottaghy, Felix M; Neumaier, Bernd

    2015-01-01

    Invited for this months cover picture is the group of Professor Bernd Neumaier at the Institute of Radiochemistry and Experimental Molecular Imaging at the University Clinic of Cologne. The cover picture shows the differences in brain metabolism of a healthy young and a healthy old subject, as well as a patient suffering from Parkinsons disease (left to right) uncovered by 6-[18F]FDOPA-positron emission tomography (PET). Morbus Parkinson occurs when nerve cells that produce dopamine begin to die. The shortage of dopamine leads to movement problems in affected individuals. 6-[18F]FDOPA is extensively used to evaluate the progression of Parkinsons disease. Bold stick projections of this PET tracer, as well as a neuronal network, are seen in the background. Unfortunately, conventional procedures to produce 6-[18F]FDOPA are cumbersome. Thus, several recent developments aim at the simplification of this radiosynthesis. In our work, we studied the applicability of the recently reported Ni-mediated radiofluorination approach for daily routine production of 6-[18F]FDOPA. For more details, see the Full Paper on p. 457 ff. PMID:26478831

  11. A Practical One-Pot Synthesis of Positron Emission Tomography (PET) Tracers via Nickel-Mediated Radiofluorination.

    Science.gov (United States)

    Zlatopolskiy, Boris D; Zischler, Johannes; Urusova, Elizaveta A; Endepols, Heike; Kordys, Elena; Frauendorf, Holm; Mottaghy, Felix M; Neumaier, Bernd

    2015-08-01

    Invited for this months cover picture is the group of Professor Bernd Neumaier at the Institute of Radiochemistry and Experimental Molecular Imaging at the University Clinic of Cologne. The cover picture shows the differences in brain metabolism of a healthy young and a healthy old subject, as well as a patient suffering from Parkinsons disease (left to right) uncovered by 6-[(18)F]FDOPA-positron emission tomography (PET). Morbus Parkinson occurs when nerve cells that produce dopamine begin to die. The shortage of dopamine leads to movement problems in affected individuals. 6-[(18)F]FDOPA is extensively used to evaluate the progression of Parkinsons disease. Bold stick projections of this PET tracer, as well as a neuronal network, are seen in the background. Unfortunately, conventional procedures to produce 6-[(18)F]FDOPA are cumbersome. Thus, several recent developments aim at the simplification of this radiosynthesis. In our work, we studied the applicability of the recently reported Ni-mediated radiofluorination approach for daily routine production of 6-[(18)F]FDOPA. For more details, see the Full Paper on p. 457 ff. PMID:26478831

  12. Microfluidics without channels: highly-flexible synthesis on a digital-microfluidic chip for production of diverse PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Van Dam, Robert Michael [Univ. of California, Los Angeles, CA (United States)

    2010-09-01

    Positron emission tomography (PET) imaging is used for fundamental studies of living biological organisms and microbial ecosystems in applications ranging from biofuel production to environmental remediation to the study, diagnosis, and treatment monitoring of human disease. Routine access to PET imaging, to monitor biochemical reactions in living organisms in real time, could accelerate a broad range of research programs of interest to DOE. Using PET requires access to short-lived radioactive-labeled compounds that specifically probe the desired living processes. The overall aims of this project were to develop a miniature liquid-handling technology platform (called “microfluidics”) that increases the availability of diverse PET probes by reducing the cost and complexity of their production. Based on preliminary experiments showing that microfluidic chips can synthesis such compounds, we aimed to advance this technology to improve its robustness, increase its flexibility for a broad range of probes, and increase its user-friendliness. Through the research activities of this project, numerous advances were made; Tools were developed to enable the visualization of radioactive materials within microfluidic chips; Fundamental advances were made in the microfluidic chip architecture and fabrication process to increase its robustness and reliability; The microfluidic chip technology was shown to produce useful quantities of an example PET probes, and methods to further increase the output were successfully pursued; A “universal” chip was developed that could produce multiple types of PET probes, enabling the possibility of “on demand” synthesis of different probes; and Operation of the chip was automated to ensure minimal radiation exposure to the operator Based on the demonstrations of promising technical feasibility and performance, the microfluidic chip technology is currently being commercialized. It is anticipated that costs of microfluidic chips can be

  13. The optimization of 18F-nucleophilic fluorination reaction and its application in synthesis of VMAT2 imaging tracer: [18F]AV-133

    International Nuclear Information System (INIS)

    Objective: The nucleophilic introduction of n.c.a. [18F]F- into alkanes by nucleophilic reaction is the main method of preparing 18F-labelled radiopharmaceuticals, and the efficient and rapid reaction is important in 18F-labelled radiopharmaceuticals. Method: Using 2-(3-substitute propoxy)naphthalene as model compound, the optimal reaction condition was achieved by comparing the different [18F]fluorination condition: 1)different leaving groups (-OTs, -I, -Br and -Cl), 2) different [18F]fluorination catalysts (Kryptofix222/K2CO3 and TBAHCO3), 3) different reaction solvent (ACN, DMSO and DMF), 4) [18F]fluorination temperature (40, 50 and 60 degree C) and 5) reaction time. The radiochemical yields were analyzed by TLC and HPLC. VMAT2 imaging tracer [18F]AV-133 was synthesized under the optimal conditions. Results: From the experiment results, the reation activity was the highest when using -OTs as the leaving group, followed by -I and -Br, -Clunder the [18F]fluorination condition of using K222/K2CO3 as catalyst and ACN as solvent. And also, the radiochemical yield raised as the reaction time and temperature increased. The higher temperature, the shorter time to reach the equilibrium. When changing the solvent from ACN to DMSO, the radiochemical yields were increased. On the contrary, the radiochemical yields were decreasing by using DMF. Comparing the catalyst K222/K2CO3 with TBAHCO3, the [18F] fluorination of -OTs gave a higher radiochemical yield in the presence of K222/K2CO3. So the optimized [18F]fluorination reaction condition was that choosing -OTs as the leaving group, the [18F]fluorination reaction was efficient and gave higher radiochemical yield catalyzed by K222/K2CO3 in DMSO at high temperature. [18F]fluorination of AV-244 was found to provide the VMAT2 imaging tracer [18F]AV-133 in 80 ± 2% radiochemical yield after reaction at 120 degree C for 3 min under optimized conditions. Conclusion: We have described an optimized condition of nucleophilic [18F

  14. Use of 65Zn as a tracer for the assessment of purification in the 68Ga-DOTANOC synthesis

    International Nuclear Information System (INIS)

    In the last years 68Ga has got into the focus of researchers and clinicians especially for radio-labeling of biomolecules; an important characteristic of this positron emitting isotope is its availability via the 68Ge/68Ga generator system: the long-lived 68Ge (t1/2=270.8 d) produces the short-lived 68Ga (t1/2=67.63 min) which decays to stable 68Zn. 68Ge breakthrough compromises 68Ga radionuclidic purity, while 68Zn might affect the specific activity of the radiopharmaceutical. In this paper we investigated the weight of these impurities in 68Ga-DOTANOC synthesis. 65Zn (t1/2=244.26 d; decay mode: EC 98.3%, β+ 1.7%) was used as a radiotracer of stable 68Zn; samples of the purification columns, wastes and product were recovered and measured with a calibrated HPGe gamma-ray spectrometry system. The results showed that 68Zn competes with 68Ga in labeling DOTANOC with a (95±2)% labeling yield; they also proved the effectiveness of the STRATA X-C cationic post-processing of the generator eluate in lowering the amount of this impurity to less than 1%. Moreover this approach, along with the purification of the final product through a STRATA X cartridge, effectively removes 68Ge breakthrough providing a 68Ga-DOTANOC radionuclidic purity of (99.9999986±0.0000006)%, superior to 99.9% required by the Pharmacopoeia Monograph on 68Ga Edotreotide injection. - Highlights: • We studied 68Ga-DOTANOC radionuclidic purity and 68Zn distribution in the synthesis. • 68Zn behavior was inspected by using cyclotron produced 65Zn as a radiotracer. • 68Zn competes with 68Ga in labeling DOTANOC with a (95±2)% labeling yield. • Effectiveness of the STRATA X-C cationic cartridge in lowering the amount of 68Zn to less than 1%. • 68Ga-DOTANOC radionuclidic purity was (99.9999986±0.0000006)%, superior to required 99.9%

  15. Synthesis and preclinical evaluation of the choline transport tracer deshydroxy-[{sup 18}F]fluorocholine ([{sup 18}F]dOC)

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, G.; Herz, M.; Hauser, A.; Schwaiger, M.; Wester, H.-J. E-mail: H.J.Wester@lrz.tum.de

    2004-10-01

    {sup 11}C-labeled choline ([{sup 11}C]CHO) and {sup 18}F-fluorinated choline analogues have been demonstrated to be valuable tracers for in vivo imaging of neoplasms by means of positron emission tomography (PET). The objective of the present study was to evaluate whether deshydroxy-[{sup 18}F]fluorocholine, ([{sup 18}F]dOC), a non-metabolizable [{sup 18}F]fluorinated choline analogue, can serve as a surrogate for cholines that are able to be phosphorylated and thus allow PET-imaging solely by addressing the choline transport system. The specificity of uptake of [{sup 18}F]dOC was compared with that of [{sup 11}C]choline ([{sup 11}C]CHO) in cultured rat pancreatic carcinoma and PC-3 human prostate cancer cells in vitro. In addition, biodistribution of [{sup 18}F]dOC and [{sup 11}C]CHO was compared in AR42J- and PC-3 tumor bearing mice. The in vitro studies revealed that membrane transport of both compounds can be inhibited in a concentration dependent manner by similar concentrations of cold choline (IC{sub 50} [{sup 18}F]dOC= 11 {mu}M; IC{sub 50} [{sup 11}C]CHO=13 {mu}M. In vitro studies with PC-3 and AR42J cells revealed that the internalized fraction of [{sup 18}F]dOC after 5 min incubation time is comparable to that of [{sup 11}C]CHO, whereas the uptake of [{sup 11}C]CHO was superior after 20 min incubation time. As for [{sup 11}C]CHO, kidney and liver were also the primary sites of uptake for [{sup 18}F]dOC in vivo. Biodistribution data after simultaneous injection of both tracers into AR42J tumor bearing mice revealed slightly higher tumor uptake for [{sup 18}F]dOC at 10 min post-injection, whereas [{sup 11}C]CHO uptake was higher at later time points. In conclusion, [{sup 18}F]dOC is taken up into AR42J rat pancreatic carcinoma and PC-3 human prostate cancer cells by a choline specific transport system. Similar transport rates of [{sup 18}F]dOC and [{sup 11}C]CHO result in comparable cellular uptake levels at early time points. In contrast to [{sup 18}F

  16. Reduced arginine availability and nitric oxide synthesis in cancer is related to impaired endogenous arginine synthesis.

    Science.gov (United States)

    Engelen, Mariëlle P K J; Safar, Ahmed M; Bartter, Thaddeus; Koeman, Fari; Deutz, Nicolaas E P

    2016-07-01

    Reduced plasma arginine (ARG) concentrations are found in various types of cancer. ARG and its product nitric oxide (NO) are important mediators in the immune function and the defense against tumour cells. It remains unclear whether the diminished systemic ARG availability in cancer is related to insufficient endogenous ARG synthesis, negatively affecting NO synthesis, and whether a dietary amino acid mixture is able to restore this. In 13 patients with advanced non-small cell lung cancer (NSCLC) and 11 healthy controls, whole body ARG and CIT (citrulline) rates of appearance were measured by stable isotope methodology before and after intake of a mixture of amino acids as present in whey protein. The conversions of CIT to ARG (indicator of de novo ARG synthesis) and ARG to CIT (marker of NO synthesis), and ARG clearance (reflecting ARG disposal capacity) were calculated. Plasma isotopic enrichments and amino acid concentrations were measured by LC-MS/MS. Conversions of CIT to ARG and ARG to CIT (P<0.05), and CIT rate of appearance (P=0.07) were lower in NSCLC. ARG rate of appearance and clearance were comparable suggesting no enhanced systemic ARG production and disposal capacity in NSCLC. After intake of the mixture, ARG rate of appearance and concentration increased (P<0.001), and ARG to CIT conversion was restored in NSCLC. In conclusion, an impaired endogenous ARG synthesis plays a role in the reduced systemic ARG availability and NO synthesis in advanced NSCLC. Nutritional approaches may restore systemic ARG availability and NO synthesis in cancer, but the clinical implication remains unclear. PMID:27129191

  17. Synthesis and biological evaluation of EGFR/HER-2 inhibitors: analogs of 5-substituted-4-anilinoquinazoline and 6,7-disubstituted-4-anilinoquinoline-3-carbonitrile: screening for development of novel PET tracers

    OpenAIRE

    Pimple, Surekha

    2014-01-01

    The aim of this project was to synthesize new PET tracers for the imaging of the EGFR/HER-2 expressing tumors and to explore PET-assisted drug discovery approach for novel EGFR/HER-2 inhibitors. To achieve this aim, several research aspects such as design, synthesis, in vitro-in vivo biological evaluation and preliminary PET studies had to be performed. We chose two classes of commercially available anticancer compounds, 5-substitued-anilinoquinazolines (reversible inhibitors) and 6,7-disubst...

  18. Predicting gemcitabine transport and toxicity in human pancreatic cancer cell lines with the positron emission tomography tracer 3'-deoxy-3'-fluorothymidine.

    Science.gov (United States)

    Paproski, Robert J; Young, James D; Cass, Carol E

    2010-02-15

    The abundance of human equilibrative nucleoside transporter 1 (hENT1) has recently been shown to be a predictive marker of benefit from gemcitabine therapy in patients with pancreatic cancer. Since hENT1 is also important for the uptake of positron emission tomography (PET) tracer 3'-deoxy-3'-fluorothymidine (FLT) in various cultured human cell lines, this study was undertaken to determine if FLT uptake predicts gemcitabine uptake and/or toxicity in a panel of human pancreatic cancer cell lines (Capan-2, AsPC-1, BxPC-3, PL45, MIA PaCa-2, and PANC-1). Capan-2 cells displayed the lowest levels of (1) extracellular nitrobenzylmercaptopurine ribonucleoside (NBMPR) binding, which represents cell-surface hENT1, (2) FLT and gemcitabine uptake during short (1-45s) and prolonged (1h) periods, and (3) gemcitabine sensitivity. Exposure to NBMPR (inhibits only hENT1) or dilazep (inhibits hENT1 and hENT2) reduced FLT and gemcitabine uptake and gemcitabine sensitivity, with dilazep having greater effects than NBMPR. Gemcitabine permeation was almost completely mediated, primarily by hENT1 and to a lesser extent by hENT2, whereas FLT permeation included a substantial component of passive diffusion. In five of six cell lines, correlations were observed between (1) FLT and gemcitabine initial rates of uptake, (2) gemcitabine uptake and gemcitabine toxicity, (3) FLT uptake and gemcitabine toxicity, and (4) ribonucleotide reductase subunit M1 expression and gemcitabine toxicity. FLT and gemcitabine uptake were comparable for predicting gemcitabine toxicity in the tested pancreatic cancer cell lines suggesting that FLT PET may provide clinically useful information about tumor gemcitabine transport capacity and sensitivity. PMID:19788890

  19. Exploring Spatial Overlap of High-Uptake Regions Derived From Dual Tracer Positron Emission Tomography–Computer Tomography Imaging Using 18F-Fluorodeoxyglucose and 18F-Fluorodeoxythymidine in Nonsmall Cell Lung Cancer Patients

    OpenAIRE

    Liu, Jing; Li, Chengqiang; Hu, Man; Lu, Jie; Shi, Xiaorong; XING, LIGANG; Sun, Xindong; FU, ZHENG; YU, JINMING; MENG, XUE

    2015-01-01

    Abstract Interest is growing in radiotherapy to nonuniformly boost radioresistant regions within nonsmall cell lung cancer (NSCLC) using molecular imaging techniques. The complexity of tumor behavior is beyond the ability of any single radiotracer to reveal. We hold dual tracer positron emission tomography–computer tomography (PET/CT) imaging with fluorodeoxyglucose (FDG) and fluorodeoxythymidine (FLT) for NSCLC patients to offer an integrated overlook of tumor biological behaviors quantitati...

  20. Novel Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET Tracer for Imaging of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Matthias Eder

    2014-06-01

    Full Text Available The detection of prostate cancer lesions by PET imaging of the prostate-specific membrane antigen (PSMA has gained highest clinical impact during the last years. 68Ga-labelled Glu-urea-Lys(Ahx-HBED-CC ([68Ga]Ga-PSMA-HBED-CC represents a successful novel PSMA inhibitor radiotracer which has recently demonstrated its suitability in individual first-in-man studies. The radiometal chelator HBED-CC used in this molecule represents a rather rarely used acyclic complexing agent with chemical characteristics favourably influencing the biological functionality of the PSMA inhibitor. The simple replacement of HBED-CC by the prominent radiometal chelator DOTA was shown to dramatically reduce the in vivo imaging quality of the respective 68Ga-labelled PSMA-targeted tracer proving that HBED-CC contributes intrinsically to the PSMA binding of the Glu-urea-Lys(Ahx pharmacophore. Owing to the obvious growing clinical impact, this work aims to reflect the properties of HBED-CC as acyclic radiometal chelator and presents novel preclinical data and relevant aspects of the radiopharmaceutical production process of [68Ga]Ga-PSMA-HBED-CC.

  1. Dual-tracer receptor concentration imaging using tracers with different tissue delivery kinetics

    Science.gov (United States)

    Tichauer, Kenneth M.; Diop, Mamadou; Elliott, Jonathan T.; Samkoe, Kimberley S.; Hasan, Tayyaba; St. Lawrence, Keith; Pogue, Brian W.

    2014-03-01

    Simultaneous dynamic fluorescent imaging of a suitable untargeted tracer in conjunction with any molecular targeted fluorescent agent has been shown to be a powerful approach for quantifying cancer-specific cell surface receptors in vivo in the presence of non-specific uptake and tracer delivery variability. The identification of a "suitable" untargeted tracer (i.e., one having equivalent plasma and tissue delivery pharmacokinetics to the targeted tracer) for every targeted tracer, however, may not always be feasible or could require extensive testing. This work presents a "deconvolution" approach capable of correcting for plasma and tissue-delivery pharmacokinetic differences between tracers by quantifying dynamic differences in targeted and untargeted tracer uptake in a receptor-free tissue (one devoid of targeted molecular species) and correcting uptake in all other tissues accordingly. This deconvolution correction approach is evaluated in theoretical models and explored in an in vivo mouse xenograft model of human glioma. In the animal experiments, epidermal growth factor receptor (EGFR: a receptor known to be overexpressed in the investigated glioma cell line) was targeted using a fluorescent tracer with very different plasma pharmacokinetics than a second untargeted fluorescent tracer. Without correcting for these differences, the dual-tracer approach yielded substantially higher estimations of EGFR concentration in all tissues than expected; however, deconvolution correction was able to produce estimates that matched ex vivo validation.

  2. Is 99mTc Glucarate a tracer of tumor necrosis?. Comparison with 18F-FDG-PET in an animal model of breast cancer and preliminary clinical experience in oncology patients

    International Nuclear Information System (INIS)

    Introduction: 99mTc-Glucarate has a structural similarity to fructose suggesting that it may enter cells using fructose transporters. Moreover, it has been suggested that 99mTc -Glucarate could interact with hystones of necrotic cells. This radiopharmaceutical has been also evaluated in patients with cerebral and myocardial necrosis and in some tumors. The aim of our study is to evaluate the effects of breast cancer microenvironment in the localization and uptake of 99mTc - Glucarate and 18F-FDG in a preclinical study performed in mice bearing human breast cancer and to evaluate the potential application of 99mTc - Glucarate as a tracer of different solid tumors. Material and methods: Micro PET-CT with 18F-FDG, micro SPECT-CT with 99mTc - Glucarate and micro magnetic resonance imaging (MRI) in MDA-435 breast cancer xenografted SCID mice were performed. We studied 3 patients with breast cancer, 3 patients with non small cell lung cancer and 3 patients with head and neck squamous cell cancer. All of them were locally advanced. Results: Micro SPECT-CT imaging showed a uniform tracer uptake in the tumoral volume whereas PET-CT images demonstrated a higher uptake in the tumor periphery with less accumulation in its center. Micro MRI imaging confirmed the central tumor necrosis. Besides, 99mTc - Glucarate was accumulated by primary and secondary lesions of breast, lung and head and neck cancer. Conclusion: 99mTc - Glucarate has the potential to constitute a relevant clinical agent for the evaluation of patients with breast, lung and head and neck cancer. These results need to be confirmed in an adequate series of patients (au)

  3. Feasibility and repeatability of PET with the hypoxia tracer [18F]HX4 in oesophageal and pancreatic cancer

    International Nuclear Information System (INIS)

    Background and purpose: To investigate the feasibility and to determine the repeatability of recurrent [18F]HX4 PET scans in patients with oesophageal (EC) and pancreatic (PC) cancer. Materials and methods: 32 patients were scanned in total; seven patients (4 EC/3 PC) were scanned 2, 3 and 4 h post injection (PI) of [18F]HX4 and 25 patients (15 EC/10 PC) were scanned twice 3.5 h PI, on two separate days (median 4, range 1–9 days). Maximum tumour to background ratio (TBRmax) and the tumour hypoxic volume (HV) (TBR > 1.0) were calculated. Repeatability was assessed using Bland–Altman analysis. Agreement in localization was calculated as the distance between the centres of mass in the HVs. Results: For EC, the TBRmax in the tumour (mean ± SD) was 1.87 ± 0.46 with a coefficient of repeatability (CoR) of 0.53 (28% of mean). The HV ranged from 3.4 to 98.8 ml with a CoR of 5.1 ml. For PC, the TBRmax was 1.72 ± 0.23 with a CoR of 0.27 (16% of mean). The HV ranged from 4.6 to 104.0 ml with a CoR of 7.8 ml. The distance between the centres of mass in the HV was 2.2 ± 1.3 mm for EC and 2.1 ± 1.5 mm for PC. Conclusions: PET scanning with [18F]HX4 was feasible in both EC and PC patients. Amount and location of elevated [18F]HX4 uptake showed good repeatability, suggesting [18F]HX4 PET could be a promising tool for radiation therapy planning and treatment response monitoring in EC and PC patients

  4. Androgen deprivation promotes intratumoral synthesis of dihydrotestosterone from androgen metabolites in prostate cancer

    OpenAIRE

    Fumio Ishizaki; Tsutomu Nishiyama; Takashi Kawasaki; Yoshimichi Miyashiro; Noboru Hara; Itsuhiro Takizawa; Makoto Naito; Kota Takahashi

    2013-01-01

    Intratumoral synthesis of dihydrotestosterone (DHT) from precursors cannot completely explain the castration resistance of prostate cancer. We showed that DHT was intratumorally synthesized from the inactive androgen metabolites 5α-androstane-3α/β,17β-diol (3α/β-diol) in prostate cancer cells via different pathways in a concentration-dependent manner. Additionally, long-term culture in androgen-deprived media increased transcriptomic expression of 17β-hydroxysteroid dehydrogenase type 6 (HSD1...

  5. Visualisation and assessment of the protein synthesis rate of lung cancer using carbon-11 tyrosine and positron emission tomography

    International Nuclear Information System (INIS)

    This study evaluated the potential role of L-(1-11C)-tyrosine positron emission tomography (TYR PET) for visualisation and quantification of protein metabolism in lung cancer. Dynamic TYR PET scans of the thorax were performed in 17 patients with lung cancer. Protein synthesis rate (PSR in μmol/min.l) and standardised uptake value (SUV, corrected for body measurements) of tumour tissue and contralateral normal tissue were calculated before and after chemotherapy or radiotherapy. All tumours [11 non-small cell lung carcinomas (NSCLCs), five small cell lung carcinomas (SCLCs), and one pleural mesothelioma] were visualised as a hot spot. The median PSR in tumour tissue was higher than that in corresponding contralateral normal lung tissue before [1.88 μmol/min.l (range 1.10-3.42) vs 0.40 μmol/min.l (range 0.12-0.86); P=0.003] and after treatment [1.33 μmol/min.l (range 0.45-2.21) vs 0.28 μmol/min.l (range 0.18-0.51); P<0.02]. In contrast to PSR of normal lung tissue, PSR of tumour tissue decreased significantly after therapy (P=0.03). Before therapy, no significant difference in PSR between NSCLCs and SCLCs was observed, but after therapy the PSR differed significantly between the subgroups [1.69 μmol/min.l (range 0.63-2.78) for NSCLC vs 0.67 μmol/min.l (range 0.45-0.92) for SCLC; P=0.03], irrespective of the treatment modality. The median SUV of tumour tissue was higher than that in corresponding contralateral normal lung both before and after therapy. Only a weak correlation between PSR and SUV was found when the latter was corrected for body surface area or lean body mass. Carbon-11 labelled tyrosine appears to be a good tracer for visualising lung cancer. PSR of tumour tissue can be used to quantify reduction in the metabolic rate of the tumour. Future studies need to be performed to determine whether TYR PET will supply additional clinical information with treatment implications in patients with lung cancer. (orig.)

  6. Packet Tracer network simulator

    CERN Document Server

    Jesin, A

    2014-01-01

    A practical, fast-paced guide that gives you all the information you need to successfully create networks and simulate them using Packet Tracer.Packet Tracer Network Simulator is aimed at students, instructors, and network administrators who wish to use this simulator to learn how to perform networking instead of investing in expensive, specialized hardware. This book assumes that you have a good amount of Cisco networking knowledge, and it will focus more on Packet Tracer rather than networking.

  7. [11C]Sorafenib: Radiosynthesis and preclinical evaluation in tumor-bearing mice of a new TKI-PET tracer

    International Nuclear Information System (INIS)

    Introduction: Tyrosine kinase inhibitors (TKIs) like sorafenib are important anticancer therapeutics with thus far limited treatment response rates in cancer patients. Positron emission tomography (PET) could provide the means for selection of patients who might benefit from TKI treatment, if suitable PET tracers would be available. The aim of this study was to radiolabel sorafenib (1) with carbon-11 and to evaluate its potential as TKI-PET tracer in vivo. Methods: Synthetic methods were developed in which sorafenib was labeled at two different positions, followed by a metabolite analysis in rats and a PET imaging study in tumor-bearing mice. Results: [methyl-11C]-1 and [urea-11C]-1 were synthesized in yields of 59% and 53%, respectively, with a purity of > 99%. The identity of the products was confirmed by coinjection on HPLC with reference sorafenib. In an in vivo metabolite analysis [11C]sorafenib proved to be stable. The percentage of intact product in blood–plasma after 45 min was 90% for [methyl-11C]-1 and 96% for [urea-11C]-1, respectively. Due to the more reliable synthesis, further research regarding PET imaging was performed with [methyl-11C]-1 in nude mice bearing FaDu (head and neck cancer), MDA-MB-231 (breast cancer) or RXF393 (renal cancer) xenografts. Highest tracer accumulation at a level of 2.52 ± 0.33 %ID/g was observed in RXF393, a xenograft line extensively expressing the sorafenib target antigen Raf-1 as assessed by immunohistochemistry. Conclusion: In conclusion, we have synthesized [11C]sorafenib as PET tracer, which is stable in vivo and has the capability to be used as PET tracer for imaging in tumor-bearing mice

  8. Radiopharmaceutical Tracers for Neural Progenitor Cells

    International Nuclear Information System (INIS)

    The Technical Report summarizes the results of the synthesis and microPET animal scanning of several compounds labeled with positron-emitting isotopes in normal, neonatal and kainic acid treated (seizure induced) rats as potential PET tracers to image the process of neurogenesis using positron emission tomography (PET). The tracers tested were 3'-deoxy-3'-[F-18]fluorothymidine ([F-18]FLT) and 5'-benzoyl-FTL, 1-(2'-deoxy-2'-[F-18]fluoro-B-D-arabinofuranosyl)-5-bromouracil (FBAU) and 3',5'-dibenzoyl-FBAU, N-[F-18]fluoroacetyl-D-glucosamine (FLAG) and tetraacetyl-FLAG, and L-[1-C-11]leucine

  9. Design, Synthesis, and In Vitro and In Vivo Evaluation of an (18)F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer.

    Science.gov (United States)

    Rosenberg, Adam J; Liu, Hui; Jin, Hongjun; Yue, Xuyi; Riley, Sean; Brown, Steven J; Tu, Zhude

    2016-07-14

    Sphingosine 1-phosphate receptor 1 (S1P1) plays a pivotal signaling role in inflammatory response; because S1P1 modulation has been identified as a therapeutic target for various diseases, a PET tracer for S1P1 would be a useful tool. Fourteen fluorine-containing analogues of S1P ligands were synthesized and their in vitro binding potency measured; four had high potency and selectivity for S1P1 (S1P1 IC50 100-fold selectivity for S1P1 over S1P2 and S1P3). The most potent ligand, 28c (IC50 = 2.63 nM for S1P1) was (18)F-labeled and evaluated in a mouse model of LPS-induced acute liver injury to determine its S1P1-binding specificity. The results from biodistribution, autoradiography, and microPET imaging showed higher [(18)F]28c accumulation in the liver of LPS-treated mice than controls. Increased expression of S1P1 in the LPS model was confirmed by immunohistochemical analysis (IHC). These data suggest that [(18)F]28c is a S1P1 PET tracer with high potential for imaging S1P1 in vivo. PMID:27280499

  10. Tracers in China oil field

    International Nuclear Information System (INIS)

    China has rich oil resources and integrated petroleum industry. The oil industry offers a large market for tracer applications. Nowadays the main stream-most frequently used tracer technologies are introduced. These technologies include tracer 'plating' method for water intake profile measurement on the injection well, inter well tracer test and inter well tracer test for residual oil evaluation. (author)

  11. Final Progress Report for Project Entitled: Quantum Dot Tracers for Use in Engineered Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Rose, Peter [Univ. of Utah, Salt Lake City, UT (United States); Bartl, Michael [Univ. of Utah, Salt Lake City, UT (United States); Reimus, Paul [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Williams, Mark [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Mella, Mike [Univ. of Utah, Salt Lake City, UT (United States)

    2015-09-12

    The objective of this project was to develop and demonstrate a new class of tracers that offer great promise for use in characterizing fracture networks in EGS reservoirs. From laboratory synthesis and testing through numerical modeling and field demonstrations, we have demonstrated the amazing versatility and applicability of quantum dot tracers. This report summarizes the results of four years of research into the design, synthesis, and characterization of semiconductor nanocrystals (quantum dots) for use as geothermal tracers.

  12. RRR-α-tocopheryl succinate inhibits human gastric cancer SGC-7901 cell growth by inducing apoptosis and DNA synthesis arrest

    OpenAIRE

    Wu, Kun; ZHAO Yan; Liu, Bai-He; Li, Yao; Liu, Fang; Guo, Jian; Yu, Wei-Ping

    2002-01-01

    AIM: To investigate the effects of growth inhibition of human gastric cancer SGC-7901 cell with RRR-α-tocopheryl succinate (VES), a derivative of natural Vitamin E, via inducing apoptosis and DNA synthesis arrest.

  13. Experiences of Gynecological Cancer through Perspectives of Existential Philosophy: A Qualitative Meta-Synthesis Study

    Directory of Open Access Journals (Sweden)

    Ozen Kulakac

    2013-09-01

    Full Text Available The aim of this study was to re-interpret qualitative studies that examined life experiences of women with gynecological cancer through the perspective of "existentialist philosophy". In this meta-synthesis study, a theoretical sampling method was used. Thirty-five studies that were accessible in full text, published in Turkish and English, were included in the meta-synthesis. The Joanna Briggs Institute’s 2011 Qualitative Assessment and Review Instrument and Weed’s meta-interpretation approach was used, respectively, to evaluate and interpret data. In this study, data pertaining to women’s experiences with cancer were re-interpreted based on five fundamental concepts of existentialist philosophy: (1Angst: In cancer’s shadow, (2Despair: I'm sorry for my losses!, (3Authenticity: Towards a new existence, (4The Absurd: Lives confined to the short distance between joy of life and existential crisis, (5The “Other” and the “Look”: Cancer: It's so hard to say! In this meta-synthesis study, it was found that women with gynecological cancer continuously bear the heavy burden of uncertainty and the threat of existential angst, and require expert, knowledgeable, and authentic care that focuses on their existence.

  14. Design and synthesis of isosteviol triazole conjugates for cancer therapy.

    Science.gov (United States)

    Khaybullin, Ravil N; Zhang, Mei; Fu, Junjie; Liang, Xiao; Li, Tammy; Katritzky, Alan R; Okunieff, Paul; Qi, Xin

    2014-01-01

    One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using "click" chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low μM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development. PMID:25405286

  15. Design and Synthesis of Isosteviol Triazole Conjugates for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Ravil N. Khaybullin

    2014-11-01

    Full Text Available One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using “click” chemistry methodology. Evaluation of these compounds against a series of cancer cell lines derived from primary and metastatic tumors demonstrated that these conjugates exhibit cytotoxic activities with IC50 in the low μM range. In addition, their anti-proliferative activities are cancer cell type specific. Taken together, our studies underscore the importance of structural diversity in achieving cancer cell type specific drug development.

  16. Synthesis and preliminary evaluation of 18F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation

    International Nuclear Information System (INIS)

    Interest remains strong for the development of a noninvasive technique for assessment of regional fatty acid oxidation rate in the myocardium. 18F-labeled 4-thia palmitate (FTP, 16-[18F]fluoro-4-thia-hexadecanoic acid) has been synthesized and preliminarily evaluated as a metabolically trapped probe of myocardial fatty acid oxidation for positron emission tomography (PET). The radiotracer is synthesized by Kryptofix 2.2.2/K2CO3 assisted nucleophilic radiofluorination of an iodo-ester precursor, followed by alkaline hydrolysis and by purification by reverse phase high performance liquid chromatography. Biodistribution studies in rats showed high uptake and long retention of FTP in heart, liver, and kidneys consistent with relatively high fatty acid oxidation rates in these tissues. Inhibition of carnitine palmitoyl-transferase-I caused an 80% reduction in myocardial uptake, suggesting the dependence of trapping on the transport of tracer into the mitochondrion. Experiments with perfused rat hearts showed that the estimates of the fractional metabolic trapping rate (FR) of FTP tracked inhibition of oxidation rate of palmitate with hypoxia, whereas the FR of the 6-thia analog 17-[18F]fluoro-6-thia-heptadecanoic acid was insensitive to hypoxia. In vivo defluorination of FTP in the rat was evidenced by bone uptake of radioactivity. A PET imaging study with FTP in normal swine showed excellent myocardial images, prolonged myocardial retention, and no bone uptake of radioactivity up to 3 h, the last finding suggesting a species dependence for defluorination of the omega-labeled fatty acid. The results support further investigation of FTP as a potential PET tracer for assessing regional fatty acid oxidation rate in the human myocardium

  17. Synthesis and preliminary evaluation of {sup 18}F-labeled 4-thia palmitate as a PET tracer of myocardial fatty acid oxidation

    Energy Technology Data Exchange (ETDEWEB)

    DeGrado, Timothy R. E-mail: trd@petsparc.mc.duke.edu; Wang Shuyan; Holden, James E.; Nickles, R. Jerome; Taylor, Michael; Stone, Charles K

    2000-04-01

    Interest remains strong for the development of a noninvasive technique for assessment of regional fatty acid oxidation rate in the myocardium. {sup 18}F-labeled 4-thia palmitate (FTP, 16-[{sup 18}F]fluoro-4-thia-hexadecanoic acid) has been synthesized and preliminarily evaluated as a metabolically trapped probe of myocardial fatty acid oxidation for positron emission tomography (PET). The radiotracer is synthesized by Kryptofix 2.2.2/K{sub 2}CO{sub 3} assisted nucleophilic radiofluorination of an iodo-ester precursor, followed by alkaline hydrolysis and by purification by reverse phase high performance liquid chromatography. Biodistribution studies in rats showed high uptake and long retention of FTP in heart, liver, and kidneys consistent with relatively high fatty acid oxidation rates in these tissues. Inhibition of carnitine palmitoyl-transferase-I caused an 80% reduction in myocardial uptake, suggesting the dependence of trapping on the transport of tracer into the mitochondrion. Experiments with perfused rat hearts showed that the estimates of the fractional metabolic trapping rate (FR) of FTP tracked inhibition of oxidation rate of palmitate with hypoxia, whereas the FR of the 6-thia analog 17-[{sup 18}F]fluoro-6-thia-heptadecanoic acid was insensitive to hypoxia. In vivo defluorination of FTP in the rat was evidenced by bone uptake of radioactivity. A PET imaging study with FTP in normal swine showed excellent myocardial images, prolonged myocardial retention, and no bone uptake of radioactivity up to 3 h, the last finding suggesting a species dependence for defluorination of the omega-labeled fatty acid. The results support further investigation of FTP as a potential PET tracer for assessing regional fatty acid oxidation rate in the human myocardium.

  18. Systematic Review and Meta-study Synthesis of Qualitative Studies Evaluating Facilitators and Barriers to Participation in Colorectal Cancer Screening.

    Science.gov (United States)

    Honein-AbouHaidar, Gladys N; Kastner, Monika; Vuong, Vincent; Perrier, Laure; Daly, Corinne; Rabeneck, Linda; Straus, Sharon; Baxter, Nancy N

    2016-06-01

    Screening reduces the incidence, morbidity, and mortality of colorectal cancer, yet participation tends to be low. We undertook a systematic review and meta-study synthesis of qualitative studies to identify facilitators and barriers to colorectal cancer screening participation. We searched major bibliographic databases for records published in all languages from inception to February 2015. Included primary studies that elicited views and perceptions towards colorectal cancer screening were appraised for relevance and quality. We used a two-stage synthesis to create an interpretation of colorectal cancer screening decisions grounded in primary studies; a thematic analysis to group themes and systematically compare studies and a meta-synthesis to generate an expanded theory of colorectal cancer screening participation. Ninety-four studies were included. The decision to participate in colorectal cancer screening depended on an individual's awareness of colorectal cancer screening. Awareness affected views of cancer, attitudes towards colorectal cancer screening modalities, and motivation for screening. Factors mediating awareness included public education to address misconceptions, primary care physician efforts to recommend screening, and the influence of friends and family. Specific barriers to participation in populations with lower participation rates included language barriers, logistical challenges to attending screening tests, and cultural beliefs. This study identifies key barriers, facilitators, and mediators to colorectal cancer screening participation. Cancer Epidemiol Biomarkers Prev; 25(6); 907-17. ©2016 AACR. PMID:27197277

  19. Synthesis, characterization, and functionalization of gold nanoparticles for cancer imaging.

    Science.gov (United States)

    Craig, Gary A; Allen, Peter J; Mason, Michael D

    2010-01-01

    This chapter describes the methodology by which mAb-F19-conjugated gold nanoparticles were prepared and used to label human pancreatic adenocarcinoma. Specifically, gold nanoparticles were coated with dithiol bearing hetero-bifunctional PEG (polyethylene glycol), and cancer-specific mAb F19 was attached by means of NHS-EDC coupling chemistry taking advantage of a carboxylic acid group on the heterobifunctional PEG. These conjugates were completely stable and were characterized by a variety of methods, including UV-Vis absorbance spectrometry, darkfield microscopy, DLS (dynamic light scattering), TEM (transmission electron microscopy), SEC (size-exclusion chromatography), and confocal microscopy. Nanoparticle bioconjugates were used to label sections of healthy and cancerous human pancreatic tissue. Labeled tissue sections were examined by darkfield microscopy and indicate that these nanoparticle bioconjugates may selectively bind to cancerous tissue and provide a means of optical contrast. PMID:20217596

  20. Colonic cancer cell polyamine synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    PhotoDynamic Therapy is a new concept for cancer treatment based on the interaction between light and a sensitizer, hematoporphyrin derivative (HPD) selectively retained by tumor cells which becomes toxic after light exposure. This effect decreases cell growth, through complex pathways. The aim of this study was to determine whether cellular polyamines, Put (Putrescine), Spd (Spermidine) and Spm (Spermine) were modified after PDT or not. These cations of small molecular weight are essential for cell growth and differentiation of normal and neoplastic cells. In this study intracellular contents of Put, Spd and Spm were determined on 2 sublines of rat colonic cancer cells cloned from the same rat cancer and forming progressive (PROb) and regressive (REGb) tumors. (author). 12 refs., 2 figs

  1. Suitability of tracers

    International Nuclear Information System (INIS)

    Hydrological tracer techniques are a means of making statements on the direction and speed of underground water. One of the simpler tasks is to find out whether there is hydrological communication between two given points. This requires a determination of the direction of flow, which places less exacting demands on the properties of the tracer than does the task of determining the flow velocity of underground water. Tracer methods can serve to infer from flow velocity the distance (flow) velocity, which is defined as the ratio between the distance between two points located in flow direction and the actual time it takes water to flow from one to the other

  2. The Experience of Caregivers Living with Cancer Patients: A Systematic Review and Meta-Synthesis

    OpenAIRE

    Peeranuch LeSeure; Supaporn Chongkham-ang

    2015-01-01

    The objectives of this meta-synthesis were to: (1) explore the experience of caregivers who were caring for cancer patients, including their perceptions and responses to the situation; and (2) describe the context and the phenomena relevant to the experience. Five databases were used: CINAHL, MEDLINE, Academic Search, Science Direct, and a Thai database known as the Thai Library Integrated System (ThaiLIS). Three sets of the context of the experience and the phenomena relevant to the experien...

  3. Synthesis and evaluation of 1'-[18F]fluorometoprolol as a potential tracer for the visualization of β-adrenoceptors with PET

    International Nuclear Information System (INIS)

    (±)-1'[18F]Fluorometoprol 4 was prepared from desisopropylmetoprolol and [18F]fluoroisopropyl tosylate 2 with a radiochemical yield of 2% [corrected for decay to end of bombardment (EOB), synthesis time 90 min]. Synthon 2 was prepared from (S)-1,2-propanediol di(p-toluenesulfonate) in 45% radiochemical yield. Compound 4 shows in two in vitro assays a similar affinity at β-adrenoceptors (about 0.3 μM) as metroprolol 5, but with a slightly higher β1/β2-adrenoceptor selectivity ratio (48.6 vs 30.7). In vivo experiments with 4 showed almost no receptor-mediated uptake in the heart probably because the affinity of (fluoro)metoprolol for the β1-adrenoceptors is too low for successful imaging. However, the in vitro experiments suggest that the fluoroisopropyl group is suitable for the synthesis of [18F]fluorinated β1-adrenergic receptor binding ligands. (Author)

  4. Synthesis and evaluation of 1'-[18F]fluorometoprolol as a potential tracer for the visualization of β-adrenoceptors with PET

    International Nuclear Information System (INIS)

    (±)-1'-[18F]Fluorometoprol 4 was prepared from desisopropylmetoprolol and [18F]fluoroisopropyl tosylate 2 with a radiochemical yield of 2% [corrected for decay to end of bombardment (EOB), synthesis time 90 min]. Synthon 2 was prepared from (S)-1,2-propanediol di(p-toluenesulfonate) in 45% radiochemical yield (EOB, 40 min). Compound 4 shows in two in vitro assays a similar affinity at β-adrenoceptors (about 0.3 μM) as metoprolol 5, but with a slightly higher β1/β2-adrenoceptor selectivity ratio (48.6 vs 30.7). In vivo experiments with 4 showed almost no receptor-mediated uptake in the heart, probably because the affinity of (fluoro)metoprolol for the β1-adrenoceptors is too low for successful imaging. However, the in vitro experiments suggest that the fluoroispropyl group is suitable for the synthesis of [18F]fluorinated β1-adrenergic receptor binding ligands. (author)

  5. Synthesis, radiosynthesis, and in vitro evaluation of [131I]-5-iodo-N-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-yl)-ethyl] -2-methoxy-benzamide as a potential tumor imaging agent

    International Nuclear Information System (INIS)

    This work reports the synthesis, radiolabeling and preliminary in vitro evaluation of [131I]-5-iodo-N-[2-(6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-yl)-ethyl] -2-methoxy-benzamide. The tributylstannylprecursor was synthesized with a yield of 38%. Radiolabeling was performed using an electrophilic iododestannylation. Tracer yield was 94%, radiochemical purity was >95%. The tracer showed high uptake in MCF-7 breast cancer cell line and therefore will be evaluated further

  6. Association of DNA sequence variation in mitochondrial DNA polymerase with mitochondrial DNA synthesis and risk of oral cancer.

    Science.gov (United States)

    Datta, Sayantan; Ray, Anindita; Roy, Roshni; Roy, Bidyut

    2016-01-10

    Enzymes responsible for mitochondrial (mt) DNA synthesis and transcription are encoded by nuclear genome and inherited mutations in these genes may play important roles in enhancing risk of precancer and cancer. Here, genetic variations in 23 functionally relevant tagSNPs in 6 genes responsible for mtDNA synthesis and transcription were studied in 522 cancer and 241 precancer (i.e. leukoplakia) patients and 525 healthy controls using Illumina Golden Gate assay to explore association with risk of oral precancer and cancer. Two SNPs, rs41553913 at POLRMT and rs9905016 at POLG2, significantly increased risk of oral leukoplakia and cancer, respectively, at both genotypic and allelic levels. Gene-environment interaction models also revealed that tobacco habits and SNPs at POLG2 and TFAM may modulate risk of both leukoplakia and cancer. In silico analysis of published data-set also revealed that variant heterozygote (TC) significantly increased transcription of POLG2 compared to wild genotype (p=0.03). Cancer tissues having variant allele genotypes (TC+CC) at POLG2 contained 1.6 times (pcancer tissues having wild genotype (TT). In conclusion, polymorphisms at POLG2 and POLRMT increased risk of oral cancer and leukoplakia, respectively, probably modulating synthesis and activity of the enzymes. Enhanced synthesis of mtDNA in cancer tissues may have implication in carcinogenesis, but the mechanism is yet to be explored. PMID:26403317

  7. Enhancing the versatility of alternate current biosusceptometry (ACB) through the synthesis of a dextrose-modified tracer and a magnetic muco-adhesive cellulose gel

    International Nuclear Information System (INIS)

    Alternate Current Biosusceptometry (ACB) is a promising bio-magnetic method, radiation free and easily performed used for gastric emptying exams. Due to development on its sensitivity level, interesting nature, noninvasiveness and low cost it has attracted a lot of attention. In this work, magnetic nanoparticles of Mn–Zn ferrite as well as dextrose-modified nanoparticles were synthesized to be used as possible tracers in ACB gastric emptying exams. In addition, a magnetic muco-adhesive gel was obtained by modifying the ferrite nanoparticles with cellulose. Based on in-vivo tests in rats, we show that the pure ferrite nanoparticles, whose isoelectric point was found to be at pH = 3.2, present a great sensitivity to pH variations along the gastrointestinal tract, while the reduction of the isoelectric point by the dextrose modification leads to suitable nanoparticles for rapid gastric emptying examinations. On the other hand, the in-vivo tests show that the muco-adhesive cellulose gel presents substantial stomach adhesion and is a potential drug delivery system easily traceable by the ACB system

  8. Enhancing the versatility of alternate current biosusceptometry (ACB) through the synthesis of a dextrose-modified tracer and a magnetic muco-adhesive cellulose gel

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Murillo L., E-mail: murillolongo@gmail.com [Niels Bohr Institute, University of Copenhagen, DK-2100 Copenhagen (Denmark); Instituto de Biociências, Universidade Estadual Paulista, CP 510, 18618–970 Botucatu SP (Brazil); Calabresi, Marcos F.; Quini, Caio; Matos, Juliana F.; Miranda, José R.A.; Saeki, Margarida J. [Instituto de Biociências, Universidade Estadual Paulista, CP 510, 18618–970 Botucatu SP (Brazil); Bordallo, Heloisa N. [Niels Bohr Institute, University of Copenhagen, DK-2100 Copenhagen (Denmark)

    2015-03-01

    Alternate Current Biosusceptometry (ACB) is a promising bio-magnetic method, radiation free and easily performed used for gastric emptying exams. Due to development on its sensitivity level, interesting nature, noninvasiveness and low cost it has attracted a lot of attention. In this work, magnetic nanoparticles of Mn–Zn ferrite as well as dextrose-modified nanoparticles were synthesized to be used as possible tracers in ACB gastric emptying exams. In addition, a magnetic muco-adhesive gel was obtained by modifying the ferrite nanoparticles with cellulose. Based on in-vivo tests in rats, we show that the pure ferrite nanoparticles, whose isoelectric point was found to be at pH = 3.2, present a great sensitivity to pH variations along the gastrointestinal tract, while the reduction of the isoelectric point by the dextrose modification leads to suitable nanoparticles for rapid gastric emptying examinations. On the other hand, the in-vivo tests show that the muco-adhesive cellulose gel presents substantial stomach adhesion and is a potential drug delivery system easily traceable by the ACB system.

  9. Design and Synthesis of Isosteviol Triazole Conjugates for Cancer Therapy

    OpenAIRE

    Ravil N. Khaybullin; Mei Zhang; Junjie Fu; Xiao Liang; Tammy Li; ALAN R. KATRITZKY; Paul Okunieff; Xin Qi

    2014-01-01

    One of the keys for successfully developing drugs against the broad spectrum of cancer cell types is structural diversity. In the current study, we focused on a family of isosteviol derivatives as potential novel antitumor agents. Isosteviol is a tetracyclic diterpenoid obtained by acid hydrolysis of steviol glycoside extracts isolated from abundant Stevia rebaudiana plants. In this work, we have designed and synthesized a panel of isosteviol triazole conjugates using “click” chemistry meth...

  10. Barriers and facilitators to cervical cancer screening in high incidence populations: A synthesis of qualitative evidence.

    Science.gov (United States)

    Driscoll, Susan D

    2016-01-01

    Despite the efficacy and availability of screening and treatment for cervical cancer, it remains the leading cause of death for women in many low resource countries. The inability or reluctance of women to use screening and treatment is the largest contributor to cervical cancer morbidity and mortality. The aim of the author in this article is to determine knowledge, attitudes, and beliefs that facilitate or hinder women's use of screening in high incidence countries through a synthesis of qualitative research. CINAHL, Medline, AnthroSource, Sociological Abstracts, Social Service Abstracts, GenderWatch, Ethnic News Watch, and ASSIA databases were queried for qualitative research published from 2008 to 2013. Ten studies meeting inclusion criteria were reviewed and analyzed using constant comparative analysis. Barriers to cervical cancer screening included fatalism, mistrust of non-traditional healthcare providers, masculine/feminine beliefs, limited knowledge, and misunderstandings of causes of cervical cancer. Facilitators included knowledge of sexual risk factors, recognition of signs and symptoms, and community/social support. Pragmatic solutions suggested by this synthesis, that may decrease barriers and enhance facilitators, involved cultural humility (a continual commitment to cultural competence), promotion of gender equality, collaboration among stakeholders, and the translation of evidence-based practices from low to high incidence populations. PMID:26496628

  11. PKLR promotes colorectal cancer liver colonization through induction of glutathione synthesis.

    Science.gov (United States)

    Nguyen, Alexander; Loo, Jia Min; Mital, Rohit; Weinberg, Ethan M; Man, Fung Ying; Zeng, Zhaoshi; Paty, Philip B; Saltz, Leonard; Janjigian, Yelena Y; de Stanchina, Elisa; Tavazoie, Sohail F

    2016-02-01

    Colorectal cancer metastasis to the liver is a major cause of cancer-related death; however, the genes and pathways that govern this metastatic colonization event remain poorly characterized. Here, using a large-scale in vivo RNAi screen, we identified liver and red blood cell pyruvate kinase (PKLR) as a driver of metastatic liver colonization. PKLR expression was increased in liver metastases as well as in primary colorectal tumors of patients with metastatic disease. Evaluation of a murine liver colonization model revealed that PKLR promotes cell survival in the tumor core during conditions of high cell density and oxygen deprivation by increasing glutathione, the primary endogenous antioxidant. PKLR negatively regulated the glycolytic activity of PKM2, the major pyruvate kinase isoenzyme known to regulate cellular glutathione levels. Glutathione is critical for metastasis, and we determined that the rate-limiting enzyme of glutathione synthesis, GCLC, becomes overexpressed in patient liver metastases, promotes cell survival under hypoxic and cell-dense conditions, and mediates metastatic liver colonization. RNAi-mediated inhibition of glutathione synthesis impaired survival of multiple colon cancer cell lines, and pharmacological targeting of this metabolic pathway reduced colonization in a primary patient-derived xenograft model. Our findings highlight the impact of metabolic reprogramming within the niche as metastases progress and suggest clinical potential for targeting this pathway in colorectal cancer. PMID:26784545

  12. Straightforward thiol-mediated protein labelling with DTPA: Synthesis of a highly active 111In-annexin A5-DTPA tracer

    OpenAIRE

    Kratz, Harald; Haeckel, Akvile; Michel, Roger; Schönzart, Lena; Hanisch, Uli; Hamm, Bernd; Schellenberger, Eyk

    2012-01-01

    Background Annexin A5 (anxA5) has been found useful for molecular imaging of apoptosis and other biological processes. Methods Here, we report an optimised two-step synthesis of annexin A5-diethylene triamine pentaacetic acid (DTPA) (anxA5-DTPA) for positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imaging with a single purification step. The use of a recombinant annexin A5 (cys-anxA5) with a single thiol group allowed regionally specific coupling, with...

  13. Synthesis and evaluation of 1'-[[sup 18]F]fluorometoprolol as a potential tracer for the visualization of [beta]-adrenoceptors with PET

    Energy Technology Data Exchange (ETDEWEB)

    Groot, T.J. de; Waarde, A. van; Elsinga, P.H.; Visser, G.M.; Vaalburg, Willem (Groningen Univ. Hospital (Netherlands)); Brodde, O.-E. (Essen Univ. (Germany). Biochemisches Forschungslabor)

    1993-07-01

    ([+-])-1'[[sup 18]F]Fluorometoprol 4 was prepared from desisopropylmetoprolol and [[sup 18]F]fluoroisopropyl tosylate 2 with a radiochemical yield of 2% [corrected for decay to end of bombardment (EOB), synthesis time 90 min]. Synthon 2 was prepared from (S)-1,2-propanediol di(p-toluenesulfonate) in 45% radiochemical yield. Compound 4 shows in two in vitro assays a similar affinity at [beta]-adrenoceptors (about 0.3 [mu]M) as metroprolol 5, but with a slightly higher [beta][sub 1]/[beta][sub 2]-adrenoceptor selectivity ratio (48.6 vs 30.7). In vivo experiments with 4 showed almost no receptor-mediated uptake in the heart probably because the affinity of (fluoro)metoprolol for the [beta][sub 1]-adrenoceptors is too low for successful imaging. However, the in vitro experiments suggest that the fluoroisopropyl group is suitable for the synthesis of [[sup 18]F]fluorinated [beta][sub 1]-adrenergic receptor binding ligands. (Author).

  14. Synthesis of Multifunctional Nanoparticles for Cancer Diagnostics and Therapeutics

    Science.gov (United States)

    Fang, Chen

    2011-12-01

    Magnetic nanoparticles (MNPs) have attracted enormous research attention due to their unique magnetic properties that enable the detection by the non-invasive medical imaging modality---magnetic resonance imaging (MRI). By incorporating advanced features, such as specific targeting, multimodality, therapeutic delivery, the detectability and applicability of MNPs have been dramatically expanded. Smart and rational design on structure, composition and surface chemistry is essential to achieving desired properties in MNP systems, such as high sensitivity and colloidal stability, target specificity and/or multimodality. The goal of this research is to develop MNP-based platforms for the detection, diagnosis and treatment of cancer. MNPs with high contrast enhancement were coated with poly(ethylene glycol) (PEG)-based polymers to render aqueous stability and confer therapeutic-loading capability. Tumor-specific MNPs were developed by functionalization of nanoparticles with chlorotoxin (CTX) or arginine-glycine-aspartic acid (RGD) that targets, respectively, MMP-2 receptor or alphavbeta3 integrin overexpressed on a variety of cancer cells. The effects of ligands' molecular targets on the temporal and spatial distribution of MNPs within tumors were also investigated both in vitro and in vivo. All MNPs exhibited excellent long-term stability in cell culture media. CTX-labeled MNP exhibited sustained accumulation, penetration and distribution in the tumor mass. These findings revealed the influence of the targeting ligands on the intratumoral distribution of the ligand-enabled nanoprobes. To demonstrate the ability of nanoparticles as drug carrier, anthracyline chemotherapeutic drugs doxorubicin and mitoxantrone were attached to iron oxide nanoparticles. The theragnostic nanoparticles showed sufficient contrast enhancement and comparable anti-neoplastic efficacy in vitro. With flexible surface chemistry, our nanoparticle platform can be used in a modular fashion to

  15. IND Regulatory & Manufacturing Resources - Cancer Imaging Program

    Science.gov (United States)

    The Cancer Imaging Program has been creating Investigational New Drug Applications (IND) for imaging agents in order to engage in multi-center clinical trials of these materials. A subset of the documents filed is being made available to the research community to implement routine synthesis of tracers at their own facilities and to assist investigators with the filing of their own INDs. The first of these document sets is for F-18 fluorothymidine (FLT).

  16. Simple synthesis of carbon-11-labeled chromen-4-one derivatives as new potential PET agents for imaging of DNA-dependent protein kinase (DNA-PK) in cancer

    International Nuclear Information System (INIS)

    Carbon-11-labeled chromen-4-one derivatives were synthesized as new potential PET agents for imaging of DNA repair enzyme DNA-dependent protein kinase (DNA-PK) in cancer. The target tracers, X-[11C]methoxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; [11C]4a–d), were prepared from their corresponding precursors, X-hydroxy-2-morpholino-4H-chromen-4-ones (X=8, 7, 6, 5; 5a–d), with [11C]CH3OTf through O-[11C]methylation and isolated by a simplified solid-phase extraction (SPE) method using a C-18 Sep-Pak Plus cartridge. The radiochemical yields decay corrected to end of bombardment (EOB), from [11C]CO2, were 40–60%. The specific activity at end of synthesis (EOS) was 185–370 GBq/μmol. - Highlights: ► New chromen-4-one derivatives were synthesized. ► New carbon-11-labeled chromen-4-one derivatives were synthesized. ► Simple solid-phase extraction (SPE) method was employed in radiosynthesis.

  17. CONVERGENT SYNTHESIS AND EVALUATION OF 18F-LABELED AZULENIC COX2 PROBES FOR CANCER IMAGING

    Directory of Open Access Journals (Sweden)

    Donald D. Nolting

    2013-01-01

    Full Text Available The overall objectives of this research are to (i develop azulene-based PET probes and (ii image COX2 as a potential biomarker of breast cancer. Several lines of research have demonstrated that COX2 is overexpressed in breast cancer and that its presence correlates with poor prognoses. While other studies have reported that COX2 inhibition can be modulated and used beneficially as a chemopreventive strategy in cancer, no viable mechanism for achieving that approach has yet been developed. This shortfall could be circumvented through in vivo imaging of COX2 activity, particularly using sensitive imaging techniques such as PET. Toward that goal, our laboratory focuses on the development of novel 18F-labled COX2 probes. We began the synthesis of the probes by transforming tropolone into a lactone, which was subjected to an [8+2] cycloaddition reaction to yield 2-methylazulene as the core ring of the probe. After exploring numerous synthetic routes, the final target molecule and precursor PET compounds were prepared successfully using convergent synthesis. Conventional 18F labeling methods caused precursor decomposition, which prompted us to hypothesize that the acidic protons of the methylene moiety between the azulene and thiazole rings were readily abstracted by a strong base such as potassium carbonate. Ultimately, this caused the precursors to disintegrate. This observation was supported after successfully using an 18F labeling strategy that employed a much milder phosphate buffer. The 18F-labeled COX2 probe was tested in a breast cancer xenograft mouse model. The data obtained via successive whole-body PET/CT scans indicated probe accumulation and retention in the tumor. Overall, the probe was stable in vivo and no defluorination was observed. A biodistribution study and Western blot analysis corroborate with the imaging data. In conclusion, this novel COX2 PET probe was shown to be a promising agent for cancer imaging and deserves further

  18. Wairakei tracer tests 1983

    International Nuclear Information System (INIS)

    Tracer tests, with and without, hot water reinjection into WK213 showed returns of tracer iodine-131; in wells in both the Waiora Valley and the eastern end of the field. The effect of reinjection at a rate of 200 cu. m/h was to reduce the arrived time from 15 to 7 days. Increasing the rate of reinjection into WK62 from 30 cu. m/h to 200 cu. m/h seemed to increase the initial velocity of the tracer wave and the distance it moved. However, returns were recorded only in the adjacent wells WK61 and WK63 with a very small, and three days delayed, response in WK43

  19. Hypoxia-induced alteration of tracer accumulation in cultured cancer cells and xenografts in mice: implications for pre-therapeutic prediction of treatment outcomes with 99mTc-sestamibi, 201Tl chloride and 99mTc-HL91

    International Nuclear Information System (INIS)

    Weak visualization of tumours in pre-therapeutic scintigrams with technetium-99m sestamibi (MIBI) is likely a predictive sign of unfavourable tumour response to radiotherapy and chemotherapy. However, factors relating to this scintigraphic finding are not well understood. The presence of hypoxic tumour cells is one of the major reasons for therapeutic failure; consequently, we attempted to determine whether oxygenation status affects 99mTc-MIBI accumulation in tumour cells. LS180 human colon cancer and T24 human bladder cancer cells were incubated in air or N2 gas at 37 C. Cellular uptake of 99mTc-MIBI was subsequently determined at 15, 60 and 120 min. Uptake of thallium-201 chloride was also assessed. Uptake of 99mTc-HL91 was assessed as a hypoxic marker. Accumulation of the tracers in LS180 xenografts was observed in mice treated with 5 mg/kg hydralazine and compared with that in untreated mice. pO2 in the medium and tumours was measured with O2 microelectrodes. N2 gas flow gradually reduced pO2 in the cell suspension to 1-2 mmHg in 60 min. Cellular uptake of 99mTc-MIBI in LS180 cells decreased by approximately 30% in N2 gas in comparison to that in air throughout the study. Hypoxia had a more prominent influence on 201Tl uptake, which displayed a reduction of approximately 60% in N2 gas at 120 min, than on 99mTc-MIBI uptake. On the other hand, N2 gas induced an increase of 170% in 99mTc-HL91 uptake at 120 min, indicating the hypoxic condition of cells. The results of in vitro assays employing the T24 cell line were similar to those obtained with the LS180 cell line. Hydralazine treatment markedly reduced 99mTc-MIBI and 201Tl accumulation in LS180 xenografts; moreover, intratumoural pO2 decreased from 14.5±6.6 mmHg to 7.6±6.2 mmHg. 99mTc-HL91 accumulation in xenografts was markedly increased by hydralazine. In conclusion, hypoxia reduced accumulation of 99mTc-MIBI and 201Tl in tumour cells. Accordingly, hypoxia may be an important factor in terms of the

  20. Tracer tests Broadlands 1980

    International Nuclear Information System (INIS)

    Two radioactive tracer tests using iodine-131 were made in conjunction with hot water reinjection tests on two wells in the Broadlands geothermal field. In each case, a return was detected to the production part of the field. In one case, as much as 30% of the water being discharged at the observation well was reinjected water. The underground flow velocity as measured by the tracer peak arrival time was 13m/day. In the other test the corresponding figures were 1% and 28 m/day. Flow paths in relation to known geological information are discussed

  1. Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    O-(2-[18F]fluoroethyl) -L-tyrosine([18F]FET) ,a fluorine-18 labeled analogue of tyrosine,has been syn-thesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is com-pleted within 50 min. The radiochemical yield is about 40%(no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid,high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle(T/M) and tumor-to-blood(T/B) of [18F]FET are similar to those of [18F]FDG,but the ratios of tumor-to-brain(T/Br) are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.

  2. Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

    Institute of Scientific and Technical Information of China (English)

    WANG MingWei; YIN DuanZhi; LI ShiQiang; WANG YongXian

    2007-01-01

    O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET), a fluorine-18 labeled analogue of tyrosine, has been synthesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is completed within 50 min. The radiochemical yield is about 40% (no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid, high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle (T/M) and tumor-to-blood (T/B) of [18F]FET are similar to those of [18F]FDG, but the ratios of tumor-to-brain (T/Br)are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.

  3. Glucocorticoid regulation in rat brain cell cultures. Hydrocortisone increases the rate of synthesis of glycerol phosphate dehydrogenase in C6 glioma cells. [Tritium tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    McGinnis, J.F.; de Vellis, J.

    1978-12-10

    Cytoplasmic glycerol phosphate dehydrogenase (sn-glycerol-3-phosphate: NAD/sup +/ 2-oxidoreductase, EC 1.1.1.8) was rapidly purified from rat skeletal muscle in high yield using a combination of classical and affinity techniques. A single band of protein having a molecular weight of 30,000 was found using dodecyl sulfate-polyacrylamide gel electrophoresis. Antisera were generated in rabbits against the purified enzyme and demonstrated to be monospecific by Ouchterlony immunodiffusion against crude homogenates from hydrocortisone-induced and uninduced C6 cells. All of the radioactivity in immunoprecipitates from (/sup 3/H)leucine-labeled cells co-migrated with purified glycerol phosphate dehydrogenase. The amount of radioactivity precipitated was directly proportional to the amount of labeled glycerol phosphate dehydrogenase present, indicating that the assay could be used to quantitate newly synthesized glycerol phosphate dehydrogenase molecules. Using these techniques, the induction of glycerol phosphate dehydrogenase activity by hydrocortisone in the C6 glioma cell line was shown to be due to an increase in the rate of synthesis of the enzyme. Analysis of the kinetics of induction and deinduction supports the above conclusion and suggests that there is essentially no change in the rate of degradation of glycerol phosphate dehydrogenase in the presence and absence of hormone.

  4. Design, synthesis, and mechanistic studies of Sansalvamide A derivatives as anti-cancer agents

    OpenAIRE

    Alexander, Leslie Diane

    2012-01-01

    Sansalvamide A (SanA) is a cyclic depsipeptide that was isolated from a marine fungus and demonstrates mid- micromolar anti-cancer activity in the NCI 60-cell line panel. Our laboratory has synthesized over 100 peptide derivatives of this molecule, 5 of which were contributed by the author of this dissertation. The design and solution-phase synthesis of these derivatives is described in Chapter 2. The author was also responsible for attaching PEG-biotin and fluorescein tags to lead SanA deriv...

  5. Synthesis of nanoscale titanium dioxide and its application in cancer therapy

    OpenAIRE

    Wang, Min; Zhou, Zhiguo; Yang, Shiping

    2015-01-01

    As an important inorganic material,titanium dioxide gets more and more attention and is used in various fields,especially in the biomedical field.This paper summarizes the main synthesis methods of titanium dioxide nanomaterial and its applications in cancer therapy area.The titanium dioxide nanomaterial can be prepared by gas,liquid and solid phase methods.Among them,we mainly introduce liquid phase methods including sol-gel method,hydrothermal method,solvothermal,and microemulsion method.We...

  6. Synthesis and Bioevaluation of Some Phenolic Diarylpropanes as Anti-Cancer Agents

    Directory of Open Access Journals (Sweden)

    Kshama Kundu

    2014-09-01

    Full Text Available A convenient synthesis of six phenolic diarylpropanes has been formulated. A CuBr 2-catalyzed regioselective reaction was the key step for bromination of the arylpropanes. All the compounds showed good cytotoxicity to the human lung cancer A549 cell line. However, only one of these compounds induced apoptosis and a G1 cell cycle arrest by augmenting cellular ROS status. Introduction of bromo-substitution at the aryl groups increased the cytotoxicity significantly, but that was mainly due to necrosis.

  7. Synthesis of nanoscale titanium dioxide and its application in cancer therapy

    Directory of Open Access Journals (Sweden)

    WANG Min

    2015-04-01

    Full Text Available As an important inorganic material,titanium dioxide gets more and more attention and is used in various fields,especially in the biomedical field.This paper summarizes the main synthesis methods of titanium dioxide nanomaterial and its applications in cancer therapy area.The titanium dioxide nanomaterial can be prepared by gas,liquid and solid phase methods.Among them,we mainly introduce liquid phase methods including sol-gel method,hydrothermal method,solvothermal,and microemulsion method.We also further describe the principles of photodynamic therapy and photoacoustic treatment in cancer treatments and applications.Finally,we get the conclusions and have an outlook at the application of titanium dioxide nanomaterials in biomedicine.

  8. Synthesis and Structure-Activity Relationship of Griseofulvin Analogues as Inhibitors of Centrosomal Clustering in Cancer Cells

    DEFF Research Database (Denmark)

    Rønnest, Mads Holger; Rebacz, Blanka; Markworth, Lene;

    2009-01-01

    Griseofulvin was identified as an inhibitor of centrosomal clustering in a recently developed assay. Centrosomal clustering is an important cellular event that enables bipolar mitosis for cancer cell lines harboring supernumerary centrosomes. We report herein the synthesis and SAR of 34 griseoful......Griseofulvin was identified as an inhibitor of centrosomal clustering in a recently developed assay. Centrosomal clustering is an important cellular event that enables bipolar mitosis for cancer cell lines harboring supernumerary centrosomes. We report herein the synthesis and SAR of 34...

  9. A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis

    OpenAIRE

    Gao, Yanzhe; Mutter-Rottmayer, Elizabeth; Greenwalt, Alicia M.; Goldfarb, Dennis; Yan, Feng; Yang, Yang; Martinez-Chacin, Raquel C.; Pearce, Kenneth H.; Tateishi, Satoshi; Major, Michael B.; Vaziri, Cyrus

    2016-01-01

    Trans-lesion synthesis (TLS) is an important DNA-damage tolerance mechanism that permits ongoing DNA synthesis in cells harbouring damaged genomes. The E3 ubiquitin ligase RAD18 activates TLS by promoting recruitment of Y-family DNA polymerases to sites of DNA-damage-induced replication fork stalling. Here we identify the cancer/testes antigen melanoma antigen-A4 (MAGE-A4) as a tumour cell-specific RAD18-binding partner and an activator of TLS. MAGE-A4 depletion from MAGE-A4-expressing cancer...

  10. Radiopharmaceutical Tracers for Neural Progenitor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Mangner, Thomas J.

    2006-09-29

    The Technical Report summarizes the results of the synthesis and microPET animal scanning of several compounds labeled with positron-emitting isotopes in normal, neonatal and kainic acid treated (seizure induced) rats as potential PET tracers to image the process of neurogenesis using positron emission tomography (PET). The tracers tested were 3'-deoxy-3'-[F-18]fluorothymidine ([F-18]FLT) and 5'-benzoyl-FTL, 1-(2'-deoxy-2'-[F-18]fluoro-B-D-arabinofuranosyl)-5-bromouracil (FBAU) and 3',5'-dibenzoyl-FBAU, N-[F-18]fluoroacetyl-D-glucosamine (FLAG) and tetraacetyl-FLAG, and L-[1-C-11]leucine.

  11. Multi-tracer syntheses at a radiopharmaceutical production centre 'A shift of paradigm'

    International Nuclear Information System (INIS)

    Full text: The positron emission tomography (PET) is an unique, non-invasive, powerful diagnostic tool at the forefront of modern functional imaging in clinical nuclear medicine. Traditionally PET is based on short-lived positron emitters ('11C 13N 15O, 18F) which are produced by low-energy cyclotrons. Due to the short half-live fast technical and chemical processes are essential for the production and the synthesis of the radiopharmaceuticals. Since not every PET center can afford to have an own production cyclotron the availability of the different PET tracers at the wide spread PET centers is limited. Furthermore, PET is widely established as a routine assessment of cancer, neurological disorders as well as coronary artery disease in humans and the diagnostic fields are rapidly growing with the development and demand of new bio tracers. At this point PET radiopharmaceutical production and distribution companies can serve such PET centers. The radionuclide 18F is suitable for long-distance distribution. The half-live of 109 min, fast synthesis times and high yields allow transportation of multiple dose vials over a 6 hours time range. This gives the possibility to operate cyclotron centers on a commercial base and distribute PET radiopharmaceuticals to hospitals and private doctors over a certain distance. In consequence, commercial radiopharmaceutical production centers are challenged to offer an high product diversity at high yield production and quality levels. Also highly optimised logistics are necessary to build up a satellite distribution system to cover the amount of activity needed for applications in PET centres away from the production site. In the present work an overview of the installation and the routine operation of ARGOS cyclotron and IASON Graz, two companies dedicated to the production and distribution of PET radiopharmaceuticals for the European market is given. It will reflect the problems of the daily production (e.g. coordination of the

  12. Xanthine tracers and their preparation

    International Nuclear Information System (INIS)

    Compounds useful as tracers in the radioimmunoassay of xanthine derivatives such as theophylline and pharmacologically related drugs are described. They are substituted xanthines in which at least one substituted radical contains radioiodine. The tracers are made by linking radioiodinatable or preradioiodinated radicals to the xanthine derivative which is to be assayed. The tracers may be employed in known radioimmunoassay techniques. (author)

  13. Radioactive tracers in Sedimentology

    International Nuclear Information System (INIS)

    First is given a broad description of the uses of radioactive tracers in Sedimentology. The general method is established, including determinations of probability and standard deviation. Following are determined: the response law of the detector, the minimum mass for statistical detection, and the minimum mass for dynamic detection. The granularity is an important variable in these calculations. Final conclusions are given, and results are compared with existing theories

  14. Tracers and Tracer Testing: Design, Implementation, Tracer Selection, and Interpretation Methods

    Energy Technology Data Exchange (ETDEWEB)

    G. Michael Shook; Shannon L.; Allan Wylie

    2004-01-01

    Conducting a successful tracer test requires adhering to a set of steps. The steps include identifying appropriate and achievable test goals, identifying tracers with the appropriate properties, and implementing the test as designed. When these steps are taken correctly, a host of tracer test analysis methods are available to the practitioner. This report discusses the individual steps required for a successful tracer test and presents methods for analysis. The report is an overview of tracer technology; the Suggested Reading section offers references to the specifics of test design and interpretation.

  15. Gluconeogenesis, liver energy metabolism and weight loss in lung cancer : dynamic studies using stable isotope tracers and 31P magnetic resonance spectroscopy

    NARCIS (Netherlands)

    S. Leij-Halfwerk (Susanne)

    1999-01-01

    textabstractWeight loss is a major problem in many types of cancer and is associated with reduced quality of life and a poor prognosis. Weight loss can also interfere with potentially curable treatment [41,561. Many uncertainties remain about the mechanisms underlying weight loss in patients with ca

  16. Sustained adrenergic signaling leads to increased metastasis in ovarian cancer via increased PGE2 synthesis.

    Science.gov (United States)

    Nagaraja, A S; Dorniak, P L; Sadaoui, N C; Kang, Y; Lin, T; Armaiz-Pena, G; Wu, S Y; Rupaimoole, R; Allen, J K; Gharpure, K M; Pradeep, S; Zand, B; Previs, R A; Hansen, J M; Ivan, C; Rodriguez-Aguayo, C; Yang, P; Lopez-Berestein, G; Lutgendorf, S K; Cole, S W; Sood, A K

    2016-05-01

    Adrenergic stimulation adversely affects tumor growth and metastasis, but the underlying mechanisms are not well understood. Here, we uncovered a novel mechanism by which catecholamines induce inflammation by increasing prostaglandin E2 (PGE2) levels in ovarian cancer cells. Metabolic changes in tumors isolated from patients with depression and mice subjected to restraint stress showed elevated PGE2 levels. Increased metabolites, PTGS2 and PTGES protein levels were found in Skov3-ip1 and HeyA8 cells treated with norepinephrine (NE), and these changes were shown to be mediated by ADRB2 receptor signaling. Silencing PTGS2 resulted in significantly decreased migration and invasion in ovarian cancer cells in the presence of NE and decreased tumor burden and metastasis in restraint stress orthotopic models. In human ovarian cancer samples, concurrent increased ADRB2, PTGS2 and PTGES expression was associated with reduced overall and progression-free patient survival. In conclusion, increased adrenergic stimulation results in increased PGE2 synthesis via ADRB2-Nf-kB-PTGS2 axis, which drives tumor growth and metastasis. PMID:26257064

  17. The Experience of Caregivers Living with Cancer Patients: A Systematic Review and Meta-Synthesis.

    Science.gov (United States)

    LeSeure, Peeranuch; Chongkham-Ang, Supaporn

    2015-01-01

    The objectives of this meta-synthesis were to: (1) explore the experience of caregivers who were caring for cancer patients, including their perceptions and responses to the situation; and (2) describe the context and the phenomena relevant to the experience. Five databases were used: CINAHL, MEDLINE, Academic Search, Science Direct, and a Thai database known as the Thai Library Integrated System (ThaiLIS). Three sets of the context of the experience and the phenomena relevant to the experience were described. The contexts were (1) having a hard time dealing with emotional devastation; (2) knowing that the caregiving job was laborious; and (3) knowing that I was not alone. The phenomenon showed the progress of the caregivers' thoughts and actions. A general phenomenon of the experience-balancing my emotion-applied to most of the caregivers; whereas, more specific phenomenon-keeping life as normal as possible and lifting life above the illness-were experienced by a lesser number of the caregivers. This review added a more thorough explanation of the issues involved in caregiving for cancer patients. A more comprehensive description of the experience of caregiving was described. The findings of this review can be used to guide clinical practice and policy formation in cancer patient care. PMID:26610573

  18. The Experience of Caregivers Living with Cancer Patients: A Systematic Review and Meta-Synthesis

    Directory of Open Access Journals (Sweden)

    Peeranuch LeSeure

    2015-11-01

    Full Text Available The objectives of this meta-synthesis were to: (1 explore the experience of caregivers who were caring for cancer patients, including their perceptions and responses to the situation; and (2 describe the context and the phenomena relevant to the experience. Five databases were used: CINAHL, MEDLINE, Academic Search, Science Direct, and a Thai database known as the Thai Library Integrated System (ThaiLIS. Three sets of the context of the experience and the phenomena relevant to the experience were described. The contexts were (1 having a hard time dealing with emotional devastation; (2 knowing that the caregiving job was laborious; and (3 knowing that I was not alone. The phenomenon showed the progress of the caregivers’ thoughts and actions. A general phenomenon of the experience—balancing my emotion—applied to most of the caregivers; whereas, more specific phenomenon—keeping life as normal as possible and lifting life above the illness—were experienced by a lesser number of the caregivers. This review added a more thorough explanation of the issues involved in caregiving for cancer patients. A more comprehensive description of the experience of caregiving was described. The findings of this review can be used to guide clinical practice and policy formation in cancer patient care.

  19. Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Sarit; Pellach, Michal [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel); Kam, Yossi [Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120 (Israel); Grinberg, Igor; Corem-Salkmon, Enav [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel); Rubinstein, Abraham [Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120 (Israel); Margel, Shlomo, E-mail: shlomo.margel@mail.biu.ac.il [Department of Chemistry, Bar-Ilan Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900 (Israel)

    2013-03-01

    Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. - Highlights: Black-Right-Pointing-Pointer Near IR human serum albumin nanoparticles were synthesized and characterized. Black-Right-Pointing-Pointer Nanoparticles were shown to be physically and chemically stable and photostable. Black-Right-Pointing-Pointer Tumor-targeting ligands were covalently conjugated to the nanoparticles. Black-Right-Pointing-Pointer Specific colon cancer tumor detection was demonstrated in chicken-embryo and rat models.

  20. Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer

    International Nuclear Information System (INIS)

    Near IR (NIR) fluorescent human serum albumin (HSA) nanoparticles hold great promise as contrast agents for tumor diagnosis. HSA nanoparticles are considered to be biocompatible, non-toxic and non-immunogenic. In addition, NIR fluorescence properties of these nanoparticles are important for in vivo tumor diagnostics, with low autofluorescence and relatively deep penetration of NIR irradiation due to low absorption of biomatrices. The present study describes the synthesis of new NIR fluorescent HSA nanoparticles, by entrapment of a NIR fluorescent dye within the HSA nanoparticles, which also significantly increases the photostability of the dye. Tumor-targeting ligands such as peanut agglutinin (PNA) and anti-carcinoembryonic antigen antibodies (anti-CEA) were covalently conjugated to the NIR fluorescent albumin nanoparticles, increasing the potential fluorescent signal in tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent HSA nanoparticles was demonstrated in a chicken embryo model and a rat model. In future work we also plan to encapsulate cancer drugs such as doxorubicin within the NIR fluorescent HSA nanoparticles for both colon cancer imaging and therapy. - Highlights: ► Near IR human serum albumin nanoparticles were synthesized and characterized. ► Nanoparticles were shown to be physically and chemically stable and photostable. ► Tumor-targeting ligands were covalently conjugated to the nanoparticles. ► Specific colon cancer tumor detection was demonstrated in chicken-embryo and rat models.

  1. Development of radioisotope tracer technology

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Joon Ha; Lee, Myun Joo; Jung, Sung Hee; Park, Soon Chul; Lim, Dong Soon; Kim, Jae Ho; Lee, Jae Choon; Lee, Doo Sung; Cho, Yong Suk; Shin, Sung Kuan

    2000-04-01

    The purpose of this study is to develop the radioisotope tracer technology, which can be used in solving industrial and environmental problems and to build a strong tracer group to support the local industries. In relation to the tracer technology in 1999, experiments to estimate the efficiencies of a sludge digester of a waste water treatment plant and a submerged biological reactor of a dye industry were conducted. As a result, the tracer technology for optimization of facilities related to wastewater treatment has been developed and is believed to contribute to improve their operation efficiency. The quantification of the experimental result was attempted to improve the confidence of tracer technology by ECRIN program which basically uses the MCNP simulation principle. Using thin layer activation technique, wear of tappet shim was estimated. Thin layer surface of a tappet shim was irradiated by proton beam and the correlation between the measured activity loss and the amount of wear was established. The equipment was developed to adjust the energy of proton which collides with the surface of tappet. The tracer project team has participated into the tracer test for estimating the efficiency of RFCC system in SK cooperation. From the experiment the tracer team has obtained the primary elements to be considered for judging the efficiency of RFCC unit. By developing the tracer techniques to test huge industrial units like RFCC, the tracer team will be able to support the local industries that require technical services to solve any urgent trouble. (author)

  2. Development of radioisotope tracer technology

    International Nuclear Information System (INIS)

    The purpose of this study is to develop the radioisotope tracer technology, which can be used in solving industrial and environmental problems and to build a strong tracer group to support the local industries. In relation to the tracer technology in 1999, experiments to estimate the efficiencies of a sludge digester of a waste water treatment plant and a submerged biological reactor of a dye industry were conducted. As a result, the tracer technology for optimization of facilities related to wastewater treatment has been developed and is believed to contribute to improve their operation efficiency. The quantification of the experimental result was attempted to improve the confidence of tracer technology by ECRIN program which basically uses the MCNP simulation principle. Using thin layer activation technique, wear of tappet shim was estimated. Thin layer surface of a tappet shim was irradiated by proton beam and the correlation between the measured activity loss and the amount of wear was established. The equipment was developed to adjust the energy of proton which collides with the surface of tappet. The tracer project team has participated into the tracer test for estimating the efficiency of RFCC system in SK cooperation. From the experiment the tracer team has obtained the primary elements to be considered for judging the efficiency of RFCC unit. By developing the tracer techniques to test huge industrial units like RFCC, the tracer team will be able to support the local industries that require technical services to solve any urgent trouble. (author)

  3. Uptake of algal carbon and the synthesis of an "essential" fatty acid by Uvigerina ex. gr. semiornata (Foraminifera within the Pakistan margin oxygen minimum zone: evidence from fatty acid biomarker and 13C tracer experiments

    Directory of Open Access Journals (Sweden)

    K. E. Larkin

    2014-01-01

    Full Text Available Foraminifera are an important component of benthic communities in oxygen depleted settings, where they potentially play a~significant role in the processing of organic matter. We tracked the uptake of a 13C-labeled algal food source into individual fatty acids in the benthic foraminiferal species, Uvigerina ex. gr. semiornata, from the Arabian Sea oxygen minimum zone (OMZ. The tracer experiments were conducted on the Pakistan Margin during the late/post monsoon period (August–October 2003. A monoculture of the diatom Thalassiosira weisflogii was 13C-labeled and used to simulate a pulse of phytoplankton in two complementary experiments. A lander system was used for in situ incubations at 140 m and for 2.5 days duration, whilst a laboratory incubation used an oxystat system to maintain ambient dissolved oxygen concentrations. These shipboard experiments were terminated after 5 days. Uptake of diatoms was rapid, with high incorporation of diatom fatty acids into foraminifera after ~2 days in both experiments. Ingestion of the diatom food source was indicated by the increase over time in the quantity of diatom biomarker fatty acids in the foraminifera and by the high percentage of 13C in many of the fatty acids present at the endpoint of both in~situ and laboratory-based experiments. These results indicate that U. ex. gr. semiornata rapidly ingested the diatom food source and that this foraminifera will play an important role in the short-term cycling of organic matter within this OMZ environment. The experiments also suggested that U. ex. gr. semiornata consumed non-labeled bacterial food items, particularly bacteria, and synthesised the polyunsaturated fatty acid 20:4(n-6 de novo. 20:4(n-6 is often abundant in benthic fauna yet its origins and function have remained unclear. This study demonstrates that U. ex. gr. semiornata is capable of de novo synthesis of this "essential fatty acid" and is potentially a major source of this dietary nutrient

  4. 99mTc-phytate is better than 99mTc-human serum albumin as a radioactive tracer for sentinel lymph node biopsy in breast cancer

    International Nuclear Information System (INIS)

    Several radioactive agents are used for sentinel lymph node biopsy (SLNB) in breast cancer, but we are still unsure which of these is best. We retrospectively compared the effectiveness of two radioactive agents, 99mTc-phytate and 99mTc-human serum albumin (HSA), when used in combination with blue dye. A consecutive series of 533 clinically node-negative patients with a collective 539 breast carcinomas were divided into two groups for treatment with SLNB. The HSA-group consisted of 264 patients (with a collective 266 breast cancers) and the P-group consisted of 269 patients (with a collective 273 breast cancers) treated with 99mTc-HSA and 99mTc-phytate, respectively, in combination with blue dye. We analyzed the identification and radioactivity of SLNs in the two groups. The identification rate of SLN was significantly higher in the P-group than in the HSA-group. The same results were produced by analysis using the radioactive agent alone, but not by using the blue dye alone. Most importantly, the highest radioactivity of SLNs per case was more than five times higher in the P-group than in the HSA-group, and this difference was significant. Our historical analysis of the two radioactive agents used in different periods could not exclude the influence of the improved skill of the surgeons. However, because the specific accumulation of phytate in SLNs was greater than that of HSA, phytate might result in a higher SLN identification rate. Thus, 99mTc-phytate is better than 99mTc-HSA as a radioactive agent for SLNB in breast cancer. (author)

  5. 68Ga-AMBA and 18 F-FDG for preclinical PET imaging of breast cancer: effect of tamoxifen treatment on tracer uptake by tumor

    International Nuclear Information System (INIS)

    Introduction: AMBA is a bombesin analogue that binds to GRPr. In a mouse model of estrogen-dependent human breast cancer, we tested whether 68Ga-AMBA can be used for PET detection of GRPr-expressing tumors and could be more accurate than 18F-FDG to monitor tumor response to hormone therapy. Methods: The radiolabeling of 68Ga-AMBA was automated using a R and D Synchrom module. ZR75-1, a breast cancer cell line, was xenografted in nude mice. 68Ga-AMBA tumor uptake was compared with that of 18F-FDG before and after treatment with tamoxifen. Results: AMBA was 68Ga-radiolabelled in 30 min with 95.3% yield and purity ≥ 98%. Prior to treatment, 68Ga-AMBA was highly concentrated into tumors (tumor to non-tumor ratio = 2.4 vs. 1.3 with 18F-FDG). With tamoxifen treatment (n = 6) 68Ga-AMBA uptake plateaued after 1 week and decreased after 2 weeks, with a significant reduction compared to controls (n = 4). In contrast the effect of tamoxifen treatment could not be appreciated using 18F-FDG. Conclusions: 68Ga-AMBA appeared better than 18F-FDG to visualize and monitor the response to hormone treatment in this breast cancer model

  6. Tracer testing for reservoir description

    Energy Technology Data Exchange (ETDEWEB)

    Brigham, W.E.; Abbaszadeh-Dehghani, M.

    1987-05-01

    When a reservoir is studied in detail for an EOR project, well-to-well tracers should be used as a tool to help understand the reservoir in a quantitative way. Tracers complement the more traditional reservoir evaluation tools. This paper discusses the concepts underlying tracer testing, the analysis methods used to produce quantitative results, and the meaning of these results in terms of conceptual picture of the reservoir. Some of the limitations of these analysis methods are discussed, along with ongoing research on tracer flow.

  7. Tracer testing for reservoir description

    International Nuclear Information System (INIS)

    When a reservoir is studied in detail for an EOR project, well-to-well tracers should be used as a tool to help understand the reservoir in a quantitative way. Tracers complement the more traditional reservoir evaluation tools. This paper discusses the concepts underlying tracer testing, the analysis methods used to produce quantitative results, and the meaning of these results in terms of conceptual picture of the reservoir. Some of the limitations of these analysis methods are discussed, along with ongoing research on tracer flow

  8. Effect of different BNCT protocols on DNA synthesis in precancerous and normal tissues in an experimental model of oral cancer

    International Nuclear Information System (INIS)

    We previously reported the therapeutic success of different BNCT protocols in the treatment of oral cancer, employing the hamster cheek pouch model. The aim of the present study was to evaluate the effect of these BNCT protocols on DNA synthesis in precancerous and normal tissue in this model and assess the potential lag in the development of second primary tumors in precancerous tissue. The data are relevant to potential control of field cancerized tissue and tolerance of normal tissue. We evaluated DNA synthesis in precancerous and normal pouch tissue 1-30 days post-BNCT mediated by BPA, GB-10 or BPA + GB-10 employing incorporation of bromo-deoxyuridine as an end-point. The BNCT-induced potential lag in the development of second primary tumors in precancerous tissue was monitored. A drastic, statistically significant reduction in DNA synthesis occurred in pacancerous tissue as early as 1 day post-BNCT and was sustained at virtually all time points until 30 days post-BNCT for all protocols. The histological categories evaluated individually within precancerous tissue (dysplasia, hyperplasia and NUMF [no unusual microscopic features]) responded similarly. DNA synthesis in normal tissue treated with BNCT oscillated around the very low pre-treatment values. A BNCT-induced lag in the development of second primary tumors was observed. BNCT induced a drastic fall in DNA synthesis in precancerous tissue that would be associated to the observed lag in the development of second primary tumors. The minimum variations in DNA synthesis in BNCT-treated normal tissue would correlate with the absence of normal tissue radiotoxicity. The present data would contribute to optimize therapeutic efficacy in the treatment of field-cancerized areas. (author)

  9. The value of PET/CT with FES or FDG tracers in metastatic breast cancer: a computer simulation study in ER-positive patients

    OpenAIRE

    Koleva-Kolarova, R.G.; Greuter, M. J. W.; van Kruchten, M; Vermeulen, K.M.; Feenstra, T; Buskens, E; Glaudemans, A. W. J. M.; de Vries, E F J; de Vries, E G E; Hospers, G A P; de Bock, G H

    2015-01-01

    Background: The aim of this study was to evaluate the effect on the number of performed biopsies and costs associated with implementing positron emission tomography (PET) and computed tomography (PET/CT) with 16α-[18F]fluoro-17β-oestradiol (FES) or 2-[18F]fluoro-2-deoxy-D-glucose (FDG) as an upfront imaging test for diagnosing metastatic breast cancer (MBC) in comparison with the standard work-up in oestrogen receptor-positive women with symptoms. Methods: A published computer simulation mode...

  10. Microfluidics: A Groundbreaking Technology for PET Tracer Production?

    Directory of Open Access Journals (Sweden)

    Björn Wängler

    2013-07-01

    Full Text Available Application of microfluidics to Positron Emission Tomography (PET tracer synthesis has attracted increasing interest within the last decade. The technical advantages of microfluidics, in particular the high surface to volume ratio and resulting fast thermal heating and cooling rates of reagents can lead to reduced reaction times, increased synthesis yields and reduced by-products. In addition automated reaction optimization, reduced consumption of expensive reagents and a path towards a reduced system footprint have been successfully demonstrated. The processing of radioactivity levels required for routine production, use of microfluidic-produced PET tracer doses in preclinical and clinical imaging as well as feasibility studies on autoradiolytic decomposition have all given promising results. However, the number of microfluidic synthesizers utilized for commercial routine production of PET tracers is very limited. This study reviews the state of the art in microfluidic PET tracer synthesis, highlighting critical design aspects, strengths, weaknesses and presenting several characteristics of the diverse PET market space which are thought to have a significant impact on research, development and engineering of microfluidic devices in this field. Furthermore, the topics of batch- and single-dose production, cyclotron to quality control integration as well as centralized versus de-centralized market distribution models are addressed.

  11. Radionuclides as tracers

    International Nuclear Information System (INIS)

    Importance of radioisotopes in medicine is because of their two characteristics: their biological behaviour is identical to their stable counterparts, and because they are radioactive their emissions can be detected by a suitable instrument. All isotopes of iodine will behave in the same way and will concentrate in the thyroid gland. There is no way of detecting the stable, natural iodine in the thyroid gland, but the presence of radioactive iodine can be detected externally in vivo by a detector. Thus, the radioactive iodine becomes a tracer, a sport of a spy, which mimics the behaviour of natural iodine and relays information to a detector. The radioactive tracers are popular because of the ease with which they can be detected in vivo and the fact that the measurement of their presence in the body can be in quantitative terms. The measurement can be very accurate and sensitive. Whenever the measurements can be done in vivo, the information is obtained in dynamic terms, as it is happening, as if the physiological events become transparent

  12. Rhodamine 123 inhibits protein synthesis in mitochondria isolated from normal and cancer tissues

    International Nuclear Information System (INIS)

    The dye rhodamine 123 (Rho 123) is well known to specifically stain mitochrondria in living cells. Its accumulation in these organelles is associated with certain toxic effects where the dye is found to inhibit bioenergetic function in normal and cancer mitochondria. Since mitochondria appear to be a target for Rho 123 interaction, the authors investigated its effects on mitochondrial protein synthesis (PS) in rat liver, and in both erythroleukemia and chloroleukemia tumors. L-(14C) leucine incorporation into mitochondria protein was used to determine the rate of PS. While the specific activity of leucine incorporation was much higher in tumor as compared to liver mitochondria, the addition of 10 μg Rho 123/ml in all tested mitochondria resulted in 75-80% inhibition. Similar results were obtained with 10 μg/ml of chloramphenicol, the specific inhibitor for mitochondrial PS. PS inhibition in the three types of mitochondria was Rho 123 concentration-dependent being about 50% at 5 μg/ml and with total inhibition at 15-20 μg/ml. Moreover, the addition of Rho 123 to mitochondria under PS condition did not trigger any ATPase activity. If present, such activity would compete for ATP which is the energy source of PS. These results demonstrate that the mitochondrial probe Rho 123 has a potent inhibitory effect on PS in both normal and cancer mitochondria

  13. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines

    International Nuclear Information System (INIS)

    The authors report that human breast cancer cells secrete a growth factor that is biologically and immunologically similar to platelet-derived growth factor (PDGF). Serum-free medium conditioned by estrogen-independent MDA-MB-231 or estrogen-dependent MCF-7 cells contains a mitogenic or competence activity that is capable of inducing incorporation of [3H] thymidine into quiescent Swiss 3T3 cells in the presence of platelet-poor plasma. Like authentic PDGF, the PDGF-like activity produced by breast cancer cells is stable after acid and heat treatment (950C) and inhibited by reducing agents. The mitogenic activity comigrates with a material of ≅30 kDa on NaDodSO4/polyacrylamide gels. Immunoprecipitation with PDGF antiserum of proteins from metabolically labeled cell lysates and conditioned medium followed by analysis on nonreducing NaDodSO4/polyacrylamide gels identified proteins of 30 and 34 kDa. Upon reduction, the 30- and 34-kDa bands were converted to 15- and 16-kDa bands suggesting that the immunoprecipitated proteins were made up of two disulfide-linked polypeptides similar to PDGF. Hybridization studies with cDNA probes for the A chain PDGF and the B chain of PDGF/SIS identified transcripts for both PDGF chains in the MCF-7 and MDA-MB-231 cells. The data summarized above provide conclusive evidence for the synthesis and hormonally regulated secretion of a PDGF-like mitogen by breast carcinoma cells. Production of a PDGF-like growth factor by breast cancer cell lines may be important in mediating paracrine stimulation of tumor growth

  14. Matrix Analysis of Tracer Transport

    CERN Document Server

    Mills, Peter

    2015-01-01

    We review matrix methods as applied to tracer transport. Because tracer transport is linear, matrix methods are an ideal fit for the problem. In particular, solutions of linear, first-order systems of ordinary differential equations (ODEs) are reviewed as well as special properties of these solutions. Detailed derivations are included

  15. A 99Tcm labeled HYNIC peptide 'tracer' libraries on continuous cellulose membrane supports

    International Nuclear Information System (INIS)

    Objective: The interference of bifunctional ligands with activities of small peptides has long been recognized. To solve the problem, the hydrazine-nicotinamide (HYNIC) conjugated peptide 'tracer' libraries were synthesized on a continuous cellulose membrane support and the 99Tcm labeled heat shock protein 70 (HSP70) binding peptides were identified by screening libraries with HSP70. Methods: Octapeptide libraries were prepared by manual spot synthesis. HYNIC peptides were C terminally attached to cellulose via a (β-Ala)2 spacer. For screening, the cellulose membranes were incubated with human HSP70 (or biotin labeled HSP70) after nonspecific blocking. Alkaline phosphatase labeled streptavidin and Ab against HSP70 were used for the detection of HSP70 binding. Human lung cancer cell lines (A549 and H460) were cultured in RPMI1640 medium supplemented with 10% fetal calf serum and antibiotics. For in vivo test, 2 x l05 cells were subcutaneously transplanted into the chest of female nude mice. Results: Quality control of HYNIC peptide libraries was good as carried out by 99Tcm labeling. Because peptide NLLRLTG had high affinity for HSP70 family members, 99Tcm-HYNIC-NLLRLTG was used as the control. Fifteen HYNIC peptides were found with HSP70 binding property. Among them, eight peptides had higher uptake (percentage activity of injection dose pergram of tissue, %ID/g) values than 99Tcm-HYNIC-NLLRLTG in tumor. 99Tcm-HYNIC-QGVLTGTR had the best distribution in tumors. Six hours after injection, the %ID/g values of 99Tcm HYNIC-QGVLTGTR and 99Tcm-HYNIC-NLLRLTG in tumor were (1.15±0.32)% ID/g and (0.75±0.24)% ID/g respectively. In vivo replace studies and heat shock stress of tumors demonstrated that 99Tcm-HYNIC-QGVLTGTR was the HSP70 binding peptide compound, but not 99Tcm-HYNIC-NLLRLTG. Conclusions: The identification of 99Tcm labeled HSP70 binding peptides from HYNIC conjugated octapeptide libraries facilitated the hypothesis of the 'tracer' libraries. The design and

  16. Prostate cancer and supportive care: a systematic review and qualitative synthesis of men's experiences and unmet needs.

    Science.gov (United States)

    King, A J L; Evans, M; Moore, T H M; Paterson, C; Sharp, D; Persad, R; Huntley, A L

    2015-09-01

    Prostate cancer is the second most common cancer in men worldwide, accounting for an estimated 1.1 million new cases diagnosed in 2012 (www.globocan.iarc.fr). Currently, there is a lack of specific guidance on supportive care for men with prostate cancer. This article describes a qualitative systematic review and synthesis examining men's experience of and need for supportive care. Seven databases were searched; 20 journal articles were identified and critically appraised. A thematic synthesis was conducted in which descriptive themes were drawn out of the data. These were peer support, support from partner, online support, cancer specialist nurse support, self-care, communication with health professionals, unmet needs (emotional support, information needs, support for treatment-induced side effects of incontinence and erectile dysfunction) and men's suggestions for improved delivery of supportive care. This was followed by the development of overarching analytic themes which were: uncertainty, reframing, and the timing of receiving treatment, information and support. Our results show that the most valued form of support men experienced following diagnosis was one-to-one peer support and support from partners. This review highlights the need for improved access to cancer specialist nurses throughout the care pathway, individually tailored supportive care and psychosexual support for treatment side effects. PMID:25630851

  17. Radon as geological tracer

    International Nuclear Information System (INIS)

    Full text: This work presents measurements of 222Rn levels performed in La Carolina gold mine and Los Condores tungsten mine at the province of San Luis, Argentina, today used for tourist visitation, and can evaluate the potential use of such radioactive noble gas as tracer or marker for geological processes in underground environments. By concentrations of 40K, 232Th and 23'8U were also measured in the walls of tunnels were determined the rocks mineral composition, what indicated that the mines have the same composition. In this sense, we used nuclear trace plastic detectors CR-39, gamma spectrometry of rock samples and Geiger-Muller (GM) monitors The patterns of radon gas transportation processes revealed that La Carolina could be interpreted through a model based on a radioactive gas confined into a single entrance tube, with constant cross section and air velocity. Los Condores, which has a second main entrance, could be interpreted through a model based on a radioactive gas confined into a two entrance tube, allowing a chimney effect for air circulation. The results showed the high potential of using 222Rn as a geological tracer. In what concerns the occupational hazard, in summer (time of more intense tourist activity in the mine) La Carolina presented a mean concentration of the radioactive noble gas that exceeds in four times the action level of 1,5 kBq m-3 recommended by the International Commission of Radiological Protection (ICRP). The chimney effect shows the low mean concentration of radon in Los Condores. (author)

  18. Synthesis and anti-cancer activity of 1,4-disubstituted imidazo[4,5-c]quinolines.

    Science.gov (United States)

    Thigulla, Yadagiri; Akula, Mahesh; Trivedi, Prakruti; Ghosh, Balaram; Jha, Mukund; Bhattacharya, Anupam

    2016-01-21

    The synthesis and anti-cancer activity evaluation of fused imidazoquinoline compounds is reported in this paper. Yb(OTf)3 has been utilized as a catalyst for the synthesis of 1,4-diaryl substituted imidazo[4,5-c]quinolines via a modified Pictet-Spengler approach. The desired imidazole ring was synthesized from imines using TosMIC (toluenesulfonylmethyl isocyanide) and subsequently functionalized at the C-4 position yielding an imidazoquinoline skeleton. Importantly, the final step was carried out without the aid of any prefunctionalization to obtain the resultant compounds in good yields. The synthesized compounds, when screened for anti-cancer activity, revealed the highest activity with 4-(2-bromophenyl)-1-phenyl-1H-imidazo[4,5-c]quinoline (IC50: 103.3 μM). PMID:26592542

  19. Green chemistry approach for the synthesis and stabilization of biocompatible gold nanoparticles and their potential applications in cancer therapy

    International Nuclear Information System (INIS)

    The biological approach to synthesis of AuNPs is eco-friendly and an ideal method to develop environmentally sustainable nanoparticles alternative to existing methods. We have developed a simple, fast, clean, efficient, low-cost and eco-friendly single-step green chemistry approach for the synthesis of biocompatible gold nanoparticles (AuNPs) from chloroauric acid (HAuCl4) using a water extract of Eclipta Alba leaves at room temperature. The AuNPs using Eclipta extract have been formed in very short time, even in less than 10 min. The as-synthesized AuNPs were thoroughly characterized by several physico-chemical techniques. The in vitro stability of as-synthesized AuNPs was studied in different buffer solutions. A plausible mechanism for the synthesis of AuNPs by Eclipta extract has been discussed. The biocompatibility of AuNPs was observed by in vitro cell culture assays. Finally, we have designed and developed a AuNPs-based drug delivery system (DDS) (Au-DOX) containing doxorubicin (DOX), a FDA approved anticancer drug. Administration of this DDS to breast cancer cells (MCF-7 and MDA-MB-231) shows significant inhibition of breast cancer cell proliferation compared to pristine doxorubicin. Therefore we strongly believe that the use of Eclipta Alba offers large-scale production of biocompatible AuNPs that can be used as a delivery vehicle for the treatment of cancer diseases. (paper)

  20. Green chemistry approach for the synthesis and stabilization of biocompatible gold nanoparticles and their potential applications in cancer therapy

    Science.gov (United States)

    Mukherjee, Sudip; Sushma, V.; Patra, Sujata; Barui, Ayan Kumar; Pal Bhadra, Manika; Sreedhar, Bojja; Ranjan Patra, Chitta

    2012-11-01

    The biological approach to synthesis of AuNPs is eco-friendly and an ideal method to develop environmentally sustainable nanoparticles alternative to existing methods. We have developed a simple, fast, clean, efficient, low-cost and eco-friendly single-step green chemistry approach for the synthesis of biocompatible gold nanoparticles (AuNPs) from chloroauric acid (HAuCl4) using a water extract of Eclipta Alba leaves at room temperature. The AuNPs using Eclipta extract have been formed in very short time, even in less than 10 min. The as-synthesized AuNPs were thoroughly characterized by several physico-chemical techniques. The in vitro stability of as-synthesized AuNPs was studied in different buffer solutions. A plausible mechanism for the synthesis of AuNPs by Eclipta extract has been discussed. The biocompatibility of AuNPs was observed by in vitro cell culture assays. Finally, we have designed and developed a AuNPs-based drug delivery system (DDS) (Au-DOX) containing doxorubicin (DOX), a FDA approved anticancer drug. Administration of this DDS to breast cancer cells (MCF-7 and MDA-MB-231) shows significant inhibition of breast cancer cell proliferation compared to pristine doxorubicin. Therefore we strongly believe that the use of Eclipta Alba offers large-scale production of biocompatible AuNPs that can be used as a delivery vehicle for the treatment of cancer diseases.

  1. Green synthesis of anisotropic gold nanoparticles for photothermal therapy of cancer.

    Science.gov (United States)

    Fazal, Sajid; Jayasree, Aswathy; Sasidharan, Sisini; Koyakutty, Manzoor; Nair, Shantikumar V; Menon, Deepthy

    2014-06-11

    Nanoparticles of varying composition, size, shape, and architecture have been explored for use as photothermal agents in the field of cancer nanomedicine. Among them, gold nanoparticles provide a simple platform for thermal ablation owing to its biocompatibility in vivo. However, the synthesis of such gold nanoparticles exhibiting suitable properties for photothermal activity involves cumbersome routes using toxic chemicals as capping agents, which can cause concerns in vivo. Herein, gold nanoparticles, synthesized using green chemistry routes possessing near-infrared (NIR) absorbance facilitating photothermal therapy, would be a viable alternative. In this study, anisotropic gold nanoparticles were synthesized using an aqueous route with cocoa extract which served both as a reducing and stabilizing agent. The as-prepared gold nanoparticles were subjected to density gradient centrifugation to maximize its NIR absorption in the wavelength range of 800-1000 nm. The particles also showed good biocompatibility when tested in vitro using A431, MDA-MB231, L929, and NIH-3T3 cell lines up to concentrations of 200 μg/mL. Cell death induced in epidermoid carcinoma A431 cells upon irradiation with a femtosecond laser at 800 nm at a low power density of 6 W/cm(2) proved the suitability of green synthesized NIR absorbing anisotropic gold nanoparticles for photothermal ablation of cancer cells. These gold nanoparticles also showed good X-ray contrast when tested using computed tomography (CT), proving their feasibility for use as a contrast agent as well. This is the first report on green synthesized anisotropic and cytocompatible gold nanoparticles without any capping agents and their suitability for photothermal therapy. PMID:24842534

  2. Tracer dispersion - experiment and CFD

    International Nuclear Information System (INIS)

    Description of tracer distribution by means of dispersion models is a method successfully used in process engineering for fifty years. Application of dispersion models in reactor engineering for characterization of flows in column apparatus, heat exchangers, etc. is summarized and experimental tracer techniques as well as CFD methods for dispersion coefficients evaluation are discussed. Possible extensions of thermal axial dispersion model (ADM) and a core-wall ADM model suitable for description of tracer dispersion in laminar flows are suggested as well as CFD implementation as 1D finite elements. (author)

  3. Proceedings of the atmospheric tracers and tracer application workshop

    International Nuclear Information System (INIS)

    In addition to presentations by participating members a general discussion was held in order to summarize and outline the goals and objectives of the workshop. A number of new low level background tracers such as heavy methanes, perfluorocarbons, multiply labeled isotopes such as 13C18O2, helium 3, in addition to sample collection techniques and analytical methods for various tracers were discussed. This report is a summary of discussions and papers presented at this workshop

  4. Proceedings of the atmospheric tracers and tracer application workshop

    Energy Technology Data Exchange (ETDEWEB)

    Barr, S.; Gedayloo, T. (comps.)

    1979-12-01

    In addition to presentations by participating members a general discussion was held in order to summarize and outline the goals and objectives of the workshop. A number of new low level background tracers such as heavy methanes, perfluorocarbons, multiply labeled isotopes such as /sup 13/C/sup 18/O/sub 2/, helium 3, in addition to sample collection techniques and analytical methods for various tracers were discussed. This report is a summary of discussions and papers presented at this workshop.

  5. Novel tracer for radiation treatment planning; Welche neuen PET-Tracer braucht die Strahlentherapie?

    Energy Technology Data Exchange (ETDEWEB)

    Schwarzenboeck, S.; Krause, B.J. [Rostock Univ. (Germany). Klinik fuer Nuklearmedizin; Herrmann, K.; Gaertner, F.; Souvatzoglou, M. [Technische Univ. Muenchen (Germany). Klinik fuer Nuklearmedizin; Klaesner, B. [Klinikum Bogenhausen, Muenchen (Germany). Inst. fuer Radiologie und Nuklearmedizin

    2011-07-15

    PET and PET/CT with innovative tracers gain increasing importance in diagnosis and therapy management, and radiation treatment planning in radio-oncology besides the widely established FDG. The introduction of [{sup 18}F]Fluorothymidine ([{sup 18}F]FLT) as marker of proliferation, [{sup 18}F]Fluoromisonidazole ([{sup 18}F]FMISO) and [{sup 18}F]Fluoroazomycin-Arabinoside ([{sup 18}F]FAZA) as tracer of hypoxia, [{sup 18}F]Fluoroethyltyrosine ([{sup 18}F]FET) and [{sup 11}C]Methionine for brain tumour imaging, [{sup 68}Ga]DOTATOC for somatostatin receptor imaging, [{sup 18}F]FDOPA for dopamine synthesis and radioactively labeled choline derivatives for imaging phospholipid metabolism have opened novel approaches to tumour imaging. Some of these tracers have already been implemented into radio-oncology: Amino acid PET and PET/CT have the potential to optimise radiation treatment planning of brain tumours through accurate delineation of tumour tissue from normal tissue, necrosis and edema. Hypoxia represents a major therapeutic problem in radiation therapy. Hypoxia imaging is very attractive as it may allow to increase the dose in hypoxic tumours potentially allowing for a better tumour control. Advances in hybrid imaging, i.e. the introduction of MR/PET, may also have an impact in radio-oncology through synergies related to the combination of molecular signals of PET and a high soft tissue contrast of MRI as well as functional MRI capabilities. (orig.)

  6. Synthesis of a theranostic agent. Radioiodinated PEGylated PLGA-indocyanine capsules and in vitro determination of their bioaffinity on ovarian, cervical and breast cancer cells

    International Nuclear Information System (INIS)

    The aim of current study is to synthesize a theranostic (multi-functional) agent, which is targeted on ovary, cervical and breast cancer types with diagnosis and treatment potential and to determine its bioaffinity by using in vitro methods. In conclusion; the designed compound (IPPP), which has fluorescence capability (from Indocyanine), encapsulated structure (with PEGylated PLGA), included an anticancer drug (Paclitaxel) for targeting and radionuclidic tracer (131I) content for tracing, has bioaffinity and promise for diagnosis and therapy on ovarian, cervical and breast cancer cell lines. (author)

  7. Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting.

    Science.gov (United States)

    Dong, Shuping; Cho, Hyung Joon; Lee, Yong Woo; Roman, Maren

    2014-05-12

    Elongated nanoparticles have recently been shown to have distinct advantages over spherical ones in targeted drug delivery applications. In addition to their oblong geometry, their lack of cytotoxicity and numerous surface hydroxyl groups make cellulose nanocrystals (CNCs) promising drug delivery vectors. Herein we report the synthesis of folic acid-conjugated CNCs for the targeted delivery of chemotherapeutic agents to folate receptor-positive cancer cells. Folate receptor-mediated cellular binding/uptake of the conjugate was demonstrated on human (DBTRG-05MG, H4) and rat (C6) brain tumor cells. Folate receptor expression of the cells was verified by immunofluorescence staining. Cellular binding/uptake of the conjugate by DBTRG-05MG, H4, and C6 cells was 1452, 975, and 46 times higher, respectively, than that of nontargeted CNCs. The uptake mechanism was determined by preincubation of the cells with the uptake inhibitors chlorpromazine or genistein. DBTRG-05MG and C6 cells internalized the conjugate primarily via caveolae-mediated endocytosis, whereas H4 cells internalized the conjugate primarily via clathrin-mediated endocytosis. PMID:24716601

  8. Near source tracers at Hanford

    International Nuclear Information System (INIS)

    Atmospheric tracer techniques are reviewed, with emphasis on the Hanford inert gas krypton-85 field technique. This technique is considerably more sophisticated than the visible and particulate tracer techniques. The krypton technique develops histories of concentration at up to 128 field locations; the particulate techniques generate only bulk time integrated samples. The krypton dispersal technique permits release of either a plume or a true puff; the particulate techniques permit continuous releases, but only approximations of puffs through short continuous releases. The Hanford krypton-85 inert gas system offers the advantages of an inert gas tracer, permits release of either puffs or plumes, and presents histories of concentration as opposed to only time-integrated concentrations. However, the approach used has the disadvantages of being usable at only short distances, is a relatively expensive system to deploy and maintain, and is restricted as to locations where it may be used due to the radioactive nature of the tracer

  9. Modelling tracer dispersion from landfills

    OpenAIRE

    Carpentieri, M.; Giambini, P; Corti, A.

    2008-01-01

    Several wind tunnel experiments of tracer dispersion from reduced-scale landfill models are presented in this paper. Different experimental set-ups, hot-wire anemometry, particle image velocimetry and tracer concentration measurements were used for the characterisation of flow and dispersion phenomena nearby the models. The main aim of these experiments is to build an extensive experimental data set useful for model validation purposes. To demonstrate the potentiality of the experimental data...

  10. Accounting for pharmacokinetic differences in dual-tracer receptor density imaging

    Science.gov (United States)

    Tichauer, K. M.; Diop, M.; Elliott, J. T.; Samkoe, K. S.; Hasan, T.; St. Lawrence, K.; Pogue, B. W.

    2014-05-01

    Dual-tracer molecular imaging is a powerful approach to quantify receptor expression in a wide range of tissues by using an untargeted tracer to account for any nonspecific uptake of a molecular-targeted tracer. This approach has previously required the pharmacokinetics of the receptor-targeted and untargeted tracers to be identical, requiring careful selection of an ideal untargeted tracer for any given targeted tracer. In this study, methodology capable of correcting for tracer differences in arterial input functions, as well as binding-independent delivery and retention, is derived and evaluated in a mouse U251 glioma xenograft model using an Affibody tracer targeted to epidermal growth factor receptor (EGFR), a cell membrane receptor overexpressed in many cancers. Simulations demonstrated that blood, and to a lesser extent vascular-permeability, pharmacokinetic differences between targeted and untargeted tracers could be quantified by deconvolving the uptakes of the two tracers in a region of interest devoid of targeted tracer binding, and therefore corrected for, by convolving the uptake of the untargeted tracer in all regions of interest by the product of the deconvolution. Using fluorescently labeled, EGFR-targeted and untargeted Affibodies (known to have different blood clearance rates), the average tumor concentration of EGFR in four mice was estimated using dual-tracer kinetic modeling to be 3.9 ± 2.4 nM compared to an expected concentration of 2.0 ± 0.4 nM. However, with deconvolution correction a more equivalent EGFR concentration of 2.0 ± 0.4 nM was measured.

  11. Evaluation of 4-[{sup 18}F]fluorobenzoyl-FALGEA-NH{sub 2} as a positron emission tomography tracer for epidermal growth factor receptor mutation variant III imaging in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lund Denholt, Charlotte, E-mail: charlotte.lund.denholt@rh.regionh.d [Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen O (Denmark); Binderup, Tina [Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen O (Denmark); Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N (Denmark); Stockhausen, Marie-Therese; Skovgaard Poulsen, Hans [Department of Radiation Biology, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O (Denmark); Spang-Thomsen, Mogens [Institute of Molecular Pathology, University of Copenhagen, 2200 Copenhagen N (Denmark); Hansen, Paul Robert [IGM-Bioorganic Chemistry, Faculty of Life Science, University of Copenhagen, 1871 Frederiksberg C (Denmark); Gillings, Nic [Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen O (Denmark); Kjaer, Andreas [Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Rigshospitalet, 2100 Copenhagen O (Denmark); Cluster for Molecular Imaging, Faculty of Health Sciences, University of Copenhagen, 2200 Copenhagen N (Denmark)

    2011-05-15

    Introduction: This study describes the radiosynthesis, in vitro and in vivo evaluation of the novel small peptide radioligand, 4-[{sup 18}F]fluorobenzoyl-Phe-Ala-Leu-Gly-Glu-Ala-NH{sub 2,} ([{sup 18}F]FBA-FALGEA-NH{sub 2}) as a positron emission tomography (PET) tracer for imaging of the cancer specific epidermal growth factor receptor (EGFR) variant III mutation, EGFRvIII. Methods: For affinity, stability and PET measurements, H-FALGEA-NH{sub 2} was radiolabelled using 4-[{sup 18}F]fluorobenzoic acid ([{sup 18}F]FBA). The binding affinity of ([{sup 18}F]FBA)-FALGEA-NH{sub 2} was measured on EGFRvIII expressing cells, NR6M. Stability studies in vitro and in vivo were carried out in blood plasma from nude mice. PET investigations of [{sup 18}F]FBA-FALGEA-NH{sub 2} were performed on a MicroPET scanner, using seven nude mice xenografted subcutaneously with human glioblastoma multiforme (GBM) tumours, expressing the EGFRvIII in its native form, and five nude mice xenografted subcutaneously with GBM tumours lacking EGFRvIII expression. Images of [{sup 18}F]FDG were also obtained for comparison. The mice were injected with 5-10 MBq of the radiolabelled peptide or [{sup 18}F]FDG. Furthermore, the gene expression of EGFRvIII in the tumours was determined using quantitative real-time PCR. Results: Radiolabelling and purification was achieved within 180 min, with overall radiochemical yields of 2.6-9.8% (decay-corrected) and an average specific radioactivity of 6.4 GBq/{mu}mol. The binding affinity (K{sub d}) of [{sup 18}F]FBA-FALGEA-NH{sub 2} to EGFRvIII expressing cells was determined to be 23 nM. The radiolabelled peptide was moderately stable in the plasma from nude mice where 53% of the peptide was intact after 60 min of incubation in plasma but rapidly degraded in vivo, where no intact peptide was observed in plasma 5 min post-injection. The PET imaging showed that [{sup 18}F]FBA-FALGEA-NH{sub 2} accumulated preferentially in the human GBM xenografts which expressed

  12. Tracers for monitoring the activity of sodium/glucose cotransporters in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Ernest M; Barrio, Jorge R; Hirayama, Bruce A; Kepe, Vladimir

    2014-09-30

    Radiolabeled tracers for sodium/glucose cotransporters (SGLTs), their synthesis, and their use are provided. The tracers are methyl or ethyl pyranosides having an equatorial hydroxyl group at carbon-2 and a C 1 preferred conformation, radiolabeled with .sup.18F, .sup.123I, or .sup.124I, or free hexoses radiolabeled with .sup.18F, .sup.123I, or .sup.124. Also provided are in vivo and in vitro techniques for using these and other tracers as analytical and diagnostic tools to study glucose transport, in health and disease, and to evaluate therapeutic interventions.

  13. Acetyl salicyclic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients

    International Nuclear Information System (INIS)

    Maspin, a 42 kDa protein produced in normal breast cells, has been shown to inhibit the invasion and metastasis of breast cancer in an animal model. Ingestion of acetylsalicylic acid (aspirin) by breast cancer patients has been reported to restore the systemic synthesis of maspin through the stimulation of systemic nitric oxide production. Studies were carried out to determine the effect of aspirin on the incidence of breast cancer metastasis, which is reported to occur in 50% of patients who have previously received chemotherapy, radiation, and/or surgery. Thirty-five female patients (aged 41-65 years) with breast cancer who had previously received these therapies took one 75 mg/70 kg body weight enteric-coated aspirin tablet every 24 h, after an adequate meal, for 3 years. Their plasma nitric oxide and maspin levels were measured. The occurrence of metastasis was ascertained monthly by a qualified oncologist, and confirmed, if necessary, by biopsy. Daily ingestion of aspirin by participants resulted in an increase in maspin levels from 0.95±0.04 to 4.63±0.05 nM after 24 h. These levels were maintained for 3 years. These studies suggest that daily ingestion of aspirin might significantly reduce the incidence of breast cancer metastasis in patients who have previously received anticancer therapies. (author)

  14. Type I Collagen Synthesis Marker Procollagen I N-Terminal Peptide (PINP) in Prostate Cancer Patients Undergoing Intermittent Androgen Suppression

    International Nuclear Information System (INIS)

    Intermittent androgen suppression (IAS) therapy for prostate cancer patients attempts to maintain the hormone dependence of the tumor cells by cycles alternating between androgen suppression (AS) and treatment cessation till a certain prostate-specific antigen (PSA) threshold is reached. Side effects are expected to be reduced, compared to standard continuous androgen suppression (CAS) therapy. The present study examined the effect of IAS on bone metabolism by determinations of serum procollagen I N-terminal peptide (PINP), a biochemical marker of collagen synthesis. A total of 105 treatment cycles of 58 patients with prostate cancer stages ≥pT2 was studied assessing testosterone, PSA and PINP levels at monthly intervals. During phases of AS lasting for up to nine months PSA levels were reversibly reduced, indicating apoptotic regression of the prostatic tumors. Within the first cycle PINP increased at the end of the AS period and peaked in the treatment cessation phase. During the following two cycles a similar pattern was observed for PINP, except a break in collagen synthesis as indicated by low PINP levels in the first months off treatment. Therefore, measurements of the serum PINP concentration indicated increased bone matrix synthesis in response to >6 months of AS, which uninterruptedly continued into the first treatment cessation phase, with a break into each of the following two pauses. In summary, synthesis of bone matrix collagen increases while degradation decreases during off-treatment phases in patients undergoing IAS. Although a direct relationship between bone matrix turnover and risk of fractures is difficult to establish, IAS for treatment of biochemical progression of prostate tumors is expected to reduce osteoporosis in elderly men often at high risk for bone fractures representing a highly suitable patient population for this kind of therapy

  15. Radioactive tracers in the sea

    International Nuclear Information System (INIS)

    Artificial radionuclides introduced to the oceans during the last four decades have proved invaluable tools for study of many processes in marine water columns and sediments. Both global and close-in fallout of radioactivity from atmospheric nuclear weapons testing have distributed these radionuclides widely, and in amounts sufficient to be useful as tracers. An additional source of considerable significance and tracer potential comes from coastal discharges of European nuclear fuel reprocessing wastes. The nature of these sources, types and amounts of radionuclides introduced and the time histories of their introduction generate a variety of tracer distributions which illuminate a broad spectrum of physical and chemical processes active over a wide range of timescales. Depending on their respective chemistries, artificial radionuclides have been demonstrated to exhibit both conservative and non-conservative properties in the oceans. Some examples are given of the uses made of soluble, conservative tracers for the study of oceanic transport processes and of non-conservative tracers for studies of processes which move them to, and mix them within, marine sediments. Sampling and measurement techniques which have been used in these studies are described

  16. Tracers can improve hydraulic fracturing

    International Nuclear Information System (INIS)

    Many methods of measuring or inferring fracture geometry during or after a frac treatment have been developed; however, few are considered practical and cost-effective. Of these techniques, post-treatment tracer and temperature surveys are most common. Problems associated with each are discussed. This article focuses on recent advances in gamma spectroscopy technology which overcome the problems associated with tracer operations. These new techniques resolve the entire gamma ray energy spectrum into distinct channels, thus enabling logging operators to discern gamma ray emissions of multiple isotopes present in the same location

  17. Synthesis and preliminary biological evaluation of radiolabeled O6-benzylguanine derivatives, new potential PET imaging agents for the DNA repair protein O6-alkylguanine-DNA alkyltransferase in breast cancer

    International Nuclear Information System (INIS)

    Novel radiolabeled O6-benzylguanine (O6-BG) derivatives, 2-amino-6-O-[11C]-[(methoxymethyl)benzyloxy]-9-methyl purines ([11C]p-O6-AMMP, 1a; [11C]m-O6-AMMP, 1b; [11C]o-O6-AMMP, 1c), 2-amino-6-O-benzyloxy-9-[11C]-[(methoxycarbonyl)methyl]purine ([11C]ABMMP, 2), and 2-amino-6-O-benzyloxy-9-[11C]-[(4'-methoxycarbonyl)benzyl]purine ([11C]ABMBP, 3), have been synthesized for evaluation as new potential positron emission tomography (PET) imaging agents for the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) in breast cancer. The appropriate precursors for radiolabeling were obtained in two to three steps from starting material 2-amino-6-chloropurine with moderate to excellent chemical yields. Tracers were prepared by O-[11C]methylation of hydroxymethyl or acid precursors using [11C]methyl triflate. Pure target compounds were isolated by solid-phase extraction (SPE) purification procedure in 45-65% radiochemical yields (decay corrected to end of bombardment), and a synthesis time of 20-25 min. The activity of unlabeled standard samples of 1-3 was evaluated via an in vitro AGT oligonucleotide assay. Preliminary findings from biological assay indicate the synthesized analogs have similar strong inhibitory effectiveness on AGT in comparison with the parent compound O6-BG. The results warrant further evaluation of these radiotracers as new potential PET imaging agents for the DNA repair protein AGT in breast cancer in vivo

  18. Size-controlled synthesis of biodegradable nanocarriers for targeted and controlled cancer drug delivery using salting out cation

    Indian Academy of Sciences (India)

    Madasamy Hari Balakrishanan; Mariappan Rajan

    2016-02-01

    Research for synthesis of size-controlled carriers is currently challenging one. In this research paper, a method for size-controlled synthesis of biodegradable nanocarriers is proposed and described. Salting out method is suitable for both hydrophilic and hydrophobic drugs for the encapsulation on carriers. This synthetic method is based on polylactic acid (PLA) and non-ionic carboxymethyl cellulose (CMC) composed by CaCl2 as salting out agent. This method permits size-controlled synthesis of particles between 50 and 400 nm simply by varying the concentration of salting out agents. We have prepared cisplatin (CDDP)-loaded PLA-CMC nanocarriers by salting out method, with varying salting out agent (CaCl2) concentrations as 0.05, 0.2, 0.35 and 0.5 M. The nanocarriers were characterized for their size, surface charge and morphology by atomic force microscope, zeta potential analyser and transmission electron microscope, respectively. The encapsulation efficiency and in-vitro drug-releasing behaviour of the nanocarriers were investigated. The cytotoxicity effect of nanocarriers and drug-loaded nanocarriers was tested against MCF-7 breast cancer cell line.

  19. Tracer-monitored flow titrations.

    Science.gov (United States)

    Sasaki, Milton K; Rocha, Diogo L; Rocha, Fábio R P; Zagatto, Elias A G

    2016-01-01

    The feasibility of implementing tracer-monitored titrations in a flow system is demonstrated. A dye tracer is used to estimate the instant sample and titrant volumetric fractions without the need for volume, mass or peak width measurements. The approach was applied to spectrophotometric flow titrations involving variations of sample and titrant flow-rates (i.e. triangle programmed technique) or concentration gradients established along the sample zone (i.e. flow injection system). Both strategies required simultaneous monitoring of two absorbing species, namely the titration indicator and the dye tracer. Mixing conditions were improved by placing a chamber with mechanical stirring in the analytical path aiming at to minimize diffusional effects. Unlike most of flow-based titrations, the innovation is considered as a true titration, as it does not require a calibration curve thus complying with IUPAC definition. As an application, acidity evaluation in vinegars involving titration with sodium hydroxide was selected. Phenolphthalein and brilliant blue FCF were used as indicator and dye tracer, respectively. Effects of sample volume, titrand/titrant concentrations and flow rates were investigated aiming at improved accuracy and precision. Results were reliable and in agreement with those obtained by a reference titration procedure. PMID:26703261

  20. Green synthesis of graphene and its cytotoxic effects in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Gurunathan S

    2013-03-01

    Full Text Available Sangiliyandi Gurunathan, Jae Woong Han, Vasuki Eppakayala, Jin-Hoi Kim Department of Animal Biotechnology, Konkuk University, Seoul, South Korea Background: This paper describes an environmentally friendly (“green” approach for the synthesis of soluble graphene using Bacillus marisflavi biomass as a reducing and stabilizing agent under mild conditions in aqueous solution. In addition, the study reported here investigated the cytotoxicity effects of graphene oxide (GO and bacterially reduced graphene oxide (B-rGO on the inhibition of cell viability, reactive oxygen species (ROS generation, and membrane integrity in human breast cancer cells. Methods: The reduction of GO was characterized by ultraviolet–visible spectroscopy. Size distribution was analyzed by dynamic light scattering. Further, X-ray diffraction and high-resolution scanning electron microscopy were used to investigate the crystallinity of graphene and the morphologies of prepared graphene, respectively. The formation of defects further supports the bio-functionalization of graphene, as indicated in the Raman spectrum of B-rGO. Surface morphology and the thickness of the GO and B-rGO were analyzed using atomic force microscopy, while the biocompatibility of GO and B-rGO were investigated using WST-8 assays on MCF-7 cells. Finally, cellular toxicity was evaluated by ROS generation and membrane integrity assays. Results: In this study, we demonstrated an environmentally friendly, cost-effective, and simple method for the preparation of water-soluble graphene using bacterial biomass. This reduction method avoids the use of toxic reagents such as hydrazine and hydrazine hydrate. The synthesized soluble graphene was confirmed using various analytical techniques. Our results suggest that both GO and B-rGO exhibit toxicity to MCF-7 cells in a dose-dependent manner, with a dose > 60 µg/mL exhibiting obvious cytotoxicity effects, such as decreasing cell viability, increasing ROS

  1. Synthesis and Characterization of a Bio-Nanocomposite for Cancer Treatment

    DEFF Research Database (Denmark)

    Longo Martins, Murillo

    , hormones, immune conditions, and mutations that occur from metabolism). These causal factors may act together or in sequence to initiate or promote the development of cancer. Cancer is treated with surgery, radiation, chemotherapy, hormone therapy, immune therapy, and targeted therapy. In the case of......Abstract Cancer is one of the biggest public health problems in the whole world. In 2014, about 585,720 Americans are expected to die of cancer, almost 1,600 people per day. Cancer is the second most common cause of death in the US, exceeded only by heart disease, accounting for nearly 1 of every 4...... deaths. Anyone can develop cancer. Since the risk of being diagnosed with cancer increases with age, most cases occur in adults who are middle aged or older. The disease is caused by both external factors (tobacco, infectious organisms, chemicals, and radiation) and internal factors (inherited mutations...

  2. Comparison of different tracer methods in detecting sentinel lymph nodes in gastric cancer%不同示踪法在胃癌前哨淋巴结检测中的应用比较

    Institute of Scientific and Technical Information of China (English)

    程黎阳; 谢正勇; 戴观荣; 赵为国; 王弘; 周宏峰

    2010-01-01

    Objective To explore the optimum sentinel lymph node (SLN) mapping method in gastric cancer. Methods The clinical data of 59 patients who were confirmed with gastric cancer at Guangzhou General Hospital of Guangzhou Military Command from January 2004 to August 2008 were retrospectively analysed. Patent blue V dye was used in 20 patients (group A), technetium-99m sulfur colloid was used in 20 patients (group B),and a combination of patent blue V dye and technetium-99m sulfur colloid were used in 19 patients (group C).The number of SLNs detected, and accuracy and false-negative rate of SLNs in diagnosing regional lymph node metastasis were analysed by t test and chi-square test. Results The numbers of SLNs detected in groups A, B and C were 38 (1.9 per case), 31 (1.6 per case) and 56 (2.9 per case), respectively. In group C, 46 SLNs were screened out by patent blue V dye and technetium-99m sulfur colloid simultaneously, six SLNs were only detected by patent blue V dye and four only by technetium-99m sulfur colloid. There was a significant difference in the number of SLNs detected among the three groups (t = 4.35, P < 0. 05 ). The number of SLNs detected in group C was significantly greater than that in groups A and B (t = 4. 21, 3. 54, P < 0.05 ). The accuracy and false-negative rate of SLNs in diagnosing regional lymph node metastasis were 95% (19/20) and 5% (1/20) in group A, 90% (18/20) and 10% (2/20) in group B, and 100% (19/19) and 0 in group C. The accuracy was significantly higher (x2 = 163.01, P < 0.05) and the false-negative rate was significantly lower in group C compared with those in groups A and B (x2 = 170. 14, P < 0. 05). Conclusion A combination of dye and radioactive tracer is a favorable method for detecting SLNs in gastric cancer.%目的 探讨理想的胃癌前哨淋巴结(SLN)检测方法.方法 前瞻性分析2004年1月至2008年8月广州军区广州总医院确诊的59例胃癌患者的临床资料,按随机数字表

  3. Help seeking behavior of women with self-discovered breast cancer symptoms: a meta-ethnographic synthesis of patient delay.

    Directory of Open Access Journals (Sweden)

    Zohreh Khakbazan

    Full Text Available BACKGROUND AND OBJECTIVE: Patient delay makes a critical contribution to late diagnosis and poor survival in cases of breast cancer. Identifying the factors that influence patient delay could provide information for adopting strategies that shorten this delay. The aim of this meta-ethnography was to synthesize existing qualitative evidence in order to gain a new understanding of help seeking behavior in women with self-discovered breast cancer symptoms and to determine the factors that influence patient delay. METHODS: The design was a meta-ethnography approach. A systematic search of the articles was performed in different databases including Elsevier, PubMed, ProQuest and SCOPUS. Qualitative studies with a focus on help seeking behaviors in women with self-discovered breast cancer symptoms and patient delay, published in the English language between 1990 and 2013 were included. The quality appraisal of the articles was carried out using the Critical Appraisal Skills Programme qualitative research checklist and 13 articles met the inclusion criteria. The synthesis was conducted according to Noblit and Hare's meta-ethnographic approach (1988, through reciprocal translational analysis and lines-of-argument. FINDINGS: The synthesis led to identification of eight repeated key concepts including: symptom detection, initial symptom interpretation, symptom monitoring, social interaction, emotional reaction, priority of medical help, appraisal of health services and personal-environmental factors. Symptom interpretation is identified as the important step of the help seeking process and which changed across the process through active monitoring of their symptoms, social interactions and emotional reactions. The perceived seriousness of the situation, priority to receive medical attention, perceived inaccessibility and unacceptability of the health care system influenced women's decision-making about utilizing health services. CONCLUSION: Help seeking

  4. Modification of non tumoral {sup 18}FMISO biodistribution, a tracer of hypoxia, under Sunitinib in patients with metastatic renal cancer;Modification de la biodistribution non tumorale du {sup 18}FMISO, un traceur d'hypoxie, chez les patients traites par sunitinib pour cancer du rein metastatique

    Energy Technology Data Exchange (ETDEWEB)

    Champion, L.; Hugonnet, F. [Hopital europeen Georges-Pompidou, Service de medecine nucleaire, 75 - Paris (France); Hugonnet, F. [Universite Paris Descartes, 75 - Paris (France)

    2010-04-15

    Objective: The purpose of the study was to find the potential impact of the Sunitinib on the captation of a tracer of the hypoxia, {sup 18}F-FMISO, on non tumoral tissues. Population and methods: It was about a multicentric prospective study on 43 patients with advanced or metastatic renal cancer, treated with Sunitinib. {sup 18}F-FMISO PET/CT scan was performed before treatment, followed with a second PET/CT scan after 4 weeks of treatment with Sunitinib. Results: We have shown a significant increase of FMISO captation under Sunitinib in the lungs (p < 0.02) and the liver (p < 0.001). We have also found a significant increase of FMISO captation under anti-angiogenic (p < 0.02) of the arterial wall partially calcified among 23/37 patients reached of atherosclerosis, without notable cardiovascular events in the follow-up of these patients. On the other hand, we highlighted a significant reduction of FMISO captation in arthrosic lesions (p < 0.05). Conclusion: {sup 18}F-FMISO PET/CT scan could be a good indicator of the potential toxicities of Sunitinib, in particular the pulmonary, hepatic and cardiovascular side effects. It also shows the potential interest of anti-angiogenic in inflammatory rheumatic diseases. (authors)

  5. Phase I and pharmacokinetic study of the polyamine synthesis inhibitor SAM486A in combination with 5-fluorouracil/leucovorin in metastatic colorectal cancer

    NARCIS (Netherlands)

    L. van Zuylen; C. Mueller; J. Verweij (Jaap); J.A. Ledermann; J. Bridgewater; A. Sparreboom (Alex); F.A.L.M. Eskens (Ferry); P. de Bruijn (Peter); I. Sklenar; A.S.Th. Planting (André); L. Choi; D. Bootle

    2004-01-01

    textabstractPURPOSE: The purpose of our study was to determine the maximum-tolerated dose, dose-limiting toxicity, safety profile, and pharmacokinetics of the polyamine synthesis inhibitor SAM486A given in combination with 5-fluorouracil/leucovorin (5-FU/LV) in cancer patients. EXP

  6. Synthesis of Apoptotic New Quinazolinone-Based Compound and Identification of its Underlying Mitochondrial Signalling Pathway in Breast Cancer Cells.

    Science.gov (United States)

    Zahedifard, Maryam; Faraj, Fadhil Lafta; Paydar, Mohammadjavad; Looi, Chung Yeng; Hasandarvish, Pouya; Hajrezaie, Maryam; Kamalidehghan, Behnam; Majid, Nazia Abdul; Khalifa, Shaden A M; Ali, Hapipah Mohd; Abdulla, Mahmood Ameen; El-Seedi, Hesham R

    2015-01-01

    The anti-carcinogenic effect of the new quinazolinone compound, named MMD, was tested on MCF-7 human breast cancer cell line. The synthesis of quinazolinone-based compounds attracted strong attention over the past few decades as an alternative mean to produce analogues of natural products. Quinazolinone compounds sharing the main principal core structures are currently introduced in the clinical trials and pharmaceutical markets as anti-cancer agents. Thus, it is of high clinical interest to identify a new drug that could be used to control the growth and expansion of cancer cells. Quinazolinone is a metabolite derivative resulting from the conjugation of 2-aminobenzoyhydrazide and 5-methoxy-2- hydroxybenzaldehyde based on condensation reactions. In the present study, we analysed the influence of MMD on breast cancer adenoma cell morphology, cell cycle arrest, DNA fragmentation, cytochrome c release and caspases activity. MCF-7 is a type of cell line representing the breast cancer adenoma cells that can be expanded and differentiated in culture. Using different in vitro strategies and specific antibodies, we demonstrate a novel role for MMD in the inhibition of cell proliferation and initiation of the programmed cell death. MMD was found to increase cytochrome c release from the mitochondria to the cytosol and this effect was enhanced over time with effective IC50 value of 5.85 ± 0.71 μg/mL detected in a 72-hours treatment. Additionally, MMD induced cell cycle arrest at G0/G1 phase and caused DNA fragmentation with obvious activation of caspase-9 and caspases-3/7. Our results demonstrate a novel role of MMD as an anti-proliferative agent and imply the involvement of mitochondrial intrinsic pathway in the observed apoptosis. PMID:25808938

  7. Tracer-tracer relations as a tool for research on polar ozone loss

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Rolf

    2010-07-01

    The report includes the following chapters: (1) Introduction: ozone in the atmosphere, anthropogenic influence on the ozone layer, polar stratospheric ozone loss; (2) Tracer-tracer relations in the stratosphere: tracer-tracer relations as a tool in atmospheric research; impact of cosmic-ray-induced heterogeneous chemistry on polar ozone; (3) quantifying polar ozone loss from ozone-tracer relations: principles of tracer-tracer correlation techniques; reference ozone-tracer relations in the early polar vortex; impact of mixing on ozone-tracer relations in the polar vortex; impact of mesospheric intrusions on ozone-tracer relations in the stratospheric polar vortex calculation of chemical ozone loss in the arctic in March 2003 based on ILAS-II measurements; (4) epilogue.

  8. New SPECT tracers: Example of tracers of proteoglycans and melanin

    International Nuclear Information System (INIS)

    The majority of research program on new radiopharmaceuticals turn to tracers used for positron emission tomography (PET). Only a few teams work on new non fluorine labeled tracers. However, the coming of SPECT/CT gamma cameras, the arrival of semi-conductors gamma cameras should boost the development of non-PET tracers. We exhibit in this article the experience acquired by our laboratory in the conception and design of two new non fluorine labelled compounds. The 99mTc-N.T.P. 15-5 (N.T.P. 15-5 for N-[tri-ethyl-ammonium]-3-propyl-[15]ane-N5) which binds to proteoglycans could be used for the diagnosis and staging of osteoarthritis and chondrosarcoma. The iodo benzamides, specific to the melanin, are nowadays compared to 18F-fluorodeoxyglucose in a phase III clinical trial for the diagnosis and detection of melanoma metastasis. Our last development focus on N-[2-(diethyl-amino)ethyl]-4 and 2-iodo benzamides respectively B.Z.A. and B.Z.A.2 hetero-aromatic analogues usable for melanoma treatment. (authors)

  9. Synthesis and Characterization of AICAR and DOX Conjugated Multifunctional Nanoparticles as a Platform for Synergistic Inhibition of Cancer Cell Growth.

    Science.gov (United States)

    Daglioglu, Cenk; Okutucu, Burcu

    2016-04-20

    The success of cancer treatment depends on the response to chemotherapeutic agents. However, malignancies often acquire resistance to drugs if they are used frequently. Combination therapy involving both a chemotherapeutic agent and molecularly targeted therapy may have the ability to retain and enhance therapeutic efficacy. Here, we addressed this issue by examining the efficacy of a novel therapeutic strategy that combines AICAR and DOX within a multifunctional platform. In this context, we reported the bottom-up synthesis of Fe3O4@SiO2(FITC)-FA/AICAR/DOX multifunctional nanoparticles aiming to neutralize survivin (BIRC5) to potentiate the efficacy of DOX against chemoresistance. The structure of nanoparticles was characterized by dynamic light scattering (DLS), zeta-potential measurement, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), and electron microscopy (SEM and STEM with EDX) techniques. Cellular uptake and cytotoxicity experiments demonstrated preferentially targeted delivery of nanoparticles and an efficient reduction of cancer cell viability in five different tumor-derived cell lines (A549, HCT-116, HeLa, Jurkat, and MIA PaCa-2). These results indicate that the multifunctional nanoparticle system possesses high inhibitory drug association and sustained cytotoxic effect with good biocompatibility. This novel approach which combines AICAR and DOX within a single platform might be promising as an antitumor treatment for cancer. PMID:26996194

  10. Synthesis of O-[2-[18F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propyl]tyrosine ([18F]FNT]) as a new class of tracer for imaging hypoxia

    International Nuclear Information System (INIS)

    For detection of hypoxic tumor tissue, all radiotracers synthesized until now, are based on the concept that cellular uptake is being controlled by diffusion. As a new approach, we chose the concept to have the tracer hypothetically transported into the cells by well known carrier systems like the amino acid transporters. For this purpose, radiosynthesis of O-[2-[18F]fluoro-3-(2-nitro-1H-imidazole-1yl)propyl]tyrosine ([18F]FNT]) was carried out from methyl 2-(benzyloxycarbonyl)-3-(4-3-(2-nitro-1H-imidazol-1-yl) -2-(tosyloxy)propoxy) phenyl)propanoate via no-carrier-added nucleophilic aliphatic substitution. After labelling, 81 ± 0.9% of labelled intermediate i.e. methyl 2-(benzyloxycarbonyl)-3-(4-(2-[18F]fluoro-3- (2-nitro-1H-imidazole-1-yl)propoxy) phenyl)propanoate was obtained at 140 deg C. At the end of radiosynthesis, [18F]FNT was obtained in an overall radiochemical yield of 40 ± 0.9% (not decay corrected) within 90 min in a radiochemical purity of >98% in a formulation ready for application in the clinical studies for PET imaging of hypoxia. (author)

  11. Synthesis and Characterization of Inhalable Flavonoid Nanoparticle for Lung Cancer Cell Targeting.

    Science.gov (United States)

    Lee, Wing-Hin; Loo, Ching-Yee; Ong, Hui-Xin; Traini, Daniela; Young, Paul M; Rohanizadeh, Ramin

    2016-02-01

    Current cancer treatments are not adequate to cure cancer disease, as most chemotherapeutic drugs do not differentiate between cancerous and non-cancerous cells; which lead to systemic toxicity and adverse effects. We have developed a promising approach to deliver a potential anti-cancer compound (curcumin) for lung cancer treatment through pulmonary delivery. Three different sizes of curcumin micellar nanoparticles (Cur-NPs) were fabricated and their cytotoxicity effects (proliferation, apoptosis, cell cycle progression) were evaluated against non-small-cell lung cancer, human lung carcinoma (A549) and human lung adenocarcinoma (Calu-3). The in vitro cytotoxicity assay showed that Cur-NPs were more effective to kill lung cancer cells compared to DMSO-solubilised raw curcumin. The potency of the anti-cancer killing activities was size-dependent. Both raw curcumin and Cur-NPs were not toxic to healthy lung cells (BEAS-2B). Smaller Cur-NPs accumulated within nucleus, membrane and cytoplasm. Cur-NPs also induced apoptosis and caused G2/M arrest in both A549 and Calu-3 cell lines. Compared to raw curcumin, Cur-NPs were more effective in suppressing the expression of the inflammatory marker, Interleukin-8 (IL8). The aerosol performance of Cur-NPs was characterized using the next generation impactor (NGI). All Cur-NPs showed promising aerosolization property with mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) ranging between 4.8-5.2 and 2.0-2.1, respectively. This study suggests that inhaled curcumin nanoparticles could potentially be used for lung cancer treatment with minimal side effects. PMID:27305771

  12. Nucleotide excision repair DNA synthesis by excess DNA polymerase beta: a potential source of genetic instability in cancer cells.

    Science.gov (United States)

    Canitrot, Y; Hoffmann, J S; Calsou, P; Hayakawa, H; Salles, B; Cazaux, C

    2000-09-01

    The nucleotide excision repair pathway contributes to genetic stability by removing a wide range of DNA damage through an error-free reaction. When the lesion is located, the altered strand is incised on both sides of the lesion and a damaged oligonucleotide excised. A repair patch is then synthesized and the repaired strand is ligated. It is assumed that only DNA polymerases delta and/or epsilon participate to the repair DNA synthesis step. Using UV and cisplatin-modified DNA templates, we measured in vitro that extracts from cells overexpressing the error-prone DNA polymerase beta exhibited a five- to sixfold increase of the ultimate DNA synthesis activity compared with control extracts and demonstrated the specific involvement of Pol beta in this step. By using a 28 nt gapped, double-stranded DNA substrate mimicking the product of the incision step, we showed that Pol beta is able to catalyze strand displacement downstream of the gap. We discuss these data within the scope of a hypothesis previously presented proposing that excess error-prone Pol beta in cancer cells could perturb the well-defined specific functions of DNA polymerases during error-free DNA transactions. PMID:10973926

  13. Effect of Eicosapentaenoic Acid on E-type Prostaglandin Synthesis and EP4 Receptor Signaling Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Gillian Hawcroft

    2010-08-01

    Full Text Available The ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA, in the free fatty acid (FFA form, has been demonstrated to reduce adenoma number and size in patients with familial adenomatous polyposis. However, the mechanistic basis of the antineoplastic activity of EPA in the colorectum remains unclear. We tested the hypothesis that EPAFFA negatively modulates synthesis of and signaling by prostaglandin (PG E2 in human colorectal cancer (CRC cells. EPA-FFA induced apoptosis of cyclooxygenase (COX-2-positive human HCA-7 CRC cells in vitro. EPA-FFA in cell culture medium was incorporated rapidly into phospholipid membranes of HCA-7 human CRC cells and acted as a substrate for COX-2, leading to reduced synthesis of PGE2 and generation of PGE3. Alone, PGE3 bound and activated the PGE2 EP4 receptor but with reduced affinity and efficacy compared with its “natural” ligand PGE2. However, in the presence of PGE2, PGE3 acted as an antagonist of EP4 receptor-dependent 3’,5’ cyclic adenosine monophosphate induction in naturally EP4 receptor-positive LoVo human CRC cells and of resistance to apoptosis in HT-29-EP4 human CRC cells overexpressing the EP4 receptor. We conclude that EPA-FFA drives a COX-2dependent “PGE2-to-PGE3 switch” in human CRC cells and that PGE3 acts as a partial agonistat the PGE2 EP4 receptor.

  14. Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics

    International Nuclear Information System (INIS)

    In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future. - Highlights: • Biosynthesis of gold and silver nanoparticles using plant leaf extract • The approach is clean, efficient, eco-friendly & economically safe. • Biosynthesized nanoparticles are biocompatible towards normal and cancer cells. • Design and development of biosynthesized nanoparticle based drug delivery systems • Biosynthesized nanoparticles could be useful for cancer and other diseases

  15. Green synthesis, characterization of gold and silver nanoparticles and their potential application for cancer therapeutics

    Energy Technology Data Exchange (ETDEWEB)

    Patra, Sujata; Mukherjee, Sudip; Barui, Ayan Kumar; Ganguly, Anirban [Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India); Sreedhar, Bojja [Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India); Patra, Chitta Ranjan, E-mail: crpatra@iict.res.in [Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana State (India)

    2015-08-01

    In the present article, we demonstrate the delivery of anti-cancer drug to the cancer cells using biosynthesized gold and silver nanoparticles (b-AuNP & b-AgNP). The nanoparticles synthesized by using Butea monosperma (BM) leaf extract are thoroughly characterized by various analytical techniques. Both b-AuNP and b-AgNP are stable in biological buffers and biocompatible towards normal endothelial cells (HUVEC, ECV-304) as well as cancer cell lines (B16F10, MCF-7, HNGC2 & A549). Administration of nanoparticle based drug delivery systems (DDSs) using doxorubicin (DOX) [b-Au-500-DOX and b-Ag-750-DOX] shows significant inhibition of cancer cell proliferation (B16F10, MCF-7) compared to pristine drug. Therefore, we strongly believe that biosynthesized nanoparticles will be useful for the development of cancer therapy using nanomedicine approach in near future. - Highlights: • Biosynthesis of gold and silver nanoparticles using plant leaf extract • The approach is clean, efficient, eco-friendly & economically safe. • Biosynthesized nanoparticles are biocompatible towards normal and cancer cells. • Design and development of biosynthesized nanoparticle based drug delivery systems • Biosynthesized nanoparticles could be useful for cancer and other diseases.

  16. Genetic variation in genes of the fatty acid synthesis pathway and breast cancer risk

    DEFF Research Database (Denmark)

    Campa, Daniele; McKay, James; Sinilnikova, Olga;

    2009-01-01

    FASN) is related to breast cancer risk and body-mass index (BMI) by studying 1,294 breast cancer cases and 2,452 controls from the European Prospective Investigation on Cancer (EPIC). We resequenced the FAS gene and combined information of SNPs found by resequencing and SNPs from public databases....... Using a tagging approach and selecting 20 SNPs, we covered all the common genetic variation of these genes. In this study we were not able to find any statistically significant association between the SNPs in the FAS, ChREBP and SREPB-1 genes and an increased risk of breast cancer overall and by......Fatty acid synthase (FAS) is the major enzyme of lipogenesis. It catalyzes the NADPH-dependent condensation of acetyl-CoA and malonyl-CoA to produce palmitic acid. Transcription of the FAS gene is controlled synergistically by the transcription factors ChREBP (carbohydrate response element...

  17. A qualitative synthesis of the evidence behind elective lymph node irradiation in oesophageal cancer

    International Nuclear Information System (INIS)

    Background and purpose: Oesophageal cancer is the sixth leading cause of cancer death worldwide and radiotherapy plays a prominent role in its treatment. The presence of lymph node (LN) metastasis has been demonstrated to be one of the most significant prognostic factors related to oesophageal cancer. The use of elective lymph node irradiation (ENI) is still a topic of persistent controversy. The conservative school is to irradiate positive lymph nodes only; the other school is to prophylactically irradiate the regional lymph node area according to different tumour sites. This review investigated the justification for including ENI in the treatment of patients with oesophageal cancer. Material and methods: We performed a systematic literature search to find surgical data about lymph node distribution depending on different tumour subgroups: early, cervical, thoracic and gastroesophageal junction cancer. Furthermore, we performed a qualitative assessment of recurrence patterns in patients treated with or without ENI to derive estimates of the potential area at risk for lymph node harvest. Results: We identified and reviewed 49 studies: 10 in early, 8 in cervical, 10 in thoracic and the remaining 21 in gastroesophageal junction cancer. In general, these studies were conclusive in incidence and location of pathologic lymph nodes for different subgroups. Data for lymph node recurrence patterns are scarce and contributed little to our review. Conclusions: This review resulted in five recommendations for radiation oncologists in daily practice. We used the available evidence about metastatic lymph node distribution to develop a careful reasonable radiation protocol for the corresponding tumour subgroups

  18. Design, Synthesis and Evaluation of N13-Substituted Evodiamine Derivatives against Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Senchuan Song

    2013-12-01

    Full Text Available Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF and simulated intestinal fluid (SIF solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3, lung cancer (H460, breast cancer (MCF-7, colon cancer (HCT-5 and glioblastoma (SF-268. The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by 2-2, 2-3, 2-16 and 3-2 was determined. The results showed: (1 among all compounds examined, 2-16 showed the highest antitumor activity and a broader spectrum of activity, with IC50 values ranging from 1–2 µM; (2 their solubility was obviously improved; (3 2-3, 2-16 and 3-2 had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed.

  19. Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer.

    Science.gov (United States)

    Bassetto, Marcella; Ferla, Salvatore; Pertusati, Fabrizio; Kandil, Sahar; Westwell, Andrew D; Brancale, Andrea; McGuigan, Christopher

    2016-08-01

    Prostate cancer (PC) is one of the major causes of male death worldwide and the development of new and more potent anti-PC compounds is a constant requirement. Among the current treatments, (R)-bicalutamide and enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in the case of castration-resistant forms. Both these drugs present a moderate antiproliferative activity and their use is limited due to the development of resistant mutants of their biological target. Insertion of fluorinated and perfluorinated groups in biologically active compounds is a current trend in medicinal chemistry, applied to improve their efficacy and stability profiles. As a means to obtain such effects, different modifications with perfluoro groups were rationally designed on the bicalutamide and enzalutamide structures, leading to the synthesis of a series of new antiproliferative compounds. Several new analogues displayed improved in vitro activity towards four different prostate cancer cell lines, while maintaining full AR antagonism and therefore representing promising leads for further development. Furthermore, a series of molecular modelling studies were performed on the AR antagonist conformation, providing useful insights on potential protein-ligand interactions. PMID:27131065

  20. Tracer tests in karst hydrogeology and speleology

    OpenAIRE

    Christopher Smart; Michiel Pronk; Joe Meiman; Nico Goldscheider

    2008-01-01

    This article presents an introduction to the fundamentals of tracing techniques and their application in cave and karst environments, illustrated by case studies from the Mammoth Cave, USA, and a small experimental site in Switzerland. The properties and limitations of the most important artificial tracers are discussed, and the available methods of tracer injection, sampling, online monitoring and laboratory analysis are presented. Fully quantitative tracer experiments result in continuous o...

  1. Principles and techniques of gamma ray tracers

    International Nuclear Information System (INIS)

    Radioactive tracer techniques provide a very sensitive means of studying physical and chemical processes in a whole variety of different media. Some of the techniques and principles of radioactive tracers and their application to practical engineering systems are discussed. Information which has been found useful in the design of high temperature liquid sodium facilities employing radio-tracers, is presented. The report deals solely with the use of gamma-emitting species as the tracer. These find particular application for in-situ studies on engineering systems where the highly penetrating properties of gamma rays are needed for detection through strongly absorbent media such as stainless steel pepe walls. (author)

  2. Use of artificial tracers in hydrology

    International Nuclear Information System (INIS)

    The IAEA has convened an Advisory Group Meeting with the following objectives: To define the role of artificial radioactive tracers for water tracing in comparison with other non-radioactive tracers. To evaluate the real needs of artificial radioactive tracers in hydrology. To identify the fields for which artificial radioactive tracers are useful as well as those in which they can be substituted by other tracers. To discuss the strategy to be adopted to overcome the difficulties derived from the restrictions on the use of radioactive tracers in hydrology. The meeting was held at IAEA Headquarters from 19 to 22 March 1990, and was attended by 30 participants from 15 Member States. The conclusions and recommendations are that the use of artificial radioactive tracers should be restricted to cases where other tracers cannot be used or do not provide the same quality of information. Tritium, iodine-131, bromine-82, chromium-51 in the form of Cr-EDTA, technetium-99m obtained from 99Mo-generators and gold-198 as an adsorbable tracer are, practically, the only radionuclides used for water tracing. The use of other radionuclides for this purpose does not appear to be necessary, possible and/or convenient. Refs, figs and tabs

  3. Quadratic tracer dynamical models tobacco growth

    International Nuclear Information System (INIS)

    In order to study the non-uniformly transferring process of some tracer dosages, we assume that the absorption of some tracer by tobacco is a quadratic function of the tracer quantity of the tracer in the case of fast absorption, whereas the exclusion of the tracer from tobacco is a linear function of the tracer quantity in the case of slow exclusion, after the tracer is introduced into tobacco once at zero time. A single-compartment quadratic dynamical model of Logistic type is established for the leaves of tobacco. Then, a two-compartment quadratic dynamical model is established for leaves and calms of the tobacco. Qualitative analysis of the models shows that the tracer applied to the leaves of the tobacco is excluded finally; however, the tracer stays at the tobacco for finite time. Two methods are also given for computing the parameters in the models. Finally, the results of the models are verified by the 32P experiment for the absorption of tobacco. (authors)

  4. Tracer a application in marine outfall studies

    International Nuclear Information System (INIS)

    The applicability of radioactive and fluorescent tracers for field studies to predict or investigate waste water transport and dispersion from marine outfalls is evaluated. The application of either instantaneous or continuous tracer release, 'in situ' detection of tracers and data processing are considered. The necessity of a combined use of tracer techniques and conventional hydrographic methods for a statistical prediction of transport and dillution of waste water are pointed out. A procedure to determine an outlet distance from the coast, which satisfy bathing water criteria is outlined. (M.A.)

  5. Curcumin-loaded silica-based mesoporous materials: Synthesis, characterization and cytotoxic properties against cancer cells.

    Science.gov (United States)

    Bollu, Vishnu Sravan; Barui, Ayan Kumar; Mondal, Sujan Kumar; Prashar, Sanjiv; Fajardo, Mariano; Briones, David; Rodríguez-Diéguez, Antonio; Patra, Chitta Ranjan; Gómez-Ruiz, Santiago

    2016-06-01

    Two different silica based (MSU-2 and MCM-41) curcumin loaded mesoporous materials V3 and V6 were synthesized and characterized by several physico-chemical techniques. Release kinetic study revealed the slow and sustained release of curcumin from those materials in blood simulated fluid (pH: 7.4). The materials V3 and V6 were found to be biocompatible in non-cancerous CHO cell line while exhibiting significant cytotoxicity in different cancer cells (human lung carcinoma cells: A549, human breast cancer cells: MCF-7, mouse melanoma cells: B16F10) compared to pristine curcumin indicating the efficacy of the mesoporous silica materials based drug delivery systems (DDSs). The generation of intracellular reactive oxygen species (ROS) and down regulation of anti-apoptotic protein leading to the induction of apoptosis were found to be the plausible mechanisms behind the anti-cancer activity of these DDSs. These results suggest that curcumin-loaded drug delivery system may be successfully employed as an alternative treatment strategy for cancer therapeutics through a nanomedicine approach in near future. PMID:27040234

  6. Methotrexate-conjugated quantum dots: synthesis, characterisation and cytotoxicity in drug resistant cancer cells.

    Science.gov (United States)

    Johari-Ahar, Mohammad; Barar, Jaleh; Alizadeh, Ali Mohammad; Davaran, Soodabeh; Omidi, Yadollah; Rashidi, Mohammad-Reza

    2016-01-01

    Methotrexate (MTX), a folic acid derivative, is a potent anticancer used for treatment of different malignancies, but possible initiation of drug resistance to MTX by cancer cells has limited its applications. Nanoconjugates (NCs) of MTX to quantum dots (QDs) may favour the cellular uptake via folate receptors (FRs)-mediated endocytosis that circumvents the efflux functions of cancer cells. We synthesised MTX-conjugated l-cysteine capped CdSe QDs (MTX-QD nanoconjugates) and evaluated their internalisation and cytotoxicity in the KB cells with/without resistancy to MTX. The NCs were fully characterised by high resolution transmission electron microscopy (HR-TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and optical spectroscopy. Upon conjugation with MTX, the photoluminescence (PL) properties of QDs altered, while an obvious quenching in PL of QDs was observed after physical mixing. The MTX-QD nanoconjugates efficiently internalised into the cancer cells, and induced markedly high cytotoxicity (IC50, 12.0 µg/mL) in the MTX-resistant KB cells as compared to the free MTX molecules (IC50,105.0 µg/mL), whereas, these values were respectively about 7.0 and 0.6 µg/mL in the MTX-sensitive KB cells. Based on these findings, the MTX-QD nanoconjugates are proposed for the targeted therapy of MTX-resistant cancers, which may provide an improved outcome in the relapsed FR-overexpressing cancers. PMID:26176269

  7. Breakthrough Cancer Pain (BTcP): a Synthesis of Taxonomy, Pathogenesis, Therapy, and Good Clinical Practice in Adult Patients in Italy

    OpenAIRE

    Zucco, Furio; Bonezzi, Cesare; Fornasari, Diego

    2014-01-01

    Pain presents in 80% of patients with advanced cancer, and 30% have periods of increased pain due to fluctuating intensity, known as breakthrough cancer pain (BTcP). BTcP is high-intensity, short-duration pain occurring in several episodes per day and is non-responsive to treatment. The clinical approach to BTcP is variable. A review of the literature was performed to provide clinicians and practitioners with a rational synthesis of the ongoing scientific debate on BTcP and to provide a basis...

  8. Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells.

    Science.gov (United States)

    McKeon, Aoife M; Egan, Alan; Chandanshive, Jay; McMahon, Helena; Griffith, Darren M

    2016-01-01

    We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70), pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i) moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii) significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ. PMID:27455212

  9. Novel Improved Synthesis of HSP70 Inhibitor, Pifithrin-μ. In Vitro Synergy Quantification of Pifithrin-μ Combined with Pt Drugs in Prostate and Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Aoife M. McKeon

    2016-07-01

    Full Text Available We describe a novel improved approach to the synthesis of the important and well-known heat shock protein 70 inhibitor (HSP70, pifithrin-μ, with corresponding and previously unreported characterisation. The first example of a combination study comprising HSP70 inhibitor pifithrin-μ and cisplatin or oxaliplatin is reported. We have determined, using the Chou-Talalay method, (i moderate synergistic and synergistic effects in co-treating PC-3 prostate cancer cells with pifithrin-μ and cisplatin and (ii significant synergistic effects including strong synergism in cotreating HT29 colorectal cancer cells with oxaliplatin and pifithrin-μ.

  10. Synthesis of Chromonylthiazolidines and Their Cytotoxicity to Human Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Hoang Le Tuan Anh

    2015-01-01

    Full Text Available Nine new chromonylthiazolidine derivatives were successfully semi-synthesized from paeonol. All of the compounds, including starting materials, the intermediate compound and products, were evaluated for their cytotoxic effects toward eight human cancer cell lines. The synthesized chromonylthiazolidines displayed weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compounds 3a and 3b showed the most selective cytotoxic effects against human epidermoid carcinoma (IC50 44.1 ± 3.6 μg/mL and breast cancer (IC50 32.8 ± 1.4 μg/mL cell lines, respectively. The results suggest that chromoylthiazolidines are potential low-cost, and selective anticancer agents.

  11. Discovery of MK-3168: A PET Tracer for Imaging Brain Fatty Acid Amide Hydrolase.

    Science.gov (United States)

    Liu, Ping; Hamill, Terence G; Chioda, Marc; Chobanian, Harry; Fung, Selena; Guo, Yan; Chang, Linda; Bakshi, Raman; Hong, Qingmei; Dellureficio, James; Lin, Linus S; Abbadie, Catherine; Alexander, Jessica; Jin, Hong; Mandala, Suzanne; Shiao, Lin-Lin; Li, Wenping; Sanabria, Sandra; Williams, David; Zeng, Zhizhen; Hajdu, Richard; Jochnowitz, Nina; Rosenbach, Mark; Karanam, Bindhu; Madeira, Maria; Salituro, Gino; Powell, Joyce; Xu, Ling; Terebetski, Jenna L; Leone, Joseph F; Miller, Patricia; Cook, Jacquelynn; Holahan, Marie; Joshi, Aniket; O'Malley, Stacey; Purcell, Mona; Posavec, Diane; Chen, Tsing-Bau; Riffel, Kerry; Williams, Mangay; Hargreaves, Richard; Sullivan, Kathleen A; Nargund, Ravi P; DeVita, Robert J

    2013-06-13

    We report herein the discovery of a fatty acid amide hydrolase (FAAH) positron emission tomography (PET) tracer. Starting from a pyrazole lead, medicinal chemistry efforts directed toward reducing lipophilicity led to the synthesis of a series of imidazole analogues. Compound 6 was chosen for further profiling due to its appropriate physical chemical properties and excellent FAAH inhibition potency across species. [(11)C]-6 (MK-3168) exhibited good brain uptake and FAAH-specific signal in rhesus monkeys and is a suitable PET tracer for imaging FAAH in the brain. PMID:24900701

  12. Effects of the source of energy and minerals on microbial protein synthesis in rumen using 35S as indicator. Part of a coordinated programme on tracer techniques in studies on the use of non-protein nitrogen in ruminants

    International Nuclear Information System (INIS)

    Part I. The effect of the nature of carbohydrates and minerals on microbial growth in vitro was studied in vitro to intensify rumen microbial protein synthesis from non-protein nitrogen, using phosphorus incorporation (PR). The nature of starch greatly influences urea utilization. Among the tropical tubers studied, yam Cayenesis and canna Edulis give lower urea utilization than cassava and yam Dumetorum. However, this can be improved by processing. The effects are greatest when the proportion of urea to processed cereal is ca. 4-5%. S-addition as sulfate improves urea utilization with both natural and purified diets. Part II. Results from the Jouy and Ghent laboratories were analyzed statistically, to check the accuracy of the 32P method for estimating microbial growth, using protein-free substrates. The linear relationship between PR and every other variable was studied. Two multivariate analyses, principal components and multiple regression, were applied. Net NH3 utilization was predicted using the equations for substrates with proteins likely to be degraded. This method appears more accurate than using the N/P ratio in microflora. Equations should only be used under the specific experiments described

  13. Tracers for Characterizing Enhanced Geothermal Systems

    Energy Technology Data Exchange (ETDEWEB)

    Karen Wright; George Redden; Carl D. Palmer; Harry Rollins; Mark Stone; Mason Harrup; Laurence C. Hull

    2010-02-01

    Information about the times of thermal breakthrough and subsequent rates of thermal drawdown in enhanced geothermal systems (EGS) is necessary for reservoir management, designing fracture stimulation and well drilling programs, and forecasting economic return. Thermal breakthrough in heterogeneous porous media can be estimated using conservative tracers and assumptions about heat transfer rates; however, tracers that undergo temperature-dependent changes can provide more detailed information about the thermal profile along the flow path through the reservoir. To be effectively applied, the thermal reaction rates of such temperature sensitive traces must be well characterized for the range of conditions that exist in geothermal systems. Reactive tracers proposed in the literature include benzoic and carboxylic acids (Adams) and organic esters and amides (Robinson et al.); however, the practical temperature range over which these tracers can be applied (100-275°C) is somewhat limited. Further, for organic esters and amides, little is known about their sorption to the reservoir matrix and how such reactions impact data interpretation. Another approach involves tracers where the reference condition is internal to the tracer itself. Two examples are: 1) racemization of polymeric amino acids, and 2) mineral thermoluminescence. In these cases internal ratios of states are measured rather than extents of degradation and mass loss. Racemization of poly-L-lactic acid (for example) is temperature sensitive and therefore can be used as a temperature-recording tracer depending on the rates of racemization and stability of the amino acids. Heat-induced quenching of thermoluminescence of pre-irradiated LiF can also be used. To protect the tracers from alterations (extraneous reactions, dissolution) in geothermal environments we are encapsulating the tracers in core-shell colloidal structures that will subsequently be tested for their ability to be transported and to protect the

  14. Metformin inhibition of mTORC1 activation, DNA synthesis and proliferation in pancreatic cancer cells: Dependence on glucose concentration and role of AMPK

    Energy Technology Data Exchange (ETDEWEB)

    Sinnett-Smith, James; Kisfalvi, Krisztina; Kui, Robert [Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, CA (United States); Rozengurt, Enrique, E-mail: erozengurt@mednet.ucla.edu [Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, CA (United States)

    2013-01-04

    Highlights: Black-Right-Pointing-Pointer Metformin inhibits cancer cell growth but the mechanism(s) are not understood. Black-Right-Pointing-Pointer We show that the potency of metformin is sharply dependent on glucose in the medium. Black-Right-Pointing-Pointer AMPK activation was enhanced in cancer cells incubated in physiological glucose. Black-Right-Pointing-Pointer Reciprocally, metformin potently inhibited mTORC1, DNA synthesis and proliferation. Black-Right-Pointing-Pointer Metformin, at low concentrations, inhibited DNA synthesis through AMPK. -- Abstract: Metformin, a widely used anti-diabetic drug, is emerging as a potential anticancer agent but the mechanisms involved remain incompletely understood. Here, we demonstrate that the potency of metformin induced AMPK activation, as shown by the phosphorylation of its substrates acetyl-CoA carboxylase (ACC) at Ser{sup 79} and Raptor at Ser{sup 792}, was dramatically enhanced in human pancreatic ductal adenocarcinoma (PDAC) cells PANC-1 and MiaPaCa-2 cultured in medium containing physiological concentrations of glucose (5 mM), as compared with parallel cultures in medium with glucose at 25 mM. In physiological glucose, metformin inhibited mTORC1 activation, DNA synthesis and proliferation of PDAC cells stimulated by crosstalk between G protein-coupled receptors and insulin/IGF signaling systems, at concentrations (0.05-0.1 mM) that were 10-100-fold lower than those used in most previous reports. Using siRNA-mediated knockdown of the {alpha}{sub 1} and {alpha}{sub 2} catalytic subunits of AMPK, we demonstrated that metformin, at low concentrations, inhibited DNA synthesis through an AMPK-dependent mechanism. Our results emphasize the importance of using medium containing physiological concentrations of glucose to elucidate the anticancer mechanism of action of metformin in pancreatic cancer cells and other cancer cell types.

  15. The Histone H3 Methyltransferase G9A Epigenetically Activates the Serine-Glycine Synthesis Pathway to Sustain Cancer Cell Survival and Proliferation

    OpenAIRE

    Ding, Jane; Li, Tai; Wang, Xiangwei; Zhao, Erhu; Choi, Jeong-Hyeon; Yang, Liqun; Zha, Yunhong; Zheng DONG; Huang, Shuang; John M. Asara; CUI, HONGJUAN; Ding, Han-Fei

    2013-01-01

    Increased activation of the serine-glycine biosynthetic pathway is an integral part of cancer metabolism that drives macromolecule synthesis needed for cell proliferation. Whether this pathway is under epigenetic control is unknown. Here we show that the histone H3 lysine 9 (H3K9) methyltransferase G9A is required for maintaining the pathway enzyme genes in an active state marked by H3K9 monomethylation and for the transcriptional activation of this pathway in response to serine deprivation. ...

  16. The design and synthesis of novel N-heterocyclic compounds, and their evaluation of anti-cancer and anti-viral activity

    OpenAIRE

    More, Vijaykumar

    2014-01-01

    2010 - 2011 The thesis entitled “The design and synthesis of novel N-heterocyclic compounds, and their evaluation of anti-cancer and anti-viral activity" is divided into three chapters. The title of the thesis clearly reflects the importance of nitrogen heterocycles compounds: in fact they are extremely pivotal structural motifs responsible for eliciting various biological activities in natural products and synthetic medicines. This has attracted the medicinal chemists towards the synth...

  17. Metformin inhibition of mTORC1 activation, DNA synthesis and proliferation in pancreatic cancer cells: Dependence on glucose concentration and role of AMPK

    International Nuclear Information System (INIS)

    Highlights: ► Metformin inhibits cancer cell growth but the mechanism(s) are not understood. ► We show that the potency of metformin is sharply dependent on glucose in the medium. ► AMPK activation was enhanced in cancer cells incubated in physiological glucose. ► Reciprocally, metformin potently inhibited mTORC1, DNA synthesis and proliferation. ► Metformin, at low concentrations, inhibited DNA synthesis through AMPK. -- Abstract: Metformin, a widely used anti-diabetic drug, is emerging as a potential anticancer agent but the mechanisms involved remain incompletely understood. Here, we demonstrate that the potency of metformin induced AMPK activation, as shown by the phosphorylation of its substrates acetyl-CoA carboxylase (ACC) at Ser79 and Raptor at Ser792, was dramatically enhanced in human pancreatic ductal adenocarcinoma (PDAC) cells PANC-1 and MiaPaCa-2 cultured in medium containing physiological concentrations of glucose (5 mM), as compared with parallel cultures in medium with glucose at 25 mM. In physiological glucose, metformin inhibited mTORC1 activation, DNA synthesis and proliferation of PDAC cells stimulated by crosstalk between G protein-coupled receptors and insulin/IGF signaling systems, at concentrations (0.05–0.1 mM) that were 10–100-fold lower than those used in most previous reports. Using siRNA-mediated knockdown of the α1 and α2 catalytic subunits of AMPK, we demonstrated that metformin, at low concentrations, inhibited DNA synthesis through an AMPK-dependent mechanism. Our results emphasize the importance of using medium containing physiological concentrations of glucose to elucidate the anticancer mechanism of action of metformin in pancreatic cancer cells and other cancer cell types.

  18. Synthesis, characterization, and application of novel biodegradable self-assembled 2-(N-phthalimido) ethyl-palmitate nanoparticles for cancer therapy

    International Nuclear Information System (INIS)

    We report the synthesis of novel biodegradable nanoparticles (NPs) which can kill the cancer cells without any additional drug loading. The NP was a self-assembled form of a phthalimide based conjugate, in which the phthalimide moiety was responsible for the anticancer activity. We describe the synthesis of a novel 2-(N-phthalimido) ethyl palmitate (PHEP-Pal) conjugate and subsequent preparation of NPs by a simple self assembly process. The successful synthesis of conjugate was confirmed by various characterization studies including nuclear magnetic resonance spectroscope, Fourier transform infrared spectroscope, TOF-liquid chromatography mass spectroscope, differential scanning calorimetry, and X-ray diffraction unit. The synthesis, shape, size, and size distribution of PHEP-Pal NPs were determined by transmission electron microscope, atomic force microscope, and dynamic light scattering technique. Finally, cell culture studies using A549 and HeLa cells were done to evaluate the anticancer effect of PHEP-Pal NPs, which demonstrated the potency of these NPs for use in cancer chemotherapy.

  19. Bottom-Up Synthesis of Metal-Ion-Doped WS₂ Nanoflakes for Cancer Theranostics.

    Science.gov (United States)

    Cheng, Liang; Yuan, Chao; Shen, Sida; Yi, Xuan; Gong, Hua; Yang, Kai; Liu, Zhuang

    2015-11-24

    Recently, two-dimensional transition metal dichalcogenides (TMDCs) have received tremendous attention in many fields including biomedicine. Herein, we develop a general method to dope different types of metal ions into WS2 nanoflakes, a typical class of TMDCs, and choose Gd(3+)-doped WS2 (WS2:Gd(3+)) with polyethylene glycol (PEG) modification as a multifunctional agent for imaging-guided combination cancer treatment. While WS2 with strong near-infrared (NIR) absorbance and X-ray attenuation ability enables contrasts in photoacoustic (PA) imaging and computed tomography (CT), Gd(3+) doping offers the nanostructure a paramagnetic property for magnetic resonance (MR) imaging. As revealed by trimodal PA/CT/MR imaging, WS2:Gd(3+)-PEG nanoflakes showed efficient tumor homing after intravenous injection. In vivo cancer treatment study further uncovered that WS2:Gd(3+)-PEG could not only convert NIR light into heat for photothermal therapy (PTT) but also enhance the ionizing irradiation-induced tumor damage to boost radiation therapy (RT). Owing to the improved tumor oxygenation after the mild PTT, the combination of PTT and RT induced by WS2:Gd(3+)-PEG resulted in a remarkable synergistic effect to destroy cancer. Our work highlights the promise of utilizing inherent physical properties of TMDC-based nanostructures, whose functions could be further enriched by elementary doping, for applications in multimodal bioimaging and synergistic cancer therapy. PMID:26445029

  20. Synthesis and Biological Evaluation of Retinoid-Chalcones as Inhibitors of Colon Cancer Cell Growth

    Science.gov (United States)

    Based on the observed anticancer activity of chalcones and retinoids, a novel class of retinoid-chalcone hybrids were designed and synthesized. As part of our ongoing studies to discover natural product based anticancer compounds, the retinoid-chalcone hybrids were tested against the colon cancer ce...

  1. Advances of small-molecule protein kinase inhibitor-based PET tracers with prospective application in pancreatic cancer%蛋白激酶小分子抑制剂PET显像研究进展及其在胰腺癌诊断中的应用前景

    Institute of Scientific and Technical Information of China (English)

    李詝; 朱朝晖; 李方

    2015-01-01

    Pancreatic cancer is one of the most common malignancies of digestive tract. The targeted therapeutic drugs and specific diagnostic probes for pancreatic cancer include antibodies, affinity ligands, polypeptides, and small-molecule protein kinase inhibitors. The research on small-molecule protein kinase inhibitors is a hot topic of both preclinical research and clinical application in recent years. The advances in this area were briefly reviewed in this article. Data indicated that H-89, a kind of isoquinoline sulfonamide small molecule, might be one of the best small-molecule protein kinase inhibitors to treat pancreatic cancer, and if labeled with positron emitter, it might become a potential PET tracer for pancreatic cancer.%胰腺癌为消化道较常见的恶性肿瘤。针对胰腺癌特异性诊断探针和靶向治疗的药物研究包括抗体、亲和体、多肽以及小分子化合物抑制剂,其中针对蛋白激酶的小分子抑制剂的研究备受关注。笔者综述了这一方向的PET示踪剂的研究进展,其中H-89作为异喹啉磺酰基类小分子化合物,可能是最好的胰腺癌蛋白激酶小分子抑制剂之一,用正电子核素标记后,可能成为较有潜力的胰腺癌PET示踪剂。

  2. Design, Synthesis, and Characterization of Folate-Targeted Platinum-Loaded Theranostic Nanoemulsions for Therapy and Imaging of Ovarian Cancer.

    Science.gov (United States)

    Patel, Niravkumar R; Piroyan, Aleksandr; Nack, Abbegial H; Galati, Corin A; McHugh, Mackenzi; Orosz, Samantha; Keeler, Amanda W; O'Neal, Sara; Zamboni, William C; Davis, Barbara; Coleman, Timothy P

    2016-06-01

    Platinum (Pt) based chemotherapy is widely used to treat many types of cancer. Pt therapy faces challenges such as dose limiting toxicities, cumulative side effects, and multidrug resistance. Nanoemulsions (NEs) have tremendous potential in overcoming these challenges as they can be designed to improve circulation time, limit non-disease tissue uptake, and enhance tumor uptake by surface modification. We designed novel synthesis of three difattyacid platins, dimyrisplatin, dipalmiplatin, and distearyplatin, suitable for encapsulation in the oil core of an NE. The dimyrisplatin, dipalmiplatin, and distearyplatin were synthesized, characterized, and loaded into the oil core of our NEs, NMI-350, NMI-351, and NMI-352 respectively. Sequestration of the difattyacid platins was accomplished through high energy microfluidization. To target the NE, FA-PEG3400-DSPE was incorporated into the surface during microfluidization. The FA-NEs selectively bind the folate receptor α (FR-α) and utilize receptor mediated endocytosis to deliver Pt past cell surface resistance mechanisms. FR-α is overexpressed in a number of oncological conditions including ovarian cancer. The difattyacid platins, lipidated Gd-DTPA, and lipidated folate were characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS), and elemental analysis. NEs were synthesized using high shear microfluidization process and characterized for size, zeta-potential, and loading efficiency. In vitro cytotoxicity was determined using KB-WT (Pt-sensitive) and KBCR-1000 (Pt-resistant) cancer cells and measured by MTT assay. Pharmacokinetic profiles were studied in CD-1 mice. NEs loaded with difattyacid platins are highly stable and had size distribution in the range of ∼120 to 150 nm with low PDI. Cytotoxicity data indicates the longer the fatty acid chains, the less potent the NEs. The inclusion of C6-ceramide, an apoptosis enhancer, and surface functionalization with folate molecules significantly increased

  3. Photothermal cancer therapy using graphitic carbon–coated magnetic particles prepared by one-pot synthesis

    Directory of Open Access Journals (Sweden)

    Lee HJ

    2014-12-01

    Full Text Available Hyo-Jeong Lee,1 Jakkid Sanetuntikul,2 Eun-Sook Choi,1 Bo Ram Lee,1 Jung-Hee Kim,1 Eunjoo Kim,1 Sangaraju Shanmugam2 1Nano and Bio Research Division, 2Department of Energy Systems Engineering, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea Abstract: We describe here a simple synthetic strategy for the fabrication of carbon-coated Fe3O4 (Fe3O4@C particles using a single-component precursor, iron (III diethylenetriaminepentaacetic acid complex. Physicochemical analyses revealed that the core of the synthesized particles consists of ferromagnetic Fe3O4 material ranging several hundred nanometers, embedded in nitrogen-doped graphitic carbon with a thickness of ~120 nm. Because of their photothermal activity (absorption of near-infrared [NIR] light, the Fe3O4@C particles have been investigated for photothermal therapeutic applications. An example of one such application would be the use of Fe3O4@C particles in human adenocarcinoma A549 cells by means of NIR-triggered cell death. In this system, the Fe3O4@C can rapidly generate heat, causing >98% cell death within 10 minutes under 808 nm NIR laser irradiation (2.3 W cm-2. These Fe3O4@C particles provided a superior photothermal therapeutic effect by intratumoral delivery and NIR irradiation of tumor xenografts. These results demonstrate that one-pot synthesis of carbon-coated magnetic particles could provide promising materials for future clinical applications and encourage further investigation of this simple method. Keywords: graphitic carbon–encapsulated magnetic nanoparticles, iron oxide, one-pot synthesis, photothermal cancer therapy

  4. In vivo cerebral protein synthesis rates with leucyl-transfer RNA used as a precursor pool: Determination of biochemical parameters to structure tracer kinetic models for positron emission tomography

    International Nuclear Information System (INIS)

    Leucine oxidation and incorporation into proteins were examined in the in vivo rat brain to determine rates and compartmentation of these processes for the purpose of structuring mathematical compartmental models for the noninvasive estimation of in vivo human cerebral protein synthesis rates (CPSR) using positron emission tomography (PET). Leucine specific activity (SA) in arterial plasma and intracellular free amino acids, leucyl-tRNA, alpha-ketoisocaproic acid (KIC), and protein were determined in whole brain of the adult rat during the first 35 min after intravenous bolus injection of L-[1-14C]leucine. Incorporation of leucine into proteins accounted for 90% of total brain radioactivity at 35 min. The lack of [14C]KIC buildup indicates that leucine oxidation in brain is transaminase limited. Characteristic specific activities were maximal between 0 to 2 min after bolus injection with subsequent decline following the pattern: plasma leucine greater than or equal to leucyl-tRNA approximately KIC greater than intracellular leucine. The time integral of leucine SA in plasma was about four times that of tissue leucine and twice those of leucyl-tRNA and KIC, indicating the existence of free leucine, leucyl-tRNA, and KIC tissue compartments, communicating directly with plasma, and separate secondary free leucine, leucyl-tRNA, and KIC tissue compartments originating in unlabeled leucine from proteolysis. Therefore, a relatively simple model configuration based on the key assumptions that (a) protein incorporation and catabolism proceed from a precursor pool communicating with the plasma space, and (b) leucine catabolism is transaminase limited is justified for the in vivo assessment of CPSR from exogenous leucine sources using PET in humans

  5. Synthesis and preclinical evaluation of carbon-11 labelled N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine as a PET tracer for NR2B subunit-containing NMDA receptors

    International Nuclear Information System (INIS)

    Introduction: The N-methyl-D-Aspartate (NMDA) receptor plays an important role in learning and memory. Overactivation is thought to play an important role in neurodegenerative disorders such as Alzheimer's disease. Currently, it is not possible to assess N-methyl-D-aspartate receptor (NMDAr) bio-availability in vivo. The purpose of this study was to develop a positron emission tomography (PET) ligand for the NR2B binding site of the NMDA receptor. Methods: N-((5-(4-fluoro-2-methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was radiolabelled with carbon-11 in the phenyl moiety. Biodistribution and blocking studies were carried out in anaesthetized mice and in non-anaesthetized rats. Results: N-((5-(4-fluoro-2-[11C]methoxyphenyl)pyridin-3-yl)methyl)cyclopentanamine was prepared in 49 ± 3% (decay-corrected) yield, affording 4.1 ± 0.3 GBq of formulated product at the end of synthesis with a radiochemical purity of > 99% and with a specific activity of 78 ± 10 GBq/μmol. Conclusion: A new NR2B PET ligand was developed in high yield. [11C]4 readily enters the brain and binds to the NR2B subunit-containing NMDAr in the rodent brain. High sigma-1 receptor binding may, however, limit its future application as a PET probe for imaging the NR2B subunit-containing NMDAr. Anaesthesia has an effect on NMDAr function and therefore can complicate interpretation of preclinical in vivo results. In addition, effects of endogenous compounds cannot be excluded. Despite these potential limitations, further studies are warranted to investigate the values of [11C]4 as an NR2B PET ligand

  6. Tracer investigations of catalytic reactions of hydrocarbons

    International Nuclear Information System (INIS)

    Tracer techniques with 14C-labelled compounds were used to investigate the isomerization of C8-aromatics and reforming of light gasoline. The investigations aimed at determining the selectivity of newly developed catalysts and at elucidating the reaction mechanisms. The appropriate tracer methods are briefly discussed including their theoretical fundamentals

  7. Polarized mixtures with ionic tracers

    Energy Technology Data Exchange (ETDEWEB)

    Magnarelli, Lorenzo [Dipartimento di Ingegneria Meccanica e Strutturale, Universita di Trento, Via Mesiano 77, 38050 Povo, Trento (Italy)], E-mail: lorenzo.magnarelli@ing.unitn.it

    2009-08-14

    A model of a polarized mixture is developed and the effects of migration of ions are also accounted for. The rate of the polarization power in some way furnishes power to the mixture. The electrical external power is calculated and by means of a requirement of invariance of the power, the standard balance laws are deduced. The ions dissolved in the mixture and subject to the electric field are considered like tracers and their migration is discussed. We show that their migration is ruled by the Nernst-Planck equation. In the final section, we adapt the description of the model to the setting of complex bodies and the microstructural evolution equations are derived.

  8. Polarized mixtures with ionic tracers

    International Nuclear Information System (INIS)

    A model of a polarized mixture is developed and the effects of migration of ions are also accounted for. The rate of the polarization power in some way furnishes power to the mixture. The electrical external power is calculated and by means of a requirement of invariance of the power, the standard balance laws are deduced. The ions dissolved in the mixture and subject to the electric field are considered like tracers and their migration is discussed. We show that their migration is ruled by the Nernst-Planck equation. In the final section, we adapt the description of the model to the setting of complex bodies and the microstructural evolution equations are derived.

  9. Specific genes involved in synthesis and editing of heparan sulfate proteoglycans show altered expression patterns in breast cancer

    International Nuclear Information System (INIS)

    The expression of a specific set of genes controls the different structures of heparan sulfate proteoglycans (HSPGs), which are involved in the growth, invasion and metastatic properties of cancerous cells. The purpose of this study is to increase knowledge of HSPG alterations in breast cancer. Twenty-three infiltrating ductal adenocarcinomas (IDCs), both metastatic and non-metastatic were studied. A transcriptomic approach to the structure of heparan sulfate (HS) chains was used, employing qPCR to analyze both the expression of the enzymes involved in their biosynthesis and editing, as well as the proteoglycan core proteins. Since some of these proteoglycans can also carry chondroitin sulfate chains, we extended the study to include the genes involved in the biosynthesis of these glycosaminoglycans. Histochemical techniques were also used to analyze tissular expression of particular genes showing significant expression differences, of potential interest. No significant change in transcription was detected in approximately 70% of analyzed genes. However, 13 demonstrated changes in both tumor types (40% showing more intense deregulation in the metastatic), while 5 genes showed changes only in non-metastatic tumors. Changes were related to 3 core proteins: overexpression of syndecan-1 and underexpression of glypican-3 and perlecan. HS synthesis was affected by lower levels of some 3-O-sulfotransferase transcripts, the expression of NDST4 and, only in non metastatic tumors, higher levels of extracellular sulfatases. Furthermore, the expression of chondroitin sulfate also was considerably affected, involving both the synthesis of the saccharidic chains and sulfations at all locations. However, the pro-metastatic enzyme heparanase did not exhibit significant changes in mRNA expression, although in metastatic tumors it appeared related to increased levels of the most stable form of mRNA. Finally, the expression of heparanase 2, which displays anti-metastatic features

  10. Facile synthesis, pharmacokinetic and systemic clearance evaluation, and positron emission tomography cancer imaging of 64Cu-Au alloy nanoclusters

    Science.gov (United States)

    Zhao, Yongfeng; Sultan, Deborah; Detering, Lisa; Luehmann, Hannah; Liu, Yongjian

    2014-10-01

    Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal biodistribution and significant renal and hepatobiliary excretion. PET imaging showed low non-specific tumor uptake, indicating its potential for active targeting of clinically relevant biomarkers in tumor and metastatic organs.Gold nanoparticles have been widely used for oncological applications including diagnosis and therapy. However, the non-specific mononuclear phagocyte system accumulation and potential long-term toxicity have significantly limited clinical translation. One strategy to overcome these shortcomings is to reduce the size of gold nanoparticles to allow renal clearance. Herein, we report the preparation of 64Cu alloyed gold nanoclusters (64CuAuNCs) for in vivo evaluation of pharmacokinetics, systemic clearance, and positron emission tomography (PET) imaging in a mouse prostate cancer model. The facile synthesis in acqueous solution allowed precisely controlled 64Cu incorporation for high radiolabeling specific activity and stability for sensitive and accurate detection. Through surface pegylation with 350 Da polyethylene glycol (PEG), the 64CuAuNCs-PEG350 afforded optimal

  11. Synthesis and Investigation of Novel Spiro-isoxazolines as Anti-Cancer Agents

    Science.gov (United States)

    Das, Prasanta; Omollo, Ann O.; Sitole, Lungile J.; McClendon, Eric; Valente, Edward J.; Raucher, Drazen; Walker, Leslie R.; Hamme, Ashton T.

    2015-01-01

    A series of structurally diverse 4-bromo spiro-isoxazolines possessing a variety of aromatic and aliphatic substituents at the 3 position, were synthesized through a 1,3-dipolar cycloaddition followed by intramolecular cyclization of a pendant hydroxyl or carboxylic acid group. The biochemical antiproliferative activity was evaluated in vitro by using two breast cancer cell lines (MCF-7 and MDA-MB-231) and two prostate cancer cell lines (PC-3 and DU-145) using the MTT viability assay, and the IC50 values were obtained. Spiro-isoxazoline derivatives bearing a p-chloro or an o-dichloro aromatic substituent at the 3-position of the isoxazoline showed considerable antitumor activities in all four cell lines with IC50 value ranging from 43μM to 56μM. PMID:25821250

  12. Synthesis and characterization of nano structures of Silica SBA-16 containing Gadolinium-159 as potential nanoparticulated system for cancer therapy

    International Nuclear Information System (INIS)

    Cancer is a leading cause of death worldwide, and malignant neoplasms of the lung, stomach, liver, colon and breast in greater numbers. And recently observed in the literature a large number of reviews where new materials, especially nanoparticle, has been studied as drug carriers and radioisotopes applied to cancer treatment. How mesoporous materials based on silica, thanks to its huge surface area and biocompatibility, have been studied intensively providing broad applications in various areas, the use of nanostructured silica SBA-16 might be a carrier specific radioisotope accumulate in the cells malignant. Thus the aim of this study is to develop in vitro studies using SBA-16 can selectively concentrate in malignant cells therapeutic amounts of the radioisotope Gadolinium-159 escorting them to death. This work was performed orderly synthesis of mesoporous silica, SBA-16 and incorporating the complex Gd-DTPA-BMA, as well as chemical and structural characterization. The techniques used to analyze the occurrence of the incorporation of the gadolinium complex in the silica matrix were elemental analysis (CHN), atomic emission spectroscopy (ICP-AES), infrared spectroscopy (FTIR), nitrogen adsorption (BET), small-angle X-ray scattering (SAXS) and thermogravimetric analysis (TG). To analyze the morphology of pure silica used the scanning electron microscopy (SEM) and transmission electron microscopy (TEM). By photon correlation spectroscopy (PCS) it was possible to obtain a measure of mean particle size, the polydispersity index (PDI) of the silica SBA-16, and the zeta potential by laser Doppler anemometry (LDA). The results of incorporation analyzed by ICP-AES indicated that the material SBA-16 had a higher rate of incorporation of gadolinium (93%). The release kinetics in simulated body fluid, showed considerable stability and low release (1%). The mesoporous silica SBA-16 showed cell viability in direct contact with cell culture. Samples with gadolinium

  13. Egg white-mediated green synthesis of silver nanoparticles with excellent biocompatibility and enhanced radiation effects on cancer cells

    Directory of Open Access Journals (Sweden)

    Lu RQ

    2012-04-01

    Full Text Available Renquan Lu1, Dapeng Yang2, Daxiang Cui2, Zhongyang Wang3, Lin Guo11Department of Clinical Laboratory, Fudan University Shanghai Cancer Center, Shanghai, 2Department of Bio-Nano-Science and Engineering, National Key Laboratory of Nano/Micro Fabrication Technology, Key Laboratory for Thin Film and Microfabrication of Ministry of Education, Institute of Micro-Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 3College of Chemistry and Chemical Engineering, Yantai University, Shan Dong Province, People's Republic of ChinaAbstract: A simple, cost-effective, and environmentally friendly approach to the aqueous-phase synthesis of silver (Ag nanoparticles was demonstrated using silver nitrate (AgNO3 and freshly extracted egg white. The bio-conjugates were characterized by UV-visible spectroscopy, transmission electron microscopy, Fourier transform infrared spectrometry, and dynamic light scattering. These results indicated that biomolecule-coated Ag nanoparticles are predominantly spherical in shape with an average size of 20 nm. The proteins of egg white, which have different functional groups, played important roles in reducing Ag+ and maintaining product attributes such as stability and dispersity. In vitro cytotoxicity assays showed that these Ag-protein bio-conjugates showed good biocompatibility with mouse fibroblast cell lines 3T3. Furthermore, X-ray irradiation tests on 231 tumor cells suggested that the biocompatible Ag-protein bio-conjugates enhanced the efficacy of irradiation, and thus may be promising candidates for use during cancer radiation therapy.Keywords: green chemistry, biosynthesis, egg white, Ag nanoparticles, X-ray irradiation

  14. Synthesis of a drug delivery vehicle for cancer treatment utilizing DNA-functionalized gold nanoparticles

    Science.gov (United States)

    Brann, Tyler

    The treatment of cancer with chemotherapeutic agents has made great strides in the last few decades but still introduces major systemic side effects. The potent drugs needed to kill cancer cells often cause irreparable damage to otherwise healthy organs leading to further morbidity and mortality. A therapy with intrinsic selective properties and/or an inducible activation has the potential to change the way cancer can be treated. Gold nanoparticles (GNPs) are biocompatible and chemically versatile tools that can be readily functionalized to serve as molecular vehicles. The ability of these particles to strongly absorb light with wavelengths in the therapeutic window combined with the heating effect of surface plasmon resonance makes them uniquely suited for noninvasive heating in biologic applications. Specially designed DNA aptamers have shown their ability to serve as drug carriers through intercalation as well as directly acting as therapeutic agents. By combining these separate molecules a multifaceted drug delivery vehicle can be created with great potential as a selective and controllable treatment for cancer. Oligonucleotide-coated GNPs have been created using spherical GNPs but little work has been reported using gold nanoplates in this way. Using the Diasynth method gold nanoplates were produced to absorb strongly in the therapeutic near infrared (nIR) window. These particles were functionalized with two DNA oligonucleotides: one serving as an intercalation site for doxorubicin, and another, AS1411, serving directly as an anticancer targeting/therapeutic agent. These functional particles were fully synthesized and processed along with confirmation of DNA functionalization and doxorubicin intercalation. Doxorubicin is released via denaturation of the DNA structure into which doxorubicin is intercalated upon the heating of the gold nanoplate well above the DNA melting temperature. This temperature increase, due to light stimulation of surface plasmon

  15. Facile synthesis of superparamagnetic Fe3O4@Au nanoparticles for photothermal destruction of cancer cells.

    Science.gov (United States)

    Ren, Jinfeng; Shen, Shun; Pang, Zhiqing; Lu, Xiaohui; Deng, Chunhui; Jiang, Xinguo

    2011-11-14

    Superparamagnetic Fe(3)O(4) nanoparticles with positive surface ξ-potential were synthesized via a solvothermal route. After Fe(3)O(4) was mixed with HAuCl(4) and NaBH(4), the reduced Au nanoparticles could be directly adsorbed onto the surface of Fe(3)O(4) nanoparticles. The as-synthesized nanocomposites were successfully applied to photothermal destruction of cancer cells. PMID:21952492

  16. Benzofuran as a promising scaffold for the synthesis of antimicrobial and antibreast cancer agents: A review

    Directory of Open Access Journals (Sweden)

    Ghadamali Khodarahmi

    2015-01-01

    Full Text Available Benzofuran as an important heterocyclic compound is extensively found in natural products as well as synthetic materials. Since benzofuran drivatives display a diverse array of pharmacological activities, an interest in developing new biologically active agents from benzofuran is still under consideration. This review highlights recent findings on biological activities of benzofuran derivatives as antimicrobial and antibreast cancer agents and lays emphasis on the importance of benzofurans as a major source for drug design and development.

  17. Cutaneous vitamin D synthesis versus skin cancer development: The Janus faces of solar UV-radiation

    OpenAIRE

    Reichrath, Jörg; Nürnberg, Bernd

    2009-01-01

    In scientific and public communities, there is an ongoing discussion how to balance between positive and negative effects of solar UV-exposure. On the one hand, solar UV-radiation represents the most important environmental risk factor for the development of non-melanoma skin cancer. Consequently, UV protection is an important measure to prevent these malignancies, especially in risk groups. Otherwise, approximately 90% of all vitamin D needed by the human body has to be formed in the skin th...

  18. Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells

    International Nuclear Information System (INIS)

    The imaging of molecular markers associated with disease offers the possibility for earlier detection and improved treatment monitoring. Receptors for gastrin-releasing peptide are overexpressed on prostate cancer cells offering a promising imaging target, and analogs of bombesin, an amphibian tetradecapeptide have been previously demonstrated to target these receptors. Therefore, the pan-bombesin analog [β-Ala11, Phe13, Nle14]bombesin-(7-14) was conjugated through a linker to dye-functionalized superparamagnetic iron oxide nanoparticles for the development of a new potential magnetic resonance imaging probe. The peptide was conjugated via click chemistry, demonstrating a complementary alternative methodology to conventional peptide-nanoparticle conjugation strategies. The peptide-functionalized nanoparticles were then demonstrated to be selectively taken up by PC-3 prostate cancer cells relative to unfunctionalized nanoparticles and this uptake was inhibited by the presence of free peptide, confirming the specificity of the interaction. This study suggests that these nanoparticles have the potential to serve as magnetic resonance imaging probes for the detection of prostate cancer.

  19. Synthesis of bombesin-functionalized iron oxide nanoparticles and their specific uptake in prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Amanda L.; Hickey, Jennifer L. [University of Western Ontario, Department of Chemistry (Canada); Ablack, Amber L.; Lewis, John D. [University of Western Ontario, Department of Oncology (Canada); Luyt, Leonard G.; Gillies, Elizabeth R., E-mail: egillie@uwo.c [University of Western Ontario, Department of Chemistry (Canada)

    2010-06-15

    The imaging of molecular markers associated with disease offers the possibility for earlier detection and improved treatment monitoring. Receptors for gastrin-releasing peptide are overexpressed on prostate cancer cells offering a promising imaging target, and analogs of bombesin, an amphibian tetradecapeptide have been previously demonstrated to target these receptors. Therefore, the pan-bombesin analog [{beta}-Ala11, Phe13, Nle14]bombesin-(7-14) was conjugated through a linker to dye-functionalized superparamagnetic iron oxide nanoparticles for the development of a new potential magnetic resonance imaging probe. The peptide was conjugated via click chemistry, demonstrating a complementary alternative methodology to conventional peptide-nanoparticle conjugation strategies. The peptide-functionalized nanoparticles were then demonstrated to be selectively taken up by PC-3 prostate cancer cells relative to unfunctionalized nanoparticles and this uptake was inhibited by the presence of free peptide, confirming the specificity of the interaction. This study suggests that these nanoparticles have the potential to serve as magnetic resonance imaging probes for the detection of prostate cancer.

  20. Synthesis and Cytotoxic Evaluation of a Series of 2-Amino-Naphthoquinones against Human Cancer Cells

    Directory of Open Access Journals (Sweden)

    Thiago A. P. de Moraes

    2014-08-01

    Full Text Available The cytotoxicity of a series of aminonaphthoquinones resulting from the reaction of suitable aminoacids with 1,4-naphthoquinone was assayed against SF-295 (glioblastoma, MDAMB-435 (breast, HCT-8 (colon, HCT-116 (colon, HL-60 (leukemia, OVCAR-8 (ovarian, NCI-H358M (bronchoalveolar lung carcinoma and PC3-M (prostate cancer cells and also against PBMC (peripheral blood mononuclear cells. The results demonstrated that all the synthetic aminonaphthoquinones had relevant cytotoxic activity against all human cancer lines used in this experiment. Five of the compounds showed high cytotoxicity and selectivity against all cancer cell lines tested (IC50 = 0.49 to 3.89 µg·mL−1. The title compounds were less toxic to PBMC, since IC50 was 1.5 to eighteen times higher (IC50 = 5.51 to 17.61 µg·mL−1 than values shown by tumour cell lines. The mechanism of cell growth inhibition and structure–activity relationships remains as a target for future investigations.

  1. Analysis of colloid and tracer breakthrough curves

    Science.gov (United States)

    Grindrod, Peter; Edwards, Mark S.; Higgo, Jenny J. W.; Williams, Geoffrey M.

    1996-02-01

    We consider the dispersion and elution of colloids and dissolved nonsorbing tracers within saturated heterogeneous porous media. Since flow path geometry in natural systems is often ill-characterized macroscopic (mean) flow rates and dispersion tensors are utilized in order to account for the sub-model scale microscopic fluctuations in media structure (and the consequent hydrodynamic profile). Even for tracer migration and dispersal this issue is far from settled. Here we consider how colloid and tracer migration phenomena can be treated consistently. Theoretical calculations for model flow geometries yield two quantitative predictions for the transport of free (not yet captured) colloids with reference to a non-sorbing dissolved tracer within the same medium: the average migration velocity of the free colloids is higher than that of the tracer; and that the ratio of the equivalent hydrodynamic dispersion rates of colloids and tracer is dependent only upon properties of the colloids and the porous medium, it is independent of pathlengths and fluid flux, once length scales are large enough. The first of these is well known, since even in simple flow paths free colloids must stay more centre stream. The second, if validated suggests how solute and colloid dispersion may be dealt with consistently in macroscopic migration models. This is crucial since dispersion is usually ill-characterized and unaddressed by the experimental literature. In this paper we present evidence based upon an existing Drigg field injection test for the validity of these predictions. We show that starting from experimental data the fitted dispersion rates of both colloids and non-sorbing tracers increase with the measured elution rates (obeying slightly different rules for tracers and colloids); and that the ratio of colloid and nonsorbing tracer elution rates, and the ratio of colloid and nonsorbing tracer dispersion rates may be dependent upon properties of the colloids and the medium (not

  2. Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer: Synthesis and Evaluation In Vitro and In Vivo.

    Science.gov (United States)

    Cohen, Allison S; Patek, Renata; Enkemann, Steven A; Johnson, Joseph O; Chen, Tingan; Toloza, Eric; Vagner, Josef; Morse, David L

    2016-02-17

    In the United States, lung cancer is the leading cause of cancer death and ranks second in the number of new cases annually among all types of cancers. Better methods or tools for diagnosing and treating this disease are needed to improve patient outcomes. The delta-opioid receptor (δOR) is reported to be overexpressed in lung cancers and not expressed in normal lung. Thus, we decided to develop a lung cancer-specific imaging agent targeting this receptor. We have previously developed a δOR-targeted fluorescent imaging agent based on a synthetic peptide antagonist (Dmt-Tic) conjugated to a Cy5 fluorescent dye. In this work, we describe the synthesis of Dmt-Tic conjugated to a longer wavelength near-infrared fluorescent (NIRF) dye, Li-cor IR800CW. Binding affinity of Dmt-Tic-IR800 for the δOR was studied using lanthanide time-resolved fluorescence (LTRF) competitive binding assays in cells engineered to overexpress the δOR. In addition, we identified lung cancer cell lines with high and low endogenous expression of the δOR. We confirmed protein expression in these cell lines using confocal fluorescence microscopy imaging and used this technique to estimate the cell-surface receptor number in the endogenously expressing lung cancer cell lines. The selectivity of Dmt-Tic-IR800 for imaging of the δOR in vivo was shown using both engineered cell lines and endogenously expressing lung cancer cells in subcutaneous xenograft models in mice. In conclusion, the δOR-specific fluorescent probe developed in this study displays excellent potential for imaging of lung cancer. PMID:26488422

  3. Tracer motion in an active dumbbell fluid

    Science.gov (United States)

    Suma, Antonio; Cugliandolo, Leticia F.; Gonnella, Giuseppe

    2016-05-01

    The diffusion properties of spherical tracers coupled through a repulsive potential to a system of active dumbbells are analyzed. We model the dumbbells’ dynamics with Langevin equations and the activity with a self-propulsive force of constant magnitude directed along the main axis of the molecules. Two types of tracers are considered. Thermal tracers are coupled to the same bath as the dumbbells while athermal tracers are not; both interact repulsively with the dumbbells. We focus our attention on the intruders’ mean square displacement and how it compares to the one of the dumbbells. We show that the dynamics of thermal intruders, with mass similar to the one of the dumbbells, display the typical four time-lag regimes of the dumbbells’ mean square displacement. The thermal tracers’ late-time diffusion coefficient depends on their mass very weakly and it is close to the one of the dumbbells at low Péclet only. Athermal tracers only have ballistic and late-time diffusive regimes. The late time diffusion coefficients of athermal tracers and dumbbells have similar values at high Péclet number when their masses are of the same order, while at low Péclet number this coefficient gets close to the one of the dumbbells only when the tracers are several order of magnitude heavier than the dumbbells. We propose a generalization of the Enskog law for dilute hard disks, that describes the athermal tracers’ mean square displacement in the form of a scaling law in terms of their mass.

  4. Using Tracer Technology to Characterize Contaminated Pipelines

    Energy Technology Data Exchange (ETDEWEB)

    Maresca, Joseph, W., Jr., Ph.D.; Bratton, Wesley, L., Ph.D., P.E.; Dickerson, Wilhelmina; Hales, Rochelle

    2005-12-30

    The Pipeline Characterization Using Tracers (PCUT) technique uses conservative and partitioning, reactive or other interactive tracers to remotely determine the amount of contaminant within a run of piping or ductwork. The PCUT system was motivated by a method that has been successfully used to characterize subsurface soil contaminants and is similar in operation to that of a gas chromatography column. By injecting a ?slug? of both conservative and partitioning tracers at one end (or section) of the piping and measuring the time history of the concentration of the tracers at the other end (or another section) of the pipe, the presence, location, and amount of contaminant within the pipe or duct can be determined. The tracers are transported along the pipe or duct by a gas flow field, typically air or nitrogen, which has a velocity that is slow enough so that the partitioning tracer has time to interact with the contaminant before the tracer slug completely passes over the contaminate region. PCUT not only identifies the presence of contamination, it also can locate the contamination along the pipeline and quantify the amount of residual. PCUT can be used in support of deactivation and decommissioning (D&D) of piping and ducts that may have been contaminated with hazardous chemicals such as chlorinated solvents, petroleum products, radioactive materials, or heavy metals, such as mercury.

  5. Synthesis and Evaluation of Nanogold Bioconjugated with Trastuzumab as a Drug for Human Breast Cancer Cell Line

    International Nuclear Information System (INIS)

    Breast cancer had been registered as the first order of cancer's leading cause of carcinoma death among Iraqi women. There are different trials to use bionanotechnology in medicine especially in the treatment of breast cancer. This work aimed to use different types of gold nanoparticles (GNPs) in application and evaluation of breast cancer cell through the following parts:- Part I: Synthesis three types of GNPs included: 1- Gold nanospheres (GN spheres) by modification of the chemical method and using different reducing agent (sodium borohydride then capping with glutathione (GSH), the other method by using GSH and the last using new reducing agent (2-Oxoglutaric acid). To the our present knowledge, this is the first report about using 2-Oxoglutaric acidas reducing agent in the synthesis of GN spheres. 2- Gold nanorods (GNRs)by using seed - mediated growth method capped with cetyltrimethyl ammonium bromide (CTAB). 3- Gold nano shells (GNSs) by using silica nanoparticles as core and seeded with gold as shell (silica-gold core shells). All the prepared types GNPs were characterized by using eight different techniques including: Atomic force microscopy (AFM),Transmission Electron Microscope (TEM), Field Emission Scanning Electron Microscopy (FESEM), UV-Vis spectroscopy, Dynamic light scattering (DLS), Fourier Transform Infrared (FTIR), Inductively Coupled Plasma- Optical Emission Spectrometry (ICP-OES), and zeta nanosizer. The measurements were done in Tarbiat Modares University (Faculty of Medicine and Faculty of Biological sciences) and Tehran University in Islamic Republic of Iran, except the techniques of ICP-OES it was done in Al-Sulaimani Universityandthat of AFM was accomplished in the Ministry of Science and Technology in Iraq . Part II: This part includes two steps: 1- Biofunctionalization i.e., modification of the surfaces of the three types of prepared GNPs by coating with thiol-poly ethylene glycol -carboxy (SH-PEG-COOH) then activation of the

  6. Synthesis, characterization, and in vivo efficacy evaluation of PGG–docetaxel conjugate for potential cancer chemotherapy

    Directory of Open Access Journals (Sweden)

    Jiang X

    2012-02-01

    Full Text Available Danbo Yang1, Sang Van2, Yingyi Shu1, Xiaoqing Liu1, Yangfeng Ge1, Xinguo Jiang3, Yi Jin2, Lei Yu1,21Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People’s Republic of China; 2Biomedical Group, Nitto Denko Technical Corporation, CA, USA; 3School of Pharmacy, Fudan University, Shanghai, People’s Republic of ChinaAim: This work is intended to develop and evaluate a biopolymeric poly(L-γ-glutamyl-glutamine (PGG–docetaxel (DTX conjugate that can spontaneously self-assemble in aqueous solutions to become nanoparticles.Methods: DTX was covalently attached to hydrophilic PGG by direct esterification, and the conjugate was characterized by proton nuclear magnetic resonance spectroscopy, molecular weight gel permeation chromatography, solubility, size distribution and morphology, and hemolysis. Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy revealed the particle size, distribution and morphology of the PGG–DTX conjugate. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460.Results: Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. The conjugate formed nanoparticles with an average diameter of 30 nm in spherical shape and unimodal particle size distribution. The conjugate exhibited about 2% hemolysis at 10 mg/mL, compared with 56% for Tween 80® at 0.4 mg/mL, and 33% for Cremophor EL® at 10 mg/mL. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460. As expected, conjugated DTX exhibited lower cytotoxicity compared to that of free DTX, in concentration

  7. Synthesis, structural characterization, and anticancer activity of a monobenzyltin compound against MCF-7 breast cancer cells

    Directory of Open Access Journals (Sweden)

    Fani S

    2015-11-01

    Full Text Available Somayeh Fani,1 Behnam Kamalidehghan,1 Kong Mun Lo,2 Najihah Mohd Hashim,1 Kit May Chow,2 Fatemeh Ahmadipour1 1Department of Pharmacy, Faculty of Medicine, 2Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia Abstract: A new monoorganotin Schiff base compound, [N-(3,5-dichloro-2-oxidobenzylidene-4-chlorobenzyhydrazidato](o-methylbenzylaquatin(IV chloride, (compound C1, was synthesized, and its structural features were investigated by spectroscopic techniques and single-crystal X-ray diffractometry. Compound C1 was exposed to several human cancer cell lines, including breast adenocarcinoma cell lines MCF-7 and MDA-MB-231, ovarian adenocarcinoma cell lines Skov3 and Caov3, and prostate cancer cell line PC3, in order to examine its cytotoxic effect for different forms of cancer. Human hepatic cell line WRL-68 was used as a normal cell line. We concentrated on the MCF-7 cell line to detect possible underlying mechanism involvement of compound C1. 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay revealed the strongest cytotoxicity of compound C1 against MCF-7 cells, with a half maximal inhibitory concentration (IC50 value of 2.5±0.50 µg/mL after 48 hours treatment. The IC50 value was >30 µg/mL in WRL-68 cells. Induced antiproliferative activity of compound C1 for MCF-7 cells was further confirmed by lactate dehydrogenase, reactive oxygen species, acridine orange/propidium iodide staining, and DNA fragmentation assays. A significant increase of lactate dehydrogenase release in treated cells was observed via fluorescence analysis. Luminescent analysis showed significant growth in intracellular reactive oxygen species production after treatment. Morphological changes of necrosis and early and late apoptosis stages were observed in treated cells after staining with acridine orange/propidium iodide. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Results of the

  8. Synthesis and biological evaluation of retinoid-chalcones as inhibitors of colon cancer cell growth

    OpenAIRE

    Mizuno, Cassia S.; Paul, Shiby; Suh, Nanjoo; Rimando, Agnes M.

    2010-01-01

    Based on the observed anticancer activity of chalcones and retinoids, a novel class of retinoid-chalcone hybrids was designed and synthesized. As part of our ongoing studies to discover natural product based anticancer compounds, the retinoid-chalcone hybrids were tested against the colon cancer cell line HT-29. Retinoid like moiety was introduced through Friedel-Crafts alkylation of toluene. Among the synthesized compounds, the cyano derivative (E)-3-(3-oxo-3-(3,5,5,8,8-pentamethyl-5,6,7,8-t...

  9. Synthesis and in Vitro Antiproliferative Activity of New Phenylaminoisoquinolinequinones against Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Virginia Delgado

    2013-01-01

    Full Text Available A variety of phenylaminoisoquinolinequinones were synthesized and tested for their antiproliferative activity against three human-tumor derived cancer cell lines. The new aminoquinones were prepared from 4-methoxycarbonyl-3-methylisoquinoline-5,8-quinone (1 via acid-induced amination and bromination reactions. Remarkable differences in antiproliferative activity were observed depending upon the location and donor capacity of the substituted phenylamino group at the quinone nucleus. The effect of the substituents on the biological activity is discussed in terms of the donor-acceptor interactions which were evaluated through the redox properties of the aminoquinones.

  10. 15N tracer kinetic studies on the validity of various 15N tracer substances for determining whole-body protein parameters in very small preterm infants

    International Nuclear Information System (INIS)

    Reliable 15N tracer substances for tracer kinetic determination of whole-body protein parameters in very small preterm infants are still a matter of intensive research, especially after some doubts have been raised about the validity of [15N]glycine, a commonly used 15N tracer. Protein turnover, synthesis, breakdown, and further protein metabolism data were determined by a paired comparison in four preterm infants. Their post-conceptual age was 32.2 +/- 0.8 weeks, and their body weight was 1670 +/- 181 g. Tracer substances applied in this study were a [15N]amino acid mixture (Ia) and [15N]glycine (Ib). In a second group of three infants with a post conceptual age of 15N-labeled 32.0 +/- 1.0 weeks and a body weight of 1,907 +/- 137 g, yeast protein hydrolysate (II) was used as a tracer substance. A three-pool model was employed for the analysis of the data. This model takes into account renal and fecal 15N losses after a single 15N pulse. Protein turnovers were as follows: 11.9 +/- 3.1 g kg-1 d-1 (Ia), 16.2 +/- 2.5 g kg-1 d-1 (Ib), and 10.8 +/- 3.0 g kg-1 d-1 (II). We were able to demonstrate an overestimation of the protein turnover when Ib was used. There was an expected correspondence in the results obtained from Ia and II. The 15N-labeled yeast protein hydrolysate is a relatively cheap tracer that allows reliable determination of whole-body protein parameters in very small preterm infants

  11. Developing a Cluster Based Parallel Ray Tracer

    OpenAIRE

    Lovell, C

    2007-01-01

    Parallel ray tracing is an important concept in computer graphics, as it allows for high quality ray traced images to be produced at a faster rate than is possible in single processor ray tracing. Presented in this paper is the conversion of a previously created single processor ray tracer to a parallel ray tracer that is capable of running on a cluster of computers. This paper presents the technical aspects of designing a parallel ray tracer by looking at the theory of transforming ray traci...

  12. Mitomycin-C+fluoropyrimidines in heavily pretreated metastatic colorectal cancer: a systematic review and evidence synthesis.

    Science.gov (United States)

    Petrelli, Fausto; Ghidini, Antonio; Inno, Alessandro; Barni, Sandro

    2016-07-01

    Mitomycin-C (MMC) combined with fluoropyrimidines has historically been used for pretreated patients with some activity in this setting, in particular, as third-line chemotherapy (CT) or beyond. We have evaluated the efficacy and safety of MMC-based therapy as a further line of CT in advanced colorectal cancer. Prospective or retrospective studies of MMC-based CT were included in the pooled analysis. PubMed, EMBASE, SCOPUS, Web of Science, the Cochrane Library database and CINAHL were searched systematically. The outcomes were progression-free survival, overall survival, overall response rate and grades 3-4 drug-related adverse events. Seventeen trials involving 681 patients were included in the analysis. Overall, the pooled average weighted progression-free survival and overall survival were 2.84 [95% confidence interval (CI) 2.5-3.1] and 7.47 (95% CI 6-8.9) months, respectively. The corresponding pooled overall response rate was 7.2% (95% CI 5.2-9.9%) and the pooled disease control rate was 38.7% (95% CI 31.7-46.3%). The G3-4 neutropenia and anaemia were the most frequent haematological toxicities (range 0-20%). Nonhaematological G3-4 toxicities were compatible with the associated agent. MMC with fluoropyrimidines represents a viable and active combination for pretreated metastatic colorectal cancer patients. It is thus an option when other agents have failed, or are unavailable or not indicated. PMID:27186954

  13. Synthesis, Characterization and Biological Evaluation of Succinate Prodrugs of Curcuminoids for Colon Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Pornchai Rojsitthisak

    2011-02-01

    Full Text Available A novel series of succinyl derivatives of three curcuminoids were synthesized as potential prodrugs. Symmetrical (curcumin and bisdesmethoxycurcumin and unsymmetrical (desmethoxycurcumin curcuminoids were prepared through aldol condensation of 2,4-pentanedione with different benzaldehydes. Esterification of these compounds with a methyl or ethyl ester of succinyl chloride gave the corresponding succinate prodrugs in excellent yields. Anticolon cancer activity of the compounds was evaluated using Caco-2 cells. The succinate prodrugs had IC50 values in the 1.8–9.6 ��M range, compared to IC50 values of 3.3–4.9 μM for the parent compounds. Curcumin diethyl disuccinate exhibited the highest potency and was chosen for stability studies. Hydrolysis of this compound in phosphate buffer at pH 7.4 and in human plasma followed pseudo first-order kinetics. In phosphate buffer, the kobs and t1/2 for hydrolysis indicated that the compound was much more stable than curcumin. In human plasma, this compound was able to release curcumin, therefore our results suggest that succinate prodrugs of curcuminoids are stable in phosphate buffer, release the parent curcumin derivatives readily in human plasma, and show anti-colon cancer activity.

  14. Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety.

    Science.gov (United States)

    Bingul, Murat; Tan, Owen; Gardner, Christopher R; Sutton, Selina K; Arndt, Greg M; Marshall, Glenn M; Cheung, Belamy B; Kumar, Naresh; Black, David StC

    2016-01-01

    Identification of the novel (E)-N'-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio)propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19-26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G₁ cell cycle arrest, as well as upregulation of the p27(kip1) cell cycle regulating protein. PMID:27428941

  15. Synthesis and evaluation of polymeric gold glyco-conjugates as anti-cancer agents.

    Science.gov (United States)

    Ahmed, Marya; Mamba, Saul; Yang, Xiao-Hong; Darkwa, James; Kumar, Piyush; Narain, Ravin

    2013-06-19

    The antitumor activity of organo-gold compounds is a focus of research from the past two decades. A variety of gold stabilizing ligands such as vitamins and xanthanes have been prepared and explored for their 'chelating effect' as well as for their antitumor activity. Dithiocarbamates (DTC) compounds and their metallic conjugates have been well explored for their antiproliferative activities. In this study, glycopolymer based DTC-conjugates are prepared by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently modified with gold(I) phosphine. These polymer-DTC derivatives and their gold compounds are tested for their in vitro toxicity in both normal and cancer cell lines. The Au(I) phosphine conjugated cationic glycopolymers of 10 kDa and 30 kDa are evaluated for their cytotoxicity profiles using MTT assay. Au(I) compounds are well-known for their mitochondrial toxicity, hence hypoxic cell lines bearing unusually enlarged mitochondria are subjected to these anticancer compounds. It is concluded that these polymeric DTC derivatives and their gold conjugates indeed show higher accumulation as well as cytotoxicity to cancer cells under hypoxic conditions in comparison to the normoxic ones. Hypoxic MCF-7 cells showed significant sensitivity toward the low molecular weight (10 kDa) glycopolymer-Au(I) complexes. PMID:23631753

  16. Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

    Directory of Open Access Journals (Sweden)

    Murat Bingul

    2016-07-01

    Full Text Available Identification of the novel (E-N′-((2-chloro-7-methoxyquinolin-3-ylmethylene-3-(phenylthiopropanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19–26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G1 cell cycle arrest, as well as upregulation of the p27kip1 cell cycle regulating protein.

  17. Development of Radioisotope Tracer Technology

    International Nuclear Information System (INIS)

    The project is aimed to develop the radiotracer technology for process optimization and trouble-shooting to establish the environmental and industrial application of radiation and radioisotopes. The advanced equipment and software such as high speed data acquisition system, RTD model and high pressure injection tool have developed. Based on the various field application to the refinery/petrochemical industries, the developed technology was transfer to NDT company for commercial service. For the environmental application of radiotracer technology, injector, detector sled, core sampler, RI and GPS data logging system are developed and field tests were implemented successfully at Wolsung and Haeundae beach. Additionally tracer technology were also used for the performance test of the clarifier in a wastewater treatment plant and for the leak detection in reservoirs. From the experience of case studies on radiotracer experiment in waste water treatment facilities, 'The New Excellent Technology' is granted from the ministry of environment. For future technology, preliminary research for industrial gamma transmission and emission tomography which are new technology combined with radioisotope and image reconstruction are carried out

  18. Compartmental modeling and tracer kinetics

    CERN Document Server

    Anderson, David H

    1983-01-01

    This monograph is concerned with mathematical aspects of compartmental an­ alysis. In particular, linear models are closely analyzed since they are fully justifiable as an investigative tool in tracer experiments. The objective of the monograph is to bring the reader up to date on some of the current mathematical prob­ lems of interest in compartmental analysis. This is accomplished by reviewing mathematical developments in the literature, especially over the last 10-15 years, and by presenting some new thoughts and directions for future mathematical research. These notes started as a series of lectures that I gave while visiting with the Division of Applied ~1athematics, Brown University, 1979, and have developed in­ to this collection of articles aimed at the reader with a beginning graduate level background in mathematics. The text can be used as a self-paced reading course. With this in mind, exercises have been appropriately placed throughout the notes. As an aid in reading the material, the e~d of a ...

  19. Cancer

    Science.gov (United States)

    ... Blood tests (which look for chemicals such as tumor markers) Bone marrow biopsy (for lymphoma or leukemia) Chest ... the case with skin cancers , as well as cancers of the lung, breast, and colon. If the tumor has spread ...

  20. Cancer

    Science.gov (United States)

    Cancer begins in your cells, which are the building blocks of your body. Normally, your body forms ... be benign or malignant. Benign tumors aren't cancer while malignant ones are. Cells from malignant tumors ...

  1. Synthesis, characterization and cytotoxic evaluation of chitosan nanoparticles: in vitro liver cancer model

    Science.gov (United States)

    Loutfy, Samah A.; Alam El-Din, Hanaa M.; Elberry, Mostafa H.; Allam, Nanis G.; Hasanin, M. T. M.; Abdellah, Ahmed M.

    2016-09-01

    To evaluate the cytotoxic effect of chitosan nanoparticles (CS-NPs) on an in vitro human liver cancer cell model (HepG2) and their possible application as a drug delivery system, we synthesized water-soluble CS-NPs, investigated their properties and extensively evaluated their cytotoxic activity on the cellular and molecular levels. A human liver cancer cell line was used as a model of human liver cancer. The CS-NPs were characterized using transmission electron microscopy, Fourier transform infrared spectroscopy, and zeta analysis. The cytotoxic effects of the CS-NPs on HepG2 cells were monitored by sulforhodamine B colorimetric assays for cytotoxicity screening and flow cytometric analysis. Molecular investigations including DNA fragmentation and the expression of some apoptotic genes on the transcriptional RNA level were conducted. Treatment of HepG2 with different concentrations of 150 nm diameter CS-NPs did not show alteration of cell morphology after 24 h of cell exposure. Also, when cells were treated with 100 μg ml‑1 of CS-NPs, 12% of them were killed and IC50 reached 239 μg ml‑1 after 48 h of cell exposure. Flow cytometry evaluation of the CS-NPs revealed mild accumulation in the G2/M phase followed by cellular DNA fragmentation after 48 h of cell exposure. Extensive evaluation of the cytotoxic effect of the CS-NPs showed messenger RNA (mRNA) apoptotic gene expression (p53, Bak, Caspase3) after 24 h of cell exposure with no expression of the mRNA of the caspase 3 gene after 48 h of cell exposure, suggesting the involvement of an intrinsic apoptotic caspase-independent pathway by increasing the exposure time of 100 μg ml‑1 of the CS-NPs. The engineered CS-NPs were controlled to a 150 nm size and charges of 40 mV and a concentration of 100 μg ml‑1 revealed a genotoxic effect on HepG2 after 48 h of cell exposure through intrinsic apoptotic caspase-independent mechanisms. Further quantitative analysis on the molecular and protein levels is still

  2. Tracers in oncology. Preclinical and clinical evaluation; Innovative Tracer in der onkologischen Diagnostik. Praeklinische und klinische Evaluierung

    Energy Technology Data Exchange (ETDEWEB)

    Krause, B.J.; Schwarzenboeck, S.; Schwaiger, M. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    2010-07-01

    In oncology, PET and PET/CT with tracers beyond FDG target more specific biological processes, such as proliferation ({sup 18}F-3'-fluoro-3'-deoxy-L-thymidine; {sup 18}F-FLT), tumour hypoxia ({sup 18}F-fluoromisonidazol; {sup 18}F-FMISO) and phospholipid metabolism (radioactively labelled choline derivates). FLT is a thymidine analogue which can be labelled with {sup 18}F. PET with {sup 18}F-FLT enables to non-invasively image and to quantify the proliferation fraction of tumours. Proliferation dependent accumulation of FLT has been demonstrated for a variety of solid and haematologic neoplasms including lung cancer, breast cancer, gastric cancer, colorectal cancer and malignant lymphoma. Furthermore, FLT has been suggested as surrogate marker for the assessment of response to treatment, especially when targeted drugs are utilized. PET imaging in particular has emerged as a promising non-invasive tool to accurately characterize tumour oxygenation. The great promise of PET/CT is its potential as a single imaging modality for whole body staging that provides anatomical and biological information on the disease as a whole. It allows a more precise estimation of the hypoxic tumour volume as well as comparisons on a voxel-by-voxel basis (parametric mapping). PET and PET/CT with hypoxia tracers thus offer the potential to optimize and individualize therapy for patients suffering from cancer. PET- and PET/CT-studies using {sup 11}C- or {sup 18}F-labeled choline derivates recently have shown promising results for re-staging prostate cancer in patients with biochemical recurrence and advanced prostate cancer. In patients with biochemical recurrence of prostate cancer after primary therapy the detection rate of {sup 11}C-choline- PET/CT shows a positive relationship with serum PSA-levels. In these patients {sup 11}C-choline PET/CT allows not only to diagnose but also to localize recurrent disease with implications on disease management (localised vs. systemic

  3. Therapeutic Education in Improving Cancer Pain Management: A Synthesis of Available Studies.

    Science.gov (United States)

    Prevost, Virginie; Delorme, Claire; Grach, Marie-Christine; Chvetzoff, Gisèle; Hureau, Magalie

    2016-07-01

    This literature review aims to synthesize available studies and to update findings in order to obtain a current, comprehensive estimate of the benefits of pain education. Forty-four original articles obtained from the PubMed database were analyzed to investigate which protocols could be most effective in improving pain management. Recent studies indicate a growing interest in evaluating patients' skills and attitudes; these include satisfaction with cancer pain treatment, patient-reported improvement, and patient participation-all of which could be dependable benchmarks for evaluating the effectiveness of educational programs. Besides pain measurement, recent studies advance support for the importance of assessing newly developed outcome criteria. In this sense, patients' active participation and decision making in their pain management are probably the most relevant goals of pain education. PMID:25991567

  4. Synthesis and characterization of a HAp-based biomarker with controlled drug release for breast cancer.

    Science.gov (United States)

    González, Maykel; Merino, Ulises; Vargas, Susana; Quintanilla, Francisco; Rodríguez, Rogelio

    2016-04-01

    A biocompatible hybrid porous polymer-ceramic material was synthesized to be used as a biomarker in the treatment of breast cancer. This device was equipped with the capacity to release medicaments locally in a controlled manner. The biomaterial was Hydroxyapatite(HAp)-based and had a controlled pore size and pore volume fraction. It was implemented externally using a sharp end and a pair of barbed rings placed opposite each other to prevent relative movement once implanted. The biomarker was impregnated with cis-diamine dichloride platinum (II) [Cl2-Pt-(NH3)2]; the rate of release was obtained using inductively coupled plasma atomic emission spectroscopy (ICP-AES), and release occurred over the course of three months. Different release profiles were obtained as a function of the pore volume fraction. The biomaterial was characterized using scanning electron microscopy (SEM) and Raman spectroscopy. PMID:26838911

  5. An in-vitro studies on green synthesis of gold nanoparticles against pathogens and cancer cells

    Directory of Open Access Journals (Sweden)

    V. Ramesh

    2015-11-01

    Full Text Available Nanotechnology is a most promising field for generating new applications in medicine. It is imperative to integrate nanoscience and medicine. The present investigation is highly warranted to through more light upon the gold nanoparticles reduced from gold salt through the active principle of medicinal plant. The special emphasis of investigation is the active principle along with gold nanoparticles against for cancer cells. The 70 - 90 nm sized particles were synthesized by using Diospyros ferrea and this confirmed by SEM. These gold nanoparticles showed a characteristic absorption peak at 540 nm in UV spectra. The possibility of protein as a stabilizing material in gold nanoparticles is revealed by FTIR analysis. Remarkably, as a result of wide screening on the application of newly synthesized gold nanoparticles their anticancer potential has been discovered using MTT assay. The antimicrobial activity of AuNPs showed effective against bacteria than the fungal strains.

  6. Synthesis of isatin thiosemicarbazones derivatives: In vitro anti-cancer, DNA binding and cleavage activities

    Science.gov (United States)

    Ali, Amna Qasem; Teoh, Siang Guan; Salhin, Abdussalam; Eltayeb, Naser Eltaher; Khadeer Ahamed, Mohamed B.; Majid, A. M. S. Abdul

    New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (kb = 5.03-33.00 × 105 M-1) for L1-L3 and L5 and (6.14-9.47 × 104 M-1) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency.

  7. Flow optimization study of a batch microfluidics PET tracer synthesizing device

    OpenAIRE

    Elizarov, Arkadij M.; Meinhart, Carl; Miraghaie, Reza; van Dam, R. Michael; Huang, Jiang; Daridon, Antoine; Heath, James R.; Kolb, Hartmuth C.

    2010-01-01

    We present numerical modeling and experimental studies of flow optimization inside a batch microfluidic micro-reactor used for synthesis of human-scale doses of Positron Emission Tomography (PET) tracers. Novel techniques are used for mixing within, and eluting liquid out of, the coin-shaped reaction chamber. Numerical solutions of the general incompressible Navier Stokes equations along with time-dependent elution scalar field equation for the three dimensional coin-shaped geometry were obta...

  8. Synthesis and characterization of rare earth molybdates nanoparticles for detection of specific prostatic cancer (PSA)

    International Nuclear Information System (INIS)

    The interest in using rare earths to investigate the properties and functions of biochemical systems as well as to determinate biological substances has increased in several fields, including biomarkers in immunology (fluoro immunoassays). Nowadays the use of lanthanides in the diagnosis of various diseases have become more important through the development of commercial diagnostic kits. As main feature, these rare earths can show a long lifetime, photo stability and emission bands of atomic like behavior and well defined, in the visible region, demonstrating unique advantages when compared to other luminescent species. The present work had as its goal to synthesize rare earth molybdates by the co-precipitation method as well as to characterize these materials by X-ray diffraction, near infrared spectroscopy, thermogravimetric analysis, scanning electronic microscopy, transmission electronic microscopy and luminescent studies. In this work, three different studied were developed: the influence of the vortex speed variation during co-precipitation in the structure of the final product, morphology and luminescence properties; the influence of the annealing temperature also in the structure, morphology and luminescence properties; and the influence of concentration of the doping in the luminescence properties. Another important step of this work was the functionalization of nanoparticles using an organosilane (APTES) to coat and establish points for binding the particles to biological species. It was proved that this process was very efficient by the characterization results and the silica incorporation was well succeeded. Specific prostatic cancer (PSA) was then linked to the functionalized nanoparticles to diagnostic prostatic cancer by fluoroimmunoassay and levels for detection were established. (author)

  9. Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Hopperton, Kathryn E., E-mail: kathryn.hopperton@mail.utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Duncan, Robin E., E-mail: robin.duncan@uwaterloo.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Bazinet, Richard P., E-mail: richard.bazinet@utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Archer, Michael C., E-mail: m.archer@utoronto.ca [Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada); Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, Canada M5S 3E2 (Canada)

    2014-01-15

    Fatty acid synthase is over-expressed in many cancers and its activity is required for cancer cell survival, but the role of endogenously synthesized fatty acids in cancer is unknown. It has been suggested that endogenous fatty acid synthesis is either needed to support the growth of rapidly dividing cells, or to maintain elevated glycolysis (the Warburg effect) that is characteristic of cancer cells. Here, we investigate both hypotheses. First, we compared utilization of fatty acids synthesized endogenously from {sup 14}C-labeled acetate to those supplied exogenously as {sup 14}C-labeled palmitate in the culture medium in human breast cancer (MCF-7 and MDA-MB-231) and untransformed breast epithelial cells (MCF-10A). We found that cancer cells do not produce fatty acids that are different from those derived from exogenous palmitate, that these fatty acids are esterified to the same lipid and phospholipid classes in the same proportions, and that their distribution within neutral lipids is not different from untransformed cells. These results suggest that endogenously synthesized fatty acids do not fulfill a specific function in cancer cells. Furthermore, we observed that cancer cells excrete endogenously synthesized fatty acids, suggesting that they are produced in excess of requirements. We next investigated whether lipogenic activity is involved in the maintenance of high glycolytic activity by culturing both cancer and non-transformed cells under anoxic conditions. Although anoxia increased glycolysis 2–3 fold, we observed no concomitant increase in lipogenesis. Our results indicate that breast cancer cells do not have a specific qualitative or quantitative requirement for endogenously synthesized fatty acids and that increased de novo lipogenesis is not required to sustain elevations in glycolytic activity induced by anoxia in these cells. - Highlights: • Fatty acid synthase (FASN) is over-expressed in cancer but its function is unknown. • We compare

  10. Fatty acid synthase plays a role in cancer metabolism beyond providing fatty acids for phospholipid synthesis or sustaining elevations in glycolytic activity

    International Nuclear Information System (INIS)

    Fatty acid synthase is over-expressed in many cancers and its activity is required for cancer cell survival, but the role of endogenously synthesized fatty acids in cancer is unknown. It has been suggested that endogenous fatty acid synthesis is either needed to support the growth of rapidly dividing cells, or to maintain elevated glycolysis (the Warburg effect) that is characteristic of cancer cells. Here, we investigate both hypotheses. First, we compared utilization of fatty acids synthesized endogenously from 14C-labeled acetate to those supplied exogenously as 14C-labeled palmitate in the culture medium in human breast cancer (MCF-7 and MDA-MB-231) and untransformed breast epithelial cells (MCF-10A). We found that cancer cells do not produce fatty acids that are different from those derived from exogenous palmitate, that these fatty acids are esterified to the same lipid and phospholipid classes in the same proportions, and that their distribution within neutral lipids is not different from untransformed cells. These results suggest that endogenously synthesized fatty acids do not fulfill a specific function in cancer cells. Furthermore, we observed that cancer cells excrete endogenously synthesized fatty acids, suggesting that they are produced in excess of requirements. We next investigated whether lipogenic activity is involved in the maintenance of high glycolytic activity by culturing both cancer and non-transformed cells under anoxic conditions. Although anoxia increased glycolysis 2–3 fold, we observed no concomitant increase in lipogenesis. Our results indicate that breast cancer cells do not have a specific qualitative or quantitative requirement for endogenously synthesized fatty acids and that increased de novo lipogenesis is not required to sustain elevations in glycolytic activity induced by anoxia in these cells. - Highlights: • Fatty acid synthase (FASN) is over-expressed in cancer but its function is unknown. • We compare utilization of

  11. Artificial radioactive tracers: a tool for oceanography

    International Nuclear Information System (INIS)

    In marine hydrodynamic, use of 125Sb as tracer and a two stages coprecipitation analysis process allows to study water motion in the Channel and in the seas of the north east of Europe from effluents of La Hague (France) reprocessing plant. Other tracers may be used: 137Cs coming principally from Sellafield (United Kingdom), and 134Cs coming from Chernobyl accident. (A.B.). 15 refs., 8 figs., 5 tabs

  12. Radioactive and kinematic tracers of feedback from massive stars

    Directory of Open Access Journals (Sweden)

    Voss R.

    2012-02-01

    Full Text Available The mixing of ejecta from young stars into the interstellar medium is an important process in the interplay between star formation and galaxy evolution. A unique window into these processes is provided by the radioactive isotopes 26Al, traced by its γ-ray decay lines at 1.8 MeV. With a mean lifetime of ∼ 1 Myr it is a long-term tracer of nucleosynthesis for massive stars. Our population synthesis code models the ejection of 26Al, together with the 60Fe, the kinetic energy and UV radiation for a population of massive stars. We have applied the code to study the nearby Orion region and the more massive Carina region and found good agreement with observational constraints.

  13. Tracer monitoring of enhanced oil recovery projects

    Science.gov (United States)

    Dugstad, Ø.; Viig, S.; Krognes, B.; Kleven, R.; Huseby, O.

    2013-05-01

    In enhanced oil recovery (EOR), chemicals are injected into the oil reservoir, either to increase macroscopic sweep efficiency, or to reduce remaining oil saturation in swept zones. Tracers can be used to identify reservoirs that are specifically suited for EOR operations. Injection of a selection of partitioning tracers, combined with frequent sample analysis of produced fluids, provides information suited for estimation of residual oil saturation. Tracers can also be used to evaluate and optimize the application of EOR chemicals in the reservoir. Suitable tracers will follow the EOR chemicals and assist in evaluation of retention, degradation or trapping. In addition to field applications, tracers also have a large potential as a tool to perform mechanistic studies of EOR chemicals in laboratory experiments. By labelling EOR chemicals with radioactive isotopes of elements such as H, C and S, detailed studies of transport mechanisms can be carried out. Co-injection of labelled compounds in dynamic flooding experiments in porous media will give information about retention or separation of the unique compounds constituting the chemical formulation. Separation of such compounds may be detrimental to obtaining the EOR effect expected. The paper gives new information of specific methods, and discusses current status for use of tracers in EOR operations.

  14. Tracer monitoring of enhanced oil recovery projects

    Directory of Open Access Journals (Sweden)

    Kleven R.

    2013-05-01

    Full Text Available In enhanced oil recovery (EOR, chemicals are injected into the oil reservoir, either to increase macroscopic sweep efficiency, or to reduce remaining oil saturation in swept zones. Tracers can be used to identify reservoirs that are specifically suited for EOR operations. Injection of a selection of partitioning tracers, combined with frequent sample analysis of produced fluids, provides information suited for estimation of residual oil saturation. Tracers can also be used to evaluate and optimize the application of EOR chemicals in the reservoir. Suitable tracers will follow the EOR chemicals and assist in evaluation of retention, degradation or trapping. In addition to field applications, tracers also have a large potential as a tool to perform mechanistic studies of EOR chemicals in laboratory experiments. By labelling EOR chemicals with radioactive isotopes of elements such as H, C and S, detailed studies of transport mechanisms can be carried out. Co-injection of labelled compounds in dynamic flooding experiments in porous media will give information about retention or separation of the unique compounds constituting the chemical formulation. Separation of such compounds may be detrimental to obtaining the EOR effect expected. The paper gives new information of specific methods, and discusses current status for use of tracers in EOR operations.

  15. Tracer kinetics: Modelling of tracer behaviour in nonlinear and nonsteady state systems exemplified by the evaluation of protein turnover in plant organs

    International Nuclear Information System (INIS)

    If nonlinear biological processes are investigated by means of tracer experiments they can be modelled with linear kinetic equations (compartment equations) as long as the total system is in a stationary state. But if nonstationary behaviour is included considerations on the kinetics of the individual processes are necessary. Within the range of biological and agricultural investigations especially first order reactions (constant fraction processes), zero order reactions (constant amount process) and saturation reactions (Michaelis-Menten-kinetics) are to be taken into account. A rigorous treatment of data based on system theory can be preceeded by graphic-algebraic procedure which may be more or less uncertain in its results but which can easily be handled. An example is given of methodological considerations concerning the combination of evaluation procedures and the discrimination between different reaction mechanisms. It treats protein turnover in 2 different parts of growing wheat plants investigated by means of an 15N-tracer experiment. Whereas in a stationary system (upper stalk section) linear tracer equations were sufficient irrespective of the true reaction mechanism, for protein synthesis in the upper leaf as a nonstationary system it was necessary to decide between the hypotheses of a zero order and a first order reaction. In accordance with statements in the literature the unambiguous result was a combination of protein synthesis as a zero order process and of protein degradation as a first order process. (orig.)

  16. Regulation of DNA synthesis and the cell cycle in human prostate cancer cells and lymphocytes by ovine uterine serpin

    Directory of Open Access Journals (Sweden)

    Hansen Peter J

    2008-01-01

    Full Text Available Abstract Background Uterine serpins are members of the serine proteinase inhibitor superfamily. Like some other serpins, these proteins do not appear to be functional proteinase inhibitors. The most studied member of the group, ovine uterine serpin (OvUS, inhibits proliferation of several cell types including activated lymphocytes, bovine preimplantation embryos, and cell lines for lymphoma, canine primary osteosarcoma and human prostate cancer (PC-3 cells. The goal for the present study was to evaluate the mechanism by which OvUS inhibits cell proliferation. In particular, it was tested whether inhibition of DNA synthesis in PC-3 cells involves cytotoxic actions of OvUS or the induction of apoptosis. The effect of OvUS in the production of the autocrine and angiogenic cytokine interleukin (IL-8 by PC-3 cells was also determined. Finally, it was tested whether OvUS blocks specific steps in the cell cycle using both PC-3 cells and lymphocytes. Results Recombinant OvUS blocked proliferation of PC-3 cells at concentrations as low as 8 μg/ml as determined by measurements of [3H]thymidine incorporation or ATP content per well. Treatment of PC-3 cells with OvUS did not cause cytotoxicity or apoptosis or alter interleukin-8 secretion into medium. Results from flow cytometry experiments showed that OvUS blocked the entry of PC-3 cells into S phase and the exit from G2/M phase. In addition, OvUS blocked entry of lymphocytes into S phase following activation of proliferation with phytohemagglutinin. Conclusion Results indicate that OvUS acts to block cell proliferation through disruption of the cell cycle dynamics rather than induction of cytotoxicity or apoptosis. The finding that OvUS can regulate cell proliferation makes this one of only a few serpins that function to inhibit cell growth.

  17. Synthesis of novel flavone derivatives possessing substituted benzamides and their biological evaluation against human cancer cells.

    Science.gov (United States)

    Yun, Bo Hee; Lee, Young Hun; Park, Kyung Tae; Jung, Su Jin; Lee, Yong Sup

    2016-09-01

    Baicalein is a well-known flavone derivative that possesses diverse biological properties, such as anticancer, antioxidant and anti-inflammatory activities. Numerous baicalein derivatives, including 5,6,7-trimethoxyflavone, have been synthesized with the aim of enhancing its inherent biological activities. In the present work, new flavones, possessing an N-aroylamine-substituent on the B-ring, were synthesized to improve the cytotoxicity of baicalein and 5,6,7-trimethoxyflavone against human cancer cell lines. The majority of the flavones synthesized exhibited greater cytotoxicity than baicalein and 5,6,7-trimethoxyflavone against HepG2 and MCF-7 cells. Among them, compounds 5n, possessing a 3-methoxybenzoylamino group, exhibited great cytotoxic effects on HepG2 (GI50=7.06μM) and MCF-7 (GI50=7.67μM) cells. In contrast, N-aroylamine-substituted 5-hydroxy-6,7-dimethoxyflavone derivatives showed greater cytotoxicity against MCF-7 than HepG2 cells, indicating that the replacement of a 5-methoxy group on the A-ring with a 5-hydroxy group has a marked influence on the cytotoxicity profile. PMID:27503682

  18. Synthesis and screening of ursolic acid-benzylidine derivatives as potential anti-cancer agents.

    Science.gov (United States)

    Dar, Bilal Ahmad; Lone, Ali Mohd; Shah, Wajaht Amin; Qurishi, Mushtaq Ahmad

    2016-03-23

    Ursolic acid present abundantly in plant kingdom is a well-known compound with various promising biological activities including, anti-cancer, anti-inflammatory, hepatoprotective, antiallergic and anti-HIV properties. Herein, a library of ursolic acid-benzylidine derivatives have been designed and synthesized using Claisen Schmidt condensation of ursolic acid with various aromatic aldehydes in an attempt to develop potent antitumor agents. The compounds were evaluated against a panel of four human carcinoma cell lines including, A-549 (lung), MCF-7 (breast), HCT-116 (colon), THP-1 (leukemia) and a normal human epithelial cell line (FR-2). The results from MTT assay revealed that all the compounds displayed high level of antitumor activities compared with the triazole analogs (previously reported) and the parent ursolic acid. However, compound 3b, the most active derivative was subjected to mechanistic studies to understand the underlying mechanism. The results revealed that compound 3b induced apoptosis in HCT-116 cell lines, arrest cell cycle in the G1 phase, caused accumulation of cytochrome c in the cytosol and increased the expression levels of caspase-9 and caspase-3 proteins. Therefore, compound 3b induces apoptosis in HCT-116 cells through mitochondrial pathway. PMID:26854375

  19. Advantages of a dual-tracer model over reference tissue models for binding potential measurement in tumors

    International Nuclear Information System (INIS)

    The quantification of tumor molecular expression in vivo could have a significant impact for informing and monitoring emerging targeted therapies in oncology. Molecular imaging of targeted tracers can be used to quantify receptor expression in the form of a binding potential (BP) if the arterial input curve or a surrogate of it is also measured. However, the assumptions of the most common approaches (reference tissue models) may not be valid for use in tumors. In this study, the validity of reference tissue models is investigated for use in tumors experimentally and in simulations. Three different tumor lines were grown subcutaneously in athymic mice and the mice were injected with a mixture of an epidermal growth factor receptor-targeted fluorescent tracer and an untargeted fluorescent tracer. A one-compartment plasma input model demonstrated that the transport kinetics of both tracers was significantly different between tumors and all potential reference tissues, and using the reference tissue model resulted in a theoretical underestimation in BP of 50% ± 37%. On the other hand, the targeted and untargeted tracers demonstrated similar transport kinetics, allowing a dual-tracer approach to be employed to accurately estimate BP (with a theoretical error of 0.23% ± 9.07%). These findings highlight the potential for using a dual-tracer approach to quantify receptor expression in tumors with abnormal hemodynamics, possibly to inform the choice or progress of molecular cancer therapies. (paper)

  20. Tracer-based prediction of thermal reservoir lifetime: scope, limitations, and the role of thermosensitive tracers

    Science.gov (United States)

    Ghergut, I.; Behrens, H.; Karmakar, S.; Licha, T.; Nottebohm, M.; Sauter, M.

    2012-04-01

    Thermal-lifetime prediction is a traditional endeavour of inter-well tracer tests conducted in geothermal reservoirs. Early tracer test signals (detectable within the first few years of operation) are expected to correlate with late-time production temperature evolutions ('thermal breakthrough', supposed to not occur before some decades of operation) of a geothermal reservoir. Whenever a geothermal reservoir can be described as a single-fracture system, its thermal lifetime will, ideally, be determined by two parameters (say, fracture aperture and porosity), whose inversion from conservative-tracer test signals is straightforward and non-ambiguous (provided that the tracer tests, and their interpretation, are performed in accordance to the rules of the art). However, as soon as only 'few more' fractures are considered, this clear-cut correlation is broken. A given geothermal reservoir can simultaneously feature a single-fracture behaviour, in terms of heat transport, and a multiple-fracture behaviour, in terms of solute tracer transport (or vice-versa), whose effective values of fracture apertures, spacings, and porosities are essentially uncorrelated between heat and solute tracers. Solute transport parameters derived from conservative-tracer tests will no longer characterize the heat transport processes (and thus temperature evolutions) taking place in the same reservoir. Parameters determining its thermal lifetime will remain 'invisible' to conservative tracers in inter-well tests. We demonstrate this issue at the example of a five-fracture system, representing a deep-geothermal reservoir, with well-doublet placement inducing fluid flow 'obliquely' to the fractures. Thermal breakthrough in this system is found to strongly depend on fracture apertures, whereas conservative-solute tracer signals from inter-well tests in the same system do not show a clear-cut correlation with fracture apertures. Only by using thermosensitive substances as tracers, a reliable

  1. [Cancer].

    Science.gov (United States)

    de la Peña-López, Roberto; Remolina-Bonilla, Yuly Andrea

    2016-09-01

    Cancer is a group of diseases which represents a significant public health problem in Mexico and worldwide. In Mexico neoplasms are the second leading cause of death. An increased morbidity and mortality are expected in the next decades. Several preventable risk factors for cancer development have been identified, the most relevant including tobacco use, which accounts for 30% of the cancer cases; and obesity, associated to another 30%. These factors, in turn, are related to sedentarism, alcohol abuse and imbalanced diets. Some agents are well knokn to cause cancer such as ionizing radiation, viruses such as the papilloma virus (HPV) and hepatitis virus (B and C), and more recently environmental pollution exposure and red meat consumption have been pointed out as carcinogens by the International Agency for Research in Cancer (IARC). The scientific evidence currently available is insufficient to consider milk either as a risk factor or protective factor against different types of cancer. PMID:27603890

  2. Proceedings of Tracer 3. International Conference on Tracers and Tracing Methods

    International Nuclear Information System (INIS)

    Tracer 3 conference is a continuation of former Tracer 1 (1998) and Tracer 2 (2001) conferences organized by CNRS - Nancy France. The objective of this 3rd conference is presentation of different aspects of tracer method applications and development of tracer methodology.The new field of activity presented at the Conference was application of stable isotopes as natural tracers for investigations of environmental processes. The conference gave the possibility for scientific information exchange between specialists from different fields of activity such as chemical engineering, chemistry, bioengineering, environmental engineering, hydrology, civil engineering, metallurgy, etc. The presentations were divided into groups covering the principal items of Conference. Section A. Fundamental development - RTD and tracer methodology, - RTD methodology and Computational Fluid Dynamics (CFD), - New tracers and detectors. Section B. Industrial applications - Environment, - Geology, hydrogeology and oil field applications, - Civil engineering, mineral engineering and metallurgy applications, - Food engineering and bioengineering, - Material engineering, - Chemical engineering. During the Conference INIS promotion materials were exposed by INIS liaison officer for Poland

  3. Long residence times - bad tracer tests?

    Science.gov (United States)

    Ghergut, Julia; Behrens, Horst; Sauter, Martin

    2015-04-01

    Tracer tests conducted at geothermal well doublets or triplets in the Upper Rhine Rift Valley [1] all face, with very few exceptions so far, one common issue: lack of conclusive tracer test results, or tracer signals still undetectable for longer than one or two years after tracer injection. While the reasons for this surely differ from site to site (Riehen, Landau, Insheim, Bruchsal, ...), its effects on how the usefulness of tracer tests is perceived by the non-tracer community are pretty much the same. The 'poor-signal' frustration keeps nourishing two major 'alternative' endeavours : (I) design and execute tracer tests in single-well injection-withdrawal (push-pull), 'instead of' inter-well flow-path tracing configurations; (II) use 'novel' tracer substances instead of the 'old' ones which have 'obviously failed'. Frustration experienced with most inter-well tracer tests in the Upper Rhine Rift Valley has also made them be regarded as 'maybe useful for EGS' ('enhanced', or 'engineered' geothermal systems, whose fluid RTD typically include a major share of values below one year), but 'no longer worthwhile a follow-up sampling' in natural, large-scale hydrothermal reservoirs. We illustrate some of these arguments with the ongoing Bruchsal case [2]. The inter-well tracer test conducted at Bruchsal was (and still is!) aimed at assessing inter-well connectivity, fluid residence times, and characterizing the reservoir structure [3]. Fluid samples taken at the geothermal production well after reaching a fluid turnover of about 700,000 m3 showed tracer concentrations in the range of 10-8 Minj per m3, in the liquid phase of each sample (Minj being the total quantity of tracer injected as a short pulse at the geothermal re-injection well). Tracer signals might actually be higher, owing to tracer amounts co-precipitated and/or adsorbed onto the solid phase whose accumulation in the samples was unavoidable (due to pressure relief and degassing during the very sampling

  4. Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells.

    Science.gov (United States)

    Tian, Yuantong; Zhao, Lijing; Wang, Ye; Zhang, Haitao; Xu, Duo; Zhao, Xuejian; Li, Yi; Li, Jing

    2016-01-01

    Aldo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aldo-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rv1 cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family 1 member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form p-p interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family 1 member C3 enzyme activity and the inhibition of 22Rv1 prostate cancer cell growth by decreasing the intracellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKR1C3 inhibitors using berberine as the lead compound. PMID:26698234

  5. Exploring Hydrofluorocarbons as Groundwater Age Tracers (Invited)

    Science.gov (United States)

    Haase, K. B.; Busenberg, E.; Plummer, L. N.; Casile, G.; Sanford, W. E.

    2013-12-01

    Groundwater dating tracers are an essential tool for analyzing hydrologic conditions in groundwater systems. Commonly used tracers for dating post-1940's groundwater include sulfur hexafluoride (SF6), chlorofluorocarbons (CFCs), 3H-3He, and other isotopic tracers (85Kr, δ2H and δ18O isotopes, etc.). Each tracer carries a corresponding set of advantages and limitations imposed by field, analytical, and interpretive methods. Increasing the number available tracers is appealing, particularly if they possess inert chemical properties and unique temporal emission histories from other tracers. Atmospherically derived halogenated trace gases continue to hold untapped potential for new tracers, as they are generally inert and their emission histories are well documented. SF5CF3, and CFC-13 were previously shown to have application as dating tracers, though their low mixing ratios and low solubility require large amounts of water to be degassed for their quantification. Two related groups of compounds, hydrochlorofluorocarbons (HCFCs) and hydrofluorocarbons (HFCs) are hypothesized to be potential age tracers, having similar mixing ratios to the CFCs and relatively high solubility. However, these compounds yield gas chromatography electron capture detector (GC-ECD) responses that are 10-2 -10-5 less than CFC-12, making purge and trap or field stripping GC-ECD approaches impractical. Therefore, in order to use dissolved HCFCs and HFCs as age tracers, different approaches are needed. To solve this problem, we developed an analytical method that uses an atomic emission detector (GC-AED) in place of an ECD to detect fluorinated compounds. In contrast to the ECD, the AED is a universally sensitive, highly linear, elementally specific detector. The new GC-AED system is being used to measure chlorodifluoromethane (HCFC-22), 1,1,1,2-tetrafluoroethane (HFC-134a), and other fluorinated compounds in one liter water samples to study their potential as age dating tracers. HCFC-22 is a

  6. Process flow measurement based on tracer techniques

    International Nuclear Information System (INIS)

    Flow measurement methods based on the tracer techniques are the transit time method as well as methods based on tracer dilution. These methods can be applied to the on-site calibration of flowmeters and to measuring the flowrate where no flowmeter is installed. The accuracy of the tracer methods depends on the prevailing measuring conditions. In this report the accuracy of the transit time method under field conditions is estimated to be 1-2% on the 99,7% confidence level. The accuracy of the isotope dilution method is estimated as slightly better, namely about 0.5% at its best. An even better accuracy, about 0.2%, could be achieved by developing the method and the measuring equipment. Tests were carried out with the transit time method for water and steam flow. While measuring water flow the effect of different measuring parameters upon the repeatability of the method were looked into. Such were the number of the detectors and the distance between the measuring points. Different means of tracer injection were tested, as well. These had less effect than expected. The accuracies achieved in steam flow measurements were of the same order of magnitude as in water flow measurements. The tracers used were 137mBa for water flow and 41Ar for steam flow measurements

  7. Simulation and interpretation of inter-well tracer tests

    International Nuclear Information System (INIS)

    In inter-well tracer tests (IWTT), chemical compounds or radioactive isotopes are used to label injection water and gas to establish well connections and fluid patterns in petroleum reservoirs. Tracer simulation is an invaluable tool to ease the interpretation of IWTT results and is also required for assisted history matching application of tracer data. In this paper we present a new simulation technique to analyse and interpret tracer results. Laboratory results are used to establish and test formulations of the tracer conservation equations, and the technique is used to provide simulated tracer responses that are compared with observed tracer data from an extensive tracer program. The implemented tracer simulation methodology use a fast post-processing of previously simulated reservoir simulation runs. This provides a fast, flexible and powerful method for analysing gas tracer behaviour in reservoirs. We show that simulation time for tracers can be reduced by factor 100 compared to solving the tracer flow equations simultaneously with the reservoir fluid flow equations. The post-processing technique, combined with a flexible built-in local tracer-grid refinement is exploited to reduce numerical smearing, particularly severe for narrow tracer pulses. (authors)

  8. Particle and tracer diffusion in complex liquids

    Science.gov (United States)

    Koynov, Kaloian; Butt, Hans-Jürgen

    2013-02-01

    The diffusion of fluorescent tracers can be studied using fluorescence correlation spectroscopy (FCS). This powerful method offers the possibility to monitor very small tracers at low concentrations, down to single molecules. Furthermore it possesses a sub-femtoliter detection volume that can be precisely positioned in a heterogeneous environment to probe the local dynamics. Despite its great potential and high versatility in addressing the diffusion and transport properties in complex systems, FCS has been predominantly applied in molecular and cell biology. Here we present some applications that are more relevant for material and soft matter science. First, we study the diffusion of single tracers with molecular sizes in undiluted polymer systems. Next, the diffusion of small molecules and semiconductor nanoparticles (quantum dots) in silica inverse opals is studied and correlated to the size and morphology of the inverse opals. Finally, we show how FCS can be used to measure the diffusion coefficient of nanoparticles at water-oil interfaces.

  9. Use of radioactive tracers in dynamic sedimentology

    International Nuclear Information System (INIS)

    In the first part, developments in the use of radioactive tracers in sedimentology are recalled together with the corresponding fields of application and the identities of the main users. The state-of-the-art in France is also discussed; The main characteristics of the method are then described and compared with those of more classical methods. The results that can be obtained with tracer methods are then outlined. The criteria employed to establish the granulometry characteristics of the tracer, the particular radioisotope to be used, and the masses and activities involved, are treated. A list is then given of the main isotopes available in France and their characteristics. The various different labelling techniques employed are studied together with their respective advantages and disadvantages. The special case of pelitic sediments is mentioned. The use of reduced model isotope generators, double labelling and applications to studies of the mud plug in the Gironde Estuary are also discussed. The methods and materials used for injecting and detecting tracers are described, emphasis being given to the economic factors associated with the use of radioactive tracers in sedimentology. The second part of the report contains two chapters: - studies of transport by driftage: presentation and analysis of results and the application of the Count Rate Balance method to obtain quantitative information on transport; - studies of in-suspension transport of fine sediments in the sea: the procedures adopted from the moment when the tracer is introduced up to the time when the results are analyzed and interpreted, enables the trajectories and mean velocities of the transported sediments to be determined together with their degree of dilution and their settling speeds and rates; it is also possible to investigate the evolution and horizontal dispersion of the sediments in this way. Results from recent experiments are presented in both parts of the report

  10. Dynamics and mechanics of tracer particles

    Science.gov (United States)

    Phillips, C. B.; Jerolmack, D. J.

    2014-06-01

    Understanding the mechanics of bed load at the flood scale is necessary to link hydrology to landscape evolution. Here we report on observations of the transport of coarse sediment tracer particles in a cobble-bedded alluvial river and a step-pool tributary, at the individual flood and multi-annual timescales. Tracer particle data for each survey are composed of measured displacement lengths for individual particles, and the number of tagged particles mobilized. For single floods we find that: measured tracer particle displacement lengths are exponentially distributed; the number of mobile particles increases linearly with peak flood Shields stress, indicating partial bed load transport for all observed floods; and modal displacement lengths scale linearly with excess shear velocity. These findings provide quantitative field support for a recently proposed modelling framework based on momentum conservation at the grain scale. Tracer displacement shows a weak correlation with particle size at the individual flood scale, however cumulative travel distance begins to show an inverse relation to grain size when measured over many transport events. The observed spatial sorting of tracers approaches that of the river bed, and is consistent with size-selective deposition models and laboratory experiments. Tracer displacement data for the step-pool and alluvial channels collapse onto a single curve - despite more than an order of magnitude difference in channel slope - when variations of critical Shields stress and flow resistance between the two are accounted for. Results show how bed load dynamics may be predicted from a record of river stage, providing a direct link between climate and sediment transport.

  11. Methodical aspects in the determination of parameters of N metabolization from 15N tracer experiments with pigs on the basis of models of N metabolism. 3

    International Nuclear Information System (INIS)

    For final product method introduced here is based on the use of 15N-L-lysine as tracer amino acid for the determination of the protein synthesis and decomposition quotas of the total body with the flux of lysine. For this purpose it is necessary to complete the N flow and N compartments of the 3-pool model by the values of lysine content. The ascertained values of protein synthesis-8.4 g/d/kg-and protein decomposition- 6.9 g/d/kg-agree very well with those determined with 15N-glycine as tracer amino acid. (author)

  12. Radionuclide tracers of submarine groundwater discharge

    International Nuclear Information System (INIS)

    Radionuclide tracers have the ability to assess the flux of submarine groundwater discharge (SGD) over a range of temporal and spatial scales. Short-lived isotopes such as 222Rn, 224Ra, and 223Ra can reveal sites where SGD impacts the coastal ocean and elucidate relationships between SGD and ocean forces such as tides and storms. Longer-lived isotopes such as 228Ra and 226Ra integrate the effects of SGD over longer scales. These isotopes can discriminate sources of SGD and evaluate total fluxes. This paper will investigate the application of radionuclide tracers to SGD in a variety of settings on different continents. (author)

  13. Selection of tracers for oil and gas evaluation

    International Nuclear Information System (INIS)

    The importance of tracer tests in reservoir descriptions is increasingly acknowledged by reservoir engineers as a method to obtain valuable dynamic information from the reservoir. The report describes the ''state-of-the art'' on tracer technology for interwell investigations. Experiences gained from a number of reported field tracer tests are reviewed, and results from detailed laboratory investigations on the static and dynamic behavior of various tracer molecules are discussed. A critical evaluation of the applicability of the various identified tracers is provided. Present and future trends in the development of tracer technology for reservoir description are sketched. 64 refs., 12 figs., 2 tabs

  14. Sleep and cancer: Synthesis of experimental data and meta-analyses of cancer incidence among some 1,500,000 study individuals in 13 countries.

    Science.gov (United States)

    Erren, T C; Morfeld, P; Foster, R G; Reiter, R J; Groß, J V; Westermann, I K

    2016-01-01

    Sleep and its impact on physiology and pathophysiology are researched at an accelerating pace and from many different angles. Experiments provide evidence for chronobiologically plausible links between chronodisruption and sleep and circadian rhythm disruption (SCRD), on the one hand, and the development of cancer, on the other. Epidemiological evidence from cancer incidence among some 1 500 000 study individuals in 13 countries regarding associations with sleep duration, napping or "poor sleep" is variable and inconclusive. Combined adjusted relative risks (meta-RRs) for female breast cancer, based on heterogeneous data, were 1.01 (95% CI: 0.97-1.06). Meta-RRs for cancers of the colorectum and of the lung in women and men and for prostate cancer were 1.08 (95% CI: 1.03-1.13), 1.11 (95% CI: 1.00-1.22) and 1.05 (95% CI: 0.83-1.33), respectively. The significantly increased meta-RRs for colorectal cancer, based on homogeneous data, warrant targeted study. However, the paramount epidemiological problem inhibiting valid conclusions about the associations between sleep and cancer is the probable misclassification of the exposures to facets of sleep over time. Regarding the inevitable conclusion that more research is needed to answer How are sleep and cancer linked in humans? we offer eight sets of recommendations for future studies which must take note of the complexity of multidirectional relationships. PMID:27003385

  15. An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine

    International Nuclear Information System (INIS)

    Radiolabeled amino acids have been used extensively in oncology both as diagnostic and therapeutic agents. In our pursuit to develop radiopharmaceuticals to target breast cancer, we were interested in determining the uptake of radioiodinated 4-iodophenylalanine, among other labeled amino acids, in breast cancer cells. In this work, we have developed an alternative method for the synthesis of this agent. The novel tin precursor, (S)-tert-butyl 2-(tert-butoxycarbonylamino)-3-(4-(tributylstannyl)phenyl)propanoate (3) was synthesized from the known, corresponding iodo derivative. Initially, the labeled 4-iodophenylalanine was synthesized from the above tin precursor in two steps with radiochemical yields of 91.6±2.7% and 83.7±1.7% (n=5), for the radioiodination (first) and deprotection (second) step, respectively. Subsequently, it was synthesized in a single step with an average radiochemical yield of 94.8±3.4% (n=5). After incubation with MCF-7 breast cancer cells for 60 min, an uptake of up to 49.0±0.7% of the input dose was seen; in comparison, the uptake of [14C]phenylalanine under the same conditions was 55.9±0.5%. Furthermore, the uptake of both tracers was inhibited to a similar degree in a concentration-dependent manner by both unlabeled phenylalanine and 4-iodophenylalanine. With [14C]phenylalanine as the tracer, IC50 values of 1.45 and 2.50 mM were obtained for Phe and I-Phe, respectively, and these values for [125I]I-Phe inhibition were 1.3 and 1.0 mM. In conclusion, an improved and convenient method for the synthesis of no-carrier-added 4-[*I]phenylalanine was developed and the radiotracer prepared by this route demonstrated an amino acid transporter-mediated uptake in MCF-7 breast cancer cells in vitro that was comparable to that of [14C]phenylalanine. - Highlights: → A new method to synthesize radioiodinated 4-iodophenylalanine. → Acid-labile protecting groups containing tin precursor. → Efficient removal of both protecting groups in a single

  16. An alternative and expedient synthesis of radioiodinated 4-iodophenylalanine

    Energy Technology Data Exchange (ETDEWEB)

    Vaidyanathan, Ganesan, E-mail: ganesan.v@duke.edu [Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710 (United States); McDougald, Darryl; Grasfeder, Linda; Zalutsky, Michael R.; Chin, Bennett [Department of Radiology, Box 3808, Duke University Medical Center, Durham, NC 27710 (United States)

    2011-10-15

    Radiolabeled amino acids have been used extensively in oncology both as diagnostic and therapeutic agents. In our pursuit to develop radiopharmaceuticals to target breast cancer, we were interested in determining the uptake of radioiodinated 4-iodophenylalanine, among other labeled amino acids, in breast cancer cells. In this work, we have developed an alternative method for the synthesis of this agent. The novel tin precursor, (S)-tert-butyl 2-(tert-butoxycarbonylamino)-3-(4-(tributylstannyl)phenyl)propanoate (3) was synthesized from the known, corresponding iodo derivative. Initially, the labeled 4-iodophenylalanine was synthesized from the above tin precursor in two steps with radiochemical yields of 91.6{+-}2.7% and 83.7{+-}1.7% (n=5), for the radioiodination (first) and deprotection (second) step, respectively. Subsequently, it was synthesized in a single step with an average radiochemical yield of 94.8{+-}3.4% (n=5). After incubation with MCF-7 breast cancer cells for 60 min, an uptake of up to 49.0{+-}0.7% of the input dose was seen; in comparison, the uptake of [{sup 14}C]phenylalanine under the same conditions was 55.9{+-}0.5%. Furthermore, the uptake of both tracers was inhibited to a similar degree in a concentration-dependent manner by both unlabeled phenylalanine and 4-iodophenylalanine. With [{sup 14}C]phenylalanine as the tracer, IC{sub 50} values of 1.45 and 2.50 mM were obtained for Phe and I-Phe, respectively, and these values for [{sup 125}I]I-Phe inhibition were 1.3 and 1.0 mM. In conclusion, an improved and convenient method for the synthesis of no-carrier-added 4-[{sup *}I]phenylalanine was developed and the radiotracer prepared by this route demonstrated an amino acid transporter-mediated uptake in MCF-7 breast cancer cells in vitro that was comparable to that of [{sup 14}C]phenylalanine. - Highlights: > A new method to synthesize radioiodinated 4-iodophenylalanine. > Acid-labile protecting groups containing tin precursor. > Efficient removal

  17. Selective synthesis of either enantiomer of an anti-breast cancer agent via a common enantioenriched intermediate

    Science.gov (United States)

    Johnson, Aaron George; Tranquilli, Marissa M.; Harris, Michael R.; Jarvo, Elizabeth R.

    2015-01-01

    A stereoselective synthesis of a bioactive triarylmethane is described. Key to the synthesis is a nickel-catalyzed Suzuki-Miyaura coupling which proceeds with retention at the benzylic center. This method is complementary to our previously reported nickel-catalyzed Kumada coupling which proceeds with inversion. Together, the two methods allow for efficient access to either enantiomer of biologically relevant triarylmethanes from a common enantioenriched intermediate. PMID:26085695

  18. Planetary Nebulae as Mass Tracers in Galaxies

    OpenAIRE

    Romanowsky, Aaron J.

    2006-01-01

    Planetary nebula are useful kinematic tracers of the stars in all galaxy types. I review recent observationally-driven developments in the study of galaxy mass profiles. These have yielded surprising results on spiral galaxy disk masses and elliptical galaxy halo masses. A key remaining question is the coupling between PNe and the underlying stellar populations.

  19. Suitability of tracers; Eignung von Tracern

    Energy Technology Data Exchange (ETDEWEB)

    Klotz, D. [GSF - Forschungszentrum fuer Umwelt und Gesundheit GmbH, Neuherberg (Germany). Inst. fuer Hydrologie

    1999-02-01

    Hydrological tracer techniques are a means of making statements on the direction and speed of underground water. One of the simpler tasks is to find out whether there is hydrological communication between two given points. This requires a determination of the direction of flow, which places less exacting demands on the properties of the tracer than does the task of determining the flow velocity of underground water. Tracer methods can serve to infer from flow velocity the distance (flow) velocity, which is defined as the ratio between the distance between two points located in flow direction and the actual time it takes water to flow from one to the other. [Deutsch] Mit Hilfe der hydrologischen Markierungstechniken koennen Aussagen ueber die Richtung und die Geschwindigkeit von Bewegungen des unterirdischen Wassers gemacht werden. Der einfachere Fall liegt vor, wenn festgestellt werden soll, ob zwischen zwei Punkten eine hydrologische Verbindung besteht. Bei dieser Fliessrichtungsbestimmung sind die Forderungen an die Eigenschaften der einzusetzenden Tracer geringer als bei der Bestimmung der Geschwindigkeit des unterirdischen Wassers. Von den Geschwindigkeiten des unterirdischen Wassers ist die Abstands-(Fliess)geschwindigkeit, die definiert ist durch das Verhaeltnis aus dem Abstand und der wahren Fliesszeit zwischen zwei in Bewegungsrichtung gelegenen Punkten, durch Tracermethoden zu bestimmen. (orig.)

  20. Using radioactive tracer technique in municipal hygiene

    International Nuclear Information System (INIS)

    Work of the A. N. Syrsin Institute of General and Municiapl Hygiene using raidoactive tracers is reviewed. The studies include research on protein metabolism in the living organism following action of unfavorable factors of the environment; determination of the paths of introduction into the organism of substances with an alien composition; and study of the rate of resorption of subcutaneous papuli. Results are shown of radioactive-tracer studies on the mechanism of action of poisonous substances on the living organism and of migration of alien chemical compounds in the organism and in objects in the environment. It is concluded that the radioactive tracer method has wide application in municipal hygiene and sanitary microbiology. The absence of laborious operations, economy of time, precision of the experiments, and the possibility of obtaining additional information on the mechanism of action of poisonous substances on the organism and the low cost of such studies compared with other methods makes the radioactive tracer method economically attractive. The studies made show the various types of use of the method in municipal hygiene and sanitary microbiology

  1. Fractal tracer distributions in turbulent field theories

    DEFF Research Database (Denmark)

    Hansen, J. Lundbek; Bohr, Tomas

    1998-01-01

    We study the motion of passive tracers in a two-dimensional turbulent velocity field generated by the Kuramoto-Sivashinsky equation. By varying the direction of the velocity-vector with respect to the field-gradient we can continuously vary the two Lyapunov exponents for the particle motion and t...

  2. Nanoparticle tracers in calcium carbonate porous media

    KAUST Repository

    Li, Yan Vivian

    2014-07-15

    Tracers are perhaps the most direct way of diagnosing subsurface fluid flow pathways for ground water decontamination and for natural gas and oil production. Nanoparticle tracers could be particularly effective because they do not diffuse away from the fractures or channels where flow occurs and thus take much less time to travel between two points. In combination with a chemical tracer they can measure the degree of flow concentration. A prerequisite for tracer applications is that the particles are not retained in the porous media as the result of aggregation or sticking to mineral surfaces. By screening eight nanoparticles (3-100 nm in diameter) for retention when passed through calcium carbonate packed laboratory columns in artificial oil field brine solutions of variable ionic strength we show that the nanoparticles with the least retention are 3 nm in diameter, nearly uncharged, and decorated with highly hydrophilic polymeric ligands. The details of these column experiments and the tri-modal distribution of zeta potential of the calcite sand particles in the brine used in our tests suggests that parts of the calcite surface have positive zeta potential and the retention of negatively charged nanoparticles occurs at these sites. Only neutral nanoparticles are immune to at least some retention. © 2014 Springer Science+Business Media.

  3. Using neural networks to describe tracer correlations

    Directory of Open Access Journals (Sweden)

    D. J. Lary

    2004-01-01

    Full Text Available Neural networks are ideally suited to describe the spatial and temporal dependence of tracer-tracer correlations. The neural network performs well even in regions where the correlations are less compact and normally a family of correlation curves would be required. For example, the CH4-N2O correlation can be well described using a neural network trained with the latitude, pressure, time of year, and methane volume mixing ratio (v.m.r.. In this study a neural network using Quickprop learning and one hidden layer with eight nodes was able to reproduce the CH4-N2O correlation with a correlation coefficient between simulated and training values of 0.9995. Such an accurate representation of tracer-tracer correlations allows more use to be made of long-term datasets to constrain chemical models. Such as the dataset from the Halogen Occultation Experiment (HALOE which has continuously observed CH4  (but not N2O from 1991 till the present. The neural network Fortran code used is available for download.

  4. Travel-time-based thermal tracer tomography

    Science.gov (United States)

    Somogyvári, Márk; Bayer, Peter; Brauchler, Ralf

    2016-05-01

    Active thermal tracer testing is a technique to get information about the flow and transport properties of an aquifer. In this paper we propose an innovative methodology using active thermal tracers in a tomographic setup to reconstruct cross-well hydraulic conductivity profiles. This is facilitated by assuming that the propagation of the injected thermal tracer is mainly controlled by advection. To reduce the effects of density and viscosity changes and thermal diffusion, early-time diagnostics are used and specific travel times of the tracer breakthrough curves are extracted. These travel times are inverted with an eikonal solver using the staggered grid method to reduce constraints from the pre-defined grid geometry and to improve the resolution. Finally, non-reliable pixels are removed from the derived hydraulic conductivity tomograms. The method is applied to successfully reconstruct cross-well profiles as well as a 3-D block of a high-resolution fluvio-aeolian aquifer analog data set. Sensitivity analysis reveals a negligible role of the injection temperature, but more attention has to be drawn to other technical parameters such as the injection rate. This is investigated in more detail through model-based testing using diverse hydraulic and thermal conditions in order to delineate the feasible range of applications for the new tomographic approach.

  5. Hybrid tracers for sentinel node biopsy

    International Nuclear Information System (INIS)

    Conventional sentinel node (SN) mapping is performed by injection of a radiocolloid followed by lymphoscintigraphy to identify the number and location of the primary tumor draining lymph node(s), the so-called SN(s). Over the last decade research has focused on the introduction of new imaging agents that can further aid (surgical) SN identification. Different tracers for SN mapping, with varying sizes and isotopes have been reported, most of which have proven their value in a clinical setting. A major challenge lies in transferring this diagnostic information obtained at the nuclear medicine department to the operating theatre thereby providing the surgeon with (image) guidance. Conventionally, an intraoperative injection of vital blue dye or a fluorescence dye is given to allow intraoperative optical SN identification. However, for some indications, the radiotracer-based approach remains crucial. More recently, hybrid tracers, that contain both a radioactive and fluorescent label, were introduced to allow for direct integration of pre- and intraoperative guidance technologies. Their potential is especially high when they are used in combination with new surgical imaging modalities and navigation tools. Next to a description of the known tracers for SN mapping, this review discusses the application of hybrid tracers during SN biopsy and how the introduction of these new techniques can further aid in translation of nuclear medicine information into the operating theatre.

  6. Forbidden calcium lines as disc tracers

    CERN Document Server

    Aret, Anna

    2015-01-01

    Forbidden emission lines are particularly valuable disc tracers, because their profiles reflect the kinematics within their formation region. Here we present a short excerpt from the results of a spectroscopic survey of evolved massive stars surrounded by high-density discs.

  7. Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): Does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

    Energy Technology Data Exchange (ETDEWEB)

    Regier, M., E-mail: mregier@uke.uni-hamburg.de [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Derlin, T. [Center for Radiology and Endoscopy, Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Schwarz, D.; Laqmani, A.; Henes, F.O.; Groth, M.; Buhk, J.-H. [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Kooijman, H. [Philips Healthcare, Clinical Application, Luebeckertordamm 5, 20099 Hamburg (Germany); Adam, G. [Center for Radiology and Endoscopy, Department of Diagnostic and Interventional Radiology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

    2012-10-15

    Introduction: To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). Materials and methods: 18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm{sup 2}) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUV{sub mean}) and maximum (SUV{sub max}) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADC{sub mean}) and minimum ADC (ADC{sub min}) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland–Altman and regression analysis were assessed. Results: Data analysis revealed a significant inverse correlation of the ADC{sub min} and SUV{sub max} (r = −0.46; p = 0.032). Testing the correlation of the ADC{sub min} and SUV{sub max} for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r = −0.47; p = 0.03) and squamouscell carcinomas (r = −0.71; p = 0.002), respectively. No significant correlation was found for the comparison of ADC{sub min} and SUV{sub mean} (r = −0.29; p = 0.27), ADC{sub mean} vs. SUV{sub mean} (r = −0.28; p = 0.31) or ADC{sub mean} vs. SUV{sub max} (r = −0.33; p = 0.23). The κ-value of 0.88 indicated a good agreement between both observers. Conclusion: This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC.

  8. Diffusion weighted MRI and 18F-FDG PET/CT in non-small cell lung cancer (NSCLC): Does the apparent diffusion coefficient (ADC) correlate with tracer uptake (SUV)?

    International Nuclear Information System (INIS)

    Introduction: To investigate the potential correlation of the apparent diffusion coefficient assessed by diffusion-weighted MRI (DWI) and glucose metabolism determined by the standardized uptake value (SUV) at 18F-FDG PET/CT in non-small cell lung cancer (NSCLC). Materials and methods: 18F-FDG PET/CT and DWI (TR/TE, 2000/66 ms; b-values, 0 and 500 s/mm2) were performed in 41 consecutive patients with histologically verified NSCLC. Analysing the PET-CT data calculation of the mean (SUVmean) and maximum (SUVmax) SUV was performed. By placing a region-of-interest (ROI) encovering the entire tumor mean (ADCmean) and minimum ADC (ADCmin) were determined by two independent radiologists. Results of 18F-FDG PET-CT and DWI were compared on a per-patient basis. For statistical analysis Pearson's correlation coefficient, Bland–Altman and regression analysis were assessed. Results: Data analysis revealed a significant inverse correlation of the ADCmin and SUVmax (r = −0.46; p = 0.032). Testing the correlation of the ADCmin and SUVmax for each histological subtype separately revealed that the inverse correlation was good for both adenocarcinomas (r = −0.47; p = 0.03) and squamouscell carcinomas (r = −0.71; p = 0.002), respectively. No significant correlation was found for the comparison of ADCmin and SUVmean (r = −0.29; p = 0.27), ADCmean vs. SUVmean (r = −0.28; p = 0.31) or ADCmean vs. SUVmax (r = −0.33; p = 0.23). The κ-value of 0.88 indicated a good agreement between both observers. Conclusion: This preliminary study is the first to verify the relation between the SUV and the ADC in NSCLC. The significant inverse correlation of these two quantitative imaging approaches points out the association of metabolic activity and tumor cellularity. Therefore, DWI with ADC measurement might represent a new prognostic marker in NSCLC

  9. Tracer Partitioning in Two-Phase Flow

    Science.gov (United States)

    Sathaye, K.; Hesse, M. A.

    2012-12-01

    The concentration distributions of geochemical tracers in a subsurface reservoir can be used as an indication of the reservoir flow paths and constituent fluid origin. In this case, we are motivated by the origin of marked geochemical gradients in the Bravo Dome natural CO2 reservoir in northeastern New Mexico. This reservoir contains 99% CO2 with various trace noble gas components and overlies the formation brine in a sloping aquifer. It is thought that magmatic CO2 entered the reservoir, and displaced the brine. This displacement created gradients in the concentrations of the noble gases. Two models to explain noble gas partitioning in two-phase flow are presented here. The first model assumes that the noble gases act as tracers and uses a first order non-linear partial differential equation to compute the volume fraction of each phase along the displament path. A one-way coupled partial differential equation determines the tracer concentration, which has no effect on the overall flow or phase saturations. The second model treats each noble gas as a regular component resulting in a three-component, two-phase system. As the noble gas injection concentration goes to zero, we see the three-component system behave like the one-way coupled system of the first model. Both the analytical and numerical solutions are presented for these models. For the process of a gas displacing a liquid, we see that a noble gas tracer with greater preference for the gas phase, such as Helium, will move more quickly along the flowpath than a heavier tracer that will more easily enter the liquid phase, such as Argon. When we include partial miscibility of both the major and trace components, these differences in speed are shown in a bank of the tracer at the saturation front. In the three component model, the noble gas bank has finite width and concentration. In the limit where the noble gas is treated as a tracer, the width of the bank is zero and the concentration increases linearly

  10. Halon-1301, a new Groundwater Age Tracer

    Science.gov (United States)

    Beyer, Monique; van der Raaij, Rob; Morgenstern, Uwe; Jackson, Bethanna

    2015-04-01

    Groundwater dating is an important tool to assess groundwater resources in regards to direction and time scale of groundwater flow and recharge and to assess contamination risks and manage remediation. To infer groundwater age information, a combination of different environmental tracers, such as tritium and SF6, are commonly used. However ambiguous age interpretations are often faced, due to a limited set of available tracers and limitations of each tracer method when applied alone. There is a need for additional, complementary groundwater age tracers. We recently discovered that Halon-1301, a water soluble and entirely anthropogenic gaseous substance, may be a promising candidate [Beyer et al, 2014]. Halon-1301 can be determined along with SF6, SF5CF3 and CFC-12 in groundwater using a gas chromatography setup with attached electron capture detector developed by Busenberg and Plummer [2008]. Halon-1301 has not been assessed in groundwater. This study assesses the behaviour of Halon-1301 in water and its suitability as a groundwater age tracer. We determined Halon-1301 in 17 groundwater and various modern (river) waters sites located in 3 different groundwater systems in the Wellington Region, New Zealand. These waters have been previously dated with tritium, CFC-12, CFC-11 and SF6 with mean residence times ranging from 0.5 to over 100 years. The waters range from oxic to anoxic and some show evidence of CFC contamination or degradation. This allows us to assess the different properties affecting the suitability of Halon-1301 as groundwater age tracer, such as its conservativeness in water and local contamination potential. The samples are analysed for Halon-1301 and SF6simultaneously, which allows identification of issues commonly faced when using gaseous tracers such as contamination with modern air during sampling. Overall we found in the assessed groundwater samples Halon-1301 is a feasible new groundwater tracer. No sample indicated significantly elevated

  11. Improved tumor identification using dual tracer molecular imaging in fluorescence guided brain surgery

    Science.gov (United States)

    Xu, Xiaochun; Torres, Veronica; Straus, David; Brey, Eric M.; Byrne, Richard W.; Tichauer, Kenneth M.

    2015-03-01

    Brain tumors represent a leading cause of cancer death for people under the age of 40 and the probability complete surgical resection of brain tumors remains low owing to the invasive nature of these tumors and the consequences of damaging healthy brain tissue. Molecular imaging is an emerging approach that has the potential to improve the ability for surgeons to correctly discriminate between healthy and cancerous tissue; however, conventional molecular imaging approaches in brain suffer from significant background signal in healthy tissue or an inability target more invasive sections of the tumor. This work presents initial studies investigating the ability of novel dual-tracer molecular imaging strategies to be used to overcome the major limitations of conventional "single-tracer" molecular imaging. The approach is evaluated in simulations and in an in vivo mice study with animals inoculated orthotopically using fluorescent human glioma cells. An epidermal growth factor receptor (EGFR) targeted Affibody-fluorescent marker was employed as a targeted imaging agent, and the suitability of various FDA approved untargeted fluorescent tracers (e.g. fluorescein & indocyanine green) were evaluated in terms of their ability to account for nonspecific uptake and retention of the targeted imaging agent. Signal-to-background ratio was used to measure and compare the amount of reporter in the tissue between targeted and untargeted tracer. The initial findings suggest that FDA-approved fluorescent imaging agents are ill-suited to act as untargeted imaging agents for dual-tracer fluorescent guided brain surgery as they suffer from poor delivery to the healthy brain tissue and therefore cannot be used to identify nonspecific vs. specific uptake of the targeted imaging agent where current surgery is most limited.

  12. Methods for conduct of atmospheric tracer studies at ANSTO

    International Nuclear Information System (INIS)

    A perfluorocarbon atmospheric tracer system has been developed to investigate atmospheric dispersion processes in the region surrounding the Lucas Heights Science and Technology Centre. This report discusses the tracer release, sampling and analysis methods

  13. Resistance absorption of some groundwater tracers in porous media

    Science.gov (United States)

    Jafari, Fateme

    2010-05-01

    Absorption of tracer to the aquifer material is among the most important factors which should be considered when a tracing program is considered. In this study, the absorption of the tracer into the porous media is analyzed experimentally for some of the most important and applied tracers as uranine, rhodamine B, eosin, potassium permanganate, sodium chloride and potassium chloride. For each tracer, effect of initial tracer concentration and percentage of fine grain sediments on tracer absorption in porous media is analyzed. According to the final results, rhodamine B and potassium permanganate have the less resistance against absorption to aquifer material, whilst eosin and uranine are the most resistant tracers among the examined ones. Key Words: Tracer, Absorption, Aquifer, Column Method

  14. Design, synthesis and evaluation of 6-aryl-indenoisoquinolone derivatives dual targeting ERα and VEGFR-2 as anti-breast cancer agents.

    Science.gov (United States)

    Tang, Zhichao; Wu, Chengzhe; Wang, Tianlin; Lao, Kejing; Wang, Yejun; Liu, Linyi; Muyaba, Moses; Xu, Pei; He, Conghui; Luo, Guoshun; Qian, Zhouyang; Niu, Shaoxiong; Wang, Lijun; Wang, Ying; Xiao, Hong; You, Qidong; Xiang, Hua

    2016-08-01

    The estrogen receptors have played important roles in breast cancer development and progression. Selective estrogen receptor modulators, such as Tamoxifen, have showed great benefits in the treatment and prevention of breast cancer. But the disadvantages of induction of endometrial cancer and drug resistance have limited their use. Multiple ligand which act at multiple biomolecular targets may exert favorable advantages of improved efficacy with lower incidence of side effects. In this work, we described the synthesis and evaluation of a series of 6-aryl-indenoisoquinolone derivatives as dual ERα and VEGFR-2 inhibitors. These compounds presented good ERα binding affinity and ERα antagonistic activity, as well as potent VEGFR-2 inhibitory potency. They also possessed excellent anti-proliferative activities against MCF-7, MDA-MB-231, Ishikawa and HUVEC cell lines. Further investigation of selective compound 21c showed that it was able to inhibit the activation of VEGFR-2 and the signaling transduction of Raf-1/MAPK/ERK pathway in MCF-7 cells. PMID:27176944

  15. FADS2 function loss at the cancer hotspot 11q13 locus diverts lipid signaling precursor synthesis to unusual eicosanoid fatty acids.

    Directory of Open Access Journals (Sweden)

    Woo Jung Park

    Full Text Available BACKGROUND: Genes coding for the fatty acid desaturases (FADS1, 2, 3 localized at the cancer genomic hotspot 11q13 locus are required for the biosynthesis of 20 carbon polyunsaturated fatty acids (PUFA that are direct eicosanoid precursors. In several cancer cell lines, FADS2 encoded Δ6 and Δ8 desaturation is not functional. METHODOLOGY/PRINCIPAL FINDINGS: Analyzing MCF7 cell fatty acids with detailed structural mass spectrometry, we show that in the absence of FADS2 activity, the FADS1 product Δ5-desaturase operates to produce 5,11,14-20∶3 and 5,11,14,17-20∶4. These PUFA are missing the 8-9 double bond of the eicosanoid signaling precursors arachidonic acid (5,8,11,14-20∶4 and eicosapentaenoic acid (5,8,11,14,17-20∶5. Heterologous expression of FADS2 restores Δ6 and Δ8-desaturase activity and normal eicosanoid precursor synthesis. CONCLUSIONS/SIGNIFICANCE: The loss of FADS2-encoded activities in cancer cells shuts down normal PUFA biosynthesis, deleting the endogenous supply of eicosanoid and downstream docosanoid precursors, and replacing them with unusual butylene-interrupted fatty acids. If recapitulated in vivo, the normal eicosanoid and docosanoid cell signaling milieu would be depleted and altered due to reduction and substitution of normal substrates with unusual substrates, with unpredictable consequences for cellular communication.

  16. Design, synthesis, and anti-breast cancer evaluation of new triarylethylene analogs bearing short alkyl- and polar amino-/amido-ethyl chains.

    Science.gov (United States)

    Kaur, Gurleen; Mahajan, Mohinder P; Pandey, Manoj K; Singh, Parvesh; Ramisetti, Srinivasa R; Sharma, Arun K

    2016-04-15

    The synthesis of novel triarylethylene analogs, designed based on well-known Selective Estrogen Receptor Modulators (SERMs), i.e., ospemifene and tamoxifen, as potential anti-breast cancer agents is described. The cytotoxic potential of these analogs against ER-positive (MCF-7) and ER-negative (MDA-MB-231) human breast cancer cell lines was determined and compared with the standards, ospemifene and tamoxifen. In initial screening, analogs 5, 14 and 15 were found to be much more effective than the standards against both the cell lines. The results showed that these novel analogs inhibit the expression of proteins involved in the migration and metastasis, compound 5 being most effective. Compound 5 inhibited the expression of MMP-9, c-Myc and Caveolin in both MCF-7 and MDA-MB-231 cells, and suppressed the invasion of ER-negative cells in a dose dependent manner. Finally, in silico docking simulations of the representative compounds in the binding sites of the estrogen receptors (ERs) indicated a good binding affinity of the compounds with the ERs, and supported their experimental toxicity against MCF-7 cancer cell lines. PMID:26972118

  17. Synthesis and biological evaluation of copper-64 radiolabeled [DUPA-6-Ahx-(NODAGA)-5-Ava-BBN(7-14)NH2], a novel bivalent targeting vector having affinity for two distinct biomarkers (GRPr/PSMA) of prostate cancer

    International Nuclear Information System (INIS)

    Gastrin-releasing peptide receptors (GRPr) and prostate-specific membrane antigen (PSMA) are two identifying biomarkers expressed in very high numbers on prostate cancer cells and could serve as a useful tool for molecular targeting and diagnosis of disease via positron-emission tomography (PET). The aim of this study was to produce the multipurpose, bivalent [DUPA-6-Ahx-(64Cu-NODAGA)-5-Ava-BBN(7-14)NH2] radioligand for prostate cancer imaging, where DUPA = (2-[3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid), a small-molecule, PSMA-targeting probe, 6Ahx = 6-aminohexanoic acid, 5-Ava = 5-aminovaleric acid, NODAGA = [2-(4,7-biscarboxymethyl)-1,4,7-(triazonan-1-yl)pentanedioic acid] (a derivative of NOTA (1,4,7-triazacyclononane-1,4,7-triacetic acid)), and BBN(7-14)NH2 = bombesin, a GRPr-specific peptide targeting probe. Methods: The PSMA/GRPr dual targeting ligand precursor [DUPA-6-Ahx-K-5-Ava-BBN(7-14)NH2], was synthesized by solid-phase and manual peptide synthesis, after which NODAGA was added via manual conjugation to the ε-amine of lysine (K). The new bivalent GRPr/PSMA targeting vector was purified by reversed-phase high performance liquid chromatography (RP-HPLC), characterized by electrospray-ionization mass spectrometry (ESI-MS), and metallated with 64CuCl2 and natCuCl2. The receptor binding affinity was evaluated in human, prostate, PC-3 (GRPr-positive) and LNCaP (PSMA-positive) cells and the tumor-targeting efficacy determined in severe combined immunodeficient (SCID) and athymic nude mice bearing PC-3 and LNCaP tumors. Whole-body maximum intensity microPET/CT images of PC-3/LNCaP tumor-bearing mice were obtained 18 h post-injection (p.i.). Results: Competitive binding assays in PC-3 and LNCaP cells indicated high receptor binding affinity for the [DUPA-6-Ahx-(natCu-NODAGA)-5-Ava-BBN(7-14)NH2] conjugate. MicroPET scintigraphy in PC-3/LNCaP tumor-bearing mice indicated that xenografted tumors were visible at 18 h p.i. with collateral, background

  18. Laplace transform in tracer kinetic modeling

    Energy Technology Data Exchange (ETDEWEB)

    Hauser, Eliete B., E-mail: eliete@pucrs.br [Instituto do Cerebro (InsCer/FAMAT/PUC-RS), Porto Alegre, RS, (Brazil). Faculdade de Matematica

    2013-07-01

    The main objective this paper is to quantify the pharmacokinetic processes: absorption, distribution and elimination of radiopharmaceutical(tracer), using Laplace transform method. When the drug is administered intravenously absorption is complete and is available in the bloodstream to be distributed throughout the whole body in all tissues and fluids, and to be eliminated. Mathematical modeling seeks to describe the processes of distribution and elimination through compartments, where distinct pools of tracer (spatial location or chemical state) are assigned to different compartments. A compartment model is described by a system of differential equations, where each equation represents the sum of all the transfer rates to and from a specific compartment. In this work a two-tissue irreversible compartment model is used for description of tracer, [{sup 18}F]2-fluor-2deoxy-D-glucose. In order to determine the parameters of the model, it is necessary to have information about the tracer delivery in the form of an input function representing the time-course of tracer concentration in arterial blood or plasma. We estimate the arterial input function in two stages and apply the Levenberg-Marquardt Method to solve nonlinear regressions. The transport of FDG across de arterial blood is very fast in the first ten minutes and then decreases slowly. We use de Heaviside function to represent this situation and this is the main contribution of this study. We apply the Laplace transform and the analytical solution for two-tissue irreversible compartment model is obtained. The only approach is to determinate de arterial input function. (author)

  19. Thermal tracer tests for characterizing a shallow alluvial aquifer

    OpenAIRE

    Wildemeersch, Samuel; Klepikova, Maria; Jamin, Pierre; Orban, Philippe; Hermans, Thomas; Brouyère, Serge; Dassargues, Alain

    2014-01-01

    Using heat as an active tracer in different types of aquifers is a topic of increasing interest [e.g. Vandenbohede et al.; 2008, Wagner et al., 2013; Read et al., 2013]. In this study, we investigate the potential interest of coupling heat and solute tracer tests for characterization of a shallow alluvial aquifer. A thermal tracer test was conducted in the alluvial aquifer of the Meuse River, Belgium. The tracing experiment consisted in simultaneously injecting heated water and a dye tracer i...

  20. A single food bolus stimulates albumin synthesis in growing piglets

    NARCIS (Netherlands)

    de Meer, K; Smolders, HC; Meesterburrie, J; de Sain-van der Velden, M; Voorbij, HAM; Okken, A; Reijngoud, DJ; Kulik, W

    2000-01-01

    Background: A stable isotope tracer method to quantify the synthesis of proteins of hepatic origin in response to feeding is described. The response of albumin synthesis on one mixed meal in a piglet model was investigated and the intragastric and intravenous administration modes of C-13-valine were

  1. Industrial tracer application in people's republic of china

    International Nuclear Information System (INIS)

    A number of important applications of radioisotopes and their compounds used as tracers in petroleum industry, metallurgical industry, mechanical industry, chemical industry, electronic industry, hydrology and water conservancy in China are introduced in this paper. And the tracer technique applied to entomology is also mentioned. The industrial tracer applications are successful and beneficial in People's Republic of China from the examples given. (author)

  2. Natural tracer profiles across argillaceous formations

    Energy Technology Data Exchange (ETDEWEB)

    Mazurek, Martin, E-mail: mazurek@geo.unibe.ch [Rock-Water Interaction, Institute of Geological Sciences, University of Bern (Switzerland); Alt-Epping, Peter [Rock-Water Interaction, Institute of Geological Sciences, University of Bern (Switzerland); Bath, Adrian [Intellisci, Willoughby on the Wolds, Loughborough LE12 6SZ (United Kingdom); Gimmi, Thomas [Rock-Water Interaction, Institute of Geological Sciences, University of Bern (Switzerland)] [Paul Scherrer Institut, 5232 Villigen PSI (Switzerland); Niklaus Waber, H. [Rock-Water Interaction, Institute of Geological Sciences, University of Bern (Switzerland); Buschaert, Stephane [Andra, Parc de la Croix Blanche, 92298 Chatenay-Malabry Cedex (France); Canniere, Pierre De; Craen, Mieke De [SCK-CEN, 2400 Mol (Belgium); Gautschi, Andreas [Nagra, 5430 Wettingen (Switzerland); Savoye, Sebastien [IRSN, 92262 Fontenay-aux-Roses Cedex (France); Vinsot, Agnes [Andra, Parc de la Croix Blanche, 92298 Chatenay-Malabry Cedex (France); Wemaere, Isabelle [SCK-CEN, 2400 Mol (Belgium); Wouters, Laurent [Ondraf/Niras, 1210 Brussels (Belgium)

    2011-07-15

    Highlights: > Solute transport processes in clay and shale formations at nine sites are examined. > Conservative pore-water tracers (e.g. Cl{sup -}, {delta}{sup 18}O, {delta}{sup 2}H, He) show regular profiles. > These indicate the dominance of diffusive transport over times of 10{sup 5}-10{sup 6} years. > The contribution of vertical advection to transport is limited or negligible. > Modelled evolution times are in line with independent palaeo-hydrogeological data. - Abstract: Argillaceous formations generally act as aquitards because of their low hydraulic conductivities. This property, together with the large retention capacity of clays for cationic contaminants, has brought argillaceous formations into focus as potential host rocks for the geological disposal of radioactive and other waste. In several countries, programmes are under way to characterise the detailed transport properties of such formations at depth. In this context, the interpretation of profiles of natural tracers in pore waters across the formations can give valuable information about the large-scale and long-term transport behaviour of these formations. Here, tracer-profile data, obtained by various methods of pore-water extraction for nine sites in central Europe, are compiled. Data at each site comprise some or all of the conservative tracers: anions (Cl{sup -}, Br{sup -}), water isotopes ({delta}{sup 18}O, {delta}{sup 2}H) and noble gases (mainly He). Based on a careful evaluation of the palaeo-hydrogeological evolution at each site, model scenarios are derived for initial and boundary pore-water compositions and an attempt is made to numerically reproduce the observed tracer distributions in a consistent way for all tracers and sites, using transport parameters derived from laboratory or in situ tests. The comprehensive results from this project have been reported in . Here the results for three sites are presented in detail, but the conclusions are based on model interpretations of the

  3. Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

    Science.gov (United States)

    Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

    2015-11-01

    Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells. PMID:26058357

  4. Microfluidic single vessel production of hypoxia tracer 1H-1-(3-[18F]-fluoro-2-hydroxy-propyl)-2-nitro-imidazole ([18F]-FMISO)

    OpenAIRE

    Yokell, Daniel L; Leece, Alicia K; Lebedev, Artem; Miraghaie, Reza; Ball, Carroll E.; Zhang, Jianzhong; Kolb, Hartmuth; Elizarov, Arkadij; Mahmood, Umar

    2012-01-01

    We report an automated synthesis of [18F]-FMISO utilizing a prototype microfluidic radiochemistry module. The instrument allows for production of the tracer with 58% ± 2% (11 runs) decay corrected yield. Total time of production, including synthesis and purification averages 60 minutes. Use of the microfluidic platform results in a specific activity of 138.6 GBq/μmol, which is higher than previously reported for conventional reactors.

  5. Synthesis of Novel β-Keto-Enol Derivatives Tethered Pyrazole, Pyridine and Furan as New Potential Antifungal and Anti-Breast Cancer Agents

    Directory of Open Access Journals (Sweden)

    Smaail Radi

    2015-11-01

    Full Text Available Recently, a new generation of highly promising inhibitors bearing β-keto-enol functionality has emerged. Reported herein is the first synthesis and use of novel designed drugs based on the β-keto-enol group embedded with heterocyclic moieties such as pyrazole, pyridine, and furan, prepared in a one-step procedure by mixed Claisen condensation. All the newly synthesized compounds were characterized by FT-IR, 1H-NMR, 13C-NMR, ESI/LC-MS, elemental analysis, and evaluated for their in vitro antiproliferative activity against breast cancer (MDA-MB241 human cell lines and fungal strains (Fusarium oxysporum f.sp albedinis FAO. Three of the synthesized compounds showed potent activity against fungal strains with IC50 values in the range of 0.055–0.092 µM. The results revealed that these compounds showed better IC50 values while compared with positive controls.

  6. Geometric Skewness in the Passive Tracer Problem

    Science.gov (United States)

    Aminian, Manuchehr; Bernardi, Francesca; Camassa, Roberto; McLaughlin, Richard

    2015-11-01

    The classic work by G.I. Taylor describes the enhanced longitudinal diffusivity of a passive tracer in laminar pipe flow. Much work since then has gone into extending this result particularly in calculating the evolution of the scalar variance. However, less work has been done to describe the asymmetry of the distribution. We present the results from a modeling effort for the general picture of how the higher moments of the tracer distribution depend on geometry. We do this via analysis of ``channel-limiting'' geometries (rectangular ducts and elliptical pipes parameterized by their aspect ratio), using both new analytical tools and Monte-Carlo simulation, which have revealed a wealth of nontrivial behavior of the distributions at short and intermediate time. Funding from NSF grant Nos.: RTG DMS-0943851, CMG ARC-1025523, and DMS-1009750.

  7. Rational design, synthesis, and biological evaluation of third generation α-noscapine analogues as potent tubulin binding anti-cancer agents.

    Directory of Open Access Journals (Sweden)

    Naresh Kumar Manchukonda

    Full Text Available Systematic screening based on structural similarity of drugs such as colchicine and podophyllotoxin led to identification of noscapine, a microtubule-targeted agent that attenuates the dynamic instability of microtubules without affecting the total polymer mass of microtubules. We report a new generation of noscapine derivatives as potential tubulin binding anti-cancer agents. Molecular modeling experiments of these derivatives 5a, 6a-j yielded better docking score (-7.252 to -5.402 kCal/mol than the parent compound, noscapine (-5.505 kCal/mol and its existing derivatives (-5.563 to -6.412 kCal/mol. Free energy (ΔG bind calculations based on the linear interaction energy (LIE empirical equation utilizing Surface Generalized Born (SGB continuum solvent model predicted the tubulin-binding affinities for the derivatives 5a, 6a-j (ranging from -4.923 to -6.189 kCal/mol. Compound 6f showed highest binding affinity to tubulin (-6.189 kCal/mol. The experimental evaluation of these compounds corroborated with theoretical studies. N-(3-brormobenzyl noscapine (6f binds tubulin with highest binding affinity (KD, 38 ± 4.0 µM, which is ~ 4.0 times higher than that of the parent compound, noscapine (KD, 144 ± 1.0 µM and is also more potent than that of the first generation clinical candidate EM011, 9-bromonoscapine (KD, 54 ± 9.1 µM. All these compounds exhibited substantial cytotoxicity toward cancer cells, with IC50 values ranging from 6.7 µM to 72.9 µM; compound 6f showed prominent anti-cancer efficacy with IC50 values ranging from 6.7 µM to 26.9 µM in cancer cells of different tissues of origin. These compounds perturbed DNA synthesis, delayed the cell cycle progression at G2/M phase, and induced apoptotic cell death in cancer cells. Collectively, the study reported here identified potent, third generation noscapinoids as new anti-cancer agents.

  8. Into the regolith: digging for hydrological tracers

    Science.gov (United States)

    Moragues-Quiroga, Cristina; Hissler, Christophe; Chabaux, François; Legout, Arnaud; Stille, Peter

    2016-04-01

    The mineralogical and trace element composition of regoliths is a source of potential tracers of water behaviour in catchment systems. We propose an assessment of the most suitable spatial tracers for water collection, mixing, storage and release processes by incorporating geochemical signatures derived from trace and major elements to the description of sources and pathways of water contributions in the stream. To date, stable isotopes are widely used to trace water sources and water transit times but they are still missing a complementary tool which allows for the identification of end-members and the understanding of mixing processes within the regolith. Trace elements are known to be powerful and precise geochemical tracers of environmental processes and, therefore, they can be useful indicators of the spatial origin and evolution of regolith materials and water chemistry. We studied a whole slate regolith profile for its mineralogical, major and trace element composition. The different regolith components were subjected to a leaching experiment in order to identify chemical zonations within and assess the potential elements mobility. Rain, soil, stream and ground waters were collected at the same location than the regolith system over 4 years, analysed for their trace and major elements composition and compared to regolith and regolith leachates data. The results deliver valuable information on exchange processes at the water-mineral interface in the different zones of the regolith. The geochemical scheme of a complete regolith and the waters it holds is here presented to prove the efficiency of trace and major elements as complementary hydrological and geochemical tracers of water migration throughout a regolith till the stream.

  9. The medical applications of radioactive tracers

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, J.G.

    1947-12-31

    This report provides a broad yet in depth overview of the use of radioactive materials as tracers in medicine and biology for the period of 1935--1947. Particular attention is paid to is of radio-sodium, radio-iodine, radio-iron, radio-phosphorus, radio-strontium, and fission products. The main thrust of this paper is human rather than animal work and focuses in work that has been published.

  10. Synthesis, structures, and selective toxicity to cancer cells of gold(I) complexes involving N-heterocyclic carbene ligands.

    Science.gov (United States)

    Boselli, Luca; Ader, Isabelle; Carraz, Maëlle; Hemmert, Catherine; Cuvillier, Olivier; Gornitzka, Heinz

    2014-10-01

    New gold(I) complexes containing two 1-[2-(diethylamino)ethyl]imidazolydene ligands have been synthesized and characterized. The X-ray structures of two key compounds are presented. All complexes have been tested for their antiproliferative activities in prostate cancer cell line PC-3. Lipophilicity (Log P) has been determined for these complexes. The most active complex has been tested for the cytotoxic activities in five human cancer cell lines and primary endothelial cells. The most active complex demonstrated a potent selectivity for cancer cells. PMID:25078312

  11. Prognostic significance of protein-calorie malnutrition in post-virus hepatitis cirrhosis and the design of diet therapy based on Chinese food using isotope tracers

    International Nuclear Information System (INIS)

    Work has been done to establish a 15N-glycine tracer method suitable for measuring whole body protein synthesis and breakdown rates in patients with hepatic insufficiency. Some preliminary experiments on the determination of low abundance deuterium and 18O in water are also presented. 19 refs, 3 figs, 3 tabs

  12. Prognostic significance of protein-calorie malnutrition in post-virus hepatitis cirrhosis and the design of diet therapy based on Chinese food using isotope tracers

    International Nuclear Information System (INIS)

    This document reports studies of the metabolism of patients with post-viral hepatitis cirrhosis. Three separate areas are investigated by means of tracer techniques: whole-body protein synthesis and breakdown; energy expenditures; and protein turnover and leucine oxidation. 12 refs, 8 tabs

  13. Tracer techniques in plant breeding programmes

    International Nuclear Information System (INIS)

    Tracer techniques may be used as a tool in plant breeding programmes either to help in the choice of parental combinations with complementary advantages or in the selection of desirable plants within the segregating populations. The second application is, however, of little practical application as the techniques involved are mostly too tedious to be used on the large populations with which the plant breeder must deal, and frequently involve unacceptable destructive sampling of his material. The physiological analysis of potential parents is of considerable importance, particularly in the improvement of crops to be grown in more fully developed countries with advanced agricultural systems. Techniques using radioactive tracers and radiation-emitting sources such as the neutron probe have played a considerable part in this work. They have been used by cereal breeders to measure photosynthesis either of individual leaves, or of undisturbed crop canopies, and by breeders of many crops in the study of the translocation of the products of photosynthesis within the plant. They have also been used in studies of the effects of plant diseases on translocation patterns, thus identifying limiting factors for which the breeder should select. Radioactive tracers have also been used in estimating varietal differences in root growth and distribution, but the results obtained from such experiments have indicated that environmental differences are greater than those between genotypes. Differences in water uptake have, however, been demonstrated using the neutron probe, though these differences appear to be much influenced by differences in the water economy of the aerial parts. (author)

  14. Radon diagnostics and tracer gas measurements

    International Nuclear Information System (INIS)

    An outline is presented of the tracer gas technique, which is used for continuous measurements of air ventilation rate (generally time-varying) and for simultaneous estimation of air ventilation rate and radon entry rate, and some of its limitations are discussed. The performance of this technique in the calculation of the air ventilation rate is demonstrated on real data from routine measurements. The potential for air ventilation rate estimation based on radon measurements only is discussed. A practical application is described of the tracer gas technique to a simultaneous estimation of the air ventilation rate and radon entry rate in a real house where the effectiveness of radon remedy was tested. The following main advantages of the CO tracer gas techniques are stressed: (i) The averaging method continuous determination of the ventilation rate with good accuracy (≤ 20 %). (ii) The newly presented and verified method based on simultaneous measurements of radon concentration and CO gas concentration enables separate continuous measurements of the radon entry rate and ventilation rate. The results of comparative measurements performed with the aim to estimate the inaccuracy in determination of radon entry rate showed acceptable and good agreement up to approximately 10 %. The results of comparative measurements performed with the aim to estimate the mutual commensuration of the method to the determination of the ventilation rate confirmed the expected unreliability the two parametric non-linear regression method, which is the most frequently used method in radon diagnostic in the Czech Republic

  15. The ATLAS DDM Tracer monitoring framework

    Science.gov (United States)

    Zang, Dongsong; Garonne, Vincent; Barisits, Martin; Lassnig, Mario; Stewart, Graeme Andrew; Molfetas, Angelos; Beermann, Thomas

    2012-12-01

    The DDM Tracer monitoring framework is aimed to trace and monitor the ATLAS file operations on the Worldwide LHC Computing Grid. The volume of traces has increased significantly since the framework was put in production in 2009. Now there are about 5 million trace messages every day and peaks can be near 250Hz, with peak rates continuing to climb, which gives the current structure a big challenge. Analysis of large datasets based on on-demand queries to the relational database management system (RDBMS), i.e. Oracle, can be problematic, and have a significant effect on the database's performance. Consequently, We have investigated some new high availability technologies like messaging infrastructure, specifically ActiveMQ, and key-value stores. The advantages of key value store technology are that they are distributed and have high scalability; also their write performances are usually much better than RDBMS, all of which are very useful for the Tracer monitoring framework. Indexes and distributed counters have been also tested to improve query performance and provided almost real time results. In this paper, the design principles, architecture and main characteristics of Tracer monitoring framework will be described and examples of its usage will be presented.

  16. Tracer technology modeling the flow of fluids

    CERN Document Server

    Levenspiel, Octave

    2012-01-01

    A vessel’s behavior as a heat exchanger, absorber, reactor, or other process unit is dependent upon how fluid flows through the vessel.  In early engineering, the designer would assume either plug flow or mixed flow of the fluid through the vessel.  However, these assumptions were oftentimes inaccurate, sometimes being off by a volume factor of 100 or more.  The result of this unreliable figure produced ineffective products in multiple reaction systems.   Written by a pioneering researcher in the field of chemical engineering, the tracer method was introduced to provide more accurate flow data.  First, the tracer method measured the actual flow of fluid through a vessel.  Second, it developed a suitable model to represent the flow in question.  Such models are used to follow the flow of fluid in chemical reactors and other process units, like in rivers and streams, or solid and porous structures.  In medicine, the tracer method is used to study the flow of chemicals—harmful  and harmless—in the...

  17. Very Massive Tracers and Higher Derivative Biases

    CERN Document Server

    Fujita, Tomohiro; Senatore, Leonardo; Vlah, Zvonimir; Angulo, Raul

    2016-01-01

    Most of the upcoming cosmological information will come from analyzing the clustering of the Large Scale Structures (LSS) of the universe through LSS or CMB observations. It is therefore essential to be able to understand their behavior with exquisite precision. The Effective Field Theory of Large Scale Structures (EFTofLSS) provides a consistent framework to make predictions for LSS observables in the mildly non-linear regime. In this paper we focus on biased tracers. We argue that in calculations at a given order in the dark matter perturbations, highly biased tracers will underperform because of their larger higher derivative biases. A natural prediction of the EFTofLSS is therefore that by simply adding higher derivative biases, all tracers should perform comparably well. We implement this prediction for the halo-halo and the halo-matter power spectra at one loop, and the halo-halo-halo, halo-halo-matter, and halo-matter-matter bispectra at tree-level, and compare with simulations. We find good agreement ...

  18. Amino acid containing thapsigargin analogues deplete androgen receptor protein via synthesis inhibition and induce the death of prostate cancer cells

    DEFF Research Database (Denmark)

    Griend, Donald J Vander; Antony, Lizamma; Dalrymple, Susan L;

    2009-01-01

    There are quantitative and/or qualitative mechanisms allowing androgen receptor (AR) growth signaling in androgen ablation refractory prostate cancer cells. Regardless of the mechanism, agents that deplete AR protein expression prevent such AR growth signaling. Thapsigargin (TG) is a highly cell......-penetrant sequiterpene-lactone that once inside cells inhibits (IC(50), approximately 10 nmol/L) critically important housekeeping SERCA 2b calcium pumps in the endoplasmic reticulum. Using a series of five genetically diverse androgen ablation refractory human prostate cancer lines (LNCaP, LAPC-4, VCaP, MDA-PCa-2b, and......-specific proteases, such as prostate-specific antigen and prostate-specific membrane antigen, or cancer-specific proteases, such as fibroblast activation protein, so that toxicity of these prodrugs is selectively targeted to metastatic sites of prostate cancer. Based on these results, these prodrugs are undergoing...

  19. Synthesis, structures, and selective toxicity to cancer cells of gold(I) complexes involving N-heterocyclic carbene ligands

    OpenAIRE

    L. Boselli; Ader, I.; Carraz, Maëlle; Hemmert, C.; Cuvillier, O.; Gornitzka, H.

    2014-01-01

    New gold(I) complexes containing two 1-[2-(diethylamino)ethyl]imidazolydene ligands have been synthesized and characterized. The X-ray structures of two key compounds are presented. All complexes have been tested for their antiproliferative activities in prostate cancer cell line PC-3. Lipophilicity (Log P) has been determined for these complexes. The most active complex has been tested for the cytotoxic activities in five human cancer cell lines and primary endothelial cells. The most active...

  20. A systematic review and thematic synthesis of quality of life in the informal carers of cancer patients with cachexia

    OpenAIRE

    Darlington, Anne-Sophie; Hopkinson, J.B.; Fitzsimmons, D.; Johnson, C.D.

    2015-01-01

    Background: informal carers of cancer patients with cachexia face additional challenges to those encountered by informal carers in general because of the central role food and eating play in everyday life. Patient weight loss and anorexia, core features of cancer cachexia, are frequent causes of distress in caregivers. Identification of quality of life (QOL) issues can inform the development of interventions for both caregivers and patients, and facilitate communication with healthcare profes...

  1. CANCER

    Directory of Open Access Journals (Sweden)

    N. Kavoussi

    1973-09-01

    Full Text Available There are many carcinogenetic elements in industry and it is for this reason that study and research concerning the effect of these materials is carried out on a national and international level. The establishment and growth of cancer are affected by different factors in two main areas:-1 The nature of the human or animal including sex, age, point and method of entry, fat metabolism, place of agglomeration of carcinogenetic material, amount of material absorbed by the body and the immunity of the body.2 The different nature of the carcinogenetic material e.g. physical, chemical quality, degree of solvency in fat and purity of impurity of the element. As the development of cancer is dependent upon so many factors, it is extremely difficult to determine whether a causative element is principle or contributory. Some materials are not carcinogenetic when they are pure but become so when they combine with other elements. All of this creates an industrial health problem in that it is almost impossible to plan an adequate prevention and safety program. The body through its system of immunity protects itself against small amounts of carcinogens but when this amount increases and reaches a certain level the body is not longer able to defend itself. ILO advises an effective protection campaign against cancer based on the Well –equipped laboratories, Well-educated personnel, the establishment of industrial hygiene within factories, the regular control of safety systems, and the implementation of industrial health principles and research programs.

  2. An atom size effect in tracer diffusion

    International Nuclear Information System (INIS)

    Published diffusion data permit an extensive comparison to be made between tracer diffusion coefficients, D, in Pb and in α-Zr, at 0.6 Tsub(m), where Tsub(m)(K) is the melting temperature of the host metal. For these metals, a striking correlation is found between D and the metallic radius, r, of the corresponding tracer element; except for the smallest r values, the correlation may be expressed in the general form: 1g D = A + exp(- br + c), where A, b and c are individual constants for each host metal. There is, for tracer diffusion in Pb, sufficient experimental data to permit the evaluation of an additional relationship between the pre-exponential factor Dsub(O), and the activation enthalpy, ΔH, in the usual expression D = D0 exp(- ΔH/RT), describing the temperature dependence of D. A combination of these relationships allows the evaluation of expressions for D0 and ΔH in which r is the only variable. Derived relations between D0 and ΔH, and ΔH and ΔH and r, are, respectively, D0 = 2.0 x 10-4 exp (0.345 ΔH)cm2s-1, and ΔH = 30.8 - exp (8.65 - 4.04 r), in which the units of ΔH and r are kcal mol-1 and A respectively. In order to compare tracer diffusion in these 'open' metals (i.e. metals with a relatively large metallic/ionic radius ratio) with tracer diffusion in a 'full' metal, values of D at 0.6 Tsub(m) have been calculated from published data for diffusion in Cu. Again it is found that 1g D tends to display an exponential dependence on r; in contrast to the results for the 'open' metals, however, 1g D is found to increase with r. Expressions derived for D0 and ΔH for diffusion in Cu, corresponding to those given above for Pb, are: D0 = 5.2 x 10-4 exp(0.152 ΔH)cm2s-1 and ΔH 43.1 + exp(17.40 - 11.94 r), in which the units of ΔH and r are as given for Pb. (author)

  3. Synthesis of new diarylamides with pyrimidinyl pyridine scaffold and evaluation of their anti-proliferative effect on cancer cell lines.

    Science.gov (United States)

    Abdelazem, Ahmed Z; Al-Sanea, Mohammad M; Park, Hyun-Mee; Lee, So Ha

    2016-02-15

    A new series of diarylamides, having a pyrimidinyl pyridine scaffold, was designed and synthesized. The target compounds were synthesized in three steps. A selected group from the target compounds was tested over a panel of 60 cancer cell lines at a single dose concentration of 10μM, and the most active compound, 5j, was further tested in a five-dose testing mode to determine its IC50 value over the 60 cell lines. In single-dose testing mode, compound 5j showed the highest growth inhibition against the NCI-60 cancer cell lines, while other tested compounds showed a weak to moderate inhibitory activity against a range of different cancer cell lines. In five-dose testing mode, compound 5j showed strong inhibitory activity in micro molar range against many cancer cell lines. Its major activity was against melanoma cancer cell lines. Therefore, compound 5j is a promising hit compound targeting this severe form of cancer. PMID:26786696

  4. Synthesis and evaluation of multi-wall carbon nanotube–paclitaxel complex as an anti-cancer agent

    Science.gov (United States)

    Ghasemvand, Fariba; Biazar, Esmaeil; Tavakolifard, Sara; Khaledian, Mohammad; Rahmanzadeh, Saeid; Momenzadeh, Daruosh; Afroosheh, Roshanak; Zarkalami, Faezeh; Shabannezhad, Marjan; Hesami Tackallou, Saeed; Massoudi, Nilofar; Heidari Keshel, Saeed

    2016-01-01

    Aim: The aim of this study was to design multi-walled carbon nanotubes (MWCNTs) loaded with paclitaxel (PTX) anti-cancer drug and investigate its anti-cancerous efficacy of human gastric cancer. Background: Carbon nanotubes (CNTs) represent a novel nano-materials applied in various fields such as drug delivery due to their unique chemical properties and high drug loading. Patients and methods: In this study, multi-walled carbon nanotubes (MWCNTs) pre-functionalized covalently with a paclitaxel (PTX) as an anti-cancer drug and evaluated by different analyses including, scanning electron microscope (SEM), particle size analyzer and cellular analyses. Results: A well conjugated of anti-cancer drug on the carbon nanotube surfaces was shown. This study demonstrates that the MWCN-PTX complex is a potentially useful system for delivery of anti-cancer drugs. The flow cytometry, CFU and MTT assay results have disclosed that MWCNT/PTXs might promote apoptosis in MKN-45 gastric adenocarcinoma cell line. Conclusion: According to results, our simple method can be designed a candidate material for chemotherapy. It has presented a few bio-related applications including, their successful use as a nano-carriers for drug transport. PMID:27458512

  5. From COX-2 inhibitor nimesulide to potent anti-cancer agent: synthesis, in vitro, in vivo and pharmacokinetic evaluation.

    Science.gov (United States)

    Zhong, Bo; Cai, Xiaohan; Chennamaneni, Snigdha; Yi, Xin; Liu, Lili; Pink, John J; Dowlati, Afshin; Xu, Yan; Zhou, Aimin; Su, Bin

    2012-01-01

    Cyclooxygenase-2 (COX-2) inhibitor nimesulide inhibits the proliferation of various types of cancer cells mainly via COX-2 independent mechanisms, which makes it a good lead compound for anti-cancer drug development. In the presented study, a series of new nimesulide analogs were synthesized based on the structure-function analysis generated previously. Some of them displayed very potent anti-cancer activity with IC(50)s around 100 nM-200 nM to inhibit SKBR-3 breast cancer cell growth. CSUOH0901 (NSC751382) from the compound library also inhibits the growth of the 60 cancer cell lines used at National Cancer Institute Developmental therapeutics Program (NCIDTP) with IC(50)s around 100 nM-500 nM. Intraperitoneal injection with a dosage of 5  mg/kg/d of CSUOH0901 to nude mice suppresses HT29 colorectal xenograft growth. Pharmacokinetic studies demonstrate the good bioavailability of the compound. PMID:22119125

  6. Design, synthesis, and biological evaluation of dibromotyrosine analogues inspired by marine natural products as inhibitors of human prostate cancer proliferation, invasion, and migration.

    Science.gov (United States)

    Sallam, Asmaa A; Ramasahayam, Sindhura; Meyer, Sharon A; El Sayed, Khalid A

    2010-11-01

    Bioactive secondary metabolites originating from dibromotyrosine are common in marine sponges, such as sponges of the Aplysina species. Verongiaquinol (1), 3,5-dibromo-1-hydroxy-4-oxocyclohexa-2,5-diene-1-acetamide, and aeroplysinin-1 are examples of such bioactive metabolites. Previous studies have shown the potent antimicrobial as well as cytotoxic properties of verongiaquinol and the anti-angiogenic activity of aeroplysinin-1. The work presented herein shows the design and synthesis of dibromotyrosine-inspired phenolic ester and ether analogues with anti-angiogenic, anti-proliferative and anti-migratory properties and negligible cytotoxicity. Several analogues were synthesized based on docking experiments in the ATP binding site of VEGFR2 and their anti-angiogenic potential and ability to inhibit angiogenesis and prostate cancer proliferation, migration and invasion were evaluated using the chick chorioallantoic membrane (CAM) assay, MTT, wound-healing, and Cultrex® BME cell invasion assay models, respectively. Analogues with high docking scores showed promising anti-angiogenic activity in the CAM assay. In general, ester analogues (5, 6, and 8-10) proved to be of higher anti-migratory activity whereas ether analogues (11-14) showed better anti-proliferative activity. These results demonstrate the potential of dibromotyrosines as promising inhibitory scaffolds for the control of metastatic prostate cancer proliferation and migration. PMID:20884214

  7. Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

    Science.gov (United States)

    Łączkowski, Krzysztof Z.; Świtalska, Marta; Baranowska-Łączkowska, Angelika; Plech, Tomasz; Paneth, Agata; Misiura, Konrad; Wietrzyk, Joanna; Czaplińska, Barbara; Mrozek-Wilczkiewicz, Anna; Malarz, Katarzyna; Musioł, Robert; Grela, Izabela

    2016-09-01

    Synthesis, characterization and investigation of antiproliferative activity of ten thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, MCF-7 and HCT116) and normal mouse fibroblast (BALB/3T3) is presented. The structures of novel compounds were determined using 1H and 13C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 5b, 5c, 5e, 5f and 5i were found to exhibit high activity against human leukaemia MV4-11 cells with IC50 values of 2.17-4.26 μg/ml. The cytotoxic activity of compound 5c and 5f against BALB/3T3 cells is up to 20 times lower than against cancer cell lines. Our results also show that compounds 5e and 5i have very strong activity against MCF-7 and HCT116 with IC50 values of 3.02-4.13 μg/ml. Moreover, spectroscopic characterization and cellular localization for selected compound were performed. In order to identify potential drug targets we perform computer simulations with DNA-binding site of hTopoI and hTopoII and quantum chemical calculation of interaction and binding energies in complexes of the five most active compounds with guanine.

  8. Multi Resolution AHB Bus Tracer with Real Time Compression for SOC

    Directory of Open Access Journals (Sweden)

    J. Jagadish Reddy

    2013-01-01

    Full Text Available AMBA (Advanced Microcontroller based Bus Architecture consists of AHB, APB, ASB and AXI. In this project we are Tracing AHB (Advanced High performance Bus signals with Real time Compression and Multi-resolution Techniques. A simple transaction on the AHB consists of an address phase and a subsequent data phase. Access to the target device is controlled through a MUX , thereby admitting bus-access to one bus-master at a time. In AHB Tracer we have to Trace Address signals, Data signals and Control signals, we have to compress them depending on AHB protocols. A multi-resolution AHB on-chip bus tracer is named as SYS_HMRBT (AHB Multi-resolution Bus Tracer and is used for monitoring. The goal is to provide better compression quality and multiple resolution traces to meet the complex SoC debugging needs. Compressing all signals at cycle-accurate-level does not always meet the debugging needs. As SOCs become more complex, the transaction level debugging becomes increasingly important, since it helps designers focus on the functional behaviors, instead of interpreting complex signals. By using this SYS_HMRBT, we can achieve 79%-96% of compression depending on selected resolution mode. Tools Used for this Project are Modelsim for Simulation, and Xilinx ISE II for Synthesis

  9. Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage.

    Science.gov (United States)

    Liu, Ling; Shah, Supriya; Fan, Jing; Park, Junyoung O; Wellen, Kathryn E; Rabinowitz, Joshua D

    2016-05-01

    The critical cellular hydride donor NADPH is produced through various means, including the oxidative pentose phosphate pathway (oxPPP), folate metabolism and malic enzyme. In growing cells, it is efficient to produce NADPH via the oxPPP and folate metabolism, which also make nucleotide precursors. In nonproliferating adipocytes, a metabolic cycle involving malic enzyme holds the potential to make both NADPH and two-carbon units for fat synthesis. Recently developed deuterium ((2)H) tracer methods have enabled direct measurement of NADPH production by the oxPPP and folate metabolism. Here we enable tracking of NADPH production by malic enzyme with [2,2,3,3-(2)H]dimethyl-succinate and [4-(2)H]glucose. Using these tracers, we show that most NADPH in differentiating 3T3-L1 mouse adipocytes is made by malic enzyme. The associated metabolic cycle is disrupted by hypoxia, which switches the main adipocyte NADPH source to the oxPPP. Thus, (2)H-labeled tracers enable dissection of NADPH production routes across cell types and environmental conditions. PMID:26999781

  10. One-pot synthesis of FePt/CNTs nanocomposites for efficient cellular imaging and cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Weihong; Zheng, Xiuwen, E-mail: xwzheng1976@163.com [Linyi University, School of Chemistry & Chemical Engineering, Shandong Provincial Key Laboratory of Detection Technology for Tumor Makers (China); Li, Shulian [Linyi Tumor Hospital (China); Zhang, Wei; Wen, Xin [Linyi University, School of Chemistry & Chemical Engineering, Shandong Provincial Key Laboratory of Detection Technology for Tumor Makers (China); Yue, Ludan [Shandong Normal University (China); Wang, Jinlong [Shandong University of Technology (China)

    2015-11-15

    Here, we developed a facile route to synthesize carbon nanotube-based FePt nanocomposites (FePt/CNTs) as a potential theranostic platform in the cancer treatment. FePt/CNTs were firstly synthesized via one-pot polyol route, and then functionalized with 6-arm-polyethylene glycol-amine polymer. The average size of FePt nanoparticles (NPs) is 3–4 nm, which is dispersed on the CNT surface (ca.50–150 nm). The as-prepared FePt NPs display high cytotoxicity by highly reactive oxygen species in cancer cells. Folic acid and fluorescein isothiocyanate are assembled onto the surface of FePt/CNTs for effective targeting of folate receptor-positive cancer cells and simultaneously for the visualization of cellular uptake. Therefore, the FePt/CNTs NPs capability of simultaneously performing diagnosis, therapy, and targeting is, therefore, promising for future potential widespread application in biomedicine.

  11. One-pot synthesis of FePt/CNTs nanocomposites for efficient cellular imaging and cancer therapy

    International Nuclear Information System (INIS)

    Here, we developed a facile route to synthesize carbon nanotube-based FePt nanocomposites (FePt/CNTs) as a potential theranostic platform in the cancer treatment. FePt/CNTs were firstly synthesized via one-pot polyol route, and then functionalized with 6-arm-polyethylene glycol-amine polymer. The average size of FePt nanoparticles (NPs) is 3–4 nm, which is dispersed on the CNT surface (ca.50–150 nm). The as-prepared FePt NPs display high cytotoxicity by highly reactive oxygen species in cancer cells. Folic acid and fluorescein isothiocyanate are assembled onto the surface of FePt/CNTs for effective targeting of folate receptor-positive cancer cells and simultaneously for the visualization of cellular uptake. Therefore, the FePt/CNTs NPs capability of simultaneously performing diagnosis, therapy, and targeting is, therefore, promising for future potential widespread application in biomedicine

  12. CityFlux perfluorocarbon tracer experiments

    Directory of Open Access Journals (Sweden)

    F. K. Petersson

    2010-01-01

    Full Text Available In June 2006, two perfluorocarbon tracer experiments were conducted in central Manchester UK as part of the CityFlux campaign. The main aim was to investigate vertical dispersion in an urban area during convective conditions, but dispersion mechanisms within the street network were also studied. Paired receptors were used in most cases where one receptor was located at ground level and one at roof level. One receptor was located on the roof of Portland Tower which is an 80 m high building in central Manchester. Source receptor distances in the two experiments varied between 120 and 600 m.

    The results reveal that maximum concentration was sometimes found at roof level rather than at ground level implying the effectiveness of convective forces on dispersion. The degree of vertical dispersion was found to be dependent on source receptor distance as well as on building height in proximity to the release site.

    Evidence of flow channelling in a street canyon was also found. Both a Gaussian profile and a street network model were applied and the results show that the urban topography may lead to highly effective flow channelling which therefore may be a very important dispersion mechanism should the right meteorological conditions prevail.

    The experimental results from this campaign have also been compared with a simple urban dispersion model that was developed during the DAPPLE framework and show good agreement with this.

    The results presented here are some of the first published regarding vertical dispersion. More tracer experiments are needed in order to further characterise vertical concentration profiles and their dependence on, for instance, atmospheric stability. The impact of urban topography on pollutant dispersion is important to focus on in future tracer experiments in order to improve performance of models as well as for our understanding of the relationship between air quality and public health.

  13. Tracer preparate and method for its production

    International Nuclear Information System (INIS)

    The injectable tracer preparate for investigations to determine the blood flow in organs or the effect of drugs on the blood flow consists of a core of ion exchanger resin coated with polyfuran or a polymer which is the reaction product of a monomer catalysable by acid or base. The nuclei have a diameter of 10 to 200 micron, the coating thickness is between 1 and 3 micron. Ions of Ce 141, Cr 51, Sr 85, Sr 46 or Co 57 of strength 0.1-100 millicurie are adsorbed on the nucleus. (DG)

  14. PET Tracers Based on Zirconium-89

    OpenAIRE

    Zhang, Yin; Hong, Hao; Cai, Weibo

    2011-01-01

    Positron emission tomography (PET) imaging with radiolabeled monoclonal antibodies has always been a dynamic area in molecular imaging. With decay half-life (3.3 d) well matched to the circulation half-lives of antibodies (usually on the order of days), 89Zr has been extensively studied over the last decade. This review article will give a brief overview on 89Zr isotope production, the radiochemistry generally used for 89Zr-labeling, and the PET tracers that have been developed using 89Zr. To...

  15. Fractal tracer distributions in turbulent field theories

    DEFF Research Database (Denmark)

    Hansen, J. Lundbek; Bohr, Tomas

    We study the motion of passive tracers in a two-dimensional turbulent velocity field generated by the Kuramoto-Sivashinsky equation. By varying the direction of the velocity-vector with respect to the field-gradient we can continuously vary the two Lyapunov exponents for the particle motion and...... thereby find a regime in which the particle distribution is a strange attractor. We compare the Lyapunov dimension to the information dimension of actual particle distributions and show that there is good agreement with the Kaplan-Yorke conjecture. Similar phenomena have been observed experimentally...

  16. Tracer Dispersion in a Multi-compartment Structure

    CERN Document Server

    Skvortsov, A; Gamble, G; Roberts, M; Ilaya, O; Pitaliadda, D

    2012-01-01

    An experimental study of the tracer dispersion in a complex structure is presented. A point source of tracer (dyed salt) was placed inside a multi-compartment structure embedded in water tank. This experimental setting corresponds to a hazardous tracer release inside the engineering structure (building, ship, aircarft etc). A system of conductivity sensors was deployed to monitor the propagation of a tracer plume in the structure, including tracer trapping inside some compartments and its release to the outside environment through the external openings. The experimental data is processed by employing the ideas of scaling and self-similarity of underlying transport processes. The established and validated scaling laws provide a rigorous way to up-scale the results of laboratory modeling to real operational scenarios and can be used as an important step in the development of risk-assessment models for the first responders to hazardous releases. Keywords: hazardous plume, tracer dispersion, diffusion and advecti...

  17. Molecular markers in breast cancer: new tools in imaging and prognosis

    OpenAIRE

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared fluorescent labeled (NIRF) tracers for detection of breast cancer. Thus far, only a few molecular imaging tracers have been taken to the clinic of which most are suitable for PET. My thesis describes the e...

  18. Measurements of waste tank passive ventilation rates using tracer gases

    International Nuclear Information System (INIS)

    This report presents the results of ventilation rate studies of eight passively ventilated high-level radioactive waste tanks using tracer gases. Head space ventilation rates were determined for Tanks A-101, AX-102, AX-103, BY-105, C-107, S-102, U-103, and U-105 using sulfur hexafluoride (SF6) and/or helium (He) as tracer gases. Passive ventilation rates are needed for the resolution of several key safety issues. These safety issues are associated with the rates of flammable gas production and ventilation, the rates at which organic salt-nitrate salt mixtures dry out, and the estimation of organic solvent waste surface areas. This tracer gas study involves injecting a tracer gas into the tank headspace and measuring its concentration at different times to establish the rate at which the tracer is removed by ventilation. Tracer gas injection and sample collection were performed by SGN Eurisys Service Corporation and/or Lockheed Martin Hanford Corporation, Characterization Project Operations. Headspace samples were analyzed for He and SF6 by Pacific Northwest National Laboratory (PNNL). The tracer gas method was first demonstrated on Tank S-102. Tests were conducted on Tank S-102 to verify that the tracer gas was uniformly distributed throughout the tank headspace before baseline samples were collected, and that mixing was sufficiently vigorous to maintain an approximately uniform distribution of tracer gas in the headspace during the course of the study. Headspace samples, collected from a location about 4 in away from the injection point and 15, 30, and 60 minutes after the injection of He and SF6, indicated that both tracer gases were rapidly mixed. The samples were found to have the same concentration of tracer gases after 1 hour as after 24 hours, suggesting that mixing of the tracer gas was essentially complete within 1 hour

  19. Atmospheric Gas Tracers in Groundwater: Theory, Sampling. Measurement and Interpretation

    International Nuclear Information System (INIS)

    Some of the atmospheric gasses posses features that are sought in an environmental tracer of hydrogeologic interest. Among these, chlorofluorocarbons, sulfur hegzafluoride, carbon tetrachloride, methyl chloroform, krypton-85 etc. have found increasing use in groundwater age dating studies during the last ten years. This paper explains the theory of their use as tracer and discusses the major concerns as related to their sampling and analyses. Factors affecting their applicability and the approach to interpret tracer gas data is briefly outlined

  20. Lidar Tracking of Multiple Fluorescent Tracers: Method and Field Test

    Science.gov (United States)

    Eberhard, Wynn L.; Willis, Ron J.

    1992-01-01

    Past research and applications have demonstrated the advantages and usefulness of lidar detection of a single fluorescent tracer to track air motions. Earlier researchers performed an analytical study that showed good potential for lidar discrimination and tracking of two or three different fluorescent tracers at the same time. The present paper summarizes the multiple fluorescent tracer method, discusses its expected advantages and problems, and describes our field test of this new technique.

  1. Magnetic Particle Imaging with Tailored Iron Oxide Nanoparticle Tracers

    OpenAIRE

    Ferguson, R. Matthew; Khandhar, Amit P.; Kemp, Scott J.; Arami, Hamed; Saritas, Emine U.; Croft, Laura R.; Konkle, Justin; Goodwill, Patrick W.; Halkola, Aleksi; Rahmer, Jürgen; Borgert, Jörn; Steven M. Conolly; Krishnan, Kannan M

    2014-01-01

    Magnetic Particle Imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI T2*-weighted imaging that are suboptimal for MPI. Here, we describe new tracers tailored to MPI's unique physics,...

  2. Tracer test feasibility assessment : Frongoch Mine tailings lagoon

    OpenAIRE

    Maurice, L.; B. Palumbo-Roe; Williams, A. T.; Banks, V.J.; Lapworth, D. J.

    2012-01-01

    The feasibility of tracer testing at the Frongoch Mine site was investigated during a two day site visit. A walkover survey identified a potential tracer injection point where a surface stream sinks into tailings deposits. Water discharges through a culvert approximately 50 m from the sinking stream. The origin of the water in the culvert is unknown but it is thought to drain the tailings area. Tracer testing could be used to determine whether this is the case. A successful tra...

  3. Compilation and analyses of results from cross-hole tracer tests with conservative tracers

    International Nuclear Information System (INIS)

    Radionuclide transport in hydrogeological formations is one of the key factors for the safety analysis of a future repository of nuclear waste. Tracer tests have therefore been an important field method within the SKB investigation programmes at several sites since the late 1970's. This report presents a compilation and analyses of results from cross-hole tracer tests with conservative tracers performed within various SKB investigations. The objectives of the study are to facilitate, improve and reduce uncertainties in predictive tracer modelling and to provide supporting information for SKB's safety assessment of a final repository of nuclear waste. More specifically, the focus of the report is the relationship between the tracer mean residence time and fracture hydraulic parameters, i.e. the relationship between mass balance aperture and fracture transmissivity, hydraulic diffusivity and apparent storativity. For 74 different combinations of pumping and injection section at six different test sites (Studsvik, Stripa, Finnsjoen, Aespoe, Forsmark, Laxemar), estimates of mass balance aperture from cross-hole tracer tests as well as transmissivity were extracted from reports or in the SKB database Sicada. For 28 of these combinations of pumping and injection section, estimates of hydraulic diffusivity and apparent storativity from hydraulic interference tests were also found. An empirical relationship between mass balance aperture and transmissivity was estimated, although some uncertainties for individual data exist. The empirical relationship between mass balance aperture and transmissivity presented in this study deviates considerably from other previously suggested relationships, such as the cubic law and transport aperture as suggested by /Dershowitz and Klise 2002/, /Dershowitz et al. 2002/ and /Dershowitz et al. 2003/, which also is discussed in this report. No clear and direct empirical relationship between mass balance aperture and hydraulic diffusivity was

  4. Compilation and analyses of results from cross-hole tracer tests with conservative tracers

    Energy Technology Data Exchange (ETDEWEB)

    Hjerne, Calle; Nordqvist, Rune; Harrstroem, Johan (Geosigma AB (Sweden))

    2010-09-15

    Radionuclide transport in hydrogeological formations is one of the key factors for the safety analysis of a future repository of nuclear waste. Tracer tests have therefore been an important field method within the SKB investigation programmes at several sites since the late 1970's. This report presents a compilation and analyses of results from cross-hole tracer tests with conservative tracers performed within various SKB investigations. The objectives of the study are to facilitate, improve and reduce uncertainties in predictive tracer modelling and to provide supporting information for SKB's safety assessment of a final repository of nuclear waste. More specifically, the focus of the report is the relationship between the tracer mean residence time and fracture hydraulic parameters, i.e. the relationship between mass balance aperture and fracture transmissivity, hydraulic diffusivity and apparent storativity. For 74 different combinations of pumping and injection section at six different test sites (Studsvik, Stripa, Finnsjoen, Aespoe, Forsmark, Laxemar), estimates of mass balance aperture from cross-hole tracer tests as well as transmissivity were extracted from reports or in the SKB database Sicada. For 28 of these combinations of pumping and injection section, estimates of hydraulic diffusivity and apparent storativity from hydraulic interference tests were also found. An empirical relationship between mass balance aperture and transmissivity was estimated, although some uncertainties for individual data exist. The empirical relationship between mass balance aperture and transmissivity presented in this study deviates considerably from other previously suggested relationships, such as the cubic law and transport aperture as suggested by /Dershowitz and Klise 2002/, /Dershowitz et al. 2002/ and /Dershowitz et al. 2003/, which also is discussed in this report. No clear and direct empirical relationship between mass balance aperture and hydraulic

  5. Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs-PEG-HER in HER2+ human breast cancer cells.

    Science.gov (United States)

    Almaki, Javad Hamzehalipour; Nasiri, Rozita; Idris, Ani; Majid, Fadzilah Adibah Abdul; Salouti, Mojtaba; Wong, Tet Soon; Dabagh, Shadab; Marvibaigi, Mohsen; Amini, Neda

    2016-03-11

    A stable, biocompatible and exquisite SPIONs-PEG-HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs-PEG were then conjugated with herceptin (HER) to permit the SPIONs-PEG-HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs-PEG-HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER-) and MDA-MB-468 (human breast cancer cells, HER-) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs-PEG-HER and SPIONs-PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs-PEG-HER and SPIONs-PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION-PEG-HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs-PEG-HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future. PMID:26861770

  6. Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs-PEG-HER in HER2+ human breast cancer cells

    Science.gov (United States)

    Hamzehalipour Almaki, Javad; Nasiri, Rozita; Idris, Ani; Majid, Fadzilah Adibah Abdul; Salouti, Mojtaba; Wong, Tet Soon; Dabagh, Shadab; Marvibaigi, Mohsen; Amini, Neda

    2016-03-01

    A stable, biocompatible and exquisite SPIONs-PEG-HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs-PEG were then conjugated with herceptin (HER) to permit the SPIONs-PEG-HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs-PEG-HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER-) and MDA-MB-468 (human breast cancer cells, HER-) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs-PEG-HER and SPIONs-PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs-PEG-HER and SPIONs-PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION-PEG-HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs-PEG-HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future.

  7. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    the perfect neuroendocrine tumor imaging tracer. (68)Ga-labeled tracers coupled to synthetic somatostatin analogs with differences in affinity for the five somatostatin receptor subtypes are now widely applied in Europe. Comparison of sensitivity between the most used tracers - (68)Ga-DOTA-Tyr3......-octreotide, (68)Ga-DOTA-Tyr3-octreotate and (68)Ga-DOTA-l-Nal3-octreotide - shows little difference and expertise on the specific tracer used, and knowledge regarding physiological uptake might be more important than in vitro-proven differences in affinity. Using isotopes such as (18)F or (64)Cu might...

  8. Microwave-assisted aqueous synthesis of new quaternary-alloyed CdSeTeS quantum dots; and their bioapplications in targeted imaging of cancer cells.

    Science.gov (United States)

    Yang, Fengzhao; Xu, Zhancheng; Wang, Jinjie; Zan, Feng; Dong, Chaoqing; Ren, Jicun

    2013-01-01

    In this study, we report for the first time a one-pot approach for the synthesis of new CdSeTeS quaternary-alloyed quantum dots (QDs) in aqueous phase by microwave irradiation. CdCl2 was used as a Cd precursor during synthesis, NaHTe and NaHSe were used as Te and Se precursors and mercaptopropionic acid (MPA) was used as a stabilizer and source of sulfur. A series of quaternary-alloyed QDs of different sizes were prepared. CdSeTeS QDs exhibited a wide emission range from 549 to 709 nm and high quantum yield (QY) up to 57.7 %. Most importantly, the quaternary-alloyed QDs possessed significantly long fluorescence lifetimes > 100 ns as well as excellent photostability. Results of high-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectroscopy (EDX) and powder X-ray diffraction (XRD) spectroscopy showed that the nanocrystals possessed a quaternary alloy structure with good crystallinity. Fluorescence correlation spectroscopy (FCS) showed that QDs possessed good water solubility and monodispersity in aqueous solution. Furthermore, CdSeTeS QDs were modified with alpha-thio-omega-carboxy poly(ethylene glycol) (HS-PEG-COOH) and the modified QDs were linked to anti-epidermal growth factor receptor (EGFR) antibodies. QDs with the EGFR antibodies as labeling probes were successfully applied to targeted imaging for EGFR on the surface of SiHa cervical cancer cells. We believe that CdSeTeS QDs can become useful probes for in vivo targeted imaging and clinical diagnosis. PMID:22696455

  9. Protein-Poly(amino acid) Nanocore-Shell Mediated Synthesis of Branched Gold Nanostructures for Computed Tomographic Imaging and Photothermal Therapy of Cancer.

    Science.gov (United States)

    Sasidharan, Sisini; Bahadur, Dhirendra; Srivastava, Rohit

    2016-06-29

    Anisotropic noble metal nanoparticles especially branched gold nanoparticles with a large absorption cross-section and high molar extinction coefficient have promising applications in biomedical field. However, sophisticated and cumbersome methodologies of synthesis along with toxic precursors pose serious concern for its use. Herein, we report the synthesis of branched gold nanostructures from protein (albumin) nanoparticles by a simple reduction method. Albumin nanoparticles were synthesized by a modified desolvation technique with poly-l-arginine (cationic poly amino acid) substituting the conventional toxic cross-linker, glutaraldehyde. In silico molecular docking was carried out to study the interaction of poly-l-arginine with albumin which revealed its binding to Pocket 1B of the A-chain of albumin. The poly-l-arginine-albumin core-shell nanoparticles of ∼100 nm in size served as a base for attachment of gold ions and its reduction to form 140 nm sized branched gold nanostructures conjugated with glutathione. These gold nanostructures exhibited near-infrared absorption λmax at 800 nm with extreme compatibility toward non cancerous (NIH 3T3), oral epithelial carcinoma (KB) cell lines, and human blood (red blood cells, platelets, and coagulation mechanisms) even up to a high concentration of 250 μg/mL. These structures demonstrated superior computed tomographic (CT) contrast ability and marked photothermal cytotoxicity on KB cells. This study reports for the first time a method to develop blood and cell compatible branched gold nanostructures from protein nanoparticles as a dual CT diagnostic and photothermal therapeutic agent. PMID:27243100

  10. Site characterization and validation - tracer migration experiment in the validation drift, report 1: Instrumentation site preparation and tracers

    International Nuclear Information System (INIS)

    The tracer migration experiment has been performed as a part of the site characterization and validation project in the Stripa experimental mine. Tracers were injected in sealed off borehole sections in the average fractured rock and in a 6 m wide fracture zone intersecting a 50 m long drift. Distances from the tracer injection sections to the drift were 10-25 m. Plastic sheets and short sumpholes were used to collect water and tracers emerging into the drift in 270 sampling areas, each with the size of 1-2 m2. Tracer concentrations were measured during 10 months and breakthrough curves were obtained for seven injection sections. This report described the experimental layout of the experiment and the equipment used. It also points at advantages/disadvantages with the two sets of tracers used in the experiment; dyes and metal complexes. (au)

  11. Tracer tests on furnaces at Metalloys Limited

    International Nuclear Information System (INIS)

    During 1980, thirteen double tests were carried out with five radioactive isotopes on three furnaces at Metalloys Limited, near Meyerton. Each double test involved the introduction of a sample of coke impregnated with lanthanum and a sample of irradiated manganese ore (54Mn or 59Fe), irradiated quartzite (46Sc), or irradiated coal (46Sc, 59Fe, and 60Co). The tests were conducted on the three large furnaces for the production of high-carbon ferromanganese, viz M10, M11, and M12. The radioactivity of samples of the metal and the slag leaving the furnace was measured by the Isotopes and Activation Division of the Atomic Energy Board (AEB). Response curves and computer analyses are presented on the elution of the tracers from the furnaces. The response curves for the tracers, which were inserted close to the electrodes, are discussed so that the salient differences between their passage through the three furnaces can be established. The results obtained give support to the findings of a dig-out carried out on furnace M10 during 1977. The metal and slag products of furnace M12 were subjected to mineralogical investigation so that the major phases in the furnace products could be determined. Details of the calculation of the mean residence time for material in furnace M12 are given in an appendix

  12. Development and automation of a novel NET-PET tracer: [11C]Me@APPI

    International Nuclear Information System (INIS)

    Introduction: The norepinephrine transporter (NET) is an important target for research in neurology and psychology and is involved in the pathophysiology of many neurodegenerative diseases such as Alzheimer's disease and attention deficient hyperactivity disorder. For visualization of NET abundance and deregulation, a novel PET tracer – [11C]Me@APPI – has been developed. Methods: For precursor synthesis, a 4-step synthesis starting from N-phenyl-o-phenylenediamine was set up. Radiosynthesis was established and optimized using standard methods and subsequently automated in a GE TRACERlabFx C Pro synthesizer. Preclinical testing was performed comprising affinity and selectivity testing on human membranes as well as stability and blood–brain-barrier-penetration using in-vitro models. Results: Precursor molecule (APPI:0) and reference compound (Me@APPI) were synthesized with 26.5% and 21.4% overall yield, respectively. So far, 1.25 ± 0.72 GBq [11C]Me@APPI with 54.35 ± 7.80 GBq/μmol specific activity were produced (n = 11). Affinity of reference compounds was determined as 8.08 ± 1.75 nM for Me@APPI and 19.31 ± 2.91 nM for APPI:0, respectively (n ≥ 9). IAM-chromatography experiments (n = 3) revealed a Pm value of 1.51 ± 0.34 for Me@APPI. Stability testing using human liver microsomes revealed that 99.5% of the tracer was found to be still intact after 60 minutes (n = 4). Conclusion: Present data indicate that [11C]Me@APPI has promising properties to become a clinically useful NET-PET-tracer. Further in-vitro and in-vivo evaluations are currently under way

  13. Collagen synthesis promoting pullulan-PEI-ascorbic acid conjugate as an efficient anti-cancer gene delivery vector.

    Science.gov (United States)

    Ambattu, Lizebona August; Rekha, M R

    2015-08-01

    Cationized pullulan (pullulan-PEI; PP) was synthesized and further modified with an anti-oxidant molecule, ascorbic acid (PPAA) at various ratios. The nanoplexes formed at an optimum ratio of 4:1 was within a size of 150nm and had a zeta potential of 9-14mV. The nanoplexes at this ratio was used for further investigations. The cell internalization and transfection efficiency of these nanoplexes were determined in presence of serum. The internalization and transfection efficiency were found to be unaffected by the presence of fetal bovine serum. Another interesting observation was that this polymer was found to have collagen synthesis promoting property. The collagen synthesis effect of these polymers was quantified and observed that PPAA3 promoted the highest. Transfection efficiency was evaluated by assessing the p53 gene expression in C6 rat glioma cells and cell death was quantified to be 96% by flow cytometry, thus establishing the high efficacy of this polymer. PMID:25933522

  14. Divergent Synthesis of Chondroitin Sulfate Disaccharides and Identification of Sulfate Motifs that Inhibit Triple Negative Breast Cancer

    Science.gov (United States)

    Wei Poh, Zhong; Heng Gan, Chin; Lee, Eric J.; Guo, Suxian; Yip, George W.; Lam, Yulin

    2015-09-01

    Glycosaminoglycans (GAGs) regulate many important physiological processes. A pertinent issue to address is whether GAGs encode important functional information via introduction of position specific sulfate groups in the GAG structure. However, procurement of pure, homogenous GAG motifs to probe the “sulfation code” is a challenging task due to isolation difficulty and structural complexity. To this end, we devised a versatile synthetic strategy to obtain all the 16 theoretically possible sulfation patterns in the chondroitin sulfate (CS) repeating unit; these include rare but potentially important sulfated motifs which have not been isolated earlier. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231.

  15. Biochemical synthesis of silver nanoprticles using filamentous fungi Penicillium decumbens (MTCC-2494) and its efficacy against A-549 lung cancer cell line.

    Science.gov (United States)

    Majeed, Shahnaz; Abdullah, Mohd Syafiq Bin; Dash, Gouri Kumar; Ansari, Mohammed Tahir; Nanda, Anima

    2016-08-01

    Biosynthesis of silver and other metallic nanoparticles is one of the emerging research area in the field of science and technology due to their potentiality, especially in the field of nano-biotechnology and biomedical sciences in order to develop nanomedicine. In our present study, Penicillium decumbens (MTCC-2494) was brought from Institute of Microbial Technology (IMTECH) Chandigarh and employed for extracellular biological synthesis of silver nanoparticles. Ag-NPs formation was appeared with a dark brown color inside the conical flask. Characterization of Ag-NPs were done by UV-Spectrophotometric analysis which showed absorption peak at 430 nm determines the presence of nanoparticles, Fourier transform infrared (FT-IR) spectroscopic analysis, showed amines and amides are the possible proteins involved in the stabilization of nanoparticles as capping agent. Atomic force Microscopy (AFM) confirmed the particle are spherical, size was around 30 to 60 nm and also the roughness of nanoparticles. Field emission scanning electron microscopy (FE-SEM) showed the topology of the nanoparticles and were spherical in shape. The biosynthesis process was found fast, ecofriendly and cost effective. Nano-silver particle was found to have a broad antimicrobial activity and also it showed good enhancement of antimicrobial activity of Carbenicillin, Piperacillin, Cefixime, Amoxicillin, Ofloxacin and Sparfloxacin in a synergistic mode. These Ag-NPs showed good anti-cancer activity at 80 μg·mL(-1)upon 24 hours of incubation and toxicity increases upon 48 hours of incubation against A-549 human lung cancer cell line and the synergistic formulation of the antibiotic with the synthesized nanoparticles was found more effective against the pathogenic bacteria studied. PMID:27608951

  16. Synthesis and biodistribution of novel magnetic-poly(HEMA–APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

    International Nuclear Information System (INIS)

    Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe3O4 particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA–APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA–APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, 131I. Thin-layer radiochromatography experiments demonstrated that 131I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA–APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 ± 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA–APH) labeled with 131I [131I-mag-poly(HEMA–APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA–APH) molecule labeled with 131I is a compound which has a significant potential for being used as an anti-cancer agent. Certain results can only be obtained whether

  17. Targeting translesion synthesis to facilitate the eradication of ovarian cancer stem cells by platinum-based therapy

    OpenAIRE

    Srivastava, Amit Kumar; Wang, Qi-En

    2015-01-01

    Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for the development of new therapies. Recently, we demonstrated that ovarian CSCs survive cisplatin treatment through enhanced expression of DNA polymerase η (Pol η). Identification of micro RNA-93 (miR-93) as the regulator of Pol η provides a novel target to improve the outcome of platinum-based therapy.

  18. Targeting translesion synthesis to facilitate the eradication of ovarian cancer stem cells by platinum-based therapy.

    Science.gov (United States)

    Srivastava, Amit Kumar; Wang, Qi-En

    2016-01-01

    Understanding the mechanisms by which cancer stem cells (CSCs) survive chemotherapy is essential for the development of new therapies. Recently, we demonstrated that ovarian CSCs survive cisplatin treatment through enhanced expression of DNA polymerase η (Pol η). Identification of micro RNA-93 (miR-93) as the regulator of Pol η provides a novel target to improve the outcome of platinum-based therapy. PMID:27308560

  19. Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells

    OpenAIRE

    Maddocks, Oliver D.K.; Christiaan F Labuschagne; Adams, Peter D; Vousden, Karen H.

    2016-01-01

    Summary: Crosstalk between cellular metabolism and the epigenome regulates epigenetic and metabolic homeostasis and normal cell behavior. Changes in cancer cell metabolism can directly impact epigenetic regulation and promote transformation. Here we analyzed the contribution of methionine and serine metabolism to methylation of DNA and RNA. Serine can contribute to this pathway by providing one-carbon units to regenerate methionine from homocysteine. While we observed this contribution under ...

  20. A new class of flavonol-based anti-prostate cancer agents: Design, synthesis, and evaluation in cell models.

    Science.gov (United States)

    Li, Xiang; Chen, Guanglin; Zhang, Xiaojie; Zhang, Qiang; Zheng, Shilong; Wang, Guangdi; Chen, Qiao-Hong

    2016-09-01

    Flavonoids are a large class of polyphenolic compounds ubiquitously distributed in dietary plants with an array of biological activities. Flavonols are a major sub-class of flavonoids featuring a hydroxyl group at C-3. Certain natural flavonols, such as quercetin and fisetin, have been shown by in vitro cell-based and in vivo animal experiments to be potential anti-prostate cancer agents. However, the Achilles' heel of flavonols as drug candidates is their moderate potency and poor pharmacokinetic profiles. This study aims to explore the substitution effect of 3-OH in flavonols on the in vitro anti-proliferative potency against both androgen-sensitive and androgen-insensitive human prostate cancer cell lines. Our first lead flavonol (3',4'-dimethoxyflavonol), eight 3-O-alkyl-3',4'-dimethoxyflavonols, and six 3-O-aminoalkyl-3',4'-dimethoxyflavonols have been synthesized through aldol condensation and the Algar-Flynn-Oyamada (AFO) reaction. The WST-1 cell proliferation assay indicates (i) that all synthesized 3-O-alkyl-3',4'-dimethoxyflavonols and 3-O-aminoalkyl-3',4'-dimethoxyflavonols are more potent than the parent 3',4'-dimethoxyflavonol and the natural flavonol quercetin in suppressing prostate cancer cell proliferation; and (ii) that incorporation of a dibutylamino group to the 3-OH group through a three- to five-carbon linker leads to the optimal derivatives with up to 292-fold enhanced potency as compared with the parent flavonol. Flow cytometry analysis showed that the most potent derivative 22 can activate PC-3 cell cycle arrest at the G2/M phase and induce PC-3 cell apoptosis. No inhibitory ability of 22 up to 50μM concentration was observed against PWR-1E normal human epithelial prostate cells, suggesting its in vitro safety profile. The results indicate that chemical modulation at 3-OH is a vital strategy to optimize flavonols as anti-prostate cancer agents. PMID:27476422

  1. Synthesis of [{sup 18}F]Xeloda as a novel potential PET radiotracer for imaging enzymes in cancers

    Energy Technology Data Exchange (ETDEWEB)

    Fei Xiangshu; Wang Jiquan; Miller, Kathy D.; Sledge, George W.; Hutchins, Gary D.; Zheng Qihuang E-mail: qzheng@iupui.edu

    2004-11-01

    Xeloda (Capecitabine), a prodrug of antitumor agent 5-fluorouracil, is the first and only oral fluoropyrimidine to be approved for use as second-line therapy in metastatic breast cancer, colorectal cancer, and other solid malignancies. Fluorine-18 labeled Xeloda may serve as a novel radiotracer for positron emission tomography (PET) to image enzymes such as thymidine phosphorylase and uridine phosphorylase in cancers. The precursor 2',3'-di-O-acetyl-5'-deoxy-5-nitro-N{sup 4}-(pentyloxycarbonyl)cytidine (11) was synthesized from D-ribose and cytosine in 8 steps with approximately 18% overall chemical yield. The reference standard 5'-deoxy-5-fluoro-N{sup 4}-(pentyloxycarbonyl)cytidine (Xeloda; 1) was synthesized from D-ribose and 5-fluorocytosine in eight steps with approximately 28% overall chemical yield. The target radiotracer 5'-deoxy-5-[{sup 18}F]fluoro-N{sup 4}-(pentyloxycarbonyl)cytidine ([{sup 18}F]Xeloda; [{sup 18}F]1) was prepared by nucleophilic substitution of the nitro-precursor with K{sup 18}F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20-30% radiochemical yields.

  2. 5-Hydroxy-7-azaindolin-2-one, a novel hybrid of pyridinol and sunitinib: design, synthesis and cytotoxicity against cancer cells.

    Science.gov (United States)

    Shah, Sajita; Lee, Chaemin; Choi, Hyukjae; Gautam, Jaya; Jang, Hyeonjin; Kim, Geum Jin; Lee, Yu-Jeong; Chaudhary, Chhabi Lal; Park, Sang Won; Nam, Tae-Gyu; Kim, Jung-Ae; Jeong, Byeong-Seon

    2016-06-01

    Angiogenesis plays important roles in tumor growth and metastasis. Sunitinib (Sutent®) is an antitumor agent targeting receptor tyrosine kinases which are involved in angiogenesis as well as cancer cell growth and survival. Using the pyridin-3-ol scaffold, which was previously reported as an excellent antioxidant and antiangiogenic platform, we have synthesized sunitinib mimics 6 by hybridizing bicyclic pyridinol 4 as a key scaffold and pyrrole-2-carbaldehydes 7 as side chains. Cytotoxicity assays showed that compounds 6 have comparable to better anticancer activity than sunitinib against five different cancer cell lines. In addition, compounds 6 showed even lower levels of cytotoxicity against normal cells, resulting in up to 26-fold better safety windows, than sunitinib. Signaling pathway-associated transcription factor reporter assay and western blot analyses revealed that apoptosis induction in MDA-MB-231 human breast cancer cells by 6F is mainly mediated through the p53 increase and down-regulation of phospho-signal transducer and activator of transcription 3 (STAT3) and its target gene products, cyclin D, Bcl-2, and survivin. The data strongly suggest that our hybrid compounds can provide a novel anticancer scaffold with improved and safer cytotoxicity profiles than sunitinib. PMID:27145715

  3. Synthesis of [18F]Xeloda as a novel potential PET radiotracer for imaging enzymes in cancers

    International Nuclear Information System (INIS)

    Xeloda (Capecitabine), a prodrug of antitumor agent 5-fluorouracil, is the first and only oral fluoropyrimidine to be approved for use as second-line therapy in metastatic breast cancer, colorectal cancer, and other solid malignancies. Fluorine-18 labeled Xeloda may serve as a novel radiotracer for positron emission tomography (PET) to image enzymes such as thymidine phosphorylase and uridine phosphorylase in cancers. The precursor 2',3'-di-O-acetyl-5'-deoxy-5-nitro-N4-(pentyloxycarbonyl)cytidine (11) was synthesized from D-ribose and cytosine in 8 steps with approximately 18% overall chemical yield. The reference standard 5'-deoxy-5-fluoro-N4-(pentyloxycarbonyl)cytidine (Xeloda; 1) was synthesized from D-ribose and 5-fluorocytosine in eight steps with approximately 28% overall chemical yield. The target radiotracer 5'-deoxy-5-[18F]fluoro-N4-(pentyloxycarbonyl)cytidine ([18F]Xeloda; [18F]1) was prepared by nucleophilic substitution of the nitro-precursor with K18F/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with the HPLC method in 20-30% radiochemical yields

  4. Non-invasive imaging of breast cancer: synthesis and study of novel near-infrared fluorescent estrogen conjugate

    Science.gov (United States)

    Jose, Iven; Vishnoi, Gargi; Deodhar, Kodand; Desai, Uday

    2005-04-01

    The use of near-infrared (NIR) spectroscopy to interrogate deeper tissue volume has shown enormous potential for molecular-based non-invasive imaging when coupled with appropriate excitable dyes. As most of the breast cancers are hormone dependent hence determination of the hormonal receptor status gains paramount importance when deciding the treatment regime for the patient. Since proliferations of the breast cancer cells are often driven by estrogen, we focus on to developing a technique to detect estrogen receptor status. As a first step, the objective of this work was to synthesize and characterize one such novel NIR fluorescent (NIRF) conjugate, which could potentially be used to detect estrogen receptors. The conjugate was synthesized by ester formation between 17-b estradiol and a cyanine dye namely: bis-1, 1-(4-sulfobutyl) indotricarbocyanine-5-carboxylic acid, sodium salt. The cyanine dye is a hydrophilic derivative of indocyanine green (ICG). The ester formed was found to have an extra binding ability with the receptor cites as compared to ICG, which was established by the partition coefficient studies. This cyanine dye has a partition coefficient less than 0.005 as compared to that of ICG (>200)[1]. In addition the ester showed enhanced fluorescent quantum yield than ICG. The replacement of the sodium ion in the ester by a larger glucosammonium ion was found to enhance the hydrophilicity and reduce the toxic effect on the cell lines. The excitation and emission peaks for the conjugate were recorded in the NIR region as 750nm and 788nm respectively. The ester developed was tested on the breast cancer cell lines MCF-7 and found non-toxic. The tagging characteristics were pivotal determinants underlying the ability of the fluorescent conjugate in binding the estrogen receptor of the breast cancer cells. This technique offers the potential of non-invasive detection of hormone receptor status in vivo and may help in decreasing the load of unnecessary biopsies

  5. Tracer Dispersion Within an Urban Environment.

    Science.gov (United States)

    Martin, D.; Shallcross, D.; Price, C.; Nickless, G.; Simmonds, P.

    2003-12-01

    The transport and dispersion of pollutants has extremely important implications for the environment on urban, regional and global scales. At the urban level localised emissions of both biogenic and anthropogenic pollutants can directly impact the health of the inhabitants. The DAPPLE (Dispersion of Air Pollutants and their Penetration into the Local Environment) project is a consortium of six universities, which involves a multidisciplinary approach to characterise relatively small-scale urban atmospheric dispersion including wind tunnel modelling, computer simulations, fieldwork and analysis. This work describes the tracer technology used to characterise atmospheric dispersion as well as preliminary results from the first tracer release experiment in Central London. A steady state finite duration release of both perfluoromethylcyclohexane (PMCH) and Sulfur Hexafluoride (SF6 ) was performed as part of the first DAPPLE campaign. These compounds were released over a fifteen-minute integrated time period with the SF6 release staggered one and a half minutes behind the PMCH. The low background concentrations of PMCH (~ 5 x 10-3 pptv) and SF6 (~5pptv) along with non-depositing and non-reactive characteristics allow for the implementation of near ideal fluid dynamic experiments. Sampling consists of a multiport ladder fitting with solenoid valves onto which a succession of sampling bags is attached. These are electrically actuated in sequential order with an integrated sampling time of three minutes. The samplers are placed at various receptor positions in the DAPPLE zone in predefined positions designed to best validate these model simulated meteorological dispersion processes. Analysis of PMCH is carried out using sample enrichment on carbon based adsorbents, separation by capillary Gas Chromatography and Negative Ion Chemical Ionisation Mass Spectrometry detection (GC-MS-NICI). SF6 concentrations are determined using fixed volume loop injections with Gas

  6. Methane emission quantification from landfills using a double tracer approach

    DEFF Research Database (Denmark)

    Scheutz, Charlotte; Samuelsson, J.; Fredenslund, Anders Michael;

    2007-01-01

    A tracer method was successfully used for quantification of the whole methane (CH4) emission from Fakse landfill. By using two different tracers the emission from different sections of the landfill could be quantified. Furthermore, is was possible to determine the emissions from local on site...

  7. Chemical tracers in Hybla Gold working room. Final report

    International Nuclear Information System (INIS)

    Chemical tracers were placed in the working room for the Hybla Gold event to aid in diagnosing flow of high-energy gases down expanding pipes leading from the room. If post-shot reentry is made, the tracers could provide valuable knowledge concerning pipe closure, mixing of gases from various locations, and volume of gas flow into various sizes of pipes

  8. Preparation of tracer 239Np from 243Am

    International Nuclear Information System (INIS)

    The aim of this work is the preparation of tracer 239Np from 243Am by extraction chromatography as a separation method that can be used as a tracer to determine the radiochemical yield of 237Np in the analysis of environmental samples. (authors)

  9. Tuning structure and mobility of solvation shells surrounding tracer additives.

    Science.gov (United States)

    Carmer, James; Jain, Avni; Bollinger, Jonathan A; van Swol, Frank; Truskett, Thomas M

    2015-03-28

    Molecular dynamics simulations and a stochastic Fokker-Planck equation based approach are used to illuminate how position-dependent solvent mobility near one or more tracer particle(s) is affected when tracer-solvent interactions are rationally modified to affect corresponding solvation structure. For tracers in a dense hard-sphere fluid, we compare two types of tracer-solvent interactions: (1) a hard-sphere-like interaction, and (2) a soft repulsion extending beyond the hard core designed via statistical mechanical theory to enhance tracer mobility at infinite dilution by suppressing coordination-shell structure [Carmer et al., Soft Matter 8, 4083-4089 (2012)]. For the latter case, we show that the mobility of surrounding solvent particles is also increased by addition of the soft repulsive interaction, which helps to rationalize the mechanism underlying the tracer's enhanced diffusivity. However, if multiple tracer surfaces are in closer proximity (as at higher tracer concentrations), similar interactions that disrupt local solvation structure instead suppress the position-dependent solvent dynamics. PMID:25833590

  10. Targeted Cancer Therapy Systems: An In Silico Study of Radiohalogenated Ligands in the Estrogen Receptor and the Synthesis of a Molecular Toolkit for the Fabrication of Customizable Nanoparticles

    Science.gov (United States)

    Barnsley, Kelton K.

    Chemotherapy is often limited by off-target toxicity and the development of multi-drug resistance in response to treatment. Strategies which reduce off-target toxicity by passively or actively targeting cancer cells may improve the efficacy of chemotherapy. Herein, two projects relating to targeted therapy are described. In the first project, the binding modes of 1,1-bis(4-hydroxyphenyl)-2-phenylethylenes (THPEs), a class of synthetic estrogens previously developed by our group, in the human estrogen receptor alpha-ligand binding domain were studied using molecular modeling programs YASARA AutoDock and Schrodinger Glide. The results were internally consistent and supported the observation that a bromine or iodine atom at the 2-position of the THPEs contributes positively to their binding in the estrogen receptor. In the second project, a "molecular toolkit" approach to the synthesis of multifunctional nanoparticles was envisioned. Our hypothesis was that the physical and chemical properties of the final product could be defined by controlling the types and relative amounts of prefunctionalized polymer units (PPUs) as well as the emulsification conditions. The design and syntheses of heterobifunctional linkers and other components for a preliminary molecular toolkit are reported, and the literature on select heterobifunctional aliphatic linkers is examined.

  11. Cell-free protein synthesis of a cytotoxic cancer therapeutic: Onconase production and a just-add-water cell-free system.

    Science.gov (United States)

    Salehi, Amin S M; Smith, Mark Thomas; Bennett, Anthony M; Williams, Jacob B; Pitt, William G; Bundy, Bradley C

    2016-02-01

    Biotherapeutics have many promising applications, such as anti-cancer treatments, immune suppression, and vaccines. However, due to their biological nature, some biotherapeutics can be challenging to rapidly express and screen for activity through traditional recombinant methods. For example, difficult-to-express proteins may be cytotoxic or form inclusion bodies during expression, increasing the time, labor, and difficulty of purification and downstream characterization. One potential pathway to simplify the expression and screening of such therapeutics is to utilize cell-free protein synthesis. Cell-free systems offer a compelling alternative to in vivo production, due to their open and malleable reaction environments. In this work, we demonstrate the use of cell-free systems for the expression and direct screening of the difficult-to-express cytotoxic protein onconase. Using cell-free systems, onconase can be rapidly expressed in soluble, active form. Furthermore, the open nature of the reaction environment allows for direct and immediate downstream characterization without the need of purification. Also, we report the ability of a "just-add-water" lyophilized cell-fee system to produce onconase. This lyophilized system remains viable after being stored above freezing for up to one year. The beneficial features of these cell-free systems make them compelling candidates for future biotherapeutic screening and production. PMID:26380966

  12. Synthesis and preliminary biological evaluation of MMP inhibitor radiotracers [11C]methyl-halo-CGS 27023A analogs, new potential PET breast cancer imaging agents

    International Nuclear Information System (INIS)

    A series of [11C]methyl-halo-CGS 27023A analogs (2-F, 1a; 4-F, 1b; 2-Cl, 1c; 3-Cl, 1d; 4-Cl, 1e; 2-Br, 1f; 3-Br, 1g; 4-Br, 1h; 4-I, 1i), novel radiolabeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) breast cancer imaging agents. The precursors halo-CGS 27023A analogs (2-F, 6a; 4-F, 6b; 2-Cl, 6c; 3-Cl, 6d; 4-Cl, 6e; 2-Br, 6f; 3-Br, 6g; 4-Br, 6h; 4-I, 6i) for radiolabeling were obtained in four steps from starting material amino acid D-valine with moderate to excellent chemical yields. Precursors were labeled by [11C]methyl triflate through 11C-O-methylation method at the aminohydroxyl position under basic conditions and isolated by solid-phase extraction (SPE) purification to produce pure target compounds in 40-60% radiochemical yields (decay corrected to end of bombardment), in 20-25 min synthesis time

  13. Novel C-17-heteroaryl steroidal CYP17 inhibitors/antiandrogens: synthesis, in vitro biological activity, pharmacokinetics, and antitumor activity in the LAPC4 human prostate cancer xenograft model.

    Science.gov (United States)

    Handratta, Venkatesh D; Vasaitis, Tadas S; Njar, Vincent C O; Gediya, Lalji K; Kataria, Ritesh; Chopra, Pankaj; Newman, Donnell; Farquhar, Rena; Guo, Zhiyong; Qiu, Yun; Brodie, Angela M H

    2005-04-21

    New chemical entities, steroidal C-17 benzoazoles (5, 6, 9 and 10) and pyrazines (14 and 15) were rationally designed and synthesized. The key reaction for synthesis of the benzoazoles involved the nucleophilic vinylic "addition-elimination" substitution reaction of 3beta-acetoxy-17-chloro-16-formylandrosta-5,16-diene (2) and benzoazole nucleophiles, while that for synthesis of pyrazines involved palladium-catalyzed cross-coupling reaction of 17-iodoandrosta-5,16-dien-3beta-ol (13) with tributylstannyl diazines. Some of the compounds were shown to be potent inhibitors of human CYP17 enzyme as well as potent antagonist of both wild type and mutant androgen receptors (AR). The most potent CYP17 inhibitors were 3beta-hydroxy-17-(1H-benzimidazole-1-yl)androsta-5,16-diene (5, code named VN/124-1), 3beta-hydroxy-17-(5(1)-pyrimidyl)androsta-5,16-diene (15) and 17-(1H-benzimidazole-1-yl)androsta-4,16-dien-3-one (6), with IC(50) values of 300, 500 and 915 nM, respectively. Compounds 5, 6, 14 and 15 were effective at preventing binding of (3)H-R1881 (methyltrienolone, a stable synthetic androgen) to both the mutant LNCaP AR and the wild-type AR, but with a 2.2- to 5-fold higher binding efficiency to the latter. Compounds 5 and 6 were also shown to be potent pure AR antagonists. The cell growth studies showed that 5 and 6 inhibit the growth of DHT-stimulated LNCaP and LAPC4 prostate cancer cells with IC(50) values in the low micromolar range (i.e., <10 microM). Their inhibitory potencies were comparable to that of casodex but remarkably superior to that of flutamide. The pharmacokinetics of compounds 5 and 6 in mice were investigated. Following s.c. administration of 50 mg/kg of 5 and 6, peak plasma levels of 16.82 and 5.15 ng/mL, respectively, occurred after 30 to 60 min, both compounds were cleared rapidly from plasma (terminal half-lives of 44.17 and 39.93 min, respectively), and neither was detectable at 8 h. Remarkably, compound 5 was rapidly converted into a metabolite

  14. Positron emission tomography tracers for imaging angiogenesis

    International Nuclear Information System (INIS)

    Position emission tomography imaging of angiogenesis may provide non-invasive insights into the corresponding molecular processes and may be applied for individualized treatment planning of antiangiogenic therapies. At the moment, most strategies are focusing on the development of radiolabelled proteins and antibody formats targeting VEGF and its receptor or the ED-B domain of a fibronectin isoform as well as radiolabelled matrix metalloproteinase inhibitors or αvβ3 integrin antagonists. Great efforts are being made to develop suitable tracers for different target structures. All of the major strategies focusing on the development of radiolabelled compounds for use with positron emission tomography are summarized in this review. However, because the most intensive work is concentrated on the development of radiolabelled RGD peptides for imaging αvβ3 expression, which has successfully made its way from bench to bedside, these developments are especially emphasized. (orig.)

  15. 210Pb as tracer of environmental processes

    International Nuclear Information System (INIS)

    210Pb is a radionuclide naturally occurring radioactive belonging to the chain of 238U. Its half-life is T1/2 = 22.23 ± 0.12 yr. There is some discrepancy in the order of 0.1% of this value and, therefore, not significantly affect the results of the chronology, affected by sources of much greater uncertainty. Assuming that 210Pb can be detected up to about 5 times its half-life, we can expect that 210Pb can provide useful information for the last 100 years or so, although this depends on the analytical techniques used and the precision of the assay. 210Pb plays an important role in the study of the environment as it is present in the atmosphere, lithosphere and hydrosphere. This tracer has been used successfully in the study of biogeochemical processes in the oceans, atmospheric deposition and anthropogenic pollution, sedimentary processes and sediment geochronology.

  16. National Biomedical Tracer Facility. Project definition study

    International Nuclear Information System (INIS)

    We request a $25 million government-guaranteed, interest-free loan to be repaid over a 30-year period for construction and initial operations of a cyclotron-based National Biomedical Tracer Facility (NBTF) in North Central Texas. The NBTF will be co-located with a linear accelerator-based commercial radioisotope production facility, funded by the private sector at approximately $28 million. In addition, research radioisotope production by the NBTF will be coordinated through an association with an existing U.S. nuclear reactor center that will produce research and commercial radioisotopes through neutron reactions. The combined facilities will provide the full range of technology for radioisotope production and research: fast neutrons, thermal neutrons, and particle beams (H-, H+, and D+). The proposed NBTF facility includes an 80 MeV, 1 mA H- cyclotron that will produce proton-induced (neutron deficient) research isotopes

  17. Use of radioactive tracers in chemical reactions

    International Nuclear Information System (INIS)

    A method for the determination of small quantities of nickel using radioactive tracers is presented. An analytical application of the displacement reaction between nickel and zinc ethylenediaminetetraacetate labeled with zinc-65 is pursued. This method is based on the extraction of radioactive zinc displaced by nickel from the zinc chelate into a dithizone-carbon tetracloride solution and the subsequent measurement of the activity of an aliquot of the extract. The method is very sensitive and nickel can be measured in concentrations as small as 0.1μg/ml or even less, depending on the specific activity of the radioreagent used. The precision and the accuracy of the method are determined. The problem of interferences, trying to eliminate them by using masking agents or by means of a previous separation between nickel and other interfering metals, is also investigated

  18. National Biomedical Tracer Facility. Project definition study

    Energy Technology Data Exchange (ETDEWEB)

    Schafer, R.

    1995-02-14

    We request a $25 million government-guaranteed, interest-free loan to be repaid over a 30-year period for construction and initial operations of a cyclotron-based National Biomedical Tracer Facility (NBTF) in North Central Texas. The NBTF will be co-located with a linear accelerator-based commercial radioisotope production facility, funded by the private sector at approximately $28 million. In addition, research radioisotope production by the NBTF will be coordinated through an association with an existing U.S. nuclear reactor center that will produce research and commercial radioisotopes through neutron reactions. The combined facilities will provide the full range of technology for radioisotope production and research: fast neutrons, thermal neutrons, and particle beams (H{sup -}, H{sup +}, and D{sup +}). The proposed NBTF facility includes an 80 MeV, 1 mA H{sup -} cyclotron that will produce proton-induced (neutron deficient) research isotopes.

  19. New SPECT and PET dementia tracers

    International Nuclear Information System (INIS)

    Single photon emission tomography (SPECT) and positron emission tomography (PET) are techniques to study in vivo neurotransmitter systems, neuro inflammation and amyloid deposits in normal human brain and in dementia. These methods used to explore the integrity of dopaminergic, cholinergic and serotonergic systems in Alzheimer's disease and in other dementias allowed to understand how the neurotransmission was modified in these disorders. Progress in the understanding of pathophysiological and clinical signs of dementia requires an evolution of the radioligands used to carry out an increasingly early and differential diagnosis in addition to monitoring the progression of disease and the effects of therapies. New emerging radiotracers for neuro inflammation or amyloid deposits are essential. In this article, new SPECT and PET tracers are presented. (authors)

  20. Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies.

    Science.gov (United States)

    Spadavecchia, Jolanda; Movia, Dania; Moore, Caroline; Maguire, Ciaran Manus; Moustaoui, Hanane; Casale, Sandra; Volkov, Yuri; Prina-Mello, Adriele

    2016-01-01

    The main objective of this study was to optimize and characterize a drug delivery carrier for doxorubicin, intended to be intravenously administered, capable of improving the therapeutic index of the chemotherapeutic agent itself, and aimed at the treatment of pancreatic cancer. In light of this goal, we report a robust one-step method for the synthesis of dicarboxylic acid-terminated polyethylene glycol (PEG)-gold nanoparticles (AuNPs) and doxorubicin-loaded PEG-AuNPs, and their further antibody targeting (anti-Kv11.1 polyclonal antibody [pAb]). In in vitro proof-of-concept studies, we evaluated the influence of the nanocarrier and of the active targeting functionality on the anti-tumor efficacy of doxorubicin, with respect to its half-maximal effective concentration (EC50) and drug-triggered changes in the cell cycle. Our results demonstrated that the therapeutic efficacy of doxorubicin was positively influenced not only by the active targeting exploited through anti-Kv11.1-pAb but also by the drug coupling with a nanometer-sized delivery system, which indeed resulted in a 30-fold decrease of doxorubicin EC50, cell cycle blockage, and drug localization in the cell nuclei. The cell internalization pathway was strongly influenced by the active targeting of the Kv11.1 subunit of the human Ether-à-go-go related gene 1 (hERG1) channel aberrantly expressed on the membrane of pancreatic cancer cells. Targeted PEG-AuNPs were translocated into the lysosomes and were associated to an increased lysosomal function in PANC-1 cells. Additionally, doxorubicin release into an aqueous environment was almost negligible after 7 days, suggesting that drug release from PEG-AuNPs was triggered by enzymatic activity. Although preliminary, data gathered from this study have considerable potential in the application of safe-by-design nano-enabled drug-delivery systems (ie, nanomedicines) for the treatment of pancreatic cancer, a disease with a poor prognosis and one of the main current

  1. Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

    Science.gov (United States)

    Spadavecchia, Jolanda; Movia, Dania; Moore, Caroline; Maguire, Ciaran Manus; Moustaoui, Hanane; Casale, Sandra; Volkov, Yuri; Prina-Mello, Adriele

    2016-01-01

    The main objective of this study was to optimize and characterize a drug delivery carrier for doxorubicin, intended to be intravenously administered, capable of improving the therapeutic index of the chemotherapeutic agent itself, and aimed at the treatment of pancreatic cancer. In light of this goal, we report a robust one-step method for the synthesis of dicarboxylic acid-terminated polyethylene glycol (PEG)-gold nanoparticles (AuNPs) and doxorubicin-loaded PEG-AuNPs, and their further antibody targeting (anti-Kv11.1 polyclonal antibody [pAb]). In in vitro proof-of-concept studies, we evaluated the influence of the nanocarrier and of the active targeting functionality on the anti-tumor efficacy of doxorubicin, with respect to its half-maximal effective concentration (EC50) and drug-triggered changes in the cell cycle. Our results demonstrated that the therapeutic efficacy of doxorubicin was positively influenced not only by the active targeting exploited through anti-Kv11.1-pAb but also by the drug coupling with a nanometer-sized delivery system, which indeed resulted in a 30-fold decrease of doxorubicin EC50, cell cycle blockage, and drug localization in the cell nuclei. The cell internalization pathway was strongly influenced by the active targeting of the Kv11.1 subunit of the human Ether-à-go-go related gene 1 (hERG1) channel aberrantly expressed on the membrane of pancreatic cancer cells. Targeted PEG-AuNPs were translocated into the lysosomes and were associated to an increased lysosomal function in PANC-1 cells. Additionally, doxorubicin release into an aqueous environment was almost negligible after 7 days, suggesting that drug release from PEG-AuNPs was triggered by enzymatic activity. Although preliminary, data gathered from this study have considerable potential in the application of safe-by-design nano-enabled drug-delivery systems (ie, nanomedicines) for the treatment of pancreatic cancer, a disease with a poor prognosis and one of the main current

  2. Suitable activated carbon-13 tracer techniques

    International Nuclear Information System (INIS)

    Feasibility and applicability studies of the proton induced gamma ray emission (PIGE) have been performed. The graphite was firstly bombarded at various proton energies to determine gamma ray yield (and, thus, sensitivities) for the reaction of interest. The accuracy for the determination of 13C abundance was checked, and the precision with which this value and ratios 13C/12C may be obtained was established by repetitive analysis samples. The performance of different standards in this determination was assessed. The mathematical treatment was developed for the determination of 13C abundance in tracer studies, and to derive the equations that govern this method of analysis from first principles, to arrive finally at a simple expression by virtue of the observed regularities. The system was calibrated by measuring the gamma ray yield form the 12C (p, γ)13N and 13C(p,γ)14N reaction as a function of known 13C enrichment. Using this experimentally determined calibration curve, unknown materials can be assayed. This technique is applicable to the analysis of samples with 13C enrichments between 0.1% and 90%. The samples of human breath natural samples were analyzed against graphite and Cylinder CO2 standards. Relative standard deviations were 13C abundance, an increase in 13C per cent isotopic abundance from the natural 1.11% (average) to only 1.39% may be ascertained. Finally, PIGE is compared with more classical techniques for analysis of 13C tracer experiments. Ease and speed are important advantages of this technique over mass spectrometry, and its error is compatible with the natural variation of biological results. (9 refs., 11 figs., 9 tabs.)

  3. Molecular dynamics investigation of tracer diffusion in a simple liquid

    International Nuclear Information System (INIS)

    Extensive Molecular-Dynamics (MD) simulations have been carried out for a model trace-solvent system made up of 100 solvent molecules and 8 tracer molecules interacting through truncated Lennard-Jones potentials. The influence of the size ratio between solute and solvent, of their mass ratio and of the solvent viscosity on the diffusivity of a small tracer were investigated. Positive deviations from a Stokes-Einstein behaviour are observed, in qualitative agreement with experimental observations. It was also observed that as tracer and solvent become increasingly dissimilar, their respective dynamics becomes decoupled. We suggest that such decouplings can be interpreted by writing their mobility of the tracer as the sum of two terms, the first one arising from a coupling between tracer dynamics and hydrodynamics modes of the solvent, and the second one describing jump motion in a locally nearly frozen environment. (author). 17 refs, 4 figs, 6 tabs

  4. Enriched noble gas isotopes: Ideal tracers for groundwater recharge

    International Nuclear Information System (INIS)

    A novel approach for tracing recharge and groundwater movement has been applied for the first time using isotopically-enriched xenon as an artificial tracer. Xenon has nine stable isotopes to choose from so recharge from multiple surface water sources can be examined. Noble gases are ideal tracers because they are inert and therefore pose no heath concerns. Furthermore, because of their low natural abundance we can dissolve small quantities into a recharge basin and still achieve a large dynamic range during dilution with native groundwater with respect to the detection limit. Once xenon is dissolved in the water and remains out of contact with the atmosphere the xenon will move conservatively with the groundwater. Absorption and retardation, associated with most other artificial tracers, is not a concern for the noble gas tracer. The goal of the first tracer experiment was to determine whether deep wells below confining layers were under the influence of recently recharged water

  5. Nanomedicine and cancer therapies

    CERN Document Server

    Sebastian, Mathew; Elias, Eldho

    2012-01-01

    Introduction Nanotechnological-Based Systems for CancerIn vivo Spectroscopy for Detection and Treatment of GBM with NPt® ImplantationNanobiotechnology for Antibacterial Therapy and DiagnosisChitosan NanoparticlesSynthesis and Biomedical Application of Silver NanoparticlesRecent Advances in Cancer Therapy Using PhytochemicalsMitochondrial Dysfunction and Cancer: Modulation by Palladium-Lipoic Acid ComplexUnity of Mind and Body: The Concept of Life Purpose DominantThuja Occidentalis and Breast Cancer ChemopreventionAntioxidants and Com

  6. Design, synthesis, and evaluation of chitosan conjugated GGRGDSK peptides as a cancer cell-targeting molecular transporter.

    Science.gov (United States)

    El-Sayed, Naglaa S; Shirazi, Amir N; El-Meligy, Magda G; El-Ziaty, Ahmed K; Nagieb, Zenat A; Parang, Keykavous; Tiwari, Rakesh K

    2016-06-01

    Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using sulfo-SMCC as a bifunctional linker to afford COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, (1)H NMR, (13)C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of a cell-impermeable cargo (e.g., F'-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer cell lines. Additionally, RGD modified and unmodified COS polymers were used to prepare nanoparticles by ionic gelation and showed particle size ranging from 187 to 338nm, and zeta potential of 12.2-18.3mV using dynamic light scattering. The efficiency of COS-NPs and COS-SMCC-RGDSK NPs was assayed for translocation of two synthetic cytotoxic agents ((2-(2-aminoethylamino)-4-(4-chlorophenyl)-6-(1H-indol-3-yl) nicotinonitrile (ACIN), and 2-(2-aminoethylamino)-6-(1H-indol-3-yl)-4-(4-methoxyphenyl)-nicotinonitrile (AMIN)) into CCRF-CEM and human prostate (DU-145) cancer cell lines. The results showed a dramatic reduction in the cell viability on their treatment with RGD targeted COS NPs in comparison to paclitaxel (PTX), free drug, and drug-loaded COS NPs. PMID:26976071

  7. Hydrothermal synthesis of titanium dioxide nanoparticles: mosquitocidal potential and anticancer activity on human breast cancer cells (MCF-7).

    Science.gov (United States)

    Murugan, Kadarkarai; Dinesh, Devakumar; Kavithaa, Krishnamoorthy; Paulpandi, Manickam; Ponraj, Thondhi; Alsalhi, Mohamad Saleh; Devanesan, Sandhanasamy; Subramaniam, Jayapal; Rajaganesh, Rajapandian; Wei, Hui; Kumar, Suresh; Nicoletti, Marcello; Benelli, Giovanni

    2016-03-01

    Mosquito vectors (Diptera: Culicidae) are responsible for transmission of serious diseases worldwide. Mosquito control is being enhanced in many areas, but there are significant challenges, including increasing resistance to insecticides and lack of alternative, cost-effective, and eco-friendly products. To deal with these crucial issues, recent emphasis has been placed on plant materials with mosquitocidal properties. Furthermore, cancers figure among the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases and 8.2 million cancer-related deaths in 2012. It is expected that annual cancer cases will rise from 14 million in 2012 to 22 million within the next two decades. Nanotechnology is a promising field of research and is expected to give major innovation impulses in a variety of industrial sectors. In this study, we synthesized titanium dioxide (TiO2) nanoparticles using the hydrothermal method. Nanoparticles were subjected to different analysis including UV-Vis spectrophotometry, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), zeta potential, and energy-dispersive spectrometric (EDX). The synthesized TiO2 nanoparticles exhibited dose-dependent cytotoxicity against human breast cancer cells (MCF-7) and normal breast epithelial cells (HBL-100). After 24-h incubation, the inhibitory concentrations (IC50) were found to be 60 and 80 μg/mL on MCF-7 and normal HBL-100 cells, respectively. Induction of apoptosis was evidenced by Acridine Orange (AO)/ethidium bromide (EtBr) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining. In larvicidal and pupicidal experiments conducted against the primary dengue mosquito Aedes aegypti, LC50 values of nanoparticles were 4.02 ppm (larva I), 4.962 ppm (larva II), 5.671 ppm (larva III), 6.485 ppm (larva IV), and 7.527 ppm (pupa). Overall, our results suggested that TiO2 nanoparticles may be

  8. Tracer migration experiments in the Stripa mine 1980-1991

    International Nuclear Information System (INIS)

    During more than 10 years, tracer experiments have been performed in the Stripa mine as part of the Stripa project to investigate the properties of both 'average' fractured rock and fracture zones. Experiments have been performed that have ranged from a few decimeters, to examine the diffusion into the rock matrix, up to tracer migration to a drift more than 50 meters from the injection point. This report compiles the results and experience that have been gained from all these tracer experiments. The experiments that are described in this report are: * The in-situ diffusion experiment where simultaneous flow and diffusion of tracers in undisturbed rock were studied over more than 3 years to validate diffusivities obtained under laboratory conditions. * Migration in a single fracture where water flow distribution and tracer transport were studied using both conservative and sorbing tracers over migration distances up to 10 meters. * The 3-D migration experiment where water inflow and tracer transport to a drift covered with 350 plastic sheet were investigated to get information on flow porosity, dispersion and channeling. The transport distances were between 10 and 56 meters from the injection points to the drift. * The channeling experiments in which the aim was to examine the channeling properties of single fractures in detail. Pressure pulse tests and tracer experiments were performed over a distances of 2 meters. * The tracer migration experiment in the validation drift where the tracer were injected mainly in a fracture zone and the collection was inside both a drift covered with plastic sheets similar to in the 3-D experiment as well as in a borehole. The distances between injection and sampling location were between 10 and 25 meters. (57 refs.) (au)

  9. Geoelectrical and colour tracer monitoring with direct push observation wells

    Science.gov (United States)

    Dietrich, P.; Dietze, M.; Hoffmann, R.

    2003-04-01

    Borehole - borehole tracer tests are a hydrogeological method to characterize groundwater flow parameters. Breakthrough curves of colour tracers, injected in one borehole and measured in one or more observation wells downstream of the first, give exact but locally very limited information about groundwater flow direction and velocity. At heterogeneous subsurface conditions a large number of investigation wells and frequent sample drawing is necessary to assure recovery of the tracer, which makes the experiments very expensive. Yet, these experiments often fail or do not give sufficient information about the flow regime in the aquifer. Monitoring of salt tracers with geoelectrical methods gives an integral information about flow parameters which in most cases is a more useful information. Especially in deeper aquifers though, it is a problem to place a high number of electrodes close enough to the moving tracer to gain precise results. To assess the mentioned problems we carried out a combined geoelectrical salt and conventional colour tracer test. Our equipment for both tests was placed in direct push boreholes, which are a lot cheaper than groundwater wells, quickly installed and much less invasive. The boreholes were installed at 10 meters distance on a 120 m long profile, to form a control plane 25 meters downstream of the tracer injection. The injection took place in three different groundwater wells at a time, to provide for a good overview of the flow regime along the control plane. We show, how integral information from the geoelectrical tracer tests can be used to design a refined borehole placement for a successful colour tracer test. Our results, quite different from groundwater modelling results, strongly support the necessity to carry out precise field tracer tests for the investigation of groundwater flow parameters.

  10. Study on Radioecology and Tracer of Iodine-129

    International Nuclear Information System (INIS)

    contaminated regions. The investigations show a strong dependence of childhood thyroid cancer incidence on thyroid exposure dose from short-lived radioiodine isotopes (i.e. 131I, 133I) released from the Chernobyl accident. However, the short half-life of 133I (20.8 h) and 131I (8.02 d) makes the evaluation of thyroid dose from these isotopes not easy. Due to the long half-life of 129I, the 129I concentration in environmental samples can be used to reconstruct the 131I and 133I dose to thyroids. Soil samples from areas in Belarus, Russia and Sweden contaminated by the Chernobyl accident were analysed for 129I and 137Cs by gamma-spectrometry. The atomic ratios of 129I/137Cs ranged from 0.10 to 0.30, with an average of 0.18. It confirmed that the 129I/137Cs ratios could be to reconstruct the deposition pattern of 131I in these areas. (3) Application of I-129 as an oceanographic tracer. By analysing the time series seaweed samples collected from the coast of Denmark, Norway, and west Greenland, seawater samples from Baltic Sea, North Sea, Belt Sea, lake water from Denmark and other Baltic Seas for 129I and 127I, the transportation, mixing and water mass from North Sea to North Atlantic, Arctic and Baltic Sea and the origination of I-129 in the Baltic Sea were studied. (4) Chemical speciation of I-129. Seawater samples from in the North Sea, Kattegat and Baltic Sea were analyzed for 129I and 127I in both iodide and iodate species and total inorganic iodine. The possibility of using this method to study the geochemical cycle of iodine in the ocean was investigated. (author)

  11. Production of gaseous tracer I2 from the sodium iodide salt

    International Nuclear Information System (INIS)

    Found in the nature in form different, the iodine has been used in diverse works in the area of the industry and health. The iodine is very unstable and volatile in the ambient temperature and the I2 is one of the diverse gaseous forms found. In this work was developed methodology for production of gaseous tracer from the sodium iodide (NaI) 0,1 M marked with 123I. The synthesis was processed with in chlorine acid (HCl) 1M and sodium iodate salt (NaIO3). The production of gas I2 initially was carried through in unit of glass with the inert material and the purpose was to study the kinetic of reaction. The synthesis occurs in the reaction bottle and the produced gas is stored in the collect bottle that contains a starch solution (5 g/100 mL water). To determine the efficiency of production of gas I2, analytic tests had been carried through, where the consumption of iodide ions of the bottle of reaction is measured. The optimization of production of the gaseous tracer was studied varying parameters as: concentration of iodide and iodate, concentration of acid and temperature. Then, the synthesis of the radiotracer was realized in the compact unit, being utilized as main reagent the salt radiated of sodium iodide, Na123I. The transportation of elementary iodine was studied by a scintillation detector NaI (2 x 2)'' placed in the reaction bottle. To acquire the data, the detector use a set of electronic modules for the acquisition of signals generated. (author)

  12. Hydroxy, carboxylic and amino acid functionalized superparamagnetic iron oxide nanoparticles: Synthesis, characterization and in vitro anti-cancer studies

    Indian Academy of Sciences (India)

    Dilaveez Rehana; Azees Khan Haleel; Aziz Kalilur Rahiman

    2015-07-01

    Superparamagnetic iron oxide nanoparticles were synthesized by simple co-precipitation method and modified with different coating agents such as ascorbic acid, hexanoic acid, salicylic acid, L-arginine and L-cysteine. The synthesized nanoparticles were characterized by various techniques such as FT IR, XRD, VSM, SEM, TEM and thermal analysis. Both bare and coated magnetites were of cubic spinel structure and spherical in shape. All the magnetite nanoparticles showed superparamagnetic behaviour with high saturated magnetization. In vitro cytotoxicity test of bare and coated nanoparticles was performed using adenocarcinoma cells, A549. Cell viability of bare and L-arginine coated magnetite nanoparticles showed IC50 value of 31.2 g/mL proving the compatibility of nanocarriers when compared to others. Hence, L-arginine coated nanoparticles were used for loading the drug paclitaxel and the observed IC50 value (7.8 g/mL) shows its potent anti-proliferative effect against A549 lung cancer cell lines. Thus, it can be speculated that the drug paclitaxel loaded L-arginine coated nanoparticles could be used as an effective drug carrier for the destruction of cancer cells.

  13. Synthesis, characterization and in vitro anti-cancer evaluation of hesperetin-loaded nanoparticles in human oral carcinoma (KB) cells

    International Nuclear Information System (INIS)

    Hesperetin (HET), a naturally occurring plant bioflavonoid present in citrus fruits, possesses potential anti-inflammatory and anti-carcinogenic activities but poor aqueous solubility limits its applications. To improve its applicability in cancer therapy, hesperetin was encapsulated in Eudragit® E (EE) 100 nanoparticles in the presence of polyvinyl alcohol (PVA) as a stabilizer and its anticancer efficacy in oral carcinoma (KB) cells was studied. Hesperetin-loaded nanoparticles (HETNPs) were prepared by nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and x-ray diffraction (XRD). The results thus displayed that the prepared nanoparticles showed a particle size in the range from 55 to 180 nm. The encapsulation efficiency of hesperetin was 83.4% obtained by UV spectroscopy. The in vitro release kinetics of hesperetin under physiological condition show initial rapid release followed by slow and sustained release. 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed higher cytotoxic efficacy of HETNPs than native hesperetin in KB cells. Further, it has been found that reactive oxygen species (ROS) generation, DNA damage and apoptotic indices in HETNPs treated cells are greater than those in native hesperetin treatment. Hence these findings demonstrate that HETNPs could be a potentially useful drug delivery system to produce better hesperetin therapeutics of cancers. (paper)

  14. Synthesis, characterization and in vitro anti-cancer evaluation of hesperetin-loaded nanoparticles in human oral carcinoma (KB) cells

    Science.gov (United States)

    Gurushankar, K.; Gohulkumar, M.; Rajendra Prasad, N.; Krishnakumar, N.

    2014-03-01

    Hesperetin (HET), a naturally occurring plant bioflavonoid present in citrus fruits, possesses potential anti-inflammatory and anti-carcinogenic activities but poor aqueous solubility limits its applications. To improve its applicability in cancer therapy, hesperetin was encapsulated in Eudragit® E (EE) 100 nanoparticles in the presence of polyvinyl alcohol (PVA) as a stabilizer and its anticancer efficacy in oral carcinoma (KB) cells was studied. Hesperetin-loaded nanoparticles (HETNPs) were prepared by nanoprecipitation method and characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and x-ray diffraction (XRD). The results thus displayed that the prepared nanoparticles showed a particle size in the range from 55 to 180 nm. The encapsulation efficiency of hesperetin was 83.4% obtained by UV spectroscopy. The in vitro release kinetics of hesperetin under physiological condition show initial rapid release followed by slow and sustained release. 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay revealed higher cytotoxic efficacy of HETNPs than native hesperetin in KB cells. Further, it has been found that reactive oxygen species (ROS) generation, DNA damage and apoptotic indices in HETNPs treated cells are greater than those in native hesperetin treatment. Hence these findings demonstrate that HETNPs could be a potentially useful drug delivery system to produce better hesperetin therapeutics of cancers.

  15. Cancer Basics

    Science.gov (United States)

    ... Cancer? Breast Cancer Colon/Rectum Cancer Lung Cancer Prostate Cancer Skin Cancer Show All Cancer Types News and Features Cancer Glossary ACS Bookstore Cancer Information Cancer Basics Cancer Prevention & Detection Signs & Symptoms of Cancer Treatments & Side Effects ...

  16. Tumor diagnosis by PET: potential of seven tracers examined in five experimental tumors including an artificial metastasis model

    International Nuclear Information System (INIS)

    The potential of seven tracers for the metabolic imaging of tumors by positron emission tomography was studied using five experimental tumor models. The tracers examined were 2-deoxy-2-[18F]fluoro-D-glucose([18F]FDG), 2-deoxy-2-[18F]fluoro-D-galactose (2-[18F]FdGal) and 2-deoxy-2-[18F]fluoro-L-fucose (2-[18F]FdFuc) for investigating energy metabolism. L-[methyl-11C]Methionine ([11C]Met) and 6-[18F]fluoro-L-fucose (6-[18F]FFuc) were used for assessing protein and glycoprotein synthesis, while [3H]thymidine ([3H]Thd) and 2-deoxy-5'-[18F]fluorouridine ([18F]FdUrd) were used to investigate nucleic acid metabolism. (Author)

  17. Evaluating uncertainties in the calibration of isotopic reference materials and multi-element isotopic tracers (EARTHTIME Tracer Calibration Part II)

    Science.gov (United States)

    McLean, Noah M.; Condon, Daniel J.; Schoene, Blair; Bowring, Samuel A.

    2015-09-01

    A statistical approach to evaluating uncertainties in the calibration of multi-element isotopic tracers has been developed and applied to determining the isotopic composition of mixed U-Pb (202 Pb-205 Pb-233 U-235 U) tracers used for accurate isotope dilution U-Pb geochronology. Our experiment, part of the EARTHTIME initiative, directly links the tracer calibration to first-principles measurements of mass and purity that are all traceable to SI units, thereby quantifying the accuracy and precision of U-Pb dates in absolute time. The calibration incorporates new more accurate and precise purity measurements for a number of commonly used Pb and U reference materials, and requires inter-relating their isotopic compositions and uncertainties. Similar methods can be used for other isotope systems that utilize multiple isotopic standards for calibration purposes. We also detail the inter-calibration of three publicly available U-Pb gravimetric solutions, which can be used to bring the same first-principles traceability to in-house U-Pb tracers from other laboratories. Accounting for uncertainty correlations in the tracer isotope ratios yields a tracer calibration contribution to the relative uncertainty of a 206 Pb/238 U date that is only half of the relative uncertainty in the 235 U/205 Pb ratio of the tracer, which was historically used to approximate the tracer related uncertainty contribution to 206 Pb/238 U dates. The tracer uncertainty contribution to 206 Pb/238 U dates has in this way been reduced to <300 ppm when using the EARTHTIME and similarly calibrated tracers.

  18. Synthesis and biological evaluation of novel folic acid receptor-targeted, β-cyclodextrin-based drug complexes for cancer treatment.

    Directory of Open Access Journals (Sweden)

    Juan-Juan Yin

    Full Text Available Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+] cancer. Water-soluble folic acid (FA-conjugated CD carriers (FACDs were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR, matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS, high performance liquid chromatography (HPLC, Fourier transform infrared spectroscopy (FTIR, and circular dichroism. Drug complexes of adamatane (Ada and cytotoxic doxorubicin (Dox with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5-2.5 nm. The host-guest association constant K a was 1,639 M(-1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+ cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release

  19. Quantification of lung cancer risk after low radon exposure and low exposure rate: synthesis from epidemiological and experimental data

    Energy Technology Data Exchange (ETDEWEB)

    Timarche, M

    2004-03-15

    Radon is a radioactive gas produced during the decay of uranium 238 that is present in soil. It was classified as a human lung carcinogen in 1988, based on evidence both from animal studies and from human studies of miners with high levels of radon exposure. Radon is present everywhere; therefore the quantification of the risk associated with exposure to it is a key public health issue. The project aimed to analyse the risk associated with radon inhalation at low doses and at low rates of exposure. It involved researchers from three different fields: epidemiology, animal experiments and mechanistic modelling and provided a unique opportunity to study the influence of dose rate, mainly in the range of low daily exposures over long periods, by analysing in parallel results from both animal and epidemiological studies. The project comprised 6 work packages (W.P.). Firstly, the partners involved in epidemiology and animal experiments worked on the validation and the analysis of the data. Secondly, the data from W.P.1 and W.P.4 were transferred to the partners involved in W.P.5 for the application of mechanistic models. In the final step a synthesis of the results was prepared. (N.C)

  20. Synthesis and anti-cancer activity evaluation of novel prenylated and geranylated chalcone natural products and their analogs.

    Science.gov (United States)

    Wang, Hao-Meng; Zhang, Li; Liu, Jiang; Yang, Zhao-Liang; Zhao, Hong-Ye; Yang, Yao; Shen, Di; Lu, Kui; Fan, Zhen-Chuan; Yao, Qing-Wei; Zhang, Yong-Min; Teng, Yu-Ou; Peng, Yu

    2015-03-01

    Four natural chalcones bearing prenyl or geranyl groups, i.e., bavachalcone (1a), xanthoangelol (1b), isobavachalcone (1c), and isoxanthoangelol (1d) were synthesized by using a regio-selective iodination and the Suzuki coupling reaction as key steps. The first total synthesis of isoxanthoangelol (1d) was achieved in 36% overall yield. A series of diprenylated and digeranylated chalcone analogs were also synthesized by alkylation, regio-selective iodination, aldol condensation, Suzuki coupling and [1,3]-sigmatropic rearrangement. The structures of the 11 new derivatives were confirmed by (1)H NMR, (13)C NMR and HRMS. The anticancer activity of these new chalcone derivatives against human tumor cell line K562 were evaluated by MTT assay in vitro. SAR studies suggested that the 5'-prenylation/geranylation of the chalcones significantly enhance their cytotoxic activity. Among them, Bavachalcone (1a) displayed the most potent cytotoxic activity against K562 with IC50 value of 2.7 μM. The morphology changes and annexin-V/PI staining studies suggested that those chalcone derivatives inhibited the proliferation of K562 cells by inducing apoptosis. PMID:25590864

  1. Quantification of lung cancer risk after low radon exposure and low exposure rate: synthesis from epidemiological and experimental data

    International Nuclear Information System (INIS)

    Radon is a radioactive gas produced during the decay of uranium 238 that is present in soil. It was classified as a human lung carcinogen in 1988, based on evidence both from animal studies and from human studies of miners with high levels of radon exposure. Radon is present everywhere; therefore the quantification of the risk associated with exposure to it is a key public health issue. The project aimed to analyse the risk associated with radon inhalation at low doses and at low rates of exposure. It involved researchers from three different fields: epidemiology, animal experiments and mechanistic modelling and provided a unique opportunity to study the influence of dose rate, mainly in the range of low daily exposures over long periods, by analysing in parallel results from both animal and epidemiological studies. The project comprised 6 work packages (W.P.). Firstly, the partners involved in epidemiology and animal experiments worked on the validation and the analysis of the data. Secondly, the data from W.P.1 and W.P.4 were transferred to the partners involved in W.P.5 for the application of mechanistic models. In the final step a synthesis of the results was prepared. (N.C)

  2. Synthesis and evaluation of naphthalene-based thiosemicarbazone derivatives as new anticancer agents against LNCaP prostate cancer cells.

    Science.gov (United States)

    Altintop, Mehlika Dilek; Sever, Belgin; Özdemir, Ahmet; Kuş, Gökhan; Oztopcu-Vatan, Pinar; Kabadere, Selda; Kaplancikli, Zafer Asim

    2016-06-01

    Fourteen new naphthalene-based thiosemicarbazone derivatives were designed as anticancer agents against LNCaP human prostate cancer cells and synthesized. MTT assay indicated that compounds 6, 8 and 11 exhibited inhibitory effect on LNCaP cells. Among these compounds, 4-(naphthalen-1-yl)-1-[1-(4-hydroxyphenyl)ethylidene)thiosemicarbazide (6), which caused more than 50% death on LNCaP cells, was chosen for flow cytometric analysis of apoptosis. Flow cytometric analysis pointed out that compound 6 also showed apoptotic effect on LNCaP cells. Compound 6 can be considered as a promising anticancer agent against LNCaP cells owing to its potent cytotoxic activity and apoptotic effect. PMID:25826149

  3. Tracer kinetic modelling of tumour angiogenesis based on dynamic contrast-enhanced CT and MRI measurements

    International Nuclear Information System (INIS)

    Technical developments in both magnetic resonance imaging (MRI) and computed tomography (CT) have helped to reduce scan times and expedited the development of dynamic contrast-enhanced (DCE) imaging techniques. Since the temporal change of the image signal following the administration of a diffusible, extracellular contrast agent (CA) is related to the local blood supply and the extravasation of the CA into the interstitial space, DCE imaging can be used to assess tissue microvasculature and microcirculation. It is the aim of this review to summarize the biophysical and tracer kinetic principles underlying this emerging imaging technique offering great potential for non-invasive characterization of tumour angiogenesis. In the first part, the relevant contrast mechanisms are presented that form the basis to relate signal variations measured by serial CT and MRI to local tissue concentrations of the administered CA. In the second part, the concepts most widely used for tracer kinetic modelling of concentration-time courses derived from measured DCE image data sets are described in a consistent and unified manner to highlight their particular structure and assumptions as well as the relationships among them. Finally, the concepts presented are exemplified by the analysis of representative DCE data as well as discussed with respect to present and future applications in cancer diagnosis and therapy. Depending on the specific protocol used for the acquisition of DCE image data and the particular model applied for tracer kinetic analysis of the derived concentration-time courses, different aspects of tumour angiogenesis can be quantified in terms of well-defined physiological tissue parameters. DCE imaging offers promising prospects for improved tumour diagnosis, individualization of cancer treatment as well as the evaluation of novel therapeutic concepts in preclinical and early-stage clinical trials. (orig.)

  4. New testosterone derivatives as semi-synthetic anticancer agents against prostate cancer: synthesis and preliminary biological evaluation.

    Science.gov (United States)

    Morin, Nathalie; Bruneau, Julie; Fortin, Sebastien; Brasseur, Kevin; Leblanc, Valerie; Asselin, Eric; Berube, Gervais

    2015-01-01

    Prostate cancer (PC) is a major health issue in the world. Treatments of localized PC are quite efficient and usually involve surgery, radiotherapy and/or hormonal therapy. Metastatic PC is however rarely curable to this day. Treatments of metastatic PC involve radiotherapy, chemotherapy and hormonal treatment such as orchiectomy, antiandrogens and luteinizing hormone-releasing hormone agonists. The suppression of tumor growth by hormonal treatment is efficient but overtime resistance still occurs and the disease progresses. Thus, more urgently than ever there is a need for discovery of new treatment options for castration-resistant PC (CRPC). Hence, we designed and tested a series of amide derivatives located at position 7α of testosterone as prospective "natural" or "semisynthetic" anticancer agents against CRPC with the goal of discovering therapeutic alternatives for the disease. This manuscript describes an efficient path towards the target molecules that are made in only 6 or 7 chemical steps from testosterone in good overall yields. This strategy can be used to make several compounds of interest that present higher biological activity than the classic antiandrogen; cyproterone acetate (3). The best testosterone-7α-amide was the N-2-pyridylethylamide (25) which was as active as the antiandrogen cyproterone acetate (3) on androgen-dependent LNCaP cells and 2.7 times more active on androgen-independent PC3 prostate cancer cells. The results obtained show the synthetic feasibility and the potential for future development of this unique class of semi-synthetic anticancer agents that offer the premise of new treatment modalities for patients afflicted with CRPC. PMID:25675439

  5. Synthesis, characterization, plasmid cleavage and cytotoxicity of cancer cells by a copper(II) complex of anthracenyl-terpyridine.

    Science.gov (United States)

    Kumar, Amit; Chinta, Jugun Prakash; Ajay, Amrendra Kumar; Bhat, Manoj Kumar; Rao, Chebrolu P

    2011-11-01

    Metallo-organic compounds are interesting to study for their antitumor activity and related applications. This paper deals with the syntheses, characterization, structure determination of a copper complex of anthracenyl terpyridine (1) and its plasmid cleavage and cytotoxicity towards different cancer cell lines. The complex binds CT-DNA through partial intercalation mode. The plasmid cleavage studies carried out using pBR322 and pUC18 resulted in the formation of all the three forms of the plasmid DNA. Plasmid cleavage studies carried out with a non-redoxable Zn(2+) complex (2) supported the role of the redox activity of copper in 1. The complex 1 showed remarkable antiproliferative activity against cancer cell lines, viz., cervical (HeLa, SiHa, CaSki), breast (MCF-7), liver (HepG2) and lung (H1299). A considerable lowering was observed in the IC(50) values of HPV-infected (viz., HeLa, SiHa, CaSki) vs. non-HPV-infected cell lines (MCF-7, HepG2, H1299). Antiproliferative activity of 1 was found to be much higher than the carboplatin when treated with the same cell lines. Incubation of the cells with 1 results in granular structures only with the HPV-infected cells and not with others as studied by phase contrast and fluorescence microscopy. The lower IC(50) value observed in case of 1 with HPV-infected cell lines may be correlated with the involvement of HPV oncoprotein. The role of HPV has been further augmented by transfecting the MCF-7 cells (originally not possessing HPV copy) with e6 oncoprotein cDNA. To our knowledge this is the first copper complex that causes cell death by interacting with HPV oncoprotein followed by exhibition of remarkable antiproliferative activity. PMID:21709916

  6. Dispersion of a tracer in the deep Gulf of Mexico

    Science.gov (United States)

    Ledwell, James R.; He, Ruoying; Xue, Zuo; DiMarco, Steven F.; Spencer, Laura J.; Chapman, Piers

    2016-02-01

    A 25 km streak of CF3SF5 was released on an isopycnal surface approximately 1100 m deep, and 150 m above the bottom, along the continental slope of the northern Gulf of Mexico, to study stirring and mixing of a passive tracer. The location and depth of the release were near those of the deep hydrocarbon plume resulting from the 2010 Deepwater Horizon oil well rupture. The tracer was sampled between 5 and 12 days after release, and again 4 and 12 months after release. The tracer moved along the slope at first but gradually moved into the interior of the Gulf. Diapycnal spreading of the patch during the first 4 months was much faster than it was between 4 and 12 months, indicating that mixing was greatly enhanced over the slope. The rate of lateral homogenization of the tracer was much greater than observed in similar experiments in the open ocean, again possibly enhanced near the slope. Maximum concentrations found in the surveys had fallen by factors of 104, 107, and 108, at 1 week, 4 months, and 12 months, respectively, compared with those estimated for the initial tracer streak. A regional ocean model was used to simulate the tracer field and help interpret its dispersion and temporal evolution. Model-data comparisons show that the model simulation was able to replicate statistics of the observed tracer distribution that would be important in assessing the impact of oil releases in the middepth Gulf.

  7. Gastrin labelled at Ipen: comparison with a commercial tracer

    International Nuclear Information System (INIS)

    Radioiodinated gastrin has been prepared at IPEN laboratory for radioimmunoassay use and submitted to a quality control evaluation. This work concludes the evaluation of quality of gastrin radioiodinated at IPEN, comparing it with a commercial tracer through the analysis of the purity and the radioimmunoassay performance. The IPEN tracer presented a higher purity when analysed on 7% polyacrylamide gel electrophoresis (85,00% against 65,81%). The 125I incorporation evaluated through thrichloroacetic acid precipitation confirmed its high purity degree (96,23% against 75,38%). In relation to the purity, in the radioimmunoassay system, the IPEN tracer presented the lower non-specific binding value (1,40% against 7,30%). The antibody titers required to bind 50% of the tracers were very similar: 1:136.000 for the IPEN and 1:152.000 for the commercial. In this way the specific binding of the radioimmunoassay was close (48,60% for the IPEN and 45,90% for the commercial) as well as the respective doses producing 50% fall in the maximum responses (45 and 40 pmol/l). Besides, the standard curves obtained with both tracers were parallels presenting very high sensitivity (0,99 pmol/l for the IPEN and 0,80 pmol/l for the commercial). Samples of internal quality control measured in the standard curves prepared with these tracers showed a high significant correlation (p<-0,001), indicating the comparable quality of our tracer with imported one. (author)

  8. Methods of 15N tracer research in biological systems

    International Nuclear Information System (INIS)

    The application of the stable isotope 15N is of increasing importance in different scientific disciplines, especially in medicine, agriculture, and the biosciences. The close correlation between the growing interest and improvements of analytical procedures resulted in remarkable advances in the 15N tracer technique. On the basis of the latest results of 15N tracer research in life sciences and agriculture methods of 15N tracer research in biological systems are compiled. The 15N methodology is considered under three headings: Chemical analysis with a description of methods of sample preparation (including different separation and isolation methods for N-containing substances of biological and agricultural origin) and special procedures converting ammonia to molecular nitrogen. Isotopic analysis with a review on the most important methods of isotopic analysis of nitrogen: mass spectrometry (including the GC-MS technique), emission spectrometry, NMR spectroscopy, and other analytical procedures. 15N-tracer techniques with a consideration of the role of the isotope dilution analysis as well as different labelling techniques and the mathematical interpretation of tracer data (modelling, N turnover experiments). In these chapters also sources of errors in chemical and isotopic analysis, the accuracy of the different methods and its importance on tracer experiments are discussed. Procedures for micro scale 15N analysis and aspects of 15N analysis on the level of natural abundance are considered. Furthermore some remarks on isotope effects in 15N tracer experiments are made. (author)

  9. Tailoring Fluorescent Dyes To Optimize a Hybrid RGD-Tracer.

    Science.gov (United States)

    Bunschoten, Anton; van Willigen, Danny M; Buckle, Tessa; van den Berg, Nynke S; Welling, Mick M; Spa, Silvia J; Wester, Hans-Jürgen; van Leeuwen, Fijs W B

    2016-05-18

    Quantitative assessment of affinity and kinetics is a critical component in the development of (receptor-targeted) radiotracers. For fluorescent tracers, such an assessment is currently not yet applied, while (small) changes in chemical composition of the fluorescent component might have substantial influence on the overall properties of a fluorescent tracer. Hybrid imaging labels that contain both a radiolabel and a fluorescent dye can be used to evaluate both the affinity (fluorescent label) and the in vivo distribution (radiolabel) of a targeted tracer. We present a hybrid label oriented and matrix-based scoring approach that enabled quantitative assessment of the influence of (overall) charge and lipophilicity of the fluorescent label on the (in vivo) characteristics of αvβ3-integrin targeted tracers. Systematic chemical alterations in the fluorescent dye were shown to result in a clear difference in the in vivo distribution of the different hybrid tracers. The applied evaluation technique resulted in an optimized targeted tracer for αvβ3-integrin, which combined the highest T/M ratio with the lowest uptake in other organs. Obviously this selection concept would also be applicable during the development of other (receptor-targeted) imaging tracers. PMID:27074375

  10. Loviisa Power Station - final disposal of reactor waste - tracer investigations

    International Nuclear Information System (INIS)

    Tracer measurements by radioactive isotopes have been carried out at the Loviisa power plant site in order to assess the suitability of the bedrock for the final disposal of low- and intermediate-level reactor waste. The aim of these tracer measurements was to study the flow geometry, the flow velocity and dispersion in the selected sections between boreholes with nonsorbing tracers. The most open fractures were selected for the measurements and so the results given in this report represent the most conductive part of the bedrock, which also bears the greatest influence on the safety analysis. The groundwater flow in fractures was caused by pumping water out of one borehole. In single-well measurements, vertical flow velocities and the locations of the hydraulically well conducting fractured zones were checked in order to facilitate the planning of the subsequent multi-well measurements. The results obtained were used to determine the sections of the boreholes suitable for injecting the tracer and to position the packers so that vertical short-circuiting flows could be prevented in boreholes between the fractured zones. The multi-well measurements were started with a short half-life tracer to find out how fast tracers would go from one borehole to another. Later long half-life tracers were used to obtain the final results. The tracers were lanthanides in the DTPA complex form. The breakthrough curves were measured both from the pumped water and from samples taken from the borehole. Combined with sampling from the borehole the tracer techniques revealed that groundwater flowed in the fractured zone through different pathways and entered the pumped borehole at several distinct depths. Simple flow models were fitted to the results to form a suitable network of pathways for subsequent safety analysis

  11. Targeted polyethylene glycol gold nanoparticles for the treatment of pancreatic cancer: from synthesis to proof-of-concept in vitro studies

    Directory of Open Access Journals (Sweden)

    Spadavecchia J

    2016-02-01

    Full Text Available Jolanda Spadavecchia,1,2,* Dania Movia,3,* Caroline Moore,3,4 Ciaran Manus Maguire,3,4 Hanane Moustaoui,2 Sandra Casale,1 Yuri Volkov,3,4 Adriele Prina-Mello3,4 1Laboratoire de Réactivité de Surface, Sorbonne Universités, UPMC Univ Paris VI, Paris, 2Centre National de la recherche française, UMR 7244, CSPBAT, Laboratory of Chemistry, Structures, and Properties of Biomaterials and Therapeutic Agents, Université Paris 13, Sorbonne Paris Cité, Bobigny, France; 3AMBER Centre, CRANN Institute, 4Department of Clinical Medicine, School of Medicine, Trinity College, Dublin, Ireland *These authors contributed equally to this work Abstract: The main objective of this study was to optimize and characterize a drug delivery carrier for doxorubicin, intended to be intravenously administered, capable of improving the therapeutic index of the chemotherapeutic agent itself, and aimed at the treatment of pancreatic cancer. In light of this goal, we report a robust one-step method for the synthesis of dicarboxylic acid-terminated polyethylene glycol (PEG-gold nanoparticles (AuNPs and doxorubicin-loaded PEG-AuNPs, and their further antibody targeting (anti-Kv11.1 polyclonal antibody [pAb]. In in vitro proof-of-concept studies, we evaluated the influence of the nanocarrier and of the active targeting functionality on the anti-tumor efficacy of doxorubicin, with respect to its half-maximal effective concentration (EC50 and drug-triggered changes in the cell cycle. Our results demonstrated that the therapeutic efficacy of doxorubicin was positively influenced not only by the active targeting exploited through anti-Kv11.1-pAb but also by the drug coupling with a nanometer-sized delivery system, which indeed resulted in a 30-fold decrease of doxorubicin EC50, cell cycle blockage, and drug localization in the cell nuclei. The cell internalization pathway was strongly influenced by the active targeting of the Kv11.1 subunit of the human Ether-à-go-go related gene

  12. Synthesis, properties, and in vivo evaluation of sustained release albumin-mitoxantrone microsphere formulations for nonsystemic treatment of breast cancer and other high mortality cancers

    Science.gov (United States)

    Hadba, Ahmad Robert

    Methods for preparing mitoxantrone (MXN)-loaded albumin microspheres for the treatment of breast cancer were developed. The effect of processing conditions on the particle size of unloaded and MXN-loaded microspheres was evaluated using multivariate analyses. The data suggested that the particle size of unloaded microspheres increased as protein concentration increased or the steric stabilizer concentration decreased. In addition, synergy between these two variables was observed. In situ-loading of MXN achieved loading efficiencies in excess of 80%. Comparable efficiencies were achieved with postsynthesis loading when the microsphere were prepared from albumin-poly(glutamic acid) blends. In vitro release of MXN in phosphate buffered saline under infinite sink conditions showed that the total amount of drug released increased as the glutaraldehyde concentration decreased. This trend was reversed when the microspheres were incubated in plasma. Nanoparticles were also prepared using ethanol desolvation. These particles were dispersible in saline and easily modified with amino acids. In addition, particle size could be varied by use of different non-ionic surfactants in the preparation. The effect of intratumoral (IT) versus intravenous (IV) drug administration on tumor response and systemic toxicity was investigated in vivo using the 16/C murine mammary adenocarcinoma tumor model. The data suggested that IT-treated animals had significantly smaller tumors and lower weight loss when compared to IV-treated animals. Furthermore, the addition of surgery to the chemotherapy further improved the survival of the animals. Pilot studies using MXN-albumin microspheres suggested that microspheres could be safely administered IT in doses up to 48 mg/kg. However, there was no evidence that this higher dose resulted in improved long term survival when compared to the 32 mg/kg dose. The maximum tolerated dose of MAN given IT was approximately 12 mg/kg. The animal studies suggested

  13. Laboratory Testing of Magnetic Tracers for Soil Erosion Measurement*1

    Institute of Scientific and Technical Information of China (English)

    HU Guo-Qing; DONG Yuan-Jie; WANG Hui; QIU Xian-Kui; WANG Yan-Hua

    2011-01-01

    Soil erosion, which includes soil detachment, transport, and deposition, is one of the important dynamic land surface processes. The magnetic tracer method is a useful method for studying soil erosion processes. In this study, five types of magnetic tracers were made with fine soil, fly ash, cement, bentonite, and magnetic powder (reduced iron powder) using the method of disk granulation. The tracers were uniformly mixed with soil and tested in the laboratory using simulated rainfall and inflow experiments to simulate the interrill and rill components of soil erosion, in order to select one or more tracers which could be used to study detachment and deposition by the erosive forces of raindrops and surface flow of water on a slope. The results showed that the five types of magnetic tracers with high magnetic susceptibility and a wide range of sizes had a range of 0.99-1.29 gcm-s in bulk density. In the interrill and rill experiments, the tracers FC1 and FC2 which consisted of fly ash and cement at ratios of 1:1 and 2:1, respectively, were transported in phase with soil particles since the magnetic susceptibility of sediment approximated that of the soil which was uneroded and the slopes of the regression equations between the detachment of sediment and magnetic tracers FC1 and FC2 were very close to the expected value of 20, which was the original soil/tracer ratio. The detachment and deposition on slopes could be accurately reflected by the magnetic susceptibility differences. The change in magnetic susceptibility depended on whether deposition or detachment occurred. However, the tracer FS which consisted of fine soil and the tracers FB1 and FB2 which consisted of fly ash and bentonite at ratios of 1:1 and 2:1, respectively, were all unsuitable for soil erosion study since there was no consistent relationship between sediment and tracer detachment for increasing amounts of runoff. Therefore, the tracers FC1 and FC2 could be used to study soil erosion by water.

  14. Tracer diffusivity and effective temperature in bacterial suspensions

    CERN Document Server

    Patteson, Alison E; Purohit, Prashant K; Arratia, Paulo E

    2015-01-01

    The dynamics of tracer particles in \\textit{E. coli} suspensions are experimentally investigated as a function of particle size and bacteria concentration. We find that tracer diffusivity is enhanced due to particle-bacteria interactions and varies non-monotonically with particle size, exhibiting a peak at sizes comparable to the bacterial length. The time scale characterizing the transition from ballistic to diffusive regime increases monotonically with \\textit{E. coli} concentration and particle size. Diffusivity measurements are then used to estimate suspension effective temperature, which varies nonlinearly with tracer size, suggesting that measures of activity are probe size dependent.

  15. Cell kinetic measurements in prostate cancer

    International Nuclear Information System (INIS)

    Purpose: Two approaches have been suggested for escalating the total dose in radiotherapy treatment of prostate cancer. One is conformal radiotherapy; the other is hyperfractionation using many small fractions. Both imply some possible prolongation in overall treatment time. To judge whether prolonged treatment schedules would be detrimental, it is necessary to know the proliferation rates in human prostate tumors, specifically, the potential doubling time (Tpot). There is a lack of data on this parameter in the literature. Methods and Materials: Seven patients with adenocarcinoma of the prostate were studied. A tracer dose of 100 mg/m2 of IUdR was infused intravenously 4-12 h before biopsies were taken. Biopsies were fixed in 70% ethanol, stored at 4 deg. C, and later prepared and stained by standard methods for flow cytometry, using the red fluorescence signal for DNA and the green fluorescence signal (fluorescein isothiocyanate) for 5-iodo-2'-deoxyuridine. The duration of DNA synthesis (Ts) was determined by the relative movement (RM) method, knowing the interval between tracer administration and biopsy. Tpot was calculated as the quotient of Ts by labeling index (LI). Results: In two of the seven tumors the LI was too low (<0.6%) for a reliable estimate of RM to be made, so no determination of Tpot was possible for these tumors. The mean LI values in the other five tumors were 2.4%, 1.4%, 1.0%, 3.0%, and 0.9%. The durations of Ts were 13.2, 9.5, 10.0, 11.7, and 12.7 h, respectively. The resulting values of Tpot were 23, 28, 42, 16, and 61 days, respectively. Conclusion: The low labeling indices in prostate tumors, also reported by others, made estimation of Ts by RM impossible in about a third of these tumors. However, five tumors yielded long estimates for Tpot, implying that prolongation from 6 to about 8 weeks should not be detrimental

  16. Synthesis and biodistribution of novel magnetic-poly(HEMA-APH) nanopolymer radiolabeled with iodine-131 and investigation its fate in vivo for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Avc Latin-Small-Letter-Dotless-I bas Latin-Small-Letter-Dotless-I , Ugur, E-mail: uguravcibasi@yahoo.com [Celal Bayar University, Department of Chemistry, Faculty of Arts and Science (Turkey); Avc Latin-Small-Letter-Dotless-I bas Latin-Small-Letter-Dotless-I , Nesibe [Ege University, Ege Higher Vocational School (Turkey); Akal Latin-Small-Letter-Dotless-I n, Hilmi Arkut; Ediz, Melis; Demiroglu, Hasan [Celal Bayar University, Department of Chemistry, Faculty of Arts and Science (Turkey); Guemueser, Fikriye Guel [Celal Bayar University, Department of Nuclear Medicine, Faculty of Medicine (Turkey); Oezcal Latin-Small-Letter-Dotless-I skan, Emir; Tuerkcan, Ceren [Ege University, Department of Biochemistry, Faculty of Science (Turkey); Uygun, Deniz Aktas [Adnan Menderes University, Department of Chemistry, Faculty of Arts and Science (Turkey); Akgoel, Sinan [Ege University, Department of Biochemistry, Faculty of Science (Turkey)

    2013-10-15

    Herein, we investigated the biological uptake, distribution, and radiopharmaceutical potential of a novel molecule based on 2-hydroxyethyl methacrylate (HEMA) and anilinephtalein (APH) in the metabolism of Albino Wistar rats. In order to achieve this, we synthesized APH using organic synthesis methods and copolymerized APH with HEMA using a common polymerization method, surfactant-free emulsion polymerization. In the presence of Fe{sub 3}O{sub 4} particles, we obtained a new generation magnetic-nano-scale polymer, magnetic-poly(HEMA-APH). This new molecule was chemically identified and approved by several characterization methods using Fourier transform infrared spectroscopy, scanning electron microscope, energy dispersive X-ray spectroscopy, electron spin resonance, atomic force microscope, and Zeta particle-size analysis. To evaluate the biological activity in live metabolism and anti-cancer potential of mag-poly(HEMA-APH), molecule was radioiodinated by a widely used labeling technique, iodogen method, with a gamma diffuser radionuclide, {sup 131}I. Thin-layer radiochromatography experiments demonstrated that {sup 131}I binded to nanopolymer with the labeling yield of 90 %. Lipophilicity and stability experiments were conducted to determine the condition of cold and labeled mag-poly(HEMA-APH) in rat blood and lipid medium. Results demonstrated that radioiodinated molecule stayed as an intact complex in rat metabolism for 24 h and experimental lipophilicity was determined as 0.12 {+-} 0.02. In vivo results obtained by imaging and biological distribution experiments indicated that mag-poly(HEMA-APH) labeled with {sup 131}I [{sup 131}I-mag-poly(HEMA-APH)] highly incorporated into tissues of the uterus, the ovarian, the prostate, and the lungs in rat metabolism. Based on these results, it may be evaluated that novel mag-poly(HEMA-APH) molecule labeled with {sup 131}I is a compound which has a significant potential for being used as an anti-cancer agent. Certain

  17. 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

  18. Synthesis and characterization of multifunctional hybrid-polymeric nanoparticles for drug delivery and multimodal imaging of cancer

    Directory of Open Access Journals (Sweden)

    Tng DJH

    2015-09-01

    Full Text Available Danny Jian Hang Tng,1,* Peiyi Song,1,* Guimiao Lin,2,3,* Alana Mauluidy Soehartono,1 Guang Yang,1 Chengbin Yang,1 Feng Yin,1 Cher Heng Tan,4 Ken-Tye Yong1 1School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore; 2The Engineering Lab of Synthetic Biology, 3Research Institute of Uropoiesis and Reproduction, School of Medicine, Shenzhen University, Shenzhen, People’s Republic of China; 4Department of Diagnostic Radiology, Tan Tock Seng Hospital, Singapore *These authors contributed equally to this work Abstract: In this study, multifunctional hybrid-polymeric nanoparticles were prepared for the treatment of cultured multicellular tumor spheroids (MCTS of the PANC-1 and MIA PaCa-2 pancreatic carcinoma cell lines. To synthesize the hybrid-polymeric nanoparticles, the poly lactic-co-glycolic acid core of the particles was loaded with Rhodamine 6G dye and the chemotherapeutic agent, Paclitaxel, was incorporated into the outer phospholipid layer. The surface of the nanoparticles was coated with gadolinium chelates for magnetic resonance imaging applications. This engineered nanoparticle formulation was found to be suitable for use in guided imaging therapy. Specifically, we investigated the size-dependent therapeutic response and the uptake of nanoparticles that were 65 nm, 85 nm, and 110 nm in size in the MCTS of the two pancreatic cancer cell lines used. After 24 hours of treatment, the MCTS of both PANC-1 and MIA PaCa-2 cell lines showed an average increase in the uptake of 18.4% for both 65 nm and 85 nm nanoparticles and 24.8% for 110 nm nanoparticles. Furthermore, the studies on therapeutic effects showed that particle size had a slight influence on the overall effectiveness of the formulation. In the MCTS of the MIA PaCa-2 cell line, 65 nm nanoparticles were found to produce the greatest therapeutic effect, whereas 12.8% of cells were apoptotic of which 11.4% of cells were apoptotic for 85

  19. Molecules as tracers of galaxy evolution

    DEFF Research Database (Denmark)

    Costagliola, F.; Aalto, S.; I. Rodriguez, M.;

    2011-01-01

    We investigate the molecular gas properties of a sample of 23 galaxies in order to find and test chemical signatures of galaxy evolution and to compare them to IR evolutionary tracers. Observation at 3 mm wavelengths were obtained with the EMIR broadband receiver, mounted on the IRAM 30 m telescope...... on Pico Veleta, Spain. We compare the emission of the main molecular species with existing models of chemical evolution by means of line intensity ratios diagrams and principal component analysis. We detect molecular emission in 19 galaxies in two 8 GHz-wide bands centred at 88 and 112 GHz. The main...... detected transitions are the J=1-0 lines of CO, 13CO, HCN, HNC, HCO+, CN, and C2H. We also detect HC3N J=10-9 in the galaxies IRAS 17208, IC 860, NGC 4418, NGC 7771, and NGC 1068. The only HC3N detections are in objects with HCO+/HCN 0.8). The brightest HC3N emission is found in IC 860, where we also...

  20. Primordial black holes as biased tracers

    CERN Document Server

    Tada, Yuichiro

    2015-01-01

    Primordial black holes (PBHs) are theoretical black holes which may be formed during the radiation dominant era and, basically, caused by the gravitational collapse of radiational overdensities. It has been well known that in the context of the structure formation in our Universe such collapsed objects, e.g., halos/galaxies, could be considered as bias tracers of underlying matter fluctuations and the halo/galaxy bias has been studied well. Employing a peak-background split picture which is known to be a useful tool to discuss the halo bias, we consider the large scale clustering behavior of the PBH and propose an almost mass-independent constraint to the scenario that dark matters (DMs) consist of PBHs. We consider the case where the statistics of the primordial curvature perturbations is almost Gaussian, but with small local-type non-Gaussianity. If PBHs account for the DM abundance, such a large scale clustering of PBHs behaves as nothing but the matter isocurvature perturbation and constrained strictly by...

  1. TRACER STUDY OF RTU GRADUATES: AN ANALYSIS

    Directory of Open Access Journals (Sweden)

    Thelma L. Ramirez

    2014-01-01

    Full Text Available This paper aimed to determine if the field of specialization in the different colleges of RTU graduates and their academic-acquired skills and competencies are related to their present occupations. A modified Graduate Tracer Study (GTS instrument was utilized to gather the quantitative data. Out of 500 questionnaires administered, there were 250 graduates returned answered questionnaires representing the three Colleges: Education, Arts and Sciences, Business and Entrepreneurial Technology. A face to face interview was also conducted in order to support the gathered data. The SPSS was used to generate results from the acquired quantitative data using the frequency counts, percentage and the Chi-square goodness of fit test. The findings revealed that the graduates claimed that their knowledge, academic-acquired skills and competencies contributed greatly in their job performance. The Chi-square goodness of fit proved that there is a significant relationship between the graduates’ fields of specialization and their occupations after graduation. Likewise, the academic-acquired skills and competencies of the graduates are relevant to their chosen occupations. The results further proved that RTU produces marketable and appropriately trained graduates with the majority landing in course-related jobs within a short period after graduation. The study also indicates that the RTU graduates possess the skills and competencies necessary to succeed in this competitive world. However eexpansion of tie-ups with private business entities is made to at least maintain the high employability level of the graduates.

  2. Positron emitting tracers for studies of cocaine

    International Nuclear Information System (INIS)

    The use of PET to study the behavior and mechanism of action of therapeutic drugs and substances of abuse can be approached from a number of perspectives. The most common approach is to measure the effect of a drug on some aspect of metabolism and requires well characterized radiotracers whose behavior in vivo can be related to a discrete biochemical transformation. A second approach is to study the labeled drug itself. This provides information on the drug's regional distribution and kinetics as well as its pharmacological profile and metabolism. Cocaine has been labeled in different positions with carbon-11 and with fluorine-18 and the stereoisomers of cocaine have also been labeled to characterize its binding and metabolism in human and baboon brain. Regional cocaine binding as measured by PET is consistent with reversible binding to striatal dopamine reuptake sites and its time course parallels the behavioral activation of cocaine. The behaviorally inactive enantiomer (+)-cocaine is rapidly metabolized in serum preventing its entry into the brain. These PET tracers are useful in understanding the neurochemical basis of cocaine's action

  3. National Biomedical Tracer Facility: Project definition study

    International Nuclear Information System (INIS)

    The Los Alamos National Laboratory is an ideal institution and New Mexico is an ideal location for siting the National Biomedical Tracer Facility (NBTF). The essence of the Los Alamos proposal is the development of two complementary irradiation facilities that combined with our existing radiochemical processing hot cell facilities and waste handling and disposal facilities provide a low cost alternative to other proposals that seek to satisfy the objectives of the NBTF. We propose the construction of a 30 MeV cyclotron facility at the site of the radiochemical facilities, and the construction of a 100 MeV target station at LAMPF to satisfy the requirements and objectives of the NBTF. We do not require any modifications to our existing radiochemical processing hot cell facilities or our waste treatment and disposal facilities to accomplish the objectives of the NBTF. The total capital cost for the facility defined by the project definition study is $15.2 M. This cost estimate includes $9.9 M for the cyclotron and associated facility, $2.0 M for the 100 MeV target station at LAMPF, and $3.3 M for design

  4. Analysis of Tracer Test at NPP site

    International Nuclear Information System (INIS)

    If radioactive materials that are contained in Nuclear Power Plants(hereafter as NPPs) are discharged by way of both direct and indirect pathways, they could have significant impact on the public and the environment in the region.1) Groundwater, one of the potential pathways of the radioactive materials discharged from the NPPs site, flows slower than the surface water and subsequently, the pollution of groundwater by the discharged radioactive materials could have an impact for a much longer period. For the construction and operation of NPPs, therefore, the applicant's safety analysis report is required to describe the characteristics of potential contamination and transport pathways in the groundwater environment, the coefficients of dispersion, groundwater velocities, travel times, hydraulic gradients, hydraulic conductivities, porosities, etc. These parameters should be demonstrated with representativeness and confidence. Thereafter the dose assessment should be performed considering the pathway and input data and using the reasonable model. 2), 3) This paper describes results from the tracer test performed near the Radioactive Waste Storage Tank of Shinkori unit 2, and the implications for the future improvement of site safety analysis

  5. National Biomedical Tracer Facility: Project definition study

    Energy Technology Data Exchange (ETDEWEB)

    Heaton, R.; Peterson, E. [Los Alamos National Lab., NM (United States); Smith, P. [Smith (P.A.) Concepts and Designs (United States)

    1995-05-31

    The Los Alamos National Laboratory is an ideal institution and New Mexico is an ideal location for siting the National Biomedical Tracer Facility (NBTF). The essence of the Los Alamos proposal is the development of two complementary irradiation facilities that combined with our existing radiochemical processing hot cell facilities and waste handling and disposal facilities provide a low cost alternative to other proposals that seek to satisfy the objectives of the NBTF. We propose the construction of a 30 MeV cyclotron facility at the site of the radiochemical facilities, and the construction of a 100 MeV target station at LAMPF to satisfy the requirements and objectives of the NBTF. We do not require any modifications to our existing radiochemical processing hot cell facilities or our waste treatment and disposal facilities to accomplish the objectives of the NBTF. The total capital cost for the facility defined by the project definition study is $15.2 M. This cost estimate includes $9.9 M for the cyclotron and associated facility, $2.0 M for the 100 MeV target station at LAMPF, and $3.3 M for design.

  6. Mean depth sea simulation using radioactive tracers

    International Nuclear Information System (INIS)

    On the basis of investigations carried out at the Department of Physics of the Vilnius Engineering Construction Institute the problem of mean depth sea simulation is studied using radioactive tracers. The rapid method of radiocesium concentration measurement in sea water is advanced. Radiocesium is adsorbed from 80-100 l of sea water within an 1.2-1.5 hour interval. The mean values of Cs-137 and Sr-90 concentrations for the three depths at different seasons in the Baltic Sea during.the period of 1973-1978 fluctuated within the limits of 0.43-1.3 pCi/l, and in the North Sea during the period of 1974-1977 - 0.81-4.0 pCi/l and 0.51-0.71 pCi/l, respectively. Periodical variations of the concentration of both nuclides in the Baltic Sea and continuous increase of the radiocesium concentration in the North Sea are noted. The results of calculation of the Cs-137 concentrations in the surface waters of the Baltic Sea by objective analysis are presented, the results obtained are discussed. A short calculation method of the vector field of the velocities and directions of the Baltic Sea currents is given, as well as the results of the calculations. An anomalous depth distribution of the concentration of both radionuclides in circulation places is observed. Calculation oft t the velocity of the passive admixture spreading in the Baltic Sea is presented

  7. In vitro effect on cancer cells: synthesis and preparation of polyurethane membranes for controlled delivery of curcumin.

    Science.gov (United States)

    Nagarajan, Selvaraj; Reddy, Bo Siva Rami; Tsibouklis, Jhon

    2011-12-01

    Urethane polymers (PU) have been prepared from low-molecular weight polylactic acid (PLA) and hexamethylene diisocyanate (HMDI) using polydimethylsiloxane (PDMS) as a chain extender. These formed the supporting polymeric matrix of curcumin-containing PU membranes which were prepared using a solvent evaporation technique. FTIR and XRD data indicated the molecular-level dispersion and random distribution of curcumin in the polymer matrix, and data were consistent with observations from tensile-strength measurements and from AFM imaging. Determination of water vapor permeability and moisture uptake measurements have indicated that the PU membrane were appropriate for use on human skin. Skin permeation studies of curcumin were consistent with zero order (R² = 0.9874) and with Korsmeyer-Peppas (R² = 0.9978) kinetics-analytical data pointed to permeation by a combination of diffusion and erosion processes, with the latter dominating. The biocompatibility of these PU membranes was indicated by in vitro cytotoxicity studies using 3T3-L1-murine fibroblast cell. The in vitro therapeutic potential of the patches was demonstrated against A549 human lung cancer cells. PMID:22021188

  8. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer

    International Nuclear Information System (INIS)

    A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC50 0.59 μM) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC50 70 nM) and 84 (IC50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC50 of 80 μM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC50 1.7 μM and 0.27 μM, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.

  9. Nitric oxide synthesis inhibition and cytotoxicity of Korean horse mussel Modiolus modiolus extracts on cancer cells in culture.

    Science.gov (United States)

    Wikarta, Jumeri Mangun; Kim, Sang Moo

    2016-08-01

    The Korean horse mussel extract was purified and fractionated by a bioassay-guided purification step. The final fraction contained seven steroid and one polycyclic aromatic compounds, in which cholest-7-en-3-ol, (3β,5α)- (58.7 %) was a main component followed by ergosta-7,22dien-3-ol (3β,5α,22E) (13.0 %). This extract exhibited strong anti-inflammatory activity determined solely through the nitric oxide inhibition assay in a dose-dependant manner with the IC50 value of 9.6 µg/mL and no cytotoxic effect on the macrophages. Moreover, it also exhibited strong cytotoxicity with the IC50 values of 21.4, 36.4, and 37.1 µg/mL against AGS, DLD-1, and HeLa cells, respectively. These results indicated that the horse mussel extract might be a functional ingredient in the prevention of inflammation and human cancers. PMID:25875500

  10. Synthesis and evaluation of thymidine kinase 1-targeting carboranyl pyrimidine nucleoside analogs for boron neutron capture therapy of cancer.

    Science.gov (United States)

    Agarwal, Hitesh K; Khalil, Ahmed; Ishita, Keisuke; Yang, Weilian; Nakkula, Robin J; Wu, Lai-Chu; Ali, Tehane; Tiwari, Rohit; Byun, Youngjoo; Barth, Rolf F; Tjarks, Werner

    2015-07-15

    A library of sixteen 2nd generation amino- and amido-substituted carboranyl pyrimidine nucleoside analogs, designed as substrates and inhibitors of thymidine kinase 1 (TK1) for potential use in boron neutron capture therapy (BNCT) of cancer, was synthesized and evaluated in enzyme kinetic-, enzyme inhibition-, metabolomic-, and biodistribution studies. One of these 2nd generation carboranyl pyrimidine nucleoside analogs (YB18A [3]), having an amino group directly attached to a meta-carborane cage tethered via ethylene spacer to the 3-position of thymidine, was approximately 3-4 times superior as a substrate and inhibitor of hTK1 than N5-2OH (2), a 1st generation carboranyl pyrimidine nucleoside analog. Both 2 and 3 appeared to be 5'-monophosphorylated in TK1(+) RG2 cells, both in vitro and in vivo. Biodistribution studies in rats bearing intracerebral RG2 glioma resulted in selective tumor uptake of 3 with an intratumoral concentration that was approximately 4 times higher than that of 2. The obtained results significantly advance the understanding of the binding interactions between TK1 and carboranyl pyrimidine nucleoside analogs and will profoundly impact future design strategies for these agents. PMID:26087030

  11. Do tobacco stimulate the production of nitric oxide by up regulation of inducible nitric oxide synthesis in cancer: Immunohistochemical determination of inducible nitric oxide synthesis in oral squamous cell carcinoma - A comparative study in tobacco habituers and non-habituers

    OpenAIRE

    B Karthik; D K Shruthi; Jasmin Singh; Anand S Tegginamani; Shailesh Kudva

    2014-01-01

    Background: Oral cancer accounts for 6% of all cancers. The most prevalent form of oral cancer is oral squamous cell carcinoma (OSCC), which accounts for 90% of the oral cancer cases. The major risk factor for development of OSCC is the use of tobacco in various forms. NO has been studied widely over the years due to its role in various physiological and pathophysiological processes, including its complex role in carcinogenesis. Materials and Methods: A total of 20 cases of OSCC in tobacco...

  12. Tetra- and mono-organotin reagents in palladium-mediated cross-coupling reactions for the labeling with carbon-11 of PET tracers

    Energy Technology Data Exchange (ETDEWEB)

    Bourdier, T.; Huiban, M.; Sobrio, F.; Perrio, C.; Barre, E. [Groupe de Dev Methodol en Tomographie par Emission de Positons, UMR CEA 2E, Universite deCaen, Centre Cyceron, F-14070 Caen Cedex (France); Fouquet, A.; Huet, A. [Laboratoire de Chimie Organique et Organometallique, UMR CNRS 3802, Univ Bordeaux I, F-33405 Talence Cedex (France)

    2008-07-01

    The palladium-catalyzed cross-coupling reactions between a (trimethylstannyl)arene and [{sup 11}C]methyl iodide (Stille reaction) or between an aryl halide and a [{sup 11}C]monomethyltin reagent issued from Lappert's stannylene, were developed for the synthesis of polyfunctional [{sup 11}C]methyl quinolines and quinoline-imides as potential tracers for positron emission tomography (PET). (authors)

  13. Applications of isotopic tracer in analysis of residual sulfonylurea herbicide

    International Nuclear Information System (INIS)

    The analysis technique of the agrochemical residue by isotopic tracer is significantly increased, and obtained substantial development. The progress of the isotopic analysis in four kinds of sulfonylurea herbicide residues was reviewed in this paper. (authors)

  14. Simulation of Tracer Transport in Porous Media: Application to Bentonites

    International Nuclear Information System (INIS)

    We present a formal framework to describe tracer transport in heterogeneous media, such as porous media like bentonites. In these media, mean field approximation is not valid because there exist some geometrical constraints and the transport is anomalous. (Author)

  15. Self-diffusion of ion-implanted tracers

    International Nuclear Information System (INIS)

    Tracer self-diffusion studies with ion-implanted stable isotopes require a high fluence of implanted ions (>1015 ions/cm2) due to the natural tracer background concentration present in a sample. Such a high fluence leads to considerable implantation damage, where a large part of the tracer is immobilized and does not take place in the diffusion process. As a consequence, diffusion profiles are observed which cannot be described with Fick's second law. In this study, a set of differential equations is presented, describing the diffusion of implanted isotopes as a trap-limited process with a sink and a source term, where the tracer atoms form immobile complexes with implantation damage-induced defects. These equations are solved numerically for the example of nitrogen diffusion in amorphous Si-B-C-N ceramics in order to illustrate diffusivity determination. The results are compared to the analytical solution of Fick's second law

  16. Our experience of blood flow measurements using radioactive tracers

    International Nuclear Information System (INIS)

    A critical study of blood flow measuring methods is proposed. After a review of the various diffusible and non-diffusible radioactive tracers and the corresponding detector systems, the principles which allow to measure blood flow from the data so obtained, are studied. There is a different principle of flow measurement for each type of tracer. The theory of flow measurement using non-diffusible tracers (human serum albumin labelled with 131I or sup(99m)Tc, 113In-labelled siderophiline) and its application to cardiac flow measurement are described first. Then the theory of flow measurement using diffusible tracers (133Xe, 85Kr) and its application to measurement of blood flow through tissues (muscles and kidney particularly) are described. A personal experience of this various flow measurements is reported. The results obtained, the difficulties encountered and the improvments proposed are developed

  17. Systems approach to tracer data in groundwater hydrology

    International Nuclear Information System (INIS)

    A brief review of current mathematical methods for the analysis of tracer data in groundwater hydrology has been given. The description of the hydrological cycle as a whole or in part, by a system (compartment) or sub-system under linear and stationary conditions is discussed. Basic concepts of transit time, residence time, their distributions in time and response characteristics of a system are outlined. From the knowledge of tracer input, output and systems response function for a generalised system, reservoir capacity and storage for given period can be estimated. Use of a time series model for environmental tracer data in discreet time scale aimed at the solution of hydrological problems e.g. mean transit time and reservoir capacity is also explored. It is concluded that the combination of tracer data with systems approach can go a long way in the study of some complex hydrological problems. (author)

  18. Application of fluorescent-and radioactive tracers in Sedimentalogy

    International Nuclear Information System (INIS)

    The development of techniques of sediment labelling, creating the possibility of using fluorescent and radioactive tracers not yet applied in Brazil, in the area of sedimentology, is studied. (A.R.H.)

  19. Hydraulic characterisation of karst systems with man-made tracers

    International Nuclear Information System (INIS)

    Tracer experiments using man-made tracers are common in hydrogeological exploration of groundwater aquifers in karst systems. In the present investigation, a convection-dispersion model (multidispersion model with consideration of several flow paths) and a single-cleft model (consideration of the diffusion between the cleft and the surrounding rock matrix) were used for evaluating tracer experiments in the main hydrological system of the saturated zone of karst systems. In addition to these extended analytical solutions, a numerical transport model was developed for investigating the influence of the transient flow rate on the flow and transport parameters. Comparative evaluations of the model approaches for the evaluation of tracer experiments were made in four different karst systems: Danube-Aach, Paderborn, Slowenia and Lurbach, of which the Danube-Aach system was considered as the most important. The investigation also comprised three supplementary experiments in order to enable a complete hydraulic characterisation of the system. (orig./SR)

  20. Tracers for the study of scavenging by rain

    International Nuclear Information System (INIS)

    The study of rain scavenging by means of tracers from crudely defined 'natural' sources has led to the idea that the resolution of physical problems of scavenging might be greatly improved by the use of artificially placed tracer. The selection of a suitable material to use in the study of strong convective systems, with measurement by neutron activation is discussed. The design, coordination and execution of a pilot experiment in a strong convective storm at Holdenville, Oklahoma, 30 May 1967 is recounted, and preliminary results of the neutron activation analysis are presented. Although statistics for the evaluation of natural background of the tracer material, indium, are not yet as numerous as desired, and the sample analyses are not all completed, the criterion for success of the pilot experiment, i.e., that the tracer be clearly identified in collected rain samples, is certainly met by the preliminary figures. (author)

  1. Advances in processes for PET radiotracer synthesis: Separation of [18F]fluoride from enriched [18O]water

    International Nuclear Information System (INIS)

    Positron emission tomography (PET) is a powerful scientific and clinical tool for the study and visualization of human physiology that can provide important information about metabolism and diseases such as cancer. At present, [18F]fluorodeoxyglucose ([18F]FDG) is the most frequently used radiotracer for the routine clinical evaluation of malignant tumors in a range of body tissues. FDG synthesis is continuously being developed to improve and simplify the synthetic procedure including the isolation of [18F]fluoride from [18O]water. There are many methods reported in literature for the isolation of [18F]fluoride, including evaporation, coat-capture–elution, the use of cation-exchange resin and electrode trapping. This review article gives an overview of some of the most common methods for the separation of [18F]fluoride ions from [18O]water, highlighting the potential strength of the methods and also problems and weaknesses for synthesis of 18F PET tracers. - Highlights: • New developments in processing of [18F]fluoride from [18O]water are detailed. • Efficient separation is required for dose-on-demand radiopharmaceuticals. • Electrode trapping of [18F]fluoride offers significant advantages for solvent exchange. • Microfluidic devices complement novel technologies for isotope separation and synthesis

  2. Fully-automated synthesis of 16β-18F-fluoro-5α-dihydrotestosterone (FDHT) on the ELIXYS radiosynthesizer

    International Nuclear Information System (INIS)

    Noninvasive in vivo imaging of androgen receptor (AR) levels with positron emission tomography (PET) is becoming the primary tool in prostate cancer detection and staging. Of the potential 18F-labeled PET tracers, 18F-FDHT has clinically shown to be of highest diagnostic value. We demonstrate the first automated synthesis of 18F-FDHT by adapting the conventional manual synthesis onto the fully-automated ELIXYS radiosynthesizer. Clinically-relevant amounts of 18F-FDHT were synthesized on ELIXYS in 90 min with decay-corrected radiochemical yield of 29±5% (n=7). The specific activity was 4.6 Ci/µmol (170 GBq/µmol) at end of formulation with a starting activity of 1.0 Ci (37 GBq). The formulated 18F-FDHT yielded sufficient activity for multiple patient doses and passed all quality control tests required for routine clinical use. - Highlights: • Manual radiosynthesis of 18F-FDHT was adapted for full automation on the ELIXYS radiosynthesizer. • Reduction with LiAlH4 was performed at room temperature to avoid cryogenic conditions. • Formulated product passed all clinical QC tests and is suitable for clinical production. • Decay-corrected radiochemical yield was 29±5% (n=7) with a synthesis time of 90 min. • Specific activity was 4.6 Ci/µmol (170 GBq/µmol) at the end of formulation

  3. Oil industry first field trial of inter-well reservoir nanoagent tracers

    Science.gov (United States)

    Kanj, Mazen Y.; Kosynkin, Dmitry V.

    2015-05-01

    This short manuscript highlights the industry's first proven reservoir nanoagents' design and demonstrates a successful multi-well field trial using these agents. Our fundamental nanoparticles tracer template, A-Dots or Arab-D Dots, is intentionally geared towards the harsh but prolific Arab-D carbonate reservoir environment of 100+°C temperature, 150,000+ppm salinity, and an abundant presence of divalent ions in the connate water. Preliminary analyses confirmed nanoparticles' breakthrough at a producer nearly 500m from the injector at the reservoir level; thus, proving the tracer nanoparticles' mobility and transport capability. This is considered industry-first and a breakthrough achievement complementing earlier accomplishments in regard to the nanoagents' reservoir stability with the first successful single well test and ease of scale up with the synthesis of one metric ton of this material. The importance of this accomplishment is not in how sophisticated is the sensing functionalities of this design but rather in its stability, mobility, scalability, and field application potentials. This renders the concept of having active, reactive, and even communicative, in-situ reservoir nanoagents for underground sensing and intervention a well anticipated near-future reality.

  4. Neonatal Respiratory Diseases in the Newborn Infant: Novel Insights from Stable Isotope Tracer Studies.

    Science.gov (United States)

    Carnielli, Virgilio P; Giorgetti, Chiara; Simonato, Manuela; Vedovelli, Luca; Cogo, Paola

    2016-01-01

    Respiratory distress syndrome is a common problem in preterm infants and the etiology is multifactorial. Lung underdevelopment, lung hypoplasia, abnormal lung water metabolism, inflammation, and pulmonary surfactant deficiency or disfunction play a variable role in the pathogenesis of respiratory distress syndrome. High-quality exogenous surfactant replacement studies and studies on surfactant metabolism are available; however, the contribution of surfactant deficiency, alteration or dysfunction in selected neonatal lung conditions is not fully understood. In this article, we describe a series of studies made by applying stable isotope tracers to the study of surfactant metabolism and lung water. In a first set of studies, which we call 'endogenous studies', using stable isotope-labelled intravenous surfactant precursors, we showed the feasibility of measuring surfactant synthesis and kinetics in infants using several metabolic precursors including plasma glucose, plasma fatty acids and body water. In a second set of studies, named 'exogenous studies', using stable isotope-labelled phosphatidylcholine tracer given endotracheally, we could estimate surfactant disaturated phosphatidylcholine pool size and half-life. Very recent studies are focusing on lung water and on the endogenous biosynthesis of the surfactant-specific proteins. Information obtained from these studies in infants will help to better tailor exogenous surfactant treatment in neonatal lung diseases. PMID:27251153

  5. Perspectives of transient tracer applications and limiting cases

    Science.gov (United States)

    Stöven, T.; Tanhua, T.; Hoppema, M.; Bullister, J. L.

    2015-09-01

    Currently available transient tracers have different application ranges that are defined by their temporal input (chronological transient tracers) or their decay rate (radioactive transient tracers). Transient tracers range from tracers for highly ventilated water masses such as sulfur hexafluoride (SF6) through tritium (3H) and chlorofluorocarbons (CFCs) up to tracers for less ventilated deep ocean basins such as argon-39 (39Ar) and radiocarbon (14C). In this context, highly ventilated water masses are defined as water masses that have been in contact with the atmosphere during the last decade. Transient tracers can be used to empirically constrain the transit time distribution (TTD), which can often be approximated with an inverse Gaussian (IG) distribution. The IG-TTD provides information about ventilation and the advective/diffusive characteristics of a water parcel. Here we provide an overview of commonly used transient tracer couples and the corresponding application range of the IG-TTD by using the new concept of validity areas. CFC-12, CFC-11 and SF6 data from three different cruises in the South Atlantic Ocean and Southern Ocean as well as 39Ar data from the 1980s and early 1990s in the eastern Atlantic Ocean and the Weddell Sea are used to demonstrate this method. We found that the IG-TTD can be constrained along the Greenwich Meridian south to 46° S, which corresponds to the Subantarctic Front (SAF) denoting the application limit. The Antarctic Intermediate Water (AAIW) describes the limiting water layer in the vertical. Conspicuous high or lower ratios between the advective and diffusive components describe the transition between the validity area and the application limit of the IG-TTD model rather than describing the physical properties of the water parcel. The combination of 39Ar and CFC data places constraints on the IG-TTD in the deep water north of the SAF, but not beyond this limit.

  6. Monodisperse magnetite nanoparticle tracers for in vivo magnetic particle imaging

    OpenAIRE

    Khandhar, Amit P.; Ferguson, R. Matthew; Arami, Hamed; Krishnan, Kannan M

    2013-01-01

    Magnetic Particle Imaging (MPI) is a new biomedical imaging modality that produces real-time, high-resolution tomographic images of superparamagnetic iron oxide (SPIO) nanoparticle tracer distributions. In this study, we synthesized monodisperse tracers for enhanced MPI performance and investigated both, their blood clearance time using a 25 kHz magnetic particle spectrometer (MPS), and biodistribution using a combination of quantitative T2-weighted MRI and tissue histology. In vitro and in v...

  7. Clustering of dark matter tracers: renormalizing the bias parameters

    OpenAIRE

    McDonald, Patrick

    2006-01-01

    A commonly used perturbative method for computing large-scale clustering of tracers of mass density, like galaxies, is to model the tracer density field as a Taylor series in the local smoothed mass density fluctuations, possibly adding a stochastic component. I suggest a set of parameter redefinitions, eliminating problematic perturbative correction terms, that should represent a modest improvement, at least, to this method. As presented here, my method can be used to compute the power spect...

  8. Radioisotope tracer application in surface and groundwater flow measurements

    International Nuclear Information System (INIS)

    The ''peak to peak'' method for measurement of water flow with the use of radioactive tracer was investigated. The theoretical basis for this method has been established. The experiments in the open channel have shown the applicability of the method. Groundwater flow was studied by injection of radioactive tracer into the bore-hole followed by gamma-logging in three different time intervals. Interpretation of gamma lows in terms of filtration velocity in various depths proved to be possible

  9. Anomalous diffusion of a tracer advected by wave turbulence

    Science.gov (United States)

    Balk, Alexander M.

    2001-02-01

    We consider the advection of a passive tracer when the velocity field is a superposition of random waves. Green's function for the turbulent transport (turbulent diffusion and turbulent drift) is derived. This Green's function is shown to imply sub-diffusive or super-diffusive behavior of the tracer. For the analysis we introduce the statistical near-identity transformation. The results are confirmed by numerical simulations.

  10. How tracer objects can improve competitive learning algorithms in astronomy

    Science.gov (United States)

    Hernandez-Pajares, M.; Floris, J.; Murtagh, F.

    The main objective of this paper is to discuss how the use of tracer objects in competitive learning can improve results in stellar classification. To do this, we work with a Kohonen network applied to a reduced sample of the Hipparcos Input Catalogue, which contains missing values. The use of synthetic stars as tracer objects allows us to determine the discrimination quality and to find the best final values of the cluster centroids, or neuron weights.

  11. Field tracer experiments: Role in the prediction of radionuclide migration. [Proceedings

    International Nuclear Information System (INIS)

    GEOTRAP is an OECD/NED Project devoted to radionuclide migration in geologic, heterogeneous media in the framework of site evaluation and safety assessment of deep repository systems for high-level and/or long-lived radioactive waste. The first GEOTRAP workshop, Field Tracer Experiments: Role in the Prediction of Radionuclide Migration (Cologne, Germany, 28--30 August 1996) was co-organized with the European Commission. It gave an overview of on-going and planned work in the study of radionuclide transport phenomena and the characterization of relevant properties of the geologic media. In addition to the papers presented at the workshop, these proceedings include a synthesis of the materials presented, the discussions that took place and the conclusions drawn, notably during working group sessions

  12. Microfluidic single vessel production of hypoxia tracer 1H-1-(3-[18F]-fluoro-2-hydroxy-propyl)-2-nitro-imidazole ([18F]-FMISO)

    International Nuclear Information System (INIS)

    We report an automated synthesis of [18F]-FMISO utilizing a prototype microfluidic radiochemistry module. The instrument allows for production of the tracer with 58%±2% (11 runs) decay corrected yield. Total time of production, including synthesis and purification averages 60 min. Use of the microfluidic platform results in a specific activity of 138.6 GBq/μ mol, which is higher than previously reported for conventional reactors. - Highlights: ► Microfluidic system is used for FMISO production. ► Decay corrected yield is 58%. ► Specific activity is of 138.6 GBq/μ mol.

  13. Determination of the self purification of streams using tracers

    International Nuclear Information System (INIS)

    A methodology for the 'in situ' evaluation of the self purification of streams is discussed. It consists of the simultaneous injection of two tracers into the stream. One of the tracers is oxidized by biochemical processes. It can be either artificially supplied to the stream or a naturally present component can be used. This tracer is used for the determination of the self purification parameters. The other tracer is conservative and allows for the hydrodynamic effects. Tests have been carried out in two streams with quite different hydrodynamic and physicochemical conditions. In the first stream, with a flow-rate of about 0.9 m3/s, urea was used as the nonconservative tracer. In the other stream, which had a flow-rate of about 5 m3/s, only a radioactive tracer has been used, and the rate of biochemical oxidation has been determined from BOD measurements. Calculations have been implemented on a digital computer. In both cases it was found that the reoxygenation rate is more conveniently determined by empirical formulas. Results from both tests have been deemed realistic by comparison with similar experiments. (Author)

  14. Tracer verification and monitoring of containment systems (II)

    International Nuclear Information System (INIS)

    A tracer verification and monitoring system, SEAtrace trademark, has been designed and field tested which uses gas tracers to evaluate, verify, and monitor the integrity of subsurface barriers. This is accomplished using an automatic, rugged, autonomous monitoring system combined with an inverse optimization code. A gaseous tracer is injected inside the barrier and an array of wells outside the barrier are monitored. When the tracer gas is detected, a global optimization code is used to calculate the leak parameters, including leak size, location, and when the leak began. The multipoint monitoring system operates in real-time, can be used to measure both the tracer gas and soil vapor contaminants, and is capable of unattended operation for long periods of time (months). The global optimization code searches multi-dimensional open-quotes spaceclose quotes to find the best fit for all of the input parameters. These parameters include tracer gas concentration histories from multiple monitoring points, medium properties, barrier location, and the source concentration. SEAtrace trademark does not attempt to model all of the nuances associated with multi-phase, multi-component flow, but rather, the inverse code uses a simplistic forward model which can provide results which are reasonably accurate. The system has calculated leak locations to within 0.5 meters and leak radii to within 0.12 meters

  15. Evaluation of four blood pump geometries: the optical tracer technique.

    Science.gov (United States)

    Rose, M L; Mackay, T G; Martin, W; Wheatley, D J

    2000-01-01

    Artificial blood pump assistance of the failing human heart can allow it to recover. Analysis of blood pump fluid flow is a useful tool for design development and thrombosis minimization. The aim of this study was to investigate fluid flow, particularly ventricular clearance rate and stagnation areas, in four different blood pump geometries and to determine the best design. The blood pumps consisted of a polyurethane ventricle, and combinations of inlet/outlet pipe angles and compression plate shapes. A video camera recorded the motion of fluid labelled with an optical tracer (Methyl Blue histological dye). A novel processing method was developed to produce colour maps of tracer concentration, experimentally calibrated. An overall picture of fluid flow in each pump geometry was generated by considering clearance curves, tracer concentration maps and inflow jet animations. Overall and local mixing coefficients are calculated for each pump. The best geometry featured straight inlet/outlet pipes and a domed compression plate. This optical tracer technique has proven convenient, economical, sensitive to low concentrations of tracer and provides instantaneous pictures of tracer distribution in a ventricle. PMID:10997058

  16. Numerical tracer test in a simulated heterogeneous aquifer

    International Nuclear Information System (INIS)

    A natural analog method is used to simulate a discrete heterogeneous transmissivity field on a dense grid. Simulated values are derived from digital terrain elevations of the Walker Lake area of Nevada. This method produces a realistic field exhibiting nested scales of heterogeneity and continuous large-scale high transmissivity structure similar to those found in fluvial sedimentary deposits. These features give rise to preferential flow patterns such as channeling which are known to have a significant effect on tracer spreading. Steady-state groundwater flow through the field is modeled by finite differences, and transport of an ideal tracer is modeled by particle tracking. The tracer residence time distribution (RTD) and apparent longitudinal dispersivity are used to characterize macrodispersive spreading through the system. The heterogeneous transmissivity and velocity fields are characterized by geostatistical methods. A series of numerical tracer tests is used to investigate macrodispersive spreading. The effects of channeling are pervasive in all experiments. Tracer RTDs are multimodal and cannot be described using a classical Fickian transport model. Despite this, the theoretical large displacement longitudinal dispersivity is in reasonable agreement with observed values. Apparent longitudinal dispersivity is found to increase with displacement distances up to mid-field and then decrease as displacement nears the downstream constant-head boundary. In the presence of channeling, apparent dispersivities calculated from the moments of the RTDs are sensitive to the location and mode, flux-weighted or uniform, of tracer injection. (Author) (16 refs., 9 figs., 2 tabs.)

  17. Fourier analysis of multi-tracer cosmological surveys

    CERN Document Server

    Abramo, L Raul; Loureiro, Arthur

    2015-01-01

    We present optimal quadratic estimators for the Fourier analysis of cosmological surveys that detect several different types of tracers of large-scale structure. Our estimators can be used to simultaneously fit the matter power spectrum and the biases of the tracers - as well as redshift-space distortions (RSDs), non-Gaussianities (NGs), or any other effects that are manifested through differences between the clusterings of distinct species of tracers. Our estimators reduce to the one by Feldman, Kaiser & Peacock (ApJ 1994, FKP) in the case of a survey consisting of a single species of tracer. We show that the multi-tracer estimators are unbiased, and that their covariance is given by the inverse of the multi-tracer Fisher matrix (Abramo, MNRAS 2013; Abramo & Leonard, MNRAS 2013). When the biases, RSDs and NGs are fixed to their fiducial values, and one is only interested in measuring the underlying power spectrum, our estimators are projected into the estimator found by Percival, Verde & Peacock ...

  18. Tracer populations in the Local Group

    Science.gov (United States)

    Watkins, Laura L.

    2011-04-01

    So often in astronomy, an object is not considered for its individual merits, but for what we may learn from its properties regarding some larger population. The existence of dark matter is a prime example of this; we cannot see it directly but we can infer its presence by noting its effects on the stars orbiting within its potential. This thesis describes how various sets of tracer populations can be used to probe the properties of a variety of galaxies in the Local Group. I begin by describing the extraction of a variable catalogue from the Sloan Digital Sky Survey Stripe 82 dataset and then use the catalogue to select a high-quality set of RR Lyrae stars. Analysing the distribution of the RR Lyraes reveals three significant substructures in the Milky Way halo: the Hercules-Aquila Cloud and the Sagittarius Stream, which were already known to exist, and the Pisces Overdensity, which was previously undetected. It is a faint, extended structure found at ~80 kpc and is of unknown origin. Altogether, I find that nearly 80% of the RR Lyraes are associated with substructures, consistent with the theory that galaxy halos are predominantly, or even entirely, made up from disrupted satellites. I also investigate the density distribution of RR Lyraes in the halo, finding that it is best fit by a broken-power-law model, in good agreement with previous work. I go on to develop a set of tracer mass estimators that build on previous work which make use of actual (and not projected) distance and proper motion data, reflecting the amount and quality of data now available to us. I show that proper motion data is, in theory, very useful and can greatly increase the accuracy of the mass estimates; in practice, however, current analysis is hampered by the large errors inherent in the proper motion data. The results are also subject to mass-anisotropy degeneracy, which current data is not yet able to break. Nevertheless, I am able to estimate the mass of the Milky Way to be M = 2.7±0

  19. Biogeochemical tracers of the marine cyanobacterium Trichodesmium

    Science.gov (United States)

    Carpenter, Edward J.; Harvey, H. Rodger; Fry, Brian; Capone, Douglas G.

    1997-01-01

    We examined the utility of several biogeochemical tracers for following the fate of the planktonic diazotrophic cyanobacterium Trichodesmium in the sea. The presence of a (CIO) fatty acid previously reported was observed in a culture of Trichodesmium but was not found in natural samples. This cyanobacterium had high concentrations of C 14 and C 16 acids, with lesser amounts of several saturated and unsaturated C 18 fatty acids. This composition was similar to that of other marine cyanobacteria. The major hydrocarbon identified was the C 17n-alkane, which was present in all samples from the five stations examined. Sterols common to algae and copepods were observed in many samples along with hopanoids representative of bacteria, suggesting a varied community structure in colonies collected from different stations. We found no unique taxonomic marker of Trichodesmium among the sterols. Measurements of the σ 15N and σ 13C in Trichodesmium samples from the SW Sargasso and NW Caribbean Seas averaged -0.4960 (range from -0.7 to -0.25960) and -12.9%0 (range from -15.2 to -11.9960), respectively, thus confirming previous observations that this cyanobacterial diazotroph has both the lowest σ 15N and highest σ 13C of any marine phytoplankter observed to date. A culture of Trichodesmium grown under diazotrophic conditions had a σ 15N between -1.3 and -3.6960. Our results support the supposition that the relatively low σ 15N and high σ 13C values observed in suspended and sediment-trapped material from some tropical and subtropical seas result from substantial input of C and N by Trichodesmium.

  20. Marine chemistry and tracer applications of radiocaesium

    International Nuclear Information System (INIS)

    The general aims of this project were to study the marine chemistry of Windscale-derived radiocaesium and to continue previous research at Glasgow University on its tracer application in Scottish waters and sediments. It was found that a considerable percentage of sediment-associated 137Cs (approximately 12 to 50%) may be contained by carbonate, oxide and organic coatings which appear to be relatively stable under a wide range of redox conditions. Whilst the partitioning of 137Cs is related to the concentration of these oxides, organics and, to a much lesser extent, carbonates, their function is predominantly to prevent 137Cs release from clay mineral exchange sites. 137Cs activities per unit sediment weight were highest in the clay fraction with its uptake by coarse sediments appearing to be controlled by clay minerals coatings formed in the marine environment and cemented partly by oxides and organics. Though the sites sampled (Clyde Sea Area (C.S.A.) and L. Etive) encompassed a wide range of sediment types, the range of estimated 137Cs distribution coefficients (KD) was relatively small (360 to 890). Coatings may thus have more influence on Kds in the coastal marine environment than particle size distributions. Apparent concentration factors (CFs) of X325, X2800 and X1910 were determined for the associated carbonate, oxide and organic coatings, for a site off Greenock. Use of 'dry' sediments appeared to produce considerably overestimated values for the degree of 137Cs fixation. Thus 'wet' sediments were used in these studies. Over the 1978-1981 period, approximately 35% of Windscale output passed through the C.S.A., diluted 26 times during transit. An estimated 0.3% of this water-borne inventory was removed into the sediments. Windscale to C.S.A. transit and residence times of 4 and 12 months respectively were derived. Monitoring the deeper levels of L. Etive allowed 137Cs to be used to trace patterns of w

  1. HYDROGEL TRACER BEADS: THE DEVELOPMENT, MODIFICATION, AND TESTING OF AN INNOVATIVE TRACER FOR BETTER UNDERSTANDING LNAPL TRANSPORT IN KARST AQUIFERS

    Energy Technology Data Exchange (ETDEWEB)

    Amanda Laskoskie, Harry M. Edenborn, and Dorothy J. Vesper

    2012-01-01

    The goal of this specific research task is to develop proxy tracers that mimic contaminant movement to better understand and predict contaminant fate and transport in karst aquifers. Hydrogel tracer beads are transported as a separate phase than water and can used as a proxy tracer to mimic the transport of non-aqueous phase liquids (NAPL). They can be constructed with different densities, sizes & chemical attributes. This poster describes the creation and optimization of the beads and the field testing of buoyant beads, including sampling, tracer analysis, and quantitative analysis. The buoyant beads are transported ahead of the dissolved solutes, suggesting that light NAPL (LNAPL) transport in karst may occur faster than predicted from traditional tracing techniques. The hydrogel beads were successful in illustrating this enhanced transport.

  2. On the time to tracer equilibrium in the global ocean

    Directory of Open Access Journals (Sweden)

    F. Primeau

    2009-02-01

    Full Text Available An important issue for the interpretation of data from deep-sea cores is the time for tracers to be transported from the sea surface to the deep ocean. Global ocean circulation models can help shed light on the timescales over which a tracer comes to equilibrium in different regions of the ocean. In this note, we discuss how the most slowly decaying eigenmode of a model can be used to obtain a relevant timescale for a tracer that enters through the sea surface to become well mixed in the ocean interior. We show how this timescale depends critically on the choice between a Neumann surface boundary condition in which the flux of tracer is prescribed, a Robin surface boundary condition in which a combination of the flux and tracer concentration is prescribed or a Dirichlet surface boundary condition in which the concentration is prescribed. Explicit calculations with a 3-box model and a three-dimensional ocean circulation model show that the Dirichlet boundary condition when applied to only part of the surface ocean greatly overestimate the time needed to reach equilibrium. As a result regional-"injection" calculations which prescribe the surface concentration instead of the surface flux are not relevant for interpreting the regional disequilibrium between the Atlantic and Pacific found in paleo-tracer records from deep-sea cores. For tracers that enter the ocean through air-sea gas exchange a prescribed concentration boundary condition can be used to infer relevant timescales if the air-sea gas exchange rate is sufficiently fast, but the boundary condition must be applied over the entire ocean surface and not only to a patch of limited area. For tracers with a slow air-sea exchange rate such as 14C a Robin-type boundary condition is more relevant and for tracers such as δ18O that enter the ocean from melt water, a Neumann boundary condition is presumably more relevant. Our three-dimensional model results based on a steady

  3. Design and synthesis of multifunctional poly(ethylene glycol)s using enzymatic catalysis for multivalent cancer drug delivery

    Science.gov (United States)

    Seo, Kwang Su

    The objective of this research was to design and synthesize multifunctional poly(ethylene glycol)s (PEG)s using enzyme-catalyzed reactions for multivalent targeted drug delivery. Based on computer simulation for optimum folate binding, a four-arm PEG star topology with Mn = 1000 g/mol was proposed. First, a four-functional core based on tetraethylene glycol (TEG) was designed and synthesized using transesterification and Michael addition reactions in the presence of Candida antarctica lipase B (CALB) as a biocatalyst. The four-functional core (HO)2-TEG-(OH)2 core was successfully prepared by the CALB-catalyzed transesterification of vinyl acrylate (VA) with TEG and then Michael addition of diethanolamine to the resulting TEG diacrylate with/without the use of solvent. The functional PEG arms with fluorescein isothiocyanate (FITC) and folic acid (FA) were prepared using both traditional organic chemistry and enzyme-catalyzed reactions. FITC was reacted with the amine group of H2N-PEG-OH in the presence of triethylamine via nucleophilic addition onto the isothiocyanate group. Then, divinyl adipate (DVA) was transesterified with the FITC-PEG-OH product in the presence of CALB to produce the FITC-PEG vinyl ester that will be attached to the four-functional core via CALC-catalyzed transesterification. For the synthesis of FA-PEG vinyl ester arm, DVA was first reacted with PEG-monobenzyl ether (BzPEG-OH) in bulk in the presence of CALB. The BzPEG vinyl ester was then transesterified with 12-bromo-1-dodecanol in the presence of CALB. Finally, BzPEG-Br was attached to FA exclusively in the gamma position using a new method. The thesis also discusses fundamental studies that were carried out in order to get better understanding of enzyme catalyzed transesterification and Michael addition reactions. First, in an effort to investigate the effects of reagent and enzyme concentrations in transesterification, vinyl methacrylate (VMA) was reacted with 2-(hydroxyethyl) acrylate (2

  4. Development of a Hybrid Tracer for SPECT and Optical Imaging of Bacterial Infections.

    Science.gov (United States)

    Welling, Mick M; Bunschoten, Anton; Kuil, Joeri; Nelissen, Rob G H H; Beekman, Freek J; Buckle, Tessa; van Leeuwen, Fijs W B

    2015-05-20

    In trauma and orthopedic surgery, infection of implants has a major impact on the outcome for patients. Infections may develop either during the initial implantation or during the lifetime of an implant. Both infections, as well as aseptic loosening of the implant, are reasons for revision of the implants. Therefore, discrimination between aseptic-mechanical-loosening and septic-bacterial-loosening of implants is critical during selection of a patient-tailored treatment policy. Specific detection and visualization of infections is a challenge because it is difficult to discriminate infections from inflammation. An imaging tracer that facilitates bacterial identification in a pre- and intraoperative setting may aid the workup for patients suspicious of bacterial infections. In this study we evaluated an antimicrobial peptide conjugated to a hybrid label, which contains both a radioisotope and a fluorescent dye. After synthesis of DTPA-Cy5-UBI29-41 and-when necessary-radiolabeling with (111)In (yield 96.3 ± 2.7%), in vitro binding to various bacterial strains was evaluated using radioactivity counting and confocal fluorescence microscopy. Intramuscular bacterial infections (S. aureus or K. pneumoniae) were also visualized in vivo using a combined nuclear and fluorescence imaging system. The indium-111 was chosen as label as it has a well-defined coordination chemistry, and in pilot studies labeling DTPA-Cy5-UBI29-41 with technetium-99m, we encountered damage to the Cy5 dye after the reduction with SnCl2. As a reference, we used the validated tracer (99m)Tc-UBI29-41. Fast renal excretion of (111)In-DTPA-Cy5-UBI29-41 was observed. Target to nontarget (T/NT) ratios were highest at 2 h post injection: radioactivity counting yielded T/NT ratios of 2.82 ± 0.32 for S. aureus and 2.37 ± 0.05 for K. pneumoniae. Comparable T/NT ratios with fluorescence imaging of 2.38 ± 0.09 for S. aureus and 3.55 ± 0.31 for K. pneumoniae were calculated. Ex vivo confocal microscopy of

  5. Heat tracer test in an alluvial aquifer: field experiment and inverse modelling

    OpenAIRE

    Klepikova, Maria; Wildemeersch, Samuel; Jamin, Pierre; Orban, Philippe; Hermans, Thomas; Nguyen, Frédéric; Brouyère, Serge; Dassargues, Alain

    2016-01-01

    Using heat as an active tracer for aquifer characterization is a topic of increasing interest. In this study, we investigate the potential of using heat tracer tests for characterization of a shallow alluvial aquifer. A thermal tracer test was conducted in the alluvial aquifer of the Meuse River, Belgium. The tracing experiment consisted in simultaneously injecting heated water and a dye tracer in a piezometer and monitoring the evolution of groundwater temperature and tracer concentration in...

  6. Heat tracer and solute tests in an alluvial aquifer: field experiment and inverse modelling

    OpenAIRE

    Dassargues, Alain; Klepikova, Maria; Jamin, Pierre; Orban, Philippe; Brouyère, Serge

    2015-01-01

    Using heat as an active tracer in different types of aquifers is a topic of increasing interest. In this study, we investigate the potential interest of using heat tracer tests for characterization of a shallow alluvial aquifer. A thermal tracer test was conducted in the alluvial aquifer of the Meuse River, Belgium. The tracing experiment consisted in simultaneously injecting heated water and a dye tracer in a piezometer and monitoring the evolution of groundwater temperature and tracer conce...

  7. Synthesis and evaluation of a peptide targeted small molecular Gd-DOTA monoamide conjugate for MR molecular imaging of prostate cancer

    OpenAIRE

    Wu, Xueming; Burden-Gulley, Susan M.; Yu, Guan-Ping; Tan, Mingqian; Lindner, Daniel; Brady-Kalnay, Susann M.; Lu, Zheng-Rong

    2012-01-01

    Tumor extracellular matrix has an abundance of cancer related proteins that can be used as biomarkers for cancer molecular imaging. Innovative design and development of safe and effective targeted contrast agents to these biomarkers would allow effective MR cancer molecular imaging with high spatial resolution. In this study, we synthesized a low molecular weight CLT1 peptide targeted Gd(III) chelate CLT1-dL-(Gd-DOTA)4 specific to clotted plasma proteins in tumor stroma for cancer MR molecula...

  8. Synthesis of 2'-deoxy-2'-[.sup.18F]fluoro-5-methyl-1-B-D-arabinofuranosyluracil (.sup.18F-FMAU)

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zibo; Cai, Hancheng; Conti, Peter S

    2014-12-16

    The present invention relates to methods of synthesizing .sup.18F-FMAU. In particular, .sup.18F-FMAU is synthesized using one-pot reaction conditions in the presence of Friedel-Crafts catalysts. The one-pot reaction conditions are incorporated into a fully automated cGMP-compliant radiosynthesis module, which results in a reduction in synthesis time and simplifies reaction conditions. The one-pot reaction conditions are also suitable for the production of 5-substituted thymidine or cytidine analogs. The products from the one-pot reaction (e.g. the labeled thymidine or cytidine analogs) can be used as probes for imaging tumor proliferative activity. More specifically, these [.sup.18F]-labeled thymidine or cytidine analogs can be used as a PET tracer for certain medical conditions, including, but not limited to, cancer disease, autoimmunity inflammation, and bone marrow transplant.

  9. Assessing preferential flow by simultaneously injecting nanoparticle and chemical tracers

    KAUST Repository

    Subramanian, S. K.

    2013-01-01

    The exact manner in which preferential (e.g., much faster than average) flow occurs in the subsurface through small fractures or permeable connected pathways of other kinds is important to many processes but is difficult to determine, because most chemical tracers diffuse quickly enough from small flow channels that they appear to move more uniformly through the rock than they actually do. We show how preferential flow can be assessed by injecting 2 to 5 nm carbon particles (C-Dots) and an inert KBr chemical tracer at different flow rates into a permeable core channel that is surrounded by a less permeable matrix in laboratory apparatus of three different designs. When the KBr tracer has a long enough transit through the system to diffuse into the matrix, but the C-Dot tracer does not, the C-Dot tracer arrives first and the KBr tracer later, and the separation measures the degree of preferential flow. Tracer sequestration in the matrix can be estimated with a Peclet number, and this is useful for experiment design. A model is used to determine the best fitting core and matrix dispersion parameters and refine estimates of the core and matrix porosities. Almost the same parameter values explain all experiments. The methods demonstrated in the laboratory can be applied to field tests. If nanoparticles can be designed that do not stick while flowing through the subsurface, the methods presented here could be used to determine the degree of fracture control in natural environments, and this capability would have very wide ranging value and applicability.

  10. Field measurements of tracer gas transport by barometric pumping

    International Nuclear Information System (INIS)

    Vertical gas motions induced by barometric pressure variations can carry radioactive gases out of the rubblized region produced by an underground nuclear explosion, through overburden rock, into the atmosphere. To better quantify transit time and amount of transport, field experiments were conducted at two sites on Pahute Mesa, Kapelli and Tierra, where radioactive gases had been earlier detected in surface cracks. At each site, two tracer gases were injected into the rubblized chimney 300-400 m beneath the surface and their arrival was monitored by concentration measurements in gas samples extracted from shallow collection holes. The first ''active'' tracer was driven by a large quantity of injected air; the second ''passive'' tracer was introduced with minimal gas drive to observe the natural transport by barometric pumping. Kapelli was injected in the fall of 1990, followed by Tierra in the fall of 1991. Data was collected at both sites through the summer of 1993. At both sites, no surface arrival of tracer was observed during the active phase of the experiment despite the injection of several million cubic feet of air, suggesting that cavity pressurization is likely to induce horizontal transport along high permeability layers rather than vertical transport to the surface. In contrast, the vertical pressure gradients associated with barometric pumping brought both tracers to the surface in comparable concentrations within three months at Kapelli, whereas 15 months elapsed before surface arrival at Tierra. At Kapelli, a quasisteady pumping regime was established, with tracer concentrations in effluent gases 1000 times smaller than concentrations thought to exist in the chimney. Tracer concentrations observed at Tierra were typically an order of magnitude smaller. Comparisons with theoretical calculations suggest that the gases are traveling through ∼1 millimeter vertical fractures spaced 2 to 4 meters apart. 6 refs., 18 figs., 3 tabs

  11. Transport of Passive Tracers in Baroclinic Wave Life Cycles

    Science.gov (United States)

    Stone, Elizabeth M.; Randel, William J.; Stanford, John L.

    1999-01-01

    The transport of passive tracers in idealized baroclinic wave life cycles is studied using output from the National Center for Atmospheric Research Community Climate Model (CCM2). Two life cycles, LCn and LCs, are simulated, starting with baroclinically unstable initial conditions similar to those used by Thorncroft et al. in their study of two life cycle paradigms. The two life cycles LCn and LCs have different initial horizontal wind shear structures that result in distinctive nonlinear development. In terms of potential vorticity-potential temperature (PV-theta) diagnostics, the LCn case is characterized by thinning troughs that are advected anti-cyclonically and equatorward, while the LCs case has broadening troughs that wrap up cyclonically and poleward. Four idealized passive tracers are included in the model to be advected by the semi-Lagrangian transport scheme of the CCM2, and their evolutions are investigated throughout the life cycles. Tracer budgets are analyzed in terms of the transformed Eulerian mean constituent transport formalism in pressure coordinates and also in isentropic coordinates. Results for both LCn and LCs show transport that is downgradient with respect to the background structure of the tracer field, but with a characteristic spatial structure that maximizes in the middle to high latitudes. For the idealized tropospheric tracers in this study, this represents a net upward and poleward transport that enhances concentrations at high latitudes. These results vary little with the initial distribution of the constituent field. The time tendency of the tracer is influenced most strongly by the eddy flux term. with the largest transport occurring during the nonlinear growth stage of the life cycle. The authors also study the transport of a lower-stratospheric tracer, to examine stratosphere-troposphere exchange for baroclinic waves.

  12. Copper Ion as a New Leakage Tracer

    Directory of Open Access Journals (Sweden)

    Modaresi J.

    2013-12-01

    Full Text Available Statement of Problem: Most failures of root canal treatments are caused by bacteria. Studies showed that the most common cause of endodontic failures were the incomplete obturation of the root canal and the lack of adequate apical seal. Some in-vitro methods are used to estimate sealing quality, generally by measuring microleakage that allows the tracer agent to penetrate the filled canal.Purpose: Conventional methods of evaluating the seal of endodontically treated teeth are complicated and have some drawbacks. We used copper ion diffusion method to assess the leakage and the results were compared to dye penetration method.Materials and Method: The crowns of 21 extracted teeth were cut off at the CEJ level. After preparing the canals, the teeth were placed in tubes containing saline. They were divided randomly into 15 experimental cases; 3 positive and 3 negative controls. Positive controls were filled by single cone without sealer while the experimental and the negative control groups were filled by lateral technique. The coronal portion of gutta was removed and 9mm was left. The external surface of each tooth was coated with nail polish. Two millimeters of apical portion was immersed into 9ml of distilled water and 0.3ml of CuSO4 solution was injected into the coronal portion. After 2 days, copper sulfate was measured by an atomic absorption spectrophotometer. The teeth were then immersed in 2% methylene blue for 24 hours, sectioned and the extent of dye penetration was measured by a stereomicroscope.Results: The maximum and minimum recorded copper ion concentrations for the experimental group were 18.37 and 2.87ppm respectively. The maximum and minimum recorded dye penetrations for the experimental group were 8.5 and 3.5mm respectively. The statistical analysis, adopting paired samples test, showed poor correlation between average recorded results of two methods.Conclusion: Based on our results, there was no significant correlation between

  13. A new PET tracer producing facility

    International Nuclear Information System (INIS)

    constructing a building, that will receive a new dedicate cyclotron, as well as the radiopharmacy laboratories. The mediate objective is supplying the regional demand of positron emitters, and offer last generation diagnosis. The starting labeled molecule is 18FDG. By the end of 2004, the level of production will be around 5 Ci/week of 18FDG, enough to fulfill the hospital's needs inside our state. The specific objective is the setting up of a PET tracer producing facility. As a mediate result we will have a reduction in costs and expenses with therapies. A final and sustained result will be a positive impact on the public health system and on the region's quality of life

  14. The synthesis of a D-glucosamine contrast agent, Gd-DTPA-DG, and its application in cancer molecular imaging with MRI

    International Nuclear Information System (INIS)

    Objective: The purpose of this study is to describe the synthesis of Gadolinium-diethylenetriamine pentaacetic acid-deoxyglucosamine (Gd-DTPA-DG) which is a D-glucosamine metabolic MR imaging contrast agent. We will also discuss its use in a pilot MRI study using a xenograft mouse model of human adenocarcinoma. Methods: This novel contrast agent was specifically studied because of its ability to 'target' metabolically active tumor tissues. In this study Gd-DTPA-DG is used to investigate how tumor tissues would react to a dose of 0.2 mmol Gd/kg over a 120 min exposure in a xenograft mouse model. These experiments used athymic mice implanted with human pulmonary adenocarcinoma (A549) as demonstrated by dynamic MRI. Alternately, another contrast agent that is not specific for targeting, Gd-DTPA, was used as the control at a similar dose of gadolinium. Efficacy of the targeted contrast agent was assessed by measuring relaxation rate in vitro and signal intensity (SI) in vivo. Statistical differences were calculated using one-way analysis of variance. Results: The synthesized Gd-DTPA-DG was shown to improve the contrast of tumor tissue in this model. Gd-DTPA-DG was also shown to have a similar pharmacokinetic rate but generated a higher relaxation rate in tumor tissues relative to the control contrast Gd-DTPA. In comparison to the pre-contrast imaging, the SI of tumor tissue in the experimental group was shown to be significantly increased at 15 min after injection of Gd-DTPA-DG (p < 0.001). The enhanced signal intensity spread from the edge of the tumor to the center and seemed to strengthen the idea that MRI performance would be useful in different tumor tissues. Conclusion: This preliminary study shows that this new chelated contrast agent, Gd-DTPA-DG, can be specifically targeted to accumulation in tumor tissue as compared to normal tissues. This targeted paramagnetic contrast agent has potential for specific cancer molecular imaging with MRI.

  15. The synthesis of a D-glucosamine contrast agent, Gd-DTPA-DG, and its application in cancer molecular imaging with MRI

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Wei [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000 (China); Chen Yue, E-mail: chenyue5523@126.com [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000 (China); Guo Dajing [Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010 (China); Huang Zhanwen; Cai Liang [Department of Nuclear Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000 (China); He Ling [West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 (China)

    2011-09-15

    Objective: The purpose of this study is to describe the synthesis of Gadolinium-diethylenetriamine pentaacetic acid-deoxyglucosamine (Gd-DTPA-DG) which is a D-glucosamine metabolic MR imaging contrast agent. We will also discuss its use in a pilot MRI study using a xenograft mouse model of human adenocarcinoma. Methods: This novel contrast agent was specifically studied because of its ability to 'target' metabolically active tumor tissues. In this study Gd-DTPA-DG is used to investigate how tumor tissues would react to a dose of 0.2 mmol Gd/kg over a 120 min exposure in a xenograft mouse model. These experiments used athymic mice implanted with human pulmonary adenocarcinoma (A549) as demonstrated by dynamic MRI. Alternately, another contrast agent that is not specific for targeting, Gd-DTPA, was used as the control at a similar dose of gadolinium. Efficacy of the targeted contrast agent was assessed by measuring relaxation rate in vitro and signal intensity (SI) in vivo. Statistical differences were calculated using one-way analysis of variance. Results: The synthesized Gd-DTPA-DG was shown to improve the contrast of tumor tissue in this model. Gd-DTPA-DG was also shown to have a similar pharmacokinetic rate but generated a higher relaxation rate in tumor tissues relative to the control contrast Gd-DTPA. In comparison to the pre-contrast imaging, the SI of tumor tissue in the experimental group was shown to be significantly increased at 15 min after injection of Gd-DTPA-DG (p < 0.001). The enhanced signal intensity spread from the edge of the tumor to the center and seemed to strengthen the idea that MRI performance would be useful in different tumor tissues. Conclusion: This preliminary study shows that this new chelated contrast agent, Gd-DTPA-DG, can be specifically targeted to accumulation in tumor tissue as compared to normal tissues. This targeted paramagnetic contrast agent has potential for specific cancer molecular imaging with MRI.

  16. HET0016, a selective inhibitor of 20-HETE synthesis, decreases pro-angiogenic factors and inhibits growth of triple negative breast cancer in mice.

    Directory of Open Access Journals (Sweden)

    Thaiz Ferraz Borin

    Full Text Available A selective inhibitor of 20-HETE synthesis, HET0016, has been reported to inhibit angiogenesis. 20-HETE has been known as a second mitogenic messenger of angiogenesis inducing growth factors. HET0016 effects were analyzed on MDA-MB-231 derived breast cancer in mouse and in vitro cell line. MDA-MB-231 tumor cells were implanted in animals' right flank and randomly assigned to early (1 and 2, starting treatments on day 0, or delayed groups (3 and 4 on day 8 after implantation of tumor. Animals received HET0016 (10 mg/kg treatment via intraperitoneal injection for 5 days/week for either 3 or 4 weeks. Control group received vehicle treatment. Tumor sizes were measured on days 7, 14, 21, and 28 and the animals were euthanized on day 22 and 29. Proteins were extracted from the whole tumor and from cells treated with 10 µM HET0016 for 4 and 24 hrs. Protein array kits of 20 different cytokines/factors were used. ELISA was performed to observe the HIF-1α and MMP-2 protein expression. Other markers were confirmed by IHC. HET0016 significantly inhibited tumor growth in all treatment groups at all-time points compared to control (p<0.05. Tumor growth was completely inhibited on three of ten animals on early treatment group. Treatment groups showed significantly lower expression of pro-angiogenic factors compared to control at 21 days; however, there was no significant difference in HIF-1α expression after treatments. Similar results were found in vitro at 24 hrs of HET0016 treatment. After 28 days, significant increase of angiogenin, angiopoietin-1/2, EGF-R and IGF-1 pro-angiogenic factors were found (p<0.05 compared to control, as well as an higher intensity of all factors were found when compared to that of 21 day's data, suggesting a treatment resistance. HET0016 inhibited tumor growth by reducing expression of different set of pro-angiogenic factors; however, a resistance to treatment seemed to happen after 21 days.

  17. TracerLPM (Version 1): An Excel® workbook for interpreting groundwater age distributions from environmental tracer data

    Science.gov (United States)

    Jurgens, Bryant C.; Böhlke, J.K.; Eberts, Sandra M.

    2012-01-01

    TracerLPM is an interactive Excel® (2007 or later) workbook program for evaluating groundwater age distributions from environmental tracer data by using lumped parameter models (LPMs). Lumped parameter models are mathematical models of transport based on simplified aquifer geometry and flow configurations that account for effects of hydrodynamic dispersion or mixing within the aquifer, well bore, or discharge area. Five primary LPMs are included in the workbook: piston-flow model (PFM), exponential mixing model (EMM), exponential piston-flow model (EPM), partial exponential model (PEM), and dispersion model (DM). Binary mixing models (BMM) can be created by combining primary LPMs in various combinations. Travel time through the unsaturated zone can be included as an additional parameter. TracerLPM also allows users to enter age distributions determined from other methods, such as particle tracking results from numerical groundwater-flow models or from other LPMs not included in this program. Tracers of both young groundwater (anthropogenic atmospheric gases and isotopic substances indicating post-1940s recharge) and much older groundwater (carbon-14 and helium-4) can be interpreted simultaneously so that estimates of the groundwater age distribution for samples with a wide range of ages can be constrained. TracerLPM is organized to permit a comprehensive interpretive approach consisting of hydrogeologic conceptualization, visual examination of data and models, and best-fit parameter estimation. Groundwater age distributions can be evaluated by comparing measured and modeled tracer concentrations in two ways: (1) multiple tracers analyzed simultaneously can be evaluated against each other for concordance with modeled concentrations (tracer-tracer application) or (2) tracer time-series data can be evaluated for concordance with modeled trends (tracer-time application). Groundwater-age estimates can also be obtained for samples with a single tracer measurement at one

  18. Partitioning Gas Tracer Technology for Measuring Water in Landfills

    Science.gov (United States)

    Briening, M. L.; Jakubowitch, A.; Imhoff, P. T.; Chiu, P. C.; Tittlebaum, M. E.

    2002-12-01

    Unstable landfills can result in significant environmental contamination and can become a risk to public health. To reduce this risk, water may be added to landfills to ensure that enough moisture exists for biodegradation of organic wastes. In this case risks associated with future breaks in the landfill cap are significantly reduced because organic material is degraded more rapidly. To modify moisture conditions and enhance biodegradation, leachate is typically collected from the bottom of the landfill and then recirculated near the top. It is difficult, though, to know how much leachate to add and where to add it to achieve uniform moisture conditions. This situation is exacerbated by the heterogeneous nature of landfill materials, which is known to cause short circuiting of infiltrating water, a process that has been virtually impossible to measure or model. Accurate methods for measuring the amount of water in landfills would be valuable aids for implementing leachate recirculation systems. Current methods for measuring water are inadequate, though, since they provide point measurements and are frequently affected by heterogeneity of the solid waste composition and solid waste compaction. The value of point measurements is significantly reduced in systems where water flows preferentially, such as in landfills. Here, spatially integrated measurements might be of greater value. In this research we are evaluating a promising technology, the partitioning gas tracer test, to measure the water saturation within landfills, the amount of free water in solid waste divided by the volume of the voids. The partitioning gas tracer test was recently developed by researchers working in the vadose zone. In this methodology two gas tracers are injected into a landfill. One tracer is non-reactive with landfill materials, while the second partitions into and out of free water trapped within the pore space of the solid waste. Chromatographic separation of the tracers occurs

  19. Natural organic compounds as tracers for biomass combustion in aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Simoneit, B.R.T. [Brookhaven National Lab., Upton, NY (United States)]|[Oregon State Univ., Corvallis, OR (United States). Coll. of Oceanic and Atmospheric Sciences; Abas, M.R. bin [Brookhaven National Lab., Upton, NY (United States)]|[Univ. of Malaya, Kuala Lumpur (Malaysia); Cass, G.R. [Brookhaven National Lab., Upton, NY (United States)]|[California Inst. of Tech., Pasadena, CA (United States). Environmental Engineering Science Dept.; Rogge, W.F. [Brookhaven National Lab., Upton, NY (United States)]|[Florida International Univ., University Park, FL (United States). Dept. of Civil and Environmental Engineering; Mazurek, M.A. [Brookhaven National Lab., Upton, NY (United States); Standley, L.J. [Academy of Natural Sciences, Avondale, PA (United States). Stroud Water Research Center; Hildemann, L.M. [Stanford Univ., CA (United States). Dept. of Civil Engineering

    1995-08-01

    Biomass combustion is an important primary source of carbonaceous particles in the global atmosphere. Although various molecular markers have already been proposed for this process, additional specific organic tracers need to be characterized. The injection of natural product organic tracers to smoke occurs primarily by direct volatilization/steam stripping and by thermal alteration based on combustion temperature. The degree of alteration increases as the burn temperature rises and the moisture content of the fuel decreases. Although the molecular composition of organic matter in smoke particles is highly variable, the molecular structures of the tracers are generally source specific. The homologous compound series and biomarkers present in smoke particles are derived directly from plant wax, gum and resin by volatilization and secondarily from pyrolysis of biopolymers, wax, gum and resin. The complexity of the organic components of smoke aerosol is illustrated with examples from controlled burns of temperate and tropical biomass fuels. Burning of biomass from temperate regions (i.e., conifers) yields characteristic tracers from diterpenoids as well as phenolics and other oxygenated species, which are recognizable in urban airsheds. The major organic components of smoke particles from tropical biomass are straight-chain, aliphatic and oxygenated compounds and triterpenoids. The precursor-to-product approach of organic geochemistry can be applied successfully to provide tracers for studying smoke plume chemistry and dispersion.

  20. Development of radioisotope tracer technology and nucleonic control system

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Joon Ha; Lee, Myun Joo; Jung, Sung Hee and others

    1999-04-01

    The purpose of this study is to develop the radioisotope tracer technology, which can be used in solving industrial and environmental problems and basic technology of nuclear control systems that are widely used for automation of industrial plants, and to build a strong tracer group to support the local industries. In relation to the tracer technology, the data acquisition system, the column scanning equipment and the detection pig for a leakage test have been developed. In order to use in analyzing data of tracer experiments, a computer program for the analysis of residence time distribution has been created as well. These results were utilized in developing the tracer technologies, such as the column scanning, the flow measurement using the dilution method, the simultaneous monitoring rotational movement of piston rings and the optimization of a waste water treatment facility, and the technologies were successfully demonstrated in the local industrial. The stripper of RFCC reactor has been examined to find an unwanted structure in it by imminent request from the industry. Related to the development of nucleonic control system, the state of art report on the technology has been written and an equipment for the analysis of asphalt content has been developed. (author)

  1. Chemical tracers of particulate emissions from commercial shipping.

    Science.gov (United States)

    Viana, Mar; Amato, Fulvio; Alastuey, Andrés; Querol, Xavier; Moreno, Teresa; Dos Santos, Saúl García; Herce, María Dolores; Fernández-Patier, Rosalía

    2009-10-01

    Despite the increase of commercial shipping around the world, data are yet relatively scarce on the contribution of these emissions to ambient air particulates. One of the reasons is the complexity in the detection and estimation of shipping contributions to ambient particulates in harbor and urban environments, given the similarity with tracers of other combustion sources. This study aimed to identify specific tracers of shipping emissions in a Mediterranean city with an important harbor (Melilla, Spain). Results showed that for 24 h PM10 and PM2.5 samples, valid tracers of commercial shipping emissions were ratios of V/Ni = 4-5 and V/EC 8 excluded the influence of shipping emissions. Other ratios (V/ S, La/Ce, Zn/Ni, Pb/Zn, OC/EC) and tracers (Pb, Zn) were also tested but did not correlate with this source. Due to the changing composition of diesel fuels, tracers in the Mediterranean Sea may not be representative in other regions of the world and vice versa. The contribution of shipping emissions to ambient particulate matter (PM) urban background levels was quantified by positive matrix factorization (PMF), resulting in 2% and 4% of mean annual PM10 levels (0.8 microg/m3 primary particles and 1.7 microg/m3 secondary particles, with 20% uncertainty) and 14% of mean annual PM2.5 levels (2.6 microg/m3). PMID:19848163

  2. Development of radioisotope tracer technology and nucleonic control system

    International Nuclear Information System (INIS)

    The purpose of this study is to develop the radioisotope tracer technology, which can be used in solving industrial and environmental problems and basic technology of nuclear control systems that are widely used for automation of industrial plants, and to build a strong tracer group to support the local industries. In relation to the tracer technology, the data acquisition system, the column scanning equipment and the detection pig for a leakage test have been developed. In order to use in analyzing data of tracer experiments, a computer program for the analysis of residence time distribution has been created as well. These results were utilized in developing the tracer technologies, such as the column scanning, the flow measurement using the dilution method, the simultaneous monitoring rotational movement of piston rings and the optimization of a waste water treatment facility, and the technologies were successfully demonstrated in the local industrial. The stripper of RFCC reactor has been examined to find an unwanted structure in it by imminent request from the industry. Related to the development of nucleonic control system, the state of art report on the technology has been written and an equipment for the analysis of asphalt content has been developed. (author)

  3. Serotonin synthesis studied with positron emission tomography, (PET)

    DEFF Research Database (Denmark)

    Honoré, Per Gustaf Hartvig; Lundquist, Pinelopi

    seroonin synthesis rate. Knowledge of altered 5HT synthesis and release in disease states may furnish basis for effective pharmacotherapy that may improve the care of psychiatric and neurological disease. Validation of PET measurements of the two PET tracers using perturbation showed that 5-hydroxy...... in the presence of NSD1015 which was used to inhibit the decarboxylation step in 5HT synthesis. 5HTP seems thus to have potential for tracking changes in the activity of the biosynthesis enzyme. In contrast, the accumulation of 5HTP was unaffected by clorgyline used to inhibit the metabolism of the...

  4. Preparation of intravenous cholesterol tracer using current good manufacturing practices.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Swaney, William P; Ostlund, Richard E

    2015-12-01

    Studies of human reverse cholesterol transport require intravenous infusion of cholesterol tracers. Because insoluble lipids may pose risk and because it is desirable to have consistent doses of defined composition available over many months, we investigated the manufacture of cholesterol tracer under current good manufacturing practice (CGMP) conditions appropriate for phase 1 investigation. Cholesterol tracer was prepared by sterile admixture of unlabeled cholesterol or cholesterol-d7 in ethanol with 20% Intralipid(®). The resulting material was filtered through a 1.2 micron particulate filter, stored at 4°C, and tested at time 0, 1.5, 3, 6, and 9 months for sterility, pyrogenicity, autoxidation, and particle size and aggregation. The limiting factor for stability was a rise in thiobarbituric acid-reacting substances of 9.6-fold over 9 months (P manufacturing methods can be achieved in the academic setting and need to be considered for critical components of future metabolic studies. PMID:26416797

  5. Natural stream flow-rates measurements by tracer techniques

    International Nuclear Information System (INIS)

    This paper presents the study of the precision obtained measuring the natural stream flow rates by tracer techniques, especially when the system presents a great slope and a bed constituted by large and extended particle size. The experiences were realized in laboratory pilot channels with flow-rates between 15 and 130 [1/s]; and in natural streams with flow-rates from 1 to 25 m3/s. Tracer used were In-133m and Br-82 for laboratory and field measurements respectively. In both cases the tracer was injected as a pulse and its dilution measured collecting samples in the measured section, at constant flow-rates, of 5[1] in laboratory experiences and 60[1] of water in field experiences. Precisions obtained at a 95% confidence level were about 2% for laboratory and 3% for field. (I.V.)

  6. Contribution to the Selection of Radioactive Tracers for Hydrogeology

    International Nuclear Information System (INIS)

    A systematic study was made of a number of anionic and cationic tracers in different terrains with distinct petrographic characteristics, allowance being made for the various physical and chemical parameters of the environment. The behaviour of 12 tracers (51Cr, 59Fe, 45Ca, 110Ag, 24Na, 137Cs, 3H, 32P, 35S, 14C, 131I, 82Br) was studied in six types of argillaceous rock (illite, vermiculite, interstratified illite-vermiculite, montmorillonite, attapulgite and kaolinite) and three sand types (siliceous, calcareous and dolomitic) in the presence of three types of water (demineralized, sea-water and various spring waters). On the basis of the results obtained from 5000 tests and measurements made during this study it is possible to select the tracer most suited to the characteristics of the terrain and the type of groundwater. (author)

  7. Contribution to the selection of radioactive tracers for hydrogeology

    International Nuclear Information System (INIS)

    A systematic study was made of a number of anionic and cationic tracers in different terrains with distinct petrographic characteristics, allowance being made for the various physical and chemical parameters of the environment. The behaviour of 12 tracers (51Cr, 59Fe, 45Ca, 110Ag, 24Na, 137Cs, 3H, 32P, 35S, 14C, 131I, 82Br) was studied in six types of argillaceous rock (illite, vermiculite, interstratified illite-vermiculite, montmorillonite, attapulgite and kaolinite) and three sand types (siliceous, calcareous and dolomitic) in the presence of three types of water (demineralized, sea-water and various spring waters). On the basis of the results obtained from 5000 tests and measurements made during this study it is possible to select the tracer most suited to the characteristics of the terrain and the type of groundwater. (author)

  8. Holdup time measurement by radioactive tracers in pulp production

    International Nuclear Information System (INIS)

    A batch of pulp was to be labelled before passing two bleaching towers of a pulp plant. Activated glass fibres were used as a tracer, which contained 24-Na with a half-life of 15 hours. It was shown in laboratory tests, that the glass fibres were suitable for transport studies of wood pulp. For use in the tests the fibres were activated and suspended in water. Due to the small diameter of the fibres (2-5 micrometers) this suspension shows physical properties very similar to the pulp. For detection six scintillation probes were mounted at different positions outside the bleaching tower. Radiation protection during the test was very easy due to the low total activity of the tracer material. Residence time distributions for both towers were measured. The successful tracer experiments show, that the method of labelling is suited for investigations of material transport in the pulp and paper industry. 3 figs., 11 refs., 2 tabs. (Author)

  9. Concentration dynamics in lakes and reservoirs. Studies using radioactive tracers

    International Nuclear Information System (INIS)

    The use of radioactive tracers for the investigation of concentration dynamics of inert soluble matter in lakes and reservoirs is reviewed. Shallow and deep stratified lakes are considered. The mechanism of mixing in lakes, flow pattern and input - output response are discussed. The methodology of the use of radioactive tracers for concentration dynamic studies is described. Examples of various investigations are reviewed. The dynamics of shallow lakes can be found and expressed in terms of transfer functions, axial dispersion models, residence time distributions and sometimes only semiquantitative information about the flow pattern. The dynamics of deep, stratified lakes is more complex and difficult to investigate with tracers. Flow pattern, horizontal and vertical eddy diffusivities, mass transfer between the hypolimnion and epilimnion are tools used for describing this dynamics. (author)

  10. Self-irradiation and ageing of radioactive tracers in immunoassays

    International Nuclear Information System (INIS)

    To determine the importance of the self-irradiation parameters during the ageing of radiotracers, the antigens 3H-testosterone, 125I-thyroxine and 125I-anti-FSH monoclonal antibody were tested after self-irradiation had been simulated by exposure in a 137Cs irradiator at an intensity of 0.3 Gy/min. For 3H-testosterone the calibration curve obtained with an irradiated tracer with gamma radiation equivalent to one year of storage was shifted in the middle by comparison with a reference tracer. In addition, there was a 20% increase in the non-specific binding, probably due to radiolysis. For 125I-thyroxine the comparative assay between calibration curves set up with an irradiated tracer with gamma radiation dose equivalent to 4 months of storage and a reference tracer showed no difference, but a drop of 2.5% in the ratio Bo/T was noticed. For antibody anti 125I-FSH there was no significant change in the calibration curve when the antibody had a gamma dose equivalent to 6 or 12 weeks o storage. But when a two month out-of-date antibody was used the slope curve (B/T) was greatly shifted. The non-specific binding was four times higher and the control serum was overestimated by 7%. A self-irradiation process seems to be greatly involved in the ageing of 3H-testosterone even when the tracer is preserved with a radioprotector. Even so, this phenomenon is only involved for gamma dose irradiation equivalent to one year of self-irradiation. Concerning 125I tracers (thyroxine and antibody anti-FSH), self-irradiation is not the main ageing factor, compared to other phenomena such as loss of specific radioactivity and loss of immunoreactivity for antibodies. (author). 5 refs, 2 figs, 3 tabs

  11. Dynamics and mechanics of bed-load tracer particles

    Science.gov (United States)

    Phillips, C. B.; Jerolmack, D. J.

    2014-12-01

    Understanding the mechanics of bed load at the flood scale is necessary to link hydrology to landscape evolution. Here we report on observations of the transport of coarse sediment tracer particles in a cobble-bedded alluvial river and a step-pool bedrock tributary, at the individual flood and multi-annual timescales. Tracer particle data for each survey are composed of measured displacement lengths for individual particles, and the number of tagged particles mobilized. For single floods we find that measured tracer particle displacement lengths are exponentially distributed; the number of mobile particles increases linearly with peak flood Shields stress, indicating partial bed load transport for all observed floods; and modal displacement distances scale linearly with excess shear velocity. These findings provide quantitative field support for a recently proposed modeling framework based on momentum conservation at the grain scale. Tracer displacement is weakly negatively correlated with particle size at the individual flood scale; however cumulative travel distance begins to show a stronger inverse relation to grain size when measured over many transport events. The observed spatial sorting of tracers approaches that of the river bed, and is consistent with size-selective deposition models and laboratory experiments. Tracer displacement data for the bedrock and alluvial channels collapse onto a single curve - despite more than an order of magnitude difference in channel slope - when variations of critical Shields stress and flow resistance between the two are accounted for. Results show how bed load dynamics may be predicted from a record of river stage, providing a direct link between climate and sediment transport.

  12. Basic Description of the Lymphatic System from the Perspective of SLN Uptake of Radioactive Tracers. Chapter 2

    International Nuclear Information System (INIS)

    The lymphatic system is part of the circulatory system. It is closely associated with the cardiovascular system because it includes a network of vessels that contributes to liquid transportation throughout the body. This circulatory system is essential for the maintenance of interstitial fluid balance, uptake of dietary fat and for body defence against invasion by disease causing agents. Lymph nodes, which contain large numbers of B and T lymphocytes and macrophages, are located along lymphatic pathways. They have two primary functions: filtering and digesting potentially harmful particles from lymph before returning it to the bloodstream and contributing to the immune surveillance provided by lymphocytes and macrophages. In their function of filtering particles or cell debris, lymph nodes may collect cancer cells that are breaking and travelling away from the primary tumour. The spread of some forms of cancer usually follows an orderly progression, spreading first to regional lymph nodes, then the next rank of lymph nodes and so on. Therefore, the first lymph node (the SLN) is more likely than other lymph nodes to contain cancer cells. If a suitable radioactive tracer, generally a nanocolloid or a dye, is administrated in the proximity of the tumour site, it will travel through the lymphatic system and be trapped in the SLN, allowing its localization using an appropriate probe or by visual determination. The size and the charge of the radioactive tracer will mainly influence the extent of radioactivity remaining at the site of injection, the rate of diffusion into the lymphatic vessels and the uptake in the SLN. Knowledge of the physiology of the lymphatic system will help to identify factors influencing the diffusion and uptake mechanism of radioactive tracers in the lymph nodes and will assist in the design of more efficient and selective SLN seeking drugs. (author)

  13. Interpretation of the tracer testing conducted in the Leuggern borehole

    International Nuclear Information System (INIS)

    Tracer testing was conducted in the Leuggern borehole from July to December 1988 to evaluate the hydraulic properties of the crystalline host rock. The tested interval was an approximately 50 m section of fractured crystalline rock at a depth of greater than 1,600 m. The testing consisted of three tracer injection/recovery periods (uranin - 44 days, eosin - 30 days, and naphtionat -14 days), which utilized tracer injection/circulation rates, ranging between 25 and 50 ml/min. During these testing periods, tracer was injected in either of two 1/4 flow lines ported at the top or bottom of the interval and recovered from the other. Following the three tracer injection periods, a natural outflow tracer recovery test was conducted from the central tubing at an average outflow of 12 l/min. The central tubing was ported near the center of the test interval. Data collected during the testing periods included: continuous monitoring of fluid temperature, injection pressure, and electrical conductivity as well as discrete measurement of flow rates, electrical conductivity, fluid temperature, and tracer concentration. Testing results indicate a downward vertical flow of approximately 195-225 ml/min in the isolated interval, from an upper fracture inflow zone to a lower fracture outflow zone. Through analysis of the dilution levels of uranin and eosin during the injection/recovery periods, and review of field data, the top of the upper inflow zone was determined to be approximately 13 m below the top flow line and the bottom of the outflow zone to be approximately 3 to 5 meters above the bottom flow line. The calculated transmissivity value of 6E-05 m2/s from observed outflow rate and pressure recovery data, is consistent with results derived from previous hydraulic packer testing in the interval. The effective porosity was determined to be 0.1. Dispersion coefficient values ranged from 1.0 m to 5.0 m. The lateral hydraulic gradient value calculated from tracer recovery analysis

  14. Forced Gradient Tracer Tests In A Highly Permeable Fault Zone

    Science.gov (United States)

    Himmelsbach, T.; Hötzl, H.; Maloszewski, P.

    1994-03-01

    In the area of a planned dam site in the southern Black Forest, an observation tunnel with boreholes drilled into an adjacent vertically orientated ore body offered nearly ideal conditions to investigate transport phenomena in a highly permeable fault and fracture zone. The experimental array, consisting of horizontal and inclined boreholes lying within distances of ten to twelve meters apart, gave the opportunity to perform forced gradient tracer tests over varying distances under fixed hydraulic boundary conditions. The breakthrough curves of the tracer experiments were analyzed using an adequate transport model. The fitting procedure yielded hydraulic parameters such as fissure and matrix porosities and first estimations of the average fracture aperture.

  15. Radioactive γ/β tracer to explore dangerous technogenic phenomena

    Science.gov (United States)

    Nagorsky, P. M.; Yakovleva, V. S.; Makarov, E. O.; Firstov, P. P.; Kondratyeva, A. G.; Stepanenko, A. A.

    2016-06-01

    A radioactive γ/β tracer to explore dangerous technogenic phenomena has been proposed: the ratio of the measured flux density of β- and γ-radiations in the surface layer of the atmosphere. The time dependence analysis of the ratio of β- and γ-pulse count rate has been carried out. A significant increase of the γ/β ratio was recorded under the cyclone passing through Japan (Fukushima) to Kamchatka. The proposed γ/β tracer can be a very sensitive indicator of nonstationary processes related to hazardous natural and technogenic phenomena.

  16. Oxygen tracer diffusion in single-crystal alumina

    Science.gov (United States)

    Cawley, James D.; Halloran, John W.; Cooper, Alfred R.

    1991-01-01

    Oxygen tracer diffusion coefficients are determined in single-crystal alumina samples with differing dopant levels using the gas-exchange technique. The diffusion direction is parallel to the c-axis and the ambient PO2 is 1 atm (100,000 Pa) for all experiments except a single run with a low PO2, approximately 10 to the -15th atm (10 to the -10th Pa) produced by a CO/CO2 mixture. The diffusion is insensitive to both impurities and ambient PO2. The insensitivities are discussed in terms of point-defect clustering. Prior tracer studies are compared and discussed.

  17. Lumped parameter models for the interpretation of environmental tracer data

    International Nuclear Information System (INIS)

    Principles of the lumped-parameter approach to the interpretation of environmental tracer data are given. The following models are considered: the piston flow model (PFM), exponential flow model (EM), linear model (LM), combined piston flow and exponential flow model (EPM), combined linear flow and piston flow model (LPM), and dispersion model (DM). The applicability of these models for the interpretation of different tracer data is discussed for a steady state flow approximation. Case studies are given to exemplify the applicability of the lumped-parameter approach. Description of a user-friendly computer program is given. (author). 68 refs, 25 figs, 4 tabs

  18. Sol-gel synthesis of magnetic TiO2 microspheres and characterization of their in vitro heating ability for hyperthermia treatment of cancer

    OpenAIRE

    Liu, Gengci; Kawashita, Masakazu; Li, Zhixia; Miyazaki, Toshiki; Kanetaka, Hiroyasu

    2015-01-01

    Common cancer treatments are invasive and lack specificity, leading to unwanted side effects. Because hyperthermia can kill cancer cells and damage proteins and structures within cells, it has been considered a novel, minimally invasive cancer treatment. However, many hyperthermia treatments cannot heat deep-seated tumors effectively and locally. Heat-generating magnetic microspheres can help address this challenge. However, current research has not produced microspheres that can be sufficien...

  19. Design and synthesis of an in vivo-efficacious PIM3 kinase inhibitor as a candidate anti-pancreatic cancer agent.

    Science.gov (United States)

    Nakano, Hirofumi; Hasegawa, Tsukasa; Saito, Nae; Furukawa, Kaoru; Mukaida, Naofumi; Kojima, Hirotatsu; Okabe, Takayoshi; Nagano, Tetsuo

    2015-12-15

    Serine/threonine kinase PIM3 is a potential therapeutic target for pancreatic cancer. Here, we describe the evolution of our previous PIM1 inhibitor 1 into PIM3 inhibitor 11 guided by use of the crystal structure of PIM1 as a surrogate to provide a basis for rational modification. Compound 11 potently inhibits PIM3 kinase activity, as well as growth of several pancreatic cancer cell lines. In a mouse xenograft model, 11 inhibited growth of human pancreatic cancer cell line PCI66 with negligible body weight loss. Thus, 11 appears to be a promising lead compound for further optimization to develop new anti-pancreatic cancer agents. PMID:26547690

  20. Analysis of blood clearance and labeled metabolites for the estrogen receptor tracer [F-18]-16α-fluorestradiol (FES)

    International Nuclear Information System (INIS)

    [F-18] 16α-Fluoroestradiol (FES) has been shown to be a tracer of estrogen receptor content in breast tumors; however, quantitative analysis of FES images is complicated by the rapid metabolism of the tracer in vivo. To optimize FES PET imaging studies and to provide an input function for the quantitative analysis of the tracer FES uptake in breast tumors, we studied the clearance and metabolism of FES in 15 breast cancer patients. FES clearance, protein binding, and metabolite production and limited assays to determine the identity of labeled metabolites were performed. These studies show that FES was rapidly cleared from the blood and metabolized; at 20 min only 20% of the circulating radioactivity was unmetabolized FES, and much of this was protein bound. The detectable metabolites in either blood or urine are conjugation products, largely the glucuronide and the sulfate of FES, and these are excreted through the kidneys at a rate comparable to their introduction into the circulation. After 20 min postinjection the blood levels of radioactivity remain fairly constant. Our results, the first report on human metabolites, are in close agreement with previous animal studies of FES metabolism. These studies show that because FES clearance is rapid and metabolite background is nearly constant, imaging starting at 20 to 30 min after injection may provide good visualization of estrogen-containing tissues. Labeled metabolites need to be accounted for in quantifying FES uptake