WorldWideScience

Sample records for medicine radiolabelled biomolecules

  1. Diagnostic and therapeutic perspectives in nuclear medicine: radiolabelled biomolecules

    International Nuclear Information System (INIS)

    Ferro F, G.; Murphy, C.A. de; Pedraza L, M.; Melendez A, L.

    2003-01-01

    From their beginning, the radiopharmaceuticals chemistry has gone to the study of the molecular chemistry. The radiopharmaceuticals are only in their capacity to detect such specific biochemical places as the receivers and the enzymes. With the recent obtaining of the complete structural sequence of the genome, it doesn't fit doubt of the importance that they have acquired the molecular images for the study from the genetic information to the alterations phenotypic in the chemistry of the human body. So, the future of the diagnostic and therapeutic nuclear medicine, practically is based in the study of protein fragments, peptide structures and chains of DNA radiolabelled for the study of the metabolism In vivo. These investigations represent a substantial change in those paradigms of the pharmaceutical development, when using the own organic capacities as source of medications, instead of considering to the organism like a simple assay tube where molecules act, like they are most of the traditional medications. The investigation of new techniques to design complex stable of Tc-99m, Re-188, Lu-177, Y-90 and Dy-166/Ho-l66 with biomolecules that don't alter the specificity and in general the molecular properties of the same ones. it is a topic of world interest in the environment of the radiopharmaceutical chemistry. In this work some achievements and perspectives are presented on those main diagnostic and therapeutic radiopharmaceuticals of third generation. (Author)

  2. Diagnostic and therapeutic perspectives in nuclear medicine: radiolabelled biomolecules; Perspectivas diagnosticas y terapeuticas en medicina nuclear: biomoleculas radiomarcadas

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G. [Gerencia de Aplicaciones Nucleares en la Salud. ININ, 11801 Mexico D.F. (Mexico); Murphy, C.A. de; Pedraza L, M. [Departamento de Medicina Nuclear. Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Melendez A, L. [Facultad de Medicina, UAEM, 50000 Toluca, Estado de Mexico (Mexico)

    2003-07-01

    From their beginning, the radiopharmaceuticals chemistry has gone to the study of the molecular chemistry. The radiopharmaceuticals are only in their capacity to detect such specific biochemical places as the receivers and the enzymes. With the recent obtaining of the complete structural sequence of the genome, it doesn't fit doubt of the importance that they have acquired the molecular images for the study from the genetic information to the alterations phenotypic in the chemistry of the human body. So, the future of the diagnostic and therapeutic nuclear medicine, practically is based in the study of protein fragments, peptide structures and chains of DNA radiolabelled for the study of the metabolism In vivo. These investigations represent a substantial change in those paradigms of the pharmaceutical development, when using the own organic capacities as source of medications, instead of considering to the organism like a simple assay tube where molecules act, like they are most of the traditional medications. The investigation of new techniques to design complex stable of Tc-99m, Re-188, Lu-177, Y-90 and Dy-166/Ho-l66 with biomolecules that don't alter the specificity and in general the molecular properties of the same ones. it is a topic of world interest in the environment of the radiopharmaceutical chemistry. In this work some achievements and perspectives are presented on those main diagnostic and therapeutic radiopharmaceuticals of third generation. (Author)

  3. Cell and biomolecule delivery for regenerative medicine

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Ian O; Ma, Peter X, E-mail: mapx@umich.ed [Department of Biologic and Materials Sciences, University of Michigan School of Dentistry, Ann Arbor, MI 48109 (United States)

    2010-02-15

    Regenerative medicine is an exciting field that aims to create regenerative alternatives to harvest tissues for transplantation. In this approach, the delivery of cells and biological molecules plays a central role. The scaffold (synthetic temporary extracellular matrix) delivers cells to the regenerative site and provides three-dimensional environments for the cells. To fulfil these functions, we design biodegradable polymer scaffolds with structural features on multiple size scales. To enhance positive cell-material interactions, we design nano-sized structural features in the scaffolds to mimic the natural extracellular matrix. We also integrate micro-sized pore networks to facilitate mass transport and neo tissue regeneration. We also design novel polymer devices and self-assembled nanospheres for biomolecule delivery to recapitulate key events in developmental and wound healing processes. Herein, we present recent work in biomedical polymer synthesis, novel processing techniques, surface engineering and biologic delivery. Examples of enhanced cellular/tissue function and regenerative outcomes of these approaches are discussed to demonstrate the excitement of the biomimetic scaffold design and biologic delivery in regenerative medicine. (topical review)

  4. Radiohalogenation of biomolecules. An experimental study on radiohalogen preparation, precursor synthesis, radiolabeling and biodistribution

    International Nuclear Information System (INIS)

    Koziorowski, J.

    1998-01-01

    Radiohalogens are widely used in nuclear medicine, both as tool for diagnostic in vivo imaging, and in radionuclide therapy. This study deals with the use of radiohalogens; separation, precursor synthesis, labeling and biological behavior. The focus is on 211 At and 124 I, the former being a candidate for nuclide therapy and the latter potentially useful for diagnostic imaging and Auger-electron based radiotherapy. For astatine the separation, labeling and some biological behavior is described, and for iodine the latter two. Astatine was separated from an irradiated bismuth target by dry distillation. A novel cryotrap was developed for the isolation of astatine and subsequent synthesis of radiolabeled compounds. 5-[ 211 At]astato-2'-deoxyuridine (AUdR) and N-succinimidyl-4-[ 211 At]astatobenzoate (SAB) were synthesized in 95% respectively 90% radiochemical yields. The former is incorporated into DNA of proliferating cells and can therefore be used as an endoradiotherapeutic agent. The latter is a conjugate for the astatination of proteins. Human epidermal growth factor (hEGF) was tagged with astatine using three approaches: a) direct labeling of native hEGF, b) conjugation with SAB, and c) direct labeling of an hEGF - 7-(3-aminopropyl)-7,8-dicarba-nido-undecaborate(1-) conjugate. The overall labeling yields were 3.5% for direct labeling, 44% for SAB and 70% for the hEGF-nido-carborane conjugate. A new route to N-succinimidyl 3- and 4- [ 124 I]iodobenzoate, two reagents for radioiodination of proteins is described affording 90% radiochemical yield. Three radioiodinated analogs of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxyam ide, a peripheral-type benzodiazepine receptor antagonist, were synthesized. All three analogs were obtained in >90% radiochemical yield. Synthesis and application of 5-[ 124 I]iodo-2'-deoxyuridine (IUdR) is presented. The closo-dodecaborate anion was evaluated as prosthetic group for radioiodination of

  5. In situ biomolecule production by bacteria; a synthetic biology approach to medicine.

    Science.gov (United States)

    Flores Bueso, Yensi; Lehouritis, Panos; Tangney, Mark

    2018-04-10

    The ability to modify existing microbiota at different sites presents enormous potential for local or indirect management of various diseases. Because bacteria can be maintained for lengthy periods in various regions of the body, they represent a platform with enormous potential for targeted production of biomolecules, which offer tremendous promise for therapeutic and diagnostic approaches for various diseases. While biological medicines are currently limited in the clinic to patient administration of exogenously produced biomolecules from engineered cells, in situ production of biomolecules presents enormous scope in medicine and beyond. The slow pace and high expense of traditional research approaches has particularly hampered the development of biological medicines. It may be argued that bacterial-based medicine has been "waiting" for the advent of enabling technology. We propose that this technology is Synthetic Biology, and that the wait is over. Synthetic Biology facilitates a systematic approach to programming living entities and/or their products, using an approach to Research and Development (R&D) that facilitates rapid, cheap, accessible, yet sophisticated product development. Full engagement with the Synthetic Biology approach to R&D can unlock the potential for bacteria as medicines for cancer and other indications. In this review, we describe how by employing Synthetic Biology, designer bugs can be used as drugs, drug-production factories or diagnostic devices, using oncology as an exemplar for the concept of in situ biomolecule production in medicine. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Radiolabeled peptides: experimental and clinical applications

    International Nuclear Information System (INIS)

    Thakur, M.L.; Pallela, V.R.

    1998-01-01

    Radiolabeled receptor specific biomolecules hold unlimited potential in nuclear medicine. During the past few years much attention has been drawn to the development radiolabeled peptides for a variety of diagnostic applications, as well as for therapy of malignant tumors. Although only one peptide, In-111-DTPA-(D)-Phe 1 -octreotide, is available commercially for oncologic imaging, many more have been examined in humans with hematological disorders, and the early results appear to be promising. Impetus generated by these results have prompted investigators to label peptides with such radionuclides as Tc-99m, I-123, F-18, Cu-64, and Y-90. This review is intended to highlight the qualities of peptides, summarize the clinical results, and address some important issues associated with radiolabeling of highly potent peptides. While doing so, various methods of radiolabeling have been described, and their strengths and weaknesses have also been discussed. (author)

  7. Label-free screening of single biomolecules through resistive pulse sensing technology for precision medicine applications

    Science.gov (United States)

    Harrer, S.; Kim, S. C.; Schieber, C.; Kannam, S.; Gunn, N.; Moore, S.; Scott, D.; Bathgate, R.; Skafidas, S.; Wagner, J. M.

    2015-05-01

    Employing integrated nano- and microfluidic circuits for detecting and characterizing biological compounds through resistive pulse sensing technology is a vibrant area of research at the interface of biotechnology and nanotechnology. Resistive pulse sensing platforms can be customized to study virtually any particle of choice which can be threaded through a fluidic channel and enable label-free single-particle interrogation with the primary read-out signal being an electric current fingerprint. The ability to perform label-free molecular screening with single-molecule and even single binding site resolution makes resistive pulse sensing technology a powerful tool for analyzing the smallest units of biological systems and how they interact with each other on a molecular level. This task is at the core of experimental systems biology and in particular ‘omics research which in combination with next-generation DNA-sequencing and next-generation drug discovery and design forms the foundation of a novel disruptive medical paradigm commonly referred to as personalized medicine or precision medicine. DNA-sequencing has approached the 1000-Dollar-Genome milestone allowing for decoding a complete human genome with unmatched speed and at low cost. Increased sequencing efficiency yields massive amounts of genomic data. Analyzing this data in combination with medical and biometric health data eventually enables understanding the pathways from individual genes to physiological functions. Access to this information triggers fundamental questions for doctors and patients alike: what are the chances of an outbreak for a specific disease? Can individual risks be managed and if so how? Which drugs are available and how should they be applied? Could a new drug be tailored to an individual’s genetic predisposition fast and in an affordable way? In order to provide answers and real-life value to patients, the rapid evolvement of novel computing approaches for analyzing big data in

  8. Radiolabeled platelets

    International Nuclear Information System (INIS)

    Datz, F.L.; Taylor, A.T.

    1986-01-01

    Initial interest in developing techniques to radiolabel platelets was spurred by the lack of an accurate method for measuring platelet life span in both normals and in thrombocytopenic patients. Early investigators could obtain only rough estimates of platelet life spans by monitoring the platelet counts of thrombocytopenic patients undergoing platelet transfusions. Labels were also sought that would allow imaging of platelets in vivo in order to better understand the pathophysiology of atherosclerosis, thrombophlebitis, and clotting disorders, and to improve the clinical diagnosis of these diseases. Two types of platelet labels were investigated: cohort (pulse) labels and random labels. Cohort labels are taken up by megakaryocytes in the bone marrow and incorporated in the DNA and other components of the forming platelet. In theory, only freshly released platelets of a uniform age are labeled. Random labels, on the other hand, tag platelets in the peripheral blood, labeling platelets of all ages

  9. Preclinical evaluation of neurotensin(8-13) analog radiolabeled with 99mTc: in vitro and in vivo characterization

    International Nuclear Information System (INIS)

    Teodoro, Rodrigo

    2010-01-01

    The radiolabeling of receptor specific biomolecules with 99m Tc using bifunctional chelator agents represents a growing field in Nuclear Medicine, specially, regarding regulatory peptides, such as Neurotensin, which are important in several essential physiological functions, particularly in tumor growth. The aim of the study was the comparative radiolabeling evaluation of the double-stabilized NT(8-13) analog with 99m Tc, via the bifunctional chelating agents 6- hydrazinonicotinamide (HYNIC) and S-acetyl-mercaptoacetyltriglycine (MAG3) in MDA-MB-231 breast cancer cell line. High radiochemical yields (> 97%) and stability toward transchelant agents was observed for both radiolabeled analogs. Also, comparable in vitro behaviour regarding the percentage of plasma protein binding (nearby 22%), metabolic stability, receptor binding affinity (nM range), and internalization/externalization rates were obtained. The greater lipophilicity found for the analog radiolabeled via MAG 3 , reflected in the major differences in biodistribution studies. The in vivo metabolic stability studies suggested that the degradation observed in the later time point (90 min) for the conjugate radiolabeled via HYNIC, leads not only to lower tumor uptake accumulation (0,44±0,02% ID/g), but also to lower tumor-to-non-tumor ratios ( 3 had been confirmed in the present study, a structural re-design aiming the reduction of the high gastrointestinal uptake must be done in order to guarantee the potential applicability of MAG 3 -radio complex. (author)

  10. A novel method of 18F radiolabeling for PET.

    NARCIS (Netherlands)

    McBride, W.J.; Sharkey, R.M.; Karacay, H.; D'Souza, C.A.; Rossi, E.A.; Laverman, P.; Chang, C.H.; Boerman, O.C.; Goldenberg, D.M.

    2009-01-01

    Small biomolecules are typically radiolabeled with (18)F by binding it to a carbon atom, a process that usually is designed uniquely for each new molecule and requires several steps and hours to produce. We report a facile method wherein (18)F is first attached to aluminum as Al(18)F, which is then

  11. Biomolecules and Natural Medicine Preparations: Analysis of New Sources of Bioactive Compounds from Ribes and Rubus spp. Buds

    Directory of Open Access Journals (Sweden)

    Dario Donno

    2016-02-01

    Full Text Available It is well known that plants are important sources for the preparation of natural remedies as they contain many biologically active compounds. In particular, polyphenols, terpenic compounds, organic acids, and vitamins are the most widely occurring groups of phytochemicals. Some endemic species may be used for the production of herbal preparations containing phytochemicals with significant bioactivity, as antioxidant activity and anti-inflammatory capacities, and health benefits. Blackberry sprouts and blackcurrant buds are known to contain appreciable levels of bioactive compounds, including flavonols, phenolic acids, monoterpenes, vitamin C, and catechins, with several clinical effects. The aim of this research was to perform an analytical study of blackcurrant and blackberry bud-preparations, in order to identify and quantify the main biomarkers, obtaining a specific phytochemical fingerprint to evaluate the single botanical class contribution to total phytocomplex and relative bioactivity, using a High Performance Liquid Chromatograph−Diode Array Detector; the same analyses were performed both on the University laboratory and commercial preparations. Different chromatographic methods were used to determine concentrations of biomolecules in the preparations, allowing for quantification of statistically significant differences in their bioactive compound content both in the case of Ribes nigrum and Rubus cultivated varieties at different harvest stages. In blackcurrant bud-extracts the most important class was organic acids (50.98% followed by monoterpenes (14.05%, while in blackberry preparations the main bioactive classes were catechins (50.06% and organic acids (27.34%. Chemical, pharmaceutical and agronomic-environmental knowledge could be important for obtaining label certifications for the valorization of specific genotypes, with high clinical and pharmaceutical value: this study allowed to develop an effective tool for the natural

  12. Radiolabelled sucralfate compositions

    International Nuclear Information System (INIS)

    Vasquez, T.E.; Bridges, R.L.; Braunstein, P.; Jansholt, A.

    1984-01-01

    A novel radiopharmaceutical composition comprising an aqueous solution or suspension containing a radiolabelled sucralfate or sucralfate derivative or precursor is claimed. The composition is effective for in vivo scintigraphic imaging of the gastrointestinal muscosal areas in humans. The sucralfate is combined with a radiolabelled albumin or other protein or protein derivative under acidic conditions

  13. Radiolabeled cellular blood elements

    International Nuclear Information System (INIS)

    Thakur, M.L.; Ezikowitz, M.D.; Hardeman, M.R.

    1985-01-01

    This book contains papers delivered by guest lectures and participants at the Advanced Study Institute's colloquium on Radiolabeled Cellular Blood Elements at Maratea, Italy on August 29, to September 9, 1982. The book includes chapters on basic cell physiology and critical reviews of data and experience in the preparation and use of radiolabeled cells, as well as reports on very recent developments, from a faculty that included experts on cell physiology in health and disease and on the technology of in vivo labeling

  14. Radiochemistry in nuclear medicine. Radiopharmaceuticals

    International Nuclear Information System (INIS)

    Samochocka, K.

    1999-01-01

    Radionuclides and radiopharmaceuticals play a kay role in nuclear medicine, both in diagnostics and therapy. Incorporation of radionuclides into biomolecules, and syntheses of radiolabelled compounds of high biological selectivity are a task for radiochemists working in the multidisciplinary field of radiopharmaceutical chemistry. The most commonly used radionuclide, 99m Tc, owes this popularity to its both nearly ideal nuclear properties in respect to medical imaging, and availability from inexpensive radionuclide generators. Also numerous other radionuclides are widely used for medical imaging and therapy. Labelling of biomolecules with radioiodine and various positron emitters is getting increasingly important. This review describes some chemical and radiochemical problems we meet while synthesizing and using 99m Tc-radiopharmaceuticals and radioiodine-labelled biomolecules. Also represented are the recent developments in the design and use of the second generation radiopharmaceuticals based on bifunctional radiochelates. Several principal routes of fast chemical synthesis concerning incorporation of short-lived positron emitters into biomolecules are outlined as well. The search for chemical structures of high biological selectivity, which would be activated by slow neutrons, is related to the method of Neutron Capture Therapy, an interesting option in nuclear medicine. (author)

  15. Potential pitfalls in the nuclear medicine imaging: Experimental models to evaluate the effect of natural products on the radiolabeling of blood constituents, bioavailability of radiopharmaceutical and on the survival of Escherichia coli strains submitted to the treatment with stannous ion

    Science.gov (United States)

    Soares, Scheila F.; Brito, Lavínia C.; Souza, Deise E.; Bernardo, Luciana C.; Oliveira, Joelma F.; Bernardo-Filho, Mario

    2006-12-01

    Single photon emission computed tomography (SPECT) allows studies of physiological or pathological processes. Red blood cells labeled with technetium-99m ( 99mTc-RBC) are used as a radiopharmaceutical in several evaluations. The radiolabeling efficiency and bioavailability of radiopharmaceuticals can be altered by natural/synthetic drugs and may induce pitfalls in the analysis of the nuclear medicine imaging. The labeling with 99mTc requires a reducing agent and stannous chloride (SnCl 2) is widely utilized. However, SnCl 2 presents a citotoxic and/or genotoxic potential in Escherichia coli ( E. coli) strains. The aim of this work was to evaluate the influence of aqueous extracts of Baccharis genistelloides (BG), Terminalia chebula (TC), Maytenus ilicifolia (MI), Cassia angustifolia (CA) and Equisetum arvense (EA) on (i) radiolabeling of blood constituents, (ii) bioavailability of sodium pertechnetate(Na 99mTcO 4) radiopharmaceutical, (iii) survival of E. coli. In vitro labeling of RBC was performed with blood ( Wistar rats) incubated with each extract, SnCl 2 and Na 99mTcO 4. Plasma (P) and blood cells (BC) were isolated, another aliquots precipitated and soluble (SF) and insoluble (IF) fractions isolated and counted. In the bioavailability of Na 99mTcO 4, Wistar rats were treated (7 days) with aqueous extract or with 0.9%NaCl, the radiopharmaceutical was administered, the animals sacrificed, the organs isolated, weighted and radioactivity counted. To evaluate the effect on the bacterial survival, E. coli was treated with: (a) SnCl 2; (b) 0.9% NaCl; (c) vegetal extract; or (d) SnCl 2 and vegetal extract. Radiolabeling efficiency showed a significantly decrease (ANOVA/Tukey post-test, pthyroid (CA) and liver (all the extracts). The alterations promoted by TC extract could be related to cardiotonic, antidiabetes and renal toxicity. The alteration in liver in EA and CA extracts could be related to its hepatoprotective activities. The extracts (EA, MI, BG) were not

  16. Radiolabeled antibody imaging

    International Nuclear Information System (INIS)

    Wahl, R.L.

    1987-01-01

    Radiolabeled antibodies, in particular monoclonal antibodies, offer the potential for the specific nuclear imaging of malignant and benign diseases in man. If this imaging potential is realized, they may also have a large role in cancer treatment. This paper reviews: (1) what monoclonal antibodies are and how they differ from polyclonal antibodies, (2) how they are produced and radiolabeled, (3) the results of preclinical and clinical trials in cancer imaging, including the utility of SPECT and antibody fragments, (4) the role of antibodies in the diagnosis of benign diseases, (5) alternate routes of antibody delivery, (6) the role of these agents in therapy, and (7) whether this technology ''revolutionizes'' the practice of nuclear radiology, or has a more limited complementary role in the imaging department

  17. Antimicrobial Peptides as Infection Imaging Agents: Better Than Radiolabeled Antibiotics

    Directory of Open Access Journals (Sweden)

    Muammad Saeed Akhtar

    2012-01-01

    Full Text Available Nuclear medicine imaging techniques offer whole body imaging for localization of number and site of infective foci inspite of limitation of spatial resolution. The innate human immune system contains a large member of important elements including antimicrobial peptides to combat any form of infection. However, development of antibiotics against bacteria progressed rapidly and gained popularity over antimicrobial peptides but even powerful antimicrobials failed to reduce morbidity and mortality due to emergence of mutant strains of bacteria resulting in antimicrobial resistance. Differentiation between infection and inflammation using radiolabeled compounds with nuclear medicine techniques has always been a dilemma which is still to be resolved. Starting from nonspecific tracers to specific radiolabeled tracers, the question is still unanswered. Specific radiolabeled tracers included antibiotics and antimicrobial peptides which bind directly to the bacteria for efficient localization with advanced nuclear medicine equipments. However, there are merits and demerits attributed to each. In the current paper, radiolabeled antibiotics and radiolabeled peptides for infection localization have been discussed starting with the background of primitive nonspecific tracers. Radiolabeled antimicrobial peptides have certain merits compared with labeled antibiotics which make them superior agents for localization of infective focus.

  18. Radiolabelled blood elements techniques and clinical applications

    International Nuclear Information System (INIS)

    Thakur, M.L.

    1992-01-01

    Over the past few years, in nuclear medicine, the diagnostic applications of radiolabelled blood elements in general, and of radiolabelled white blood cells in particular, have become increasingly popular. This is primarily due to the introduction of lipid soluble 111 In-oxine as an agent, which not only is an excellent and a reliable tracer for blood cells but also enables the investigators to study the in vivo cell kinetics and map the localization of labelled cells by external gamma scintigraphy. The tracer has the modest half life of 67 hours and decays with the emission of two gamma photons (173 and 247 keV) in high abundance. This technique has provided a powerful tool to study the in vivo cell kinetics in health and localize abnormal lesions in diseases which invoke intense focal cellular concentration

  19. Radiolabeling of methionine containing proteins and peptides

    International Nuclear Information System (INIS)

    Garlick, R.K.; Jirousek, L.

    1986-01-01

    A process for radiolabeling methionine-containing peptides and proteins is disclosed. The process comprises the steps of oxidizing the protein or peptide, radiolabeling and reducing the radiolabeled protein or peptide. (author)

  20. Radiolabeling of biological vectors by poly-aza-macrocyclic complexes

    International Nuclear Information System (INIS)

    Moreau, M.

    2012-01-01

    This work conducted at the 'Institut de Chimie Moleculaire de l'Universite de Bourgogne' carries at first on the synthesis of bifunctional chelating agents suitable for the chelation of trivalent radio-metals, including indium-111. The greater part of this work was then dedicated to the grafting of a DOTA derivative bifunctional chelating agent on different antibodies or fragments of monoclonal antibodies: trastuzumab (anti-HER2 treatment of breast cancer), cetuximab (anti EGFR, treatment of many cancers, including colorectal cancer) and abciximab (antiplatelet). Particular attention was paid to the characterization of various immuno-conjugates. The critical step of this thesis consisted in the indium-111 radiolabeling of two previously prepared immuno-conjugates: trastuzumab and cetuximab. These steps of radiolabelling allowed us to determine the immunoreactive fraction and affinity of each radiotracer. Thus, we were able to study the in vivo biodistribution of the radiotracers in tumour-bearing mice by SPECT-CT. We also developed an original method for the labeling of a Fab antibody fragment in order to monitor the biodistribution of the antiplatelet agent (abciximab). Finally, we also validated the concept of multimodal imaging through grafting and radiolabeling of a bimodal agent for optical and SPECT imaging on bacterial lipopolysaccharide. Thanks to this work, we gained an expertise in antibodies radiolabeling. The results obtained allow to consider the labeling of antibodies or other biomolecules, and the use of other radionuclides for PET imaging and radioimmunotherapy. (author)

  1. Radiolabeled derivatives of folic acid

    International Nuclear Information System (INIS)

    1980-01-01

    Derivatives of folic acid are described, in which the α-carboxyl group is substituted with an amino compound having an aromatic or heterocyclic ring substituent which is capable of being radiolabelled. Particularly mentioned as a radiolabel is 125 I. (author)

  2. Potential pitfalls in the nuclear medicine imaging: Experimental models to evaluate the effect of natural products on the radiolabeling of blood constituents, bioavailability of radiopharmaceutical and on the survival of Escherichia coli strains submitted to the treatment with stannous ion

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Scheila F. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Brito, Lavinia C. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Souza, Deise E. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Bernardo, Luciana C. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Oliveira, Joelma F. [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil); Bernardo-Filho, Mario [Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Laboratorio de Radiofarmacia Experimental, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro, 87, Rio de Janeiro, RJ 20551-030 (Brazil)]. E-mail: bernardo@uerj.br

    2006-12-20

    Single photon emission computed tomography (SPECT) allows studies of physiological or pathological processes. Red blood cells labeled with technetium-99m ({sup 99m}Tc-RBC) are used as a radiopharmaceutical in several evaluations. The radiolabeling efficiency and bioavailability of radiopharmaceuticals can be altered by natural/synthetic drugs and may induce pitfalls in the analysis of the nuclear medicine imaging. The labeling with {sup 99m}Tc requires a reducing agent and stannous chloride (SnCl{sub 2}) is widely utilized. However, SnCl{sub 2} presents a citotoxic and/or genotoxic potential in Escherichia coli (E. coli) strains. The aim of this work was to evaluate the influence of aqueous extracts of Baccharis genistelloides (BG), Terminalia chebula (TC), Maytenus ilicifolia (MI), Cassia angustifolia (CA) and Equisetum arvense (EA) on (i) radiolabeling of blood constituents (ii) bioavailability of sodium pertechnetate(Na{sup 99m}TcO{sub 4}) radiopharmaceutical (iii) survival of E. coli. In vitro labeling of RBC was performed with blood (Wistar rats) incubated with each extract, SnCl{sub 2} and Na{sup 99m}TcO{sub 4}. Plasma (P) and blood cells (BC) were isolated, another aliquots precipitated and soluble (SF) and insoluble (IF) fractions isolated and counted. In the bioavailability of Na{sup 99m}TcO{sub 4}, Wistar rats were treated (7 days) with aqueous extract or with 0.9%NaCl, the radiopharmaceutical was administered, the animals sacrificed, the organs isolated, weighted and radioactivity counted. To evaluate the effect on the bacterial survival, E. coli was treated with: (a) SnCl{sub 2}; (b) 0.9% NaCl; (c) vegetal extract; or (d) SnCl{sub 2} and vegetal extract. Radiolabeling efficiency showed a significantly decrease (ANOVA/Tukey post-test, p<0.05) after treatment with BG, TC, MI and CA extracts. The bioavailability results showed that the uptake of Na{sup 99m}TcO{sub 4} was altered significantly (unpaired t-student test, p<0.05) in blood, lungs (CA

  3. Frustration in biomolecules.

    Science.gov (United States)

    Ferreiro, Diego U; Komives, Elizabeth A; Wolynes, Peter G

    2014-11-01

    Biomolecules are the prime information processing elements of living matter. Most of these inanimate systems are polymers that compute their own structures and dynamics using as input seemingly random character strings of their sequence, following which they coalesce and perform integrated cellular functions. In large computational systems with finite interaction-codes, the appearance of conflicting goals is inevitable. Simple conflicting forces can lead to quite complex structures and behaviors, leading to the concept of frustration in condensed matter. We present here some basic ideas about frustration in biomolecules and how the frustration concept leads to a better appreciation of many aspects of the architecture of biomolecules, and especially how biomolecular structure connects to function by means of localized frustration. These ideas are simultaneously both seductively simple and perilously subtle to grasp completely. The energy landscape theory of protein folding provides a framework for quantifying frustration in large systems and has been implemented at many levels of description. We first review the notion of frustration from the areas of abstract logic and its uses in simple condensed matter systems. We discuss then how the frustration concept applies specifically to heteropolymers, testing folding landscape theory in computer simulations of protein models and in experimentally accessible systems. Studying the aspects of frustration averaged over many proteins provides ways to infer energy functions useful for reliable structure prediction. We discuss how frustration affects folding mechanisms. We review here how the biological functions of proteins are related to subtle local physical frustration effects and how frustration influences the appearance of metastable states, the nature of binding processes, catalysis and allosteric transitions. In this review, we also emphasize that frustration, far from being always a bad thing, is an essential feature

  4. Methods to obtain radiolabelled monocrotaline

    International Nuclear Information System (INIS)

    Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J.

    1996-01-01

    Crotalaria spectabilis, a plant found in many areas of the world is associated with the pyrrolizidine alkaloid monocrotaline. Monocrotaline when injected subcutaneously in Sprague Dawley rats has been utilized for years to create a condition known to mimic pulmonary hypertension in humans. We attempted to determine the optimum conditions for the biosynthesis of radiolabelled monocrotaline. Our work describes the plant growth conditions and the time periods associated with the production of radiolabelled monocrotaline. In addition, the incorporation of 14 CO 2 or [2,3- 3 H]-putrescine dihydrochloride and the specific activity plus the amount(s) of recovered radiolabelled monocrotaline are discussed. We conclude that the most efficient and cost effective method for the biosynthesis of radiolabelled monocrotaline is still the utilization of 14 CO 2 . (author)

  5. Methods to obtain radiolabelled monocrotaline

    Energy Technology Data Exchange (ETDEWEB)

    Lame, M.W.; Morin, D.; Wilson, D.W.; Segall, H.J. [University of California, Davis, CA (United States)

    1996-12-01

    Crotalaria spectabilis, a plant found in many areas of the world is associated with the pyrrolizidine alkaloid monocrotaline. Monocrotaline when injected subcutaneously in Sprague Dawley rats has been utilized for years to create a condition known to mimic pulmonary hypertension in humans. We attempted to determine the optimum conditions for the biosynthesis of radiolabelled monocrotaline. Our work describes the plant growth conditions and the time periods associated with the production of radiolabelled monocrotaline. In addition, the incorporation of {sup 14}CO{sub 2} or [2,3-{sup 3}H]-putrescine dihydrochloride and the specific activity plus the amount(s) of recovered radiolabelled monocrotaline are discussed. We conclude that the most efficient and cost effective method for the biosynthesis of radiolabelled monocrotaline is still the utilization of {sup 14}CO{sub 2}. (author).

  6. Radiolabelling of cholera toxin

    International Nuclear Information System (INIS)

    Santos, R.G.; Neves, Nicoli M.J.; Abdalla, L.F.; Brandao, R.L.; Etchehebehere, L.; Lima, M.E. de; Nicoli, J.R.

    1999-01-01

    Binding of cholera toxin to ganglioside receptors of enterocyte microvilli catalyzes the activation of adenylate cyclase causing a rise in cAMP which final result is a copious diarrhea. Saccharomyces boulardii, a nonpathogenic yeast has been used to prevent diarrhea. Although the antidiarrheic properties of S. boulardii are widely recognized, this yeast has been used on empirical basis, and the mechanism of this protective effect is unknown. The addition of cholera toxin to S. boulardii induces the raising of cAMP that triggers the activation of neutral trehalase. This suggests that toxin specifically binding to cells, is internalized and active the protein phosphorylation cascade. Our objective is labeling the cholera toxin to verify the presence of binding sites on yeast cell surfaces for the cholera toxin. Cholera toxin was radiolabelled with Na 125 I by a chloramine-T method modified from Cuatrecasas and Griffiths et alii. The 125 I-Cholera toxin showed a specific radioactivity at about 1000 cpm/fmol toxin. Biological activity of labeled cholera toxin measured by trehalase activation was similar to the native toxin. (author)

  7. Radiolabelling of cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Santos, R.G.; Neves, Nicoli M.J. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN), Belo Horizonte, MG (Brazil); Abdalla, L.F.; Brandao, R.L.; Etchehebehere, L. [Ouro Preto Univ., MG (Brazil). Escola de Farmacia. Lab. de Fisiologia e Bioquimica de Microorganismos; Lima, M.E. de [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Bioquimica e Imunologia; Nicoli, J.R. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Microbiologia

    1999-11-01

    Binding of cholera toxin to ganglioside receptors of enterocyte microvilli catalyzes the activation of adenylate cyclase causing a rise in cAMP which final result is a copious diarrhea. Saccharomyces boulardii, a nonpathogenic yeast has been used to prevent diarrhea. Although the antidiarrheic properties of S. boulardii are widely recognized, this yeast has been used on empirical basis, and the mechanism of this protective effect is unknown. The addition of cholera toxin to S. boulardii induces the raising of cAMP that triggers the activation of neutral trehalase. This suggests that toxin specifically binding to cells, is internalized and active the protein phosphorylation cascade. Our objective is labeling the cholera toxin to verify the presence of binding sites on yeast cell surfaces for the cholera toxin. Cholera toxin was radiolabelled with Na {sup 125} I by a chloramine-T method modified from Cuatrecasas and Griffiths et alii. The {sup 125} I-Cholera toxin showed a specific radioactivity at about 1000 cpm/fmol toxin. Biological activity of labeled cholera toxin measured by trehalase activation was similar to the native toxin. (author) 5 refs., 3 figs.; e-mail: nevesmj at urano.cdtn.br

  8. Development of radioactively labelled cancer seeking biomolecules for targeted radiotherapy

    International Nuclear Information System (INIS)

    Varvarigou, A.D.; Archimandritis, S.C.

    2000-01-01

    Within the framework of the above project we are studying the labelling of biomolecules, peptides and antibodies, with radionuclides emitting β - and γ radiation. More specifically, for the time being, we have investigated the labelling of peptides with Re-188 and of antibodies with Sm-153 and Re-188. The radiolabelled derivatives are further evaluated in vivo for possible application in Oncology. For these radiobiological studies we are trying to apply ectopic and orthotopic tumour animal models and to develop, in collaboration with other national and foreign institutes, proper imaging devices for small animal imaging

  9. Frustration in Biomolecules

    Science.gov (United States)

    Ferreiro, Diego U.; Komives, Elizabeth A.; Wolynes, Peter G.

    2014-01-01

    Biomolecules are the prime information processing elements of living matter. Most of these inanimate systems are polymers that compute their own structures and dynamics using as input seemingly random character strings of their sequence, following which they coalesce and perform integrated cellular functions. In large computational systems with a finite interaction-codes, the appearance of conflicting goals is inevitable. Simple conflicting forces can lead to quite complex structures and behaviors, leading to the concept of frustration in condensed matter. We present here some basic ideas about frustration in biomolecules and how the frustration concept leads to a better appreciation of many aspects of the architecture of biomolecules, and how biomolecular structure connects to function. These ideas are simultaneously both seductively simple and perilously subtle to grasp completely. The energy landscape theory of protein folding provides a framework for quantifying frustration in large systems and has been implemented at many levels of description. We first review the notion of frustration from the areas of abstract logic and its uses in simple condensed matter systems. We discuss then how the frustration concept applies specifically to heteropolymers, testing folding landscape theory in computer simulations of protein models and in experimentally accessible systems. Studying the aspects of frustration averaged over many proteins provides ways to infer energy functions useful for reliable structure prediction. We discuss how frustration affects folding mechanisms. We review here how a large part of the biological functions of proteins are related to subtle local physical frustration effects and how frustration influences the appearance of metastable states, the nature of binding processes, catalysis and allosteric transitions. We hope to illustrate how Frustration is a fundamental concept in relating function to structural biology. PMID:25225856

  10. Radiolabelled peptides: New radiopharmaceuticals for targeted therapy

    International Nuclear Information System (INIS)

    Chinol, M.

    2001-01-01

    Radiolabelled peptides have been the focus of an increasing interest by the nuclear medicine community within the last few years. This has mainly been due to successful development of one of these peptides, somatostatin, as a tool to visualise various pathologic conditions known to express a high number of somatostatin receptors. Somatostatin receptors have been identified in different tumours such as neuroendocrine tumours, tumours of the central nervous system, breast, lung and lymphatic tissue. These observations served as the biomolecular basis for the clinical use of radiolabelled somatostatin analogs, which are at present of great interest for diagnostic and therapeutic applications. A promising somatostatin analogue, DOTA-D-Phe 1 -Ty 3 -octreotide, named DOTATOC, has shown favourable biodistribution and high affinity binding to SSTR2 and SSTR5, high hydrophilicity and ease of labelling and stability with 111 In and 90 Y. A clinical trial aimed at evaluating the biodistribution and dosimetry of DOTATOC radiolabelled with 111 In, in anticipation of therapy trials with 90 Y-DOTATOC in patients was undertaken. 111 In-DOTATOC showed favourable pharmacokinetics (fast blood clearance and urinary excretion) and biodistribution, and high affinity to tumours expressing somatostatin receptors (thus, a high residence time in tumour). These results are promising for therapy trials with 90 Y-DOTAOC, for which radiation dosimetry appears acceptable for normal organs (including the red marrow). Moreover, labelling conditions of DOTATOC with 90 Y has been optimised in order to achieve labelling yields of more than 98% and specific activities of greater than 60 GBq (1.6 Ci)/μmol. (author)

  11. Radionuclide therapy of cancer with radiolabeled antibodies.

    NARCIS (Netherlands)

    Boerman, O.C.; Koppe, M.J.; Postema, E.J.; Corstens, F.H.M.; Oyen, W.J.G.

    2007-01-01

    Radioimmunotherapy (RIT) using radiolabeled monoclonal antibodies (MAbs) directed against tumor-associated antigens has evolved from an appealing concept to one of the standard treatment options for patients with non-Hodgkin's lymphoma (NHL). Inefficient localization of radiolabeled MAbs to

  12. Blood cells radiolabelling achievements, challanges, and prospects

    International Nuclear Information System (INIS)

    Weininger, Jolie; Trumper, Jacob

    1987-01-01

    A study in performed about the different ways of blood cells radiolabelling. The labelling of red blood cells (RBCs), compared with that of other blood cells, is facilitated by several factors such as a) RBCs are the most abundant of all cellular blood elements, b) they are relatively easy to separate and manipulate in vitro, c) in vitro they are less dependent on energy and nutricional requirements, d) they are easy to label due to the presence of a variety of cellular transport mechanism. 99m Tc was reconized and became as the ideal radioisotope for nuclear medicine imaging. After considerations about RBCs radiolabelling, it is presented a new in vitro technique based on the BNL kit, developed by Srivastava and co-workers. The Sorep optimized one-vial labelling method for 2 ml whole blood. In vivo and in vivo/in vitro labelling are presented too, the last method seems to combine the superior binding efficiency of in vitro labelling with the convenience of in vitro labelling. Lipophilic chelates of 111 In with oxine, acetylacetone, tropolone and mercaptopyridine N-oxide have been used successfully for labelling platelets and leukocytes. A very promising aproach is the labelling of cells with monoclonal antibodies and the developing optimized methods for in vitro labelling with various radionuclides such as 123 I, 125 I, 131 I, 111 I and 99m Tc. The advantages of the antibody technique over conventional cell labelling are shown. (M.E.L.) [es

  13. Microfluidic Radiometal Labeling Systems for Biomolecules

    Energy Technology Data Exchange (ETDEWEB)

    Reichert, D E; Kenis, P J. A.

    2011-12-29

    In a typical labeling procedure with radiometals, such as Cu-64 and Ga-68; a very large (~ 100-fold) excess of the non-radioactive reactant (precursor) is used to promote rapid and efficient incorporation of the radioisotope into the PET imaging agent. In order to achieve high specific activities, careful control of reaction conditions and extensive chromatographic purifications are required in order to separate the labeled compounds from the cold precursors. Here we propose a microfluidic approach to overcome these problems, and achieve high specific activities in a more convenient, semi-automated fashion and faster time frame. Microfluidic reactors, consisting of a network of micron-sized channels (typical dimensions in the range 10 - 300¼m), filters, separation columns, electrodes and reaction loops/chambers etched onto a solid substrate, are now emerging as an extremely useful technology for the intensification and miniaturization of chemical processes. The ability to manipulate, process and analyze reagent concentrations and reaction interfaces in both space and time within the channel network of a microreactor provides the fine level of reaction control that is desirable in PET radiochemistry practice. These factors can bring radiometal labeling, specifically the preparation of radio-labeled biomolecules such as antibodies, much closer to their theoretical maximum specific activities.

  14. Recovery of Biomolecules from Food Wastes — A Review

    Directory of Open Access Journals (Sweden)

    Antonietta Baiano

    2014-09-01

    Full Text Available Food wastes are produced by a variety of sources, ranging from agricultural operations to household consumption. About 38% occurs during food processing. At present, the European Union legislation encourages the exploitation of co-products. This valorisation can be achieved through the extraction of high-value components such as proteins, polysaccharides, fibres, flavour compounds, and phytochemicals, which can be re-used as nutritionally and pharmacologically functional ingredients. Extraction can proceed according to solid-liquid extraction, Soxhlet extraction, pressurized fluid extraction, supercritical fluid extraction, ultrasound-assisted extraction, microwave-assisted extraction, pulsed electric field extraction, and enzyme-assisted extraction. Nevertheless, these techniques cannot be used indiscriminately and their choice depends on the type of biomolecules and matrix, the scale processing (laboratory or industrial, the ratio between production costs and economic values of the compounds to be extracted. The vegetable wastes include trimmings, peelings, stems, seeds, shells, bran, residues remaining after extraction of oil, starch, sugar, and juice. The animal-derived wastes include wastes from bred animals, wastes from seafood, wastes from dairy processing. The recovered biomolecules and by-products can be used to produce functional foods or as adjuvants in food processing or in medicinal and pharmaceutical preparations. This work is an overview of the type and amounts of food wastes; food waste legislation; conventional and novel techniques suitable for extracting biomolecules; food, medicinal and pharmaceutical uses of the recovered biomolecules and by-products, and future trends in these areas.

  15. Radiolabeled antibodies for cancer imaging and therapy.

    Science.gov (United States)

    Barbet, Jacques; Bardiès, Manuel; Bourgeois, Mickael; Chatal, Jean-François; Chérel, Michel; Davodeau, François; Faivre-Chauvet, Alain; Gestin, Jean-François; Kraeber-Bodéré, Françoise

    2012-01-01

    Radiolabeled antibodies were studied first for tumor detection by single-photon imaging, but FDG PET stopped these developments. In the meantime, radiolabeled antibodies were shown to be effective in the treatment of lymphoma. Radiolabeling techniques are well established and radiolabeled antibodies are a clinical and commercial reality that deserves further studies to advance their application in earlier phase of the diseases and to test combination and adjuvant therapies including radiolabeled antibodies in hematological diseases. In solid tumors, more resistant to radiations and less accessible to large molecules such as antibodies, clinical efficacy remains limited. However, radiolabeled antibodies used in minimal or small-size metastatic disease have shown promising clinical efficacy. In the adjuvant setting, ongoing clinical trials show impressive increase in survival in otherwise unmanageable tumors. New technologies are being developed over the years: recombinant antibodies and pretargeting approaches have shown potential in increasing the therapeutic index of radiolabeled antibodies. In several cases, clinical trials have confirmed preclinical studies. Finally, new radionuclides, such as lutetium-177, with better physical properties will further improve the safety of radioimmunotherapy. Alpha particle and Auger electron emitters offer the theoretical possibility to kill isolated tumor cells and microscopic clusters of tumor cells, opening the perspective of killing the last tumor cell, which is the ultimate challenge in cancer therapy. Preliminary preclinical and preliminary clinical results confirm the feasibility of this approach.

  16. Fullerene–biomolecule conjugates and their biomedicinal applications

    Directory of Open Access Journals (Sweden)

    Yang X

    2013-12-01

    Full Text Available Xinlin Yang,1 Ali Ebrahimi,1 Jie Li,1,2 Quanjun Cui11Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA, USA; 2School of Materials Science, Beijing Institute of Technology, Beijing, People's Republic of ChinaAbstract: Fullerenes are among the strongest antioxidants and are characterized as "radical sponges." The research on biomedicinal applications of fullerenes has achieved significant progress since the landmark publication by Friedman et al in 1993. Fullerene–biomolecule conjugates have become an important area of research during the past 2 decades. By a thorough literature search, we attempt to update the information about the synthesis of different types of fullerene–biomolecule conjugates, including fullerene-containing amino acids and peptides, oligonucleotides, sugars, and esters. Moreover, we also discuss in this review recently reported data on the biological and pharmaceutical utilities of these compounds and some other fullerene derivatives of biomedical importance. While within the fullerene–biomolecule conjugates, in which fullerene may act as both an antioxidant and a carrier, specific targeting biomolecules conjugated to fullerene will undoubtedly strengthen the delivery of functional fullerenes to sites of clinical interest.Keywords: fullerene, amino acid, peptide, oligonucleotide, sugar, ester

  17. Development of radioactively labelled cancer seeking biomolecules for targeted radiotherapy. Greece

    International Nuclear Information System (INIS)

    Varvarigou, Alexandra D.; Archimandritis, Spyridon C.

    2000-01-01

    Within the framework of the above project we are studying the labelling of biomolecules, peptides and antibodies, with radionuclides emitting β - and γ radiation. More specifically, for the time being, we have investigated the labelling of peptides with Re-188 and of antibodies with Sm-153 and Re-188. The radiolabelled derivatives are further evaluated in vivo for possible application in Oncology. For these radiobiological studies we are trying to apply ectopic and orthotopic tumour animal models and to develop, in collaboration with other national and foreign institutes, proper imaging devices for small animal imaging

  18. Recent developments in monoclonal antibody radiolabeling techniques

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.; Mease, R.C.

    1989-01-01

    Monoclonal antibodies (MAbs) have shown the potential to serve as selective carriers of radionuclides to specific in vivo antigens. Accordingly, there has been an intense surge of research activity in an effort to develop and evaluate MAb-based radiopharmaceuticals for tumor imaging (radioimmunoscintigraphy) and therapy (radioimmunotherapy), as well as for diagnosing nonmalignant diseases. A number of problems have recently been identified, related to the MAbs themselves and to radiolabeling techniques, that comprise both the selectivity and the specificity of the in vivo distribution of radiolabeled MAbs. This paper will address some of these issues and primarily discuss recent developments in the techniques for radiolabeling monoclonal antibodies that may help resolve problems related to the poor in vivo stability of the radiolabel and may thus produce improved biodistribution. Even though many issues are identical with therapeutic radionuclides, the discussion will focus mainly on radioimmunoscintigraphic labels. 78 refs., 6 tabs.

  19. Recent developments in monoclonal antibody radiolabeling techniques

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Mease, R.C.

    1989-01-01

    Monoclonal antibodies (MAbs) have shown the potential to serve as selective carriers of radionuclides to specific in vivo antigens. Accordingly, there has been an intense surge of research activity in an effort to develop and evaluate MAb-based radiopharmaceuticals for tumor imaging (radioimmunoscintigraphy) and therapy (radioimmunotherapy), as well as for diagnosing nonmalignant diseases. A number of problems have recently been identified, related to the MAbs themselves and to radiolabeling techniques, that comprise both the selectivity and the specificity of the in vivo distribution of radiolabeled MAbs. This paper will address some of these issues and primarily discuss recent developments in the techniques for radiolabeling monoclonal antibodies that may help resolve problems related to the poor in vivo stability of the radiolabel and may thus produce improved biodistribution. Even though many issues are identical with therapeutic radionuclides, the discussion will focus mainly on radioimmunoscintigraphic labels. 78 refs., 6 tabs

  20. Radiolabeled monoclonal antibodies: a review

    International Nuclear Information System (INIS)

    Toledo e Souza, I.T. de; Okada, H.

    1990-05-01

    Since the description by Kohler and Milstein 1975 of their technique for producing monoclonal antibodies of predefined specificity, it has become a mainstay in most laboratories that utilize immunochemical techniques to study problems in basic, applied or clinical research. Paradoxically, the very success of monoclonal antibodies has generated a literature which is now so vast and scattered that it has become difficult to obtain a perspective. This brief review represents the distillation of many publications relating to the production and use of monoclonaal antibodies as radiopharmaceuticals. Significant advances were made possible in the last few years by combined developments in the fields of tumor-associated antigens and of monoclonal antibodies. In fact monoclonal antibodies against some well defined tumor-associated antigens, has led to significantly greater practical possibilities for producing highly specific radiolabeled antibodies as radiopharmaceuticals for diagnosis and therapy of human tumors. One of the main requirements of this methodology is the availability of stable radiopharmaceutical reagents which after labeling in vivo injection retain the capacity of specific interaction with the defined antigen and their molecular integrity. Since injection into human is the objetive of this kind of study all the specifications of radiopharmaceutical have to be fulfilled e.g. sterility, apirogenicity and absence of toxicity. (author) [pt

  1. [Radiolabeled antibodies for cancer treatment].

    Science.gov (United States)

    Barbet, Jacques; Chatal, Jean-François; Kraeber-Bodéré, Françoise

    2009-12-01

    The first treatment ever by radio-immunotherapy (RIT) was performed by William H. Beierwaltes in 1951 and was a success. Fifty years later, the main question is to find ways of extending the success of radiolabelled anti-CD20 antibodies in indolent non-Hodgkin's lymphoma to other forms of cancer. Solid tumours are much more radioresistant than lymphomas, but they respond to RIT if the lesions are small. Clinical situations of residual or minimal disease are thus the most likely to benefit from RIT in the adjuvant or consolidation settings. For disseminated disease, like leukemias or myelomas, the problem is different: beta- particles emitted by the radioactive atoms classically used for cancer treatment (iodine-131 or yttrium-90) disperse their energy in large volumes (ranges 1 mm to 1 cm) and are not very effective against isolated cells. Advances in RIT progress in two directions. One is the development of pretargeting strategies in which the antibody is not labelled but used to provide binding sites to small molecular weight radioactivity vectors (biotin, haptens). These techniques have been shown to increase tumour to non-target uptake ratios and anti-tumour efficacy has been demonstrated in the clinic. The other approach is the use of radionuclides adapted to the various clinical situations. Lutetium-177 or copper-67, because of the lower energy of their emission, their relatively long half-life and good gamma emission, may significantly improve RIT efficacy and acceptability. Beyond that, radionuclides emitting particles such as alpha particles or Auger electrons, much more efficient to kill isolated tumour cells, are being tested for RIT in the clinic. Finally, RIT should be integrated with other cancer treatment approaches in multimodality protocols. Thus RIT, now a mature technology, should enter a phase of well designed and focused clinical developments that may be expected to afford significant therapeutic advances.

  2. BSDB: the Biomolecule Stretching Database

    Science.gov (United States)

    Cieplak, Marek; Sikora, Mateusz; Sulkowska, Joanna I.; Witkowski, Bartlomiej

    2011-03-01

    Despite more than a decade of experiments on single biomolecule manipulation, mechanical properties of only several scores of proteins have been measured. A characteristic scale of the force of resistance to stretching, Fmax , has been found to range between ~ 10 and 480 pN. The Biomolecule Stretching Data Base (BSDB) described here provides information about expected values of Fmax for, currently, 17 134 proteins. The values and other characteristics of the unfolding proces, including the nature of identified mechanical clamps, are available at www://info.ifpan.edu.pl/BSDB/. They have been obtained through simulations within a structure-based model which correlates satisfactorily with the available experimental data on stretching. BSDB also lists experimental data and results of the existing all-atom simulations. The database offers a Protein-Data-Bank-wide guide to mechano-stability of proteins. Its description is provided by a forthcoming Nucleic Acids Research paper. Supported by EC FUNMOL project FP7-NMP-2007-SMALL-1, and European Regional Development Fund: Innovative Economy (POIG.01.01.02-00-008/08).

  3. Advances in infectious foci imaging using 99mTc radiolabelled antibiotics

    International Nuclear Information System (INIS)

    Seyedeh Fatemeh Mirshojaei

    2015-01-01

    Conventional methods of infection diagnosis, relying on experimental tests and culture of organisms from infected foci have continued to developing new technologies and automation. Nuclear medicine is a reliable diagnostic technique capable to detect infectious foci in human disease. A wide range of radiolabeled agents have been evaluated for demonstrating their ability to distinguish microbial infectious lesions. New researches continue to be made on the use of radiolabeled antibiotics which as well as being highly specific in the diagnosis of infection would be useful in monitoring of disease treatment. Here, the new approaches of infection scintigraphic imaging by radiolabeled antibiotics are thoroughly discussed in order to assess and compare their diagnostic value as targeting imaging radiopharmaceuticals. (author)

  4. Biomolecule-based nanomaterials and nanostructures.

    Science.gov (United States)

    Willner, Itamar; Willner, Bilha

    2010-10-13

    Biomolecule-nanoparticle (or carbon nanotube) hybrid systems provide new materials that combine the unique optical, electronic, or catalytic properties of the nanoelements with the recognition or biocatalytic functions of biomolecules. This article summarizes recent applications of biomolecule-nanoparticle (or carbon nanotubes) hybrid systems for sensing, synthesis of nanostructures, and for the fabrication of nanoscale devices. The use of metallic nanoparticles for the electrical contacting of redox enzymes with electrodes, and as catalytic labels for the development of electrochemical biosensors is discussed. Similarly, biomolecule-quantum dot hybrid systems are implemented for optical biosensing, and for monitoring intracellular metabolic processes. Also, the self-assembly of biomolecule-metal nanoparticle hybrids into nanostructures and functional nanodevices is presented. The future perspectives of the field are addressed by discussing future challenges and highlighting different potential applications.

  5. A review: radiolabeled synthesis of pesticides

    International Nuclear Information System (INIS)

    Li Juying; Han Ailiang; Wang Haiyan; Wang Wei; Ye Qingfu

    2010-01-01

    Isotope tracer technique has been widely applied in studies of metabolism, mode action, fate and environmental behavior of pesticides. In such studies, the key point is to obtain suitable radiolabelled compounds. However, the radiotracers, especially the labelled pesticides which are novel compounds with complex structures and longer synthesis routes, are usually unavailable from domestic and /or foreign markets. Therefore, it is essential to explore the synthesis methods of radiolabelled pesticides, which are quite different from the conventional nonradiosynthesis, and are requested to obtain higher yield. This article is a review on current status of choosing the available radionuclide and labelled position, the main synthesis methods and problems in the process of preparing radiolabelled pesticides. (authors)

  6. Radiolabelled RGD peptides for imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Gaertner, F.C.; Schwaiger, M.; Beer, A.J. [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany); Kessler, H. [Technische Universitaet Muenchen, Institute for Advanced Study and Center of Integrated Protein Science, Department of Chemistry, Garching (Germany); King Abdulaziz University, Chemistry Department, Faculty of Science, Jeddah (Saudi Arabia); Wester, H.-J. [Institute for Pharmaceutical Radiochemistry, Garching (Germany)

    2012-02-15

    Imaging of angiogenesis has become increasingly important with the rising use of targeted antiangiogenic therapies like bevacizumab (Avastin). Non-invasive assessment of angiogenic activity is in this respect interesting, e.g. for response assessment of such targeted antiangiogenic therapies. One promising approach of angiogenesis imaging is imaging of specific molecular markers of the angiogenic cascade like the integrin {alpha}{sub v}{beta}{sub 3}. For molecular imaging of integrin expression, the use of radiolabelled peptides is still the only approach that has been successfully translated into the clinic. In this review we will summarize the current data on imaging of {alpha}{sub v}{beta}{sub 3} expression using radiolabelled RGD peptides with a focus on tracers already in clinical use. A perspective will be presented on the future clinical use of radiolabelled RGD peptides including an outlook on potential applications for radionuclide therapy. (orig.)

  7. Gene transfer strategies for improving radiolabeled peptide imaging and therapy

    International Nuclear Information System (INIS)

    Rogers, B.E.; Buchsbaum, D.J.; Zinn, K.R.

    2000-01-01

    Utilization of molecular biology techniques offers attractive options in nuclear medicine for improving cancer imaging and therapy with radiolabeled peptides. Two of these options include utilization of phage-panning to identify novel tumor specific peptides or single chain antibodies and gene transfer techniques to increase the antibodies and gene transfer techniques to increase the number of antigen/receptor sites expressed on malignant cells. The group has focused on the latter approach for improving radiolabeled peptide imaging and therapy. The most widely used gene transfer vectors in clinical gene therapy trials include retrovirus, cationic lipids and adenovirus. It has been utilized adenovirus vectors for gene transfer because of their ability to accomplish efficient in vivo gene transfer. Adenovirus vectors encoding the genes for a variety of antigens/receptors (carcinoembryonic antigen, gastrin-releasing peptide receptor, somatostatin receptor subtype 2 (SSTr2) have all shown that their expression is increased on cancer cells both in vitro and in vivo following adenovirus infection. Of particular interest has been the adenovirus encoding for SSTr2 (AdCMVSSTr2). Various radioisotopes have been attached to somatostatin analogues for imaging and therapy of SSTr2-positive tumors both clinically and in animal models. The use of these analogues in combination with AdCMVSSTr2 is a promising approach for improving the detection sensitivity and therapeutic efficacy of these radiolabeled peptides against solid tumors. In addition, it has been proposed the use of SSTr2 as a marker for imaging the expression of another cancer therapeutic transgene (e.g. cytosine deaminase, thymidine kinase) encoded within the same vector. This would allow for non-invasive monitoring of gene delivery to tumor sites

  8. Composition and method for stabilizing radiolabelled compounds using thiocarbonylated diethylenetriamines

    International Nuclear Information System (INIS)

    Tzodikov, N.R.

    1984-01-01

    Radiolabelled compounds, such as amino acids, nucleosides, vitamins and drugs, are stabilised against radiolytic decomposition by adding a solution of a thiocarbonylated diethylenetriamine to a solution of the radiolabelled compound. (author)

  9. Detection of inflammatory lesions with radiolabelled immunoglobulins

    International Nuclear Information System (INIS)

    Blok, D.; Rijksuniversiteit Leiden; Ogtrop, M. van; Arndt, J.W.; Camps, J.A.J.; Feitsma, R.I.J.; Pauwels, E.K.J.

    1990-01-01

    Previous reports on the use of radiolabelled immunoglobulins led us to undertake a pilot experiment in an animal model to investigate the potentials sodium pertechnate Tc 99m-immunoglobulin scintigraphy in the detection of infectious foci. Mice infected in one leg with staphylococcus infection in were injected with sodium pertechnote Tc 99m-immunoglobulin, albumin aggregated technetium Tc 99m or gallium citrate Ga 67. The results obtained by scintigraphy suggested a specific accumulation of radiolabelled immunoglobulin at the site of infection. Visualization of the infection and the image quality, especially the 6- and 24-h images, were clearly enhanced after the use of immunoglobulin preparations as compared with those labelled with gallium. (orig.)

  10. Chitosan Microspheres as Radiolabeled Delivery Devices

    International Nuclear Information System (INIS)

    Permtermsin, Chalermsin; Ngamprayad, Tippanan; Phumkhem, Sudkanung; Srinuttrakul, Wannee; Kewsuwan, Prartana

    2007-08-01

    Full text: This study optimized conditions for preparing, characterizing, radiolabeled of chitosan microspheres and the biodistribution of 99mTc-Chitosan microspheres after intravenous administration. Particle size distribution of the microspheres was determined by light scattering. Zeta potential was studied by dynamic light scattering and electrophoresis technique. Biodistribution studies were performed by radiolabeling using 99mTc. The results shown that geometric mean diameter of the microspheres was found to be 77.26?1.96 ?m. Microsphere surface charge of chitosan microspheres was positive charge and zeta potential was 25.80 ? 0.46 mV. The labeling efficiency for this condition was more than 95% and under this condition was stable for at least 6 h. Radioactivity

  11. Monitoring radiolabelled antacid preparations in the stomach

    International Nuclear Information System (INIS)

    May, H.A.; Wilson, C.G.; Hardy, J.G.

    1984-01-01

    Radiolabelled antacid preparations have been monitored in the stomach using gamma scintigraphy. The stomach contents were labelled with technetium-99m and two antacid preparations with indium-113m. It has been shown that the antacid containing aluminium hydroxide and magnesium oxide mixed and emptied with the other stomach contents. An alginate containing preparation tended to float on the food and emptied only slowly from the stomach. (Auth.)

  12. Biomolecules for Removal of Heavy Metal.

    Science.gov (United States)

    Singh, Namita Ashish

    2017-01-01

    Patents reveal that heavy metals are natural constituents of the earth's crust, but some heavy metals like cadmium, lead, mercury, arsenic etc. are injurious to living organisms at higher concentration. Nowadays, anthropogenic activities have altered geochemical cycles and biochemical balance of heavy metals. Biomolecules are used nowadays for removal of heavy metals compared to other synthetic biosorbents due to their environmental friendly nature and cost effectiveness. The goal of this work is to identify the role of biomolecules like polysaccharides, polypeptides, natural compounds containing aromatic acid etc. for heavy metal removal by bio sorption. It has been observed that efficiency of biomolecules can be increased by functionalization e.g. cellulose functionalization with EDTA, chitosan with sulphur groups, alginate with carboxyl/ hydroxyl group etc. It was found that the porous structure of aerogel beads improves both sorption and kinetic properties of the material. Out of polypeptides metallothionein has been widely used for removal of heavy metal up to 88% from seawater after a single centrifugation. These cost effective functionalized biomolecules are significantly used for remediation of heavy metals by immobilizing these biomolecules onto materials. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Thermodynamic stability of biomolecules and evolution.

    Science.gov (United States)

    Chakravarty, Ashim K

    2017-08-01

    The thermodynamic stability of biomolecules in the perspective of evolution is a complex issue and needs discussion. Intra molecular bonds maintain the structure and the state of internal energy (E) of a biomolecule at "local minima". In this communication, possibility of loss in internal energy level of a biomolecule through the changes in the bonds has been discussed, that might earn more thermodynamic stability for the molecule. In the process variations in structure and functions of the molecule could occur. Thus, E of a biomolecule is likely to have energy stature for minimization. Such change in energy status is an intrinsic factor for evolving biomolecules buying more stability and generating variations in the structure and function of DNA molecules undergoing natural selection. Thus, the variations might very well contribute towards the process of evolution. A brief discussion on conserved sequence in the light of proposition in this communication has been made at the end. Extension of the idea may resolve certain standing problems in evolution, such as maintenance of conserved sequences in genome of diverse species, pre- versus post adaptive mutations, 'orthogenesis', etc. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Immobilizing Biomolecules Near the Diffraction Limit

    DEFF Research Database (Denmark)

    Skovsen, Esben; Petersen, Maria Teresa Neves; Gennaro, Ane Kold Di

    2009-01-01

    be used to print arrays of biomolecules and to immobilize biomolecules according to any specific pattern on a planar substrates with micrometer scale resolution. In this paper we show that we can immobilize proteins according to diffraction patterns of UV light. We also show that the feature size...... of the immobilized patterns can be as small as the diffraction limit for the excitation light, and that the immobilized patterns correspond to the diffraction pattern used to generate it. The flexibility of this new technology will in principle make it possible to create any pattern of biomolecules onto a substrate......, which can be generated by a UV diffraction pattern. Such patterns can have sub-micron feature sizes and could therefore be of great relevance for present and future nanotechnological applications....

  15. Reaction between protein radicals and other biomolecules

    DEFF Research Database (Denmark)

    Østdal, Henrik; Davies, Michael Jonathan; Andersen, Henrik J

    2002-01-01

    The present study investigates the reactivity of bovine serum albumin (BSA) radicals towards different biomolecules (urate, linoleic acid, and a polypeptide, poly(Glu-Ala-Tyr)). The BSA radical was formed at room temperature through a direct protein-to-protein radical transfer from H(2)O(2......)-activated immobilized horseradish peroxidase (im-HRP). Subsequently, each of the three different biomolecules was separately added to the BSA radicals, after removal of im-HRP by centrifugation. Electron spin resonance (ESR) spectroscopy showed that all three biomolecules quenched the BSA radicals....... Subsequent analysis showed a decrease in the concentration of urate upon reaction with the BSA radical, while the BSA radical in the presence of poly(Glu-Ala-Tyr) resulted in increased formation of the characteristic protein oxidation product, dityrosine. Reaction between the BSA radical and a linoleic acid...

  16. Radiolabeled colloid scintigraphy and assessment of clinical outcome in patients with alcoholic liver disease

    International Nuclear Information System (INIS)

    Bhatia, N.

    1990-01-01

    This paper evaluates the efficiency of radiolabeled colloid imaging in the determination of clinical outcome for patients with alcoholic liver disease (ALD). Tc-99m sulfur colloid or albumin colloid studies were evaluated for 74 patients referred to the nuclear medicine service for assessment of ALD or cirrhosis. Images were graded for splenic activity relative to liver on a scale of 1-5 (5 being normal), bone marrow activity on a scale of 0-3 (3 being normal), and spleen volume on a scale of 0-2 (2 being normal). A composite colloid shift index (CSI) was calculated by adding the three-individual category scores for each radiolabeled colloid study (1 being greatest colloid shift and 10 being least colloid shift). One-year survival was determined from hospital records for 55 of the 74 patients

  17. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

    Directory of Open Access Journals (Sweden)

    Ricardo Costa

    2013-01-01

    Full Text Available Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT scans, magnetic resonance imaging (MRI, and positron emission tomography (PET/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU.

  18. A printed electronic platform for the specific detection of biomolecules

    Science.gov (United States)

    Doumbia, A.; Webb, M.; Turner, M. L.; Behrendt, J. M.; Wilson, R.

    2017-08-01

    The rapid detection of disease specific biomarkers in a clinically relevant range using a low-cost sensor can facilitate the development of individual treatment plans for a given patient, known as precision, personalized or genomic medicine. In the recent decade Electrolyte-Gated Organic Field Effect Transistors (EGOFETs), a subtype of OFETs where the dielectric is replaced by an electrolyte, have attracted a great deal of attention for sensing applications. This is due to their capacity to operate at low voltage (market are not yet achieved. In this contribution, we describe the development of a stable and reproducible EGOFET sensor that is able to detect biomolecules selectively in real-time. Facile and scalable techniques are used to prepare arrays of these devices. The selectivity of individual EGOFETs is investigated by immobilization of specific ligands to the target molecule of interest on the gate electrode within a microfluidic flow cell.

  19. Radiolabeled amino acids : Basic aspects and clinical applications in oncology

    NARCIS (Netherlands)

    Jager, PL; Vaalburg, W; Pruim, J; de Vries, EGE; Langen, KJ; Piers, DA

    As the applications of metabolic imaging are expanding, radiolabeled amino acids may gain increased clinical interest, This review first describes the basic aspects of amino acid metabolism, then continues with basic aspects of radiolabeled amino acids, and finally describes clinical applications,

  20. Study on the preparation and stability of 188Re biomolecules via EHDP

    International Nuclear Information System (INIS)

    Ferro-Flores, G.; Garcia-Salinas, L.; Paredes-Gutierrez, L.; Hashimoto, K.; Melendez-Alafort, L.; Murphy, C.A.

    2001-01-01

    A direct labelling technique via ethane-1-hydroxy-1,1-diphosphonic acid (EHDP) as a weak competing ligand was developed for the preparation of several biomolecules: 188 Re-monoclonal antibody ior cea1 against carcinoembryonic antigen ( 188 Re-MoAb), biotinylated 188 Re-MoAb ( 188 Re-MoAb-biotin), 188 Re-polyclonal IgG ( 188 Re-IgG), 188 Re-peptide (somatostatine analogue peptide b-(2-naphtyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-amide), 188 Re-MoAb fragments ( 188 Re-F(ab') 2 ) and biotinylated 188 Re-F(ab') 2 ( 188 Re-F(ab') 2 -biotin). The reaction conditions such as pH, temperature, weak ligand concentration and stannous chloride concentration were optimized during the radiolabelling of each biomolecule. Before the labelling procedure, disulphide bridge groups of the biomolecules were reduced with 2-mercaptoethanol (2-ME). To obtain 188 Re labelled antibodies and peptides in high radiochemical yields (>90%) via EHDP, it was necessary to use acidic conditions and a high concentration of stannous chloride to allow the redox reaction Re +7 →Re +5 :Re +4 . The labelling of MoAb and F(ab') 2 with 188 Re via EHDP was also evaluated employing a pretargeted technique by avidin-biotin strategy in normal mice, demonstrating that the 188 Re-labelled biotinylated antibodies are stable complexes in vivo. The 188 Re-peptide complex prepared by this method, was stable for 24 h and no radiolytic degradation was observed. (author)

  1. Possible therapeutic use of radiolabeled cisplatin

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Alexandre S.; Bernardes, Felipe D.; Gonçalves, Natalia A.Z., E-mail: asleal@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    The cisplatin, cis-diamminedichloroplatinum (II), (NH{sub 3}){sub 2}PtCl{sub 2} or (CDDP) is a very common chemotherapeutical agent used in the treatment of ovary, lungs, testicle, head and neck carcinoma. It has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular cancers. However, because of the drug resistance and numerous undesirable side effects, a lot of work involving new formulations or administration of the CDDP has been done. In this work, we present a preliminary discussion about the possibilities of using the radiolabeled CDDP or CDDP⁎, as new alternative therapy. The works based on previous very positive in-vitro results of using the CDDP⁎ compared to CDDP in the cytotoxic effect of some kind of tumor cells. The preparation and characterization of the CDDP⁎ as well as the dose of CDDP⁎ required are presented and discussed. (author)

  2. Quantum dots and their interaction with biomolecules

    OpenAIRE

    Stanisavljević, Maja

    2015-01-01

    In this study CdTe QDs were synthetized via microwave irradiation method. Further they have been modified for purposes of their interaction with biomolecules using different conjugation approaches. Applied conjugation chemistries were non-specific interaction, streptavidin-biotin affinity. Glutathione modified CdTe QDs of 2 nm size were capable of non-specific interaction with major groove of DNA, while streptavidin modified CdTe QDs served as specific linker for biotinylated oligonucleotides...

  3. Preparation of 1D nanostructures using biomolecules

    Energy Technology Data Exchange (ETDEWEB)

    Pruneanu, Stela; Olenic, Liliana; Kacso, Irina [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath, 400293 Cluj-Napoca (Romania); Tudoran, Lucian Barbu [Babes-Bolyai University, Electron Microscopy Center, 1 Mihail Kogalniceanu, 400006 Cluj-Napoca (Romania); Al-Said, Said A Farha; Hassanien, Reda; Houlton, Andrew; Horrocks, Benjamin R, E-mail: stela.pruneanu@itim-cj.r [School of Chemistry, Bedson Building, Newcastle University, Newcastle upon Tyne, NE1 7RU (United Kingdom)

    2009-08-01

    In this paper we have shown that one-dimensional (1D) particle arrays can be obtained using biomolecules, like DNA or amino-acids. Nano-arrays of silver and gold were prepared in a single-step synthesis, by exploiting the binding abilities of {lambda}-DNA and L-Arginine. The morphology and optical properties of these nanostructures were investigated using AFM, TEM and UV-Vis absorption spectroscopy.

  4. Osteomyelitis diagnosis by 99mTc radiolabeled aptamers

    International Nuclear Information System (INIS)

    Santos, S.R.; Ferreira, I.M.; Andrade, A.S.R.; Barros, A.L.B.; Cardoso, V.N.; Diniz, O.F.

    2015-01-01

    Osteomyelitis, which is characterized by progressive inflammatory destruction and new opposition of bone, is still a difficult infection to treat. The clinical diagnosis in late stages is achieved easily, but an early diagnosis is more challenging. Staphylococcus aureus is a common agent found in osteomyelitis and bone prostheses infection. Diagnosis by scintigraphy has advantages because it is a non-invasive procedure and is able to perform an early diagnosis even before anatomic changes. Thus, nuclear medicine could contribute to an accurate diagnosis since specific radiopharmaceuticals were developed. In this study, aptamers selected to Staphylococcus aureus were labeled with 99m Tc and used for bacteria identification in an osteomyelitis experimental model. The aptamers selected to S. aureus were directly labelled with 99m Tc and were evaluated by biodistribution studies. Wistar rats with intraosseous infection in the right paw were used. A random aptamer labelled with 99m Tc was as control. Six animals were used in each group. The aptamers labeled with 99m Tc were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 2,23 ± 0,20, after 3 h. The control group presented a target/non-target ratio 1,08 ± 0.23. The results indicated that the radiolabeled aptamers were able to identify specifically the infection foci and they should be further explored for infection diagnosis by scintigraphy. (author)

  5. Osteomyelitis diagnosis by {sup 99m}Tc radiolabeled aptamers

    Energy Technology Data Exchange (ETDEWEB)

    Santos, S.R.; Ferreira, I.M.; Andrade, A.S.R., E-mail: sararoberta7@hotmail.com, E-mail: imendesf@yahoo.com.br, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Barros, A.L.B.; Cardoso, V.N.; Diniz, O.F., E-mail: brancodebarros@yahoo.com.br, E-mail: valbertcardoso@yahoo.com.br, E-mail: simoneodilia@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Departamento de Analises Clinicas e Toxicologicas

    2015-07-01

    Osteomyelitis, which is characterized by progressive inflammatory destruction and new opposition of bone, is still a difficult infection to treat. The clinical diagnosis in late stages is achieved easily, but an early diagnosis is more challenging. Staphylococcus aureus is a common agent found in osteomyelitis and bone prostheses infection. Diagnosis by scintigraphy has advantages because it is a non-invasive procedure and is able to perform an early diagnosis even before anatomic changes. Thus, nuclear medicine could contribute to an accurate diagnosis since specific radiopharmaceuticals were developed. In this study, aptamers selected to Staphylococcus aureus were labeled with {sup 99m}Tc and used for bacteria identification in an osteomyelitis experimental model. The aptamers selected to S. aureus were directly labelled with {sup 99m}Tc and were evaluated by biodistribution studies. Wistar rats with intraosseous infection in the right paw were used. A random aptamer labelled with {sup 99m}Tc was as control. Six animals were used in each group. The aptamers labeled with {sup 99m}Tc were able to identify the infection foci caused by S. aureus displaying a target/non-target ratio of 2,23 ± 0,20, after 3 h. The control group presented a target/non-target ratio 1,08 ± 0.23. The results indicated that the radiolabeled aptamers were able to identify specifically the infection foci and they should be further explored for infection diagnosis by scintigraphy. (author)

  6. Possibilities in improvement of the specific biodistribution by means of radiolabelled antibodies after complexation

    International Nuclear Information System (INIS)

    Heinrich, H.

    1990-01-01

    The applicability of labeled by different nuclides poly- or monoclonal antibodies in nuclear medicine diagnostics is restricted by incidental consequences. Overhigh background activities and/or high (additional) binding reactivities in the liver are troublesome. Hence we examined if the lokalizing biodistribution of labeled antibodies regarding the target organ can be improved by complexation with metal ions. The investigations were carried out with the pancreas of four Beagle dogs. Xenogenic polyclonal antibodies were refined by passing down the gammaglobulin fraction of rabbit serum a sephadex G 200 - column three times and hence radiolabeled by Na 131 I. Then the antibodies were injected i.p. either as complete molecules or as partially digested by pepsin fragments F(ab) 2 -fragments in order to avoid nonspecific Fc interactions. In preparing the i.p. injection another part of the antibody preparations both complete and fragments had been complexed with copper ions in an alkaline buffer giving a stable copper-protein-complex (Biuret-complex). Undergoing scanning and after killing the dogs the organ deposition of the radiolabel had been observed and noticed. The complexation with copper of radiolabeled antibodies improves strikingly the specific target organ uptake. Because of inflammatory and other incidental consequences the Fc-fragments should be removed by digestion with enzymes. Higher specific organ uptake should be obtainable if the poyclonal antibody fraction is more refined specifically by immunosorption with respect to its affinity to the specific antigenic structures. (orig.) [de

  7. Preparation and biodistribution of radiolabeled fullerene C60 nanocrystals

    International Nuclear Information System (INIS)

    Nikolic, Nadezda; Vranjes-Duric, Sanja; Jankovic, Drina; Dokic, Divna; Mirkovic, Marija; Bibic, Natasa; Trajkovic, Vladimir

    2009-01-01

    The present study describes for the first time a procedure for the radiolabeling of fullerene (C 60 ) nanocrystals (nanoC 60 ) with Na 125 I, as well as the biodistribution of radiolabeled nanoC 60 ( 125 I-nanoC 60 ). The solvent exchange method with tetrahydrofuran was used to make colloidal water suspensions of radiolabeled nanoC 60 particles. The radiolabeling procedure with the addition of Na 125 I to tetrahydrofuran during dissolution of C 60 gave a higher radiochemical yield of radiolabeled nanoC 60 particles in comparison to the second option, in which Na 125 I was added after C 60 was dissolved. Using photon correlation spectroscopy and transmission electron microscopy, 125 I-nanoC 60 particles were found to have a crystalline structure and a mean diameter of 200-250 nm. The 125 I-nanoC 60 had a particularly high affinity for human serum albumin, displaying 95% binding efficiency after 1 h. Biodistribution studies of 125 I-nanoC 60 in rats indicated significant differences in tissue accumulation of 125 I-nanoC 60 and the radioactive tracer Na 125 I. The higher accumulation of radiolabeled nanoC 60 was observed in liver and spleen, while accumulation in thyroid, stomach, lungs and intestines was significantly lower in comparison to Na 125 I. In addition to being useful for testing the biological distribution of nanoC 60 , the described radiolabeling procedure might have possible applications in cancer radiotherapy.

  8. System for exposing animals to radiolabeled diesel exhaust

    International Nuclear Information System (INIS)

    Lopez, J.A.; Wolf, I.; Wolff, R.K.; Sun, J.D.; Mokler, B.V.

    1981-01-01

    One approach to determining the deposition and fate of inhaled diesel particles is the conduct of inhalation exposure studies with radiolabeled diesel fuel. A system was designed, constructed and tested for the simultaneous exposure of animals to radiolabeled diesel exhaust and collection of large quantities of radiolabeled diesel exhaust particles from a single cylinder diesel engine. The system performance was characterized and evaluated over a range of operating conditions: 0 to 1800 watts of engine load, 1000 to 2500 rpm and dilution air rates of 1:2 and 1:10. The exposure system met required design and operating criteria for safety, portability, space and flexibility

  9. Bombesin and Neurotensin Receptor Targeting Using Radiolabeled Peptide Analogs

    NARCIS (Netherlands)

    M. de Visser (Monique)

    2007-01-01

    textabstractSomatostatin receptor-targeting peptides are widely used for imaging and therapy of neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumor patients with radiolabeled somatostatin analogs has resulted in symptomatic improvement, prolonged survival and

  10. The role of radiolabelled compounds in preclinical drug development

    International Nuclear Information System (INIS)

    Hawkins, D.R.

    1988-01-01

    The role of radiolabelled compounds in the development of new drugs is discussed, with particular reference to their use in toxicological, metabolic and pharmacokinetic studies for the pre-clinical safety evaluation of new drugs. (U.K.)

  11. Reaction between protein radicals and other biomolecules

    DEFF Research Database (Denmark)

    Østdal, Henrik; Davies, Michael Jonathan; Andersen, Henrik J

    2002-01-01

    The present study investigates the reactivity of bovine serum albumin (BSA) radicals towards different biomolecules (urate, linoleic acid, and a polypeptide, poly(Glu-Ala-Tyr)). The BSA radical was formed at room temperature through a direct protein-to-protein radical transfer from H(2)O(2....... Subsequent analysis showed a decrease in the concentration of urate upon reaction with the BSA radical, while the BSA radical in the presence of poly(Glu-Ala-Tyr) resulted in increased formation of the characteristic protein oxidation product, dityrosine. Reaction between the BSA radical and a linoleic acid...

  12. Porous solid ion exchange wafer for immobilizing biomolecules

    Science.gov (United States)

    Arora, Michelle B.; Hestekin, Jamie A.; Lin, YuPo J.; St. Martin, Edward J.; Snyder, Seth W.

    2007-12-11

    A porous solid ion exchange wafer having a combination of a biomolecule capture-resin and an ion-exchange resin forming a charged capture resin within said wafer. Also disclosed is a porous solid ion exchange wafer having a combination of a biomolecule capture-resin and an ion-exchange resin forming a charged capture resin within said wafer containing a biomolecule with a tag. A separate bioreactor is also disclosed incorporating the wafer described above.

  13. Radiolabeling Strategies for Tumor-Targeting Proteinaceous Drugs

    Directory of Open Access Journals (Sweden)

    Grant Sugiura

    2014-02-01

    Full Text Available Owing to their large size proteinaceous drugs offer higher operative information content compared to the small molecules that correspond to the traditional understanding of druglikeness. As a consequence these drugs allow developing patient-specific therapies that provide the means to go beyond the possibilities of current drug therapy. However, the efficacy of these strategies, in particular “personalized medicine”, depends on precise information about individual target expression rates. Molecular imaging combines non-invasive imaging methods with tools of molecular and cellular biology and thus bridges current knowledge to the clinical use. Moreover, nuclear medicine techniques provide therapeutic applications with tracers that behave like the diagnostic tracer. The advantages of radioiodination, still the most versatile radiolabeling strategy, and other labeled compounds comprising covalently attached radioisotopes are compared to the use of chelator-protein conjugates that are complexed with metallic radioisotopes. With the techniques using radioactive isotopes as a reporting unit or even the therapeutic principle, care has to be taken to avoid cleavage of the radionuclide from the protein it is linked to. The tracers used in molecular imaging require labeling techniques that provide site specific conjugation and metabolic stability. Appropriate choice of the radionuclide allows tailoring the properties of the labeled protein to the application required. Until the event of positron emission tomography the spectrum of nuclides used to visualize cellular and biochemical processes was largely restricted to iodine isotopes and 99m-technetium. Today, several nuclides such as 18-fluorine, 68-gallium and 86-yttrium have fundamentally extended the possibilities of tracer design and in turn caused the need for the development of chemical methods for their conjugation.

  14. {sup 13}C DNP of biomolecules dissolved in water

    Energy Technology Data Exchange (ETDEWEB)

    Dollmann, Bjoern C.; Gruss, Konstantin; Jagschies, Lasse; Spiess, Hans W.; Hinderberger, Dariush; Muennemann, Kerstin [Max-Planck-Institute for Polymer Research, Mainz (Germany); Schreiber, Laura M. [Section of Medical Physics, Mainz University Medical Center, Mainz (Germany)

    2010-07-01

    Nuclear magnetic resonance (NMR) and related techniques have become indispensable tools with innumerable applications in physics, chemistry, biology and medicine. One of the main obstacles in NMR is its notorious lack of sensitivity, which is due to the low equilibrium polarization of nuclear spins at ambient temperature. This disadvantage becomes obvious if low {gamma} nuclei are employed for NMR spectroscopy and MR imaging or when small sample volumes should be investigated. However, this obstacle could be overcome by in vitro hyperpolarization of molecules via dynamic nuclear polarization (DNP). One major issue of this approach is the limited lifetime of the hyperpolarized state, which restricts the application and detection of the hyperpolarized molecules to roughly three times T{sub 1}. Therefore a lot of effort is put into the hyperpolarization of biomolecules with long spin lattice relaxation times. In this work, we present direct Overhauser-type DNP enhancement of {sup 13}C in solution at ambient temperatures. For a 5 {mu} l sample of 10 M {sup 13}C-enriched urea with 40 mM TEMPOL dissolved in water we measured a {sup 13}C signal enhancement of -335 in a commercial X-band electromagnet.

  15. 123I and 13I purification for biomolecules labelling

    International Nuclear Information System (INIS)

    Catanoso, Marcela Forli

    2011-01-01

    The 123 I and 131 I are iodine radioisotopes widely used in Nuclear Medicine. The radioisotope 123 I is used in diagnosis through the SPECT technique and is routinely produced at IPEN in cyclotron through the reaction: '1 24 Xe (p, 2n) '1 23 Cs -> 123 Xe -> 123 I. The radioisotope 131 I is used both in diagnosis and therapy due to its physical characteristics of decay by β - and its γ-ray emissions that are softened with the use of specific collimators for diagnosis. It is routinely produced at IPEN using the nuclear reactor through the indirect reaction: 130 Te (n, γ) -> 131 Te -> 131 I, irradiating compounds containing Te. The radiopharmaceuticals prepared with these radioisotopes go through rigorous quality control tests and the chemical purity of the primary radioisotopes 123 I and 131 I are within the permissible limits currently defined. However, the presence of some chemical contaminants can prejudice the biomolecules labeling (monoclonal antibodies and peptides), that will produce radiopharmaceuticals of first generation to the oncology area. The aim of this work was to obtain a new purification method of these radioisotopes, allowing the labeling of biomolecules and also to established a process control on those radioisotopes. The methodology was separated on 3 steps: Evaluation of '1 23 I e 131 I radionuclidic purity using a hyper pure germanium detector, chemical purity using ICP-OES and the retention and elution study of 131 I in several absorbers to choose the most appropriate for the purification tests analyzing the behavior of the possible contaminants. The radionuclidic analyses showed the presence of Te and Co on 131 I samples and Te, Tc e Co on 123 I samples. The chemical purity analyses showed the presence of Al and Mo in 123 I, coming from the window material of the target holder and the presence of Al and Te in 131 I samples, coming from the target holder and the target, respectively. The retention and elution study selected the most

  16. Cold atmospheric plasma sterilization: from bacteria to biomolecules

    Science.gov (United States)

    Kong, Michael

    2009-10-01

    Although ionized gases have been known to have biological effects for more than 100 years, their impact on the practice in healthcare service became very significant only recently. Today, plasma-based surgical tools are used for tissue reduction and blood coagulation as surgical procedures. Most significant however is the speed at which low-temperature gas plasmas are finding new applications in medicine and biology, including plasma sterilization, wound healing, and cancer therapies just to name a few. In the terminology of biotechnology, the ``pipeline'' is long and exciting. This presentation reviews the current status of the field with a particular emphasis on plasma inactivation of microorganisms and biomolecules, for which comprehensive scientific evidence has been obtained. Some of the early speculations of biocidal plasma species are now being confirmed through a combination of optical emission spectroscopy, laser-induced fluorescence, mass spectrometry, fluid simulation and biological sensing with mutated bacteria. Similarly, fundamental studies are being performed to examine cell components targeted by gas plasmas, from membrane, through lipid and membrane proteins, to DNA. Scientific challenge is significant, as the usual complexity of plasma dynamics and plasma chemistry is compounded by the added complication that cells are live and constantly evolving. Nevertheless, the current understanding of plasma inactivation currently provides strong momentum for plasma decontamination technologies to be realized in healthcare. We will discuss the issue of protein and tissue contaminations of surgical instruments and how cold atmospheric plasmas may be used to degrade and reduce their surface load. In the context of plasma interaction with biomolecules, we will consider recent data of plasma degradation of adhesion proteins of melanoma cells. These adhesion proteins are important for cancer cell migration and spread. If low-temperature plasmas could be used to

  17. Positron Emission Tomography Imaging Using Radiolabeled Inorganic Nanomaterials

    Science.gov (United States)

    Sun, Xiaolian; Cai, Weibo; Chen, Xiaoyuan

    2015-01-01

    CONSPECTUS Positron emission tomography (PET) is a radionuclide imaging technology that plays an important role in preclinical and clinical research. With administration of a small amount of radiotracer, PET imaging can provide a noninvasive, highly sensitive, and quantitative readout of its organ/tissue targeting efficiency and pharmacokinetics. Various radiotracers have been designed to target specific molecular events. Compared with antibodies, proteins, peptides, and other biologically relevant molecules, nanoparticles represent a new frontier in molecular imaging probe design, enabling the attachment of different imaging modalities, targeting ligands, and therapeutic payloads in a single vector. We introduce the radiolabeled nanoparticle platforms that we and others have developed. Due to the fundamental differences in the various nanoparticles and radioisotopes, most radiolabeling methods are designed case-by-case. We focus on some general rules about selecting appropriate isotopes for given types of nanoparticles, as well as adjusting the labeling strategies according to specific applications. We classified these radiolabeling methods into four categories: (1) complexation reaction of radiometal ions with chelators via coordination chemistry; (2) direct bombardment of nanoparticles via hadronic projectiles; (3) synthesis of nanoparticles using a mixture of radioactive and nonradioactive precursors; (4) chelator-free postsynthetic radiolabeling. Method 1 is generally applicable to different nanomaterials as long as the surface chemistry is well-designed. However, the addition of chelators brings concerns of possible changes to the physicochemical properties of nanomaterials and detachment of the radiometal. Methods 2 and 3 have improved radiochemical stability. The applications are, however, limited by the possible damage to the nanocomponent caused by the proton beams (method 2) and harsh synthetic conditions (method 3). Method 4 is still in its infancy

  18. Pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin and biotin

    International Nuclear Information System (INIS)

    Rosebrough, S.F.

    1993-01-01

    The extraordinarily high affinity of avidin and streptavidin for biotin may be exploited in a two-step approach for delivering radiolabeled biotin derivatives suitable for imaging and therapy to target-bound streptavidin or avidin conjugated monoclonal antibodies (MAbs). The in vivo pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin (SA) and DTPA-biocytinamide (DTPA-biotin) were studied in the rabbit and dog. SA circulated in the blood similar to other 60 kDa proteins, avidin cleared immediately and DTPA-biotin exhibited plasma clearance by glomerular filtration. (author)

  19. Radiolabelled aptamers for tumour imaging and therapy

    International Nuclear Information System (INIS)

    Perkins, A.C.; Missailidis, S.

    2005-01-01

    Full text: The growth in biotechnology has led to new techniques for the design, selection and production of ligands capable of molecular recognition. One promising approach is the production of specific receptor binding molecules based on specific nucleic acid sequences that are capable of recognising a wide array of target molecules. These oligonuclide ligands are known as aptamers. The technology that allows production of aptamer molecules is known as systematic evolution of ligands by exponential enrichment (SELEX). We have used combinatorial chemistry techniques coupled with polymerase chain reaction (PCR) to rapidly select aptamers from degenerate libraries that bind with high affinity and specificity to the protein core of the MUC1 antigen, a tumour marker previously extensively used in tumour imaging and therapy. MUC1 is widely expressed by normal glandular epithelial cells, however this expression is dramatically increased when the cells become malignant. This has been well documented for breast and ovarian cancer, as well as some lung, pancreatic and prostate cancers. Recently it has also been shown that MUC1 is a valuable marker for bladder and has been used for the imaging and targeted therapy of bladder cancer. The aptamer selection process was performed on affinity chromatography matrices. After ten rounds of selection and amplification, aptamers were cloned and sequenced. Post SELEX amino modifications have been used to confer nuclease resistance and coupling potential. The aptamers bound to MUC1 antigen with a Kd of 5nm and high specificity, demonstrated by fluorescent microscopy on MUC1-expressing tumour cells. Using peptide coupling reactions, we have successfully attached chelators for Tc-99m radiolabelling. Two of the constructs tested were based on mono-aptamer chelator complexes, one with commercially available MAG3 and one with a novel designed cyclen-based chelator. The other two constructs were based on the use of multi-aptamer complexes

  20. Noncovalent Labeling of Biomolecules with Red and Near- Infrared Dyes

    Directory of Open Access Journals (Sweden)

    Lucjan Strekowski

    2004-02-01

    Full Text Available Biopolymers such as proteins and nucleic acids can be labeled with a fluorescent marker to allow for their detection. Covalent labeling is achieved by the reaction of an appropriately functionalized dye marker with a reactive group on a biomolecule. The recent trend, however, is the use of noncovalent labeling that results from strong hydrophobic and/or ionic interactions between the marker and biomolecule of interest. The main advantage of noncovalent labeling is that it affects the functional activity of the biomolecule to a lesser extent. The applications of luminescent cyanine and squarylium dyes are reviewed.

  1. Recent Trends in Bioorthogonal Click-Radiolabeling Reactions Using Fluorine-18

    Directory of Open Access Journals (Sweden)

    Doreen Pietzsch

    2013-07-01

    Full Text Available The increasing application of positron emission tomography (PET in nuclear medicine has stimulated the extensive development of a multitude of novel and versatile bioorthogonal conjugation techniques especially for the radiolabeling of biologically active high molecular weight compounds like peptides, proteins or antibodies. Taking into consideration that the introduction of fluorine-18 (t1/2 = 109.8 min proceeds under harsh conditions, radiolabeling of these biologically active molecules represents an outstanding challenge and is of enormous interest. Special attention has to be paid to the method of 18F-introduction. It should proceed in a regioselective manner under mild physiological conditions, in an acceptable time span, with high yields and high specific activities. For these reasons and due to the high number of functional groups found in these compounds, a specific labeling procedure has to be developed for every bioactive macromolecule. Bioorthogonal strategies including the Cu-assisted Huisgen cycloaddition and its copper-free click variant, both Staudinger Ligations or the tetrazine-click reaction have been successfully applied and represent valuable alternatives for the selective introduction of fluorine-18 to overcome the afore mentioned obstacles. This comprehensive review deals with the progress and illustrates the latest developments in the field of bioorthogonal labeling with the focus on the preparation of radiofluorinated building blocks and tracers for molecular imaging.

  2. Preliminary investigations on the preparation of gold nanoparticles intrinsically radiolabeled with 199Au

    International Nuclear Information System (INIS)

    Vimalnath, K.V.; Chakraborty, Sudipta; Dash, Ashutosh

    2016-01-01

    Radiolabeled nanoparticles are of great interest in the current perspective of the nuclear medicine. Water dispersible materials with nanoscale dimensions are finding role in biomedical application owing to their size. These particles can access otherwise unreachable regions in tumor mainly due to Enhanced Permeability and Retention (EPR) effect. Nanoparticles of gold (AuNPs) can bind to a wide range of biologically active molecules with functional groups that have high affinity for the gold surface. Sulfur containing compounds (e.g. thiols, disulfides), organic phosphates, amines, PEG, etc. are some of the well known surface modifiers. Functional thiolates, oligonucleotides, peptides and PEGs are introduced upon subsequent bimolecular substitution of a ligand by a functional thiol easily attached to AuNPs. Owing to its favourable decay characteristics 199 Au (T 1/2 = 3.15 d, E âmax = 474 keV, Eg 158.4 keV (36.9 %) and 208.2 keV (8.4 %)) is an attractive radionuclide for theragnostic applications. In the present work, we have carried out preliminary radiochemical investigations on the preparation of gold nanoparticles intrinsically radiolabeled with 199 Au for its potential utility as a theragnostic agent targeted delivery to the tumors

  3. Integrity of 111In-radiolabeled superparamagnetic iron oxide nanoparticles in the mouse

    International Nuclear Information System (INIS)

    Wang, Haotian; Kumar, Rajiv; Nagesha, Dattatri; Duclos, Richard I.; Sridhar, Srinivas; Gatley, Samuel J.

    2015-01-01

    Introduction: Iron-oxide nanoparticles can act as contrast agents in magnetic resonance imaging (MRI), while radiolabeling the same platform with nuclear medicine isotopes allows imaging with positron emission tomography (PET) or single-photon emission computed tomography (SPECT), modalities that offer better quantification. For successful translation of these multifunctional imaging platforms to clinical use, it is imperative to evaluate the degree to which the association between radioactive label and iron oxide core remains intact in vivo. Methods: We prepared iron oxide nanoparticles stabilized by oleic acid and phospholipids which were further radiolabeled with 59 Fe, 14 C-oleic acid, and 111 In. Results: Mouse biodistributions showed 111 In preferentially localized in reticuloendothelial organs, liver, spleen and bone. However, there were greater levels of 59 Fe than 111 In in liver and spleen, but lower levels of 14 C. Conclusions: While there is some degree of dissociation between the 111 In labeled component of the nanoparticle and the iron oxide core, there is extensive dissociation of the oleic acid component

  4. Photochemical synthesis of biomolecules under anoxic conditions

    Science.gov (United States)

    Folsome, Clair; Brittain, Andrew; Zelko, Michael

    1983-03-01

    We report the long-wavelength UV anoxic photosynthesis of uracil, various sugars (including deoxyribose and glycoaldehyde), amino acids, and other organic photoproducts. These reactions occur in mixtures of water, calcium carbonate, formaldehyde and hydrazine. Our data demonstrate that under several sets of conditions biomolecules can be formed in variety and abundance from reduced compounds (formaldehyde and hydrazine) derived from anoxic dinitrogen/carbon dioxide environments. The formaldehyde concentrations were varied from 10 mM to 0.005 mM, and the hydrazine concentrations were varied from 1 mM to 0.01 mM. The highest of these reactant concentrations were 500 and 6 times greater than those reported for earlier experiments upon the synthesis of these precursors from CO2 or N2, while the lowest of reactant concentrations employed here were 0.5 (formaldehyde) and 0.006 (hydrazine). Product yields were greatest when the hydrazine/formaldehyde ratio was 1, and when the reactant concentrations were low. These data suggest that organic products can be formed in variety from those amounts of formaldehyde and hydrazine precursors which are themselves formed under anoxic UV photochemical conditions. Hence these various reactions would seem to have prebiotic relevance. The UV 254 nm photon flux employed was 100 times higher than unattenuated solar flux. Durations of UV exposure were 24 hrs and 72 hrs. No experiments have been addressed to the possibility of UV flux dependency.

  5. Quantification of tannin content in Phyllanthus emblica using radiolabeled BSA by precipitation method

    International Nuclear Information System (INIS)

    Jyothi, K.S.; Rai, Ashitha; Rasmi, R.R.; Somashekarappa, H.M.; Shenoy, K.B.

    2013-01-01

    Phyllanthus emblica, commonly referred to as 'Indian gooseberry' or 'Amla' is used both as medicine and astonic to build up vitality and vigor. It is one of the constituent of a popular Ayurvedic formulation Triphala churna. Literature shows that there is increasing interest in exploring drugs obtained from plants with a high content of tannins. Tannins, polyphenolic compounds of various molecular weights are found abundantly in nature and have the ability to precipitate proteins. The study aims at quantification of the tannin content of Phyllanthus emblica by radiolabeled Bovine Serum Albumin (BSA) method and to study the antioxidant activity of the crude fruit extract and of the tannin precipitated with BSA from the extract. The fruit was extracted with methanol in the soxhlet apparatus. Precipitation methods like sensitive radiolabeled BSA in which tannins in the plant fruit extract complex with BSA which is quantified by gamma counter along with the reference standards like tannic and gallic acid. Other precipitation method is the radial diffusion assay in which tannin molecules migrate through agarose gel which is impregnated with the protein, BSA. The tannin-protein complex is formed in the gel which appears as a ring. The diameter of the ring is a measure of protein precipitation/binding capacity of tannins. Another method involves precipitation of tannins by polyvinyl poly pyrrolidone (PVPP) and then the total phenol in the supernatant. The difference in the total phenol and that of the supernatant gives the total amount of tannin present in the extract. Antioxidant activity of the crude fruit extract and the tannin present in the extract was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), Hydrogen peroxide scavenging assay. Results show that the total phenol content of the plant was found to be 0.135% in dry matter. The tannin content as shown by the PVPP precipitation method was 12.588 mg while that of Radiolabeled BSA method gave around 10 mg which is

  6. Current status and future developments in radiolabelled immunoassays

    International Nuclear Information System (INIS)

    Edwards, R.

    1998-01-01

    Radioisotopes are used extensively in medical practice and their use in RIA or IRMA usually represent a small proportion of the total. Radiolabelled immunoassays based on 125 I constitute a simple didactic, cost effective and robust technology which is still regarded as the reference method in many clinical applications. The IAEA has implemented many successful programmes using the ''bulk reagent'' approach, involving 68 countries in all the different regions. The main achievements have been in technology transfer with self sufficiency in production for some countries; training of large numbers of staff; quality control and quality assurance schemes; devolution of screening programmes for neonatal congenital hypothryoidism. Alternatives to the use of radioisotopic tracers are constrained by many factors and are often only available in restricted commercial packages. They are often not suitable for technology transfer programmes and often lack any didactic component in addition to a relative high cost. The production of radiolabels using 125 I is both simple and adaptable. In addition expertise in their preparation and purification is widespread even in developing countries. Together with the ease of producing antibodies, the facts have made 125 I-radiolabelled immunoassays ideal for investigative procedures for many research activities (30,31) particularly in the medical context where radioisotopes are commonly used. In conclusion, even a superficial examination of public health statistics for various countries throughout the continents indicates a need for a simple, inexpensive and robust analytical tool. In this light, there is a predicted continuing role for radiolabelled immunoassays. (author)

  7. Reducing renal uptake of radiolabeled peptides using albumin fragments.

    NARCIS (Netherlands)

    Vegt, E.; Eerd-Vismale, J.E.M. van; Eek, A.; Oyen, W.J.G.; Wetzels, J.F.M.; Jong, M. de; Russel, F.G.M.; Masereeuw, R.; Gotthardt, M.; Boerman, O.C.

    2008-01-01

    In most types of peptide receptor radionuclide therapy, the maximum activity dose that can be administered is limited by high and persistent renal retention of the radiolabeled peptides, which is, at least partly, mediated by the megalin receptor. Several agents that interfere with renal

  8. Homing of radiolabelled recombinant interleukin-2 activated natural ...

    Indian Academy of Sciences (India)

    Homing of radiolabelled recombinant interleukin-2 activated natural killer cells and their efficacy in adoptive immunotherapy against murine fibrosarcoma. Anuradha Rai Ashim ... Department of Zoology, St Joseph's College, Darjeeling 734 104, India; Centre for Life Sciences, North Bengal University, Siliguri 734 430, India ...

  9. Radioimmunodetection of human tumors with radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Douillard, J.Y.; Chatal, J.F.; Vignoud, J.; Fumoleau, P.; Le Mevel, B.P.; Saccavini, J.C.

    1985-01-01

    The present study reports the use of radiolabeled monoclonal antibodies prospectively as a diagnostic method in order to localize tumor sites in patients with a suspicion of recurrence or metastasis based on isolated elevation of serum tumor markers. Results of immunoscintigraphy are compared to data obtained with more conventional investigations including essentially ultra sonography and CT scan. (Auth.)

  10. Radiolabeled antibodies and RGD-peptides for the treatment of ovarian cancer.

    NARCIS (Netherlands)

    Janssen, M.L.H.

    2004-01-01

    In this thesis, preclinical studies on new treatment modalities for ovarian cancer are descibed, applying radiolabeled antibodies and radiolabeled RGD-peptides. In chapter 2 a study is described comparing the therapeutic efficacy of the antibody HMFG1 radiolabeled with several beta-emitting

  11. Development of Radiolabeled compounds using reactor-produced radionuclides

    International Nuclear Information System (INIS)

    Choi, Sun Ju; Park, K. B.; Park, S. H.

    2007-06-01

    To establish a robust technology for radiopharmaceutical development, we focused on the configuration of fundamental development of radiolabeled compounds for radioimmunotherapy and drug delivery as well as the development of bifunctional chelating agents and radiolabeling methods for the radiopharmaceuticals with highly specific activity to deliver sufficient number of radionuclides to the target site. In this project, we aim to improve the quality of life and the public welfare by fostering the medical application of radioisotopes for the effective treatment of malignant diseases and by developing efficient radiolabeling methods of specific bio-active materials with radioisotopes and new candidates for radiopharmaceutical application. We have established the procedure for the preparation of radiolabeled antibody and biotin with radioisotopes such as 166 Ho, 131 I, 90 Y and 111 In for tumour targeting. In the future, these technologies will be applicable to development of radioimmunotherapeutic drug. The combination treatment of radioisotope with anti-cancer agents or chemotherapeutic agents may produce a synergistic static effects in the tumour and this synergism would be exerted via gene level through the activation of a cell death pathway. The combination therapy may be very beneficial for cancer treatment and this can overcome not only the hazards of unnecessary exposure to high radiation level during therapy, but also the tendency for drug resistance caused by chemotherapy. To develop new drug delivery system suitable for CT imaging agent, a chitosan derivative and radiolabed Folate-targeted polymer with 131 I were synthesized. We also carried out the development of DTPA derivatives for CT imaging agent, radiolabeled precursor, and established a highly efficient radiolabeling methodology with lanthanide nuclide. In order to develop neuroreceptor targeting compounds, we synthesized WAY-100635 compound and 99m Tc(CO) 3 precursor from Chrysamine G derivatives

  12. Cellular content of biomolecules in sub-seafloor microbial communities

    DEFF Research Database (Denmark)

    Braun, Stefan; Morono, Yuki; Becker, Kevin W.

    2016-01-01

    Microbial biomolecules, typically from the cell envelope, can provide crucial information about distribution, activity, and adaptations of sub-seafloor microbial communities. However, when cells die these molecules can be preserved in the sediment on timescales that are likely longer than...... the lifetime of their microbial sources. Here we provide for the first time measurements of the cellular content of biomolecules in sedimentary microbial cells. We separated intact cells from sediment matrices in samples from surficial, deeply buried, organic-rich, and organic-lean marine sediments by density...... content. We find that the cellular content of biomolecules in the marine subsurface is up to four times lower than previous estimates. Our approach will facilitate and improve the use of biomolecules as proxies for microbial abundance in environmental samples and ultimately provide better global estimates...

  13. Cellular content of biomolecules in sub-seafloor microbial communities

    Science.gov (United States)

    Braun, Stefan; Morono, Yuki; Becker, Kevin W.; Hinrichs, Kai-Uwe; Kjeldsen, Kasper U.; Jørgensen, Bo B.; Lomstein, Bente Aa.

    2016-09-01

    Microbial biomolecules, typically from the cell envelope, can provide crucial information about distribution, activity, and adaptations of sub-seafloor microbial communities. However, when cells die these molecules can be preserved in the sediment on timescales that are likely longer than the lifetime of their microbial sources. Here we provide for the first time measurements of the cellular content of biomolecules in sedimentary microbial cells. We separated intact cells from sediment matrices in samples from surficial, deeply buried, organic-rich, and organic-lean marine sediments by density centrifugation. Amino acids, amino sugars, muramic acid, and intact polar lipids were analyzed in both whole sediment and cell extract, and cell separation was optimized and evaluated in terms of purity, separation efficiency, taxonomic resemblance, and compatibility to high-performance liquid chromatography and mass spectrometry for biomolecule analyses. Because cell extracts from density centrifugation still contained considerable amounts of detrital particles and non-cellular biomolecules, we further purified cells from two samples by fluorescence-activated cell sorting (FACS). Cells from these highly purified cell extracts had an average content of amino acids and lipids of 23-28 fg cell-1 and 2.3 fg cell-1, respectively, with an estimated carbon content of 19-24 fg cell-1. In the sediment, the amount of biomolecules associated with vegetative cells was up to 70-fold lower than the total biomolecule content. We find that the cellular content of biomolecules in the marine subsurface is up to four times lower than previous estimates. Our approach will facilitate and improve the use of biomolecules as proxies for microbial abundance in environmental samples and ultimately provide better global estimates of microbial biomass.

  14. An integrated platform for biomolecule interaction analysis

    Science.gov (United States)

    Jan, Chia-Ming; Tsai, Pei-I.; Chou, Shin-Ting; Lee, Shu-Sheng; Lee, Chih-Kung

    2013-02-01

    We developed a new metrology platform which can detect real-time changes in both a phase-interrogation mode and intensity mode of a SPR (surface plasmon resonance). We integrated a SPR and ellipsometer to a biosensor chip platform to create a new biomolecular interaction measurement mechanism. We adopted a conductive ITO (indium-tinoxide) film to the bio-sensor platform chip to expand the dynamic range and improve measurement accuracy. The thickness of the conductive film and the suitable voltage constants were found to enhance performance. A circularly polarized ellipsometry configuration was incorporated into the newly developed platform to measure the label-free interactions of recombinant human C-reactive protein (CRP) with immobilized biomolecule target monoclonal human CRP antibody at various concentrations. CRP was chosen as it is a cardiovascular risk biomarker and is an acute phase reactant as well as a specific prognostic indicator for inflammation. We found that the sensitivity of a phaseinterrogation SPR is predominantly dependent on the optimization of the sample incidence angle. The effect of the ITO layer effective index under DC and AC effects as well as an optimal modulation were experimentally performed and discussed. Our experimental results showed that the modulated dynamic range for phase detection was 10E-2 RIU based on a current effect and 10E-4 RIU based on a potential effect of which a 0.55 (°/RIU) measurement was found by angular-interrogation. The performance of our newly developed metrology platform was characterized to have a higher sensitivity and less dynamic range when compared to a traditional full-field measurement system.

  15. Multi-state modeling of biomolecules.

    Directory of Open Access Journals (Sweden)

    Melanie I Stefan

    2014-09-01

    Full Text Available Multi-state modeling of biomolecules refers to a series of techniques used to represent and compute the behavior of biological molecules or complexes that can adopt a large number of possible functional states. Biological signaling systems often rely on complexes of biological macromolecules that can undergo several functionally significant modifications that are mutually compatible. Thus, they can exist in a very large number of functionally different states. Modeling such multi-state systems poses two problems: the problem of how to describe and specify a multi-state system (the "specification problem" and the problem of how to use a computer to simulate the progress of the system over time (the "computation problem". To address the specification problem, modelers have in recent years moved away from explicit specification of all possible states and towards rule-based formalisms that allow for implicit model specification, including the κ-calculus, BioNetGen, the Allosteric Network Compiler, and others. To tackle the computation problem, they have turned to particle-based methods that have in many cases proved more computationally efficient than population-based methods based on ordinary differential equations, partial differential equations, or the Gillespie stochastic simulation algorithm. Given current computing technology, particle-based methods are sometimes the only possible option. Particle-based simulators fall into two further categories: nonspatial simulators, such as StochSim, DYNSTOC, RuleMonkey, and the Network-Free Stochastic Simulator (NFSim, and spatial simulators, including Meredys, SRSim, and MCell. Modelers can thus choose from a variety of tools, the best choice depending on the particular problem. Development of faster and more powerful methods is ongoing, promising the ability to simulate ever more complex signaling processes in the future.

  16. Dosimetric aspects of radiolabeled antibodies for tumor therapy

    International Nuclear Information System (INIS)

    Humm, J.L.

    1986-01-01

    Radioimmunotherapy (RIT) is rapidly attracting interest as a potential new weapon in the arsenal for cancer therapy. This article concentrates on some of the dosimetric aspects affecting the potential success of RIT, and examines factors which influence the choice of a radiolabel for RIT. No radionuclide is likely to give an optimum tumor/nontumor insult for all tumor types; therefore, the concept of matching the source to tumor morphology is introduced. Lists of candidate radionuclides are given, classified according to the type of decay, range, and energy of the emission. The article examines how the choice of radionuclide for radiolabeling the antibody affects the local energy deposition in the tumor. Both the effect of tumor size on the energy absorbed fraction and the problem of antibody binding heterogeneity are discussed. The approach to RIT is to relate the choice of radionuclide to the physical properties of the tumor. 26 references

  17. Magnetically Directed Targeting Aggregation of Radiolabelled Ferrite Nanoparticles

    Directory of Open Access Journals (Sweden)

    Yuh-Feng Wang

    2011-01-01

    Full Text Available Ferrite magnetic nanoparticles (Fe3O4 or iron (II,III oxide; 15–25 nm of diameter were developed. These magnetic nanoparticles are a potential vehicle for magnetically induced target aggregation in living animals. In this preliminary study, the radiochemical purity for the radiolabeled magnetic nanoparticles was examined, and the possibility of the magnetically induced targeting of the radio-nanoparticles was evaluated. Our results showed that radiolabeled ferrite nanoparticles can be used as magnetic targeting agents with high labeling efficiency and stability. These particles can be distributed within living animals via intravenous injection, and the biodistribution of the particles can be potentially controlled by external magnetism. These evaluations will be the groundwork for the future development of delivery techniques for radiopharmaceuticals through external magnetic control.

  18. Method for radiolabeling proteins with technetium-99m

    International Nuclear Information System (INIS)

    Crockford, D.R.; Rhodes, B.A.

    1984-01-01

    In accordance with this invention, a substrate to be radiolabeled with technetium-99m is admixed with a buffered stannous chloride composition having a pH between about 4.5 and about 8.5 wherein the stannous chloride is produced from a non-oxidized tin source, the buffered stannous chloride is purged of oxygen and the buffer comprises a mixture of alkali metal biphthalate and an alkali metal tartrate. Alternatively, the buffer may include alkali metal borate or gentisate. The stannous chloride solution is admixed with the buffer and the resultant mixture is neutralized with sodium hydroxide. The neutralized solution then is admixed with the substrate eventually to be radiolabeled with technetium-99m. This solution is allowed to incubate for several hours (usually over 15 hours) in the absence of oxygen and at room temperature

  19. Localisation and mechanism of renal retention of radiolabelled somatostatin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Barone, Raffaella [UCL, Centre of Nuclear Medicine and Laboratory of PET, Brussels (Belgium); Visser, Theo J. [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2005-10-01

    Radiolabelled somatostatin analogues, such as octreotide and octreotate, are used for tumour scintigraphy and radionuclide therapy. The kidney is the most important critical organ during such therapy owing to the reabsorption and retention of radiolabelled peptides. The aim of this study was to investigate in a rat model both the localisation and the mechanism of renal uptake after intravenous injection of radiolabelled somatostatin analogues. The multi-ligand megalin/cubilin receptor complex, responsible for reabsorption of many peptides and proteins in the kidney, is an interesting candidate for renal endocytosis of these peptide analogues. For localisation studies, ex vivo autoradiography and micro-autoradiography of rat kidneys were performed 1-24 h after injection of radiolabelled somatostatin analogues and compared with the renal anti-megalin immunohistochemical staining pattern. To confirm a role of megalin in the mechanism of renal retention of [{sup 111}In-DTPA]octreotide, the effects of three inhibitory substances were explored in rats. Renal ex vivo autoradiography showed high cortical radioactivity and lower radioactivity in the outer medulla. The distribution of cortical radioactivity was inhomogeneous. Micro-autoradiography indicated that radioactivity was only retained in the proximal tubules. The anti-megalin immunohistochemical staining pattern showed a strong similarity with the renal [{sup 111}In-DTPA]octreotide ex vivo autoradiograms. Biodistribution studies showed that co-injection of positively charged d-lysine reduced renal uptake to 60% of control. Sodium maleate reduced renal [{sup 111}In-DTPA]octreotide uptake to 15% of control. Finally, cisplatin pre-treatment of rats reduced kidney uptake to 70% of control. Renal retention of [{sup 111}In-DTPA]octreotide is confined to proximal tubules in the rat kidney, in which megalin-mediated endocytosis may play an important part. (orig.)

  20. An immunoglobulin E assay using radiolabelled Fab' and ammonium sulfate

    International Nuclear Information System (INIS)

    Wilcsek, R.J.; Hamburger, R.N.

    1978-01-01

    An immunochemical assay is described in which a radiolabelled antibody fragment, Fab', is bound specifically to immunoglobulin E (IgE), and precipitated with ammonium sulfate. The radioactivity in the precipitate is a measure of the amount of IgE in the sample. Results for six serum samples are compared using the double antibody and ammonium sulfate methods as well as the papωr radioimmunosorbent test (PRIST)

  1. Purification of radiolabeled RNA products using denaturing gel electrophoresis

    OpenAIRE

    Adachi, Hironori; Yu, Yi-Tao

    2014-01-01

    This unit discusses a basic method for purification of radiolabeled RNAs using denaturing polyacrylamide gel electrophoresis. The method consists of a number of experimental procedures, including total RNA preparation from yeast cells, isolation of a specific RNA from total yeast RNA, RNA 3' terminal labeling using nucleotide (5’[32P]pCp) addition (via ligation), denaturing (8 M urea) polyacrylamide gel electrophoresis, and RNA extraction from the gel slice. Key points for achieving good elec...

  2. Radiolabeling and targeting of lipidic nanocapsules for applications in radioimmunotherapy.

    Science.gov (United States)

    Jestin, E; Mougin-Degraef, M; Faivre-Chauvet, A; Remaud-Le Saëc, P; Hindre, F; Benoit, J P; Chatal, J F; Barbet, J; Gestin, J F

    2007-03-01

    Radioimmunotherapy is limited in some cases by the low radioactive doses delivered to tumor cells by antibodies or pretargeted haptens. In order to increase this dose, lipidic nanocapsules (LNC) with a hydrophobic core are proposed as radionuclide vectors that could be targeted to cancer cells by a bispecific anti-tumor x anti-hapten antibody after incorporation of different haptens in the nanocapsule membrane. To bind different radionuclides to the nanocapsules, several bifunctional chelating agents (BCA) were used to form stable complexes with the radionuclides. Some of them are hydrophilic for LNC shell while others are lipophilic to radiolabel the core. Poly(ethylene glycols) (PEG) were used to increase the residence time in blood. Since PEG can modify haptens recognition by the bispecific antibody and radiolabeling efficiency, haptens, BCA or Bolton-Hunter reagent (BH) were attached to the PEG extremity to optimize accessibility. Specific constructs (DSPE-PEG-haptens, DSPE-PEG-BCA, and DSPE-PEG-BH) were synthesized to develop these new radiolabeled vector formulations. Large amounts of PEG have been introduced by a postinsertion method without important change in nanocapsule size and properties. The nanocapsule core was radiolabeled with a lipophilic [(99m)Tc]SSS complex. Serum stability studies showed that this (99m)Tc-labeling method was efficient for at least 20 h. Concerning the nanocapsule surface, several methods have been performed for (111)In-labeling by using DSPE-PEG-DTPA and for (125)I-labeling with DSPE-PEG-BH. The nanocapsules labeling feasibility with a variety of radionuclides and their stability were demonstrated in this paper.

  3. Comparison of radiolabeling efficiency of peptides containing the RGD domain using the Tc-99M and I-131 radioisotopes

    Energy Technology Data Exchange (ETDEWEB)

    Sobral, Danielle V.; Cabral, Francisco Romero; Malavolta, Luciana [Santa Casa de São Paulo, SP (Brazil). Faculdade de Ciências Médicas; Durante, Ana C. Ranucci; Miranda, Ana C. Camargo; Barbosa, Marycel R. F.Figols de [Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, SP (Brazil)

    2017-07-01

    Full text: Introduction: Radiolabeled peptides have become very important in nuclear medicine and oncology in recent years mainly because they represent the molecular basis for in vivo imaging and radiopharmaceutical therapy with high specificity and affinity for over expressed receptors in tumors (Thno 2(5):481-501, 2012 / Drug Discov. Today. 7:1224-1232, 2012). In this context, peptides containing the RGD domain which possess high affinity for the αvβ3 integrin receptor have become an important tool in a wide variety tumor, including glioblastoma (Exp. Opin. Drug Deliv. 8:1041- 1056, 2011). Objective: The goal of this work was to compare the radiolabeling efficiency of the GRGDYV and GRGDHV peptides when radiolabeled with the {sup 131}I and {sup 99m}Tc radioisotopes, respectively, as well as, to evaluate the features of synthesized complexes. Methods: The GRGDYV and GRGDHV fragments were manually synthesized by peptide synthesis in solid phase accordingly to the Fmoc protocol and purified by preparative HPLC. The GRGDYV and GRGDHV peptides were radiolabeled with the I-131 and Tc-99m radioisotopes respectively, through of the direct method of radiolabeling. The radioiodination was evaluated and optimized using the methodology of Chloramine-T and for the peptide containing the histidine aminoacid the tricarbonyl method was used. Radiochemical yield analyses of [{sup 131}I]-GRGDYV and [{sup 99m}Tc]-GRGDHV peptides were performed by thin layer chromatography on silica gel TLC-SG (Al) in ACN 95%. The radiolabeled peptides were purified by using solid phase extraction (Sep-Pak C18 filter). The stability studies were realized at 2, 24, 48 and 72 hours in room temperature and refrigerate (4 deg C) for [{sup 131}I]-GRGDYV and up to 6 hours for the fragment [{sup 99m}Tc]-GRGDHV. Partition coefficient was determinate for both radiopeptides. Results: The peptides [{sup 131}I]-GRGDYV and [{sup 99m}Tc]-GRGDHV were efficiently synthesized, radiolabeled and showed

  4. Radiolabeling, biodistribution and tumor imaging of stealth liposomes containing methotrexate

    International Nuclear Information System (INIS)

    Subramanian, N; Arulsudar, N; Chuttani, K; Mishra, P; Sharma, R.K; Murthy, R.S.R

    2003-01-01

    To study the utility of sterically stabilized liposomes (stealth liposomes) in tumor scintigraphy by studying its biodistribution and accumulation in target tissue after radiolabeling with Technetium-99m (99mTC). Conventional and Stealth liposomes were prepared by lipid film hydration method using methotrexate as model anticancer drug. Radiolabeling of the liposomes was carried out by direct labeling using reduced 99mTc. Experimental conditions for maximum labeling yield were optimized. The stability studies were carried out to check binding strength of the radiolabeled complexes. The blood kinetic study was carried out in rabbits after giving the labeled complex by intravenous administration through ear vein. The biodistribution studies were carried out in the Ehrlich ascites tumor (EAT) bearing mice after intravenous administration through tail vein, showed prolonged circulation in blood and significant increase in the accumulation in tumor for the sterically stabilized liposomes compared to the conventional liposomes. The gamma scintigraphic image shows the distribution of the stealth liposomes in liver, spleen, kidney and tumor. The study gives precise idea about the use of stealth liposomes in tumor scintigraphy and organ distribution studies (Au)

  5. Constraint methods that accelerate free-energy simulations of biomolecules

    International Nuclear Information System (INIS)

    Perez, Alberto; MacCallum, Justin L.; Coutsias, Evangelos A.; Dill, Ken A.

    2015-01-01

    Atomistic molecular dynamics simulations of biomolecules are critical for generating narratives about biological mechanisms. The power of atomistic simulations is that these are physics-based methods that satisfy Boltzmann’s law, so they can be used to compute populations, dynamics, and mechanisms. But physical simulations are computationally intensive and do not scale well to the sizes of many important biomolecules. One way to speed up physical simulations is by coarse-graining the potential function. Another way is to harness structural knowledge, often by imposing spring-like restraints. But harnessing external knowledge in physical simulations is problematic because knowledge, data, or hunches have errors, noise, and combinatoric uncertainties. Here, we review recent principled methods for imposing restraints to speed up physics-based molecular simulations that promise to scale to larger biomolecules and motions

  6. Understanding small biomolecule-biomaterial interactions: a review of fundamental theoretical and experimental approaches for biomolecule interactions with inorganic surfaces.

    Science.gov (United States)

    Costa, Dominique; Garrain, Pierre-Alain; Baaden, Marc

    2013-04-01

    Interactions between biomolecules and inorganic surfaces play an important role in natural environments and in industry, including a wide variety of conditions: marine environment, ship hulls (fouling), water treatment, heat exchange, membrane separation, soils, mineral particles at the earth's surface, hospitals (hygiene), art and buildings (degradation and biocorrosion), paper industry (fouling) and more. To better control the first steps leading to adsorption of a biomolecule on an inorganic surface, it is mandatory to understand the adsorption mechanisms of biomolecules of several sizes at the atomic scale, that is, the nature of the chemical interaction between the biomolecule and the surface and the resulting biomolecule conformations once adsorbed at the surface. This remains a challenging and unsolved problem. Here, we review the state of art in experimental and theoretical approaches. We focus on metallic biomaterial surfaces such as TiO(2) and stainless steel, mentioning some remarkable results on hydroxyapatite. Experimental techniques include atomic force microscopy, surface plasmon resonance, quartz crystal microbalance, X-ray photoelectron spectroscopy, fluorescence microscopy, polarization modulation infrared reflection absorption spectroscopy, sum frequency generation and time of flight secondary ion mass spectroscopy. Theoretical models range from detailed quantum mechanical representations to classical forcefield-based approaches. Copyright © 2012 Wiley Periodicals, Inc.

  7. Radiolabeling, quality control and radiochemical purity assessment of {sup 99m}Tc-HYNIC-TOC

    Energy Technology Data Exchange (ETDEWEB)

    Melero, Laura T.U.H.; Araujo, Elaine B.; Mengatti, Jair [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    Somatostatine receptors are widely expressed by several tumors, especially of the neuroendocrine origin. In vivo images of these tumors using radiolabeled somatostatine analogues became a useful clinical tool in oncology. The aim of this work was the radiolabeling of the somatostatine analogue HYNIC-TOC with 99mTc as well as the evaluation of the radiochemical stability and quality control of labeled complex. 99mTc-HYNIC-TOC was produced by labeling conditions using 20 {mu}g of peptide, 20 mg of tricine and 10 mg of EDDA as coligands, 1110 MBq of 99mTc (99Mo-99mTc IPEN-TEC generator) and 15 {mu}g of SnCl{sub 2}.2H{sub 2}O. The reaction proceeds for 10 minutes at boiling water bath. Radiochemical purity of labeled preparation was evaluated by different chromatographic systems: ITLC-SG in methanol:ammonium acetate (1:1); TLC-SG in sodium citrate buffer 0.1 N pH 5.0 and methylethylketone, and HPLC employing column C-18, 5 {mu}m, 4.6 mm x 250 mm, UV (220 nm), radioactivity detectors, 1 mL/minute flow of acetonitrile and trifluoroacetic acid solution 0.1 %. Labeled compound has been found radiochemically stable for 5 hours and radiochemical purity was higher than 90 %. The thin layer chromatographic systems enabled the separation of radiochemical species presented in the labeled mixture as well as HPLC system. The labeling procedure studied resulted in high radiochemical yield and easy preparation. Future works include the preparation of a lyophilized reagent to make feasible the preparation of 99mTc-HYNIC-TOC at nuclear medicine services in order to study the clinical potential of the radiopharmaceutical in diagnostic and staging of neuroendocrine tumors. (author)

  8. Radiolabeling, quality control and radiochemical purity assessment of 99mTc-HYNIC-TOC

    International Nuclear Information System (INIS)

    Melero, Laura T.U.H.; Araujo, Elaine B.; Mengatti, Jair

    2009-01-01

    Somatostatine receptors are widely expressed by several tumors, especially of the neuroendocrine origin. In vivo images of these tumors using radiolabeled somatostatine analogues became a useful clinical tool in oncology. The aim of this work was the radiolabeling of the somatostatine analogue HYNIC-TOC with 99mTc as well as the evaluation of the radiochemical stability and quality control of labeled complex. 99mTc-HYNIC-TOC was produced by labeling conditions using 20 μg of peptide, 20 mg of tricine and 10 mg of EDDA as coligands, 1110 MBq of 99mTc (99Mo-99mTc IPEN-TEC generator) and 15 μg of SnCl 2 .2H 2 O. The reaction proceeds for 10 minutes at boiling water bath. Radiochemical purity of labeled preparation was evaluated by different chromatographic systems: ITLC-SG in methanol:ammonium acetate (1:1); TLC-SG in sodium citrate buffer 0.1 N pH 5.0 and methylethylketone, and HPLC employing column C-18, 5 μm, 4.6 mm x 250 mm, UV (220 nm), radioactivity detectors, 1 mL/minute flow of acetonitrile and trifluoroacetic acid solution 0.1 %. Labeled compound has been found radiochemically stable for 5 hours and radiochemical purity was higher than 90 %. The thin layer chromatographic systems enabled the separation of radiochemical species presented in the labeled mixture as well as HPLC system. The labeling procedure studied resulted in high radiochemical yield and easy preparation. Future works include the preparation of a lyophilized reagent to make feasible the preparation of 99mTc-HYNIC-TOC at nuclear medicine services in order to study the clinical potential of the radiopharmaceutical in diagnostic and staging of neuroendocrine tumors. (author)

  9. In vitro and in vivo motility studies of radiolabelled sperm cells

    International Nuclear Information System (INIS)

    Balogh, L.; Szasz, F.; Janoki, Gy.A.; Toth, L.; Zoldag, L.; Huszenicza, Gy.

    1994-01-01

    A new method for radiolabelling of sperm cells with 99m Tc HM-PAO (hexamethyl-propylene-amine-oxide) - LEUCO-SCINT kit, is investigated. The labelling technique for fresh rabbit, bull, sheep and horse as well as frozen-thawed bull sperm was optimized. The optimum conditions for sperm cell labelling (incubation volume, incubation time, initial activity of 99m Tc HM-PAO, cell number) yielded a high labelling efficiency (70-80%) and survival rate (50-60%). The labelled sperm cells were used to study their motility in vitro. The migrating at 37 o C cells incubated capillary tubes containing bovine cervical mucus. The tubes were cut and the activity of the parts measured and valued. We compared the results of living and killed sperm cells and the label alone by the change of species and running time. Ten minutes after the labelling procedures the total activity of microtubes was 2-3 times higher and the activity distribution was different from the results obtained 3 hours after the labelling. The sperm migration in vivo in the living female animals using a non invasive technique was also visualized. The sperm flow was clearly demonstrated in 3 different animal model (rabbit, ewe, hen) under gamma camera. The comparison of the in vivo migration of rabbit and bull sperm cells showed that the homologous sperm migrated faster and farther. On study of bull sperm migration in the ewe genital tract the cornu uteri was clearly visualized. In the hen model the whole genital tract was demonstrated with considerable free activity in the cavum abdominal 24 hours after the artificial insemination. The new method is developed and manufactured by NRIRR, Budapest, originally designed for radiolabelling leucocytes. The 99m Tc HM-PAO Labelled sperm cells with their retained migration properties are suitable for in vitro motility assays and in vitro migration studies in both human and veterinary medicine. (author)

  10. DPPH and oxygen free radicals as pro-oxidant of biomolecules.

    Science.gov (United States)

    Letelier, María Eugenia; Molina-Berríos, Alfredo; Cortés-Troncoso, Juan; Jara-Sandoval, José; Holst, Marianne; Palma, Karina; Montoya, Margarita; Miranda, Dante; González-Lira, Víctor

    2008-03-01

    Numerous investigations exist about the alterations that oxygen free radicals can provoke on biomolecules; these modifications can be prevented and/or reversed by different antioxidants agents. On the other hand, 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), a stable nitrogen synthetic radical, is used to evaluate the antioxidant capacity of medicinal herbal products; however, the structural changes that this radical provoke on the herbal active principles are not clear yet. In this work, we compared the redox reactivity of oxygen free radicals and DPPH radical on phospholipids and protein thiol groups present in rat liver microsomes. Cu2+/ascorbate was used as generator system of oxygen free radical and as antioxidant, an extract of Buddleja globosa's leaves. Cu2+/ascorbate provoked microsomal lipid peroxidation, microsomal thiols oxidation and oxygen consumption; all of these phenomena were inhibited by B. globosa extract. On the other hand, DPPH was bleached in different extension by the herbal extract and phosphatidyl choline; beside, DPPH decreased microsomal thiols content, but this phenomenon were not prevented by the herbal extract. Furthermore, DPPH did not induce oxygen consumption and neither modified the oxygen consumption induced by Cu2+/ascorbate. Distinct redox mechanisms may explain the differences between the reactivity of DPPH and oxygen free radicals on biomolecules, which is discussed.

  11. Radiolabeling parameters of 177Lu-DOTA-RITUXIMAB

    International Nuclear Information System (INIS)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de

    2013-01-01

    Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of 177 LuCl 3 , reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

  12. Elevated Lipoprotein(A Impairs Platelet Radiolabeling Yield

    Directory of Open Access Journals (Sweden)

    Susanne Granegger

    2015-02-01

    Full Text Available Objectives: Platelet radiolabeling in clinical routine usually results in labeling efficiencies (LE above 80%. A variety of risk factors and clinical conditions are known to impair platelet labeling yield, among them elevated triglycerides and low-density lipoproteins. The potential influence of lipoprotein(a (Lp(a, an atherogenic lipoprotein particle containing a kringle subunit, which is widely found in the proteins of fibrinolysis pathway, has never been studied. Normal Lp(a levels range below 30 mg/ dl. The exact prevalence of elevated Lp(a is unknown, most likely ranging below 10%. Even more rare is an isolated elevation despite an otherwise normal lipoprotein profile. Methods: We examined the role of isolated elevated Lp(a (> 50 mg/dl, ranging up to 440 mg/dl compared to patients with normal lipid profile. Platelets were radiolabeled with in-111-oxine at 37 °C for 5 minutes using ISORBE-consensus methodology. Results: The findings indicate that already at levels below 100 mg/dl Lp(a decreases LE. LE assessment after cross-incubation of hyper-Lp(a platelets with normal Lp(a plasma and vice versa reveals that platelets rather than the plasmatic environment are responsible for the deterioration of labeling yield. This behavior already has been reported for elevated low-density lipoproteins. Apparently, the quantitative influence of LDL and Lp(a/mg is comparable. Plotting the sum of LDL and Lp(a versus LE reveals a clear significant negative correlation. Conclusion: As extremely elevated Lp(a, particularly above 150 mg/dl, may significantly impair labeling results. We therefore recommend to include extremely elevated Lp(a into the list of parameters, which should be known before performing radiolabeling of human platelets.

  13. Radiolabeling parameters of {sup 177}Lu-DOTA-RITUXIMAB

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: adriana.avfernandes@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of {sup 177}LuCl{sub 3}, reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

  14. Synthesis of selenium nanorods with assistance of biomolecule

    Indian Academy of Sciences (India)

    Abstract. Nanorods of one-dimensional (1D) trigonal selenium (t-Se) are synthesized using biomolecule substances for five different aging times (1 h, 2 h, 3 h, 1 day and 4 days) by precipitation method. XRD analysis indicates a shift of the (1 0 1) plane towards higher diffraction angle for 1 day aging time. It is observed that ...

  15. A radiolabel release microassay for phagocytic killing of Candida albicans

    International Nuclear Information System (INIS)

    Bistoni, F.; Baccarini, M.; Blasi, E.; Marconi, P.; Puccetti, P.

    1982-01-01

    The chromium-51 release technique for quantifying intracellular killing of radiolabelled Candida albicans particles was exploited in a microassay in which murine and human phagocytes acted as effectors under peculiarly simple conditions. At appropriate effector: target ratios and with a 4 h incubation, up to 50% specific chromium release could be detected in the supernatant with no need for opsonization or lysis of phagocytes. This simple microassay permits easy-to-perform, simultaneous testing of a variety of different phagocytes even if only available in limited amounts, and provides an objective measurement of intracellular killing of Candida albicans. (Auth.)

  16. Purification of radiolabeled RNA products using denaturing gel electrophoresis.

    Science.gov (United States)

    Adachi, Hironori; Yu, Yi-Tao

    2014-01-06

    This unit discusses a basic method for purification of radiolabeled RNAs using denaturing polyacrylamide gel electrophoresis. The method consists of a number of experimental procedures, including total RNA preparation from yeast cells, isolation of a specific RNA from total yeast RNA, RNA 3'-terminal labeling using nucleotide (5' [(32) P]pCp) addition (via ligation), denaturing (8 M urea) polyacrylamide gel electrophoresis, and RNA extraction from the gel slice. Key points for achieving good electrophoretic separation of RNA are also discussed. Copyright © 2014 John Wiley & Sons, Inc.

  17. Effects of Passiflora edulis flavicarpa on the radiolabeling of blood constituents, morphology of red blood cells and on the biodistribution of sodium pertechnetate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rebello, B.M. [Programa de Pos-Graduacao em Ciencias da Saude, Universidade Federal do Rio Grande no Norte, Rio Grande do Norte (Brazil); Laboratorio de Radiofarmacia Experimental, Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro 87, Fundos, 4o andar, 20551030, Rio de Janeiro (Brazil); Moreno, S.R.F. [Laboratorio de Radiofarmacia Experimental, Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro 87, Fundos, 4o andar, 20551030, Rio de Janeiro (Brazil); Programa de Pos-Graduacao em Ciencias Medicas, Universidade Federal Fluminense, Niteroi (Brazil); Godinho, C.R.; Neves, R.F. [Programa de Pos-Graduacao em Ciencias da Saude, Universidade Federal do Rio Grande no Norte, Rio Grande do Norte (Brazil); Laboratorio de Radiofarmacia Experimental, Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro 87, Fundos, 4o andar, 20551030, Rio de Janeiro (Brazil); Fonseca, A.S. [Laboratorio de Radiofarmacia Experimental, Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro 87, Fundos, 4o andar, 20551030, Rio de Janeiro (Brazil)], E-mail: adenilso@uerj.br; Bernardo-Filho, M. [Programa de Pos-Graduacao em Ciencias da Saude, Universidade Federal do Rio Grande no Norte, Rio Grande do Norte (Brazil); Laboratorio de Radiofarmacia Experimental, Departamento de Biofisica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Avenida 28 de Setembro 87, Fundos, 4o andar, 20551030, Rio de Janeiro (Brazil); Medeiros, A.C. [Programa de Pos-Graduacao em Ciencias da Saude, Universidade Federal do Rio Grande no Norte, Rio Grande do Norte (Brazil)

    2008-12-15

    The aim of this study was to evaluate possible effects of Passiflora edulis flavicarpa (P. flavicarpa) extract on the labeling of blood constituents with {sup 99m}Tc, on the morphology of red blood cells, and on the biodistribution of sodium pertechnetate (sodium {sup 99m}Tc). Male Wistar rats were treated with either P. flavicarpa extract or 0.9% NaCl. After that, radiolabeling of blood constituents, morphological analysis of red blood cells and biodistribution of sodium {sup 99m}Tc was evaluated. Radiolabeling of blood constituents and shape of red blood cells were not modified, but a significant (p<0.05) alteration of the biodistribution of sodium {sup 99m}Tc was observed after treatment with P. flavicarpa extract. Although our results were obtained with animals, they could contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in nuclear medicine.

  18. The interplay of biomolecules and water at the origin of the active behavior of living organisms

    Science.gov (United States)

    Del Giudice, E.; Stefanini, P.; Tedeschi, A.; Vitiello, G.

    2011-12-01

    It is shown that the main component of living matter, namely liquid water, is not an ensemble of independent molecules but an ensemble of phase correlated molecules kept in tune by an electromagnetic (e.m) field trapped in the ensemble. This field and the correlated potential govern the interaction among biomolecules suspended in water and are in turn affected by the chemical interactions of molecules. In particular, the phase of the coherent fields appears to play an important role in this dynamics. Recent experiments reported by the Montagnier group seem to corroborate this theory. Some features of the dynamics of human organisms, as reported by psychotherapy, holistic medicine and Eastern traditions, are analyzed in this frame and could find a rationale in this context.

  19. The interplay of biomolecules and water at the origin of the active behavior of living organisms

    International Nuclear Information System (INIS)

    Del Giudice, E; Stefanini, P; Tedeschi, A; Vitiello, G

    2011-01-01

    It is shown that the main component of living matter, namely liquid water, is not an ensemble of independent molecules but an ensemble of phase correlated molecules kept in tune by an electromagnetic (e.m) field trapped in the ensemble. This field and the correlated potential govern the interaction among biomolecules suspended in water and are in turn affected by the chemical interactions of molecules. In particular, the phase of the coherent fields appears to play an important role in this dynamics. Recent experiments reported by the Montagnier group seem to corroborate this theory. Some features of the dynamics of human organisms, as reported by psychotherapy, holistic medicine and Eastern traditions, are analyzed in this frame and could find a rationale in this context.

  20. Molecular methods in nuclear medicine therapy

    International Nuclear Information System (INIS)

    Lee, Kyung Han

    2001-01-01

    Nuclear medicine has traditionally contributed to molecular oncology by allowing noninvasive monitoring of tumor metabolism, growth and genetic changes, thereby providing a basis for appropriate biology-based treatment planning. However, NM techniques are now being applied as an active therapeutic tool in novel molecular approaches for cancer treatment. Such areas include research on cancer therapy with radiolabeled ligands or oligonucleotides, and utilization of synergism between NM radiotherapy and gene transfer techniques. Here we will focus on novel aspects of nuclear medicine therapy

  1. Quantitative autoradiographic mapping of focal herpes simplex virus encephalitis using a radiolabeled antiviral drug

    International Nuclear Information System (INIS)

    Price, R.

    1984-01-01

    A method of mapping herpes simplex viral infection comprising administering a radiolabeled antiviral active 5-substituted 1-(2'-deoxy-2'-substituted-D-arabinofuranosyl) pyrimidine nucleoside to the infected subject, and scanning the area in which the infection is to be mapped for the radiolabel

  2. Radiolabeling polymeric micelles for in vivo evaluation : a novel, fast, and facile method

    NARCIS (Netherlands)

    Laan, A.C.; Santini, Costanza; Jennings, Laurence; de Jong, Marion; Bernsen, Monique R.; Denkova, A.G.

    2016-01-01

    Background: Single photon emission computed tomography (SPECT) is an indispensable tool in the determination of the in vivo fate of polymeric micelles. However, for this purpose, the micelles need to be radiolabeled, and almost all radiolabeling procedures published to date involve the

  3. Radiolabeling polymeric micelles for in vivo evaluation: a novel, fast, and facile method

    NARCIS (Netherlands)

    A.C. Laan (Adrianus C.); C. Santini (Costanza); L. Jennings (Laurence); M. De Jong (Marion); M.R. Bernsen (Monique); A.G. Denkova (Antonia G.)

    2016-01-01

    textabstractBackground: Single photon emission computed tomography (SPECT) is an indispensable tool in the determination of the in vivo fate of polymeric micelles. However, for this purpose, the micelles need to be radiolabeled, and almost all radiolabeling procedures published to date involve the

  4. Radiolabeling polymeric micelles for in vivo evaluation : A novel, fast, and facile method

    NARCIS (Netherlands)

    Laan, A.C.; Santini, C.; Jennings, L.; De Jong, M.; Bernsen, M.R.; Denkova, A.G.

    2016-01-01

    Background Single photon emission computed tomography (SPECT) is an indispensable tool in the determination of the in vivo fate of polymeric micelles. However, for this purpose, the micelles need to be radiolabeled, and almost all radiolabeling procedures published to date involve the conjugation of

  5. Development of 90Sr/90Y Generator Systems Based on SLM Techniques for Radiolabelling of Therapeutic Biomolecules with 90Y. Chapter 14

    International Nuclear Information System (INIS)

    Thu, N.T.; Van Dong, D.; Van Cuong, B.; Van Khoa, C.; Cam Hoa, V.T.

    2015-01-01

    Yttrium-90 is one of the most useful radionuclides for radioimmunotherapeutic applications, especially for labelling peptides and antibodies. Studies were carried out to develop a 90 Sr/ 90 Y generator system based on the SLM technique. Two stages of 90 Sr/ 90 Y generator systems were developed at different activity levels of 5, 20, 50 and 100 mCi and operated with semiautomation in sequential mode. In the first stage of the system, PC88A based SLM was used, which transported 90 Y from a nitric acid medium containing 0.01–4M HNO 3 . In the second stage, the 90 Y from the first stage was transferred to the first compartment of the second stage using carbamoylmethyl phosphine oxide (CMPO) based SLM where 1M acetic acid was used as the receiving phase for 90 Y. Quality control was carried out for the products of 90 Y using EPC with paper chromatography and Tec control chromatography. Peptides and antibodies were labelled using the 90 Y product obtained from the generator developed in house. (author)

  6. Surface Treatment of Polymeric Materials Controlling the Adhesion of Biomolecules

    Directory of Open Access Journals (Sweden)

    Willy Zorzi

    2012-08-01

    Full Text Available This review describes different strategies of surface elaboration for a better control of biomolecule adsorption. After a brief description of the fundamental interactions between surfaces and biomolecules, various routes of surface elaboration are presented dealing with the attachment of functional groups mostly thanks to plasma techniques, with the grafting to and from methods, and with the adsorption of surfactants. The grafting of stimuli-responsive polymers is also pointed out. Then, the discussion is focused on the protein adsorption phenomena showing how their interactions with solid surfaces are complex. The adsorption mechanism is proved to be dependent on the solid surface physicochemical properties as well as on the surface and conformation properties of the proteins. Different behaviors are also reported for complex multiple protein solutions.

  7. Surface Treatment of Polymeric Materials Controlling the Adhesion of Biomolecules

    Science.gov (United States)

    Poncin-Epaillard, Fabienne; Vrlinic, Tjasa; Debarnot, Dominique; Mozetic, Miran; Coudreuse, Arnaud; Legeay, Gilbert; El Moualij, Benaïssa; Zorzi, Willy

    2012-01-01

    This review describes different strategies of surface elaboration for a better control of biomolecule adsorption. After a brief description of the fundamental interactions between surfaces and biomolecules, various routes of surface elaboration are presented dealing with the attachment of functional groups mostly thanks to plasma techniques, with the grafting to and from methods, and with the adsorption of surfactants. The grafting of stimuli-responsive polymers is also pointed out. Then, the discussion is focused on the protein adsorption phenomena showing how their interactions with solid surfaces are complex. The adsorption mechanism is proved to be dependent on the solid surface physicochemical properties as well as on the surface and conformation properties of the proteins. Different behaviors are also reported for complex multiple protein solutions. PMID:24955631

  8. Models and algorithms for biomolecules and molecular networks

    CERN Document Server

    DasGupta, Bhaskar

    2016-01-01

    By providing expositions to modeling principles, theories, computational solutions, and open problems, this reference presents a full scope on relevant biological phenomena, modeling frameworks, technical challenges, and algorithms. * Up-to-date developments of structures of biomolecules, systems biology, advanced models, and algorithms * Sampling techniques for estimating evolutionary rates and generating molecular structures * Accurate computation of probability landscape of stochastic networks, solving discrete chemical master equations * End-of-chapter exercises

  9. Optical Sensors for Biomolecules Using Nanoporous Sol-Gel Materials

    Science.gov (United States)

    Fang, Jonathan; Zhou, Jing C.; Lan, Esther H.; Dunn, Bruce; Gillman, Patricia L.; Smith, Scott M.

    2004-01-01

    An important consideration for space missions to Mars is the ability to detect biosignatures. Solid-state sensing elements for optical detection of biological entities are possible using sol-gel based biologically active materials. We have used these materials as optical sensing elements in a variety of bioassays, including immunoassays and enzyme assays. By immobilizing an appropriate biomolecule in the sol-gel sensing element, we have successfully detected analytes such as amino acids and hormones. In the case of the amino acid glutamate, the enzyme glutamate dehydrogenase was the immobilized molecule, whereas in the case of the hormone cortisol, an anti-cortisol antibody was immobilized in the sensing element. In this previous work with immobilized enzymes and antibodies, excellent sensitivity and specificity were demonstrated in a variety of formats including bulk materials, thin films and fibers. We believe that the sol-gel approach is an attractive platform for bioastronautics sensing applications because of the ability to detect a wide range of entities such as amino acids, fatty acids, hopanes, porphyrins, etc. The sol-gel approach produces an optically transparent 3D silica matrix that forms around the biomolecule of interest, thus stabilizing its structure and functionality while allowing for optical detection. This encapsulation process protects the biomolecule and leads to a more "rugged" sensor. The nanoporous structure of the sol-gel matrix allows diffusion of small target molecules but keeps larger, biomolecules immobilized in the pores. We are currently developing these biologically active sol-gel materials into small portable devices for on-orbit cortisol detection

  10. Novel in Vitro Efficiency of Chitosan Biomolecule against Trichomonas gallinae

    OpenAIRE

    Tavassoli, M; Imani, A; Tajik, H; Moradi, M; Pourseyed, SH

    2012-01-01

    Background: Development of new natural agents for parasitic diseases treatment has unexpectedly increased to overcome effectively against emergence and re-emergence of parasitic diseases, the appearance of drug resistant organisms and toxic side effects of current agents. The aim of the study was to evaluate antiprotozoal activities of chitosan biomolecule on trophozoites of Trichomonas gallinae.Methods: The antitrichomonal activity of various low molecular weight chitosan concentrations incl...

  11. Immobilization of different biomolecules by atomic force microscopy

    Directory of Open Access Journals (Sweden)

    Hölzel Ralph

    2010-05-01

    Full Text Available Abstract Background Micrometer resolution placement and immobilization of probe molecules is an important step in the preparation of biochips and a wide range of lab-on-chip systems. Most known methods for such a deposition of several different substances are costly and only suitable for a limited number of probes. In this article we present a flexible procedure for simultaneous spatially controlled immobilization of functional biomolecules by molecular ink lithography. Results For the bottom-up fabrication of surface bound nanostructures a universal method is presented that allows the immobilization of different types of biomolecules with micrometer resolution. A supporting surface is biotinylated and streptavidin molecules are deposited with an AFM (atomic force microscope tip at distinct positions. Subsequent incubation with a biotinylated molecule species leads to binding only at these positions. After washing streptavidin is deposited a second time with the same AFM tip and then a second biotinylated molecule species is coupled by incubation. This procedure can be repeated several times. Here we show how to immobilize different types of biomolecules in an arbitrary arrangement whereas most common methods can deposit only one type of molecules. The presented method works on transparent as well as on opaque substrates. The spatial resolution is better than 400 nm and is limited only by the AFM's positional accuracy after repeated z-cycles since all steps are performed in situ without moving the supporting surface. The principle is demonstrated by hybridization to different immobilized DNA oligomers and was validated by fluorescence microscopy. Conclusions The immobilization of different types of biomolecules in high-density microarrays is a challenging task for biotechnology. The method presented here not only allows for the deposition of DNA at submicrometer resolution but also for proteins and other molecules of biological relevance that

  12. Transport phenomena of polar biomolecules and colloids : perspectives through simulation

    OpenAIRE

    Terämä, Emma

    2007-01-01

    The thesis focuses on the transport of polar biomolecules and colloid particles studied through atomistic and coarse-grained simulation techniques. The thesis is comprised of two themes complementing one another. First we concentrate on the structural and dynamical aspects of alcohol molecules in lipid bilayers with varying degree of unsaturation. Second, the thesis employs dielectrophoresis to elucidate the non-equilibrium transport phenomena of nano-sized colloidal particles. The former is ...

  13. Functionalization of titanium dioxide nanotubes with biomolecules for biomedical applications.

    Science.gov (United States)

    Oliveira, Weslley F; Arruda, Isabel R S; Silva, Germana M M; Machado, Giovanna; Coelho, Luana C B B; Correia, Maria T S

    2017-12-01

    Titanium (Ti) and its alloys are extensively used in the manufacture of implants because they have biocompatibility. The production of a nanostructured surface can be achieved by means of titanium dioxide nanotubes (TNTs) which can have dimensions equivalent to the nanometric components of human bone, in addition to increasing the efficiency of such implants. The search is ongoing for ways to improve the performance of these TNTs in terms of their functionalization through coating these nanotubular matrices with biomolecules. The biocompatibility of the functionalized TNTs can be improved by promoting rapid osseointegration, by preventing the adhesion of bacteria on such surfaces and/or by promoting a more sustained local release of drugs that are loaded into such TNTs. In addition to the implants, these nanotubular matrices have been used in the manufacture of high-performance biosensors capable of immobilizing principally enzymes on their surfaces, which has possible use in disease diagnosis. The objective of this review is to show the main techniques of immobilization of biomolecules in TNTs, evidencing the most recent applications of bioactive molecules that have been functionalized in the nanotubular matrices for use in implants and biosensors. This surveillance also proposes a new class of biomolecules that can be used to functionalize these nanostructured surfaces, lectins. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Applications of polymers for biomolecule immobilization in electrochemical biosensors

    International Nuclear Information System (INIS)

    Teles, F.R.R.; Fonseca, L.P.

    2008-01-01

    Polymers are becoming inseparable from biomolecule immobilization strategies and biosensor platforms. Their original role as electrical insulators has been progressively substituted by their electrical conductive abilities, which opens a new and broad scope of applications. In addition, recent advances in diagnostic chips and microfluidic systems, together with the requirements of mass-production technologies, have raised the need to replace glass by polymeric materials, which are more suitable for production through simple manufacturing processes. Conducting polymers (CPs), in particular, are especially amenable for electrochemical biosensor development for providing biomolecule immobilization and for rapid electron transfer. It is expected that the combination of known polymer substrates, but also new transducing and biocompatible interfaces, with nanobiotechnological structures, like nanoparticles, carbon nanotubes (CNTs) and nanoengineered 'smart' polymers, may generate composites with new and interesting properties, providing higher sensitivity and stability of the immobilized molecules, thus constituting the basis for new and improved analytical devices for biomedical and other applications. This review covers the state-of-the-art and main novelties about the use of polymers for immobilization of biomolecules in electrochemical biosensor platforms

  15. Radiolabelled peptides vs. nanoparticle-peptide complexes for medical applications

    International Nuclear Information System (INIS)

    Ferro F, G.

    2007-01-01

    Full text: The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been provided and the peptide-receptor radionuclide therapy for malignant tumors is a real treatment option. Targeted entry into cells is an increasingly important area of research. The diagnoses and treatment of disease by novel methods would be enhanced greatly by the efficient transport of materials to living cell nuclei. Membrane-trans locating peptides complexed to nanoparticles are small enough (30 nm) to cross the nuclear membrane and to enter the cell via receptor-mediated endocytosis, emerging as a new type of pharmaceuticals. Pharmacokinetic properties and molecular specificity of iron or gold nanoparticle-peptide complexes that do not induce biological toxicity is a topic of world interest in current and future medical investigations. Some perspectives and achievements on the preparation, pharmacokinetics and dosimetry of radiolabelled peptides versus nanoparticle-peptide complexes for medical applications are presented. (Author)

  16. Utilisation of radiolabeled antibiotic for the diagnosis of infectious foci

    International Nuclear Information System (INIS)

    Khammassi, Sabrine; Gharbi, Sabrine

    2009-01-01

    Nuclear imaging is a non-invasive exploration technique, used for rapid diagnostic of infectious disease .Thus, for osteoarticular infection scintigraphic techniques were proposed to ameliorate the diagnostic sensibility and the use of radiolabeled antibiotics as imaging agents of infectious loci become more and more recognized. In this work, a new sulfanil amid derivative, the N sulfanilamide-ferrocene-carboxamide was chemically synthesized then labeled with technetium-99m, with a radiochemical yield, 87 pour cent. In in-vitro studies were done with E.coli. first , the up-take of labeled molecule was estimated as 40 pour cent. Then, the bacteriostatic al effect of the molecule was de terminated by considering the Optical Density at 600 nm. The obtained results, encourage us to do more, with biodistribution on normal and infected mice; with Staphylococcus aureus. Then to carry out scintigraphic imaging with gamma camera to check out the potentiality of the molecule as an infectious imaging agent. (Author)

  17. Radioimmunoimaging of experimental gliomas using radiolabelled monoclonal antibodies

    International Nuclear Information System (INIS)

    Glaessner, H.

    1986-01-01

    The biodistribution and tumour uptake of radiolabelled (131 I) glioma-seeking monoclonal antibodies (14 AC1) and their F(ab') 2 fragments were investigated in nude mice having received glioma transplants. Radioimmunoimaging by external scintigraphy at 48 and 96 hours pointed to a superior tumour localisation by the fragments that was clearly related to the dose. Wholebody determinations of the biokinetic behaviour led to the following results: Faster clearance anc more ready elimination from the blood pool for the fragments, preferential uptake in the tumour; intact antibodies; binding in the liver, spleen and lungs. The study confirmed the value of fragments of monoclonal antibodies in the diagnosis of tumours and pointed to the possibility of using intact monoclonal antibodies as carriers of radioisotopes and cytotoxic drugs within the scope of therapeutic programmes. (TRV) [de

  18. Therapy with radiolabelled somatostatin analogs in neuroendocrine tumors

    International Nuclear Information System (INIS)

    Kunikowska, J.; Krolicki, L.

    2007-01-01

    In the 80's the discovery of somatostatin receptors expression on NET cells enabled the application of somatostatin analogues in diagnosis and therapy. Initially, 'cold' somatostatin analogs were used for therapeutical purpose, with overall good clinical response, but with minimal anti-proliferation effect. Furthermore, radiolabelled receptor-binding peptides have been shown to be an important class of radiopharmaceuticals for tumor diagnosis and therapy with minimal side-effects. Specific binding between receptor on tumor cell and peptide with beta emitting radionuclide act not only on tumor related symptoms but also on tumor cell via radiotoxic effect of beta radiation. Discoveries of next receptor combinations, allow the work over synthesis and applications of next receptors' analogs both in diagnosis and in therapy. Due to complex characteristics of NET's, the use therapeutic 'cocktail' containing the variety analogs may be of great importance. (author)

  19. Radiolabeled peptides in the diagnosis and therapy of oncological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Weiner, Ronald E. E-mail: weiner@adp.uchc.edu; Thakur, Mathew L

    2002-11-01

    There has been an exponential growth in the development of radiolabeled peptides for diagnostic and therapeutic applications in oncology. Peptides have fast clearance, rapid tissue penetration, low antigenicity and can be produced easily and inexpensively. However, peptides have problems with in vivo catabolism, unwanted physiological effects, and chelate attachment. The approved {sup 111}In-DTPA-OctreoScan, a somatostatin receptor binder, is well established for diagnosis of neuroendocrine tumors. NeoTect, an approved, {sup 99m}Tc-labeled, somatostatin-receptor-binding analogue has good specificity for lung cancer detection. The receptors for Vasoactive Intestinal Peptide, Cholecystokinin-B/gastrin, Bombesin, Epidermal Growth Factor, and Alpha Melanocyte Stimulating Hormone and the Integrin, {alpha}{sub v}{beta}{sub 3}, are under active investigation as targets. Octreotide and its analogues labeled with {sup 111}In, {sup 90}Y, {sup 64}Cu or {sup 177}Lu are under study for the treatment of patients with promising results.

  20. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann

    This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete...... as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent‐like copolymers......‐life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A glycerolipid and a cholesteryl ether were synthesized with free primary alcohols and a series of their sulphonates (Ms, Ts, Tf) were...

  1. Development of Novel Radio-labeled Materials using Research Reactor

    International Nuclear Information System (INIS)

    Choi, Sun Ju; Hong, Y. D.; Choi, K. H.

    2010-04-01

    In this project, we aim to develop the novel radiomaterials using reactor-produced radioisotope for the targeted therapy of cancer. At initial stage, we have examined the effect of beta particle-emission radionuclides on the proliferation of various types of tumor cells and found that beta particle emission radionuclides significantly inhibited the proliferation of tumor cells. We have synthesized new bifunctional chelating agents (BFCAs) for bio-conjugation with bio-active molecules, such as peptide and antibody, and radioabeling with radionuclide. For targeted radiotherapy, we have prepared target materials and radiolabeled with various radionuclides using BFCAs and obtained candidate materials for the treatment of melanoma. We have next treated melanoma-induced animals with candidate radiopharmaceuticals. The tumor growth was significantly reduced by treatment with candidates, and survival rate of the animals was prolonged, suggesting that candidate radiopharmaceuticals are promising agents for the treatment of melanoma

  2. Aspects of monitoring and quality assurance for radiolabeled antibodies

    International Nuclear Information System (INIS)

    Barber, D.E.

    1992-06-01

    This report provides an informational resource and guide for the US Nuclear Regulatory Commission (NRC) and NRC licensees who produce or use radiolabeled antibodies (RABs). Components of quality assurance programs related to the production and use of RABs are reviewed and evaluated, and recommendations are made on dosage calibrations, exposure control, monitoring, and personnel requirements. Special emphasis is placed on dose calibrators because these instruments are used extensively to measure the dosage of radiopharmaceuticals to be administered to patients. The difficulties of using dose calibrators to quantify dosages of beta- and alpha-emitters are discussed. The advantages and disadvantages of using other instruments are examined, and recommendations are made on the types of instruments to be used for different applications. 46 refs., 8 tabs

  3. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia], e-mail: samanta@usp.br, e-mail: nnascime@ipen.br; Andrade Junior, Heitor F. de [Instituto de Medicina Tropical de Sao Paulo (IMTSP), Sao Paulo, SP (Brazil)], e-mail: hfandrad@usp.br; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia], e-mail: jaosso@ipen.br

    2009-07-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, {sup 122}Sb and {sup 124}Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  4. Development of radioactively labelled cancer seeking biomolecules for targeted therapy

    International Nuclear Information System (INIS)

    Pillai, M.R.A.

    2000-01-01

    The work done towards the development of bifunctional chelating agents, modified peptide and their radiolabelling studies with 90 Y and 188 Re are reported. Bifunctional chelating agents DOTA, TETA and DAHPES were synthesised. DOTA-Lanreotide (Mauritius) was synthesised from lanreotide. 90 Y and 188 Re used in the studies were obtained from 90 Sr- 90 Y and 188 W- 188 Re generators. Complexation studies of DOTA and Mauritius with 90 Y and that of DAHPES and EC with 188 Re were carried out. Cell labelling of 90 Y-DOTA-Lanreotide with a cell line expressing somatostatin receptors was also carried out

  5. SSTR-Mediated Imaging in Breast Cancer: Is There a Role for Radiolabeled Somatostatin Receptor Antagonists?

    Science.gov (United States)

    Dalm, Simone U; Haeck, Joost; Doeswijk, Gabriela N; de Blois, Erik; de Jong, Marion; van Deurzen, Carolien H M

    2017-10-01

    Recent studies have shown enhanced tumor targeting by novel somatostatin receptor (SSTR) antagonists compared with clinically widely used agonists. However, these results have been obtained mostly in neuroendocrine tumors, and only limited data are available for cancer types with lower SSTR expression, including breast cancer (BC). To date, two studies have reported higher binding of the antagonist than the agonist in BC, but in both studies only a limited number of cases were evaluated. In this preclinical study, we further investigated whether the application of an SSTR antagonist can improve SSTR-mediated BC imaging in a large panel of BC specimens. We also generated an in vivo BC mouse model and performed SPECT/MRI and biodistribution studies. Methods: Binding of 111 In-DOTA-Tyr 3 -octreotate (SSTR agonist) and 111 In-DOTA-JR11 (SSTR antagonist) to 40 human BC specimens was compared using in vitro autoradiography. SSTR2 immunostaining was performed to confirm SSTR2 expression of the tumor cells. Furthermore, binding of the radiolabeled SSTR agonist and antagonist was analyzed in tissue material from 6 patient-derived xenografts. One patient-derived xenograft, the estrogen receptor-positive model T126, was chosen to generate in vivo mouse models containing orthotopic breast tumors for in vivo SPECT/MRI and biodistribution studies after injection with 177 Lu-DOTA-Tyr 3 -octreotate or 177 Lu-DOTA-JR11. Results: 111 In-DOTA-JR11 binding to human BC tissue was significantly higher than 111 In-DOTA-Tyr 3 -octreotate binding ( P immunostaining confirmed SSTR2 expression on the tumor cells. SPECT/MRI of the mouse model found better tumor visualization with the antagonist. This result was in line with the significantly higher tumor uptake of the radiolabeled antagonist than of the agonist as measured in biodistribution studies 285 min after radiotracer injection (percentage injected dose per gram of tissue: 1.92 ± 0.43 vs. 0.90 ± 0.17; P = 0.002). Conclusion: SSTR

  6. Preparation of crotalus venom radiolabeled with technetium{sup 99m} as a tool for biodistribution study

    Energy Technology Data Exchange (ETDEWEB)

    Pujatti, Priscilla Brunelli; Santos, Raquel Gouvea dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN), Belo Horizonte, MG (Brazil)]. E-mail: santosr@cdtn.br; Simal, Carlos Jorge Rodrigues [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Faculdade de Medicina

    2005-10-15

    Technetium-{sup 99m} ({sup 99m} Tc) has been the radionuclide of choice for nuclear medicine procedures and experimental research. Because of its optimal nuclear properties, {sup 99m} Tc is suitable for high efficiency detection with the advantage of reduced radiological waste. Crotalus venom (CV) has been shown to reduce tumors in clinical studies and tissue distribution studies are very important for clinical use. The goal of this work was to obtain CV labeled with {sup 99m} Tc which preserves its biological activity. After labeling, biological activity was assessed by hemolytic activity evaluation. Labeled and crude venom caused indirect hemolysis provided that the incubation medium contained an exogenous source of lecithin. High yield radiolabeled-CV was obtained and biological activity was preserved. The results suggest that {sup 99m} Tc-CV can be a useful tool for biodistribution studies. (author)

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

    International Nuclear Information System (INIS)

    Costa, Renata Ferreira

    2012-01-01

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

  8. Preparation and radiolabeling of human serum albumin (HSA)-coated magnetite nanoparticles for magnetically targeted therapy.

    Science.gov (United States)

    Chunfu, Zhang; Jinquan, Cao; Duanzhi, Yin; Yongxian, Wang; Yanlin, Feng; Jiajü, Tan

    2004-12-01

    In this paper, we describe the preparation of human serum albumin-coated magnetic particles of about 200 nm in diameter with narrow size distribution radiolabeled with 188Re for the purpose of magnetically targeted therapy. The optimum radiolabeling conditions are: SnCl2 x 2H2O 8 mg/ml, citric acid 20 mg/ml, vitamin C 8 mg/ml, labeling volume 500 microl and a reaction time of 3 h. The stability of the radiolabeled particles is suitable for in vivo study.

  9. The Importance of Phytoplankton Biomolecule Availability for Secondary Production

    Directory of Open Access Journals (Sweden)

    Elina T. Peltomaa

    2017-10-01

    Full Text Available The growth and reproduction of animals is affected by their access to resources. In aquatic ecosystems, the availability of essential biomolecules for filter-feeding zooplankton depends greatly on phytoplankton. Here, we analyzed the biochemical composition, i.e., the fatty acid, sterol and amino acid profiles and concentrations as well as protein, carbon, nitrogen, and phosphorus content of 17 phytoplankton monocultures representing the seven most abundant phytoplankton classes in boreal and sub-arctic lakes. To examine how the differences in the biochemical composition between phytoplankton classes affect their nutritional quality for consumers, we assessed the performance of Daphnia, on these diets. Furthermore, we defined the most important biomolecules regulating the somatic growth and reproduction of Daphnia, expecting that higher concentrations of certain biomolecules are needed for reproduction than for growth. Finally, we combined these results with phytoplankton field data from over 900 boreal and sub-arctic lakes in order to estimate whether the somatic growth of Daphnia is sterol-limited when the natural phytoplankton communities are cyanobacteria-dominated. Our analysis shows that Daphnia grows best with phytoplankton rich in sterols, ω-3 fatty acids, protein, and amino acids. Their reproduction follows food sterol and ω-3 concentration as well as C:P-ratio being two times higher in Daphnia feeding on cryptophytes than any other diet. Interestingly, we found that a high dietary ω-6 fatty acid concentration decreases both somatic growth and reproduction of Daphnia. When combined with phytoplankton community composition field data, our results indicate that zooplankton is constantly limited by sterols in lakes dominated by cyanobacteria (≥40% of total phytoplankton biomass, and that the absence of cryptophytes can severely hinder zooplankton production in nature.

  10. Low-energy electron scattering from molecules, biomolecules and surfaces

    CERN Document Server

    Carsky, Petr

    2011-01-01

    Since the turn of the 21st century, the field of electron molecule collisions has undergone a renaissance. The importance of such collisions in applications from radiation chemistry to astrochemistry has flowered, and their role in industrial processes such as plasma technology and lighting are vital to the advancement of next generation devices. Furthermore, the development of the scanning tunneling microscope highlights the role of such collisions in the condensed phase, in surface processing, and in the development of nanotechnology.Low-Energy Electron Scattering from Molecules, Biomolecule

  11. Simple approach to study biomolecule adsorption in polymeric microfluidic channels

    Energy Technology Data Exchange (ETDEWEB)

    Gubala, Vladimir, E-mail: V.Gubala@kent.ac.uk [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland); Medway School of Pharmacy, University of Kent, Central Avenue, Anson 120, Chatham Maritime, Kent ME4 4TB (United Kingdom); Siegrist, Jonathan; Monaghan, Ruairi; O' Reilly, Brian; Gandhiraman, Ram Prasad [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland); Daniels, Stephen [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland); National Centre for Plasma Science and Technology (NCPST), Dublin City University, Dublin 9 (Ireland); Williams, David E. [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland); MacDiarmid Institute for Advanced Materials and Nanotechnology, School of Chemical Sciences, University of Auckland, Auckland 1142 (New Zealand); Ducree, Jens [Biomedical Diagnostics Institute (BDI), National Centre for Sensor Research (NCSR), Dublin City University, Dublin 9 (Ireland)

    2013-01-14

    Highlights: Black-Right-Pointing-Pointer A simple tool to assess biomolecule adsorption onto the surfaces of microchannels. Black-Right-Pointing-Pointer Development for dilution by surface-adsorption based depletion of protein samples. Black-Right-Pointing-Pointer It can easily be done using a readily available apparatus like a spin-coater. Black-Right-Pointing-Pointer The assessment tool is facile and quantitative. Black-Right-Pointing-Pointer Straightforward comparison of different surface chemistries. - Abstract: Herein a simple analytical method is presented for the characterization of biomolecule adsorption on cyclo olefin polymer (COP, trade name: Zeonor{sup Registered-Sign }) substrates which are widely used in microfluidic lab-on-a-chip devices. These Zeonor{sup Registered-Sign} substrates do not possess native functional groups for specific reactions with biomolecules. Therefore, depending on the application, such substrates must be functionalized by surface chemistry methods to either enhance or suppress biomolecular adsorption. This work demonstrates a microfluidic method for evaluating the adsorption of antibodies and oligonucleotides surfaces. The method uses centrifugal microfluidic flow-through chips and can easily be implemented using common equipment such as a spin coater. The working principle is very simple. The user adds 40 L of the solution containing the sample to the starting side of a microfluidic channel, where it is moved through by centrifugal force. Some molecules are adsorbed in the channel. The sample is then collected at the other end in a small reservoir and the biomolecule concentration is measured. As a pilot application, we characterized the adsorption of goat anti-human IgG and a 20-mer DNA on Zeonor{sup Registered-Sign }, and on three types of functionalized Zeonor: 3-aminopropyltriethoxysilane (APTES) modified surface with mainly positive charge, negatively charged surface with immobilized bovine serum albumin (BSA), and

  12. Medicinal plants: production and biochemical characterization

    International Nuclear Information System (INIS)

    Chunzhao Liu; Zobayed, S.M.A; Murch, S.J.; Saxena, P.K.

    2002-01-01

    Recent advances in the area of biotechnology offer some possibility for the development of new technologies for the conservation, characterization and mass production of medicinal plant species, (i.e. in vitro cell culture techniques for the mass production of sterile, consistent, standardized medicinal plant materials). This paper discussed the following subjects - plant tissue culture, de novo shoot organogenesis, de novo root organogenesis, somatic embryogenesis, large scale propagation in bioreactors and discovery of unique biomolecules

  13. An Efficient and Straightforward Method for Radiolabeling of Nanoparticles with {sup 64}Cu via Click Chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong-Eun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Kim, Kwangmeyung [Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 136-791 (Korea, Republic of); Park, Sang Hyun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Department of Radiobiotechnology and Applied Radioisotope Science, Korea University of Science and Technology, Deajeon 305-350 (Korea, Republic of)

    2015-07-01

    Recently, nanoparticles have received a great deal of interest in diagnosis and therapy applications. Since nanoparticles possess intrinsic features that are often required for a drug delivery system and diagnosis, they have potential to be used as platforms for integrating imaging and therapeutic functions, simultaneously. Intrinsic issues that are associated with theranostic nanoparticles, particularly in cancer treatment, include an efficient and straightforward radiolabeling method for understanding the in vivo biodistribution of nanoparticles to reach the tumor region, and monitoring therapeutic responses. Herein, we investigated a facile and highly efficient strategy to prepare radiolabeled nanoparticles with {sup 64}Cu via a strain-promoted azide, i.e., an alkyne cycloaddition strategy, which is often referred to as click chemistry. First, the azide (N3) group, which allows for the preparation of radiolabeled nanoparticles by copper-free click chemistry, was incorporated into glycol chitosan nanoparticles (CNPs). Second, the strained cyclooctyne derivative, dibenzyl cyclooctyne (DBCO) conjugated with a 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (DOTA) chelator, was synthesized for preparing the pre-radiolabeled alkyne complex with {sup 64}Cu radionuclide. Following incubation with the {sup 64}Cu-radiolabeled DBCO complex (DBCO-PEG4-Lys-DOTA-{sup 64}Cu with high specific activity, 18.5 GBq/μ mol), the azide-functionalized CNPs were radiolabeled successfully with {sup 64}Cu, with a high radiolabeling efficiency and a high radiolabeling yield (>98%). Importantly, the radiolabeling of CNPs by copper-free click chemistry was accomplished within 30 min, with great efficiency in aqueous conditions. After {sup 64}Cu-CNPs were intravenously administered to tumor-bearing mice, the real time, in vivo biodistribution and tumor-targeting ability of {sup 64}Cu-CNPs were quantitatively evaluated by micro-PET images of tumor-bearing mice. These results

  14. Regional blood volume in man determined by radiolabelled erythrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Vissing, S.F.; Nielsen, S.L.

    1988-06-01

    The purpose of the present study was to develop a non-invasive method capable of measuring the regional blood volume in the peripheral circulation. External counting of autologous radiolabelled erythrocytes was performed by dynamic scintigraphy of the calf. During short venous stasis, synchronous changes in segmental blood volumes were recorded by plethysmography, thereby obtaining a calibration factor. The recordings were performed with the position of the calf varying between elevated, horizontal and lowered before and after 4.5 min venous stasis with a tourniquet pressure of 57 mmHg applied above the knee. The mean blood volume comprised 3.2 (1.2) ml per 100 ml tissue in the elevated position, 6.0 (1.6) in the horizontal position and 9.8 (2.6) in the lowered position. Correspondingly, the blood volume increase during venous stasis was 120%, 60% and 20% in the three positions. Studies of the reproducibility showed a coefficient of variation of 13.5%. The present study suggests that the method of blood volume measuring should be further evaluated to study the function of capacitance vessels.

  15. A radiolabeled antiglobulin test for crossmatching platelet transfusions

    International Nuclear Information System (INIS)

    Kickler, T.S.; Braine, H.G.; Ness, P.M.; Koester, A.; Bias, W.

    1983-01-01

    Despite the use of HLA-matched platelets for alloimmunized recipients, transfusion failures occur. In order to reduce these failures, researchers investigated the use of a radiolabeled antiglobulin technique for platelet crossmatching. The principle of the test is that of an indirect Coombs test using 125 I labeled goat anti-human IgG. Incompatibility is determined by calculating a radioactivity antiglobulin test (RAGT) index. Using this technique, researchers performed 89 crossmatches on 19 leukemic or aplastic patients who were refractory to random donor platelets and receiving varying degrees of HLA-matched platelets. Effectiveness of the transfusion was assessed from the posttransfusion corrected platelet count increment (CCI) determined at 1 and 20 hr. When the RAGT index was 1.9 or less, the mean CCI at 1 lhr was 17,570 +/- 7003/cu mm, n . 55. When the RAGT index was 2.0 or greater, the mean CCI was 4237 +/- 4100/cu mm, n . 34. At 20 hr when the RAGT index was 1.9 or less, the mean CCI was 8722 +/- 3143/cu mm, n . 33, and when the index was 2.0 or greater, the mean CCI was 571 +/- 1286/cu mm, n . 23. Using this technique, one false negative resulted. Nine positive crossmatches with good increments at 1 hr were found; at 20 hr, however, the survival of these units was zero. These data suggest that this method is a useful adjunct in the selection of platelets in the refractory patient

  16. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Ingemann Jensen, A.T.

    2013-06-01

    This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent-like copolymers, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A

  17. Synthesis and applications of radiolabelled drugs in pharmaceutical development

    International Nuclear Information System (INIS)

    Landvatter, S.W.; Heys, J.R.; Garner, K.T.; Mack, J.F.; Senderoff, S.G.; Shu, A.Y.; Villani, A.J.; Saunders, D.

    1994-01-01

    Radiolabelled drugs play a vital role in the development of new pharmaceuticals including application in drug discovery, pre-clinical development and clinical development. The synthesis of these pharmaceuticals in tritium or carbon-14 labelled form poses many challenges for the synthetic organic chemist. The actual choice of synthetic route must take into account the small scale, limited choice and high cost of labelled precursors, and the positioning of the label into a metabolically stable position. There are, however, a number of synthetic strategies available for overcoming these constraints. Although in some C-14 syntheses the requisite labelled raw material can be purchased and the existing synthesis adapted for labelling, frequently the synthetic challenge is the synthesis of a structurally simple, yet commercially unavailable, labelled precursor (e.g., γ-butyrolactone-[2- 14 C], cyclohexanone-[ 3 H], CuCN-[ 14 C], 2-furancarboxaldehyde-[ 14 C]). Another useful strategy in C-14 synthesis is the conversion of an advanced intermediate, or perhaps the unlabelled product itself, into a precursor which can then be reconverted into the labelled version of the intermediate. Occasionally, a new total synthesis must be developed. In addition to these strategies, tritium labelling can uniquely take advantage of exchange labelling techniques, synthesis and reduction of unsaturated precursors, or tritium-halogen replacement reactions. Examples of these strategies and use of the labelled products are discussed

  18. Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy

    Directory of Open Access Journals (Sweden)

    Wiebke Sihver

    2014-03-01

    Full Text Available The epidermal growth factor receptor (EGFR has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment.

  19. Microassay for measurement of binding of radiolabelled ligands to cell surface molecules

    International Nuclear Information System (INIS)

    Woof, J.M.; Burton, D.R.

    1988-01-01

    An improved technique for measuring the binding of radiolabelled ligands to cell surface molecules has been developed by modification of a procedure using centrifugation through a water-immiscible oil to separate free and cell-bound ligand. It maximises the percentage of ligand bound since cell-bound and free ligand can be separated easily and reproducibly even when very small reaction volumes are used. This permits low levels of ligand radiolabelling and relatively low numbers of cells to be used

  20. Raman spectroscopy detection of biomolecules in biocrusts from differing environmental conditions

    Science.gov (United States)

    Miralles, I.; Jorge-Villar, S. E.; van Wesemael, B.; Lázaro, R.

    2017-01-01

    Lichens and cyanobacteria colonize inhospitable places covering a wide climate range due to their different survival strategies, such as the synthesis of protective biomolecules. The effect of ecological factors on the synthesis of biomolecules has not been widely analysed. This study aimed to assess the effects of four factors (species, microclimate, seasonality and hydration state) and their interactions on the biomolecule frequency detected by Raman Spectroscopy. We included cyanobacterial biocrusts, and the lichens Diploschistes diacapsis, Squamarina lentigera, and Lepraria isidiata; two contrasted microclimates (typical and marginal), two contrasted seasons (hot and dry vs cool and wet) and two hydration states (dry and wet). ;Species; was the most influential factor in the identity and frequency of the main biomolecules. Microclimatic differences in the range of the local specific habitats only influenced the biomolecules in cyanobacteria. There was a quadruple interaction among the factors, the effects being different mainly depending on the species. At D. diacapsis, the production of their main biomolecules depended on microclimate, although it also depended on seasonality. Nevertheless, in L. isidiata and S. lentigera microclimatic differences did not significantly affect the production of biomolecules. In the lichen species, the microhabitats exposed to relatively larger incident radiation did not show significantly larger relative frequency of photoprotective biomolecules. No clear connection between higher production of oxalates and drier microhabitats was found, suggesting that the synthesis of oxalates is not related to water reserve strategy. The pros and cons of monitor biomolecules in biocrust by Raman spectrometry were also discussed.

  1. Novel in Vitro Efficiency of Chitosan Biomolecule against Trichomonas gallinae.

    Science.gov (United States)

    Tavassoli, M; Imani, A; Tajik, H; Moradi, M; Pourseyed, Sh

    2012-01-01

    Development of new natural agents for parasitic diseases treatment has unexpectedly increased to overcome effectively against emergence and re-emergence of parasitic diseases, the appearance of drug resistant organisms and toxic side effects of current agents. The aim of the study was to evaluate antiprotozoal activities of chitosan biomolecule on trophozoites of Trichomonas gallinae. The antitrichomonal activity of various low molecular weight chitosan concentrations including 125, 250, 500 and 1250 µg ml(-1) against T. gallinae trophozoites cultured in trypticase-yeast extract-maltose medium supplemented with heat-inactivated cold horse serum was evaluated in vitro. Samples containing medium without chitosan were also assayed as controls. The mortality rates at 0, 3 and 6 h post treatment with all concentrations were significantly different from control group (P<0.05). Treated trophozoites showed more susceptibility to the highest concentration reaching mortality rate of 100% at 3h post inoculation. However, at this time, results for 125, 250 and 500 µg ml(-1) were 93%, 95% and 96.7%, respectively. The results demonstrate that the application of chitosan biomolecule is a promising option for treatment of trichomoniasis in pigeons.

  2. Biosurfactants: Multifunctional Biomolecules of the 21st Century.

    Science.gov (United States)

    Santos, Danyelle Khadydja F; Rufino, Raquel D; Luna, Juliana M; Santos, Valdemir A; Sarubbo, Leonie A

    2016-03-18

    In the era of global industrialisation, the exploration of natural resources has served as a source of experimentation for science and advanced technologies, giving rise to the manufacturing of products with high aggregate value in the world market, such as biosurfactants. Biosurfactants are amphiphilic microbial molecules with hydrophilic and hydrophobic moieties that partition at liquid/liquid, liquid/gas or liquid/solid interfaces. Such characteristics allow these biomolecules to play a key role in emulsification, foam formation, detergency and dispersal, which are desirable qualities in different industries. Biosurfactant production is considered one of the key technologies for development in the 21st century. Besides exerting a strong positive impact on the main global problems, biosurfactant production has considerable importance to the implantation of sustainable industrial processes, such as the use of renewable resources and "green" products. Biodegradability and low toxicity have led to the intensification of scientific studies on a wide range of industrial applications for biosurfactants in the field of bioremediation as well as the petroleum, food processing, health, chemical, agricultural and cosmetic industries. In this paper, we offer an extensive review regarding knowledge accumulated over the years and advances achieved in the incorporation of biomolecules in different industries.

  3. Novel in Vitro Efficiency of Chitosan Biomolecule Against Trichomonas Gallinae

    Directory of Open Access Journals (Sweden)

    SH Pourseyed

    2012-02-01

    Full Text Available Background: Development of new natural agents for parasitic diseases treatment has unexpectedly increased to overcome effectively against emergence and re-emergence of parasitic diseases, the appearance of drug resistant organisms and toxic side effects of current agents. The aim of the study was to evaluate antiprotozoal activities of chitosan biomolecule on trophozoites of Trichomonas gallinae.Methods: The antitrichomonal activity of various low molecular weight chitosan concentrations including 125, 250, 500 and 1250 μg ml-1 against T. gallinae trophozoites cultured in trypticase-yeast extract-maltose medium supplemented with heat-inactivated cold horse serum was evaluated in vitro. Samples containing medium without chitosan were also assayed as controls.Results: The mortality rates at 0, 3 and 6 h post treatment with all concentrations were significantly different from control group (P<0.05. Treated trophozoites showed more susceptibility to the highest concentration reaching mortality rate of 100% at 3h post inoculation. However, at this time, results for 125, 250 and 500 μg ml-1 were 93%, 95% and 96.7%, respectively.Conclusion: The results demonstrate that the application of chitosan biomolecule is a promising option for treatment of trichomoniasis in pigeons.

  4. Biosurfactants: Multifunctional Biomolecules of the 21st Century

    Directory of Open Access Journals (Sweden)

    Danyelle Khadydja F. Santos

    2016-03-01

    Full Text Available In the era of global industrialisation, the exploration of natural resources has served as a source of experimentation for science and advanced technologies, giving rise to the manufacturing of products with high aggregate value in the world market, such as biosurfactants. Biosurfactants are amphiphilic microbial molecules with hydrophilic and hydrophobic moieties that partition at liquid/liquid, liquid/gas or liquid/solid interfaces. Such characteristics allow these biomolecules to play a key role in emulsification, foam formation, detergency and dispersal, which are desirable qualities in different industries. Biosurfactant production is considered one of the key technologies for development in the 21st century. Besides exerting a strong positive impact on the main global problems, biosurfactant production has considerable importance to the implantation of sustainable industrial processes, such as the use of renewable resources and “green” products. Biodegradability and low toxicity have led to the intensification of scientific studies on a wide range of industrial applications for biosurfactants in the field of bioremediation as well as the petroleum, food processing, health, chemical, agricultural and cosmetic industries. In this paper, we offer an extensive review regarding knowledge accumulated over the years and advances achieved in the incorporation of biomolecules in different industries.

  5. Comparison of endogenous and radiolabeled bile acid excretion in patients with idiopathic chronic diarrhea

    International Nuclear Information System (INIS)

    Schiller, L.R.; Bilhartz, L.E.; Santa Ana, C.A.

    1990-01-01

    Fecal recovery of radioactivity after ingestion of a bolus of radiolabeled bile acid is abnormally high in most patients with idiopathic chronic diarrhea. To evaluate the significance of this malabsorption, concurrent fecal excretion of both exogenous radiolabeled bile acid and endogenous (unlabeled) bile acid were measured in patients with idiopathic chronic diarrhea. Subjects received a 2.5-microCi oral dose of taurocholic acid labeled with 14C in the 24th position of the steroid moiety. Endogenous bile acid excretion was measured by a hydroxysteroid dehydrogenase assay on a concurrent 72-h stool collection. Both radiolabeled and endogenous bile acid excretion were abnormally high in most patients with chronic diarrhea compared with normal subjects, even when equivoluminous diarrhea was induced in normal subjects by ingestion of osmotically active solutions. The correlation between radiolabeled and endogenous bile acid excretion was good. However, neither radiolabeled nor endogenous bile acid excretion was as abnormal as is typically seen in patients with ileal resection, and none of these diarrhea patients responded to treatment with cholestyramine with stool weights less than 200 g. These results suggest (a) that this radiolabeled bile acid excretion test accurately reflects excess endogenous bile acid excretion; (b) that excess endogenous bile acid excretion is not caused by diarrhea per se; (c) that spontaneously occurring idiopathic chronic diarrhea is often associated with increased endogenous bile acid excretion; and (d) that bile acid malabsorption is not likely to be the primary cause of diarrhea in most of these patients

  6. Integrative self-assembly of functional hybrid nanoconstructs by inorganic wrapping of single biomolecules, biomolecule arrays and organic supramolecular assemblies.

    Science.gov (United States)

    Patil, Avinash J; Li, Mei; Mann, Stephen

    2013-08-21

    Synthesis of functional hybrid nanoscale objects has been a core focus of the rapidly progressing field of nanomaterials science. In particular, there has been significant interest in the integration of evolutionally optimized biological systems such as proteins, DNA, virus particles and cells with functional inorganic building blocks to construct mesoscopic architectures and nanostructured materials. However, in many cases the fragile nature of the biomolecules seriously constrains their potential applications. As a consequence, there is an on-going quest for the development of novel strategies to modulate the thermal and chemical stabilities, and performance of biomolecules under adverse conditions. This feature article highlights new methods of "inorganic molecular wrapping" of single or multiple protein molecules, individual double-stranded DNA helices, lipid bilayer vesicles and self-assembled organic dye superstructures using inorganic building blocks to produce bio-inorganic nanoconstructs with core-shell type structures. We show that spatial isolation of the functional biological nanostructures as "armour-plated" enzyme molecules or polynucleotide strands not only maintains their intact structure and biochemical properties, but also enables the fabrication of novel hybrid nanomaterials for potential applications in diverse areas of bionanotechnology.

  7. Integrative self-assembly of functional hybrid nanoconstructs by inorganic wrapping of single biomolecules, biomolecule arrays and organic supramolecular assemblies

    Science.gov (United States)

    Patil, Avinash J.; Li, Mei; Mann, Stephen

    2013-07-01

    Synthesis of functional hybrid nanoscale objects has been a core focus of the rapidly progressing field of nanomaterials science. In particular, there has been significant interest in the integration of evolutionally optimized biological systems such as proteins, DNA, virus particles and cells with functional inorganic building blocks to construct mesoscopic architectures and nanostructured materials. However, in many cases the fragile nature of the biomolecules seriously constrains their potential applications. As a consequence, there is an on-going quest for the development of novel strategies to modulate the thermal and chemical stabilities, and performance of biomolecules under adverse conditions. This feature article highlights new methods of ``inorganic molecular wrapping'' of single or multiple protein molecules, individual double-stranded DNA helices, lipid bilayer vesicles and self-assembled organic dye superstructures using inorganic building blocks to produce bio-inorganic nanoconstructs with core-shell type structures. We show that spatial isolation of the functional biological nanostructures as ``armour-plated'' enzyme molecules or polynucleotide strands not only maintains their intact structure and biochemical properties, but also enables the fabrication of novel hybrid nanomaterials for potential applications in diverse areas of bionanotechnology.

  8. 68Ga-THP-PSMA: A PET Imaging Agent for Prostate Cancer Offering Rapid, Room-Temperature, 1-Step Kit-Based Radiolabeling.

    Science.gov (United States)

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

    2017-08-01

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

  9. Liposome imaging agents in personalized medicine

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Hansen, Anders Elias; Gabizon, Alberto

    2012-01-01

    that selectively localize in tumor tissue can transport both drugs and imaging agents, which allows for a theranostic approach with great potential in personalized medicine. Radiolabeling of liposomes have for many years been used in preclinical studies for evaluating liposome in vivo performance and has been...... an important tool in the development of liposomal drugs. However, advanced imaging systems now provide new possibilities for non-invasive monitoring of liposome biodistribution in humans. Thus, advances in imaging and developments in liposome radiolabeling techniques allow us to enter a new arena where we...... start to consider how to use imaging for patient selection and treatment monitoring in connection to nanocarrier based medicines. Nanocarrier imaging agents could furthermore have interesting properties for disease diagnostics and staging. Here, we review the major advances in the development...

  10. Current status of cancer immunodetection with radiolabeled human monoclonal antibodies.

    Science.gov (United States)

    De Jager, R; Abdel-Nabi, H; Serafini, A; Pecking, A; Klein, J L; Hanna, M G

    1993-04-01

    The use of radiolabeled murine monoclonal antibodies (MoAbs) for cancer immunodetection has been limited by the development of human antimouse antibodies (HAMA). Human monoclonal antibodies do not elicit a significant human antihuman (HAHA) response. The generation and production of human monoclonal antibodies met with technical difficulties that resulted in delaying their clinical testing. Human monoclonal antibodies of all isotypes have been obtained. Most were immunoglobulin (Ig) M directed against intracellular antigens. Two antibodies, 16.88 (IgM) and 88BV59 (IgG3k), recognize different epitopes on a tumor-associated antigen, CTA 16.88, homologous to cytokeratins 8, 18, and 19. CTA 16.88 is expressed by most epithelial-derived tumors including carcinomas of the colon, pancreas, breast, ovary, and lung. The in vivo targeting by these antibodies is related to their localization in nonnecrotic areas of tumors. Repeated administration of 16.88 over 5 weeks to a cumulative dose of 1,000 mg did not elicit a HAHA response. Two of 53 patients developed a low titer of HAHA 1 to 3 months after a single administration of 88BV59. Planar imaging of colorectal cancer with Iodine-131 (131I)-16.88 was positive in two studies in 9 of 12 and 16 of 20 patients preselected by immunohistochemistry. Tumors less than 2 cm in diameter are usually not detected. The lack of immunogenicity and long tumor residence time (average = 17 days) makes 16.88 a good candidate for therapy. Radioimmunlymphoscintigraphy with indium-111 (111In)-LiLo-16.88 administered by an intramammary route was used in the presurgical staging of primary breast cancer. The negative predictive value of lymph node metastases for tumors less than 3 cm was 90.5%. Planar and single photon emission computed tomography imaging of colorectal carcinoma with technetium-99m (99mTc) 88BV59 was compared with computed tomography (CT) scan in 36 surgical patients. The antibody scan was more sensitive than the CT scan in detecting

  11. Simple approach to study biomolecule adsorption in polymeric microfluidic channels.

    Science.gov (United States)

    Gubala, Vladimir; Siegrist, Jonathan; Monaghan, Ruairi; O'Reilly, Brian; Gandhiraman, Ram Prasad; Daniels, Stephen; Williams, David E; Ducrée, Jens

    2013-01-14

    Herein a simple analytical method is presented for the characterization of biomolecule adsorption on cyclo olefin polymer (COP, trade name: Zeonor(®)) substrates which are widely used in microfluidic lab-on-a-chip devices. These Zeonor(®) substrates do not possess native functional groups for specific reactions with biomolecules. Therefore, depending on the application, such substrates must be functionalized by surface chemistry methods to either enhance or suppress biomolecular adsorption. This work demonstrates a microfluidic method for evaluating the adsorption of antibodies and oligonucleotides surfaces. The method uses centrifugal microfluidic flow-through chips and can easily be implemented using common equipment such as a spin coater. The working principle is very simple. The user adds 40 L of the solution containing the sample to the starting side of a microfluidic channel, where it is moved through by centrifugal force. Some molecules are adsorbed in the channel. The sample is then collected at the other end in a small reservoir and the biomolecule concentration is measured. As a pilot application, we characterized the adsorption of goat anti-human IgG and a 20-mer DNA on Zeonor(®), and on three types of functionalized Zeonor: 3-aminopropyltriethoxysilane (APTES) modified surface with mainly positive charge, negatively charged surface with immobilized bovine serum albumin (BSA), and neutral, hydrogel-like film with polyethylene glycol (PEG) characteristics. This simple analytical approach adds to the fundamental understanding of the interaction forces in real, microfluidic systems. This method provides a straightforward and rapid way to screen surface compositions and chemistry, and relate these to their effects on the sensitivity and resistance to non-specific binding of bioassays using them. In an additional set of experiments, the surface area of the channels in this universal microfluidic chip was increased by precision milling of microscale

  12. Radiolabeling, characterization and preliminary studies of 90Y-octreotate

    International Nuclear Information System (INIS)

    Klementyeva, O.E.; Bruskin, A.B.; Larenkov, A.A.; Kodina, G.E.; Korsunsky, V.N.

    2015-01-01

    Full text of publication follows. Introduction: Overexpression of the somatostatin receptors in neuroendocrine tumors has become the molecular basis for the use of somatostatin analogues in diagnosis and therapy for these neoplasms. The high energy (maximum 2.2 MeV) and penetration range (R 95 5.7 mm) of β-particles from 90 Y are advantageous, with a direct killing of somatostatin receptor positive cells and a crossfire effect which hits nearby receptor-negative tumour cells [Ref. 1]. Aim: the investigation of the reaction conditions for the preparation of 90 Y-Octreotate and its in vitro characterization. Materials and methods: DOTA-Octreotate (Farm-Syntez Ltd.) and 88 YCl 3 (V/O Isotop) were used without purification. 88 Y-Octreotate was prepared in acetate buffer solution and its radiochemical purity was controlled by ITLC. In-vitro experiments were carried out with melanoma B16. Studies of internalization were performed as described in [Ref. 2]. Results: the maximal accumulation in the cells was observed after 90 min from the beginning of incubation and was about 3.9%. In our experiments, we found high level of internalization of the surface-bound 88 Y-Octreotate into B16 cells. Maximal internalization level was 80% after 60 min of incubation. Conclusion: the optimal conditions for effective labeling (> 95%) of DOTA-Octreotate were found. The results obtained using the gamma-emitting 88 Y, provide a basis for in vivo research 90 Y octreotate as radiotherapeutic agent. References: [Ref. 1] Bodei, L.; Pepe, G.; Paganelli, G.; Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors with somatostatin analogues. Eur. Rev. Med. Pharmacol. Sci., 2010; v. 14: 347-351. [Ref. 2] Garcia Garayoa E., Allemann-Tannahill L., et al. In vitro and in vivo evaluation of new radiolabeled neurotensin (8-13) analogs with high affinity for NT1 receptors. Nucl. Med. Biol. 2001; 28: 75-84. (authors)

  13. In vitro evaluation of radiolabeled aptamers for colon carcinoma diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Correa, C.R.; Ferreira, I.M; Santos, S.R.; Faria, L.S.; Andrade, A.S.R., E-mail: crisrcorrea@gmail.com, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Goes, A.M., E-mail: goes@icb.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Inst. de Ciencias Biologicas. Dept. de Imunologia e Bioquimica

    2013-07-01

    Cancer is a leading cause of death worldwide, representing a major public health problem worldwide. Colorectal cancers accounts around 8% of all deaths for cancer in 2008, is the fourth most lethal. Many colorectal cancer markers, such as carcinoembryonic antigen (CEA), A33, and CSA-p, have been studied as the therapeutic targets in preclinical or clinical settings. CEA is a complex intracellular glycoprotein produced by about 90% of colorectal cancers. Since its discovery in 1965, a very large number of studies have been carried out to determine the effectiveness of CEA as clinically useful tumor markers. Aptamers are short single-stranded nucleic acid oligomers (DNA or RNA) that can form specific and complex three-dimensional structures which can bind with high affinity to specific targets, they are functionally equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small size, and non-immunogenic. The aim of this study was develop anti-CEA aptamers for use as imaging agents. The aptamers are obtained through by SELEX (systematic evolution of ligands by exponential enrichment), in which aptamers are selected from a library of random sequences of synthetic DNA by repetitive binding of the oligonucleotides to target molecule. These aptamers were confirmed to have affinity and specific binding for T84 cell line (target cell), showed by fluorescence microscopic images. Individual aptamers sequences that bound T84 cells were {sup 32}P-radiolabeled and incubated at different concentrations on cell monolayers, to monitor the aptamers affinity binding. The selected aptamers can identify colon cancer cell line. This aptamers could be further developed for early disease detection as radiopharmaceuticals, as well as prognostic markers, of colorectal cancers. (author)

  14. Radiolabeled Zn-DPA as a potential infection imaging agent

    International Nuclear Information System (INIS)

    Liu Xinrong; Cheng Dengfeng; Gray, Brian D.; Wang Yuzhen; Akalin, Ali; Rusckowski, Mary; Pak, Koon Y.; Hnatowich, Donald J.

    2012-01-01

    Introduction: A zinc-dipicolylamine analog (Zn-DPA) conjugated with a fluorophore (PSVue®794) has been shown to image bacterial infections in mice. However, radiolabeled Zn-DPA has not previously been considered for nuclear imaging of infection. Methods: Both 111 In-labeled DOTA-biotin and Zn-DPA-biotin were combined using streptavidin (SA) as a noncovalent linker. Mice injected intramuscularly with Streptococcus pyogenes (infection model) or with lipopolysaccharide (LPS) (inflammation model) were coinjected intravenously with 6 μg of DPA as PSVue794 and as 111 In-DOTA-biotin/SA/biotin-Zn-DPA. Periodic fluorescent and SPECT (single photon emission computed tomography)/CT (computed tomography) images were acquired, and biodistributions were obtained at 22 h. Results: Histological examination confirmed the validity of both the infection and inflammation animal models. Both the whole-body optical and nuclear images showed obvious accumulations in the target thigh in both models at all time points. At 22 h, the average target thigh accumulation of 111 In was 1.66%ID/g (S.D. 0.15) in the infection mice compared to 0.58%ID/g (S.D. 0.07) in the inflammation mice (P 111 In target/normal thigh ratio was 2.8 fold higher in the infection animals compared to the inflammation animals. Conclusions: These preliminary results show that Zn-DPA within streptavidin targets S. pyogenes-infected mice similarly to its free fluorescent analogue. The significantly higher accumulation in the live bacterial infection thigh compared to that of the LPS-induced inflammation thigh suggests that Zn-DPA may be a promising imaging agent to distinguish between bacterial infections and sterile inflammations.

  15. Radiolabeled prostate-specific membrane antigen small-molecule inhibitors.

    Science.gov (United States)

    Will, Leon; Sonni, Ida; Kopka, Klaus; Kratochwil, Clemens; Giesel, Frederik L; Haberkorn, Uwe

    2017-06-01

    Prostate cancer (PC) is one of the most common malignancies worldwide. Prostate-specific membrane antigen (PSMA) has been found to be expressed in most PCs and represents an ideal target for diagnostic and therapeutic purposes. Numerous PSMA tracers have been recently developed. This review aims to provide an overview on the clinical influence of PSMA tracers in primary staging, biochemical recurrence (BCR) of PC and advanced, metastatic PC. Additionally, the use of PSMA tracers in systemic radioligand therapy (RLT) of metastatic castration-resistant prostate cancer (mCRPC), as well as non-prostatic specific uptake of PSMA tracers and the use of PSMA imaging to manage therapy have been described. A computerized search of the literature (PubMed) was conducted in order to find evidence on the role of PSMA tracers in the diagnosis and therapy of PC. PSMA positron-emission tomography/computed tomography (PET/CT) outperforms conventional imaging in the settings of primary PC, BCR and advanced PC. Especially in BCR of PC, PSMA PET/CT shows clinical value with significantly higher detection rates than standard modalities. The use of PSMA PET/CT resulted in a change of the therapeutic management in up to half of the cases. Regarding RLT, smaller studies were able to show positive clinical effects of 177Lu-labeled PSMA tracers without the occurrence of severe side effects. The currently available data clearly shows that PSMA targeting has a clinical impact on the diagnosis of PC, and that RLT using radiolabeled PSMA tracers has high potentiality in the settings of resistance to conventional therapeutic approaches.

  16. Modification of biomolecules and combined actions by radiation

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Lee, J. W.; Kim, J. H.; Choi, J. I.; Song, B. S.; Kim, J. K.; Park, J. H.; Lee, Y. J.; Ryu, S. H.; Sung, N. Y.; Cha, M. K.; Nam, J. Y.; Park, J. Y.; Cho, E. R.; Ryu, T. H.

    2011-12-01

    Advanced Radiation Technology Institute is a government-supported institute for radiation research and application. It has focused on development of fundamentals for radiation applications based on the existing radiation technology, and on enhancement of biological effectiveness of radiation through theoretical approach to the combined actions of radiation with another factor. Application of radiation technology together with the existing technologies to enhance the physical, chemical, biological characteristics through modification of biomolecules resulted in creation of de novo materials of scientific and industrial values. A theoretical model for combined action of radiation with another physico-chemical factor has been established. Conclusively the results of this study can provide scientific bases for maximizing the efficacy of ionizing radiation in relation to industrial applications

  17. Modification of Biomolecules and Combined Actions by Radiation

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Yang, J. S.; Lee, J. E.

    2010-12-01

    Basic knowledge necessary for the future R and D plans can be derived from the results of this study. This study has focused on development of fundamentals for radiation applications based on the existing radiation technology, and on enhancement of biological effectiveness of radiation through theoretical approach to the combined actions of radiation with another factor. Application of radiation technology together with the existing technologies to enhance the physical, chemical, biological characteristics through modification of biomolecules will lead to creation of de novo scientific and industrial values. A mathematical model for the combined action of ionizing radiation with another factor has been established. Prediction and optimization of the maximum value of synergistic interaction and the conditions for it are possible by means of the established model. Conclusively the results of this study can provide scientific bases for enhancing the biological efficacy of ionizing radiation in relation to industrial applications

  18. Laser desorption mass spectrometry for biomolecule detection and its applications

    Science.gov (United States)

    Winston Chen, C. H.; Sammartano, L. J.; Isola, N. R.; Allman, S. L.

    2001-08-01

    During the past few years, we developed and used laser desorption mass spectrometry for biomolecule detections. Matrix-assisted laser desorption/ionization (MALDI) was successfully used to detect DNA fragments with the size larger than 3000 base pairs. It was also successfully used to sequence DNA with both enzymatic and chemical degradation methods to produce DNA ladders. We also developed MALDI with fragmentation for direct DNA sequencing for short DNA probes. Since laser desorption mass spectrometry for DNA detection has the advantages of fast speed and no need of labeling, it has a great potential for molecular diagnosis for disease and person identification by DNA fingerprinting. We applied laser desorption mass spectrometry to succeed in the diagnosis of cystic fibrosis and several other nerve degenerative diseases such as Huntington's disease. We also succeeded in demonstrating DNA typing for forensic applications.

  19. Laser desorption mass spectrometry for biomolecule detection and its applications

    International Nuclear Information System (INIS)

    Winston Chen, C.H.; Allman, S.L.; Sammartano, L.J.; Isola, N.R.

    2001-01-01

    During the past few years, we developed and used laser desorption mass spectrometry for biomolecule detections. Matrix-assisted laser desorption/ionization (MALDI) was successfully used to detect DNA fragments with the size larger than 3000 base pairs. It was also successfully used to sequence DNA with both enzymatic and chemical degradation methods to produce DNA ladders. We also developed MALDI with fragmentation for direct DNA sequencing for short DNA probes. Since laser desorption mass spectrometry for DNA detection has the advantages of fast speed and no need of labeling, it has a great potential for molecular diagnosis for disease and person identification by DNA fingerprinting. We applied laser desorption mass spectrometry to succeed in the diagnosis of cystic fibrosis and several other nerve degenerative diseases such as Huntington's disease. We also succeeded in demonstrating DNA typing for forensic applications

  20. Interfacial water thickness at inorganic nanoconstructs and biomolecules: Size matters

    Science.gov (United States)

    Cardellini, Annalisa; Fasano, Matteo; Chiavazzo, Eliodoro; Asinari, Pietro

    2016-04-01

    Water molecules in the proximity of solid nanostructures influence both the overall properties of liquid and the structure and functionality of solid particles. The study of water dynamics at solid-liquid interfaces has strong implications in energy, environmental and biomedical fields. This article focuses on the hydration layer properties in the proximity of Carbon Nanotubes (CNTs) and biomolecules (proteins, polypeptides and amino acids). Here we show a quantitative relation between the solid surface extension and the characteristic length of water nanolayer (δ), which is confined at solid-liquid interfaces. Specifically, the size dependence is attributed to the limited superposition of nonbonded interactions in case of small molecules. These results may facilitate the design of novel energy or biomedical colloidal nanosuspensions, and a more fundamental understanding of biomolecular processes influenced by nanoscale water dynamics.

  1. Assembly and actuation of nanomaterials using active biomolecules.

    Energy Technology Data Exchange (ETDEWEB)

    Spoerke, Erik David; Thayer, Gayle Echo; de Boer, Maarten Pieter; Bunker, Bruce Conrad; Liu, Jun; Corwin, Alex David; Gaudioso, Jennifer Marie; Sasaki, Darryl Yoshio; Boal, Andrew Kiskadden; Bachand, George David; Trent, Amanda M.; Bachand, Marlene; Rivera, Susan B.; Koch, Steven John

    2005-11-01

    The formation and functions of living materials and organisms are fundamentally different from those of synthetic materials and devices. Synthetic materials tend to have static structures, and are not capable of adapting to the functional needs of changing environments. In contrast, living systems utilize energy to create, heal, reconfigure, and dismantle materials in a dynamic, non-equilibrium fashion. The overall goal of the project was to organize and reconfigure functional assemblies of nanoparticles using strategies that mimic those found in living systems. Active assembly of nanostructures was studied using active biomolecules to drive the organization and assembly of nanocomposite materials. In this system, kinesin motor proteins and microtubules were used to direct the transport and interactions of nanoparticles at synthetic interfaces. In addition, the kinesin/microtubule transport system was used to actively assemble nanocomposite materials capable of storing significant elastic energy. Novel biophysical measurement tools were also developed for measuring the collective force generated by kinesin motor proteins, which will provide insight on the mechanical constraints of active assembly processes. Responsive reconfiguration of nanostructures was studied in terms of using active biomolecules to mediate the optical properties of quantum dot (QD) arrays through modulation of inter-particle spacing and associated energy transfer interaction. Design rules for kinesin-based transport of a wide range of nanoscale cargo (e.g., nanocrystal quantum dots, micron-sized polymer spheres) were developed. Three-dimensional microtubule organizing centers were assembled in which the polar orientation of the microtubules was controlled by a multi-staged assembly process. Overall, a number of enabling technologies were developed over the course of this project, and will drive the exploitation of energy-driven processes to regulate the assembly, disassembly, and dynamic

  2. Platinum(II) complexes as spectroscopic probes for biomolecules

    Energy Technology Data Exchange (ETDEWEB)

    Ratilla, E.

    1990-09-21

    The use of platinum(II) complexes as tags and probes for biomolecules is indeed advantageous for their reactivities can be selective for certain purposes through an interplay of mild reaction conditions and of the ligands bound to the platinum. The use of {sup 195}Pt NMR as a method of detecting platinum and its interactions with biomolecules was carried out with the simplest model of platinum(II) tagging to proteins. Variable-temperature {sup 195}Pt NMR spectroscopy proved useful in studying the stereodynamics of complex thioethers like methionine. The complex, Pt(trpy)Cl{sup +}, with its chromophore has a greater potential for probing proteins. It is a noninvasive and selective tag for histidine and cysteine residues on the surface of cytochrome c at pH 5. The protein derivatives obtained are separable, and the tags are easily quantitated and differentiated through the metal-to-ligand charge transfer bands which are sensitive to the environment of the tag. Increasing the pH to 7.0 led to the modification by Pt(trpy)Cl{sup +}of Arg 91 in cytochrome c. Further studies with guanidine-containing ligands as models for arginine modification by Pt(trpy)Cl{sup +} showed that guanidine can act as a terminal ligand and as a bridging ligand. Owing to the potential utility of Pt(trpy)L{sup n+} as electron dense probes of nucleic acid structure, interactions of this bis-Pt(trpy){sup 2+} complex with nucleic acids was evaluated. Indeed, the complex interacts non-covalently with nucleic acids. Its interactions with DNA are not exactly the same as those of its precedents. Most striking is its ability to form highly immobile bands of DNA upon gel electrophoresis. 232 refs.

  3. Arbuscular mycorrhizal fungi and vermicompost to maximize the production of foliar biomolecules in Passiflora alata Curtis seedlings.

    Science.gov (United States)

    Oliveira, Melquisedec S; Campos, Maryluce A S; Silva, Fábio S B

    2015-02-01

    Arbuscular mycorrhizal fungi (AMF) are soil organisms that associate with plant roots and promote plant growth, increasing the concentration of secondary metabolites, which are molecules of interest to the pharmaceutical industry. Passiflora alata is a Brazilian medicinal plant that is used as a raw material for anxiolytic phytotherapeutic agents. The anxiolytic properties are related to the presence of biomolecules in the plant material, principally flavonoids. The objective of this study was to evaluate the effect of inoculation with AMF and organic fertilization on the production of soluble carbohydrates and total foliar proteins, phenols and flavonoids in P. alata seedlings. There was an effect of the tested treatments on the analyzed variables. Seedlings inoculated and cultivated in soil to which 0.15 kg vermicompost kg(-1) had been added showed increased growth and production of primary and secondary metabolites compared with treatments with lower levels of manure, which did not differ from those cultivated in soil with 0.2 kg vermicompost kg(-1). The inoculation of P. alata seedlings with Gigaspora albida is an alternative to maximize the production of pharmacologically important foliar biomolecules, especially flavonoids, with benefits that vary in accordance with the fertility of the soil. © 2014 Society of Chemical Industry.

  4. Determination of the three-dimensional structure for weakly aligned biomolecules by NMR spectroscopy

    International Nuclear Information System (INIS)

    Shahkhatuni, Astghik A; Shahkhatuni, Aleksan G

    2002-01-01

    The key achievements and the potential of NMR spectroscopy for weakly aligned biomolecules are considered. Due to weak alignment, it becomes possible to determine a number of NMR parameters dependent on the orientation of biomolecules, which are averaged to zero in usual isotropic media. The addition of new orientational constraints to standard procedures of 3D structure determination markedly increases the achievable accuracy. The possibility of structure determination for biomolecules using only orientation-dependent parameters without invoking other NMR data is discussed. The methods of orientation, experimental techniques, and calculation methods are systematised. The main results obtained and the prospects of using NMR spectroscopy of weakly aligned systems to study different classes of biomolecules and to solve various problems of molecular biology are analysed. Examples of biomolecules whose structures have been determined using orientation-dependent parameters are given. The bibliography includes 508 references.

  5. Prospects in nuclear medicine

    International Nuclear Information System (INIS)

    Pink, V.; Johannsen, B.; Muenze, R.

    1990-01-01

    In nuclear medicine, a sequence of revolutioning research up to the simple and efficient application in routine has always then taken place when in an interdisciplinary teamwork new radiochemical tracers and/or new instrumentation had become available. At present we are at the beginning of a phase that means to be in-vivo-biochemistry, the targets of which are molecular interactions in the form of enzymatic reactions, ligand-receptor interactions or immunological reactions. The possibility to use positron-emitting radionuclides of bioelements in biomolecules or drugs to measure their distribution in the living organism by positron-emission tomography (PET) is gaining admittance into the pretentious themes of main directions of medical research. Diagnostic routine application of biochemically oriented nuclear medicine methods are predominantly expected from the transmission of knowledge in PET research to the larger appliable emission tomography with gamma-emitting tracers (SPECT). (author)

  6. Intracellular delivery of nanomaterials for sub-cellular imaging and tracking of biomolecules

    Science.gov (United States)

    Medepalli, Krishna Kiran

    Nanomaterials have many intriguing applications in biology and medicine. Unique properties such as enhanced electrical properties, increased chemical reactivity and resistance to degradation, novel optical properties and comparable size to that of biological systems have led to their use in various biomedical applications. The most important applications of nanomaterials for medicine are in drug delivery and imaging. This research focuses on utilizing the biocompatibility of single walled Carbon nanotubes (SWCNTs) and optical properties colloidal quantum dots (QDs) for cellular drug delivery and imaging of biomolecules. The first part of this research deals with single walled carbon nanotubes which are excellent candidates for targeted drug delivery applications due their unique structural and functional properties. However, prior to their use in therapeutics, their biocompatibility needs to be thoroughly investigated. The objectives of this research were to establish the biocompatibility of SWCNTs and demonstrate their use as drug delivery carriers into cells. Blood, a living tissue, is chosen as the biological system as it contains various cells which can potentially interact with SWCNTs during the delivery mechanism. The interactions of these cells in the blood (specifically white blood cells or leukocytes) with the SWCNTs provide vital information regarding the immune response of the host to the nanotubes. This research investigates the immune response of white blood cells due to SWCNTs via (a) direct interaction---presence of nanotubes in the blood and, (b) indirect interaction---presentation of nanotubes by antigen-presenting-cells to white blood cells. These two interactions recreate the innate and adaptive immune responses occurring in the body to any foreign substance. SWCNTs are functionalized with single stranded DNA (ss-DNA), which serves as a dispersant of nanotubes as well as a backbone for further attachment of other biomolecules of interest

  7. Radiolabeling human peripheral blood stem cells for positron emission tomography (PET imaging in young rhesus monkeys.

    Directory of Open Access Journals (Sweden)

    Alice F Tarantal

    Full Text Available These studies focused on a new radiolabeling technique with copper ((64Cu and zirconium ((89Zr for positron emission tomography (PET imaging using a CD45 antibody. Synthesis of (64Cu-CD45 and (89Zr-CD45 immunoconjugates was performed and the evaluation of the potential toxicity of radiolabeling human peripheral blood stem cells (hPBSC was assessed in vitro (viability, population doubling times, colony forming units. hPBSC viability was maintained as the dose of (64Cu-TETA-CD45 increased from 0 (92% to 160 µCi/mL (76%, p>0.05. Radiolabeling efficiency was not significantly increased with concentrations of (64Cu-TETA-CD45 >20 µCi/mL (p>0.50. Toxicity affecting both growth and colony formation was observed with hPBSC radiolabeled with ≥40 µCi/mL (p0.05, and a trend towards increased radiolabeling efficiency was noted as the dose of (89Zr-Df-CD45 increased, with a greater level of radiolabeling with 160 µCi/mL compared to 0-40 µCi/mL (p<0.05. A greater than 2,000 fold-increase in the level of (89Zr-Df-CD45 labeling efficiency was observed when compared to (64Cu-TETA-CD45. Similar to (64Cu-TETA-CD45, toxicity was noted when hPBSC were radiolabeled with ≥40 µCi/mL (p<0.05 (growth, colony formation. Taken together, 20 µCi/mL resulted in the highest level of radiolabeling efficiency without altering cell function. Young rhesus monkeys that had been transplanted prenatally with 25×10(6 hPBSC expressing firefly luciferase were assessed with bioluminescence imaging (BLI, then 0.3 mCi of (89Zr-Df-CD45, which showed the best radiolabeling efficiency, was injected intravenously for PET imaging. Results suggest that (89Zr-Df-CD45 was able to identify engrafted hPBSC in the same locations identified by BLI, although the background was high.

  8. In vivo and in vitro evaluation of dota-lanreotide radiolabelled with gallium-67

    International Nuclear Information System (INIS)

    Aldegheri, Eliane Bernardes

    2005-01-01

    One of the refinements of modern Nuclear Medicine is the capacity of providing dynamic and kinetics images of the administered radiopharmaceutical, reproducing its transport mechanism, action sites, receptor binding and excretion route. With the continues technological advances new radiopharmaceuticals have been developed in order to express higher specificity and with higher characters of affinity between receptor/complex. One radiopharmaceutical is formed by a reagent or bio molecule that has in its structure a radioisotope, that has the objectives of carrying it to the organs of affinity or to benign or malign tumoral process. Somatostatin inhibits the growing and proliferation of several tumoral cells. Somatostatin analogs bind to somatostatic receptors that are expressed in different kind of neoplasia DOTA-LANREOTIDE (DOTALAN) is an octapeptide analog to somatostatin. The interest of labeling the bio conjugate with gallium-67 in Nuclear Medicine comes from its physical, chemical and biological properties. Besides its gamma radiation, useful in the diagnosis of inflammation and infection foci, 67 Ga emits Auger electrons (0.1 - 8 keV) and conversion electrons (80 - 90 keV), making it attractive to internal radiotherapy if the vectors used to lead the radionuclide to the tumoral cell are internalized. The objective of this work was to develop a methodology of labelling DOTA-LANREOTIDE with 67 Ga, optimizing the labelling variables and its quality control. The novelty aspect was the comparison between labeling with national and imported 67 Ga, in its original and purified forms. The purification of 67 Ga was essential to reach yields higher than 90%. The radiolabelled bio conjugate peptides must be free of metallic contaminants that could compete in the labeling process. The following procedure was established after studying the labeling parameters: mass of peptide of 10 μg (6nmol), pH5, final reaction volume of 170 μL of the labelled and 67 Ga activity of 222

  9. Microbial contamination detection at low levels by [125]I radiolabeling

    Science.gov (United States)

    Summers, David; Karouia, Fathi

    Contamination of mission spacecraft is an ongoing issue. A broad diversity of microorganisms have been detected in clean rooms where spacecraft are assembled. Some of which, depicted as oligotroph, are of special regard, as they are capable of colonizing inorganic surfaces like metal, and have been shown to be a concern for forward contamination of pristine celestial bodies. Currently, the NASA standard assay is the only approved assay intended for the enumeration of spores and heterotrophic microbial populations. However, culture-based microbial detection methods underestimate the viable microbial population. More recently, adenosine triphosphate (ATP) bioluminescence and limulus amebocyte lysate (LAL) assays, which employ measure-ments of selected metabolic products as a proxy of biomass, have been used successfully to circumvent the necessity of the growth of microorganisms in order to estimate the biodurdens associated with spacecraft assembly facility. However, these methods have limitation in the amount of cells that can be detected, i.e., 103 cells, and the type of microorganisms respec-tively. This work seeks to develop a new highly sensitive method for the determination of bioburdens (and the detection of microorganisms and life) that is independant of the type of organism while preserving a good turn-around time for analysis for planetary protection purposes. The assay is based on the detection of the organism's protein by labeling them by radioiodination, 125 I, of aromatic rings on tyrosine amino acids residues. Radiolabeling techniques are inherently sensitive and 125 I, in particular, benefits from a 60 day half-life, providing greater activity and signal per unit number of labels. Furthermore, microorganisms can contain over 50% of protein by dry weight. Thus, just one label per protein increases the sensitivity, compared to the ATP and LAL assays, by one and three orders of magnitude by using standard detection methods and the use of multiphoton

  10. Investigation of bacterial adherence to a non-precious alloy with radiolabeling method

    International Nuclear Information System (INIS)

    Sonugelen, M.; Iyiyapici Destan, U.; Oeztuerk, B.; Yurt Lambrecht, F.

    2006-01-01

    The objective of this study was to investigate the bacterial adherence to a non-precious alloy with radiolabeling method. S. mutans, E. coliand C. albicanswere labeled with 99m Tc by using stannous chloride and their radiolabeling yields were calculated. After the labeling procedure, metal disks (3 mm x 10 mm) were treated with microorganisms. The amount of labeled microorganisms adhered on metal surfaces was determined by activity measurements. The labeling yields for S. mutans, E. coliand C. albicanswere 69.95 ± 7.58%, 78.84 ± 0.44% and 79.71 ± 10.17%, respectively. The mean values for adherence for S. mutans, E. coliand C. albicans on metal samples were 7.02 ± 2.18%, 0.96 ± 0.49% and 8.80 ± 8.24%, respectively. The radiolabeling method could be considered as safe and precise for determining the adherence of microorganisms. (author)

  11. Current status and future perspectives of in vivo small animal imaging using radiolabeled nanoparticles

    International Nuclear Information System (INIS)

    Loudos, George; Kagadis, George C.; Psimadas, Dimitris

    2011-01-01

    Small animal molecular imaging is a rapidly expanding efficient tool to study biological processes non-invasively. The use of radiolabeled tracers provides non-destructive, imaging information, allowing time related phenomena to be repeatedly studied in a single animal. In the last decade there has been an enormous progress in related technologies and a number of dedicated imaging systems overcome the limitations that the size of small animal possesses. On the other hand, nanoparticles (NPs) gain increased interest, due to their unique properties, which make them perfect candidates for biological applications. Over the past 5 years the two fields seem to cross more and more often; radiolabeled NPs have been assessed in numerous pre-clinical studies that range from oncology, till HIV treatment. In this article the current status in the tools, applications and trends of radiolabeled NPs reviewed.

  12. Current status and future perspectives of in vivo small animal imaging using radiolabeled nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Loudos, George, E-mail: gloudos@teiath.gr [Department of Medical Instruments Technology, Technological Educational Institute of Athens, AG. Spyridonos 28, Egaleo 12210 (Greece); Kagadis, George C., E-mail: gkagad@gmail.com [Department of Medical Physics, School of Medicine, University of Patras, P.O. Box 13273, GR-265 04 Rion (Greece); Psimadas, Dimitris, E-mail: dpsimad@chem.uoa.gr [Department of Medical Instruments Technology, Technological Educational Institute of Athens, AG. Spyridonos 28, Egaleo 12210 (Greece); Institute of Radioisotopes and Radiodiagnostic Products, National Center of Scientific Research ' Demokritos' , P.O. 60228, 153 10 Agia Paraskevi, Athens (Greece)

    2011-05-15

    Small animal molecular imaging is a rapidly expanding efficient tool to study biological processes non-invasively. The use of radiolabeled tracers provides non-destructive, imaging information, allowing time related phenomena to be repeatedly studied in a single animal. In the last decade there has been an enormous progress in related technologies and a number of dedicated imaging systems overcome the limitations that the size of small animal possesses. On the other hand, nanoparticles (NPs) gain increased interest, due to their unique properties, which make them perfect candidates for biological applications. Over the past 5 years the two fields seem to cross more and more often; radiolabeled NPs have been assessed in numerous pre-clinical studies that range from oncology, till HIV treatment. In this article the current status in the tools, applications and trends of radiolabeled NPs reviewed.

  13. Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Slatter, J.G. [Pharmacia Corp., Peapack, NJ (United States); Sams, J.P.; Easter, J.A. [Pharmacia Corp., Kalamazoo, MI (United States)] [and others

    2003-05-01

    Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [{sup 14}C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [{sup 14}C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [{sup 14}C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled {sup 14}CO{sub 2}. After 7 daily [{sup 14}C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C{sub max} and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

  14. Indirect calculation of monoclonal antibodies in nanoparticles using the radiolabeling process with technetium 99 metastable as primary factor: Alternative methodology for the entrapment efficiency.

    Science.gov (United States)

    Helal-Neto, Edward; Cabezas, Santiago Sánchez; Sancenón, Félix; Martínez-Máñez, Ramón; Santos-Oliveira, Ralph

    2018-05-10

    The use of monoclonal antibodies (Mab) in the current medicine is increasing. Antibody-drug conjugates (ADCs) represents an increasingly and important modality for treating several types of cancer. In this area, the use of Mab associated with nanoparticles is a valuable strategy. However, the methodology used to calculate the Mab entrapment, efficiency and content is extremely expensive. In this study we developed and tested a novel very simple one-step methodology to calculate monoclonal antibody entrapment in mesoporous silica (with magnetic core) nanoparticles using the radiolabeling process as primary methodology. The magnetic core mesoporous silica were successfully developed and characterised. The PXRD analysis at high angles confirmed the presence of magnetic cores in the structures and transmission electron microscopy allowed to determine structures size (58.9 ± 8.1 nm). From the isotherm curve, a specific surface area of 872 m 2 /g was estimated along with a pore volume of 0.85 cm 3 /g and an average pore diameter of 3.15 nm. The radiolabeling process to proceed the indirect determination were well-done. Trastuzumab were successfully labeled (>97%) with Tc-99m generating a clear suspension. Besides, almost all the Tc-99m used (labeling the trastuzumab) remained trapped in the surface of the mesoporous silica for a period as long as 8 h. The indirect methodology demonstrated a high entrapment in magnetic core mesoporous silica surface of Tc-99m-traztuzumab. The results confirmed the potential use from the indirect entrapment efficiency methodology using the radiolabeling process, as a one-step, easy and cheap methodology. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Electrochemical immobilization of biomolecules on gold surface modified with monolayered L-cysteine

    International Nuclear Information System (INIS)

    Honda, Mitsunori; Baba, Yuji; Sekiguchi, Tetsuhiro; Shimoyama, Iwao; Hirao, Norie

    2014-01-01

    Immobilization of organic molecules on the top of a metal surface is not easy because of lattice mismatch between organic and metal crystals. Gold atoms bind to thiol groups through strong chemical bonds, and a self-assembled monolayer of sulfur-terminated organic molecules is formed on the gold surface. Herein, we suggested that a monolayer of L-cysteine deposited on a gold surface can act as a buffer layer to immobilize biomolecules on the metal surface. We selected lactic acid as the immobilized biomolecule because it is one of the simplest carboxyl-containing biomolecules. The immobilization of lactic acid on the metal surface was carried out by an electrochemical method in an aqueous environment under the potential range varying from − 0.6 to + 0.8 V. The surface chemical states before and after the electrochemical reaction were characterized using X-ray photoelectron spectroscopy (XPS). The N 1s and C 1s XPS spectra showed that the L-cysteine-modified gold surface can immobilize lactic acid via peptide bonds. This technique might enable the immobilization of large organic molecules and biomolecules. - Highlights: • Monolayer l-cysteine deposited on Au surface as a buffer layer to immobilize biomolecules. • Lactic acid as the immobilized biomolecule as it is simple carboxyl-containing biomolecule. • X-ray photoelectron spectroscopy (XPS) of surface chemical states, before and after. • L-cysteine-modified Au surface can immobilize lactic acid via peptide bonds

  16. Watching Conformations of Biomolecules: a Microwave Spectroscopy Approach

    Science.gov (United States)

    Lopez, J. C.

    2011-06-01

    The combination of laser ablation with Fourier transform microwave spectroscopy in supersonic jets (LA-MB-FTMW) has made possible the gas-phase study of solid biomolecules with high melting points. In the experiment, solids are efficiently vaporized by a high-energy laser pulse, supersonically expanded into a evacuated Fabry-Perot cavity and characterised by their rotational spectra. Recent improvements such as the use of picosecond pulse lasers, new ablation nozzles and the extension of the range of the spectrometers to low frequecy have notably increased the sensitivity of our experimental setup. To date different α-, β- and γ-amino acids have been studied using this technique, making possible the characterization of their preferred conformations and gaining insight in the role of intramolecular interactions. Even in conformationally challenging systems the different rotamers of such biomolecules can be identified by rotational spectroscopy as can be illustrated by the assignment of six low-energy conformers in cysteine and aspartic acid, seven in serine and threonine,^a and nine in γ-amino butyric acid (GABA). In all cases the low-energy conformers have been conclusive identified from their experimental rotational and 14N quadrupole coupling constants. The spectra of neurotransmitters and of the nucleic acid bases uracil, thymine, cytosine and guanine have also been studied and their preferred conformers or tautomeric forms determined. The complexes between amino acids and nucleic acid bases with water have also been investigated to obtain information on the possible changes induced in the conformational or tautomeric preferences by the addition of solvent molecules. J. L. Alonso, C. Pérez, M. E. Sanz, J. C. López, S. Blanco, Phys. Chem. Chem. Phys. 11, 617-627 (2009) and references therein M. E. Sanz, J. C. López, J. L. Alonso, Phys. Chem. Chem. Phys., 12, 3573-3578 (2010) S. Blanco, J. C. López, S. Mata and J. L. Alonso, Angew. Chem. Int. Ed. 49, 9187

  17. Novel functionalized fluorescent polymeric nanoparticles for immobilization of biomolecules

    Science.gov (United States)

    Jain, Swati; Chattopadhyay, Sruti; Jackeray, Richa; Abid, C. K. V. Zainul; Singh, Harpal

    2013-07-01

    Novel, size controlled fluorescent polymeric nanoparticles (FPNP) were synthesized having acetoacetoxy functionality on the surface for immobilization of biomolecules which can be utilized as biomarkers and labels in fluoroimmunoassays. Core-shell nanoparticles of poly(styrene, St-methyl methacrylate, MMA-acetoacetoxy ethyl methacrylate, AAEM), stabilized by various concentrations of surfactant, sodium lauryl sulphate (SLS), were obtained by facile miniemulsion co-polymerization encapsulated with pyrene molecules in their hydrophobic core. Analytical, spectroscopic and imaging characterization techniques revealed the formation of stable, monodisperse, spherical nano sized particles exhibiting high luminescence properties. Particles with 1% SLS (S1) showed good dispersion stability and fluorescence intensity and were chosen as ideal candidates for further immobilization studies. Steady state fluorescence studies showed 10 times higher fluorescence intensity of S1 nanoparticles than that of pyrene solution in solvent-toluene at the same concentration. Environmental factors such as pH, ionic strength and time were found to have no effect on fluorescence intensity of FPNPs. Surface β-di-ketone groups were utilized for the covalent immobilization of enzyme conjugated antibodies without any activation or pre-treatment of nanoparticles.Novel, size controlled fluorescent polymeric nanoparticles (FPNP) were synthesized having acetoacetoxy functionality on the surface for immobilization of biomolecules which can be utilized as biomarkers and labels in fluoroimmunoassays. Core-shell nanoparticles of poly(styrene, St-methyl methacrylate, MMA-acetoacetoxy ethyl methacrylate, AAEM), stabilized by various concentrations of surfactant, sodium lauryl sulphate (SLS), were obtained by facile miniemulsion co-polymerization encapsulated with pyrene molecules in their hydrophobic core. Analytical, spectroscopic and imaging characterization techniques revealed the formation of stable

  18. Radiation physics and chemistry of biomolecules. Recent developments

    Science.gov (United States)

    Spotheim-Maurizot, Melanie

    2016-11-01

    A chapter of the book ;Radiation chemistry. From basics to application in materials and life sciences (EDP Science, Paris, France, 2008); was devoted to the state-of-the-art in the research on ionizing radiation (IR) effects on biomolecules. An update, eight years later, seemed pertinent enough to the editors of this journal who accepted to dedicate a Special Issue to the latest developments in this area of high interest for cancer radiotherapy, nuclear workers' radioprotection and food radiosterilisation. We sincerely thank them and the authors who accepted to present reviews of their most recent work. Obviously, only a small part of the research in the fascinating domain of molecular radiobiology can be covered here. Some articles are presenting the contribution of biophysical models and computational techniques to the understanding of IR effects on molecules such as DNA and proteins, or on larger systems such as chromatin, chromosomes and even cells (Nikjoo et al., Štěpán & Davídková, Ballarini & Carante, and Nikitaki et al.). In these papers, as well as in many others, several qualities of IR are compared in order to explain the observed differences of effects. The damages induced by the low energy electrons and new techniques involved in their study are discussed in great detail (Sanche and Fromm & Boulanouar). The chemistry behind the IR induced damages (single or clustered), studied in many laboratories around the world is presented in several papers (Cadet & Wagner, Sevilla et al., Chatgilialoglu et al., and Greenberg). One of them addresses a very useful comparison between the effects of IR and UV exposure on DNA (Ravanat & Douki). The majority of the papers in this Special Issue is dealing with DNA and this reflects the real situation: damages of DNA are more studied than those of other biomolecules. This is due to the role of DNA as main support of hereditary information. Nevertheless, more and more studies are outlining the influence of epigenetic

  19. Si Nanopores Development for External Control of Transport of Biomolecules

    Energy Technology Data Exchange (ETDEWEB)

    Ileri, N; Tringe, J; Letant, S; Palozoglu, A; Stroeve, P; Faller, R

    2008-06-13

    Nazar Ileri has been involved in an independent, multidisciplinary effort to create a new class of molecular sieves for proteins and viruses. Her experimental work has been performed concurrently at two campuses, LLNL and UC Davis, while theoretical components have been largely accomplished at UC Davis. As will be described, the devices she is creating have great potential to improve very significantly the efficiency and selectivity of molecular transport over what is presently available from state-of-the-art membranes. Our biotechnology training program is based on an integrated study of the transport of biomolecules through conically-shaped, nanoporous silicon membranes. The overall objective of this effort is to demonstrate an efficient, highly selective membrane technology that is manufacturable for macroscopic areas and can be employed in sensing, diagnostic and biomedical applications. Our specific aims are to (1) fabricate and characterize the physical characteristics of the membranes, (2) to demonstrate their utility for molecular transport and separation, and (3) to develop models that will facilitate understanding of these devices as well as improved performance of the next generation of devices. We have proposed that the conical pores have superior performance characteristics compared to other porous filters. To study this hypothesis, complementary approaches from different disciplines, such as membrane synthesis, experiment, and molecular simulation need to be combined. This provides an ideal training environment for a future leader in biotechnology. Hence, for this study, Nazar Ileri has started to carry out a full range of experimental and theoretical investigations under our guidance. First, she has begun fabrication of filters with conical/pyramidal pores. She characterized the pores by AFM and SEM, and analyzed the images using wavelets and other mathematical tools. She has also started to conduct biomolecule transport experiments to compare the

  20. Method for radio imaging the myocardium of mammals using radio-labelled lipophil cations

    International Nuclear Information System (INIS)

    1984-01-01

    The invention relates to a method for the radio imaging of myocardia of mammals by concentrating a radiolabelled cation in myocardial tissue and by producing a radiograph using imaging techniques. According to the invention, it is found that a group of substances shows a preference to myocardial tissues upon intravenous injection in mammals. The characteristic of the invention is that radiolabelled quaternary ammonium, quaternary phosphorous or quaternary arsenic compounds with at least two aryl groups are intravenously injected. These substances provide a sufficiently high radioactivity giving an approved diagnostic image of the myocardium. (G.J.P.)

  1. Radiolabelling of antibodies with indium: Use of diethylenetriaminepentaacetic acid (DTPA) as chelating agent

    International Nuclear Information System (INIS)

    Loetscher, H.

    1986-01-01

    /sup 111/In/sup 3+/ was used to radiolabel the F(ab')/sub 2/ fragment of a monoclonal antibody (b-12) raised against a surface antigen of a mammalian breast tumor cell line (5). The in vivo distribution of the radiolabel was analyzed in mice bearing a transplant of fixed tumor cells in the left thigh. The results demonstrate that DTPA can be efficiently coupled to a tumor specific F(ab')/sub 2/ fragment and loaded with /sup 111/In/sup 3+/ yielding a stable, highly labelled complex

  2. Natural Biomolecules and Protein Aggregation: Emerging Strategies against Amyloidogenesis

    Directory of Open Access Journals (Sweden)

    Antonella Sgarbossa

    2012-12-01

    Full Text Available Biomolecular self-assembly is a fundamental process in all organisms. As primary components of the life molecular machinery, proteins have a vast array of resources available to them for self-assembly in a functional structure. Protein self-assembly, however, can also occur in an aberrant way, giving rise to non-native aggregated structures responsible for severe, progressive human diseases that have a serious social impact. Different neurodegenerative disorders, like Huntington’s, Alzheimer’s, and spongiform encephalopathy diseases, have in common the presence of insoluble protein aggregates, generally termed “amyloid,” that share several physicochemical features: a fibrillar morphology, a predominantly beta-sheet secondary structure, birefringence upon staining with the dye Congo red, insolubility in common solvents and detergents, and protease resistance. Conformational constrains, hydrophobic and stacking interactions can play a key role in the fibrillogenesis process and protein–protein and peptide–peptide interactions—resulting in self-assembly phenomena of peptides yielding fibrils—that can be modulated and influenced by natural biomolecules. Small organic molecules, which possess both hydrophilic and hydrophobic moieties able to bind to peptide/protein molecules through hydrogen bonds and hydrophobic and aromatic interactions, are potential candidates against amyloidogenesis. In this review some significant case examples will be critically discussed.

  3. Microbial Diversity in Extreme Marine Habitats and Their Biomolecules.

    Science.gov (United States)

    Poli, Annarita; Finore, Ilaria; Romano, Ida; Gioiello, Alessia; Lama, Licia; Nicolaus, Barbara

    2017-05-16

    Extreme marine environments have been the subject of many studies and scientific publications. For many years, these environmental niches, which are characterized by high or low temperatures, high-pressure, low pH, high salt concentrations and also two or more extreme parameters in combination, have been thought to be incompatible to any life forms. Thanks to new technologies such as metagenomics, it is now possible to detect life in most extreme environments. Starting from the discovery of deep sea hydrothermal vents up to the study of marine biodiversity, new microorganisms have been identified, and their potential uses in several applied fields have been outlined. Thermophile, halophile, alkalophile, psychrophile, piezophile and polyextremophile microorganisms have been isolated from these marine environments; they proliferate thanks to adaptation strategies involving diverse cellular metabolic mechanisms. Therefore, a vast number of new biomolecules such as enzymes, polymers and osmolytes from the inhabitant microbial community of the sea have been studied, and there is a growing interest in the potential returns of several industrial production processes concerning the pharmaceutical, medical, environmental and food fields.

  4. GroPBS: Fast Solver for Implicit Electrostatics of Biomolecules

    Directory of Open Access Journals (Sweden)

    Franziska eBertelshofer

    2015-11-01

    Full Text Available Knowledge about the electrostatic potential on the surface of biomolecules or biomembranes under physiological conditions is an important step in the attempt to characterize the physico-chemical properties of these molecules and in particular also their interactions with each other. Additionally, knowledge about solution electrostatics may guide also the design of molecules with specified properties. However, explicit water models come at a high computational cost, rendering them unsuitable for large design studies or for docking purposes. Implicit models with the water phase treated as a continuum require the numerical solution of the Poisson-Boltzmann Equation (PBE. Here, we present a new flexible program for the numerical solution of the PBE, allowing for different geometries, and the explicit and implicit inclusion of membranes. It involves a discretization of space and the computation of the molecular surface. The PBE is solved using finite differences, the resulting set of equations is solved using a Gauss-Seidel method. It is shown for the example of the sucrose transporter ScrY that the implicit inclusion of a surrounding membrane has a strong effect also on the electrostatics within the pore region and thus need to be carefully considered e.g. in design studies on membrane proteins.

  5. Hybrid carbon nanomaterials for electrochemical detection of biomolecules

    International Nuclear Information System (INIS)

    Laurila, Tomi

    2015-01-01

    Electrochemical detection of different biomolecules in vivo is a promising path towards in situ monitoring of human body and its functions. However, there are several major obstacles, such as sensitivity, selectivity and biocompatiblity, which must be tackled in order to achieve reliably and safely operating sensor devices. Here we show that by utilizing hybrid carbon materials as electrodes to detect two types of neurotransmitters, dopamine and glutamate, several advantages over commonly used electrode materials can be achieved. In particular, we will demonstrate here that it is possible to combine the properties of different carbon allotropes to obtain hybrid materials with greatly improved electrochemical performance. Three following examples of the approach are given: (i) diamond-like carbon (DLC) thin film electrodes with different layer thicknesses, (ii) multi-walled carbon nanotubes grown directly on top of DLC and (iii) carbon nanofibres synthesized on top of DLC thin films. Detailed structural and electrochemical characterization is carried out to rationalize the reasons behind the observed behvior. In addition, results from the atomistic simulations are utilized to obtain more information about the properties of the amorphous carbon thin films. (paper)

  6. Quantification of specific bindings of biomolecules by magnetorelaxometry

    Directory of Open Access Journals (Sweden)

    Steinhoff Uwe

    2008-03-01

    Full Text Available Abstract The binding reaction of the biomolecules streptavidin and anti-biotin antibody, both labelled by magnetic nanoparticles (MNP, to biotin coated on agarose beads, was quantified by magnetorelaxometry (MRX. Highly sensitive SQUID-based MRX revealed the immobilization of the MNP caused by the biotin-streptavidin coupling. We found that about 85% of streptavidin-functionalised MNP bound specifically to biotin-agarose beads. On the other hand only 20% of antibiotin-antibody functionalised MNP were specifically bound. Variation of the suspension medium revealed in comparison to phosphate buffer with 0.1% bovine serum albumin a slight change of the binding behaviour in human serum, probably due to the presence of functioning (non heated serum proteins. Furthermore, in human serum an additional non-specific binding occurs, being independent from the serum protein functionality. The presented homogeneous bead based assay is applicable in simple, uncoated vials and it enables the assessment of the binding kinetics in a volume without liquid flow. The estimated association rate constant for the MNP-labelled streptavidin is by about two orders of magnitude smaller than the value reported for free streptavidin. This is probably due to the relatively large size of the magnetic markers which reduces the diffusion of streptavidin. Furthermore, long time non-exponential kinetics were observed and interpreted as agglutination of the agarose beads.

  7. Interfacial water thickness at inorganic nanoconstructs and biomolecules: Size matters

    Energy Technology Data Exchange (ETDEWEB)

    Cardellini, Annalisa; Fasano, Matteo; Chiavazzo, Eliodoro; Asinari, Pietro, E-mail: pietro.asinari@polito.it

    2016-04-29

    Water molecules in the proximity of solid nanostructures influence both the overall properties of liquid and the structure and functionality of solid particles. The study of water dynamics at solid–liquid interfaces has strong implications in energy, environmental and biomedical fields. This article focuses on the hydration layer properties in the proximity of Carbon Nanotubes (CNTs) and biomolecules (proteins, polypeptides and amino acids). Here we show a quantitative relation between the solid surface extension and the characteristic length of water nanolayer (δ), which is confined at solid–liquid interfaces. Specifically, the size dependence is attributed to the limited superposition of nonbonded interactions in case of small molecules. These results may facilitate the design of novel energy or biomedical colloidal nanosuspensions, and a more fundamental understanding of biomolecular processes influenced by nanoscale water dynamics. - Highlights: • Properties of the water hydration layer are investigated. • New relation between extension of solid size and hydration layer established. • Possible impact on rational design of nanosuspensions.

  8. Atomic level analysis of biomolecules by the scanning atom probe

    International Nuclear Information System (INIS)

    Nishikawa, Osamu; Taniguchi, Masahiro; Ikai, Atsushi

    2009-01-01

    Utilizing the unique features of the scanning atom probe (SAP) the binding states of the biomolecules, leucine and methionine, are investigated at atomic level. The molecules are mass analyzed by detecting a single atom and/or clustering atoms field evaporated from a specimen surface. Since the field evaporation is a static process, the evaporated clustering atoms are closely related with the binding between atoms forming the molecules. For example, many thiophene radicals are detected when polythiophene is mass analyzed by the SAP. In the present study the specimens are prepared by immersing a micro cotton ball of single walled carbon nanotubes (SWCNT) in the leucine or methionine solution. The mass spectra obtained by analyzing the cotton balls exhibit singly and doubly ionized carbon ions of SWCNT and the characteristic fragments of the molecules, CH 3 , CHCH 3 , C 4 H 7 , CHNH 2 and COOH for leucine and CH 3 , SCH 3 , C 2 H 4 , C 4 H 7 , CHNH 2 and COOH for methionine.

  9. Direct patterning of nanoparticles and biomolecules by liquid nanodispensing.

    Science.gov (United States)

    Fabié, Laure; Agostini, Pierre; Stopel, Martijn; Blum, Christian; Lassagne, Benjamin; Subramaniam, Vinod; Ondarçuhu, Thierry

    2015-03-14

    We report on the localized deposition of nanoparticles and proteins, nano-objects commonly used in many nanodevices, by the liquid nanodispensing (NADIS) technique which consists in depositing droplets of a solution through a nanochannel drilled at the apex of an AFM tip. We demonstrate that the size of spots can be adjusted from microns down to sub-50 nm by tuning the channel diameter, independently of the chemical nature of the solute. In the case of nanoparticles, we demonstrated the ultimate limit of the method and showed that large arrays of single (or pairs of) nanoparticles can be reproducibly deposited. We further explored the possibility to deposit different visible fluorescent proteins using NADIS without loss of protein function. The intrinsic fluorescence of these proteins is characteristic of their structural integrity; the retention of fluorescence after NADIS deposition demonstrates that the proteins are intact and functional. This study demonstrates that NADIS can be a viable alternative to other scanning probe lithography techniques since it combines high resolution direct writing of nanoparticles or biomolecules with the versatility of liquid lithography techniques.

  10. Investigation of damage mechanism by ionising radiation on biomolecules

    International Nuclear Information System (INIS)

    Lau How Mooi

    1996-01-01

    Occupational radiation hazard is a very controversial subject. Effects from high radiation doses are well known from past experiences. However, hazard from low doses is still a subject that is hotly debated upon until now. The occupational dosimetry used now is based on a macroscopic scale. Lately, microdosimetry is fast gaining recognition as a more superior way of measuring hazard. More importantly, scientists are researching the basic damage mechanism that leads to biological effects by ionising radiation. In this report, a simulation study of the basic damage mechanism is discussed . This simulation is based upon Monte Carlo calculations and using polyuridylic acid (Poly-U) as the DNA model This simulation tries to relate the physics and chemistry of interactions of ionising radiation with biomolecules. The computer codes used in this simulation, OREC and RADLYS were created by Hamm et al. (1983) in Oak Ridge National Laboratory. The biological endpoints in this simulation are the strand break and base release of the DNA, which is the precursor of all biological effects. These results are compared with model studies that had been done experimentally to check the validity of this simulation. The G-values of strand break and base release from this simulation were -2.35 and 2.75 and compared well with results from irradiation experiments by von Sonntag (I 98 7) from Max Plank's Institute, Germany

  11. Comparison of biomolecules on the basis of Molecular Interaction Potentials

    Directory of Open Access Journals (Sweden)

    Rodrigo Jordi

    2002-01-01

    Full Text Available Molecular Interaction Potentials (MIP are frequently used for the comparison of series of compounds displaying related biological behaviors. These potentials are interaction energies between the considered compounds and relevant probes. The interaction energies are computed in the nodes of grids defined around the compounds. There is a need of detailed and objective comparative analyses of MIP distributions in the framework of structure-activity studies. On the other hand, MIP-based studies do not have to be restricted to series of small ligands, since such studies present also interesting possibilities for the analysis and comparison of biological macromolecules. Such analyses can benefit from the application of new methods and computational approaches. The new software MIPSim (Molecular Interaction Potentials Similarity analysis has recently been introduced with the purpose of analyzing and comparing MIP distributions of series of biomolecules. This program is transparently integrated with other programs, like GAMESS or GRID, which can be used for the computation of the potentials to be analyzed or compared. MIPSim incorporates several definitions of similarity coefficients, and is capable of combining several similarity measures into a single one. On the other hand, MIPSim can perform automatic explorations of the maximum similarity alignments between pairs of molecules.

  12. Tumor uptake of intravenously administered radiolabeled antibodies in ovarian carcinoma patients in relation to antigen expression and other tumor characteristics

    NARCIS (Netherlands)

    Buist, M. R.; Kenemans, P.; Molthoff, C. F.; Roos, J. C.; den Hollander, W.; Brinkhuis, M.; Baak, J. P.

    1995-01-01

    To study factors that possibly influence the heterogeneous tumor uptake of radiolabeled antibodies, tissues from 34 ovarian-carcinoma patients were obtained 2 to 8 days after i.v. injection with radiolabeled murine OV-TL3 or chimeric MOv18 (cMOv18). The tumor uptake and the ratio of tumor to normal

  13. (99m)Tc-aprotinin - optimisation and validation of radiolabelling kits for routine preparation for diagnostic imaging of amyloidosis

    DEFF Research Database (Denmark)

    Denholt, Charlotte; Gillings, Nic

    2016-01-01

    Technetium-99m aprotinin was prepared from an optimised radiolabelling kit formulation containing aprotinin, alkaline buffer and stannous chloride (reducing agent) and radiolabelled using (99m) Tc-pertechnetate. The labelling was achieved within 25 min, with radiochemical purities of >98%....

  14. Radiolabeling of Ceftriaxone with 99mTc as a Targeting Radiopharmaceutical for Staphylococcus Aureus Detection in Mouse Model

    Directory of Open Access Journals (Sweden)

    Akram Fazli

    2012-03-01

    Full Text Available Introduction Bacterial infection is one of the major causes of morbidity and mortality especially in developing countries. Nuclear medicine has an important role in helping the diagnosis of deep-seated infections by developing more specific radiopharmaceuticals. The aim of this study was to evaluate 99mTc-labeling ceftriaxone as a new radiopharmaceutical for Staphylococcus aureus infection imaging in nuclear medicine. Materials and Methods Radiolabeling of ceftriaxone was carried out by adding 370 MBq of 99mTc to 10 mg of ceftriaxone in the presence of 50 µg of SnCl2.2H2O at pH=5. The radiochemical purity and stability tests at room temperature and human blood serum were evaluated with ITLC. Intramuscular infection was induced by injection of Staphylococcus aureus into the left thigh muscle of the mice. The biodistribution of 99mTc-ceftriaxone was studied in normal and infected mice at various times post-injection. Results Radiochemical purity of the product was 94.5±5.4% with a good stability at room temperature and human serum, 80.6% and 71.2% after 24 h, respectively. The biodistribution studies showed the localization of 99mTc-ceftriaxone at the site of infection with high sensitivity without any significant accumulation in vital organs. Conclusion Due to the ease of 99mTc-ceftriaxone conjugation method, high labeling efficiency, and high uptake in the infected muscle, it may provide a promising candidate as a targeting radiopharmaceutical for imaging infectious foci due to Staphylococcus aureus in nuclear medicine.

  15. Interest of radiolabelled leukocyte scintigraphy in the diagnosis of osteo-articular infection; Interet de la scintigraphie aux polynucleaires marques dans le diagnostic des infections osteo-articulaires

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, Ph.; Monet, A.; Guyot, M.; Jeandot, R. [Hopital Pellegrin, Service de Medecine Nucleaire, 33 - Bordeaux (France)

    2004-12-15

    The diagnosis of osteo-articular infection, particularly after orthopedic implant surgery, is often difficult to confirm; so, only the combination of clinical, biological and radiological tests can help the clinician to propose, in a strict aseptic procedure, the surgical specimen harvesting which can alone reach the final positive or negative diagnosis of infection. Nevertheless, all those tests don't have enough accuracy in some cases to confirm the necessity to realize a surgical procedure which can present septic risk. So, nuclear imaging has long been recognized as an effective method for helping in management of such patients. Among isotopic procedures, only radiolabelled leukocyte scintigraphy is actually considered as the most accurate method. But, literature review reports heterogeneous studies considering patient characteristics, gold standard for diagnosis, nuclear medicine procedure variety which makes comparison difficult. Indeed, diagnostic performances can be different considering infection after orthopedic surgery, presence of implant or not, acute or chronic process, microbiological gold standard or long clinical follow-up, the combination of different isotopic procedures and their interpretation. So, an evaluation of the radiolabelled leukocyte scintigraphy in each institute seems to be important to answer as well as possible to clinician questions. (author)

  16. Toward the Atomic-Level Mass Analysis of Biomolecules by the Scanning Atom Probe.

    Science.gov (United States)

    Nishikawa, Osamu; Taniguchi, Masahiro

    2017-04-01

    In 1994, a new type of atom probe instrument, named the scanning atom probe (SAP), was proposed. The unique feature of the SAP is the introduction of a small extraction electrode, which scans over a specimen surface and confines the high field, required for field evaporation of surface atoms in a small space, between the specimen and the electrode. Thus, the SAP does not require a sharp specimen tip. This indicates that the SAP can mass analyze the specimens which are difficult to form in a sharp tip, such as organic materials and biomolecules. Clean single wall carbon nanotubes (CNT), made by high-pressure carbon monoxide process are found to be the best substrates for biomolecules. Various amino acids and dipeptide biomolecules were successfully mass analyzed, revealing characteristic clusters formed by strongly bound atoms in the specimens. The mass analysis indicates that SAP analysis of biomolecules is not only qualitative, but also quantitative.

  17. Laser Raman and infra-red spectra of biomolecule: 5-aminouracil

    Indian Academy of Sciences (India)

    1–4] on substituted biomolecules. These molecules do not occur freely in natural bi- ological metabolism. The understanding of the vibrational spectra of free molecules might be helpful in understanding specific biological processes and in the ...

  18. Morphological changes of calcite single crystals induced by graphene-biomolecule adducts

    Science.gov (United States)

    Calvaresi, Matteo; Di Giosia, Matteo; Ianiro, Alessandro; Valle, Francesco; Fermani, Simona; Polishchuk, Iryna; Pokroy, Boaz; Falini, Giuseppe

    2017-01-01

    Calcite has the capability to interact with a wide variety of molecules. This usually induces changes in shape and morphology of crystals. Here, this process was investigated using sheets of graphene-biomolecule adducts. They were prepared and made dispersible in water through the exfoliation of graphite by tip sonication in the presence tryptophan or N-acetyl-D-glucosamine. The crystallization of calcium carbonate in the presence of these additives was obtained by the vapor diffusion method and only calcite formed. The analysis of the microscopic observations showed that the graphene-biomolecule adducts affected shape and morphology of rhombohedral {10.4} faced calcite crystals, due to their stabilization of additional {hk.0} faces. The only presence of the biomolecule affected minimally shape and morphology of calcite crystals, highlighting the key role of the graphene sheets as 2D support for the adsorption of the biomolecules.

  19. Nanostructured raspberry-like gelatin microspheres for local delivery of multiple biomolecules

    NARCIS (Netherlands)

    Diba, M.; Pape, B.; Klymov, A.; Zhang, Y.; Song, J.; Lowik, D.; Seyednejad, H.; Leeuwenburgh, S.C.G.

    2017-01-01

    Multicompartment particles, which are particles composed of smaller building units, have gained considerable interest during the past decade to facilitate simultaneous and differential delivery of several biomolecules in various applications. Supercritical carbon dioxide (CO2) processing is an

  20. Synthesis of radiolabeled racemic and enanthiomeric antiarrhythmic agents

    International Nuclear Information System (INIS)

    Hsi, R.S.P.; Stolle, W.T.; Stelzer, L.S.; Hester, J.B.; Perricone, S.C.

    1992-01-01

    Ventricular fibrillation is a leading cause of fatality in patients suffering from cardiovascular disorders. Among approaches to treating cardiac dysrhythmia with medicinal agents is the use of compounds categorized as open-quotes Class IIIclose quotes antiarrhythmic agents to prolong cardiac action potential and increase the refractoriness of cardiac tissues without affecting the sodium current. Investigations into structural requirements necessary for such biological activities led to the synthesis of a series of aniline-propanolamine derivatives. This report describes the preparation of carbon-14 and tritium labeled forms of racemic and enantiomeric forms of these derivatives for conducting drug disposition studies in test animals and human subjects

  1. SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications

    DEFF Research Database (Denmark)

    Nilsson, Christa; Barrios-Lopez, Brianda; Kallinen, Annukka

    2013-01-01

    We have developed a highly efficient method for the radiolabeling of phytantriol (PHYT)/oleic acid (OA)-based hexosomes based on the surface chelation of technetium-99m ((99m)Tc) to preformed hexosomes using the polyamine 1, 12-diamino-3, 6, 9-triazododecane (SpmTrien) as chelating agent. We also...

  2. Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides.

    NARCIS (Netherlands)

    Vegt, E.; Eek, A.; Oyen, W.J.G.; Jong, M. de; Gotthardt, M.; Boerman, O.C.

    2010-01-01

    PURPOSE: In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of

  3. In vivo VEGF imaging with radiolabeled bevacizumab in a human ovarian tumor xenograft

    NARCIS (Netherlands)

    Nagengast, Wouter B.; Hospers, Geke A.; Mulder, Nanno H.; de Jong, Johan R.; Hollema, Harry; Brouwers, Adrienne H.; van Dongen, Guns A.; Perk, Lars R.; Lub-de Hooge, Marjolijn N.

    Vascular endothelial growth factor (VEGF), released by tumor cells, is an important growth factor in tumor angiogenesis. The humanized monoclonal antibody bevacizumab blocks VEGF-induced tumor angiogenesis by binding, thereby neutralizing VEGF. Our aim was to develop radiolabeled bevacizumab for

  4. Radiolabeling of VEGF(165) with Tc-99m to evaluate VEGFR expression in tumor angiogenesis

    NARCIS (Netherlands)

    Galli, Filippo; Artico, Marco; Taurone, Samanta; Manni, Isabella; Bianchi, Enrica; Piaggio, Giulia; Weintraub, Bruce D.; Szkudlinski, Mariusz W.; Agostinelli, Enzo; Dierckx, Rudi A. J. O.; Signore, Alberto

    Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool

  5. Extraction, radiolabeling and in vivo biological evaluation of {sup 131}I labeled egonol glycosides extract

    Energy Technology Data Exchange (ETDEWEB)

    Akguel, Yurdanur; Pazar, Erdinc [Ege Univ., Izmir (Turkey). Chemistry Dept.; Yilmaz, Habibe; Sanlier, Senay Hamarat [Ege Univ., Izmir (Turkey). Biochemistry Dept.; Lambrecht, Fatma Yurt [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications; Yilmaz, Osman [Dokuz Eyluel Univ., Izmir (Turkey). Dept. of Lab. Animal Science

    2015-09-01

    Crude extract of S. officinalis L. was found to have suspending agent, hemolytic, antitumor, antioxidant and antimicrobial activities. Its major components benzofurans and benzofuran glycosides have antifungal, anticancer, antibacterial and anticomplement activities and display acetylcholinesterase-cyclooxygenase inhibitory and cytotoxic properties. Recently, it has been reported that egonolgentiobioside is a valuable target for structural modification and warrants further investigation for its potential as a novel pharmaceutical tool for the prevention of estrogen deficiency induced diseases. The aim of the current study is to perform in vivo biological evaluation of a glycosides extract, which was isolated from the fruits endocarp of Styrax officinalis L, identified as egonolgentiobioside and homoegonolgentiobioside and labeled with {sup 131}I. The radiolabeled glycosides extract was labeled with {sup 131}I with high yield. The labeled obtained radiolabeled compound was found to be quite stable and lipophilic. In order to determine its tissue distribution, an in vivo study was performed using healthy female Albino Wistar rats injected by {sup 131}I-glycosides. The biodistribution results showed that clearance of the radiolabeled compound is through the hepatobiliary pathway. The experimental study indicated that the radiolabeled glycosides extract accumulated in the large intestine. Therefore, the potential of {sup 131}I-glycosides might be evaluated in colon cancer cell lines and this might be a promising of tumor-imaging agent.

  6. Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

    International Nuclear Information System (INIS)

    England, Christopher G.; Rui, Lixin; Cai, Weibo

    2017-01-01

    Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. (orig.)

  7. Enhanced specificity in immunoscreening of expression cDNA clones using radiolabeled antigen overlay

    International Nuclear Information System (INIS)

    Chao, S.; Chao, L.; Chao, J.

    1989-01-01

    A highly sensitive and specific method has been developed for immunoscreening clones from an expression cDNA library. The procedures utilize a radiolabeled antigen detection method described originally for the immunoblotting of plasma proteins. Screening of rat alpha 1-antitrypsin clones was used. Comparison between Western blots of alpha 1-antitrypsin using both labeled antigen and protein A detection methods showed that the former yielded lower background and greater sensitivity than the latter. Further, this technique was shown to have a lower detection limit of less than 20 ng through Western blot analysis of varying concentrations of alpha 1-antitrypsin. The procedures are based on the expression of the protein by cDNA clones containing the DNA inserts in the correct reading frame. Following the transfer of phage proteins to nitrocellulose membranes, the bivalent antibodies bind monovalently to both nitrocellulose-bound-antigen in the phage lysates and radiolabeled antigen. The radiolabeled antigen overlay method is superior to the protein A detection method in sensitivity, specificity and reproducibility. This improved method can be applied in general for screening expression cDNA libraries, provided that the specific antiserum and radiolabeled antigen are available

  8. Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies

    Energy Technology Data Exchange (ETDEWEB)

    England, Christopher G. [University of Wisconsin School of Medicine and Public Health, Department of Medical Physics, Madison, WI (United States); Rui, Lixin [University of Wisconsin School of Medicine and Public Health, Department of Medicine, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI (United States); Cai, Weibo [University of Wisconsin School of Medicine and Public Health, Department of Medical Physics, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Carbone Cancer Center, Madison, WI (United States); University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States)

    2017-03-15

    Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future. (orig.)

  9. Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

    International Nuclear Information System (INIS)

    Marik, Jan; Tartis, Michaelann S.; Zhang, Hua; Fung, Jennifer Y.; Kheirolomoom, Azadeh; Sutcliffe, Julie L.; Ferrara, Katherine W.

    2007-01-01

    Synthesis of a radiolabeled diglyceride, 3-[ 18 F]fluoro-1,2-dipalmitoylglycerol [[ 18 F]fluorodipalmitin ([ 18 F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of 18 F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43±10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [ 18 F]FDP with a decay-corrected yield of 70±8% (n=4). PET imaging and biodistribution studies were performed with free [ 18 F]FDP and liposome-incorporated [ 18 F]FDP. Freely injected [ 18 F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [ 18 F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [ 18 F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers

  10. Development of bioMEMS device and package for a spatially programmable biomolecule assembly

    Science.gov (United States)

    Park, Jung Jin

    We report facile in situ biomolecule assembly at readily addressable sites in microfluidic channels after complete fabrication and packaging of the microfluidic device. Aminopolysaccharide chitosan's pH responsive and chemically reactive properties allow electric signal-guided biomolecule assembly onto conductive inorganic surfaces from the aqueous environment, preserving the activity of the biomolecules. Photoimageable SU8 is used on a Pyrex bottom substrate to create microfluidic channels and a PDMS layer is sealed to the SU8 microchannel by compression of their respective substrates between additional top and bottom Plexiglas plates at the package level. Transparent and non-permanently packaged device allows consistently leak-free sealing, simple in situ and ex situ examination of the assembly procedures, fluidic input/outputs for transport of aqueous solutions, and electrical ports to guide the assembly onto the patterned gold electrode sites within the channel. Facile post-fabrication in-situ biomolecule assembly of internal electrodes is demonstrated using electrodeposition of a chitosan film on a patterned gold electrode. Both in situ fluorescence and ex situ profilometer results confirm chitosan-mediated in situ biomolecule assembly, demonstrating a simple approach to direct the assembly of biological components into a completely fabricated device. We believe that this strategy holds significant potential as a simple and generic biomolecule assembly approach for future applications in complex biomolecular or biosensing analyses as well as in sophisticated microfluidic networks as anticipated for future lab-on-a chip.

  11. Bio-NCs - the marriage of ultrasmall metal nanoclusters with biomolecules

    Science.gov (United States)

    Goswami, Nirmal; Zheng, Kaiyuan; Xie, Jianping

    2014-10-01

    Ultrasmall metal nanoclusters (NCs) have attracted increasing attention due to their fascinating physicochemical properties. Today, functional metal NCs are finding growing acceptance in biomedical applications. To achieve a better performance in biomedical applications, metal NCs can be interfaced with biomolecules, such as proteins, peptides, and DNA, to form a new class of biomolecule-NC composites (or bio-NCs in short), which typically show synergistic or novel physicochemical and physiological properties. This feature article focuses on the recent studies emerging at the interface of metal NCs and biomolecules, where the interactions could impart unique physicochemical properties to the metal NCs, as well as mutually regulate biological functions of the bio-NCs. In this article, we first provide a broad overview of key concepts and developments in the novel biomolecule-directed synthesis of metal NCs. A special focus is placed on the key roles of biomolecules in metal NC synthesis. In the second part, we describe how the encapsulated metal NCs affect the structure and function of biomolecules. Followed by that, we discuss several unique synergistic effects observed in the bio-NCs, and illustrate them with examples highlighting their potential biomedical applications. Continued interdisciplinary efforts are required to build up in-depth knowledge about the interfacial chemistry and biology of bio-NCs, which could further pave their ways toward biomedical applications.

  12. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

    International Nuclear Information System (INIS)

    Malviya, G.; Dierckx, R.A.; Conti, F.; Chianelli, M.; Scopinaro, F.; Signore, A.

    2010-01-01

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-α, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with 99m Tc or 111 In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for therapy decision-making and

  13. In vitro and in vivo analysis of radiolabeled clindamycin hydrogel gel by radioscintigraphic techniques

    International Nuclear Information System (INIS)

    Kumar, N.; Datta, M.; Chopra, M.K.; Soni, N.L.; Mittal, G.; Singh, T.; Bhatnagar, A.; Bhawna

    2010-01-01

    Full text: Acne is one of the common dermatological problems caused by microorganism Acne vulgaris, therefore being used commonly in the treatment of acne. Clindamycin is the 7- deoxy, 7- chloro congener of the lincomycin, a macrolide antibiotic derived from Streptomyces lincolnensis. This study was performed for in-vitro and in-vivo estimation of radiolabeled clindamycin hydrogel using radioscintigraphic techniques for transdermal permeation. Clindamycin was supplied as a gift sample by Glenmark Research Laboratory (Mumbai, India) and other chemicals and reagents used were of analytical grade and were purchased from Merck Chemicals (India). Clindamycin was radiolabeled with 99m Tc-pertechnetate using stannous chloride as a reducing agent. Radiolabeled clindamycin was characterized for its stability at room temperature and in physiological conditions (serum). Clindamycin hydrogel was prepared by dispersion of radiolabeled clindamycin in carbopol 980 containing polaxomer as surfactant and methyl paraben as preservative solution. The prepared hydrogel was analysed for in vitro analysis via franz diffusion cell and in vivo studies were performed in balb-C mice for biodistribution and skin permeation and were analysed by radiometry. The results obtained showed labeling efficiency of clindamycin was more than 90%, and that was consistent and the radiolabeled drug was stable upto 24 hrs in serum. In vitro release studies showed an increased release rate till four hours and it's become plateaus after 4 hours. In vivo biodistribution studies were showed 99m Tc clindamycin hydrogel remains stable and follow predominantly hepatic excretion. Biodistribution pattern suggests late redistribution from a storage sight, probably, body fats

  14. Evaluation of new radiopharmaceuticals: synthesis, evaluation, and biodistribution of radiolabelled peptide of VCAM-1 and αvβ3

    International Nuclear Information System (INIS)

    Ardisson, V.

    2006-07-01

    The new development of nuclear medicine implies the search of new isotopes but also for new vectors specific of functions or metabolic pathways. We investigated new radiopharmaceuticals intended for new diagnostic approaches of two physiopathological mechanisms frequently met in our populations: the atherosclerosis vulnerable plaque and the tumor angio genesis. We studied and optimized the iodine and 99 m-technetium radiolabelling, of a series of peptides in order to allow the in vivo use of these tracers for imaging studies in animals and possibly in humans. The radioiodination, was carried out by electrophilic substitution, and technetium was linked by a tri-carbonyl B.F.C.A. (Isolink). The reaction parameters were defined so that the labelling reactions presents a high radiochemical purity (>95%), and a high specificity activity. The reactions are fast and reproducible. Various physicochemical properties: lipo-solubility, stability of labelling, and pharmacokinetic properties: non specific binding, metabolization and organ biodistribution of peptides in animal model, were studied. These results indicate which peptide may be a suitable candidate for targeting trials. (author)

  15. Possibilities in improvement of the specific biodistribution by means of radiolabelled antibodies after complexation. Untersuchungen ueber Moeglichkeiten der Verbesserung der spezifischen Organbindung mit Hilfe von anti-Organ-Antikoerpern durch Komplexbildung

    Energy Technology Data Exchange (ETDEWEB)

    Heinrich, H. (Rostock Univ., Klinik fuer Radiologie, Abt. fuer Experimentelle Nuklearmedizin (Germany))

    1990-01-01

    The applicability of labeled by different nuclides poly- or monoclonal antibodies in nuclear medicine diagnostics is restricted by incidental consequences. Overhigh background activities and/or high (additional) binding reactivities in the liver are troublesome. Hence we examined if the lokalizing biodistribution of labeled antibodies regarding the target organ can be improved by complexation with metal ions. The investigations were carried out with the pancreas of four Beagle dogs. Xenogenic polyclonal antibodies were refined by passing down the gammaglobulin fraction of rabbit serum a sephadex G 200 - column three times and hence radiolabeled by Na{sup 131}I. Then the antibodies were injected i.p. either as complete molecules or as partially digested by pepsin fragments F(ab){sub 2}-fragments in order to avoid nonspecific Fc interactions. In preparing the i.p. injection another part of the antibody preparations both complete and fragments had been complexed with copper ions in an alkaline buffer giving a stable copper-protein-complex (Biuret-complex). Undergoing scanning and after killing the dogs the organ deposition of the radiolabel had been observed and noticed. The complexation with copper of radiolabeled antibodies improves strikingly the specific target organ uptake. Because of inflammatory and other incidental consequences the Fc-fragments should be removed by digestion with enzymes. Higher specific organ uptake should be obtainable if the poyclonal antibody fraction is more refined specifically by immunosorption with respect to its affinity to the specific antigenic structures. (orig.).

  16. Nuclear Medicine

    Science.gov (United States)

    ... Parents/Teachers Resource Links for Students Glossary Nuclear Medicine What is nuclear medicine? What are radioactive tracers? ... funded researchers advancing nuclear medicine? What is nuclear medicine? Nuclear medicine is a medical specialty that uses ...

  17. Effect of membrane hydrophilization on ultrafiltration performance for biomolecules separation

    International Nuclear Information System (INIS)

    Susanto, H.; Roihatin, A.; Aryanti, N.; Anggoro, D.D.; Ulbricht, M.

    2012-01-01

    We characterized the membranes before and after modification. ► We examined the unmodified and modified membranes for biomolecules filtration. ► All the modifications changed the membrane characteristics and the membrane performance. ► All the modifications resulted in UF membranes having higher resistance towards fouling.

  18. MDVRY: a polarizable classical molecular dynamics package for biomolecules

    Science.gov (United States)

    Souaille, M.; Loirat, H.; Borgis, D.; Gaigeot, M. P.

    2009-02-01

    The MDVRY classical molecular dynamics package is presented for the study of biomolecules in the gas and liquid phase. Electrostatic polarization has been implemented in the formalism of point induced dipoles following the model of Thole. Two schemes have been implemented for the calculation of induced dipoles, i.e. resolution of the self-consistent equations and a 'Car-Parrinello' dynamical approach. In this latter, the induced dipoles are calculated at each time step of the dynamics through the dynamics of additional degrees of freedom associated with the dipoles. This method saves computer time and allows to study polarized solvated proteins at a very low CPU cost. The program is written in C-language and runs on LINUX machines. A detailed manual of the code is given. The main features of the package are illustrated taking on examples of proteins in the gas phase or immersed in liquid water. Program summaryProgram title: MDVRY Catalogue identifier: AEBY_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEBY_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 39 156 No. of bytes in distributed program, including test data, etc.: 277 197 Distribution format: tar.bz2 Programming language: C Computer: Linux machines with FFTW Fourier Transform package installed Operating system: Linux machines, SUSE & RedHat distributions Classification: 3, 16.13, 23 External routines: FFTW ( http://www.fftw.org/) Nature of problem: Molecular Dynamics Software package. Solution method: Velocity Verlet algorithm. The implemented force field is composed of intra-molecular interactions and inter-molecular interactions (electrostatics, polarization, van der Waals). Polarization is accounted through induced point dipoles at each atomic site. Supplementary degrees of freedom are

  19. A new algorithm for construction of coarse-grained sites of large biomolecules.

    Science.gov (United States)

    Li, Min; Zhang, John Z H; Xia, Fei

    2016-04-05

    The development of coarse-grained (CG) models for large biomolecules remains a challenge in multiscale simulations, including a rigorous definition of CG representations for them. In this work, we proposed a new stepwise optimization imposed with the boundary-constraint (SOBC) algorithm to construct the CG sites of large biomolecules, based on the s cheme of essential dynamics CG. By means of SOBC, we can rigorously derive the CG representations of biomolecules with less computational cost. The SOBC is particularly efficient for the CG definition of large systems with thousands of residues. The resulted CG sites can be parameterized as a CG model using the normal mode analysis based fluctuation matching method. Through normal mode analysis, the obtained modes of CG model can accurately reflect the functionally related slow motions of biomolecules. The SOBC algorithm can be used for the construction of CG sites of large biomolecules such as F-actin and for the study of mechanical properties of biomaterials. © 2015 Wiley Periodicals, Inc.

  20. Different size biomolecules anchoring on porous silicon surface: fluorescence and reflectivity pores infiltration comparative studies

    Energy Technology Data Exchange (ETDEWEB)

    Giovannozzi, Andrea M.; Rossi, Andrea M. [National Institute for Metrological Research, Thermodynamic Division, Strada delle Cacce 91, 10135 Torino (Italy); Renacco, Chiara; Farano, Alessandro [Ribes Ricecrhe Srl, Via Lavoratori Vittime del Col du Mont 24, 11100 Aosta (Italy); Derosas, Manuela [Biodiversity Srl, Via Corfu 71, 25124 Brescia (Italy); Enrico, Emanuele [National Institute for Metrological Research, Electromagnetism Division, Strada delle Cacce 91, 10135 Torino (Italy)

    2011-06-15

    The performance of porous silicon optical based biosensors strongly depends on material nanomorphology, on biomolecules distribution inside the pores and on the ability to link sensing species to the pore walls. In this paper we studied the immobilization of biomolecules with different size, such as antibody anti aflatoxin (anti Aflatox Ab, {proportional_to}150 KDa), malate dehydrogenase (MDH, {proportional_to}36KDa) and metallothionein (MT, {proportional_to}6KDa) at different concentrations on mesoporous silicon samples ({proportional_to}15 nm pores diameter). Fluorescence measurements using FITC- labeled biomolecules and refractive index analysis based on reflectivity spectra have been employed together to detect the amount of proteins bound to the surface and to evaluate their diffusion inside the pores. Here we suggest that these two techniques should be used together to have a better understanding of what happens at the porous silicon surface. In fact, when pores dimensions are not perfectly tuned to the protein size a higher fluorescence signal doesn't often correspond to a higher biomolecules distribution inside the pores. When a too much higher concentration of biomolecule is anchored on the surface, steric crowd effects and repulsive interactions probably take over and hinder pores infiltration, inducing a small or absent shift in the fringe pattern even if a higher fluorescence signal is registered. (copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  1. Chitosan-mediated in situ biomolecule assembly in completely packaged microfluidic devices.

    Science.gov (United States)

    Park, Jung Jin; Luo, Xiaolong; Yi, Hyunmin; Valentine, Theresa M; Payne, Gregory F; Bentley, William E; Ghodssi, Reza; Rubloff, Gary W

    2006-10-01

    We report facile in situ biomolecule assembly at readily addressable sites in microfluidic channels after complete fabrication and packaging of the microfluidic device. Aminopolysaccharide chitosan's pH responsive and chemically reactive properties allow electric signal-guided biomolecule assembly onto conductive inorganic surfaces from the aqueous environment, preserving the activity of the biomolecules. A transparent and nonpermanently packaged device allows consistently leak-free sealing, simple in situ and ex situ examination of the assembly procedures, fluidic input/outputs for transport of aqueous solutions, and electrical ports to guide the assembly onto the patterned gold electrode sites within the channel. Both in situ fluorescence and ex situ profilometer results confirm chitosan-mediated in situ biomolecule assembly, demonstrating a simple approach to direct the assembly of biological components into a completely fabricated device. We believe that this strategy holds significant potential as a simple and generic biomolecule assembly approach for future applications in complex biomolecular or biosensing analyses as well as in sophisticated microfluidic networks as anticipated for future lab-on-a-chip devices.

  2. Preparation and biodistribution of {sup 59}Fe-radiolabelled iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail: martinapospisilova@gmail.com; Zapotocky, Vojtech; Nesporova, Kristina [Contipro a.s (Czech Republic); Laznicek, Milan; Laznickova, Alice [Charles University, Faculty of Pharmacy in Hradec Králové (Czech Republic); Zidek, Ondrej; Cepa, Martin; Vagnerova, Hana; Velebny, Vladimir [Contipro a.s (Czech Republic)

    2017-02-15

    We report on the {sup 59}Fe radiolabelling of iron oxide nanoparticle cores through post-synthetic isotope exchange ({sup 59}Fe-IONP{sub ex}) and precursor labelling ({sup 59}Fe-IONP{sub pre}). Scanning electron microscopy and dynamic light scattering measurements showed no impact of radiolabelling on nanoparticle size or morphology. While incorporation efficiencies of these methods are comparable—83 and 90% for precursor labelling and post-synthetic isotope exchange, respectively—{sup 59}Fe-IONP{sub pre} exhibited much higher radiochemical stability in citrated human plasma. Quantitative ex vivo biodistribution study of {sup 59}Fe-IONP{sub pre} coated with triethylene glycol was performed in Wistar rats. Following the intravenous administration, high {sup 59}Fe concentration was observed in the lung and the organs of the reticuloendothelial system such as the liver, the spleen and the femur.

  3. Use of radiolabeled monoclonal anti-B1 antibody for B lymphocyte imaging in Rhesus monkeys

    International Nuclear Information System (INIS)

    Letvin, N.L.; Zalutsky, M.R.; Chalifoux, L.V.; Atkins, H.L.

    1987-01-01

    Imaging tissues rich in B lymphocytes in man using a radiolabeled monoclonal anti-B cell antibody would be extremely useful in the clinical staging of non-Hodgkins lymphomas. Studies were done in rhesus monkeys using radiolabeled monoclonal anti-B1 antibody to determine the feasibility of such an approach. Immunohistologic studies demonstrated that infused monoclonal anti-B1 binds in vivo with specificity to B cells in lymph nodes and spleen. The kinetics of clearance of 131 I-labeled anti-B1 were determined. The B lymphocyte-rich spleen could be readily visualized by gamma camera scanning without significant background and without the need for image intensification or blood background subtraction techniques. These data support the feasibility of using anti-B1 for staging B cell lymphomas in man. (author)

  4. Technical Report (Final): Development of Solid State Reagents for Preparing Radiolabeled Imaging Agents

    Energy Technology Data Exchange (ETDEWEB)

    Kabalka, George W

    2011-05-20

    The goal of this research was on the development of new, rapid, and efficient synthetic methods for incorporating short-lived radionuclides into agents of use in measuring dynamic processes. The initial project period (Year 1) was focused on the preparation of stable, solid state precursors that could be used to efficiently incorporate short-lived radioisotopes into small molecules of use in biological applications (environmental, plant, and animal). The investigation included development and evaluation of new methods for preparing carbon-carbon and carbon-halogen bonds for use in constructing the substrates to be radiolabeled. The second phase (Year 2) was focused on developing isotope incorporation techniques using the stable, boronated polymeric precursors. The final phase (Year 3), was focused on the preparation of specific radiolabeled agents and evaluation of their biodistribution using micro-PET and micro-SPECT. In addition, we began the development of a new series of polymeric borane reagents based on polyethylene glycol backbones.

  5. Langmuir hydrogen dissociation approach in radiolabeling carbon nanotubes and graphene oxide

    International Nuclear Information System (INIS)

    Badun, Gennadii A.; Chernysheva, Maria G.; Eremina, Elena A.; Egorov, Alexander V.; Grigorieva, Anastasia V.

    2016-01-01

    Carbon-based nanomaterials have piqued the interest of several researchers. At the same time, radioactive labeling is a powerful tool for studying processes in different systems, including biological and organic; however, the introduction of radioactive isotopes into carbon-based nanomaterial remains a great challenge. We have used the Langmuir hydrogen dissociation method to introduce tritium in single-walled carbon nanotubes and graphene oxide. The technique allows us to achieve a specific radioactivity of 107 and 27 Ci/g for single-layer graphene oxide and single-walled carbon nanotubes, respectively. Based on the analysis of characteristic Raman modes at 1350 and 1580 cm -1 , a minimal amount of structural changes to the nanomaterials due to radiolabeling was observed. The availability of a simple, nondestructive, and economic technique for the introduction of radiolabels to single-walled carbon nanotubes and graphene oxide will ultimately expand the applicability of these materials.

  6. An Alternate, Egg-Free Radiolabeled Meal Formulation for Gastric-Emptying Scintigraphy.

    Science.gov (United States)

    Garrigue, Philippe; Bodin-Hullin, Aurore; Gonzalez, Sandra; Sala, Quentin; Guillet, Benjamin

    2017-07-01

    Tc-radiolabeled scrambled eggs (SEs) are most often used as the ingested solid phase for gastric-emptying scintigraphy, leading egg-reluctant patients to avoid the examination. We formulated and validated 2 egg-free alternate meals, in the absence of any commercialized formulation: chocolate mug cake (MC) and scrambled tofu (ST). Six healthy volunteers underwent gastric-emptying scintigraphy after ingesting Tc-radiolabeled MC, ST, or SE. Gastric retention indexes did not change significantly between formulations (% of overtime variation to SE: MC 7.75% ± 7.1%, ST 7.17% ± 5.8%; P = 0.6618, not statistically significant), suggesting MC and ST as interesting egg-free alternatives.

  7. Langmuir hydrogen dissociation approach in radiolabeling carbon nanotubes and graphene oxide

    Energy Technology Data Exchange (ETDEWEB)

    Badun, Gennadii A.; Chernysheva, Maria G.; Eremina, Elena A.; Egorov, Alexander V. [Lomonosov Moscow State Univ. (Russian Federation). Dept. of Chemistry; Grigorieva, Anastasia V. [Lomonosov Moscow State Univ., Moscow (Russian Federation). Dept. of Materials Science

    2016-11-01

    Carbon-based nanomaterials have piqued the interest of several researchers. At the same time, radioactive labeling is a powerful tool for studying processes in different systems, including biological and organic; however, the introduction of radioactive isotopes into carbon-based nanomaterial remains a great challenge. We have used the Langmuir hydrogen dissociation method to introduce tritium in single-walled carbon nanotubes and graphene oxide. The technique allows us to achieve a specific radioactivity of 107 and 27 Ci/g for single-layer graphene oxide and single-walled carbon nanotubes, respectively. Based on the analysis of characteristic Raman modes at 1350 and 1580 cm{sup -1}, a minimal amount of structural changes to the nanomaterials due to radiolabeling was observed. The availability of a simple, nondestructive, and economic technique for the introduction of radiolabels to single-walled carbon nanotubes and graphene oxide will ultimately expand the applicability of these materials.

  8. Nanomedicine, nanotechnology in medicine

    Science.gov (United States)

    Boisseau, Patrick; Loubaton, Bertrand

    2011-09-01

    Nanomedicine is a relatively new field of science and technology. It looks sometimes ill defined and interpretations of that term may vary, especially between Europe and the United States. By interacting with biological molecules, therefore at nanoscale, nanotechnology opens up a vast field of research and application. Interactions between artificial molecular assemblies or nanodevices and biomolecules can be understood both in the extracellular medium and inside the human cells. Operating at nanoscale allows to exploit physical properties different from those observed at microscale such as the volume/surface ratio. The investigated diagnostic applications can be considered for in vitro as well as for in vivo diagnosis. In vitro, the synthesised particles and manipulation or detection devices allow for the recognition, capture, and concentration of biomolecules. In vivo, the synthetic molecular assemblies are mainly designed as a contrast agent for imaging. A second area exhibiting a strong development is "nanodrugs" where nanoparticles are designed for targeted drug delivery. The use of such carriers improves the drug biodistribution, targeting active molecules to diseased tissues while protecting healthy tissue. A third area of application is regenerative medicine where nanotechnology allows developing biocompatible materials which support growth of cells used in cell therapy. The application of nanotechnology to medicine raises new issues because of new uses they allow, for instance: Is the power of these new diagnostics manageable by the medical profession? What means treating a patient without any clinical signs? Nanomedicine can contribute to the development of a personalised medicine both for diagnosis and therapy. There exists in many countries existing regulatory frameworks addressing the basic rules of safety and effectiveness of nanotechnology based medicine, whether molecular assemblies or medical devices. However, there is a need to clarify or to

  9. Synthesis, radiolabeling and biodistribution of a new opioid glucuronide derivative. Ethyl-morphine glucuronide (em-glu)

    International Nuclear Information System (INIS)

    Enginar, H.

    2012-01-01

    In current study, ethyl-morphine (em) was synthesized from the morphine and glucuronidated via enzymatic mechanism. The conjugated glucuronide ethyl-morphine (em-glu) was radiolabeled with 131 I using iodogen method. The quality control studies of radiolabeled compound ( 131 I-em-glu) were done with Thin Layer Radio Chromatography to confirm the radiolabeling efficiency. Biodistribution studies of 131 I labeled em-glu were run on healthy male Albino Wistar rats. The distribution figures demonstrated that 131 I-em-glu was eliminated through the small intestine, large intestine and accumulated in urinary bladder both receptor blocked and unblocked biodistribution studies. A greater uptake of the radiolabeled substance was observed in the m.pons, hypothalamus and mid brain than in the other branches of the rats' brains. (author)

  10. Tumor affinity of radiolabeled peanut agglutinin compared with that of Ga-67 citrate in animal models

    International Nuclear Information System (INIS)

    Yokoyama, K.; Aburano, T.; Watanabe, N.; Kawabata, S.; Ishida, H.; Mukai, K.; Tonami, N.; Hisada, K.

    1985-01-01

    Peanut agglutinin (PNA) binds avidly to the immunodominant group of the tumor associated T antigen. The purpose of this study was to evaluate oncodiagnostic potential of radiolabeled PNA in animal models. PNA was labeled with I-125 or I-131 by Iodogen and also with In-111 by cyclic DTPA anhydride. The biological activity of PNA was examined by a hemaglutination titer with a photometer before and after labeling. Animal tumor models used were Lewis Lung Cancer(LLC), B-16 Melanotic Melanoma(MM), Yoshida Sarcoma(YS), Ehrlich Ascites Tumor(EAT and Hepatoma AH109A(HAH). Inflammatory tissue induced by turpentine oil was used as an abscess model. Serial scintigraphic images were obtained following IV injections of 100 μCi of I-131 or In-111-DTPA-PNA. The tumor affinity of Ga-67 citrate was studied to compare that of radiolabeled PNA. Tissue biodistribution was studied in EAT bearing mice. All of these tumor models except HAH were clearly visible by radiolabeled PNA without subtraction techniques. In the models of LLC and EAT, PNA showed the better accumulation into the tumor tissue than Ga-67 citrate. In YS and MM, PNA represented almost the same accumulation as Ga-67 citrate. The localization of PNA into abscess tissue wasn't found although Ga-67 citrate markedly accumulated into abscess tissue as well as tumor tissue. The clearance of PNA from tumor was slower than those from any other organs. Tumor to muscle ratio was 5.1 at 48hrs. and tumor to blood ratio increased with time to 2.3 at 96hrs. These results suggested that radiolabeled PNA may have a potential in the detection of tumor

  11. Albumin-derived peptides efficiently reduce renal uptake of radiolabelled peptides

    International Nuclear Information System (INIS)

    Vegt, Erik; Eek, Annemarie; Oyen, Wim J.G.; Gotthardt, Martin; Boerman, Otto C.; Jong, Marion de

    2010-01-01

    In peptide-receptor radionuclide therapy (PRRT), the maximum activity dose that can safely be administered is limited by high renal uptake and retention of radiolabelled peptides. The kidney radiation dose can be reduced by coinfusion of agents that competitively inhibit the reabsorption of radiolabelled peptides, such as positively charged amino acids, Gelofusine, or trypsinised albumin. The aim of this study was to identify more specific and potent inhibitors of the kidney reabsorption of radiolabelled peptides, based on albumin. Albumin was fragmented using cyanogen bromide and six albumin-derived peptides with different numbers of electric charges were selected and synthesised. The effect of albumin fragments (FRALB-C) and selected albumin-derived peptides on the internalisation of 111 In-albumin, 111 In-minigastrin, 111 In-exendin and 111 In-octreotide by megalin-expressing cells was assessed. In rats, the effect of Gelofusine and albumin-derived peptides on the renal uptake and biodistribution of 111 In-minigastrin, 111 In-exendin and 111 In-octreotide was determined. FRALB-C significantly reduced the uptake of all radiolabelled peptides in vitro. The albumin-derived peptides showed different potencies in reducing the uptake of 111 In-albumin, 111 In-exendin and 111 In-minigastrin in vitro. The most efficient albumin-derived peptide (peptide 6), was selected for in vivo testing. In rats, 5 mg of peptide 6 very efficiently inhibited the renal uptake of 111 In-minigastrin, by 88%. Uptake of 111 In-exendin and 111 In-octreotide was reduced by 26 and 33%, respectively. The albumin-derived peptide 6 efficiently inhibited the renal reabsorption of 111 In-minigastrin, 111 In-exendin and 111 In-octreotide and is a promising candidate for kidney protection in PRRT. (orig.)

  12. Preparation and characterization of high-specific activity radiolabeled 50 S measles virus RNA

    International Nuclear Information System (INIS)

    Spruance, S.L.; Ashton, B.N.; Smith, C.B.

    1980-01-01

    A method is described to radiolabeled measles virus RNA for hybridization studies. Tritiated nucleosides were added to the media of measles virus infected Vero cells and negative-strand (genome) RNA with a specific activity of 6X10 5 c.p.m./μg was purified from viral nucleocapsids. 50 S RNA was the sole RNA present in nucleocapsids and self-annealed to 50% due to the presence of 25% 50 S plus-strands (anti-genomes). (Auth.)

  13. Evaluation of a technique for the intraoperative detection of a radiolabelled monoclonal antibody against colorectal cancer

    International Nuclear Information System (INIS)

    Waddington, W.A.; Todd-Pokropek, A.; Short, M.D.; Davidson, B.R.; Boulos, P.B.; Middlesex Hospital, London

    1991-01-01

    Occult tumour deposits may be localised at operation with a radiation detecting probe following the administration of a radiolabelled monoclonal antibody (MoAb) recognising a tumour-associated antigen. We have recently evaluated the clinical usefulness of this technique in detecting primary colorectal tumours targetted with an indium-111 MoAb. In the present study the physical characteristics of the two detector systems used were investigated; a sodium iodide [NaI(Tl)] scintilation detector and a cadmium telluride (CdTe) semiconductor probe. Limitations of the technique in use have been examined by testing the statistical significance of tumour detecting using an abdominal phantom based on the currently available clinical biodistribution data for tumour uptake of radiolabelled MoAbs. The effect of tumour volume, antibody uptake, collimation and counting conditions was examined. Results indicate that tumours of 10-ml volume may be detected with the NaI(Tl) probe at the lowest levels of radiolabelled antibody uptake currently reported in the literature but that at higher published levels, lesions as small as 1 ml may be identified with both detector systems. Detector sensitivity and limited antibody specificity restrict the usefulness of the technique, although moderate improvements in tumour uptake may allow the detection of tumour deposits not clinically apparent. The statistical significance criterion used for this study could be an accurate and reliable indicator for tumour detection in vivo. (orig.)

  14. Radiolabeling of VEGF165 with 99mTc to evaluate VEGFR expression in tumor angiogenesis.

    Science.gov (United States)

    Galli, Filippo; Artico, Marco; Taurone, Samanta; Manni, Isabella; Bianchi, Enrica; Piaggio, Giulia; Weintraub, Bruce D; Szkudlinski, Mariusz W; Agostinelli, Enzo; Dierckx, Rudi A J O; Signore, Alberto

    2017-06-01

    Angiogenesis is the main process responsible for tumor growth and metastatization. The principal effector of such mechanism is the vascular endothelial growth factor (VEGF) secreted by cancer cells and other components of tumor microenvironment. Radiolabeled VEGF analogues may provide a useful tool to noninvasively image tumor lesions and evaluate the efficacy of anti-angiogenic drugs that block the VEGFR pathway. Aim of the present study was to radiolabel the human VEGF165 analogue with 99mTechnetium (99mTc) and to evaluate the expression of VEGFR in both cancer and endothelial cells in the tumor microenvironment. 99mTc-VEGF showed in vitro binding to HUVEC cells and in vivo to xenograft tumors in mice (ARO, K1 and HT29). By comparing in vivo data with immunohistochemical analysis of excised tumors we found an inverse correlation between 99mTc-VEGF165 uptake and VEGF histologically detected, but a positive correlation with VEGF receptor expression (VEGFR1). Results of our studies indicate that endogenous VEGF production by cancer cells and other cells of tumor microenvironment should be taken in consideration when performing scintigraphy with radiolabeled VEGF, because of possible false negative results due to saturation of VEGFRs.

  15. Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging

    Directory of Open Access Journals (Sweden)

    Vadim Bernard-Gauthier

    2015-12-01

    Full Text Available Over the last 20 years, intensive investigation and multiple clinical successes targeting protein kinases, mostly for cancer treatment, have identified small molecule kinase inhibitors as a prominent therapeutic class. In the course of those investigations, radiolabeled kinase inhibitors for positron emission tomography (PET imaging have been synthesized and evaluated as diagnostic imaging probes for cancer characterization. Given that inhibitor coverage of the kinome is continuously expanding, in vivo PET imaging will likely find increasing applications for therapy monitoring and receptor density studies both in- and outside of oncological conditions. Early investigated radiolabeled inhibitors, which are mostly based on clinically approved tyrosine kinase inhibitor (TKI isotopologues, have now entered clinical trials. Novel radioligands for cancer and PET neuroimaging originating from novel but relevant target kinases are currently being explored in preclinical studies. This article reviews the literature involving radiotracer design, radiochemistry approaches, biological tracer evaluation and nuclear imaging results of radiolabeled kinase inhibitors for PET reported between 2010 and mid-2015. Aspects regarding the usefulness of pursuing selective vs. promiscuous inhibitor scaffolds and the inherent challenges associated with intracellular enzyme imaging will be discussed.

  16. Development of radiolabeled mannose-dextran conjugates for sentinel lymph node detection

    International Nuclear Information System (INIS)

    Fernandez Nunez, Eutimio Gustavo

    2011-01-01

    Early diagnosis of tumors and metastasis is the current cornerstone in public health policies directed towards the fights against cancer. In breast cancer and melanoma, the sentinel lymph node biopsy has been widely used for diagnoses of metastasis. The minor impact in patient of this technique compared with total nodes dissection and the accurate definition of therapeutic strategies have powered its spreading. The aim of this work was the development of radiolabeled dextran-mannose conjugates for diagnosis using the stable technetium core [ 99m Tc(CO)3] + . Cysteine, a trident ligand, was attached to the conjugates backbone, as a chelate for 99m Tc labeling. Radiolabeling conditions established for all products considered in this study showed high radiochemical purities (> 90%) and specific activities (>59,9 MBq/nmol) as well and high stability obtained through in vitro tests. The lymphatic node uptake increased significantly (4-folds) when mannose units were added to the conjugates compared with those without this monosaccharide. The radiolabeled cysteine-mannose-dextran conjugate with 30 kDa ( 99m Tc - DCM2) showed the best performance at different injected activities among the studied tracers. Concentrations of this radio complex higher than 1 M demonstrated an improvement of lymph node uptakes. Comparisons of 99m Tc - DCM2 performance with commercial radiopharmaceuticals in Brazil market for lymph node detection showed its upper profile. (author)

  17. Composite Scaffold of Poly(Vinyl Alcohol) and Interfacial Polyelectrolyte Complexation Fibers for Controlled Biomolecule Delivery

    Science.gov (United States)

    Cutiongco, Marie Francene A.; Choo, Royden K. T.; Shen, Nathaniel J. X.; Chua, Bryan M. X.; Sju, Ervi; Choo, Amanda W. L.; Le Visage, Catherine; Yim, Evelyn K. F.

    2015-01-01

    Controlled delivery of hydrophilic proteins is an important therapeutic strategy. However, widely used methods for protein delivery suffer from low incorporation efficiency and loss of bioactivity. The versatile interfacial polyelectrolyte complexation (IPC) fibers have the capacity for precise spatiotemporal release and protection of protein, growth factor, and cell bioactivity. Yet its weak mechanical properties limit its application and translation into a viable clinical solution. To overcome this limitation, IPC fibers can be incorporated into polymeric scaffolds such as the biocompatible poly(vinyl alcohol) hydrogel (PVA). Therefore, we explored the use of a composite scaffold of PVA and IPC fibers for controlled biomolecule release. We first observed that the permeability of biomolecules through PVA films were dependent on molecular weight. Next, IPC fibers were incorporated in between layers of PVA to produce PVA–IPC composite scaffolds with different IPC fiber orientation. The composite scaffold demonstrated excellent mechanical properties and efficient biomolecule incorporation. The rate of biomolecule release from PVA–IPC composite grafts exhibited dependence on molecular weight, with lysozyme showing near-linear release for 1 month. Angiogenic factors were also incorporated into the PVA–IPC grafts, as a potential biomedical application of the composite graft. While vascular endothelial growth factor only showed a maximum cumulative release of 3%, the smaller PEGylated-QK peptide showed maximum release of 33%. Notably, the released angiogenic biomolecules induced endothelial cell activity thus indicating retention of bioactivity. We also observed lack of significant macrophage response against PVA–IPC grafts in a rabbit model. Showing permeability, mechanical strength, precise temporal growth factor release, and bioinertness, PVA–IPC fibers composite scaffolds are excellent scaffolds for controlled biomolecule delivery in soft tissue

  18. Composite scaffold of poly(vinyl alcohol and interfacial polyelectrolyte complexation fibers for controlled biomolecule delivery

    Directory of Open Access Journals (Sweden)

    Marie Francene Arnobit Cutiongco

    2015-02-01

    Full Text Available Controlled delivery of hydrophilic proteins is an important therapeutic strategy. However, widely used methods for protein delivery suffer from low incorporation efficiency and loss of bioactivity. The versatile interfacial polyelectrolyte complexation (IPC fibers have the capacity for precise spatiotemporal release and protection of protein, growth factor and cell bioactivity. Yet its weak mechanical properties limit its application and translation into a viable clinical solution. To overcome this limitation, IPC fibers can be incorporated into polymeric scaffolds such as the biocompatible poly(vinyl alcohol hydrogel (PVA. Therefore, we explored the use of a composite scaffold of PVA and IPC fibers for controlled biomolecule release. We first observed that the permeability of biomolecules through PVA films were dependent on molecular weight, with lysozyme showing near-linear release for 1 month. Next, IPC fibers were incorporated in between layers of PVA to produce PVA-IPC composite scaffolds with different IPC fiber orientation. The composite scaffold demonstrated excellent mechanical properties and efficient biomolecule incorporation. The rate of biomolecule release from PVA-IPC composite grafts exhibited dependence on molecular weight. Angiogenic factors were also incorporated into the PVA-IPC grafts, as a potential biomedical application of the composite graft. While vascular endothelial growth factor only showed a maximum cumulative release of 3%, the smaller PEGylated-QK peptide showed maximum release of 33%. Notably, the released angiogenic biomolecules induced endothelial cell metabolic activity thus indicating retention of bioactivity. We also observed lack of significant macrophage response against PVA-IPC grafts in a rabbit model. Showing permeability, mechanical strength, precise temporal growth factor release and bioinertness, PVA-IPC fibers composite scaffolds are excellent scaffolds for controlled biomolecule delivery in soft

  19. Photopatterning of self assembled monolayers on oxide surfaces for the selective attachment of biomolecules.

    Science.gov (United States)

    Hazarika, Pompi; Behrendt, Jonathan M; Petersson, Linn; Wingren, Christer; Turner, Michael L

    2014-03-15

    The immobilization of functional biomolecules to surfaces is a critical process for the development of biosensors for disease diagnostics. In this work we report the patterned attachment of single chain fragment variable (scFv) antibodies to the surface of metal oxides by the photodeprotection of self-assembled monolayers, using near-UV light. The photodeprotection step alters the functionality at the surface; revealing amino groups that are utilized to bind biomolecules in the exposed regions of the substrate only. The patterned antibodies are used for the detection of specific disease biomarker proteins in buffer and in complex samples such as human serum. © 2013 Elsevier B.V. All rights reserved.

  20. Chemical design of radiolabeled antibody fragments for low renal radioactivity levels.

    Science.gov (United States)

    Arano, Y; Fujioka, Y; Akizawa, H; Ono, M; Uehara, T; Wakisaka, K; Nakayama, M; Sakahara, H; Konishi, J; Saji, H

    1999-01-01

    The renal uptake of radiolabeled antibody fragments presents a problem in targeted imaging and therapy. We hypothesized that the renal radioactivity levels of radiolabeled antibody fragments could be reduced if radiolabeled compounds of urinary excretion were released from glomerularly filtered antibody fragments before they were incorporated into renal cells by the action of brush border enzymes, present on the lumen of renal tubules. 3'-[131I]Iodohippuryl N(epsilon)-maleoyl-L-lysine ([131I]HML) was conjugated with a thiolated Fab fragment because the glycyl-lysine sequence in HML is a substrate for a brush border enzyme and metaiodohippuric acid is released by cleavage of the linkage. Fab fragments were also radiolabeled by direct radioiodination (125I-Fab) or by conjugation with meta-[125I]-iodohippuric acid via an amide bond [N-(5-maleimidopentyl) 3'-iodohippuric acid amide ([125I]MPH-Fab)] or an ester bond [maleimidoethy 3'-iodohippurate ([125I]MIH-Fab)] by procedures similar to those used for [131I]HML-Fab. In biodistribution experiments in mice, [131I]HML-Fab demonstrated markedly low renal radioactivity levels with kidney:blood ratios of radioactivity of 1 from 10 min to 1 h due to rapid release of meta-[131I]iodohippuric acid. [125]MIH-Fab and 1251-Fab reached their peak ratios of 3.8 and 7.3 at 1 h, respectively, and [125I]MPH-Fab showed the maximum ratio of 16.8 at 6 h. In subcellular distribution studies, both [125I]MIH-Fab and 125I-Fab showed migration of radioactivity from the membrane to the lysosomal fraction of the renal cells from 10 to 30 min postinjection, whereas the majority of the radioactivity was detected only in the membrane fraction after administration of [131I]HML-Fab at both time points. In nude mice, [131I]HML-Fab showed one-quarter of the renal radioactivity of simultaneously administered 125I-Fab without impairing the target radioactivity levels 3 h after injection. These findings indicated that HML is a useful reagent for targeted

  1. Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

    International Nuclear Information System (INIS)

    Liu, Guozheng; Dou, Shuping; He, Jiang; Liu, Xinrong; Rusckowski, Mary; Hnatowich, Donald J.

    2007-01-01

    Pretargeting with phosphorodiamidate morpholino oligomers (MORFs) involves administration of a MORF-conjugated anti-tumor antibody such as MN14 as a pretargeting agent before that of the radiolabeled complementary MORF (cMORF) as the effector. The dosages of the pretargeting agent and effector, the pretargeting interval, and the detection time are the four pretargeting variables. The goal of this study was to develop a semiempirical description capable of predicting the biodistribution of the radiolabeled effector in pretargeted mice and then to compare predictions with experimental results from pretargeting studies in tumored animals in which the pretargeting interval and the detection time were both fixed but the dosages of both the effector and the pretargeting agent were separately varied. Pretargeting studies in LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated with MORF and the cMORF radiolabeled with 99m Tc. A description was developed based on our previous observations in the same mouse model of the blood and tumor levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the kidney accumulation of labeled cMORF. The predicted values were then compared with the experimental values. The predicted biodistribution of the radiolabeled effector and the experimental data were in gratifying agreement in normal organs, suggesting that the description of the pretargeting process was reliable. The tumor accumulations occasionally fell outside two standard deviations of that predicted, but after tumor size correction, good agreement between predicted and experimental values was observed here as well. A semiempirical description of the biodistribution of labeled cMORF was capable of predicting the biodistribution of the radiolabeled effector in the pretargeted tumored mouse model, demonstrating that the underlying pretargeting concepts are correct. We

  2. Approaches in the design of 99mTc based peptide radiolabelling for tumour targeting

    International Nuclear Information System (INIS)

    Yokoyama, A.; Horiuchi, K.; Arano, Y.

    2001-01-01

    One of the major drawbacks in diagnostic and/or therapeutic uses of peptides radiolabelled with radiometals via bifunctional chelating agents (BCA) is their accumulation in excretory organs such as liver or kidney. Thus, the aim of the project is centred in the search for chemical and radiochemical approaches to reduce radioactivity accumulated in excretory organs while preserving the in vivo receptor binding affinity of the peptide. During the first stage a suitable procedure using the F-moc-chemistry (solid phase) was developed and synthesis of DTPA-D-Phen1-Octreotide and DTPA-L-Phen1-Octreotide was carried out. During the synthesis, the need to improve the yield demanded the synthesis of a DTPA derivative holding only one reactive carboxylic group to avoid side intermolecular reaction. The availability of both isomeric conjugated octreotide led to their radiolabelling with 111 In. Their metabolic studies in animals indicated that the degradation rate of the peptide containing the natural aminoacid, 111 In DTPA-L-Phen1-Octreotide, was slightly higher than the corresponding D-aminoacid derivative, as expected. Stability of the peptide during radiolabelling with 99m Tc was then studied, requiring the use of variable agents such as ascorbic acid, dithionite and stannous ion. The selected peptide, RC-160, was provided by the IAEA and, as reference compounds, corresponding iodinated and radioiodinated peptides were synthesized. Demonstration of the stability of the peptide was carried out using disodium 2-nitro-5-thiosulfobenzoate (NTBS) and the lack of Bunte salt formation served as an indication of the stability of the disulfide bond under various mild conditions required for the future radiolabelling with 99m Tc. The knowledge gained served in moving to the next stage of 99m Tc radiolabelling using HYNIC as the BCA and tricine as co-ligands. The biodistribution studies demonstrated great accumulation on excretory organs. This led us to look for a model protein

  3. Controlling plasmon coupling in biomolecule-linked metal nanoparticle assemblies

    Science.gov (United States)

    Sebba, David S.

    Molecular control of plasmon coupling is investigated in biomolecule-linked nanoparticle assemblies in two-particle, small cluster, and extended network formats. The relationship between structure and optical properties is explored through comparison of measured spectra with simulated spectra calculated using structural models based upon measured structural parameters. A variety of techniques are used to characterize nanoparticle assemblies, including ensemble extinction and elastic scattering spectroscopy, single-assembly scattering spectroscopy, transmission electron microscopy, and dynamic light scattering. Initially, molecular control of plasmon coupling is investigated in ˜100 nm assemblies composed of 13 nm gold "satellite" particles tethered by duplex DNA to a 50 nm gold "core" particle. Comparison of core-satellite assemblies formed with duplex DNA tethers of varying length demonstrates that, while core-satellite separation is controlled by the number of base pairs in the DNA tether, structural properties such as core:satellite ratio and yield are independent of DNA tether length. Thus, plasmon coupling within these assemblies is determined by the number of base pairs in the duplex DNA tether; compact assemblies in which tethers are composed of fewer base pairs exhibit plasmon bands that are red-shifted relative to the bands of extended assemblies, indicating increased plasmon coupling in the compact assemblies. Subsequently, core-satellite assemblies are formed with reconfigurable DNA nanostructure tethers that modulate interparticle separation in response to a molecular stimulus. Assembly reconfiguration from a compact to an extended state results in blue-shifting of the assembly plasmon resonance, indicating reduced interparticle coupling and lengthening of the core-satellite tether. Comparison between measured and simulated spectra revealed a close correspondence and provided validation of the structural models that link assembly plasmonic properties

  4. Labelling techniques of biomolecules for targeted radiotherapy. Final report of a co-ordinated research project 1998-2002

    International Nuclear Information System (INIS)

    2003-07-01

    optimization of radiolabelling techniques with beta emitting radioisotopes, including quality control procedures and evaluation of the labelled products in in vitro and in vivo models. Biomolecule carriers that were considered for investigation included somatostatin analogues like lanreotide, Tyr-octreotide, ior-P1394 and vasointestinal peptide (VIP), as well as anti-CEA monoclonal antibody. Using either the bifunctional chelate approach or direct reductive exposure of -SH groups, labelling of these biomolecules with therapeutic radionuclides was pursued. Through these attempts it was expected to identify one or two agents with high radiochemical purity and labelling efficiency for further evaluation. Promising agents would be selected for further investigation using biodistribution studies in animals and uptake in tumour bearing animals. Fifteen selected research institutes from Argentina, Austria, Brazil, Cuba, Greece, Finland, Hungary, India, Italy, Mexico, Pakistan, Peoples Republic of China, Romania, Thailand and Uruguay with recognized expertise in the field of therapeutic radionuclides and radiopharmaceutical research were selected to participate in the CRP. The first research co-ordination meeting to plan the work and define the research protocols to be investigated was held in Milan, Italy in July 1998. At this meeting it was decided to concentrate the efforts on two radionuclides, 188Re and 90Y, which are produced by generator systems and result in carrier free products; lanreotide was selected as a model peptide. Synthesis of the bifunctional chelating agent DOTA was also recommended for the labelling of biomolecules with 90Y. The development of the corresponding coupling techniques, optimization of protocols for direct and indirect labelling of lanreotide and anti-carcino embryonic antigen (CEA) monoclonal antibody and in vitro evaluation in cell lines and membrane receptors were also included in the work plan for the following period. IgG labelled with 131I and

  5. Radiolabeled antibody therapy in non-Hodgkins lymphoma: radiation protection, isotope comparisons and quality of life issues.

    Science.gov (United States)

    Silverman, Daniel H; Delpassand, Ebrahim S; Torabi, Farzad; Goy, Andre; McLaughlin, Peter; Murray, James L

    2004-04-01

    Anti-CD20 antibodies radiolabeled with I-131 tositumomab (Bexxar) or Y-90-Ibritumomab tiuxetan (Zevalin), are similarly efficacious in treating chemotherapy-refractory non-Hodgkin's lymphoma. The relative merits of both radioimmunoconjugates with respect to practical issues, including radiation exposure risk, the advantages and disadvantages of the respective isotopes and other parameters that could affect a patient's quality of life are also important. I-131-labeled antibody treatment often requires inpatient hospitalization due to the inherent risk of exposure from gamma emissions, and patients and families should follow detailed instructions to prevent undue exposure. Other issues relevant to patients and medical staff include: (1) the need for dosimetry to calculate effective therapeutic doses of I-131-labeled anti-B1 (Bexxar) compared with the lack of correlation of dosimetry with marrow toxicity for IDEC-Y2B8 (Zevalin), (2) determining the acute and long-term toxic effects of each agent, (3) time commitments for nuclear medicine staff and patients along with the relative ease of administration, and (4) cost considerations. A more challenging future issue will be to determine the optimal use of Bexxar and Zevalin alone and in combination in ways that will significantly affect patient outcome without compromising quality of life. The recent demonstration of significant response rates in patients having chemotherapy-refractory Non-Hodgkin's Lymphoma (NHL) using both on I-131- and Y-90-labeled anti-CD20 antibodies with minimal toxicity has stimulated comparison of I-131 tositumomab (Bexxar) and Ibritumomab tiuxetan (Zevalin) in terms of radiation safety requirements, the advantages and disadvantages of both radionuclides, and quality-of-life (QOL) issues. Therefore, in this review, we attempt to compare the relative merits of (Bexxar and Zevalin) and address important practical considerations that may influence patient and physician choices regarding treatment

  6. Light-induced immobilisation of biomolecules as an attractive alternative to microdroplet dispensing-based arraying technologies

    DEFF Research Database (Denmark)

    Crookshanks, Meg; Skovsen, Esben; Petersen, Maria Teresa Neves

    2007-01-01

    The present work shows how UV ‘light-induced molecular immobilisation' (LIMI) of biomolecules onto thiol reactive surfaces can be used to make biosensors, without the need for traditional microdispensing technologies. Using ‘LIMI,' arrays of biomolecules can be created with a high degree of repro...

  7. The Polygonal Model: A Simple Representation of Biomolecules as a Tool for Teaching Metabolism

    Science.gov (United States)

    Bonafe, Carlos Francisco Sampaio; Bispo, Jose Ailton Conceição; de Jesus, Marcelo Bispo

    2018-01-01

    Metabolism involves numerous reactions and organic compounds that the student must master to understand adequately the processes involved. Part of biochemical learning should include some knowledge of the structure of biomolecules, although the acquisition of such knowledge can be time-consuming and may require significant effort from the student.…

  8. Tapered Optical Fiber Sensor for Label-Free Detection of Biomolecules

    Directory of Open Access Journals (Sweden)

    Xingwei Wang

    2011-03-01

    Full Text Available This paper presents a fast, highly sensitive and low-cost tapered optical fiber biosensor that enables the label-free detection of biomolecules. The sensor takes advantage of the interference effect between the fiber’s first two propagation modes along the taper waist region. The biomolecules bonded on the taper surface were determined by demodulating the transmission spectrum phase shift. Because of the sharp spectrum fringe signals, as well as a relatively long biomolecule testing region, the sensor displayed a fast response and was highly sensitive. To better understand the influence of various biomolecules on the sensor, a numerical simulation that varied biolayer parameters such as thickness and refractive index was performed. The results showed that the spectrum fringe shift was obvious to be measured even when the biolayer was only nanometers thick. A microchannel chip was designed and fabricated for the protection of the sensor and biotesting. Microelectromechanical systems (MEMS fabrication techniques were used to precisely control the profile and depth of the microchannel on the silicon chip with an accuracy of 2 μm. A tapered optical fiber biosensor was fabricated and evaluated with an Immune globulin G (IgG antibody-antigen pair.

  9. Cellular Viscosity in Prokaryotes and Thermal Stability of Low Molecular Weight Biomolecules.

    Science.gov (United States)

    Cuecas, Alba; Cruces, Jorge; Galisteo-López, Juan F; Peng, Xiaojun; Gonzalez, Juan M

    2016-08-23

    Some low molecular weight biomolecules, i.e., NAD(P)H, are unstable at high temperatures. The use of these biomolecules by thermophilic microorganisms has been scarcely analyzed. Herein, NADH stability has been studied at different temperatures and viscosities. NADH decay increased at increasing temperatures. At increasing viscosities, NADH decay rates decreased. Thus, maintaining relatively high cellular viscosity in cells could result in increased stability of low molecular weight biomolecules (i.e., NADH) at high temperatures, unlike what was previously deduced from studies in diluted water solutions. Cellular viscosity was determined using a fluorescent molecular rotor in various prokaryotes covering the range from 10 to 100°C. Some mesophiles showed the capability of changing cellular viscosity depending on growth temperature. Thermophiles and extreme thermophiles presented a relatively high cellular viscosity, suggesting this strategy as a reasonable mechanism to thrive under these high temperatures. Results substantiate the capability of thermophiles and extreme thermophiles (growth range 50-80°C) to stabilize and use generally considered unstable, universal low molecular weight biomolecules. In addition, this study represents a first report, to our knowledge, on cellular viscosity measurements in prokaryotes and it shows the dependency of prokaryotic cellular viscosity on species and growth temperature. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  10. The minimum amount of "matrix " needed for matrix-assisted pulsed laser deposition of biomolecules

    DEFF Research Database (Denmark)

    Tabetah, Marshall; Matei, Andreea; Constantinescu, Catalin

    2014-01-01

    of coarse-grained molecular dynamics simulations are performed for a model lysozyme-water system, where the water serves the role of volatile "matrix" that drives the ejection of the biomolecules. The simulations reveal a remarkable ability of a small (5-10 wt %) amount of matrix to cause the ejection...

  11. Biomolecule Analogues 2-Hydroxypyridine and 2-Pyridone Base Pairing on Ice Nanoparticles

    Czech Academy of Sciences Publication Activity Database

    Rubovič, Peter; Pysanenko, Andriy; Lengyel, Jozef; Nachtigallová, Dana; Fárník, Michal

    2016-01-01

    Roč. 120, č. 27 (2016), s. 4720-4730 ISSN 1089-5639 R&D Projects: GA ČR GA14-14082S Institutional support: RVO:61388955 ; RVO:61388963 Keywords : doped nanoparticles * argon * biomolecules Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.847, year: 2016

  12. Electrochemistry of single molecules and biomolecules, molecular scale nanostructures, and low-dimensional systems

    DEFF Research Database (Denmark)

    Nazmutdinov, Renat R.; Zinkicheva, Tamara T.; Zinkicheva, Tamara T.

    2018-01-01

    Electrochemistry at ultra-small scales, where even the single molecule or biomolecule can be characterized and manipulated, is on the way to a consolidated status. At the same time molecular electrochemistry is expanding into other areas of sophisticated nano- and molecular scale systems including...

  13. Sensitive Detection of Biomolecules by Surface Enhanced Raman Scattering using Plant Leaves as Natural Substrates

    Directory of Open Access Journals (Sweden)

    Sharma Vipul

    2017-01-01

    Full Text Available Detection of biomolecules is highly important for biomedical and other biological applications. Although several methods exist for the detection of biomolecules, surface enhanced Raman scattering (SERS has a unique role in greatly enhancing the sensitivity. In this work, we have demonstrated the use of natural plant leaves as facile, low cost and eco-friendly SERS substrates for the sensitive detection of biomolecules. Specifically, we have investigated the influence of surface topography of five different plant leaf based substrates, deposited with Au, on the SERS performance by using L-cysteine as a model biomolecule. In addition, we have also compared the effect of sputter deposition of Au thin film with dropcast deposition of Au nanoparticles on the leaf substrates. Our results indicate that L-cysteine could be detected with high sensitivity using these plant leaf based substrates and the leaf possessing hierarchical micro/nanostructures on its surface shows higher SERS enhancement compared to a leaf having a nearplanar surface. Furthermore, leaves with drop-casted Au nanoparticle clusters performed better than the leaves sputter deposited with a thin Au film.

  14. Self-organized pattern formation of biomolecules at silicon surfaces: Intended application of a dislocation network

    Energy Technology Data Exchange (ETDEWEB)

    Kittler, M. [IHP, Im Technologiepark 25, 15236 Frankfurt (Oder) (Germany)]. E-mail: kittler@ihp-microelectronics.com; Yu, X. [IHP, Im Technologiepark 25, 15236 Frankfurt (Oder) (Germany); Vyvenko, O.F. [IHP, Im Technologiepark 25, 15236 Frankfurt (Oder) (Germany); Birkholz, M. [IHP, Im Technologiepark 25, 15236 Frankfurt (Oder) (Germany); Seifert, W. [IHP, Im Technologiepark 25, 15236 Frankfurt (Oder) (Germany); Reiche, M. [MPI fuer Mikrostrukturphysik, Weinberg 2, 06120 Halle (Germany); Wilhelm, T. [MPI fuer Mikrostrukturphysik, Weinberg 2, 06120 Halle (Germany); Arguirov, T. [BTU Cottbus, Experimental-Physik II, Konrad-Wachsmann-Allee 1, 03046 Cottbus (Germany); Wolff, A. [IPHT, Albert-Einstein-Str. 9, 07745 Jena (Germany); Fritzsche, W. [IPHT, Albert-Einstein-Str. 9, 07745 Jena (Germany); Seibt, M. [IV. Physikalisches Institut, Georg-August-Universitaet Goettingen, Friedrich-Hund-Platz 1, 37077 Goettingen (Germany)

    2006-07-15

    Defined placement of biomolecules at Si surfaces is a precondition for a successful combination of Si electronics with biological applications. We aim to realize this by Coulomb interaction of biomolecules with dislocations in Si. The dislocations form charged lines and they will be surrounded with a space charge region being connected with an electric field. The electric stray field in a solution of biomolecules, caused by dislocations located close to the Si surface, was estimated to yield values up to few kVcm{sup -1}. A regular dislocation network can be formed by wafer direct bonding at the interface between the bonded wafers in case of misorientation. The adjustment of misorientation allows the variation of the distance between dislocations in a range from 10 nm to a few {mu}m. This is appropriate for nanobiotechnology dealing with protein or DNA molecules with sizes in the nm and lower {mu}m range. Actually, we achieved a distance between the dislocations of 10-20 nm. Also the existence of a distinct electric field formed by the dislocation network was demonstrated by the technique of the electron-beam-induced current (EBIC). Because of the relatively short range of the field, the dislocations have to be placed close to the surface. We positioned the dislocation network in an interface being 200 nm parallel to the Si surface by layer transfer techniques using hydrogen implantation and bonding. Based on EBIC and luminescence data we postulate a barrier of the dislocations at the as bonded interface < 100 meV. We plan to dope the dislocations with metal atoms to increase the electric field. We demonstrated that regular periodic dislocation networks close to the Si surface formed by bonding are realistic candidates for self-organized placing of biomolecules. Experiments are underway to test whether biomolecules decorate the pattern of the dislocation lines.

  15. Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1

    International Nuclear Information System (INIS)

    Watanabe, Ayahisa; Nishijima, Ken-ichi; Zhao, Songji; Tamaki, Nagara; Kuge, Yuji; Tanaka, Yoshikazu; Itoh, Takeshi; Takemoto, Hiroshi

    2012-01-01

    Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes. Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of 123 I-GLP-1 or 123 I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using 125 I-GLP-1 or 125 I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured. In the noninvasive imaging studies, a relatively high accumulation level of 123 I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of 123 I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of 123 I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using 125 I-labeled peptides. The AUC of 125 I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1. This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals. (author)

  16. Production, Purification and Radiolabelling of Zirconium-89 for Positron Emission Tomography (PET) Radiopharmaceuticals

    International Nuclear Information System (INIS)

    Azhari Kasbollah; Azahari Kasbollah; Eu, Peter

    2014-01-01

    Zirconium-89 ( 89 Zr), a radionuclide with a half-life of 78.4 hours, is suitable for imaging tumours using positron emission tomography (PET) when labelled with monoclonal antibodies. 89 Zr can be produced from Yttrium-89 ( 89 Y) by a process of cyclotron bombardment with 89 Y(p, n) 89 Zr reaction. Purification and radiolabelling processes must be developed before 89 Zr can be used for monoclonal antibody PET imaging. The main aim of this study was to produce 89 Zr using 89 Y solid targets through irradiation in a 12 MeV medical cyclotron at low currents using the 89 Y(p, n) 89 Zr reaction for PET imaging in a preclinical condition. Gamma spectrum analyses determined energy peaks of 511 keV and 909 keV indicating that 89 Zr radionuclide had been successfully produced. 89 Zr was then purified through a hydroxamate resin column and radiolabelled to a monoclonal antibody (trastuzumab). Experiments on biodistribution together with PET imaging of female balb/c nude mice having the HER2 positive LS174T colorectal tumour was undertaken to validate the successful radiolabelling procedure between 89 Zr and trastuzumab. PET images at 24 hours showed a selective accumulation of 89 Zr-Df-Trastuzumab in tumour-bearing mice with good tumour tracer uptake in the right flank, as well as cardiac uptake, a significant presence of HER2 receptor expression on the heart, demonstrated that the conjugated Df-Trastuzumab was successfully labelled with 89 Zr. (author)

  17. Comparison of radiolabeled choline and ethanolamine as probe for cancer detection.

    Science.gov (United States)

    Mintz, Akiva; Wang, Limin; Ponde, Datta E

    2008-05-01

    Recently [11C] or [18F] labeled choline has been developed as a promising tracer for cancer detection. However choline may not be best agent, as the development of in vivo 1H-decoupled, NOE-enhanced 31P- MRS enabled the resolution of the resonances of phosphorylethanolamine (PEt) and phosphorylcholine (PCho) peaks that normally overlap under the broad phosphomonoester peak (PME). In human non-Hodgkin's lymphoma in vivo, the PEt/PCho ratio was reported as 2.9 +/- 1.0 (n = 11). The objective of this work was to compare radiolabeled choline with ethanolamine as an agent for cancer detection using various cancer cell lines. Cell uptake of [14C] ethanolamine and [14C] N, N'-dimethyl ethanolamine was compared to [14C] choline uptake in a wide variety of different cancer cell lines. Our data clearly demonstrates that, ethanolamine and N, N'-dimethyl ethanolamine showed 2-7 fold more uptake than choline. We showed that proliferating fibroblasts have significantly higher uptake of ethanolamine and N, N'-dimethyl-ethanolamine, than does growth arrested fibroblasts. Time course studies in A172 cells indicate continuous linear uptake of ethanolamine after four hours of tracer exposure, which was halted if tracer containing, media was replaced with regular media after one hour. The androgen stimulated and depleted study with prostate cancer cell lines showed that increased trapping of radiotracers in cells is well correlated with their proliferation status. We carried out comparison of radiolabeled choline and ethanolamine by cell uptake study using 8 different cancer cell lines. To evaluate the response of radiotracers towards proliferation we also carried out their cell uptake study of androgen dependent and androgen independent cells in androgen stipulated and deprived media. Our data demonstrate that ethanolamine and N, N'-dimethyl ethanolamine are taken up by a wide variety of tumor cells significantly better (2-7 fold) than the clinically utilized radiolabeled choline

  18. Radiolabeled monoclonal antibodies in the diagnosis and treatment of malignant melanoma

    International Nuclear Information System (INIS)

    Divgi, C.R.; Larson, S.M.

    1989-01-01

    The use of antibodies directed against tumors has found increasing usefulness after the discovery by Kohler and Milstein of hybridoma technology, which made it possible to obtain monoclonal antibody (MoAb) that reacted specifically against a particular epitope on a particular antigen site. Relative tumor specificity and a lack of significant toxicity, together with the ability to link radionuclides (both halogens and metals) without significant deterioration of biologic behavioral characteristics such as immunoreactivity, have enabled widespread use of radiolabeled MoAbs in several malignancies, including and especially malignant melanoma. There is a significant body of data indicating that radiolabeled MoAbs directed against melanoma-associated antigens have an important role in the detection and therapy of metastatic malignant melanoma. Detection of visceral disease, while currently suboptimal, will in the future improve with optimization of SPECT imaging using 99mTc-labeled MoAb Fab fragments. This may result in an attenuated or absent antimouse response, especially after one injection, unless of course coinfused with either specific and/or nonspecific intact immunoglobulin (Ig). Radiolabeled fragments play an important role in radioimmunotherapy in metastatic melanoma. This role may be enhanced by the development of newer chelating agents that will decrease nonspecific hepatic uptake of radionuclide, enabling the use of beta-emitting radiometals such as 90Y. The recent report demonstrating diminished hepatic uptake of 99mTc-labeled anti-high molecular weight antigen (HMWA) Fab shows promise, since the same labeling technique can be used to deliver radiotherapeutic agents such as 186Re, which may be labeled to MoAb with methods similar to those used for 99mTc.82 references

  19. Phenotypic imaging and gallium-68 radiolabeled peptides: Beyond the somatostatin analogs;Imagerie phenotypique et peptides radiomarques au gallium-68: au-dela des analogues de la somatostatine

    Energy Technology Data Exchange (ETDEWEB)

    Couturier, O.; Lacoeuille, F.; Lefebvre, C.; Hindre, F.; Vervueren, L.; Bouchet, F.; Le Jeune, J.J. [Universite d' Angers, Service de medecine nucleaire universitaire, 49 - Angers (France); Universite d' Angers, Inserm U646, 49 - Angers (France); Hustinx, R. [Departement de medecine nucleaire universitaire, domaine universitaire du Sart Tilman, Liege (Belgium)

    2010-05-15

    Receptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides in the clinic are analogs of somatostatin. However, other radiolabeled analogs have also been developed and assessed in vitro and in vivo and some of them are already in clinical use. For instance, radiolabeled analogs of alpha-melanocyte-stimulating hormone (alpha-M.S.H.), neurotensin, vasoactive intestinal peptide (VIP), bombesin (B.N.), substance P (S.P.), cholecystokinin (C.C.K.), integrin. This review focuses on gallium-68 radiolabeled peptides developed for PET imaging, except for somatostatin analogs, which are discussed in another article. (authors)

  20. Whole-body effective half-lives for radiolabeled antibodies and related issues

    Energy Technology Data Exchange (ETDEWEB)

    Kaurin, D.G.L.; Carsten, A.L.; Baum, J.W.; Barber, D.E.

    1996-08-01

    Radiolabeled antibodies (RABs) are being developed and used in medical imaging and therapy in rapidly increasing numbers. Data on the whole body half effective half-lives were calculated from external dose rates obtained from attending physicians and radiation safety officers at participating institutions. Calculations were made using exponential regression analysis of data from patients receiving single and multiple administrations. Theses data were analyzed on the basis of age, sex, isotope label, radiation energy, antibody type, disease treated, administration method, and number of administrations.

  1. Alternate radiolabeled markers for detecting metabolic activity of Mycobacterium leprae residing in murine macrophages

    International Nuclear Information System (INIS)

    Prasad, H.K.; Hastings, R.C.

    1985-01-01

    This study demonstrated the utility of using 4% NaOH as a murine macrophage cell-solubilizing agent to discriminate between host macrophage metabolism and that of intracellular Mycobacterium leprae. A 4% concentration of NaOH had no deleterious effect on labeled mycobacteria. Thereby, alternate radiolabeled indicators of the metabolic activity of intracellular M. leprae could be experimented with. Significant incorporation of 14 C-amino acid mixture, [ 14 C]leucine, [ 14 C]uridine, and carrier-free 32 P was observed in cultures containing freshly extracted (''live'') strains of M. leprae as compared with control cultures containing autoclaved bacilli

  2. Computer-assisted high-pressure liquid chromatography of radio-labelled phenylthiohydantoin amino acids

    International Nuclear Information System (INIS)

    Bhown, A.S.; Mole, J.E.; Hollaway, W.L.; Bennet, J.C.

    1978-01-01

    A computer-controlled high-pressure liquid chromatographic (HPLC) system is described to identify in vitro phenyl [ 35 S]isothiocyanate-labelled phenylthiohydantoin (PTH) amino acids from a solid-phase sequencer. Each radio-labelled amino acid from the sequencer is added to a PTH amino acid standard and the mixture separated by HPLC using a computer, programmed to detect a slope change in the absorbance. Individual fractions corresponding to the PTH amino acids are collected and counted. The sensitivity of the system is demonstrated on 700 pmoles of lysozyme. (Auth.)

  3. Advance of apoptosis imaging with radiolabeled annexin V in tumor research

    International Nuclear Information System (INIS)

    Huang Daijuan

    2003-01-01

    One of the most important reasons that cause tumor is decrease or complete absence of apoptosis of tumor cells. Conversely successful anti-tumor therapy is correlated with the introduction of apoptosis into tumor cells. Radiolabeled annexin V is used to image in vivo the phosphatidylserine (PS) that explode on the outer surface of cell membrane after apoptosis so that apoptosis can be detected on the early stage. This imaging method can be introduced into the research of tumor in order to help direct the choose of tumor therapy, inspect the effect and evaluate the prognosis

  4. Radiolabeled phosphonium salts as mitocondrial voltage sensors for positron emission tomography myocardial imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Yon; Min, Jung Joon [Dept. of Nuclear Medicine,Chonnam National University Medical School and Hwasun Hospital, Gwangju (Korea, Republic of)

    2016-09-15

    Despite substantial advances in the diagnosis of cardiovascular disease, {sup 18}F-labeled positron emission tomography (PET) radiopharmaceuticals remain necessary to diagnose heart disease because clinical use of current PET tracers is limited by their short half-life. Lipophilic cations such as phosphonium salts penetrate the mitochondrial membranes and accumulate in mitochondria of cardiomyocytes in response to negative inner-transmembrane potentials. Radiolabeled tetraphenyl phosphonium cation derivatives have been developed as myocardial imaging agents for PET. In this review, a general overview of these radiotracers, including their radiosynthesis, in vivo characterization, and evaluation is provided and clinical perspectives are discussed.

  5. Radiolabeled Peptide Scaffolds for PET/SPECT - Optical in Vivo Imaging of Carbohydrate-Lectin Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Deutscher, Susan

    2014-09-30

    The objective of this research is to develop phage display-selected peptides into radio- and fluoresecently- labeled scaffolds for the multimodal imaging of carbohydrate-lectin interactions. While numerous protein and receptor systems are being explored for the development of targeted imaging agents, the targeting and analysis of carbohydrate-lectin complexes in vivo remains relatively unexplored. Antibodies, nanoparticles, and peptides are being developed that target carbohydrate-lectin complexes in living systems. However, antibodies and nanoparticles often suffer from slow clearance and toxicity problems. Peptides are attractive alternative vehicles for the specific delivery of radionuclides or fluorophores to sites of interest in vivo, although, because of their size, uptake and retention may be less than antibodies. We have selected high affinity peptides that bind a specific carbohydrate-lectin complex involved in cell-cell adhesion and cross-linking using bacteriophage (phage) display technologies (1,2). These peptides have allowed us to probe the role of these antigens in cell adhesion. Fluorescent versions of the peptides have been developed for optical imaging and radiolabeled versions have been used in single photon emission computed tomography (SPECT) and positron emission tomography (PET) in vivo imaging (3-6). A benefit in employing the radiolabeled peptides in SPECT and PET is that these imaging modalities are widely used in living systems and offer deep tissue sensitivity. Radiolabeled peptides, however, often exhibit poor stability and high kidney uptake in vivo. Conversely, optical imaging is sensitive and offers good spatial resolution, but is not useful for deep tissue penetration and is semi-quantitative. Thus, multimodality imaging that relies on the strengths of both radio- and optical- imaging is a current focus for development of new in vivo imaging agents. We propose a novel means to improve the efficacy of radiolabeled and fluorescently

  6. Whole-body effective half-lives for radiolabeled antibodies and related issues

    International Nuclear Information System (INIS)

    Kaurin, D.G.L.; Carsten, A.L.; Baum, J.W.; Barber, D.E.

    1996-08-01

    Radiolabeled antibodies (RABs) are being developed and used in medical imaging and therapy in rapidly increasing numbers. Data on the whole body half effective half-lives were calculated from external dose rates obtained from attending physicians and radiation safety officers at participating institutions. Calculations were made using exponential regression analysis of data from patients receiving single and multiple administrations. Theses data were analyzed on the basis of age, sex, isotope label, radiation energy, antibody type, disease treated, administration method, and number of administrations

  7. Distribution and pharmacokinetics of radiolabeled monoclonal antibody OC 125 after intravenous and intraperitoneal administration in gynecologic tumors

    International Nuclear Information System (INIS)

    Haisma, H.J.; Moseley, K.R.; Battaile, A.; Griffiths, T.C.; Knapp, R.C.

    1988-01-01

    Radiolabeled monoclonal antibodies may be useful for radioimmunotherapy of gynecologic tumors. Iodine 131-labeled F(ab')2 fragments of a monoclonal antibody, OC 125, with specificity for ovarian carcinoma, were used to study the distribution and pharmacokinetics of this antibody in patients with gynecologic tumors. The radiolabeled antibody was injected intravenously or intraperitoneally into 10 patients suspected of having ovarian cancer. Blood and urine samples were used for pharmacokinetic studies, and biopsy specimens were examined for the uptake of antibody. The serum half-life of the labeled antibody was 30 hours after intravenous administration, with 20% of the injected dose per liter detected at 24 hours. After intraperitoneal injection, the appearance of antibody in serum was slow, with a maximum level of 1.4% of the injected dose per liter at 24 hours. Urinary excretion of the radiolabeled antibody was similar for intravenous and intraperitoneal administration, with approximately 50% of the injected dose excreted after 48 hours. Intraperitoneal administration of the radiolabeled antibody resulted in a higher uptake of antibody in the tumor and a lower uptake of antibody in normal tissues. On the basis of this limited study, intraperitoneal administration of radiolabeled antibody is preferred over intravenous administration for radioimmunotherapy of ovarian cancer

  8. Aerospace Medicine

    Science.gov (United States)

    Michaud, Vince

    2015-01-01

    NASA Aerospace Medicine overview - Aerospace Medicine is that specialty area of medicine concerned with the determination and maintenance of the health, safety, and performance of those who fly in the air or in space.

  9. Nuclear Medicine.

    Science.gov (United States)

    Badawi, Ramsey D.

    2001-01-01

    Describes the use of nuclear medicine techniques in diagnosis and therapy. Describes instrumentation in diagnostic nuclear medicine and predicts future trends in nuclear medicine imaging technology. (Author/MM)

  10. Radiolabeled leukocytes

    International Nuclear Information System (INIS)

    Datz, F.L.; Taylor, A.T.

    1986-01-01

    Leukocytes are a heterogeneous group of nucleated cells that follow similar patterns of differentiation in the bone marrow. Although the various leukocyte cell types perform somewhat different functions, they act as a group to protect the host from hazards of the internal and external environment, such as infection and neoplasia, and they assist in the repair of damaged tissue. Leukocytes spend a small fraction of their life in the peripheral blood, using it only for transportation to sites where they are needed to perform their defensive functions. In adults, the mature types of leukocytes are neutrophils (59 percent of the leukocyte population), lymphocytes (34 percent), monocytes (four percent), eosinophils (three percent), and basophils (0.5 percent). Neutrophils, eosinophils, and basophils all contain nuclei with finitely granular, evenly distributed chromatin and are collectively called granulocytes. In addition to the main categories of leukocytes listed above, there are subsets of many of these classes of cells; for example, natural killer cells are a subset of lymphocytes

  11. Radiolabeled platelets

    International Nuclear Information System (INIS)

    Cunningham, D.A.; Siegel, B.A.

    1982-01-01

    The experimental applications of labeled platelets have expanded greatly since the development of an efficient labeling agent with physical properties suitable for external imaging. The role of both In-111- and Cr-51-labeled platelets in routine clinical studies is discussed. In the case of Cr-51, use is likely to remain confined to occasional platelet kinetic studies. In contrast, the potential applications of In-111-labeled platelets are much broader in scope, but as yet human studies remain in the investigative stage. The available data suggest that the technique is highly specific for various thrombotic processs but rather insensitive and time consuming in its present form

  12. Radiolabelled neoglycopeptides

    International Nuclear Information System (INIS)

    Krohn, K.A.; Vera, D.R.; Stadalnik, R.C.

    1984-01-01

    This patent provides a composition comprising a galactosyl or glucosyl substituted serum albumin, having from about 5 to 40 galactosyl or glucosyl groups, combined with a reductant for pertechnetate sufficient to provide Tc-99m in an amount of from about 1 to 100 mCi/mg albumin

  13. Effect of biomolecules adsorption on oxide layers developed on metallic materials used in cooling water systems

    International Nuclear Information System (INIS)

    Torres-Bautista, Blanca-Estela

    2014-01-01

    This thesis was carried out in the frame of the BIOCOR ITN European project, in collaboration with the industrial partner RSE S.p.A. (Italy). Metallic materials commonly used in cooling systems of power plants may be affected by bio-corrosion induced by biofilm formation. The objective of this work was to study the influence of biomolecules adsorption, which is the initial stage of biofilm formation, on the electrochemical behaviour and the surface chemical composition of three metallic materials (70Cu-30Ni alloy, 304L stainless steel and titanium) in seawater environments. In a first step, the interactions between a model protein, the bovine serum albumin (BSA), and the surface of these materials were investigated. Secondly, tightly bound (TB) and loosely bound (LB) extracellular polymeric substances (EPS), that play a fundamental role in the different stages of biofilm formation, maturation and maintenance, were extracted from Pseudomonas NCIMB 2021 marine strain, and their effects on oxide layers were also evaluated. For that purpose, electrochemical measurements (corrosion potential E(corr) vs time, polarization curves and electrochemical impedance spectroscopy (EIS)) performed during the very first steps of oxide layers formation (1 h immersion time) were combined to surface analysis by X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ions mass spectrometry (ToF-SIMS). Compared to 70Cu-30Ni alloy in static artificial seawater (ASW) without biomolecules, for which a thick duplex oxide layer (outer redeposited Cu 2 O layer and inner oxidized nickel layer) is shown, the presence of BSA, TB EPS and LB EPS leads to a mixed oxide layer (oxidized copper and nickel) with a lower thickness. In the biomolecules-containing solutions, this oxide layer is covered by an adsorbed organic layer, mainly composed of proteins. A model is proposed to analyse impedance data obtained at E(corr). The results show a slow-down of the anodic reaction in the presence

  14. Scintigraphic detection of peptic lesions with the method of radiolabelled sucralfate

    International Nuclear Information System (INIS)

    Naumovski, J.; Kovkarova, E.; Simova, N.; Janevik-Ivanovska, E.; Georgievska- Kuzmanovska, S.

    2003-01-01

    Background. Sucralfate is an antiulcer agent that after peroral application strongly adheres to mucosal defects and in that way provides a protective barrier to further damage from acid and pepsin. If radiolabelled with a gamma isotope, it could be detected under a gamma camera pointing lesions to which it adhered. With the aim to confirm a suitable noninvasive method for investigation of caustic lesions of the upper gastrointestinal tract we evaluated in a preliminary study the validity of the radiolabelled Sucralfate scintigraphy in detection of peptic disease. Patients and methods. With that purpose, 35 patients after an endoscopic examination underwent scintigraphy with Tc-99m-DTPA sucralfate. Patients were divided in two groups: a group of 20 patients with endoscopic confirmed peptic disease and a control group of 15 persons who had not any disease of the upper gastrointestinal tract. Results. Using the test for clinical evaluation of a new method, the scan showed sensitivity of 75 %, specificity of 100 % and accuracy of 85.7 %. Conclusions. Scintigraphy with Tc-99m-DTPA Sucralfate promoting it as an additional method, complementary to routine investigations in detecting mucosal lesions. (author)

  15. Radiolabeling and physicochemical characterization of boron nitride nanotubes functionalized with glycol chitosan polymer

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Daniel Cristian Ferreira; Ferreira, Tiago Hilario; Ferreira, Carolina de Aguiar; Sousa, Edesia Martins Barros de, E-mail: sousaem@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG) Belo Horizonte, MG (Brazil). Lab. de Materiais Nanoestruturados para Bioaplicacoes; Cardoso, Valbert Nascimento, E-mail: cardosov@farmacia.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Fac. de Farmacia

    2011-07-01

    In the last years, some nanostructured systems has proposed as new drugs and radioisotopes delivery systems, aiming the diagnosis and treatment of many diseases, including the cancer. Among these systems, the Boron Nitride Nanotubes (BNNTs) showed adequate characteristics to be applied in biomedical area, due to its high stability and considerable biocompatibility. However, due to its hydrophobic characteristics, these applications are limited and its behavior in vivo (guinea pigs) is unexplored yet. Seeking to overcome this problems, in the present work, we functionalized the BNNTs (noncovalent wrapped) with glycol chitosan (GC), a biocompatible and stable polymer, in order to disperse it in water. The results showed that BNNTs were well dispersed in water with mean size and polydispersity index suitable to conduct biodistribution studies in mice. The nanostructures were physicochemical and morphologically characterized by Scanning Electron Microscopy (SEM), X-ray diffraction (XRD) and Raman Spectroscopy. The results revealed that the functionalization process with glycol chitosan was obtained with successfully on BNNTs surface. Furthermore, we developed a radiolabeling protocol with {sup 99m}Tc radioisotope in functionalized BNNTs, aiming in future, to conduct image biodistribution studies in mice. The results revealed that the nanotubes were radiolabeled with radiochemical purity above of 90%, being considered suitable to scintigraphic image acquisition. (author)

  16. Gastrointestinal behavior of orally administered radiolabeled erythromycin pellets in man as determined by gamma scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Digenis, G.A.; Sandefer, E.P.; Parr, A.F.; Beihn, R.; McClain, C.; Scheinthal, B.M.; Ghebre-Sellassie, I.; Iyer, U.; Nesbitt, R.U.; Randinitis, E. (Univ. of Kentucky, Lexington (USA))

    1990-07-01

    The behavior of single 250-mg doses of a multiparticulate form of erythromycin base (ERYC(R)), each including five pellets radiolabeled with neutron-activated samarium-153, was observed by gamma scintigraphy in seven male subjects under fasting and nonfasting conditions. The residence time and locus of radiolabeled pellets within regions of the gastrointestinal tract were determined and were correlated with plasma concentrations of erythromycin at coincident time points. Administration of food 30 minutes postdosing reduced fasting plasma erythromycin Cmax and area under the plasma erythromycin versus time curve (AUC) values by 43% and 54%, respectively. Mean peak plasma concentration of erythromycin (Cmax) in the fasting state was 1.64 micrograms/mL versus 0.94 micrograms/mL in the nonfasting state. Total oral bioavailability, as determined by mean AUC (0-infinity) of the plasma erythromycin concentration versus time curve, was 7.6 hr/micrograms/mL in the fasted state, versus 3.5 hr/micrograms/mL in the nonfasting state. Mean time to peak plasma erythromycin concentration (tmax) in the fasting state was 3.3 hours, versus 2.3 hours in the nonfasting state. Plasma concentrations of erythromycin in both fasting and nonfasting states were within acceptable therapeutic ranges.

  17. Gastrointestinal behavior of orally administered radiolabeled erythromycin pellets in man as determined by gamma scintigraphy

    International Nuclear Information System (INIS)

    Digenis, G.A.; Sandefer, E.P.; Parr, A.F.; Beihn, R.; McClain, C.; Scheinthal, B.M.; Ghebre-Sellassie, I.; Iyer, U.; Nesbitt, R.U.; Randinitis, E.

    1990-01-01

    The behavior of single 250-mg doses of a multiparticulate form of erythromycin base (ERYC(R)), each including five pellets radiolabeled with neutron-activated samarium-153, was observed by gamma scintigraphy in seven male subjects under fasting and nonfasting conditions. The residence time and locus of radiolabeled pellets within regions of the gastrointestinal tract were determined and were correlated with plasma concentrations of erythromycin at coincident time points. Administration of food 30 minutes postdosing reduced fasting plasma erythromycin Cmax and area under the plasma erythromycin versus time curve (AUC) values by 43% and 54%, respectively. Mean peak plasma concentration of erythromycin (Cmax) in the fasting state was 1.64 micrograms/mL versus 0.94 micrograms/mL in the nonfasting state. Total oral bioavailability, as determined by mean AUC (0-infinity) of the plasma erythromycin concentration versus time curve, was 7.6 hr/micrograms/mL in the fasted state, versus 3.5 hr/micrograms/mL in the nonfasting state. Mean time to peak plasma erythromycin concentration (tmax) in the fasting state was 3.3 hours, versus 2.3 hours in the nonfasting state. Plasma concentrations of erythromycin in both fasting and nonfasting states were within acceptable therapeutic ranges

  18. Phase I-II study of radiolabeled antibody integrated in the treatment of primary hepatic malignancies

    International Nuclear Information System (INIS)

    Order, S.E.; Klein, J.L.; Ettinger, D.; Alderson, P.; Siegelman, S.; Leichner, P.

    1984-01-01

    Primary intrahepatic malignancies have been demonstrated to contain tumor associated antigens which bind radiolabelled anti-CEA and anti-ferritin antibodies. The present study reports the toxicity and possible therapeutic efficacy of radiolabelled antibodies that were administered at 50 and 100 millicurie doses following combination radiation and chemotherapy. Three of 10 patients who entered into the study completed therapy on schedule and have had remissions of 7, 9, and 18 months; 2 of the 3 patients were alive at 1 and 2 years after treatment. Of 5 patients who were administered radioimmunoglobulin, the singular toxicity was 3 weeks of marrow hypoplasia in one patient who subsequently recovered. The remaining 5 patients were at various stages of protocol treatment prior to immunoglobulin treatment. Eight of the 10 patients have had computer analysis of sequential computerized axial tomography (CAT) scans obtained during the course of therapy and at follow up examination. No major organ toxicity was noted. Clinical remissions were documented by computer analysis of the CAT scans to determine the percent of residual tumor

  19. Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

    International Nuclear Information System (INIS)

    Blankenberg, F.G.; Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A.; Tait, J.F.; Post, A.M.; Strauss, H.W.

    2001-01-01

    Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

  20. Effects of radiolabelled monoclonal antibody infusion on blood leukocytes in cancer patients

    International Nuclear Information System (INIS)

    Gridley, D.S.; Slater, J.M.; Stickney, D.R.

    1990-01-01

    This study was undertaken to investigate the effects of a single infusion of radiolabelled murine monoclonal antibody (MAb) on peripheral blood leukocytes in cancer patients. Eleven patients with disseminated colon cancer, malignant melanoma, or lung adenocarcinoma were infused with 111In-labelled anti-ZCE 025, anti-p97 type 96.5c, or LA 20207 MAb, respectively. Blood samples were obtained before infusion, immediately after infusion (1 hr), and at 4 and 7 days postinfusion. Flow cytometry analysis of CD3+, CD4+, CD8+, CD16+, and CD19+ lymphocytes showed increasing CD4:CD8 ratios in seven patients after infusion. This phenomenon was not restricted to antibody subclass or to type of cancer. Two of the remaining patients exhibited a marked post-infusion increase in CD8+ cells. In all three patients with malignant melanoma, decreasing levels of CD16+ lymphocytes were noted after infusion and natural killer cell cytotoxicity showed fluctuations which paralleled the changes in the CD16+ subpopulation. Oxygen radical production by phagocytic cells was markedly affected in three subjects. These results suggest that a single infusion of radiolabelled murine MAb may alter the balance of critical lymphocyte subpopulations and modulate other leukocyte responses in cancer patients

  1. CT-guided radiolabelled aerosol studies for assessing pulmonary impairment in children with bronchiectasis

    International Nuclear Information System (INIS)

    Pifferi, M.; Baldini, M.; Caramella, D.; Bartolozzi, C.; Di Mauro, M.; Cangiotti, A.M.

    2000-01-01

    Objective. To determine whether CT-guided mucociliary clearance studies allow differentiation between bronchiectasis associated with primary ciliary dyskinesia (PCD) and those unrelated to congenital or genetically transmitted defects. Materials and methods. Fifteen children aged 4-18 years with a CT diagnosis of bronchiectasis were included in the study. Six had PCD, while in nine cases no congenital disorder was demonstrated. Results. CT showed bronchiectasis in 26 (29 %) of 90 lung regions. Radiolabelled aerosol studies were conducted globally for each lung and on the regions affected by bronchiectasis. Global half-time of activity (t 1/2 ) values of patients with PCD were significantly higher (P 1/2 values. Patients with bronchiectasis unrelated to congenital disorders showed significantly higher regional t 1/2 values in the affected regions with respect to the corresponding global pulmonary t 1/2 (P < 0.06). Conclusions. The combination of morphological CT information with functional data concerning the clearance of radiolabelled aerosol adds to our understanding of pulmonary impairment in children with bronchiectasis. In particular, regional studies allow the recognition of different mucociliary clearance patterns in bronchiectasis associated with PCD and those unrelated to congenital or genetically transmitted defects. (orig.)

  2. Preparation and characterization of radiolabeled magnetic nanoparticles as an imaging agent

    Science.gov (United States)

    İçhedef, Çiğdem; Teksöz, Serap; Ünak, Perihan; Medine, Emin İ.; Ertay, Türkan; Bekiş, Recep

    2012-08-01

    Magnetic nanoparticles were prepared by a reduction-precipitation method and coated with an amino silane coupling agent. Guanine (Gua) was conjugated to the magnetic nanoparticles (MNPs) using glutaraldehyde as a cross-linker. Common techniques (Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, and vibrating electron microscopy) were used to assess the properties of the particles. Structural investigations showed that amino silane-coated MNPs had a particle size of about 40-60 nm in diameter with a spherical morphology. The guanine-conjugated MNPs were radiolabeled with 99mTc(I)-tricarbonyl core (99mTc(CO)3-MNP-Gua) with a labeling yield of 72 ± 4 %. Pure radiolabeled magnetic particles were obtained by washing them with saline solution, and the radiochemical purity of 99mTc(CO)3-MNP-Gua was 98 ± 2 % in the final solution. The biologic distribution of guanine MNPs was assessed in New Zealand rabbits using a gamma camera. In the in vivo experiment, a high level of radioactivity was observed in the lungs and liver soon after intravenous administration of 99mTc(CO)3-MNP-Gua.

  3. The use of radiolabelled milk proteins to study thermally-induced interactions in milk systems

    International Nuclear Information System (INIS)

    Noh, B.

    1988-01-01

    Heat induced complexes between milk proteins are of considerable importance in determining the heat stability and rennin clottability of milk products. Thiol-disulfide interchange reactions have been suggested as the principal reaction mechanism for complex formation. Studies to data have not adequately established the mechanism and stoichiometry of complex formation in situ in total milk system. Tracer amounts of 14 C-β-lactoglobulin and α-lactalbumin were heated under various conditions. After clotting with rennet, radioactivity retained in the curd was counted to estimate extent of interaction of β-lactoglobulin with casein. 14 C- and 3 H-Methyl labelled proteins were used for the preparation of radiolabelled artificial casein micelles. These micelles with radiolabelled whey proteins were heated and heat-induced complexes were separated on Sephacryl S-300 eluting with 6 M guanidine hydrochloride to break all non-covalent bonds. Further separation of the protein complexes was obtained using CPG-10 or Sephacryl S-1000. The ratios of 3 H to 14 C labelled proteins in the protein complexes suggested that the stoichiometries of k-, α s2 -casein, β-lactoglobulin and α-lactalbumin in the heat-induced complexes varied as a function of the heat treatment

  4. Radiolabelling of nanoparticles by proton irradiation: temperature control in nanoparticulate powder targets

    Science.gov (United States)

    Holzwarth, Uwe; Bulgheroni, Antonio; Gibson, Neil; Kozempel, Jan; Cotogno, Giulio; Abbas, Kamel; Simonelli, Federica; Cydzik, Izabela

    2012-06-01

    Radiolabelled nanoparticles are useful tools for biodistribution or cellular uptake studies related to the risk assessment of nanomaterials. Such studies are ideally carried out with industrially manufactured nanoparticles. Irradiation of small quantities of such nanoparticles, in the form of dry powders, with neutrons or light ions allows radiolabelling while preserving their biologically relevant properties. However, nanoparticle powders exhibit poor thermal conductivity and may overheat under irradiation. Their effective thermal conductivity is not known and conventional temperature measurement methods are difficult to apply. Reasonably accurate temperature data could be derived from post-irradiation X-ray diffraction studies on anatase ST-01 TiO2-nanoparticles, with a primary particle size of 7 nm, subjected to proton beams of different intensities. The anatase-to-rutile phase transition starting at about 750 °C was identified by observing rutile peaks in X-ray diffraction patterns. The onset of growth of single diffracting TiO2-domains at around 200 °C was revealed by shape analysis of the diffraction peaks. Identifying these reference temperatures allowed a calibration of the calculated temperature profile. The effective thermal conductivity in the TiO2 powder target was found to be close to that of air trapped in interstices of the nanoparticulate powder. This suggests that the contribution of the nanoparticles to the heat removal from the target is negligible, thus necessitating the use of thin nanoparticle layers in the target in order to facilitate cooling and prevent thermally induced alterations of the nanoparticles.

  5. Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats

    Energy Technology Data Exchange (ETDEWEB)

    Blankenberg, F.G. [Div. of Pediatric Radiology, Stanford, CA (United States); Wen, P.; Dai, M.; Zhu, D.; Panchal, S.N.; Valantine, H.A. [Division of Cardiovascular Medicine, Department of Medicine, Stanford, California (United States); Tait, J.F. [Dept. of Laboratory Medicine, Univ. of Washington, Seattle (United States); Post, A.M.; Strauss, H.W. [Div. of Nuclear Medicine, Stanford Univ., CA (United States)

    2001-12-01

    Background: Migration of monocytes into the arterial wall is an early finding of atherosclerosis. Monocytes are attracted to sites of vascular endothelial cell injury, the initiating event in the development of atheromatous disease, by a chemokine known as monocyte chemoattractant protein-1 (MCP-1). Injured vascular endothelial and smooth muscle cells selectively secrete MCP-1. Objective: This study was performed to determine if radiolabeled MCP-1 would co-localize at sites of monocyte/macrophage concentration in an experimental model of transplant-induced vasculopathy in diabetic animals. Materials and methods: Hearts from 3-month-old male Zucker rats, heterozygote (Lean) or homozygote (Fat) for the diabetes-associated gene fa, were transplanted into the abdomens of genetically matched recipients. Lean and Fat animals were then fed normal or high-fat diets for 90 days. Results: At 90 days significant increases (P < 0.013) of MCP-1 graft uptake were seen at imaging and confirmed on scintillation gamma well counting studies in Lean (n = 5) and Fat (n = 12) animals, regardless of diet, 400 % and 40 %, above control values, respectively. MCP-1 uptake of native and grafted hearts correlated with increased numbers of perivascular macrophages (P < 0.02), as seen by immunostaining with an antibody specific for macrophages (ED 2). Conclusion: Radiolabeled MCP-1 can detect abnormally increased numbers of perivascular mononuclear cells in native and grafted hearts in prediabetic rats. MCP-1 may be useful in the screening of diabetic children for early atherosclerotic disease. (orig.)

  6. A study of radiolabelling parameters of 1/5 fractionated cardiolite

    International Nuclear Information System (INIS)

    Forster, M.; Snowdon, G.M.

    1997-01-01

    Full text: Fractionation of Cardiolite (Dupont Pharma) has in recent times become increasingly popular in order to minimise costs in our funds-strapped public health system. We investigated the following parameters which are known to potentially affect 1/5 Cardiolite radiolabelling efficiency: 1. Radioactivity-4 to 12 GBq per vial. 2. Total volumes-2.5 and 6.5 mL per vial. 3. Boiling times-2 to 10 minutes. 4. Extra stannous chloride concentration-16 and 32 mg. 5. Quality control procedure-ITLC-SG v. Sep Pak Lite column chromatography. The addition of extra stannous chloride was essential to achieve radiochemical purity >90%. Increasing the total vial volume had a deleterious effect on radiochemical purity. A radiochemical purity >90% was achieved after four minutes boiling of 1/5 fractionated Cardiolite radiolabelled with an activity of up to 10 GBq [ 99m Tc] sodium pertechnetate provided 32 μg 99m Tc stannous chloride was added to the Cardiolite vial prior to the addition of sodium pertechnetate. The ITLC-SG quality control method gave a constantly higher radiochemical purity estimation (∼ 3%) than the Sep Pak Lite method. This was assumed to be due to a radiochemical impurity not detected by ITLC-SG but confirmed on HPLC via personal communication with the radiochemists from St George Hospital, Sydney

  7. Radiolabelling of nanoparticles by proton irradiation: temperature control in nanoparticulate powder targets

    International Nuclear Information System (INIS)

    Holzwarth, Uwe; Bulgheroni, Antonio; Gibson, Neil; Kozempel, Jan; Cotogno, Giulio; Abbas, Kamel; Simonelli, Federica; Cydzik, Izabela

    2012-01-01

    Radiolabelled nanoparticles are useful tools for biodistribution or cellular uptake studies related to the risk assessment of nanomaterials. Such studies are ideally carried out with industrially manufactured nanoparticles. Irradiation of small quantities of such nanoparticles, in the form of dry powders, with neutrons or light ions allows radiolabelling while preserving their biologically relevant properties. However, nanoparticle powders exhibit poor thermal conductivity and may overheat under irradiation. Their effective thermal conductivity is not known and conventional temperature measurement methods are difficult to apply. Reasonably accurate temperature data could be derived from post-irradiation X-ray diffraction studies on anatase ST-01 TiO 2 -nanoparticles, with a primary particle size of 7 nm, subjected to proton beams of different intensities. The anatase-to-rutile phase transition starting at about 750 °C was identified by observing rutile peaks in X-ray diffraction patterns. The onset of growth of single diffracting TiO 2 -domains at around 200 °C was revealed by shape analysis of the diffraction peaks. Identifying these reference temperatures allowed a calibration of the calculated temperature profile. The effective thermal conductivity in the TiO 2 powder target was found to be close to that of air trapped in interstices of the nanoparticulate powder. This suggests that the contribution of the nanoparticles to the heat removal from the target is negligible, thus necessitating the use of thin nanoparticle layers in the target in order to facilitate cooling and prevent thermally induced alterations of the nanoparticles.

  8. Intravenous avidin chase improved localization of radiolabeled streptavidin in intraperitoneal xenograft pretargeted with biotinylated antibody

    International Nuclear Information System (INIS)

    Zhang Meili; Sakahara, Harumi; Yao Zhengsheng; Saga, Tsuneo; Nakamoto, Yuhi; Sato, Noriko; Nakada, Hiroshi; Yamashina, Ikuo; Konishi, Junji

    1997-01-01

    In the present study, we examined the effect of avidin administered intravenously (i.v.) on the biodistribution of radiolabeled streptavidin in mice bearing intraperitoneal (IP) xenografts pretargeted with biotinylated antibody. Tumors were established in nude mice by IP inoculation of LS180 human colon cancer cells. Monoclonal antibody MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected IP into the IP tumor-bearing mice. Radioiodinated streptavidin was administered IP or i.v. 48 h after pretargeting of biotinylated antibody. Avidin was administered i.v. 30 min prior to streptavidin injection. The localization of radioiodinated streptavidin in the tumor pretargeted with biotinylated antibody was significantly higher than that without pretargeting and that of radioiodinated MLS128 by the one-step method. Avidin administration significantly accelerated the clearance of radioiodinated streptavidin in blood and other normal tissues and increased the tumor-to-blood radioactivity ratio regardless of administration route of streptavidin. The i.v. avidin chase improved tumor localization of radiolabeled streptavidin in the IP xenografts pretargeted with biotinylated antibody

  9. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer

    International Nuclear Information System (INIS)

    Lima, Clarice Maria de

    2011-01-01

    Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with β - emitting radioisotopes. The Substance P (SP) is an 11- amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH 2 . The use of SP labeled with different radionuclides including 177 Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, over expressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with 177 Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity of lutetium-177 chloride and mass of DOTA-SP. The radiochemical purity of preparations were analyzed by chromatographic techniques. The stability of 17L u -DOTA- SP radiolabeled with low activity of 177 Lu was evaluated for different time at 2-8 degree C or incubated in human serum. The stability of the labeled with high activity of 177 Lu was also analyzed in the presence of gentisic acid (6 mg / mL) added after the labeling reaction. The labeled conditions in low and high activity were subjected to evaluation for the ability to cause oxidation of methionine residue, adding the D-L- methionine amino acid to the reaction medium (6 mg / mL) and subsequent chromatographic evaluation. In vitro study with 177 Lu-DOTA-SP, radiolabeled in the absence and presence

  10. Evaluation of 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds

    International Nuclear Information System (INIS)

    Kim, Dong Hyun; Choe, Yearn Seong; Kim, Byung-Tae

    2010-01-01

    Click chemistry is a useful approach for the preparation of novel radiopharmaceuticals. In this study, we evaluated 4-[ 18 F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds. Our results showed that nucleophilic substitution of 4-tosyloxy-1-butyne with K[ 18 F]F produces vinyl acetylene as well as 4-[ 18 F]fluoro-1-butyne, while the same reaction using 5-tosyloxy-1-pentyne gives exclusively 5-[ 18 F]fluoro-1-pentyne. Thus, ω-[ 18 F]fluoro-1-alkynes with chain lengths longer than four carbons may be better radiolabeled synthons for use in click chemistry.

  11. Nuclear medicine

    International Nuclear Information System (INIS)

    Lentle, B.C.

    1986-01-01

    Several growth areas for nuclear medicine were defined. Among them were: cardiac nuclear medicine, neuro-psychiatric nuclear medicine, and cancer diagnosis through direct tumor imaging. A powerful new tool, Positron Emission Tomography (PET) was lauded as the impetus for new developments in nuclear medicine. The political environment (funding, degree of autonomy) was discussed, as were the economic and scientific environments

  12. Immobilization of biomolecules onto surfaces according to ultraviolet light diffraction patterns

    International Nuclear Information System (INIS)

    Bjoern Petersen, Steffen; Kold di Gennaro, Ane; Neves-Petersen, Maria Teresa; Skovsen, Esben; Parracino, Antonietta

    2010-01-01

    We developed a method for immobilization of biomolecules onto thiol functionalized surfaces according to UV diffraction patterns. UV light-assisted molecular immobilization proceeds through the formation of free, reactive thiol groups that can bind covalently to thiol reactive surfaces. We demonstrate that, by shaping the pattern of the UV light used to induce molecular immobilization, one can control the pattern of immobilized molecules onto the surface. Using a single-aperture spatial mask, combined with the Fourier transforming property of a focusing lens, we show that submicrometer (0.7 μm) resolved patterns of immobilized prostate-specific antigen biomolecules can be created. If a dual-aperture spatial mask is used, the results differ from the expected Fourier transform pattern of the mask. It appears as a superposition of two diffraction patterns produced by the two apertures, with a fine structured interference pattern superimposed.

  13. Recent advances in chemical functionalization of nanoparticles with biomolecules for analytical applications.

    Science.gov (United States)

    Oh, Ju-Hwan; Park, Do Hyun; Joo, Jang Ho; Lee, Jae-Seung

    2015-11-01

    The recent synthetic development of a variety of nanoparticles has led to their widespread application in diagnostics and therapeutics. In particular, the controlled size and shape of nanoparticles precisely determine their unique chemical and physical properties, which is highly attractive for accurate analysis of given systems. In addition to efforts toward controlling the synthesis and properties of nanoparticles, the surface functionalization of nanoparticles with biomolecules has been intensively investigated since the mid-1990s. The complicated yet programmable properties of biomolecules have proved to substantially enhance and enrich the novel functions of nanoparticles to achieve "smart" nanoparticle materials. In this review, the advances in chemical functionalization of four types of representative nanoparticle with DNA and protein molecules in the past five years are critically reviewed, and their future trends are predicted.

  14. Analysis of gate underlap channel double gate MOS transistor for electrical detection of bio-molecules

    Science.gov (United States)

    Ajay; Narang, Rakhi; Saxena, Manoj; Gupta, Mridula

    2015-12-01

    In this paper, an analytical model for gate drain underlap channel Double-Gate Metal-Oxide-Semiconductor Field-Effect Transistor (DG-MOSFET) for label free electrical detection of biomolecules has been proposed. The conformal mapping technique has been used to derive the expressions for surface potential, lateral electric field, energy bands (i.e. conduction and valence band) and threshold voltage (Vth). Subsequently a full drain current model to analyze the sensitivity of the biosensor has been developed. The shift in the threshold voltage and drain current (after the biomolecules interaction with the gate underlap channel region of the MOS transistor) has been used as a sensing metric. All the characteristic trends have been verified through ATLAS (SILVACO) device simulation results.

  15. Heart failure - medicines

    Science.gov (United States)

    CHF - medicines; Congestive heart failure - medicines; Cardiomyopathy - medicines; HF - medicines ... will need to take most of your heart failure medicines every day. Some medicines are taken once ...

  16. Density functional theory calculations and molecular dynamics simulations of the adsorption of biomolecules on graphene surfaces.

    Science.gov (United States)

    Qin, Wu; Li, Xin; Bian, Wen-Wen; Fan, Xiu-Juan; Qi, Jing-Yao

    2010-02-01

    There is increasing attention in the unique biological and medical properties of graphene, and it is expected that biomaterials incorporating graphene will be developed for the graphene-based drug delivery systems and biomedical devices. Despite the importance of biomolecules-graphene interactions, a detailed understanding of the adsorption mechanism and features of biomolecules onto the surfaces of graphene is lacking. To address this, we have performed density functional theory (DFT) and molecular dynamics (MD) methods exploring the adsorption geometries, adsorption energies, electronic band structures, adsorption isotherms, and adsorption dynamics of l-leucine (model biomolecule)/graphene composite system. DFT calculations confirmed the energetic stability of adsorption model and revealed that electronic structure of graphene can be controlled by the adsorption direction of l-leucine. MD simulations further investigate the potential energy and van der Waals energy for the interaction processes of l-leucine/graphene system at different temperatures and pressures. We find that the van der Waals interaction between the l-leucine and the graphene play a dominant role in the adsorption process under a certain range of temperature and pressure, and the l-leucine molecule could be adsorbed onto graphene spontaneously in aqueous solution.

  17. Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells

    Science.gov (United States)

    Shalek, Alex K.; Robinson, Jacob T.; Karp, Ethan S.; Lee, Jin Seok; Ahn, Dae-Ro; Yoon, Myung-Han; Sutton, Amy; Jorgolli, Marsela; Gertner, Rona S.; Gujral, Taranjit S.; MacBeath, Gavin; Yang, Eun Gyeong; Park, Hongkun

    2010-01-01

    A generalized platform for introducing a diverse range of biomolecules into living cells in high-throughput could transform how complex cellular processes are probed and analyzed. Here, we demonstrate spatially localized, efficient, and universal delivery of biomolecules into immortalized and primary mammalian cells using surface-modified vertical silicon nanowires. The method relies on the ability of the silicon nanowires to penetrate a cell’s membrane and subsequently release surface-bound molecules directly into the cell’s cytosol, thus allowing highly efficient delivery of biomolecules without chemical modification or viral packaging. This modality enables one to assess the phenotypic consequences of introducing a broad range of biological effectors (DNAs, RNAs, peptides, proteins, and small molecules) into almost any cell type. We show that this platform can be used to guide neuronal progenitor growth with small molecules, knock down transcript levels by delivering siRNAs, inhibit apoptosis using peptides, and introduce targeted proteins to specific organelles. We further demonstrate codelivery of siRNAs and proteins on a single substrate in a microarray format, highlighting this technology’s potential as a robust, monolithic platform for high-throughput, miniaturized bioassays. PMID:20080678

  18. Computational On-Chip Imaging of Nanoparticles and Biomolecules using Ultraviolet Light

    Science.gov (United States)

    Daloglu, Mustafa Ugur; Ray, Aniruddha; Gorocs, Zoltan; Xiong, Matthew; Malik, Ravinder; Bitan, Gal; McLeod, Euan; Ozcan, Aydogan

    2017-03-01

    Significant progress in characterization of nanoparticles and biomolecules was enabled by the development of advanced imaging equipment with extreme spatial-resolution and sensitivity. To perform some of these analyses outside of well-resourced laboratories, it is necessary to create robust and cost-effective alternatives to existing high-end laboratory-bound imaging and sensing equipment. Towards this aim, we have designed a holographic on-chip microscope operating at an ultraviolet illumination wavelength (UV) of 266 nm. The increased forward scattering from nanoscale objects at this short wavelength has enabled us to detect individual sub-30 nm nanoparticles over a large field-of-view of >16 mm2 using an on-chip imaging platform, where the sample is placed at ≤0.5 mm away from the active area of an opto-electronic sensor-array, without any lenses in between. The strong absorption of this UV wavelength by biomolecules including nucleic acids and proteins has further enabled high-contrast imaging of nanoscopic aggregates of biomolecules, e.g., of enzyme Cu/Zn-superoxide dismutase, abnormal aggregation of which is linked to amyotrophic lateral sclerosis (ALS) - a fatal neurodegenerative disease. This UV-based wide-field computational imaging platform could be valuable for numerous applications in biomedical sciences and environmental monitoring, including disease diagnostics, viral load measurements as well as air- and water-quality assessment.

  19. Computational On-Chip Imaging of Nanoparticles and Biomolecules using Ultraviolet Light

    KAUST Repository

    Daloglu, Mustafa Ugur

    2017-03-09

    Significant progress in characterization of nanoparticles and biomolecules was enabled by the development of advanced imaging equipment with extreme spatial-resolution and sensitivity. To perform some of these analyses outside of well-resourced laboratories, it is necessary to create robust and cost-effective alternatives to existing high-end laboratory-bound imaging and sensing equipment. Towards this aim, we have designed a holographic on-chip microscope operating at an ultraviolet illumination wavelength (UV) of 266 nm. The increased forward scattering from nanoscale objects at this short wavelength has enabled us to detect individual sub-30 nm nanoparticles over a large field-of-view of >16 mm2 using an on-chip imaging platform, where the sample is placed at ≤0.5 mm away from the active area of an opto-electronic sensor-array, without any lenses in between. The strong absorption of this UV wavelength by biomolecules including nucleic acids and proteins has further enabled high-contrast imaging of nanoscopic aggregates of biomolecules, e.g., of enzyme Cu/Zn-superoxide dismutase, abnormal aggregation of which is linked to amyotrophic lateral sclerosis (ALS) - a fatal neurodegenerative disease. This UV-based wide-field computational imaging platform could be valuable for numerous applications in biomedical sciences and environmental monitoring, including disease diagnostics, viral load measurements as well as air- and water-quality assessment.

  20. Raman Microscopy: A Noninvasive Method to Visualize the Localizations of Biomolecules in the Cornea.

    Science.gov (United States)

    Kaji, Yuichi; Akiyama, Toshihiro; Segawa, Hiroki; Oshika, Tetsuro; Kano, Hideaki

    2017-11-01

    In vivo and in situ visualization of biomolecules without pretreatment will be important for diagnosis and treatment of ocular disorders in the future. Recently, multiphoton microscopy, based on the nonlinear interactions between molecules and photons, has been applied to reveal the localizations of various molecules in tissues. We aimed to use multimodal multiphoton microscopy to visualize the localizations of specific biomolecules in rat corneas. Multiphoton images of the corneas were obtained from nonlinear signals of coherent anti-Stokes Raman scattering, third-order sum frequency generation, and second-harmonic generation. The localizations of the adhesion complex-containing basement membrane and Bowman layer were clearly visible in the third-order sum frequency generation images. The fine structure of type I collagen was observed in the corneal stroma in the second-harmonic generation images. The localizations of lipids, proteins, and nucleic acids (DNA/RNA) was obtained in the coherent anti-Stokes Raman scattering images. Imaging technologies have progressed significantly and been applied in medical fields. Optical coherence tomography and confocal microscopy are widely used but do not provide information on the molecular structure of the cornea. By contrast, multiphoton microscopy provides information on the molecular structure of living tissues. Using this technique, we successfully visualized the localizations of various biomolecules including lipids, proteins, and nucleic acids in the cornea. We speculate that multiphoton microscopy will provide essential information on the physiological and pathological conditions of the cornea, as well as molecular localizations in tissues without pretreatment.

  1. Recent trends in carbon nanomaterial-based electrochemical sensors for biomolecules: A review

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Cheng; Denno, Madelaine E.; Pyakurel, Poojan; Venton, B. Jill, E-mail: jventon@virginia.edu

    2015-08-05

    Carbon nanomaterials are advantageous for electrochemical sensors because they increase the electroactive surface area, enhance electron transfer, and promote adsorption of molecules. Carbon nanotubes (CNTs) have been incorporated into electrochemical sensors for biomolecules and strategies have included the traditional dip coating and drop casting methods, direct growth of CNTs on electrodes and the use of CNT fibers and yarns made exclusively of CNTs. Recent research has also focused on utilizing many new types of carbon nanomaterials beyond CNTs. Forms of graphene are now increasingly popular for sensors including reduced graphene oxide, carbon nanohorns, graphene nanofoams, graphene nanorods, and graphene nanoflowers. In this review, we compare different carbon nanomaterial strategies for creating electrochemical sensors for biomolecules. Analytes covered include neurotransmitters and neurochemicals, such as dopamine, ascorbic acid, and serotonin; hydrogen peroxide; proteins, such as biomarkers; and DNA. The review also addresses enzyme-based electrodes that are used to detect non-electroactive species such as glucose, alcohols, and proteins. Finally, we analyze some of the future directions for the field, pointing out gaps in fundamental understanding of electron transfer to carbon nanomaterials and the need for more practical implementation of sensors. - Highlights: • We review the types of carbon nanomaterials used in electrochemical sensors. • Different materials and sensor designs are compared for classes of biomolecules. • Future challenges of better sensor design and implementation are assessed.

  2. In vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins

    International Nuclear Information System (INIS)

    Dadachova, Ekaterina; Rivera, Johanna; Revskaya, Ekaterina; Nakouzi, Antonio; Cahill, Sean M.; Blumenstein, Michael; Xiao, Hui; Rykunov, Dmitry; Casadevall, Arturo

    2008-01-01

    Introduction: There is a lot of interest towards creating therapies and vaccines for Bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. Systemic injection of lethal factor (LF), edema factor (EF) and protective antigen (PA) in mice produces toxicity, and this protocol is commonly used to investigate the efficacy of specific antibodies in passive protection and vaccine studies. Availability of toxins labeled with imageable radioisotopes would allow to demonstrate their tissue distribution after intravenous injection at toxin concentration that are below pharmacologically significant to avoid masking by toxic effects. Methods: LF, EF and PA were radiolabeled with 188 Re and 99m Tc, and their performance in vitro was evaluated by macrophages and Chinese hamster ovary cells toxicity assays and by binding to macrophages. Scintigraphic imaging and biodistribution of intravenously (IV) injected 99m Tc-and 123 I-labeled toxins was performed in BALB/c mice. Results: Radiolabeled toxins preserved their biological activity. Scatchard-type analysis of the binding of radiolabeled PA to the J774.16 macrophage-like cells revealed 6.6x10 4 binding sites per cell with a dissociation constant of 6.7 nM. Comparative scintigraphic imaging of mice injected intravenously with either 99m Tc-or 123 I-labeled PA, EF and LF toxins demonstrated similar biodistribution patterns with early localization of radioactivity in the liver, spleen, intestines and excretion through kidneys. The finding of renal excretion shortly after IV injection strongly suggests that toxins are rapidly degraded which could contribute to the variability of mouse toxigenic assays. Biodistribution studies confirmed that all three toxins concentrated in the liver and the presence of high levels of radioactivity again implied rapid degradation in vivo. Conclusions: The availability of 188 Re and 99m Tc-labeled PA, LF and EF toxins allowed us to

  3. Development of radioactively labelled cancer seeking biomolecules for targeted therapy. India

    International Nuclear Information System (INIS)

    Pillai, M.R.A.

    2000-01-01

    The work done towards the development of bifunctional chelating agents, modified peptide and their radiolabelling studies with 90 Y and 188 Re are reported. Bifunctional chelating agents DOTA, TETA and DAHPES were synthesised. DOTA-Lanreotide (Mauritius) was synthesised from Lanreotide. 90 Y and 188 Re used in the studies were obtained from 90 Sr- 90 Y and 188 W- 188 Re generators. Complexation studies of DOTA and Mauritius with 90 Y and that of DAHPES and EC with 188 Re were carried out. Cell labelling of 90 Y-DOTA-Lanreotide with a cell line expressing somatostatin receptors was also carried out

  4. Decommissioning of a Radioactive Facility Used for Biomolecule Labeling and Biological Effects

    International Nuclear Information System (INIS)

    Yagüe, L.; Navarro, N.; Álvarez, A.; Quiñones, J.

    2015-01-01

    This paper presents the measurement methodology designed for the final status survey of an old radioactive facility, used as radiolabeling lab. Its declassification as radioactive facility required the radiological characterization of all walls, structures and materials at the facility in order to reuse its outbuilding for conventional use. To demonstrate compliance with the declassification criteria, the design of the final status survey was performed applying MARSSIM(1) (Multi-Agency Radiation Survey and Site Investigation Manual) methodology and using different measurement techniques depending on the radioactive isotopes in the inventory of the facility, their half-lives and emission characteristics.

  5. Synthesis of radiolabelled aryl azides from diazonium salts: experimental and computational results permit the identification of the preferred mechanism.

    Science.gov (United States)

    Joshi, Sameer M; de Cózar, Abel; Gómez-Vallejo, Vanessa; Koziorowski, Jacek; Llop, Jordi; Cossío, Fernando P

    2015-05-28

    Experimental and computational studies on the formation of aryl azides from the corresponding diazonium salts support a stepwise mechanism via acyclic zwitterionic intermediates. The low energy barriers associated with both transition structures are compatible with very fast and efficient processes, thus making this method suitable for the chemical synthesis of radiolabelled aryl azides.

  6. Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [177Lu-DOTA0,Tyr 3]octreotate

    NARCIS (Netherlands)

    B. de Keizer (Bart); M.O. van Aken (Maarten); R.A. Feelders (Richard); W.W. de Herder (Wouter); B.L. Kam (Boen); M. van Essen (Martijn); E.P. Krenning (Eric); D. Kwekkeboom (Dik)

    2008-01-01

    textabstractIntroduction: Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin

  7. Effect of highly radiolabelled 2,4-dinitrochlorobenzene (DNCB) on experimental DNCB contact dermatitis in guinea pigs

    International Nuclear Information System (INIS)

    Filipp, G.; Biro, G.; Bahmer, F.; Mitschke, H.; Lehmann, G.

    1984-01-01

    With the aid of epicutaneous application of 2,4-dinitrochlorobenzene (DNCB) solution in acetone, we induced a cutaneous allergic reaction of the delayed type. Our question was whether the development of the DNCB cutaneous sensitivity could be suppressed by highly radiolabelled DNCB. On the basis of the clonal selection theory and our own results with other in vivo-experimental animal models, one could suppose that the highly radiolabelled DNCB as haptens binds to the Ig-membrane receptors of the genetically determined T-lymphocyte clone, and that the conjugated radioactivity ( 125 I) causes a selective radioactive damage to this competent T-lymphocyte subpopulation. By means of intracardially applied radiolabelled DNCB, we are able to induce either complete or very significant suppression of the cutaneous DNCB immune response. In the second experiment, the highly radiolabelled DNCB was not able to inhibit sensitization to a simultaneously applied 4-ethoxy-methylene-2-phenyl-oxazolone (oxazolone). This result clearly demonstrates the antigen specificity of this form of immune suppression. (author)

  8. Synthesis and Radiolabeling of Modified Peptides Attached to Heterocyclic Rings and Their Possible Medical Applications

    International Nuclear Information System (INIS)

    Shams El-Din, H.A.A.

    2012-01-01

    Keeping in mind the pharmacological potential of heterocyclic rings as well as the advantage of biodegradability and biocompatibility of amino acids/peptides, in this thesis we were prompted for the following: 1. Synthesis of novel dipeptide derivatives coupled with different heterocyclic rings (pyridine, 1,2,4-triazol-pyridine, 1,3,4-oxadiazolpyridine and tetrazol-pyridine rings). 2. Characterization of the synthesized compounds on the basis of their spectral data (IR, Mass and 1 H-NMR spectra). 3. Study their antimicrobial activity as one of their expected biological activities. 4. Study the radioiodination of some synthesized dipeptide derivatives. 5. Study the biodistribution of the radiolabeled compounds in normal mice as preliminary studies for the possibility of using them as agents for imaging and treatment.

  9. The spreading of radiolabelled fatty suppository bases in the human rectum

    International Nuclear Information System (INIS)

    Sugito, Keiko; Ogata, Hiroyasu; Noguchi, Masahiro; Kogure, Takahashi; Takano, Masaaki; Maruyama, Yuzo; Sasaki, Yasuhito

    1988-01-01

    The purpose of this study was to develop a radiolabelling method for assessing the spreading of fatty suppository bases (Witepsol H-5, W-35 and S-55), and to apply this technique to the evaluation of suppository disposition in the human rectum. 99m/Tc was bound chemically to the bases Witepsol H-5 and W-35, and mixed physically with Witepsol S-55. The spreading of each suppository base was monitored by gamma-scintigraphy following rectal administration. The mean radioactivity remaining at the inserted region 4 h after administration was 44.2% of total activity. The mean perpendicular maximum spreading distance from this region was 7.7 cm on the scintigram near to the sigmoid colon. Defecation was suggested to be a factor influencing the spread of suppository bases. However, there was no clear relationship between the type of suppository base used and the extent of its spread within the rectum. 6 refs.; 4 figs.; 1 table

  10. Biodistribution parameters and radiation absorbed dose estimates for radiolabeled human low density lipoprotein

    International Nuclear Information System (INIS)

    Hay, R.V.; Ryan, J.W.; Williams, K.A.; Atcher, R.W.; Brechbiel, M.W.; Gansow, O.A.; Fleming, R.M.; Stark, V.J.; Lathrop, K.A.; Harper, P.V.

    1992-01-01

    The authors propose a model to generate radiation absorbed dose estimates for radiolabeled low density lipoprotein (LDL), based upon eight studies of LDL biodistribution in three adult human subjects. Autologous plasma LDL was labeled with Tc-99m, I-123, or In-111 and injected intravenously. Biodistribution of each LDL derivative was monitored by quantitative analysis of scintigrams and direct counting of excreta and of serial blood samples. Assuming that transhepatic flux accounts for the majority of LDL clearance from the bloodstream, they obtained values of cumulated activity (A) and of mean dose per unit administered activity (D) for each study. In each case highest D values were calculated for liver, with mean doses of 5 rads estimated at injected activities of 27 mCi, 9 mCi, and 0.9 mCi for Tc-99m-LDL, I-123-LDL, and In-111-LDL, respectively

  11. The development, commercialization, and clinical context of yttrium-90 radiolabeled resin and glass microspheres

    Directory of Open Access Journals (Sweden)

    Mark A. Westcott, MD

    2016-10-01

    Full Text Available Selective internal radiation therapy has emerged as a well-accepted therapeutic for primary and metastatic hepatic malignancies. This therapeutic modality requires the combined efforts of multiple medical disciplines to ensure the safe delivery of yttrium-90 (90Y-labeled microspheres. The development of this therapy followed decades of clinical research involving tumor vascularity and microsphere development. Today, it is essential that treating physicians have a thorough understanding of hepatic tumor vascularity and 90Y microsphere characteristics before undertaking this complex intervention. This review explores the contributions of early investigators of this therapy, as well as the development, US Food and Drug Administration approval, manufacturing process, and attributes of the 2 commercially available 90Y radiolabeled microsphere device to clarify the key physical differences between the products.

  12. CT-SPECT fusion to correlate radiolabeled monoclonal antibody uptake with abdominal CT findings

    International Nuclear Information System (INIS)

    Kramer, E.L.; Noz, M.E.; Sanger, J.J.; Megibow, A.J.; Maguire, G.Q.

    1989-01-01

    To enhance the information provided by computed tomography (CT) and single photon emission computed tomography (SPECT) performed with radiolabeled, anti-carcinoembryonic antigen monoclonal antibody (MoAb), the authors performed fusion of these types of images from eight subjects with suspected colorectal adenocarcinoma. Section thickness and pixel size of the two studies were matched, coordinates of corresponding points from each study were identified, and CT sections were translated, rotated, and reprojected to match the corresponding SPECT scans. The CT-SPECT fusion enabled identification of anatomic sites of tumor-specific MoAb accumulation in four cases, showed non-specific MoAb accumulation in two, and helped confirm information only suggested by the two studies separately in one

  13. Use of a microwave cavity to reduce reaction times in radiolabelling with [11C]cyanide

    International Nuclear Information System (INIS)

    Thorell, J.-O.; Stone-Elander, S.; Elander, N.

    1992-01-01

    Advantages of using a microwave cavity over thermal treatment are demonstrated for radiolabelling reactions with [ 11 C]cyanide. For comparison purposes, two literature syntheses involving typical cyanide chemistry at rather vigorous conditions were investigated: cyano-de-halogenation with subsequent hydrolysis of the nitrile and the Bucher-Strecker synthesis of an aromatic amino acid. Comparable yields were obtained with intensities <100 W in reaction times that were 1/15 to 1/20th those used in thermal methods. Even rates of slower nucleophilic substitutions could be increased by manipulating the polarity of the medium. For the short-lived radionuclide carbon-11, such time gains result in radioactivity gains at the end-of-synthesis on the order of 70-100%. (Author)

  14. Use of isotopically radiolabelled GM3 ganglioside to study metabolic alterations in Salla disease

    International Nuclear Information System (INIS)

    Chigorno, Vanna; Valsecchi, Manuela; Nicolini, Marco; Sonnino, Sandro

    1997-01-01

    We report the preparation of radioactive GM3 ganglioside and its use in the study of sialic acid storage disorders. For the first time GM3 was isotopically radiolabelled in three positions of the molecule: at the sialic acid acetyl group, [ 3 H-Neu5Ac]GM3, at the Cl of the fatty acid moiety, [ 1 4C-Stearoyl]GM3, and at C3 of sphingosine, [ 3 H-Sph]GM3. The radioactive GM3 administered to cultured human fibroblasts from a patient suffering from Salla disease was taken up by the cells and metabolized. An analysis of the distribution of radioactivity within the ganglioside metabolic derivatives showed an accumulation of free sialic acid and ceramide in the pathological cells. (author). 25 refs., 2 figs., 1 tab

  15. Echinococcus granulosus: the potential use of specific radiolabelled antibodies in diagnosis by immunoscintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Rogan, M.T.; Morris, D.L.; Pritchard, D.I.; Perkins, A.C. (Nottingham Univ. (UK))

    1990-05-01

    Diagnosis of hydatid disease in man is frequently dependent on the imaging of cysts in situ by techniques such as ultrasonography and CAT scans. Such methods are useful but are not specific and can lead to errors in diagnosis. The present work reports preliminary experiments on the development of a specific imaging technique for hydatid cysts using radiolabelled antibodies. A purified preparation of antigen B of hydatid fluid was used to raise polyclonal antisera in rabbits and the resulting affinity-purified IgG labelled with {sup 131}I. Gerbils with an established Echinococcus granulosus infection were injected intraperitoneally with the labelled antibody and imaged 48 h later with a gamma camera. Hydatid cysts could be identified within the peritoneal cavity and post-mortem assessment of activity showed the cysts to contain approximately four times as much activity as the surrounding organs thereby indicating successful targeting of the antibody to the cysts. (author).

  16. The alginate layer for improving doxorubicin release and radiolabeling stability of chitosan hydrogels

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeong Il; Lee, Chang Moon; Jeong, Hwan Seok; Hwang, Hyo Sook; Lim, Seok Tae; Sohn, Myung Hee; Jeong, Hwan Jeong [Dept. of Nuclear Medicine and Therapeutic Medicine Research Center, Cyclotron Research Center, Institute for Medical Science, Biomedical Research Institute, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Lee, Chang Moon [Dept. of Biomedical Engineering, Chonnam National University, Yeosu (Korea, Republic of)

    2015-12-15

    Chitosan hydrogels (CSH) formed through ionic interaction with an anionic molecule are suitable as a drug carrier and a tissue engineering scaffold. However, the initial burst release of drugs from the CSH due to rapid swelling after immersing in a biofluid limits their wide application as a drug delivery carrier. In this study, alginate layering on the surface of the doxorubicin (Dox)-loaded and I-131-labeled CSH (DI-CSH) was performed. The effect of the alginate layering on drug release behavior and radiolabeling stability was investigated. Chitosan was chemically modified using a chelator for I-131 labeling. After labeling of I-131 and mixing of Dox, the chitosan solution was dropped into tripolyphosphate (TPP) solution using an electrospinning system to prepare spherical microhydrogels. The DI-CSH were immersed into alginate solution for 30 min to form the crosslinking layer on their surface. The formation of alginate layer on the DI-CSH was confirmed by Fourier transform infrared spectroscopy (FT-IR) and zeta potential analysis. In order to investigate the effect of alginate layer, studies of in vitro Dox release from the hydrogels were performed in phosphate buffered in saline (PBS, pH 7.4) at 37 °C for 12 days. The radiolabeling stability of the hydrogels was evaluated using ITLC under different experimental condition (human serum, normal saline, and PBS) at 37 °C for 12 days. Formatting the alginate-crosslinked layer on the CSH surface did not change the spherical morphology and the mean diameter (150 ± 10 μm). FT-IR spectra and zeta potential values indicate that alginate layer was formed successfully on the surface of the DI-CSH. In in vitro Dox release studies, the total percentage of the released Dox from the DI-CSH for 12 days were 60.9 ± 0.8, 67.3 ± 1.4, and 71.8 ± 2.5 % for 0.25, 0.50, and 1.00 mg Dox used to load into the hydrogels, respectively. On the other hand, after formatting alginate layer, the percentage of the

  17. 'Label and go' - A fast and easy radiolabelling method for pellets

    Energy Technology Data Exchange (ETDEWEB)

    Philippe, C.; Mien, L.-K. [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Salar-Behzadi, S. [Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Knaeusl, B. [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Wadsak, W. [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Inorganic Chemistry, University of Vienna, A-1090 Vienna (Austria); Dudczak, R.; Kletter, K. [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Viernstein, H. [Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Mitterhauser, M. [Department of Nuclear Medicine, Medical University of Vienna, A-1090 Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, A-1090 Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

    2010-03-15

    For the development and process optimization of pharmaceutical equipment, it is important to investigate the underlying processes. Taking the fluidized bed technology as an example, the study of particle flow pattern and convection of the particles within the functional unity is essential for construction and process improvement. With positron emission particle tracking (PEPT) it is possible to study the real-time particle motion with radiolabelled particles. We established a fast and simple labelling technique with [{sup 18}F]fluoride for pellets composed of Avicel and anion exchange resin. The uptake of activity ranged from 1.3% to 1.7% per mg and 8.6% to 16.3% per pellet. A specific binding of [{sup 18}F]fluoride with increasing degree of anion exchange resin in the pellets could be observed.

  18. Radiolabeling of intact dosage forms by neutron activation: effects on in vitro performance

    International Nuclear Information System (INIS)

    Parr, A.; Jay, M.

    1987-01-01

    Compressed tablets containing various quantities of stable isotopes of Ba, Er, and Sm for use in neutron activation studies were evaluated for the effect of stable isotope incorporation on tablet hardness and disintegration times. At concentrations likely to be used in scintigraphic studies employing neutron activation as a radiolabeling method, no significant effect on in vitro parameters were observed. While the incorporation of stable isotopes influenced tablet hardness to a greater degree than disintegration time, irradiation of tablets in a neutron flux of 4.4 x 10(13) n/cm2 sec had a direct effect on tablet disintegration time. Thus, future neutron activation studies should focus on minimizing the amount of stable isotope to be incorporated with the formulation while using the shortest feasible irradiation time

  19. Comparative study between phenol and imidazole derivatives in radiolabeling of some steroid hormones

    International Nuclear Information System (INIS)

    Sallam, Kh.M.

    2010-01-01

    A phenol or imidazole ring is rarely present in steroid hormones, So, the molecule of steroid hormone requires chemical modification by addition of an iodinable residue like phenol or imedazole. So that the comparative study between phenol derivatives, include tyrosine methyl ester (TME) and tyramine, and imidazole derivatives, like histamine and histedine methyl ester (HME), for radiolabeling of some steroid hormones include estradiol and testosterone is the aim of the present study. The conjugation step was carried using mixed anhydride method and followed by radioiodination using iodogen as an oxidizing agent. Purification step was carried out using high performance liquid chromatography (HPLC). Optimization and validation of the tracer were carried out. Immunoreactivity of the all obtained tracers was check by using specific polyclonal antibodies. The results indicated that imidazols derivatives are more suitable from immunoreactivity view and storage period.

  20. Tc-99m Radiolabeled Alendronate Sodium Microemulsion: Characterization and Permeability Studies across Caco-2 Cells.

    Science.gov (United States)

    Elitez, Yetkin; Ekinci, Meliha; Ilem-Ozdemir, Derya; Gundogdu, Evren; Asikoglu, Makbule

    2017-06-12

    Alendronate sodium (ALD) is used orally but it is poorly absorbed from the gastrointestinal (GI) tract. For this reason, microemulsion system was chosen to evaluate ALD from the GI tract after oral delivery. This study was aimed to prepare water-in-oil (w/o) microemulsion formulation of ALD and evaluate the permeability of ALD microemulsion from Caco-2 cell lines with radioactive and non-radioactive studies. The ALD microemulsion was developed by using pseudo-ternary phase diagram and composed of Soybean oil, Colliphor EL, Tween 80, Transcutol and distilled water. The prepared ALD microemulsion was characterized by physical appearance, droplet size, viscosity, pH, electrical conductivity and refractive index. The stability of the formulation was investigated for 6 months at 25±2°C/60±5% of relative humidity (RH) as well as at 40±2°C/75±5% RH. After that 1 mg of ALD was radiolabeled with 99mTc and added to microemulsion. The permeability studies were performed with both 99mTc-ALD microemulsion and ALD microemulsion. The experimental results suggested that ALD microemulsion presented adequate stability with droplet size varying from 37.8±0.9 to 39.9±1.2 nm during incubation time. In addition, ALD microemulsion was radiolabeled with high labeling efficiency (>95%). In non-radioactive study, ALD permeability was found to be 45 μg.mL-1 and microemulsion has high permeability percentage when compared to another study. The novel w/o microemulsion formulation has been developed for oral delivery of ALD. Based on the results, permeability of ALD could be significantly improved by the microemulsion formulation. In addition, 99mTc-ALD microemulsion in capsule can be used for bone disease treatment and diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Botulinum neurotoxin type A radiolabeled at either the light or the heavy chain

    International Nuclear Information System (INIS)

    Dekleva, M.L.; DasGupta, B.R.; Sathyamoorthy, V.

    1989-01-01

    Botulinum neurotoxin (NT) has two distinct structural regions called L and H chains (approximately 50 and approximately 100 kDa, respectively). Although the H chain is responsible for binding of the NT to neuronal cells, it is not known which of the subunits is internalized and therefore responsible for causing the blockage of acetylcholine release in susceptible neuronal cells. In this report we describe for the first time the preparation of type A NT which is selectively radiolabeled at either the L or the H chain subunit. Such NT preparations will be useful as tools for determining the distribution of L and H chains in poisoned neuronal cells and the role that each subunit plays in inducing toxicity. The L and H chains of the NT (approximately 150 kDa) were separated, purified, and then individually radiolabeled by reductive methylation of the lysine residues using [3H]- or [14C]formaldehyde. The labeled L and H chains were reconjugated with the complementary unlabeled L and H chains. Formation of -S-S- and noncovalent bonds between the L and H chains regenerated the approximately 150 kDa NT. Autoradiographs of sodium dodecyl sulfate polyacrylamide gels confirmed that each reconstituted NT preparation was labeled at only one subunit chain. NT selectively labeled at either the L or the H chain had specific radioactivities of ca. 25-30 and 45-55 microCi/mumol, respectively, and toxicity (mouse LD50/mg protein) values of 2.2 +/- 1.1 X 10(7) and 3.0 +/- 1.0 X 10(7), respectively. A linear increase in the specific radioactivity of L and H chain subunits was observed with increasing concentrations of 3H- or 14C-labeled formaldehyde in the reaction mixture and with increasing concentrations of L or H chain in the reaction mixture

  2. Targeted Killing of Virally Infected Cells by Radiolabeled Antibodies to Viral Proteins

    Science.gov (United States)

    Dadachova, Ekaterina; Patel, Mahesh C; Toussi, Sima; Apostolidis, Christos; Morgenstern, Alfred; Brechbiel, Martin W; Gorny, Miroslaw K; Zolla-Pazner, Susan; Casadevall, Arturo; Goldstein, Harris

    2006-01-01

    Background The HIV epidemic is a major threat to health in the developing and western worlds. A modality that targets and kills HIV-1-infected cells could have a major impact on the treatment of acute exposure and the elimination of persistent reservoirs of infected cells. The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo. Methods and Findings Antibodies to HIV-1 envelope glycoproteins gp120 and gp41 labeled with radioisotopes bismuth 213 (213Bi) and rhenium 188 (188Re) selectively killed chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells (hPBMCs) in vitro. Treatment of severe combined immunodeficiency (SCID) mice harboring HIV-1-infected hPBMCs in their spleens with a 213Bi- or 188Re-labeled monoclonal antibody (mAb) to gp41 resulted in a 57% injected dose per gram uptake of radiolabeled mAb in the infected spleens and in a greater than 99% elimination of HIV-1-infected cells in a dose-dependent manner. The number of HIV-1-infected thymocytes decreased 2.5-fold in the human thymic implant grafts of SCID mice treated with the 188Re-labeled antibody to gp41 compared with those treated with the 188Re-control mAb. The treatment did not cause acute hematologic toxicity in the treated mice. Conclusions The current study demonstrates the effectiveness of HIV-targeted radioimmunotherapy and may provide a novel treatment option in combination with highly active antiretroviral therapy for the eradication of HIV. PMID:17090209

  3. Diabetes Medicines

    Science.gov (United States)

    Diabetes means your blood glucose, or blood sugar, levels are too high. If you can't control your diabetes with wise food choices and physical activity, you may need diabetes medicines. The kind of medicine you take depends ...

  4. Herbal Medicine

    Science.gov (United States)

    ... for its scent, flavor, or therapeutic properties. Herbal medicines are one type of dietary supplement. They are ... and fresh or dried plants. People use herbal medicines to try to maintain or improve their health. ...

  5. The polygonal model: A simple representation of biomolecules as a tool for teaching metabolism.

    Science.gov (United States)

    Bonafe, Carlos Francisco Sampaio; Bispo, Jose Ailton Conceição; de Jesus, Marcelo Bispo

    2018-01-01

    Metabolism involves numerous reactions and organic compounds that the student must master to understand adequately the processes involved. Part of biochemical learning should include some knowledge of the structure of biomolecules, although the acquisition of such knowledge can be time-consuming and may require significant effort from the student. In this report, we describe the "polygonal model" as a new means of graphically representing biomolecules. This model is based on the use of geometric figures such as open triangles, squares, and circles to represent hydroxyl, carbonyl, and carboxyl groups, respectively. The usefulness of the polygonal model was assessed by undergraduate students in a classroom activity that consisted of "transforming" molecules from Fischer models to polygonal models and vice and versa. The survey was applied to 135 undergraduate Biology and Nursing students. Students found the model easy to use and we noted that it allowed identification of students' misconceptions in basic concepts of organic chemistry, such as in stereochemistry and organic groups that could then be corrected. The students considered the polygonal model easier and faster for representing molecules than Fischer representations, without loss of information. These findings indicate that the polygonal model can facilitate the teaching of metabolism when the structures of biomolecules are discussed. Overall, the polygonal model promoted contact with chemical structures, e.g. through drawing activities, and encouraged student-student dialog, thereby facilitating biochemical learning. © 2017 by The International Union of Biochemistry and Molecular Biology, 46(1):66-75, 2018. © 2017 The International Union of Biochemistry and Molecular Biology.

  6. Microfossils, biomolecules and biominerals in carbonaceous meteorites: implications to the origin of life

    Science.gov (United States)

    Hoover, Richard B.

    2012-11-01

    Environmental and Field Emission Scanning Electron Microscopy (ESEM and FESEM) investigations have shown that a wide variety of carbonaceous meteorites contain the remains of large filaments embedded within freshly fractured interior surfaces of the meteorite rock matrix. The filaments occur singly or in dense assemblages and mats and are often encased within carbon-rich, electron transparent sheaths. Electron Dispersive X-ray Spectroscopy (EDS) spot analysis and 2D X-Ray maps indicate the filaments rarely have detectable nitrogen levels and exhibit elemental compositions consistent with that interpretation that of the meteorite rock matrix. Many of the meteorite filaments are exceptionally well-preserved and show evidence of cells, cell-wall constrictions and specialized cells and processes for reproduction, nitrogen fixation, attachment and motility. Morphological and morphometric analyses permit many of the filaments to be associated with morphotypes of known genera and species of known filamentous trichomic prokaryotes (cyanobacteria and sulfur bacteria). The presence in carbonaceous meteorites of diagenetic breakdown products of chlorophyll (pristane and phytane) along with indigenous and extraterrestrial chiral protein amino acids, nucleobases and other life-critical biomolecules provides strong support to the hypothesis that these filaments represent the remains of cyanobacteria and other microorganisms that grew on the meteorite parent body. The absence of other life-critical biomolecules in the meteorites and the lack of detectable levels of nitrogen indicate the filaments died long ago and can not possibly represent modern microbial contaminants that entered the stones after they arrived on Earth. This paper presents new evidence for microfossils, biomolecules and biominerals in carbonaceous meteorites and considers the implications to some of the major hypotheses for the Origin of Life.

  7. Recovery of biomolecules from marinated herring (Clupea harengus) brine using ultrafiltration through ceramic membranes

    DEFF Research Database (Denmark)

    Gringer, Nina; Hosseini, Seyed Vali; Svendsen, Tore

    2015-01-01

    Marinated herring processing brines, which are usually discarded, are rich in salt, protein, non-protein nitrogen, iron, fatty acids, antioxidant and even possess enzymatic activity. This study investigated the performance of ceramic ultrafiltration of two herring spice brines with a major focus...... on recovery of high value biomolecules such as proteins, fatty acids, minerals, and phenolic compounds. Chemical and biological oxygen demand (COD, BOD5) as well as total suspended solids (TSS) were also measured to follow the performance of the ultrafiltration. The retentates contained 75-82% (95% TSS...

  8. Plastic Trash goes Biohybrid"-Rapid and Selective Functionalization of Inert Plastic Surfaces with Biomolecules

    DEFF Research Database (Denmark)

    Schiller, Stefan M; Kambhampati, Dev; Stengel, Gudrun

    2010-01-01

    The covalent functionalization of "inert" polymers such as polypropylene with biomolecules for biocompatible or biosensor surfaces is challenging. Here we present a powerful approach to covalently modify "inert" macromolecular surfaces with biomacromolecules reusing old plastic material. A special...... emphasis was placed on easily accessible materials and a process which is easy, fast, efficient, cheap, and reliable. "Plastic trash" (lids from Eppendorf® pipet tip containers) was used as a polymer substrate to demonstrate the use/reuse of commercial packing material to covalently modify this material...

  9. The origin of methane and biomolecules from a CO2 cycle on terrestrial planets

    Czech Academy of Sciences Publication Activity Database

    Civiš, Svatopluk; Knížek, Antonín; Ivanek, Ondřej; Kubelík, Petr; Zukalová, Markéta; Kavan, Ladislav; Ferus, Martin

    2017-01-01

    Roč. 1, č. 10 (2017), s. 721-726 E-ISSN 2397-3366 R&D Projects: GA ČR GA17-05076S; GA ČR GA13-07724S Grant - others:Akademie věd - GA AV ČR(CZ) R200401721; Akademie věd - GA AV ČR(CZ) R200401521 Institutional support: RVO:61388955 Keywords : biomolecules * CO2 cycle on terrestrial planets * Mars Subject RIV: CF - Physical ; Theoretical Chemistry OBOR OECD: Physical chemistry

  10. Studies of metal-biomolecule systems in liquids with beta-detected NMR

    CERN Document Server

    Walczak, Michal

    2017-01-01

    My internship took place within a small research team funded via the European Research Council (ERC Starting Grant: Beta-Drop NMR) at ISOLDE. It was devoted to laser spin-polarization and beta-detected NMR techniques and their future applications in chemistry and biology. I was involved in the design and tests of the beta-NMR spectrometer which will be used in the upcoming experiments. In this way I have been exposed to many topics in physics (atomic and nuclear physics), experimental techniques (vacuum technology, lasers, beta detectors, electronics, DAQ software), as well as chemistry and biology (NMR on metal ions, metal ion binding to biomolecules, quantum chemistry calculations).

  11. Immobilization of biomolecules onto surfaces according to ultraviolet light diffraction patterns

    DEFF Research Database (Denmark)

    Petersen, Steffen B.; Gennaro, Ane Kold Di; Neves Petersen, Teresa

    2010-01-01

    We developed a method for immobilization of biomolecules onto thiol functionalized surfaces according to UV diffraction patterns. UV light-assisted molecular immobilization proceeds through the formation of free, reactive thiol groups that can bind covalently to thiol reactive surfaces. We...... demonstrate that, by shaping the pattern of the UV light used to induce molecular immobilization, one can control the pattern of immobilized molecules onto the surface. Using a single-aperture spatial mask, combined with the Fourier transforming property of a focusing lens, we show that submicrometer (0.7 mu...

  12. Mass spectrometry in structural biology and biophysics architecture, dynamics, and interaction of biomolecules

    CERN Document Server

    Kaltashov, Igor A; Desiderio, Dominic M; Nibbering, Nico M

    2012-01-01

    The definitive guide to mass spectrometry techniques in biology and biophysics The use of mass spectrometry (MS) to study the architecture and dynamics of proteins is increasingly common within the biophysical community, and Mass Spectrometry in Structural Biology and Biophysics: Architecture, Dynamics, and Interaction of Biomolecules, Second Edition provides readers with detailed, systematic coverage of the current state of the art. Offering an unrivalled overview of modern MS-based armamentarium that can be used to solve the most challenging problems in biophysics, structural biol

  13. From Phosphorous to Arsenic: Changing the Classic Paradigm for the Structure of Biomolecules

    Directory of Open Access Journals (Sweden)

    Mark Brown

    2012-05-01

    Full Text Available Biomolecules are composed primarily of the elements carbon, nitrogen, hydrogen, oxygen, sulfur, and phosphorus. The structured assembly of these elements forms the basis for proteins, nucleic acids and lipids. However, the recent discovery of a new bacterium, strain GFAJ-1 of the Halomonadaceae, has shaken the classic paradigms for the architecture of life. Mounting evidence supports the claim that these bacteria substitute arsenic for phosphorus in macromolecules. Herein, we provide a brief commentary and fuel the debate related to what may be a most unusual organism.

  14. Isolation, biosynthesis and biological activity of alkaloids of Tylophora asthmatica, a versatile medicinal plant

    International Nuclear Information System (INIS)

    Mulchandani, N.B.

    1987-01-01

    Tylophorine and related new alkaloids have been isolated from Tylophora asthmatics, Pergularia pallida and Ficus hispida plants. Biosynthesis of this group of alkaloids has been carried out using various labelled precursors for the first time and from the systematic degradation of the isolated radiolabelled tylophorine, it has been concluded that these alkaloids arise from one molecule each of tyrosine, phenylalanine and ornithine. The interactions of Tylophora alkaloids particularly tylophorinidine with biomolecules such as lysozyme and bovine serum albumin have also been studied and binding characteristics determined. It was found that Tylophora alkaloid extract possesses antianaphylactic activity as observed in passive peritoneal anaphylaxis in rats. The drug also possessed mild antihistaminic and anticholinergic activities. Studies of the extract on the bronchial smooth muscle both in vivo and in vitro did not reveal bronchiodilator potential of the drug. In addition, the distribution and metabolism of the drug was studied in vivo using 14 C radiolabelled alkaloids prepared by biosynthetic method. This study further revealed its usefulness since the drug is absorbed by vital organs and also it is not metabolised into fragments which could cause some other damage. Tylophora alkaloids have also been found to be anti-mutagenic. 10 tables, 5 figures, 24 refs. (author)

  15. Renal brush border enzyme-cleavable linkages for low renal radioactivity levels of radiolabeled antibody fragments.

    Science.gov (United States)

    Akizawa, Hiromichi; Imajima, Mitsuo; Hanaoka, Hirofumi; Uehara, Tomoya; Satake, Satoshi; Arano, Yasushi

    2013-02-20

    We previously demonstrated that Fab fragments labeled with 3'-[(131)I]iodohippuryl N(ε)-maleoyl-l-lysine ([(131)I]HML) showed low renal radioactivity from early postinjection time, due to a liberation of m-[(131)I]iodohippuric acid by the action of renal brush border enzymes. Since there are lots of enzymes on renal brush border membrane, peptide linkages other than the glycyl-l-lysine were evaluated as the cleavable linkages to explore the chemical design. In this study, we evaluated four peptide linkages with a general formula of m-iodobenzoyl-glycyl-X (X: l-tyosine O-methyl, l-asparagine, l-glutamine, and N(ε)-Boc-l-lysine). In vitro studies using renal brush border membrane vesicles (BBMVs) demonstrated that 3'-[(125)I]iodohippuryl O-methyl-l-tyrosine (2c) liberated the highest amount of m-[(125)I]iodohippuric acid among the four substrates and the change in the linkage structure altered enzyme species responsible for the hydrolysis reaction. To further assess the applicability of the linkage, a radioiodination reagent containing a glycyl-tyrosine linkage, 3'-[(125)I]iodohippuryl O-((2-maleimidoethyl)carbamoyl)methyl-l-tyrosine (HMT, 12c), was designed, synthesized, and subsequently conjugated to an Fab fragment. [(125)I]HMT-Fab exhibited renal radioactivity levels similar to and significantly lower than [(125)I]HML-Fab and directly radioiodinated Fab, while the blood clearance rates of the three were similar. The analyses of urine for 24 h postinjection of [(125)I]HMT-Fab showed that m-[(125)I]iodohippuric acid was excreted as the major radiometabolite. The findings indicated that glycyl-tyrosine linkage is also available to reduce renal radioactivity levels of radioiodinated Fab fragments, due to liberation of m-iodohippuric acid by the action of enzymes present on renal brush border membrane. These findings suggest that an appropriate selection of peptide linkages would allow the liberation of a designed radiolabeled compound from covalently conjugated

  16. Study of conjugation and radiolabeling of monoclonal antibody rituximab for use in radionuclide therapy

    International Nuclear Information System (INIS)

    Massicano, Adriana Vidal Fernandes

    2011-01-01

    Lymphomas are tumors originated from the transformation of a lymphocyte in the lymphatic system. The most common lymphoma is the Non-Hodgkin Lymphoma (NHL). Advances in immunology and molecular biology have been improving NHL's detection and treatment strategies development, such as Radioimmunotherapy (RIT). Rituximab is an anti-CD20 monoclonal antibody used as immunotherapeutic to treat refractory or relapsed NHL. The goal of the present work was to conjugate this antibody to DOTA-NHS-ester bifunctional chelator and to radiolabel it with 177 Lu radioisotope in order to develop a radio immunotherapeutic agent for NHL's treatment. Different rituximab to DOTA molar ratios (1:5, 1:10, 1:20, 1:50, 1:250, 1:500 and 1:1000) were evaluated in order to determine the best condition for obtaining the highest radiochemical purity of radio immunotherapeutic. The stability of the unlabeled immuno conjugated was evaluated by high performance liquid chromatography (HPLC) for up to 240 days in different storage conditions. The stability of the labeled preparations was evaluated either after storing at 2-8 degree C or incubation in human serum at 37 degree C. The binding to serum proteins was also determined. In vivo studies were performed in healthy Swiss mice, in order to characterize the biological properties of labeled conjugate. Finally, preliminary studies of radio immuno conjugated competitive binding to CD20 positive Raji cells were carried out in order to analyze if the process of conjugation and radiolabeling compromises the immunoreactivity of the antibody. The conjugation applying lower antibody to chelator molar ratios (1:5, 1:10 and 1:20) showed high stability when stored for up to 240 days in different conditions. The HPLC analysis showed that the monoclonal antibody conjugated in molar ratio 1:50 was labeled with higher radiochemical purity (> 95%) when purified in PD-10 column. This conjugate showed reasonable stability at 2-8 degree C. The analysis of the

  17. Synchrotron and small bio-molecules in gas phase and liquid environment: new opportunities in Brazil

    International Nuclear Information System (INIS)

    Naves de Brito, A.

    2011-01-01

    Full text: Two techniques are critically related to the photoelectric law, namely: photoelectron spectroscopy and photoelectron-photoion coincidence spectroscopy. Both are strongly used now a day within synchrotron laboratories. Our group is employing both to investigate fragmentation of bio-molecules in gas phase such as amino acids and DNA basis using V UV and soft x-ray photons. In the near future lager scale instruments developed in Brazil will allow unique opportunities to apply these two spectroscopic methods to molecules immersed in liquids such as water. We will present details from this advanced x-ray source and experimental stations with capabilities not present in other places in the world. Experiments connected to the molecular origin of live will be shown. Among them an experiment where we mimic the atmosphere at Titan moon producing bio- molecules will discussed. Another experiment will be presented where we test the Panspermia viability using special bacteria. We will also present experiments where frozen simple molecules connected to pre-biotic mate- rial are bombardment by UV photons and energetic particles showing interesting trends. Spectroscopic studies of gas phase photo-fragmentation of bio-molecules may be critical to understand in the future these molecules immersed in liquids. We plan to spend some time showing our recent results in this area. (author)

  18. Recent trends in carbon nanomaterial-based electrochemical sensors for biomolecules: A review

    Science.gov (United States)

    Yang, Cheng; Denno, Madelaine E.; Pyakurel, Poojan; Venton, B. Jill

    2015-01-01

    Carbon nanomaterials are advantageous for electrochemical sensors because they increase the electroactive surface area, enhance electron transfer, and promote adsorption of molecules. Carbon nanotubes (CNTs) have been incorporated into electrochemical sensors for biomolecules and strategies have included the traditional dip coating and drop casting methods, direct growth of CNTs on electrodes and the use of CNT fibers and yarns made exclusively of CNTs. Recent research has also focused on utilizing many new types of carbon nanomaterials beyond CNTs. Forms of graphene are now increasingly popular for sensors including reduced graphene oxide, carbon nanohorns, graphene nanofoams, graphene nanorods, and graphene nanoflowers. In this review, we compare different carbon nanomaterial strategies for creating electrochemical sensors for biomolecules. Analytes covered include neurotransmitters and neurochemicals, such as dopamine, ascorbic acid, and serotonin; hydrogen peroxide; proteins, such as biomarkers; and DNA. The review also addresses enzyme-based electrodes that are used to detect non-electroactive species such as glucose, alcohols, and proteins. Finally, we analyze some of the future directions for the field, pointing out gaps in fundamental understanding of electron transfer to carbon nanomaterials and the need for more practical implementation of sensors. PMID:26320782

  19. Biomolecules in the treatment of lichen planus refractory to corticosteroid therapy: Clinical and histopathological assessment.

    Science.gov (United States)

    Piñas, Laura; Alkhraisat, Mohammad Hamdan; Suárez-Fernández, Ricardo; Anitua, Eduardo

    2018-03-01

    Local deficit of several biomolecules have been described in oral lichen planus (OLP). Such a deficit impairs cellular functions and cell-matrix communication. Assess the efficacy of the local application of autologous biomolecules in the treatment of erosive OLP. In this study, the use of plasma rich in growth factors (PRGF) as a source of blood-derived and autologous growth factors and proteins were tested in erosive oral lichen planus refractory to corticosteroids. Histopathological features of the disease were also analysed at the time of diagnosis. Clinical data were the number of recurrences and achievement of pain reduction and complete healing of the lesions. A total of 10 patients with erosive OLP refractory to treatment by corticosteroids were included in the study. All patients were females with a mean age of 48±12years. A complete remission of the disease was achieved after one infiltration of PRGF in 8 patients. Only 2 patients required a total of 2 infiltrations to heal. Hydropic degeneration of the epithelium basal layer, band-like subepithelial lymphocytic infiltration and fibrin deposits in the epithelium were observed in all patients. Interestingly plasma cells were present in 2 patients. All patients presenting plasma cells healed after only one PRGF infiltration. However, 2 patients out of 6 (no plasma cells) required 2 infiltrations. The local administration of autologous local factors could overcome the deficit of biomolecular clues and thus improve cell functions and restore cell-matrix communication. Copyright © 2017 Elsevier GmbH. All rights reserved.

  20. Potential Biomolecules and Current Treatment Technologies for Diabetic Foot Ulcer: an Overview.

    Science.gov (United States)

    Khashim, Zenith; Samuel, Shila; Duraisamy, Nallusamy; Krishnan, Kathiravan

    2017-05-18

    Diabetic foot ulceration remains a major challenge and is one of the most expensive and leading causes of major and minor amputations among patients with diabetic foot ulcer. Hence the purpose of this review is to emphasize on potential molecular markers involved in diabetic foot ulcer physiology, the efficacy of different types of dressing materials, adjunct therapy and newer therapeutic approach like nanoparticles for the treatment of diabetic foot ulcer. We conducted a systematic literature review search by using Pubmed and other web searches. The quality evidence of diabetic foot ulcer biomolecules and treatments was collected, summarized and compared with other studies. The present investigation suggested that impaired wound healing in diabetic patients is an influence of several factors. All the advanced therapies and foot ulcer dressing materials are not suitable for all types of diabetic foot ulcers, however more prospective follow ups and in vivo and in vitro studies are needed to draw certain conclusion. Several critical wound biomolecules have been identified and are in need to be investigated in diabetic foot ulcers. The application of biocompatible nanoparticles holds a promising approach for designing dressing materials for the treatment of diabetic foot ulcer. Understanding the cellular and molecular events and identifying the appropriate treatment strategies for different foot ulcer grades will reduce recurrence of foot ulcer and lower limb amputation. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Correlation dynamics and enhanced signals for the identification of serial biomolecules and DNA bases

    International Nuclear Information System (INIS)

    Ahmed, Towfiq; Haraldsen, Jason T; Balatsky, Alexander V; Rehr, John J; Di Ventra, Massimiliano; Schuller, Ivan

    2014-01-01

    Nanopore-based sequencing has demonstrated a significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multilayered graphene-based nanopore device architecture for the recognition of single biomolecules. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new ‘multi-point cross-correlation’ technique for identification of DNA bases or other molecules on the single molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multilayered graphene nanopore system to illustrate the advantages of the proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology. (paper)

  2. Correlation dynamics and enhanced signals for the identification of serial biomolecules and DNA bases

    Science.gov (United States)

    Ahmed, Towfiq; Haraldsen, Jason T.; Rehr, John J.; Di Ventra, Massimiliano; Schuller, Ivan; Balatsky, Alexander V.

    2014-03-01

    Nanopore-based sequencing has demonstrated a significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multilayered graphene-based nanopore device architecture for the recognition of single biomolecules. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new ‘multi-point cross-correlation’ technique for identification of DNA bases or other molecules on the single molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multilayered graphene nanopore system to illustrate the advantages of the proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology.

  3. [INVITED] Surface plasmon cavities on optical fiber end-facets for biomolecule and ultrasound detection

    Science.gov (United States)

    Yang, Tian; He, Xiaolong; Zhou, Xin; Lei, Zeyu; Wang, Yalin; Yang, Jie; Cai, De; Chen, Sung-Liang; Wang, Xueding

    2018-05-01

    Integrating surface plasmon resonance (SPR) devices upon single-mode fiber (SMF) end facets renders label-free sensing systems that have a simple dip-and-read configuration, a small form factor, high compatibility with fiber-optic techniques, and invasive testing capability. Such devices are not only low cost replacement of current equipments in centralized laboratories, but also highly desirable for opening paths to new applications of label-free optical sensing technologies, such as point-of-care immunological tests and intravascular ultrasound imaging. In this paper, we explain the requirements and challenges for such devices from the perspectives of biomolecule and ultrasound detection applications. In such a context, we review our recent work on SMF end-facet SPR cavities. This include a glue-and-strip fabrication method to transfer a nano-patterned thin gold film to the SMF end-facet with high yield, high quality and high alignment precision, the designs of distributed Bragg reflector (DBR) and distributed feedback (DFB) SPR cavities that couple efficiently with the SMF guided mode and reach quality factors of over 100, and the preliminary results for biomolecule interaction sensing and ultrasound detection. The particular advantages and potential values of these devices have been discussed, in terms of sensitivity, data reliability, reproducibility, bandwidth, etc.

  4. Simplified TiO2 force fields for studies of its interaction with biomolecules

    Science.gov (United States)

    Luan, Binquan; Huynh, Tien; Zhou, Ruhong

    2015-06-01

    Engineered TiO2 nanoparticles have been routinely applied in nanotechnology, as well as in cosmetics and food industries. Despite active experimental studies intended to clarify TiO2's biological effects, including potential toxicity, the relation between experimentally inferred nanotoxicity and industry standards for safely applying nanoparticles remains somewhat ambiguous with justified concerns. Supplemental to experiments, molecular dynamics simulations have proven to be efficacious in investigating the molecular mechanism of a biological process occurring at nanoscale. In this article, to facilitate the nanotoxicity and nanomedicine research related to this important metal oxide, we provide a simplified force field, based on the original Matsui-Akaogi force field but compatible to the Lennard-Jones potentials normally used in modeling biomolecules, for simulating TiO2 nanoparticles interacting with biomolecules. The force field parameters were tested in simulating the bulk structure of TiO2, TiO2 nanoparticle-water interaction, as well as the adsorption of proteins on the TiO2 nanoparticle. We demonstrate that these simulation results are consistent with experimental data/observations. We expect that simulations will help to better understand the interaction between TiO2 and molecules.

  5. [Expedition medicine].

    Science.gov (United States)

    Donlagić, Lana

    2009-01-01

    Expedition and wildeness medicine is a term that combines rescue medicine, sport medicine as well as more specific branches as polar or high altitude medicine. It is being intensively studied both at the reaserch institutes and on expeditions. Ophtalmologists are concentrated on the reaserch of HARH (High Altitude Retinal Hemorrhage), neurologists on HACE reaserch (High Altitude Cerebral Edema), psychologists are developing tests to decsribe cognitive functions and many physicians are being trained to work in extreme enviroment. The result of all this effort are numerous new findings in pathophysiology and therapy of altitude illness, increased security on expedition and further development of expeditionism.

  6. Nuclear medicine

    International Nuclear Information System (INIS)

    Anon.

    1993-01-01

    The area of nuclear medicine, the development of artificially produced radioactive isotopes for medical applications, is relatively recent. Among the subjects covered in a lengthy discussion are the following: history of development; impact of nuclear medicine; understanding the most effective use of radioisotopes; most significant uses of nuclear medicine radioimmunoassays; description of equipment designed for use in the field of nuclear medicine (counters, scanning system, display systems, gamma camera); description of radioisotopes used and their purposes; quality control. Numerous historical photographs are included. 52 refs

  7. 2-Bromo-6-[(18) F]fluoropyridine: two-step fluorine-18 radiolabelling via transition metal-mediated chemistry.

    Science.gov (United States)

    Betts, Helen M; Robins, Edward G

    2014-04-01

    Novel radiolabelling methods are important for the development of new tracers for positron emission tomography. Direct nucleophilic fluorination of aromatic rings with [(18) F]fluoride is limited to activated substrates, restricting the application of this approach. Inspired by transition metal-mediated transformations, a fluorine-18 synthon was prepared to supplement the radiolabelling methods available for molecules unsuitable for direct labelling. 2-Bromo-6-[(18) F]fluoropyridine (denoted [(18) F]1) was prepared in high yield, and palladium-mediated cross-coupling reactions were exemplified. High incorporation of fluoride and efficient cross-coupling reactions demonstrate that compound [(18) F]1 holds promise as a new synthon for construction of fluorine-18-labelled molecules via transition metal-mediated reactions. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Radiolabeling of a wound-inducible pyridoxal phosphate utilizing protein from tomato: evidence for its identification as ACC synthase

    International Nuclear Information System (INIS)

    Privalle, L.S.; Graham, J.S.; Caughey, P.A.

    1986-01-01

    Aminocyclopropane 1-carboxylic acid (ACC) synthase, a pyridoxal phosphate utilizing enzyme, catalyzes the conversion of S-adenosylmethionine to ACC, the rate limiting step in the biosynthesis of the plant hormone, ethylene. Ethylene, besides being involved in normal plant growth processes, is also produced in response to stress, e.g. wounding, pathogen infection, etc. The authors report the partial purification (400 fold) of ACC synthase from wounded pink tomato pericarp by classical techniques including ammonium sulfate precipitation, ion exchange and phenyl sepharose chromatography. Further purification results in a decrease in specific activity apparently due to the instability of the enzyme and the low levels present in plant tissue. Radiolabeling of a pyridoxal phosphate-utilizing protein in the ACC synthase enriched fraction was achieved. Evidence that this radiolabeled protein is ACC synthase will be presented. Amino acid sequence determination of putative ACC synthase-derived peptides is underway

  9. Elucidating the role of dissolution in CeO{sub 2} nanoparticle plant uptake by smart radiolabeling

    Energy Technology Data Exchange (ETDEWEB)

    Schymura, Stefan; Hildebrand, Heike; Franke, Karsten [Institute of Resource Ecology, Helmholtz-Zentrum Dresden-Rossendorf, Leipzig (Germany); Fricke, Thomas [Vita34 AG, Business Unit BioPlanta, Leipzig (Germany); University of Bonn, Institute of Crop Science and Resource Conservation, Division Plant Nutrition (Germany)

    2017-06-19

    The identification of major uptake pathways in plants is an important factor when evaluating the fate of manufactured nanoparticles in the environment and the associated risks. Using different radiolabeling techniques we were able to show a predominantly particulate uptake for CeO{sub 2} nanoparticles in contrast to a possible uptake in the form of ionic cerium. (copyright 2017 Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim)

  10. Rapid, radiolabeled-microculture method that uses macrophages for in vitro evaluation of Mycobacterium leprae viability and drug susceptibility.

    Science.gov (United States)

    Mittal, A; Sathish, M; Seshadri, P S; Nath, I

    1983-04-01

    This paper describes a microculture rapid assay using radiolabeling and mouse macrophages to determine the viability and the drug susceptibility or resistance of Mycobacterium leprae. Comparison of M. leprae resident macrophage cultures maintained in 96-well flat-bottomed plates showed results for viability and susceptibility or resistance to dapsone that were similar to results for concurrent cultures in Leighton tubes with greater numbers of bacilli and macrophages.

  11. Rapid, Radiolabeled-Microculture Method That Uses Macrophages for In Vitro Evaluation of Mycobacterium leprae Viability and Drug Susceptibility

    OpenAIRE

    Mittal, A.; Sathish, M.; Seshadri, P. S.; Nath, Indira

    1983-01-01

    This paper describes a microculture rapid assay using radiolabeling and mouse macrophages to determine the viability and the drug susceptibility or resistance of Mycobacterium leprae. Comparison of M. leprae resident macrophage cultures maintained in 96-well flat-bottomed plates showed results for viability and susceptibility or resistance to dapsone that were similar to results for concurrent cultures in Leighton tubes with greater numbers of bacilli and macrophages.

  12. Renal uptake and retention of radiolabeled somatostatin, bombesin, neurotensin, minigastrin and CCK analogues: species and gender differences

    International Nuclear Information System (INIS)

    Melis, Marleen; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Rolleman, Edgar; Jong, Marion de

    2007-01-01

    Introduction: During therapy with radiolabeled peptides, the kidney is most often the critical organ. Newly developed peptides are evaluated preclinically in different animal models before their application in humans. In this study, the renal retention of several radiolabeled peptides was compared in male and female rats and mice. Methods: After intravenous injection of radiolabeled peptides [somatostatin, cholecystokinin (CCK), minigastrin, bombesin and neurotensin analogues], renal uptake was determined in both male and female Lewis rats and C57Bl mice. In addition, ex vivo autoradiography of renal sections was performed to localize accumulated radioactivity. Results: An equal distribution pattern of renal radioactivity was found for all peptides: high accumulation in the cortex, lower accumulation in the outer medulla and no radioactivity in the inner medulla of the kidneys. In both male rats and mice, an increasing renal uptake was found: [ 111 In-DTPA]CCK8 111 In-DTPA-Pro 1 ,Tyr 4 ]bombesin∼[ 111 In-DTPA] neurotensin 111 In-DTPA]octreotide 111 In-DTPA]MG0. Renal uptake of [ 111 In-DTPA]octreotide in rats showed no gender difference, and renal radioactivity was about constant over time. In mice, however, renal uptake in females was significantly higher than that in males and decreased rapidly over time in both genders. Moreover, renal radioactivity in female mice injected with [ 111 In-DTPA]octreotide showed a different localization pattern. Conclusions: Regarding the renal uptake of different radiolabeled peptides, both species showed the same ranking order. Similar to findings in patients, rats showed comparable and constant renal retention of radioactivity in both genders, in contrast to mice. Therefore, rats appear to be the more favorable species for the study of the renal retention of radioactivity

  13. Synthesis of radio-labeled caffeyl alcohol- and 5-hydroxyconiferyl alcohol-4-O-β-D-glucosides

    International Nuclear Information System (INIS)

    Matsui, Naoyuki; Fukushima, Kazuhiko; Terashima, Noritsugu; Yasuda, Seiichi

    1996-01-01

    Syntheses of caffeyl alcohol-4-O-β-D-glucoside and 5-hydroxyconiferyl alcohol-4-O-β-D-glucoside were achieved with radio-labeling with 14 C at the glucose residue and with 3 H at the side chain γ-position of aglycon. The treatment of these compounds with commercially available β-glucosidase gave the corresponding aglycons, caffeyl alcohol, and 5-hydroxyconiferyl alcohol. (author)

  14. Radiolabelling of n- and i-colchicines with positron emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Kothari, P.J.; Cai, S.; Finn, R.D. [Memorial Sloan Kettering Cancer Center, NY (United States)] [and others

    1995-05-01

    Colchicine, a naturally occurring alkaloid and a potent inhibitor of cellular mitosis, is a member of the multi-drug resistance family of drugs. As a potential indicator of multi-drug resistance, the C-10 methoxy group of n-colchicine and C-9 methoxy group of i-colchicine have been radiolabelled. The syntheses of {sup 11}C-labelled n- and i-colchicines have been achieved by allowing desmethyl colchicine to react with {sup 11}C-iodomethane. The isomeric colchicines were purified and isolated by reversed phase HPLC in greater than 90% radiochemical and chemical purity. Using {sup 13}C-iodomethane, {sup 13}C-labelled n- and i-colchicines have also been synthesized for their evaluation at magnetic resonance imaging (MRI) agents. The restrictions imposed by short half-life of the carbon-11 compound prompted our investigation into the syntheses of fluorine-18 labelled colchicine analogues. The nucleophilic displacement of trifluoromthanesulfonate by {sup 18}F-anion yielded a mixture of {sup 18}F-labelled desmethoxy colchicines. The data suggest that the isolation of fluorine-18 analogue is possible and the compound potentially applicable to multi-drug resistance evaluations.

  15. Radiolabeling of mammalian spermatozoa and their use to monitor sperm transport in females

    International Nuclear Information System (INIS)

    Lorton, S.P.; Gatley, S.J.; Lieberman, L.M.; First, N.L.

    1980-01-01

    Radiolabeling of mammalian spermatozoa with 131 I, 67 Ga, 111 In, and /sup 99m/Tc was investigated. Spermatozoa were labeled with /sup 99m/Tc for in vivo studies because of a high labeling yield (70 to 90%) combined with the lack of impairment of sperm motility. Ovariectomized sheep were brought into estrus by sequential administration of progesterone and estradiol cyprionate. Sheep were necropsied up to 6 hours after insemination with /sup 99m/Tc-labeled ram sperm and their reproductive tracts were resected and examined with a rectilinear scanner. Radioactivity was clearly observed in the fallopian tubes, with larger amounts in the vaginas, cervices, and uteri. In contrast, when /sup 99m/Tc-spermatozoa were replaced with /sup 99m/TcO 4 - , much less radioactivity remained in the reproductive tract at resection and this was evenly distributed. Some label left the /sup 99m/Tc-spermatozoa in vivo, but radioactivity remained on the cells long enough to consider attempting to monitor sperm transport in vivo in a suitable species

  16. Platelet crossmatch tests using radiolabelled staphylococcal protein A or peroxidase anti-peroxidase in alloimmunised patients

    International Nuclear Information System (INIS)

    Yam, P.; Petz, L.D.; Scott, E.P.; Santos, S.

    1984-01-01

    Refractoriness to random-donor platelets as a result of alloimmunization remains a major problem in long-term platelet transfusion therapy despite the use of HLA-matched platelets. A study has been made of two methods for detection of platelet associated IgG as platelet crossmatch tests for the selection of platelet donors. These methods use radiolabelled staphylococcal protein A( 125 I-SPA) and peroxidase anti-peroxidase (PAP), respectively. One hundred and ten crossmatch tests using 125 I-SPA were performed retrospectively in 18 alloimmunized patients. The results indicated that the predictive value of a positive or a negative test was 87%; the sensitivity was 73% and the specificity was 95%. Results with the PAP test were similar. The HLA types were known for 48 donor-recipient pairs. With few exceptions, there was a correlation between the results of the platelet crossmatch tests and the effectiveness of platelet transfusion regardless of the degree of HLA match. These results indicate that platelet crossmatch tests may be valuable even when closely HLA matched donors are not available. A large-scale prospective study is warranted, particularly in highly immunized patients. (author)

  17. The gastrointestinal emptying and transit of radiolabelled oral dosage forms in the pig

    International Nuclear Information System (INIS)

    Anderson, D. L.; Kirkwood, I.D.; Chatterton, B.E.; Bartholomeusz, F.D.L.; Sansom, L.N.

    1998-01-01

    Full text: By developing an animal model, the costs and time as well as the number of human studies involved to assess new oral pharmaceutical dosage forms could be greatly reduced. To validate the pig as a suitable model, the solid, liquid and particle gastric emptying rates (both fed and fasting) are required The aims were to:- train the pigs to be scanned under a variety of conditions, design and manufacture scanning cages, develop a scintigraphic imaging method in the pig, design a suitable system for the oral delivery of an intact radiolabelled capsule, acquire images providing information on the anatomical position and in-vivo performance of the capsule, perform a series of gastric emptying studies. Liquid emptying data shows a 50% emptying time of 15 minutes in the pig (human 4-31 min). Solid emptying in the sedated pig is poor at 2 hours. In the unsedated pig the maximum time for a solid study has been 45 minutes. This study has provided some useful information regarding the gastrointestinal anatomy of pigs. The preliminary data indicates that the model has potential. In the future, a simultaneous scintigraphic and pharmacokinetic study of drug absorption will be performed

  18. The gastrointestinal emptying and transit of radiolabelled oral dosage forms in the pig

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, D. L.; Kirkwood, I.D.; Chatterton, B.E.; Bartholomeusz, F.D.L.; Sansom, L.N. [Royal Adelaide Hospital, Adelaide, SA (Australia). Department of Nuclear Medicine

    1998-06-01

    Full text: By developing an animal model, the costs and time as well as the number of human studies involved to assess new oral pharmaceutical dosage forms could be greatly reduced. To validate the pig as a suitable model, the solid, liquid and particle gastric emptying rates (both fed and fasting) are required The aims were to:- train the pigs to be scanned under a variety of conditions, design and manufacture scanning cages, develop a scintigraphic imaging method in the pig, design a suitable system for the oral delivery of an intact radiolabelled capsule, acquire images providing information on the anatomical position and in-vivo performance of the capsule, perform a series of gastric emptying studies. Liquid emptying data shows a 50% emptying time of 15 minutes in the pig (human 4-31 min). Solid emptying in the sedated pig is poor at 2 hours. In the unsedated pig the maximum time for a solid study has been 45 minutes. This study has provided some useful information regarding the gastrointestinal anatomy of pigs. The preliminary data indicates that the model has potential. In the future, a simultaneous scintigraphic and pharmacokinetic study of drug absorption will be performed

  19. Characterization of the association of radiolabeled bleomycin A2 with HeLa cells

    International Nuclear Information System (INIS)

    Roy, S.N.; Horwitz, S.B.

    1984-01-01

    The association of [ 3 H]bleomycin A2 and Cu(II):[ 3 H]bleomycin A2 with HeLa cells has been characterized. Under the conditions of our experiments, approximately 0.1% of the total drug in the medium associates with HeLa cells. Both forms of the drug bind to HeLa cells in a specific and saturable manner, with a Km of 20 microM and a Vmax of 2.5 pmol/min/10(6) cells. Scatchard analysis of the specific binding data demonstrates a single set of high-affinity binding sites. Cytotoxic activities of both forms of the drug are similar, with a 50% lethal dose of 0.5 microM at 48 hr. The specific binding in HeLa cells of either the labeled metal-free drug or its copper complex is reversible by a 100-fold excess of either unlabeled drug. Interaction of the drug with cells is temperature sensitive but is unaffected by metabolic poisons, suggesting that this process is not energy dependent. Isolation of DNA from HeLa cells incubated with the drug indicates that 1 mol of either [ 3 H]bleomycin A2 or Cu(II):[ 3 H]bleomycin A2 binds per 10(8) nucleotides. Further studies with the radiolabeled drug are required to define precisely the mechanisms involved in bleomycin uptake and compartmentalization within the cell

  20. A simple method for enzymatic synthesis of unlabeled and radiolabeled Hydroxycinnamate-CoA

    Energy Technology Data Exchange (ETDEWEB)

    Rautergarten, Carsten; Baidoo, Edward; Keasling, Jay; Vibe Scheller, Henrik

    2011-07-20

    Hydroxycinnamate coenzyme A (CoA) thioesters are substrates for biosynthesis of lignin and hydroxycinna- mate esters of polysaccharides and other polymers. Hence, a supply of these substrates is essential for investigation of cell wall biosynthesis. In this study, three recombinant enzymes, caffeic acid 3-O-methyltransferase, 4-coumarate- CoA ligase 1, and 4-coumarate-CoA ligase 5, were cloned from wheat, tobacco, and Arabidopsis, respectively, and were used to synthesize {sup 14}C-feruloyl-CoA, caffeoyl-CoA, p-coumaroyl-CoA, feruloyl-CoA, and sinapoyl-CoA. The corresponding hydroxycinnamoyl-CoA thioesters were high-performance liquid chromatography purified, the only extraction/purification step necessary, with total yields between 88-95%. Radiolabeled {sup 14}C-feruloyl-CoA was generated from caffeic acid and S-adenosyl-{sup 14}C-methionine under the combined action of caffeic acid 3-O-methyltransferase and 4-coumarate-CoA ligase 1. About 70% of {sup 14}C-methyl groups from S-adenosyl methionine were incorporated into the final product. The methods presented are simple, fast, and efficient for the preparation of the hydroxycinnamate thioesters.

  1. Radiolabeled antibody in tumor imaging and therapy: iodine and radiometal chelates

    International Nuclear Information System (INIS)

    Berg, W.T.A.

    1987-01-01

    The use of radiolabeled monoclonal antibody in tumor imaging and therapy was evaluated using the Rauscher murine erythroleukemia. Antibody labeled with radioiodine or with DTPA-based radiometal chelates was compared with respect to in vitro and in vivo chemical stability of isotope incorporation, tumor targeting and catabolism, and efficacy. The radiometals studied were: 47 scandium, for imaging and therapy; 67 gallium and 111 indium for imaging; and 90 yttrium and 212 bismuth for therapy. Experiments using 153 Gd-labeled antibody demonstrated that insufficient gadolinium could be targeted to the tumor for use as a contrast agent in magnetic resonance imaging. Labeling was efficient and resulted in 70 to 90 percent incorporation of all isotopes except 67 Ga, which was only adventitiously bound to immunoglobulin. As assessed by reduction of splenomegaly, 90 Y-labeled specific antibody was 2- to 3-fold more potent in tumor therapy than control immunoglobulin whereas 131 I-labeled preparations were equipotent. Treatment with 90 Y-labeled antibody produced mild, reversible leukopenia, whereas marrow suppression limited the administrable dose of 131 I-labeled immunoglobulin. In vitro. 212 Bi-labeled specific antibody again appeared 2- to 3-fold more potent in cell killing than control antibody

  2. Radiolabelled molecules for imaging the translocator protein (18 kDa) using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Dolle, F.; Luus, C.; Reynolds, A.; Kassiou, M. [CEA, Institut d' Imagerie BioMedicale, Service Hospitalier Frederic Joliot, Orsay (France)

    2009-07-01

    The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor (PBR), was originally identified as an alternate binding site for the central benzodiazepine receptor (CBR) ligand, diazepam, in the periphery, but has now been distinguished as a novel site. The TSPO is ubiquitously expressed in peripheral tissues but only minimally in the healthy brain and increased levels of TSPO expression have been noted in neuro inflammatory conditions such as Alzheimer's disease, Parkinson's disease and stroke. This increase in TSPO expression has been reported to coincide with the process of micro-glial activation, whereby the brain's intrinsic immune system becomes active. Therefore, by using recently developed high affinity, selective TSPO ligands in conjunction with functional imaging modalities such as positron emission tomography (PET), it becomes possible to study the process of micro-glial activation in the living brain. A number of high affinity ligands, the majority of which are C, N-substituted acetamide derivatives, have been successfully radiolabelled and used in in vivo studies of the TSPO and the process of micro-glial activation. This review highlights recent achievements (up to December 2008) in the field of functional imaging of the TSPO as well as the radio-syntheses involved in such studies. (authors)

  3. Synthesis of a radiolabeled cyclodepsipeptide [{sup 3}H-methyl]PF1022A

    Energy Technology Data Exchange (ETDEWEB)

    Pleiss, U. [Bayer AG, Wuppertal (Germany). Metabolism and Isotope Chemistry; Harder, A.; Turberg, A.; Londershausen, M.; Mencke, N.; Jeschke, P.; Bonse, G. [Bayer AG, Monheim (Germany). Agricultural Centre; Iinuma, K. [Meiji Seika Kaisha Ltd., Kanagawa (Japan)

    1996-01-01

    For receptor binding studies and the elucidation of the mode of action of the potent anthelmintic compound PF1022A a tritium labeled compound with very high specific activity was necessary. Tritium was introduced into the compound by methylation of the [bis-N-demethyl]precursor of PF1022A (PF1022-219). The identity of [bis-N-methyl-{sup 3}H]PF1022A was determined by LC/MS. After synthesis and purification, 88.9 {mu}g [bis-N-methyl-{sup 3}H]PF1022A were available showing a specific activity of 162 Ci/mmol (5,99 TBq/mmol) determined by mass spectrometry. The total activity was 15 mCi (555 MBq). Radiolabeled PF1022A showed an efficient and specific binding to a membrane fraction from Ascaris suum. Displacement by unlabeled PF1022A was half-maximal at about 40 nM. At 100-fold higher concentrations the biologically much less effective optical antipodean (PF1022-001) competed for maximal 40% of the [{sup 3}H]PF1022A-binding in the Ascaris suum membrane preparation. In-vitro comparison of PF1022A with its optical antipdean revealed a more than 100-fold higher anthelmintic activity of PF1022A against Heterakis spumosa, Nippostrongylus brasiliensis and Trichinella spiralis. (author).

  4. Radiolabeled keratin: an undigestible marker for gastro-intestinal transit investigations

    International Nuclear Information System (INIS)

    Bedig, G.; Tellier, P.; Vulpillat, M.

    1983-01-01

    A new marker for undigestible food is described in this paper. Labeling of keratin fibers with radioactive chromium 51 was operated by a simple process. A 90 % labeling efficiency was obtained. Assessment of in vitro chromium binding stability was performed by incubating fibers in different solutions (24 hours, 37 0 C). Remaining activity on fibers was found to be 92+-2% in a pepsin solution, and 97+-1% in a pancreatic extract solution. Acid or basic solutions (pH 1 to pH 11) did not yield significant elution. In Man, scintigraphic views displayed a focal distribution of the radioactivity in the digestive tractus. Patient's irradiation during such an exploration was estimated by dosimetric calculation and found to be acceptable. Scintigraphic survey of fibers progression was possible throughout the whole digestive tractus, particularly in the intestine. This marker should become mainly interesting for intestinal studies, since it is one of the only two undigestible markers, with radiolabeled alpha-cellulose. Properties related to its original structure, and advantages of a simple labeling process should be valuable in a promizing way of exploration [fr

  5. Radiolabeling and autoradiographic tracing of Toxocara canis larvae in male mice

    International Nuclear Information System (INIS)

    Wade, S.E.; Georgi, J.R.

    1987-01-01

    Artificially hatched infective larvae of Toxocara canis were labeled with 75 Se in Medium 199 (Gibco) containing 75 Se-methionine. Male CD-1 mice were infected with radiolabeled larvae by intragastric intubation or by intraperitoneal injection. At intervals of 3-56 days mice were killed and the organs prepared for compressed organ autoradiography. Radioactivity of parasitic larvae showed an exponential decrease with time, reflecting catabolism of label with a biological half life of 26 days (effective half life of 21 days) making possible experiments lasting several months. Total body larva counts, estimated by total body autoradiography, displayed an overall downward trend, but the rate of reduction was probably not constant because no significant positive or negative trends were noted from day 14 onward in the numbers of larvae. The carcass accumulated the greatest number of larvae followed by the central nervous system, liver, and lung in that order. When the numbers of larvae were considered in relationship to the mass of tissue, there were 4 groupings: central nervous system, liver, lung, carcass, and kidney, and genito-urinary organ, pelt, and intestine. No significant difference between intragastric and intraperitoneal administration was observed in the larval distribution after the larvae had left the initial site of deposition

  6. Radiolabeling and autoradiographic tracing of Toxocara canis larvae in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Wade, S.E.; Georgi, J.R.

    1987-02-01

    Artificially hatched infective larvae of Toxocara canis were labeled with /sup 75/Se in Medium 199 (Gibco) containing /sup 75/Se-methionine. Male CD-1 mice were infected with radiolabeled larvae by intragastric intubation or by intraperitoneal injection. At intervals of 3-56 days mice were killed and the organs prepared for compressed organ autoradiography. Radioactivity of parasitic larvae showed an exponential decrease with time, reflecting catabolism of label with a biological half life of 26 days (effective half life of 21 days) making possible experiments lasting several months. Total body larva counts, estimated by total body autoradiography, displayed an overall downward trend, but the rate of reduction was probably not constant because no significant positive or negative trends were noted from day 14 onward in the numbers of larvae. The carcass accumulated the greatest number of larvae followed by the central nervous system, liver, and lung in that order. When the numbers of larvae were considered in relationship to the mass of tissue, there were 4 groupings: central nervous system, liver, lung, carcass, and kidney, and genito-urinary organ, pelt, and intestine. No significant difference between intragastric and intraperitoneal administration was observed in the larval distribution after the larvae had left the initial site of deposition.

  7. Incorporation of radiolabeled whey proteins into casein micelles by heat processing

    International Nuclear Information System (INIS)

    Noh, B.; Richardson, T.

    1989-01-01

    Skim milk was heated at .70, 95, and 140 degree C to simulate the processes of pasteurization, forewarming, and UHT sterilization, and the specific interactions between α-lactalbumin or β-lactoglobulin and the caseins studied using tracer amounts of added 14 C-labeled whey protein. Radioactivities of the whey and of the washed casein pellets from renneted skim milk were measured and the extent of the interaction estimated. Upon heating skim milk at 70 degree C for 45 s, less than 2% β-lactoglobulin and less than .3% α-lactalbumin were incorporated into the curd. Heating at 95 degree C for .5 to 20 min resulted in 58 to 85% of the β-lactoglobulin and 8 to 55% of the α-lactalbumin becoming associated with the curd. Heating at 140 degree C for 2 and 4 s caused 43 and 54% of the β-lactoglobulin and 9 and 12% of the α-lactalbumin, respectively, to be bound to the curd fraction. The radiolabeling technique is very sensitive and useful for tracing low levels of interaction between whey proteins and casein in heated milk systems

  8. The radiolabeled monoclonal antibodies in immunoscintigraphy and radioimmunotherapy: current state and perspectives

    International Nuclear Information System (INIS)

    Chatal, J. F.

    2000-01-01

    The antibodies can be satisfactorily labelled with technitium-99 m or indium-111 for tumor immunoscintigraphy. The immunoscintigraphy is not useful for the primary tumor diagnosis. It can be useful for the diagnosis of the some cancer extension and for recurrent tumor visualization. The immunoscintigraphy is widely competed with Positron Emission Tomography (PET) which gives accurate results. In the future the immunoscintigraphy, in pre-therapeutic stage, contribute to the estimation of the dose delivered to the tumor and to normal organs for adopting or not a radioimmunotherapy. The antibodies can also be labeled with Iodine-131 for an application in radioimmunotherapy (RIT). The RIT is efficient in the non-Hodgkin's lymphoma treatment because of their great radiosensitivity. Until now the results have been very modest in solid tumor treatment but methodological and biotechnological progresses have to improve the efficiency especially for the small tumors. In the future iodine-131 which requires the confinement (very expensive) of patients will be substituted by yttrium-90 beta emitter, more energetic than iodine-131 and can be injected in walking case. In the long term, the alpha emitter radionuclides (astatine-211 or bismuth-213) can be used for hematologic cancer treatment. In conclusion the future of radiolabeled monoclonal antibodies is essentially therapeutic. The radioimmunotherapy associated to the chemotherapy give promising perspectives for the radiosensitive cancer treatment and in general small solid tumor treatment (F.M.)

  9. Radiolabeling of human platelets using four radiopharmaceuticals with Tc-99m

    International Nuclear Information System (INIS)

    Portillo L, M.C.; Godoy, C.

    1991-01-01

    The present investigation work has been done in an evaluation of four different radiopharmaceuticals with Tin II (Glucoheptonate, Pyrophosphate, Citrate and DTPA), with the purpose of determining which one of the four would be obtained a higher rate of radiolabeling of platelets with Tc-99m. In order to evaluate the four radiopharmaceuticals it was procede to the separation and labeling of the human platelets. It was worked with samples of blood from five pacients, and the platelets from each one of them were labeled with the radiopharmaceuticals-Tc-99m. Then was observed a significant difference among the four radiopharmaceuticals studied, with a reliable level of 0.05 being the Glucoheptonate-Tc-99m the best to label platelets, obtaining with the same 50.23% of labeling efficiency, while for DTPA, Pyrophosphate and Citrate, It was obtained 33.42%, 29.82% and |2.62% respectively. Also, it was studied the biodistribution of the labeled platelets, using Glucoheptonate-Tc-99m as a radiopharamceutical. The biodistribution was studied in white mice at different times and it was founded that the place of biodistribution of the labeled platelets is given in greater percentage in the liver, spleen, lungs and kydneis. (Author)

  10. Foliar leaching, translocation, and biogenic emission of 35S in radiolabeled loblolly pines

    International Nuclear Information System (INIS)

    Garten, C.T. Jr.

    1990-01-01

    Foliar leaching, basipetal (downward) translocation, and biogenic emission of sulfur (S), as traced by 35 S, were examined in a field study of loblolly pines. Four trees were radiolabeled by injection with amounts of 35 S in the 6-8 MBq range, and concentrations in needle fall, stemflow, throughfall, and aboveground biomass were measured over a period of 15-20 wk after injection. The contribution of dry deposition to sulfate-sulfur (SO 4 2- -S) concentrations in net throughfall (throughfall SO 4 2- -S concentration minus that in incident precipitation) beneath all four trees was > 90%. Calculations indicated that about half of the summertime SO 2 dry deposition flux to the loblolly pines was fixed in the canopy and not subsequently leached by rainfall. Based on mass balance calculations, 35 S losses through biogenic emissions from girdled trees were inferred to be 25-28% of the amount injected. Estimates based on chamber methods and mass balance calculations indicated a range in daily biogenic S emission of 0.1-10 μg/g dry needles. Translocation of 35 S to roots in nongirdled trees was estimated to be between 14 and 25% of the injection. It is hypothesized that biogenic emission and basipetal translocation of S (and not foliar leaching) are important mechanisms by which forest trees physiologically adapt to excess S in the environment

  11. Incorporation of radiolabeled whey proteins into casein micelles by heat processing

    Energy Technology Data Exchange (ETDEWEB)

    Noh, B.; Richardson, T. (Univ. of California, Davis (USA))

    1989-07-01

    Skim milk was heated at .70, 95, and 140{degree}C to simulate the processes of pasteurization, forewarming, and UHT sterilization, and the specific interactions between {alpha}-lactalbumin or {beta}-lactoglobulin and the caseins studied using tracer amounts of added {sup 14}C-labeled whey protein. Radioactivities of the whey and of the washed casein pellets from renneted skim milk were measured and the extent of the interaction estimated. Upon heating skim milk at 70{degree}C for 45 s, less than 2% {beta}-lactoglobulin and less than .3% {alpha}-lactalbumin were incorporated into the curd. Heating at 95{degree}C for .5 to 20 min resulted in 58 to 85% of the {beta}-lactoglobulin and 8 to 55% of the {alpha}-lactalbumin becoming associated with the curd. Heating at 140{degree}C for 2 and 4 s caused 43 and 54% of the {beta}-lactoglobulin and 9 and 12% of the {alpha}-lactalbumin, respectively, to be bound to the curd fraction. The radiolabeling technique is very sensitive and useful for tracing low levels of interaction between whey proteins and casein in heated milk systems.

  12. Imaging the adrenal glands with radiolabeled inhibitors of enzymes: concise communication

    International Nuclear Information System (INIS)

    Beierwaltes, W.H.; Wieland, D.M.; Mosley, S.T.; Swanson, D.P.; Sarkar, S.D.; Freitas, J.E.; Thrall, J.H.; Herwig, K.R.

    1978-01-01

    Although radioiodinated cholesterols furnished the first noninvasive imaging of the adrenal glands, it would be desirable to decrease the time for imaging and decrease the radiation dose. The relative tissue distributions of two radiolabeled enzyme inhibitors [ 3 H] metyrapol and 1-125-SKF-12185 were studied in dogs and man. Their percentage uptakes and target-to-nontarget ratios were similar. The adrenals of three dogs were imaged sharply at 2 hr after injection with 4-6 mCi of I-131-SKF-12185, confirmed by subsequent imaging with 1 mCi of I-131-6-beta-19-nor cholesterol at 5 days after injection. The use of 1 mCi of I-123-SKF will pemit imaging of the adrenals in 1-2 hr and will decrease the radiation dose in the human to 0.76 rads to the adrenal, 0.18 rads to the ovaries and 1.7 rads to the liver

  13. Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy †

    Science.gov (United States)

    Sihver, Wiebke; Pietzsch, Jens; Krause, Mechthild; Baumann, Michael; Steinbach, Jörg; Pietzsch, Hans-Jürgen

    2014-01-01

    The epidermal growth factor receptor (EGFR) has evolved over years into a main molecular target for the treatment of different cancer entities. In this regard, the anti-EGFR antibody cetuximab has been approved alone or in combination with: (a) chemotherapy for treatment of colorectal and head and neck squamous cell carcinoma and (b) with external radiotherapy for treatment of head and neck squamous cell carcinoma. The conjugation of radionuclides to cetuximab in combination with the specific targeting properties of this antibody might increase its therapeutic efficiency. This review article gives an overview of the preclinical studies that have been performed with radiolabeled cetuximab for imaging and/or treatment of different tumor models. A particularly promising approach seems to be the treatment with therapeutic radionuclide-labeled cetuximab in combination with external radiotherapy. Present data support an important impact of the tumor micromilieu on treatment response that needs to be further validated in patients. Another important challenge is the reduction of nonspecific uptake of the radioactive substance in metabolic organs like liver and radiosensitive organs like bone marrow and kidneys. Overall, the integration of diagnosis, treatment and monitoring as a theranostic approach appears to be a promising strategy for improvement of individualized cancer treatment. PMID:24603603

  14. Effect of age, calcium source, and radiolabeling method on whole body 47Ca retention in the rat.

    Science.gov (United States)

    Andon, M B; Kanerva, R L; Schulte, M C; Smith, K T

    1993-10-01

    In a longitudinal study we determined the effect of animal age as well as Ca source and radiolabeling method on Ca bioavailability by measuring whole body 47Ca retention (WBR) in male Sprague-Dawley rats. The WBR assay was performed without surgery or anesthesia, and the same groups of animals were studied at 8, 16, 20, and 32 wk of age. Rats were administered a 6-mg radiolabeled oral dose of Ca as Ca citrate malate (CCM) or intrinsically or extrinsically labeled CaCO3 or hydroxyapatite (HAP). Fractional Ca retention was measured from the 72-h postdose WBR divided by WBR at time 0. WBR was significantly affected by Ca source with CCM > CaCO3 > HAP at all ages (P < 0.001). The rank order and relative bioavailabilities of these Ca salts in the rat model agreed well with literature values for Ca absorption in adult humans. Although percent WBR decreased significantly with advancing age (P < 0.001), the mean rate of decline (-3.4%/wk) was not affected by Ca source. Extrinsic radiolabeling overestimated (approximately 20%) Ca bioavailability when the rats were young. However, the magnitude of this effect diminished with advancing animal age and was not significant across all ages (repeated measures analysis of variance P = 0.10).

  15. Preparation, characterization, and microbial degradation of specifically radiolabeled [14C]lignocelluloses from marine and fresh water macrophytes

    International Nuclear Information System (INIS)

    Benner, R.; Maccubbin, A.E.; Hodson, R.E.

    1984-01-01

    Specifically radiolabeled [ 14 C-lignin]lignocelluloses were prepared from the aquatic macrophytes Spartina alterniflora, Juncus roemerianus, Rhizophora mangle, and Carex walteriana by using [ 14 C]phenylalanine, [ 14 C]tyrosine, and [ 14 C]cinnamic acid as precursors. Specifically radiolabeled [ 14 C-polysaccharide]lignocelluloses were prepared by using [ 14 C]glucose as precursor. The rates of microbial degradation varied among [ 14 C-lignin]lignocelluloses labeled with different lignin precursors within the same plant species. In herbaceous plants, significant amounts (8 to 24%) of radioactivity from [ 14 C]phenylalanine and [ 14 C]tyrosine were found associated with protein. Microbial degradation of radiolabeled protein resulted in overestimation of lignin degradation rates in lignocelluloses derived from herbaceous aquatic plants. Other differences in degradation rates among [ 14 C-lignin]lignocelluloses from the same plant species were attributable to differences in the amount of label being associated with ester-linked subunits of peripheral lignin. After acid hydrolysis of [ 14 C-polysaccharide]lignocelluloses, radioactivity was detected in several sugars, although most of the radioactivity was distributed between glucose and xylose. After 576 h of incubation with salt marsh sediments, 38% of the polysaccharide component and between 6 and 16% of the lignin component (depending on the precursor) of J. roemerianus lignocellulose was mineralized to 14 CO 2 ; during the same incubation period, 30% of the polysaccharide component and between 12 and 18% of the lignin component of S. alterniflora lignocellulose was mineralized

  16. Vulnerable Medicine

    Science.gov (United States)

    Bochner, Arthur P.

    2009-01-01

    In "Narrative Medicine: Honoring the Stories of Illness," Rita Charon paints an original and humane portrait of what it can mean to be a doctor, to live a life immersed in sickness and dedicated to wellness. Charon drops the veil, inviting readers to look at the secret, subjective, emotional face of medicine, a zone of self-censored feelings and…

  17. Quantification of biomolecules in herring (Clupea harengus) industry processing waters and their recovery using electroflocculation and ultrafiltration

    DEFF Research Database (Denmark)

    Osman, Ali; Gringer, Nina; Svendsen, Tore

    2015-01-01

    Four types of herring industry processing waters; refrigerated sea water (RSW), storage water (SW), processing water from cutting (PW) and pre-salting brines (SB) were subjected to chemical characterization and biomolecule recovery using electroflocculation (EF) and ultrafiltration (UF...... and magnesium were the dominating trace elements. EF plus UF in series recovered up to 80% proteins and fatty acids from SB's and reduced chemical oxygen demand by 70%. Foaming and emulsifying properties of biomolecules were improved or unaffected by EF/UF treatment. To conclude, large amounts of biomass...

  18. [The clinical value of sentinel lymph node detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck by methylene blue method and radiolabeled tracer method].

    Science.gov (United States)

    Zhao, Xin; Xiao, Dajiang; Ni, Jianming; Zhu, Guochen; Yuan, Yuan; Xu, Ting; Zhang, Yongsheng

    2014-11-01

    To investigate the clinical value of sentinel lymph node (SLN) detection in laryngeal and hypopharyngeal carcinoma patients with clinically negative neck (cN0) by methylene blue method, radiolabeled tracer method and combination of these two methods. Thirty-three patients with cN0 laryngeal carcinoma and six patients with cN0 hypopharyngeal carcinoma underwent SLN detection using both of methylene blue and radiolabeled tracer method. All these patients were accepted received the injection of radioactive isotope 99 Tc(m)-sulfur colloid (SC) and methylene blue into the carcinoma before surgery, then all these patients underwent intraopertive lymphatic mapping with a handheld gamma-detecting probe and blue-dyed SLN. After the mapping of SLN, selected neck dissections and tumor resections were peformed. The results of SLN detection by radiolabeled tracer, dye and combination of both methods were compared. The detection rate of SLN by radiolabeled tracer, methylene blue and combined method were 89.7%, 79.5%, 92.3% respectively. The number of detected SLN was significantly different between radiolabeled tracer method and combined method, and also between methylene blue method and combined method. The detection rate of methylene blue and radiolabeled tracer method were significantly different from combined method (P methylene blue can improve the detection rate and accuracy of sentinel lymph node detection. Furthermore, sentinel lymph node detection can accurately represent the cervical lymph node status in cN0 laryngeal and hypopharyngeal carcinoma.

  19. An alternative origin for extraterrestrial biomolecules from the hot and ionized photosphere of the protosolar nebula.

    Science.gov (United States)

    Bekaert, D. V.; Derenne, S.; Tissandier, L.; Marrocchi, Y.; Anquetil, C.; Marty, B.

    2017-12-01

    Organic matter (OM) synthesized from plasma experiments (so-called Nebulotron) can provide an insight into the processes of organosynthesis within the ionized gas phase of the protosolar nebula (PSN). Organic materials recovered from Nebulotron experiments have a record of success in reproducing key features of chondritic insoluble organic matter (IOM), including the aromatic/aliphatic and soluble/insoluble ratios [1], the occurrence of D/H hot and cold spots [2], spectral features as well as elementary and isotopic patterns observed in trapped noble gases [3]. However, up until now little attention has been paid to the soluble fraction of the recovered OM (SOM). In this study, a high-vacuum plasma setting was designed to produce organic condensates from a CO-N2-H2 gas mixture reminiscent of the PSN. The chemical diversity of the synthetized SOM has been investigated by gas chromatography - mass spectrometry. Our results show that a large range of biomolecules detected in meteorites and comets could have been directly synthetized from the gas phase of the PSN under high ionization rates and temperatures > 800 K. Among other molecules, urea, formamide, glycerol, hydantoin, carboxylic acids, as well as amino acid and nucleobase derivatives are reported. While photochemical processing of interstellar icy grains or asteroidal aqueous alteration are often advocated for the origin of biomolecules in extraterrestrial samples, our results suggest that biomolecule production was also effective in the hot and ionized photosphere of the PSN. Interestingly, solid-state 13C Nuclear Magnetic Resonance spectra of the Nebulotron IOM, indicates that they are very low in aromatics relative to extraterrestrial samples. Given that aromatic units in meteoritic IOM likely result from the cyclization/aromatization of aliphatic chains in the gas [1], Nebulotron-like aliphatic materials could represent the initial precursors of meteoritic OM [4]. These materials would be widespread in the

  20. Tailoring Bond Cleavage in Gas-Phase Biomolecules by Low Energy Electrons

    Science.gov (United States)

    Ptasinska, Sylwia

    2014-10-01

    The high energy quanta of impinging radiation can generate a large number (about 5x104) of secondary electrons per 1 MeV of energy deposited. When ejected in condensed phase water, the kinetic energy distribution of these free or quasi-free electrons is peaked below 10 eV. Low energy electrons also dominate in the secondary emission from biomolecular targets exposed to different energies of primary radiation. Due to the complexity of the radiation-induced processes in the condensed-phase environment, mechanisms of secondary electrons induced damage in biomolecules (BM) still need to be investigated. However, based on results from theory and different experiments accumulated within the last decade, it is now possible to determine the fundamental mechanisms that are involved in many chemical reactions induced in isolated gas-phase biomolecules by low energy electrons. The central finding of earlier research was the discovery of the bond- and site- selectivity in the dissociative electron attachment (DEA) process to biomolecules. It has been demonstrated that by tuning the energy of the incoming electron we can gain control over the location of the bond cleavage. These studies showed the selectivity in single bond cleavage reactions leading to the formation of the dehydrogenated closed shell anion (BM-H)- or the complementary reaction leading to H-. The loss of a hydrogen atom or an anion is fast compared with ring cleavage and the excision of heavier fragments and, hence, this reaction can compete efficiently with autodetachment. Moreover, site selectivity has been also observed in the metastable anion formation via the DEA process. Such delayed fragmentation was studied recently for the dehydrogenated closed-shell anion conversion into NCO- upon DEA proceeded a few μ sec after electron attachment, indicating a rather slow unimolecular decomposition. Interestingly, site selectivity was observed in the prompt as well as the metastable NCO- formation in DEA. The

  1. Identification of Biomolecular Building Blocks by Recognition Tunneling: Stride towards Nanopore Sequencing of Biomolecules

    Science.gov (United States)

    Sen, Suman

    DNA, RNA and Protein are three pivotal biomolecules in human and other organisms, playing decisive roles in functionality, appearance, diseases development and other physiological phenomena. Hence, sequencing of these biomolecules acquires the prime interest in the scientific community. Single molecular identification of their building blocks can be done by a technique called Recognition Tunneling (RT) based on Scanning Tunneling Microscope (STM). A single layer of specially designed recognition molecule is attached to the STM electrodes, which trap the targeted molecules (DNA nucleoside monophosphates, RNA nucleoside monophosphates or amino acids) inside the STM nanogap. Depending on their different binding interactions with the recognition molecules, the analyte molecules generate stochastic signal trains accommodating their "electronic fingerprints". Signal features are used to detect the molecules using a machine learning algorithm and different molecules can be identified with significantly high accuracy. This, in turn, paves the way for rapid, economical nanopore sequencing platform, overcoming the drawbacks of Next Generation Sequencing (NGS) techniques. To read DNA nucleotides with high accuracy in an STM tunnel junction a series of nitrogen-based heterocycles were designed and examined to check their capabilities to interact with naturally occurring DNA nucleotides by hydrogen bonding in the tunnel junction. These recognition molecules are Benzimidazole, Imidazole, Triazole and Pyrrole. Benzimidazole proved to be best among them showing DNA nucleotide classification accuracy close to 99%. Also, Imidazole reader can read an abasic monophosphate (AP), a product from depurination or depyrimidination that occurs 10,000 times per human cell per day. In another study, I have investigated a new universal reader, 1-(2-mercaptoethyl)pyrene (Pyrene reader) based on stacking interactions, which should be more specific to the canonical DNA nucleosides. In addition

  2. Study radiolabeling of urea-based PSMA inhibitor with 68-Galliu: Comparative evaluation of automated and not automated methods

    International Nuclear Information System (INIS)

    Alcarde, Lais Fernanda

    2016-01-01

    The methods for clinical diagnosis of prostate cancer include rectal examination and the dosage of the prostatic specific antigen (PSA). However, the PSA level is elevated in about 20 to 30% of cases related to benign pathologies, resulting in false positives and leading patients to unnecessary biopsies. The prostate specific membrane antigen (PSMA), in contrast, is over expressed in prostate cancer and founded at low levels in healthy organs. As a result, it stimulated the development of small molecule inhibitors of PSMA, which carry imaging agents to the tumor and are not affected by their microvasculature. Recent studies suggest that the HBED-CC chelator intrinsically contributes to the binding of the PSMA inhibitor peptide based on urea (Glu-urea-Lys) to the pharmacophore group. This work describes the optimization of radiolabeling conditions of PSMA-HBED-CC with 68 Ga, using automated system (synthesis module) and no automated method, seeking to establish an appropriate condition to prepare this new radiopharmaceutical, with emphasis on the labeling yield and radiochemical purity of the product. It also aimed to evaluate the stability of the radiolabeled peptide in transport conditions and study the biological distribution of the radiopharmaceutical in healthy mice. The study of radiolabeling parameters enabled to define a non-automated method which resulted in high radiochemical purity (> 95 %) without the need for purification of the labeled peptide. The automated method has been adapted, using a module of synthesis and software already available at IPEN, and also resulted in high synthetic yield (≥ 90%) specially when compared with those described in the literature, with the associated benefit of greater control of the production process in compliance with Good Manufacturing Practices. The study of radiolabeling parameters afforded the PSMA-HBED-CC- 68 Ga with higher specific activity than observed in published clinical studies (≥ 140,0 GBq/μmol), with

  3. Use Medicines Safely

    Science.gov (United States)

    ... Medicines Safely Print This Topic En español Use Medicines Safely Browse Sections The Basics Overview Prescription Medicines ... Medicines 1 of 7 sections The Basics: Prescription Medicines There are different types of medicine. The 2 ...

  4. Structural Change of Biomolecules and Application of Synergistic Interaction by Radiation

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Kim, J. H.; Yang, J. S.

    2008-12-01

    It is expected that motivation and basic technologies for the future R and D plans can be provided from the results of this study. This study has been done to develop fundamentals for radiation applications based on the existing radiation technology, and to establish technical basis for enhancing efficacy of radiation utilization by studying the simultaneous application of ionizing radiation with another factor. Application of radiation technology together with the existing technologies to enhance the physical, chemical, biological characteristics through structural changes of biomolecules will exert a favorable influence on the creation of de novo scientific and industrial values. A theoretical model for the combined action of ionizing radiation with another factor can make it possible to predict a prior the maximum value of synergistic interaction and the conditions for it. Furthermore, the results of this study give a clues for establishment of fundamental theories associated with positive efficacy of radiation applications

  5. Hydrogels Based on Ag+ -Modulated Assembly of 5'-Adenosine Monophosphate for Enriching Biomolecules.

    Science.gov (United States)

    Hu, Yuanyuan; Xie, Dong; Wu, Yang; Lin, Nangui; Song, Aixin; Hao, Jingcheng

    2017-11-07

    Supramolecular hydrogels obtained by combining 5'-adenosine monophosphate (AMP) with Ag + were fabricated in this work. Their gelation capability was enhanced by increasing the concentration of Ag + or decreasing the pH. The gels are very sensitive to light, which endows them with potential applications as visible-light photosensitive materials. Coordination between the nucleobase of AMP and Ag + , as well as π-π stacking of nucleobases, are considered to be the main driving forces for self-assembly. The hydrogels successfully achieved the encapsulation and enrichment of biomolecules. Hydrogen bonding between the amino group of guest molecules and silver nanoparticles along the nanofibers drives the enrichment and is considered to be a crucial interaction. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Automated astatination of biomolecules - a stepping stone towards multicenter clinical trials

    DEFF Research Database (Denmark)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom

    2015-01-01

    To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical...... and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting...... vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method...

  7. BioVEC: a program for biomolecule visualization with ellipsoidal coarse-graining.

    Science.gov (United States)

    Abrahamsson, Erik; Plotkin, Steven S

    2009-09-01

    Biomolecule Visualization with Ellipsoidal Coarse-graining (BioVEC) is a tool for visualizing molecular dynamics simulation data while allowing coarse-grained residues to be rendered as ellipsoids. BioVEC reads in configuration files, which may be output from molecular dynamics simulations that include orientation output in either quaternion or ANISOU format, and can render frames of the trajectory in several common image formats for subsequent concatenation into a movie file. The BioVEC program is written in C++, uses the OpenGL API for rendering, and is open source. It is lightweight, allows for user-defined settings for and texture, and runs on either Windows or Linux platforms.

  8. Recent results for electron scattering from biomolecules and molecules formed due to plasma treatment of biomass

    Science.gov (United States)

    Brunger, Michael

    2016-09-01

    We have been concentrating our recent experimental studies, for determining absolute cross sections, on both biomolecules (e.g. pyrimidine and benzoquinone) and molecules that result when biomass undergoes treatment by plasmas (e.g. phenol and furfural). All this work was supported and informed by computations from the Brazilian SMC groups and the Madrid IAM-SCAR group. A major rationale for these investigations was to provide cross section data for relevant modelling studies, and in this talk I will also present some results from those modelling studies. Possible further investigations will be canvassed in this presentation. Work done in conjunction with: D. B. Jones, L. Campbell, R. D. White, S. J. Buckman, M. A. P. Lima, M. C. A. Lopes, M. H. F. Bettega, M. T. do N. Varella, R. F. da Costa, G. García, P. Limão-Vieira, D. H. Madison, O. Ingólfsson and many other friends and colleagues.

  9. Ancient biomolecules: their origins, fossilization, and role in revealing the history of life.

    Science.gov (United States)

    Briggs, Derek E G; Summons, Roger E

    2014-05-01

    The discovery of traces of a blood meal in the abdomen of a 50-million-year-old mosquito reminds us of the insights that the chemistry of fossils can provide. Ancient DNA is the best known fossil molecule. It is less well known that new fossil targets and a growing database of ancient gene sequences are paralleled by discoveries on other classes of organic molecules. New analytical tools, such as the synchrotron, reveal traces of the original composition of arthropod cuticles that are more than 400 my old. Pigments such as melanin are readily fossilized, surviving virtually unaltered for ∼200 my. Other biomarkers provide evidence of microbial processes in ancient sediments, and have been used to reveal the presence of demosponges, for example, more than 635 mya, long before their spicules appear in the fossil record. Ancient biomolecules are a powerful complement to fossil remains in revealing the history of life. © 2014 WILEY Periodicals, Inc.

  10. Simple and universal model for electron-impact ionization of complex biomolecules

    Science.gov (United States)

    Tan, Hong Qi; Mi, Zhaohong; Bettiol, Andrew A.

    2018-03-01

    We present a simple and universal approach to calculate the total ionization cross section (TICS) for electron impact ionization in DNA bases and other biomaterials in the condensed phase. Evaluating the electron impact TICS plays a vital role in ion-beam radiobiology simulation at the cellular level, as secondary electrons are the main cause of DNA damage in particle cancer therapy. Our method is based on extending the dielectric formalism. The calculated results agree well with experimental data and show a good comparison with other theoretical calculations. This method only requires information of the chemical composition and density and an estimate of the mean binding energy to produce reasonably accurate TICS of complex biomolecules. Because of its simplicity and great predictive effectiveness, this method could be helpful in situations where the experimental TICS data are absent or scarce, such as in particle cancer therapy.

  11. High-frequency AC electrospray ionization source for mass spectrometry of biomolecules.

    Science.gov (United States)

    Chetwani, Nishant; Cassou, Catherine A; Go, David B; Chang, Hsueh-Chia

    2010-11-01

    A novel high-frequency alternating current (AC) electrospray ionization (ESI) source has been developed for applications in mass spectrometry. The AC ESI source operates in a conical meniscus mode, analogous to the cone-jet mode of direct current (DC) electrosprays but with significant physical and mechanistic differences. In this stable conical-meniscus mode at frequencies greater than 50 kHz, the low mobility ions, which can either be cations or anions, are entrained within the liquid cone and ejected as droplets that eventually form molecular ions, thus making AC ESI a viable tool for both negative and positive mode mass spectrometry. The performance of the AC ESI source is qualitatively shown to be frequency-dependent and, for larger bio-molecules, the AC ESI source produced an ion signal intensity that is an order of magnitude higher than its DC counterpart. Copyright © 2010. Published by Elsevier Inc.

  12. Elemental speciation in biomolecules by LC-ICP-MS with magnetic sector and collision cell instruments

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jin [Iowa State Univ., Ames, IA (United States)

    1999-11-08

    A methodology that can monitor and identify inorganic elements in biological and environmental systems was developed. Size exclusion chromatography (SEC) separates biomolecules, which are then nebulized by a microconcentric nebulizer. The resulting aerosol is desolved and introduced into either a high resolution ICP-MS device or a quadrupole device with a collision cell. Because of the high sensitivity and spectral resolution and high sample introduction efficiency, many unusual or difficult elements, such as Cr, Se, Cd and U, can be observed at ambient levels bound to proteins in human serum. These measurements are made in only a few minutes without preliminary isolation and preconcentration steps. Serum samples can be titrated with spikes of various elements to determine which proteins bind a given metal and oxidation state. Experiments concerning the effects of breaking disulfide linkages and denaturation on metal binding in proteins were also investigated. Elemental distribution in liver extract was also obtained.

  13. Elemental speciation in biomolecules by LC-ICP-MS with magnetic sector and collision cell instruments

    International Nuclear Information System (INIS)

    Wang, Jin

    1999-01-01

    A methodology that can monitor and identify inorganic elements in biological and environmental systems was developed. Size exclusion chromatography (SEC) separates biomolecules, which are then nebulized by a microconcentric nebulizer. The resulting aerosol is desolved and introduced into either a high resolution ICP-MS device or a quadrupole device with a collision cell. Because of the high sensitivity and spectral resolution and high sample introduction efficiency, many unusual or difficult elements, such as Cr, Se, Cd and U, can be observed at ambient levels bound to proteins in human serum. These measurements are made in only a few minutes without preliminary isolation and preconcentration steps. Serum samples can be titrated with spikes of various elements to determine which proteins bind a given metal and oxidation state. Experiments concerning the effects of breaking disulfide linkages and denaturation on metal binding in proteins were also investigated. Elemental distribution in liver extract was also obtained

  14. Electrolyte gated TFT biosensors based on the Donnan's capacitance of anchored biomolecules

    Science.gov (United States)

    Manoli, Kyriaki; Palazzo, Gerardo; Macchia, Eleonora; Tiwari, Amber; Di Franco, Cinzia; Scamarcio, Gaetano; Favia, Pietro; Mallardi, Antonia; Torsi, Luisa

    2017-08-01

    Biodetection using electrolyte gated field effect transistors has been mainly correlated to charge modulated transduction. Therefore, such platforms are designed and studied for limited applications involving relatively small charged species and much care is taken in the operating conditions particularly pH and salt concentration (ionic strength). However, there are several reports suggesting that the device conductance can also be very sensitive towards variations in the capacitance coupling. Understanding the sensing mechanism is important for further exploitation of these promising sensors in broader range of applications. In this paper, we present a thorough and in depth study of a multilayer protein system coupled to an electrolyte gated transistor. It is demonstrated that detection associated to a binding event taking place at a distance of 30 nm far from the organic semiconductor-electrolyte interface is possible and the device conductance is dominated by Donnan's capacitance of anchored biomolecules.

  15. Synthesis of the copper chelator TGTA and evaluation of its ability to protect biomolecules from copper induced degradation during copper catalyzed azide-alkyne bioconjugation reactions.

    Science.gov (United States)

    Ekholm, F S; Pynnönen, H; Vilkman, A; Koponen, J; Helin, J; Satomaa, T

    2016-01-21

    One of the most successful bioconjugation strategies to date is the copper(I)-catalyzed cycloaddition reaction (CuAAC), however, the typically applied reaction conditions have been found to degrade sensitive biomolecules. Herein, we present a water soluble copper chelator which can be utilized to protect biomolecules from copper induced degradation.

  16. Shielding biomolecules from effects of radiation by Mars analogue minerals and soils

    Science.gov (United States)

    Ertem, G.; Ertem, M. C.; McKay, C. P.; Hazen, R. M.

    2017-07-01

    Organic compounds have been delivered over time to Mars via meteorites, comets and interplanetary dust particles. The fate of organic material on the surface of Mars must be affected by the Martian environment, in particular by ultraviolet (UV) and other ionizing radiation. Penetration depth of UV radiation into soils is in the sub-millimetre to millimetre range and depends on the properties of the soil. The aim of this research is to study the possible protective role of Martian analogue minerals and soils for survivability of biomolecules against UV radiation and to compare their decomposition rates within a 1 mm-thick portion of the surface. Results demonstrated that minerals offer significant protection to biomolecules purine, pyrimidine and uracil against UV photolysis. In the absence of these minerals, organic compounds are completely degraded when subjected directly to UV photolysis equivalent to only 5 Martian day's exposure. However, similar UV exposure of organics dried from solution onto powdered calcium carbonate (calcite; CaCO3), calcium sulphate (anhydrite; CaSO4), clay-bearing Atacama dessert soil and 7 Å clay mineral kaolinite [Al2Si2O5(OH)4] results in only 1-2% loss of organics. Mixtures of purine and uracil with calcium carbonate exposed to gamma radiation of 3 Gy (3 Gray), which corresponds to approximately 15 000 days on Mars, results in up to 10% loss of organics. By contrast, these organic compounds completely decomposed upon mixing with iron oxide (Fe2O3) before UV irradiation. As the search for extinct or extant life on Mars has been identified as a goal of top priority in NASA's Mars Exploration Program and continues with several missions planned to the red planet by both NASA and the European Space Agency (ESA) in the next few decades, our findings may play a useful role in identifying optimal target sites on the Martian surface for future missions.

  17. IL 7: Theoretical investigation of the ultrafast dissociation of ionized biomolecules immersed in water

    International Nuclear Information System (INIS)

    Vuilleumier, R.; Herve du Penhoat, M.A.; Politis, M.F.; Gaigeot, M.P.; Lopez-Tarifa, P.; Alcami, M.; Martin, F.; Tavernelli, I.

    2010-01-01

    We apply time-dependent density functional theory and Ehrenfest dynamics to investigate, at a molecular level, direct and indirect effects of ionising radiations in DNA, in the particular case of irradiation by swift heavy ions such as those used in hadron therapy. Molecular double ionisation arising from irradiation by swift heavy ions (about 10% of ionisation events by ions whose velocity is about the third of speed of light), as a primary event, though maybe less probable than other events resulting from the electronic cascading (for instance, electronic excitations, electron attachments), may be systematically more damageable (and more lethal), as supported by studies of damages created by K holes in DNA. In the past recent years, we have developed the modeling at the microscopic level of the early stages of the Coulomb explosion of DNA molecules immersed in liquid water that follows the irradiation by swift heavy ions. To that end, Time-Dependent Density Functional Theory molecular dynamics simulations (TD-DFT MD) have been developed where localised Wannier orbitals are propagated. This latter enables to separate molecular orbitals of each water molecule from the molecular orbitals of the biomolecule. We find that the double ionisation of one molecule of the liquid sample, either one water molecule from the solvent or the biomolecule, may both be responsible for the formation of an atomic oxygen as a direct consequence of the molecule Coulomb explosion. The chemical reactivity of the produced atomic oxygen with other radicals present in the medium will ultimately lead to chemical products that are harmful to DNA. We will review our theoretical methodology and results on the production of atomic oxygen as a result of the double ionisation of water or as a result of the double ionisation of the Uracil RNA base will be presented. (authors)

  18. Creating "living" polymer surfaces to pattern biomolecules and cells on common plastics.

    Science.gov (United States)

    Li, Chunyan; Glidle, Andrew; Yuan, Xiaofei; Hu, Zhixiong; Pulleine, Ellie; Cooper, Jon; Yang, Wantai; Yin, Huabing

    2013-05-13

    Creating patterns of biomolecules and cells has been applied widely in many fields associated with the life sciences, including diagnostics. In these applications it has become increasingly apparent that the spatiotemporal arrangement of biological molecules in vitro is important for the investigation of the cellular functions found in vivo. However, the cell patterning techniques often used are limited to creating 2D functional surfaces on glass and silicon. In addition, in general, these procedures are not easy to implement in conventional biological laboratories. Here, we show the formation of a living poly(ethylene glycol) (PEG) layer that can be patterned with visible light on plastic surfaces. This new and simple method can be expanded to pattern multiple types of biomolecule on either a previously formed PEG layer or a plastic substrate. Using common plastic wares (i.e., polyethylene films and polystyrene cell culture Petri-dishes), we demonstrate that these PEG-modified surfaces have a high resistance to protein adsorption and cell adhesion, while at the same time, being capable of undergoing further molecular grafting with bioactive motifs. With a photomask and a fluid delivery system, we illustrate a flexible way to immobilize biological functions with a high degree of 2D and 3D spatial control. We anticipate that our method can be easily implemented in a typical life science laboratory (without the need for specialized lithography equipment) offering the prospect of imparting desirable properties to plastic products, for example, the creation of functional microenvironments in biological studies or reducing biological adhesion to surfaces.

  19. Nanostructured raspberry-like gelatin microspheres for local delivery of multiple biomolecules.

    Science.gov (United States)

    Diba, Mani; Pape, Bram; Klymov, Alexey; Zhang, Yang; Song, Jiankang; Löwik, Dennis W P M; Seyednejad, Hajar; Leeuwenburgh, Sander C G

    2017-08-01

    Multicompartment particles, which are particles composed of smaller building units, have gained considerable interest during the past decade to facilitate simultaneous and differential delivery of several biomolecules in various applications. Supercritical carbon dioxide (CO 2 ) processing is an industrial technology widely used for large-scale synthesis and processing of materials. However, the application of this technology for production of multicompartment particles from colloidal particles has not yet been explored. Here, we report the formation of raspberry-like gelatin (RLG) microparticles composed of gelatin nanoparticles as colloidal building blocks through supercritical CO 2 processing. We show that these RLG microparticles exhibit a high stability upon dispersion in aqueous media without requiring chemical cross-linking. We further demonstrate that these microparticles are cytocompatible and facilitate differential release of two different model compounds. The strategy presented here can be utilized as a cost-effective route for production of various types of multicompartment particles using colloidal particles with suitable interparticle interactions. Multicompartment particles have gained considerable interest during the past decade to facilitate simultaneous and differential delivery of multiple biomolecules in various biomedical applications. Nevertheless, common methods employed for the production of such particles are often complex and only offer small-scale production. Here, we report the formation of raspberry-like gelatin (RLG) microparticles composed of gelatin nanoparticles as colloidal building blocks through supercritical CO 2 processing. We show that these microparticles are cytocompatible and facilitate differential release of two model compounds with different molecular sizes, promising successful applications in various biomedical areas. Summarizing, this paper presents a novel strategy that can be utilized as a cost-effective route for

  20. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

    Energy Technology Data Exchange (ETDEWEB)

    Monteiro, Paulo Henrique Silva; Souza, Thiago Ferreira de; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Lima, Mariana da Cunha Lopes de; Santos, Allan Oliveira; Ramos, Celso Darío, E-mail: paulohsm42@gmail.com [Universidade de Campinas (UNICAMP), SP (Brazil). Escola de Medicina; Mengatti Jair [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

    2017-11-15

    Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ({sup 67}Ga) citrate scintigraphy. Materials And Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of {sup 99m}Tc-EDDA-HYNIC-TOC, and 21 after injection of {sup 111}In-DTPA-octreotide. All patients also underwent {sup 67}Ga citrate imaging, except for one patient who died before the {sup 67}Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by {sup 67}Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than {sup 67}Ga uptake in 11 of the 20 patients with positive images and similar to {sup 67}Ga uptake in the other 9 patients. The only patient who did not undergo {sup 67}Ga scintigraphy underwent {sup 99m}Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with {sup 99m}Tc-EDDA-HYNIC-TOC or {sup 111}In-DTPA-octreotide seems to be a good alternative to {sup 67}Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. (author)

  1. Triple Therapy of HER2+ Cancer Using Radiolabeled Multifunctional Iron Oxide Nanoparticles and Alternating Magnetic Field.

    Science.gov (United States)

    Zolata, Hamidreza; Afarideh, Hossein; Davani, Fereydoun Abbasi

    2016-11-01

    By using radio-labeled multifunctional superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF), we carried out targeted hyperthermia, drug delivery, radio-immunotherapy (RIT), and controlled chemotherapy of cancer tumors. We synthesized and characterized Indium-111-labeled, Trastuzumab and Doxorubicin (DOX)-conjugated APTES-PEG-coated SPIONs in our previous work. Then, we evaluated their capability in SPECT/MRI (single photon emission computed tomography/magnetic resonance imaging) dual modal molecular imaging, targeting, and controlled release. In this research, AMF was introduced to evaluate therapeutic effects of magnetic hyperthermia on radionuclide-chemo therapy of HER2 + cells and tumor (HER2 + )-bearing mice. In vitro and in vivo experiments using synthesized complex were repeated under an AMF (f: 100 KHz, H: 280 Gs). Instead of an intra-tumor injection in most hyperthermia experiments, SPIONs were injected to the tail vein, based on our delivery strategies. For magnetic delivery, we held a permanent Nd-B-Fe magnet near the tumor region. The results showed that simultaneous magnetic hyperthermia enhanced SKBR3 cancer cells, killing by 24%, 28%, 33%, and 80% at 48 hours post-treatment for treated cells with (1) bare SPIONs; (2) antibody-conjugated, DOX-free, surface-modified SPIONs; (3) 111 In-labeled, antibody-conjugated surface-modified SPIONs; and (4) 111 In-labeled, antibody- and DOX-conjugated surface-modified SPIONs, respectively. Moreover, tumor volume inhibitory rate was 85% after a 28 day period of treatment. By using this method, multimodal imaging-guided, targeted hyperthermia, RIT, and controlled chemotherapy could be achievable in the near future.

  2. The fate of purified radio-labelled alkaline phosphatase from the liver in the organism

    International Nuclear Information System (INIS)

    Herbert, V.

    1981-01-01

    Alkaline phosphatase (AP) from dog liver was enriched by a factor of 5.444 in various steps. Rabbit antiserum to the purified AP was produced; 125-I was used then to radiolabel the highly purified AP. Four dogs were cholecystectomized and subsequently received an extracorporal drainage of the bile ducts. Decrease rate of total radio-activity and of PBI in the serum was determined in one dog; likewise in three other dogs before and one week after occlusion of their main bile ducts. In addition, radioactivity above the organs was measured in some animals at short intervals. In the dogs with main bile duct drainage, bile was collected continuously for up to 70 h, samples were taken, and residual bile plus native dog bile were re-infused into the distal choledochus catheter. Total radioactivity, PBI and immunoprecipitability with antibodies were determined in the bile and serum samples. AP, GOT, CPT and bilirubin were determined in some serum samples. In addition, total radioactivity excreted by urine was established. Results show injected 125-I-AP to be rapidly stored in the liver and not to be excreted via bile to a decisive extent. The fact that 125-I-AP is not excreted via bile is further indicated by the identical decrease rate of injected 125-I-AP in the serum in dogs with and without main bile duct occlusion. Injected 125-I-AP appears to be metabolized very rapidly in the liver as is indicated by the rapid decrease of immuno precipitability of 125-I-AP in the serum. (orig./MG) [de

  3. Studies on binding of radiolabeled thyrotropin to cultured human thyroid cells

    International Nuclear Information System (INIS)

    Yamamoto, M.; Rapoport, B.

    1978-01-01

    A line of cultured human thyroid adenoma cells was used in a study designed to compare the stimulatory effect of TSH on cellular cAMP generation with the binding of radiolabeled TSH to the cells. At 37 C, specific binding of [ 125 I]TSH to suspensions of thyroid cells was maximal at 20 min and was reversed by the addition of excess TSH. Unlike the generation of cellular cAMP in response to TSH stimulation, which was maximal at pH 7.5, the binding of [ 125 ]TSH to the cells was maximal at pH 5.5 and progressively declined up to pH 8.5. Increasing NaCl concentrations progressively inhibited cellular binding of TSH; at physiological salt concentrations, almost no TSH binding was detectable. Competitive inhibition studies of [ 125 I]TSH binding to cells revealed a binding site with a dissociation constant of 5.5 x 10 -8 M at pH 7.4. GH, PRL, hCG, FSH, insulin, and glucagon did not compete with [ 125 I)TSH binding. ACTH, however, was a potent inhibitor of [ 125 I]TSH binding. Despite this inhibitory effect on TSH binding, ACTH had little or no effect on cellular cAMP generation. High concentrations of ACTH did not inhibit the biological effect of TSH on cAMP generation. Specific binding of [ 125 I]TSH to empty plastic culture dishes was time dependent, reversible, and displayed a hormonal specificity identical to binding to thyroid cells. The effects of pH and NaCl concentrations on TSH binding to dishes were similarbut not identical to those on cellular binding. This study raises serious questions as to the biological significance of [ 125 I]TSH binding to cultured human thyroid cells

  4. Radiolabelled GLP-1 receptor antagonist binds to GLP-1 receptor-expressing human tissues

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, PO Box 62, Berne (Switzerland)

    2014-06-15

    Radiolabelled glucagon-like peptide 1 (GLP-1) receptor agonists have recently been shown to successfully image benign insulinomas in patients. For the somatostatin receptor targeting of tumours, however, it was recently reported that antagonist tracers were superior to agonist tracers. The present study therefore evaluated various forms of the {sup 125}iodinated-Bolton-Hunter (BH)-exendin(9-39) antagonist tracer for the in vitro visualization of GLP-1 receptor-expressing tissues in rats and humans and compared it with the agonist tracer {sup 125}I-GLP-1(7-36)amide. Receptor autoradiography studies with {sup 125}I-GLP-1(7-36)amide agonist or {sup 125}I-BH-exendin(9-39) antagonist radioligands were performed in human and rat tissues. The antagonist {sup 125}I-BH-exendin(9-39) labelled at lysine 19 identifies all human and rat GLP-1 target tissues and GLP-1 receptor-expressing tumours. Binding is of high affinity and is comparable in all tested tissues in its binding properties with the agonist tracer {sup 125}I-GLP-1(7-36)amide. For comparison, {sup 125}I-BH-exendin(9-39) with the BH labelled at lysine 4 did identify the GLP-1 receptor in rat tissues but not in human tissues. The GLP-1 receptor antagonist exendin(9-39) labelled with {sup 125}I-BH at lysine 19 is an excellent GLP-1 radioligand that identifies human and rat GLP-1 receptors in normal and tumoural tissues. It may therefore be the molecular basis to develop suitable GLP-1 receptor antagonist radioligands for in vivo imaging of GLP-1 receptor-expressing tissues in patients. (orig.)

  5. SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Silva Monteiro

    2017-10-01

    Full Text Available Abstract Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs in systemic granulomatous infections in comparison with gallium-67 (67Ga citrate scintigraphy. Materials and Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99mTc-EDDA-HYNIC-TOC, and 21 after injection of 111In-DTPA-octreotide. All patients also underwent 67Ga citrate imaging, except for one patient who died before the 67Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67Ga uptake in 11 of the 20 patients with positive images and similar to 67Ga uptake in the other 9 patients. The only patient who did not undergo 67Ga scintigraphy underwent 99mTc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99mTc-EDDA-HYNIC-TOC or 111In-DTPA-octreotide seems to be a good alternative to 67Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

  6. Radiolabelling and evaluation of a novel sulfoxide as a PET imaging agent for tumor hypoxia

    International Nuclear Information System (INIS)

    Laurens, Evelyn; Yeoh, Shinn Dee; Rigopoulos, Angela; Cao, Diana; Cartwright, Glenn A.; O'Keefe, Graeme J.; Tochon-Danguy, Henri J.; White, Jonathan M.; Scott, Andrew M.; Ackermann, Uwe

    2014-01-01

    [ 18 F]FMISO is the most widely validated PET radiotracer for imaging hypoxic tissue. However, as a result of the pharmacokinetics of [ 18 F]FMISO a 2 h wait between tracer administration and patient scanning is required for optimal image acquisition. In order to develop hypoxia imaging agents with faster kinetics, we have synthesised and evaluated several F-18 labelled anilino sulfoxides. In this manuscript we report on the synthesis, in vitro and in vivo evaluation of a novel fluoroethyltriazolyl propargyl anilino sulfoxide. The radiolabelling of the novel tracer was achieved via 2-[ 18 F]fluoroethyl azide click chemistry. Radiochemical yields were 23 ± 4% based on 2-[ 18 F]fluoroethyl azide and 7 ± 2% based on K[ 18 F]F. The radiotracer did not undergo metabolism or defluorination in an in vitro assay using S9 liver fractions. Imaging studies using SK-RC-52 tumors in BALB/c nude mice have indicated that the tracer may have a higher pO 2 threshold than [ 18 F]FMISO for uptake in hypoxic tumors. Although clearance from muscle was faster than [ 18 F]FMISO, uptake in hypoxic tumors was slower. The average tumor to muscle ratio at 2 h post injection in large, hypoxic tumors with a volume greater than 686 mm 3 was 1.7, which was similar to the observed ratio of 1.75 for [ 18 F]FMISO. Although the new tracer showed improved pharmacokinetics when compared with the previously synthesised sulfoxides, further modifications to the chemical structure need to be made in order to offer significant in vivo imaging advantages over [ 18 F]FMISO

  7. Characterization of the radiolabeled metabolite of tau PET tracer {sup 18}F-THK5351

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Ryuichi [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Furumoto, Shozo; Tago, Tetsuro; Iwata, Ren; Tashiro, Manabu [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Katsutoshi, Furukawa; Ishiki, Aiko; Tomita, Naoki; Arai, Hiroyuki [Tohoku University, Department of Geriatrics and Gerontology, Institute of Development, Aging and Cancer, Sendai (Japan); Yanai, Kazuhiko [Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku University School of Medicine, Department of Pharmacology, Sendai (Japan); Kudo, Yukitsuka [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Okamura, Nobuyuki [Tohoku University, Division of Neuro-imaging, Institute of Development, Aging and Cancer, Sendai (Japan); Tohoku University, Cyclotron and Radioisotope Center, Sendai (Japan); Tohoku Medical and Pharmaceutical University, Division of Pharmacology, Faculty of Medicine, Sendai (Japan)

    2016-11-15

    {sup 18}F-THK5351 is a novel radiotracer developed for in vivo imaging of tau pathology in the brain. For the quantitative assessment of tau deposits in the brain, it is important that the radioactive metabolite does not enter the brain and that it does not bind to tau fibrils. The purpose of the study was to identify a radiolabeled metabolite of {sup 18}F-THK5351 in blood samples from human subjects and to characterize its pharmacological properties. Venous blood samples were collected from three human subjects after injection of {sup 18}F-THK5351 and the plasma metabolite was measured by high performance thin layer chromatography. In addition, mass spectrometry analysis and enzymatic assays were used to identify this metabolite. Mice were used to investigate the blood-brain barrier permeability of the radioactive metabolite. Furthermore, the binding ability of the metabolite to tau aggregates was evaluated using autoradiography and binding assays using human brain samples. About 13 % of the unmetabolized radiotracer was detectable in human plasma at 60 min following the injection of {sup 18}F-THK5351. The isolated radiometabolite of {sup 18}F-THK5351 was the sulphoconjugate of THK5351. This metabolite could be produced in vitro by incubating THK5351 with liver but not brain homogenates. The metabolite did not penetrate the blood-brain barrier in mice, and exhibited little binding to tau protein aggregates in post-mortem human brain samples. These results suggest that the sole metabolite detectable in plasma seems to be generated outside the brain and does not cross into the brain, which does not affect quantitative analysis of PET images. (orig.)

  8. Preparation of monoclonal antibodies against cardiac myosin and some radiolabelling studies

    International Nuclear Information System (INIS)

    Bapat, K.; Venkatesh, M.; Pillai, M.R.A.; Sarma, H.D.; Sainis, K.B.

    1998-01-01

    Monoclonal antibodies were raised against myosin, a specific indicator of myocardial infarction and labelled with 125 I and 99m Tc. Human cardiac myosin was isolated from normal human heart and was used for raising the monoclonal antibodies by the hybridoma technique. Antibody producing clones were identified by ELISA and cloning was done by the limiting dilution technique. Of the 13 clones obtained, 4 were deemed suitable for further studies. The antibodies were grown in ascites, purified, isotyped and their cross reactions with other forms of myosin were estimated. All the clones showed negligible cross reaction with rabbit myosin, but reacted to different extents with bovine skeletal myosin. The most avid antibody Mab-4G4 was chosen for further labelling studies. Mab-4G4 was labelled with 125 I using different oxidising agents such as iodogen, chloramine-T and lactoperoxidase. Purified radioiodinated antibody with radiochemical purity >95% could be obtained by gel filtration. Immunoreactivity was retained as tested by binding to myosin immobilised on a solid support. Mab-4G4 was also labelled with 99m Tc using stannous tartrate as the reducing agent. Radiolabelling yield was ∼60%, the purity was >95% and the immunoreactivity was retained. Both the labelled preparations were tested for bio-distribution in normal and infarcted rats. The activity accumulation in the infarcted region was ∼ 1.5 and 3.5 times as that in normal heart muscle for 125 I and 99m Tc labelled Mab-4G4 respectively. The major problem with the iodinated antibody was the in vivo deiodination resulting in very high percentage of activity in the thyroid. Although the fraction of the total activity associated with the infarcted heart is not very impressive, the fact that the activities with the infarcted and normal hearths are significantly different is heartening. With further optimisation of labelling and use of F(ab)'2 fragments, better delineation of the infarct sites is aspired. (author)

  9. Synthesis and radiolabelling of novel nitrogen mustards for the imaging of hypoxic tissue

    International Nuclear Information System (INIS)

    Falzon, C.; Ackermann, U.; Tochon-Danguy, H.J.; O'Keefe, G.J.; White, J.; Spratt, N.; Howells, D.; Scott, A.M.

    2005-01-01

    Hypoxic tissue is of great significance in stroke and oncology. Among the radiotracers currently used to detect hypoxia, derivatives based on the 2-nitro-imidazole ring such as FMISO or FAZA have received considerable attention in medical imaging. Unfortunately, due to slow clearance of these tracers from normoxic tissue a waiting period of two hours is required between tracer injection and the scanning of the patient. In addition the target to background ratio is low and the quality of the image is therefore poor. Nitrogen mustards are another class of compounds that have great affinity to hypoxic tissue. Derivatives of these compounds labelled with a positron emitting radionuclide, such as [ 18 F], may allow for the imaging of hypoxic regions in the ischemic penumbra. It therefore, may be a useful diagnostic tool in stroke. Radiolabeled N-(2-[ 18 F]-fluoroethyl)-N-(2-chloroethyl)-4-methylsulfinylaniline was successfully synthesised using a potassium fluoride kryptofix complex, giving the desired product in 40% radiochemical yield (10 min at 100 Degrees C). In vitro analysis to determine the stability of the radiotracer in plasma and saline indicated no defluorination. Biological evaluation studies of the radiotracer were undertaken using a rat stroke model (Middle cerebral Arterial Occlusion (MCAO)) to determine whether the ischemic penumbra can be imaged using PET. 150//Ci (5.5MBq) of the radiotracer was injected into the tail vein of the rat immediately after the MCAO. The rat was sacrificed 2 hours post injection and ex-vivo autoradiography was performed. Uptake of the radiotracer was observed in hypoxic regions of the brain (n=6). Dynamic PET images revealed that the ischemic penumbra can be imaged 15 minutes post injection of this tracer. With these promising results, we are now synthesizing other analogues to determine their relationship between selectivity for hypoxic tissue and brain uptake

  10. Metabolic fate of radiolabeled palmitate in ischemic canine myocardium: implications for positron emission tomography

    International Nuclear Information System (INIS)

    Rosamond, T.L.; Abendschein, D.R.; Sobel, B.E.; Bergmann, S.R.; Fox, K.A.

    1987-01-01

    Interpretation of dynamic and integrated myocardial tomograms requires elucidation of the biochemical fate of the tracer and characterization of its tissue distribution and rate of efflux. The fate of [1- 11 C] and [1- 14 C]palmitate was studied in 13 open-chest dogs during control or ischemic extracorporeal perfusion of the left circumflex coronary artery. Residue detection of myocardial radioactivity, and radio-biochemical analyses of sequential transmural biopsies and arterial and coronary venous effluent were performed for 30 min after intracoronary bolus administration of tracer. In control hearts, 10.3% of initially extracted tracer was retained in tissue (2.9% in triglyceride, 3.5% in phospholipid, and 3.9% in other lipid and aqueous fractions), 73.7% was oxidized, and 16.1% back-diffused unaltered. With ischemia (pump flow 10% of normal), 28.1% was retained (18% in triglyceride, 6.0% in phospholipid, and 4.1% in other lipid and aqueous fractions), 27.2% was oxidized, and 44.4% back diffused (p less than 0.05 compared to control). Throughout the 30-min study interval, triglyceride, diglyceride, and nonesterified fatty acid comprised a significantly greater fraction of initially extracted radioactivity in ischemic than in control hearts. Thus, during ischemia externally detected clearance rates cannot be used as a direct measure of fatty acid metabolism because of marked influences on efflux of nonmetabolized radiolabeled palmitate and the distribution of tracer retained in tissue. Quantitative measurements of specific metabolic processes by tomography will require development and validation of tracers confined to individual metabolic pathways or pools

  11. Fragmentation study of isolated and nano-solvated biomolecules induced by collision with multiply charged ions and neutral particles

    International Nuclear Information System (INIS)

    Bernigaud, V.

    2009-01-01

    This thesis concerns a gas phase study of the fragmentation of bio-molecular systems induced by slow collisions with multiply charged ions (in the keV-region), alkali atoms and rare gases. The main objective was to study the physical processes involved in the dissociation of highly electronically excited systems. In order to elucidate the intrinsic properties of certain biomolecules (porphyrins and amino acids) we have performed experiments in the gas phase with isolated systems. The obtained results demonstrate the high stability of porphyrins after electron removal and attachment. Furthermore, a dependence of the fragmentation pattern produced by multiply charged ions on the isomeric structure of the alanine molecule has been shown. In a second part of the thesis, a strong influence of the environment of the biomolecule on the fragmentation channels, their modification and their new opening, has been clearly proven. This phenomenon occurs in the presence of other surrounding biomolecules (clusters of nucleobases) as well as for molecules of a solvent (molecules of water, methanol and acetonitrile) in which the biomolecule is embedded. In order to extend these studies to larger systems, a new experimental set-up, based on an electro-spray ion source combined with a quadrupole mass filter has been developed. Due to the successful tests and proposed improvements of the device future experiments will become available concerning the fragmentation of large charged and solvated bio-molecular systems induced by collision processes. (author) [fr

  12. Combinational Effect of Cell Adhesion Biomolecules and Their Immobilized Polymer Property to Enhance Cell-Selective Adhesion

    Directory of Open Access Journals (Sweden)

    Rio Kurimoto

    2016-01-01

    Full Text Available Although surface immobilization of medical devices with bioactive molecules is one of the most widely used strategies to improve biocompatibility, the physicochemical properties of the biomaterials significantly impact the activity of the immobilized molecules. Herein we investigate the combinational effects of cell-selective biomolecules and the hydrophobicity/hydrophilicity of the polymeric substrate on selective adhesion of endothelial cells (ECs, fibroblasts (FBs, and smooth muscle cells (SMCs. To control the polymeric substrate, biomolecules are immobilized on thermoresponsive poly(N-isopropylacrylamide-co-2-carboxyisopropylacrylamide (poly(NIPAAm-co-CIPAAm-grafted glass surfaces. By switching the molecular conformation of the biomolecule-immobilized polymers, the cell-selective adhesion performances are evaluated. In case of RGDS (Arg-Gly-Asp-Ser peptide-immobilized surfaces, all cell types adhere well regardless of the surface hydrophobicity. On the other hand, a tri-Arg-immobilized surface exhibits FB-selectivity when the surface is hydrophilic. Additionally, a tri-Ile-immobilized surface exhibits EC-selective cell adhesion when the surface is hydrophobic. We believe that the proposed concept, which is used to investigate the biomolecule-immobilized surface combination, is important to produce new biomaterials, which are highly demanded for medical implants and tissue engineering.

  13. Influence of Pluronic F127 on the distribution and functionality of inkjet-printed biomolecules in porous nitrocellulose substrates

    NARCIS (Netherlands)

    Mujawar, L.H.; Amerongen, van A.; Norde, W.

    2015-01-01

    The distribution of inkjet-printed biomolecules in porous nitrocellulose substrates often results in a non-homogeneous spot morphology commonly referred to as 'doughnut-shaped' spots. We have studied the influence of Pluronic F127 (an amphiphilic surfactant) on the functionality of inkjet-printed

  14. Influence of Pluronic F127 on the distribution and functionality of inkjet-printed biomolecules in porous nitrocellulose substrates

    NARCIS (Netherlands)

    Mujawar, Liyakat Hamid; van Amerongen, Aart; Norde, Willem

    The distribution of inkjet-printed biomolecules in porous nitrocellulose substrates often results in a non-homogeneous spot morphology commonly referred to as 'doughnut-shaped' spots. We have studied the influence of Pluronic F127 (an amphiphilic surfactant) on the functionality of inkjet-printed

  15. Distribution of biomolecules in porous nitrocellulose membrane pads using confocal laser scanning microscopy and high-speed cameras

    NARCIS (Netherlands)

    Mujawar, L.H.; Maan, A.A.; Khan, M.K.I.; Norde, W.; Amerongen, van A.

    2013-01-01

    The main focus of our research was to study the distribution of inkjet printed biomolecules in porous nitrocellulose membrane pads of different brands. We produced microarrays of fluorophore-labeled IgG and bovine serum albumin (BSA) on FAST, Unisart, and Oncyte-Avid slides and compared the spot

  16. Distribution of Biomolecules in Porous Nitrocellulose Membrane Pads Using Confocal Laser Scanning Microscopy and High-Speed Cameras

    NARCIS (Netherlands)

    Mujawar, Liyakat Hamid; Maan, Abid Aslam; Khan, Muhammad Kashif Iqbal; Norde, Willem; van Amerongen, Aart

    2013-01-01

    The main focus of our research was to study the distribution of inkjet printed biomolecules in porous nitrocellulose membrane pads of different brands. We produced microarrays of fluorophore-labeled IgG and bovine serum albumin (BSA) on FAST, Unisart, and Oncyte-Avid slides and compared the spot

  17. Optimization and characterization of biomolecule immobilization on silicon substrates using (3-aminopropyl)triethoxysilane (APTES) and glutaraldehyde linker

    Energy Technology Data Exchange (ETDEWEB)

    Gunda, Naga Siva Kumar [Department of Mechanical Engineering, University of Alberta, Edmonton, Canada T6G 2G8 (Canada); Singh, Minashree [Department of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada T6G 1C9 (Canada); Norman, Lana [Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada T6G 2V4 (Canada); Kaur, Kamaljit [Department of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada T6G 1C9 (Canada); Mitra, Sushanta K., E-mail: sushanta.mitra@ualberta.ca [Department of Mechanical Engineering, University of Alberta, Edmonton, Canada T6G 2G8 (Canada)

    2014-06-01

    In the present work, we developed and optimized a technique to produce a thin, stable silane layer on silicon substrate in a controlled environment using (3-aminopropyl)triethoxysilane (APTES). The effect of APTES concentration and silanization time on the formation of silane layer is studied using spectroscopic ellipsometry and Fourier transform infrared spectroscopy (FTIR). Biomolecules of interest are immobilized on optimized silane layer formed silicon substrates using glutaraldehyde linker. Surface analytical techniques such as ellipsometry, FTIR, contact angle measurement system, and atomic force microscopy are employed to characterize the bio-chemically modified silicon surfaces at each step of the biomolecule immobilization process. It is observed that a uniform, homogenous and highly dense layer of biomolecules are immobilized with optimized silane layer on the silicon substrate. The developed immobilization method is successfully implemented on different silicon substrates (flat and pillar). Also, different types of biomolecules such as anti-human IgG (rabbit monoclonal to human IgG), Listeria monocytogenes, myoglobin and dengue capture antibodies were successfully immobilized. Further, standard sandwich immunoassay (antibody–antigen–antibody) is employed on respective capture antibody coated silicon substrates. Fluorescence microscopy is used to detect the respective FITC tagged detection antibodies bound to the surface after immunoassay.

  18. Experimental investigation of the reaction window in double charge transfer process involving biomolecule target FeTPPCl

    International Nuclear Information System (INIS)

    Li, B; Ma, X; Chen, L; Brédy, R; Bernard, J; Montagne, G; Martin, S

    2012-01-01

    In the study of ion induced fragmentation of gas phase biomolecule FeTPPCl, a reaction window was experimentally determined. The populations of individual fragmentation channels of parent dications FeTPPCl 2+ were found to be modulated by such a reaction window. A shift to lower energy was observed using projectile ions H + comparing to the case of F + impact.

  19. Alternative Medicine

    Science.gov (United States)

    ... valid therapies, delaying proven treatment for serious conditions. Holistic Treatments Holistic medicine is a system of health care ... techniques including meditation, biofeedback and relaxation training. While holistic treatments can be part of a good physical regimen, ...

  20. Nuclear medicine

    International Nuclear Information System (INIS)

    Chamberlain, M.J.

    1986-01-01

    Despite an aggressive, competitive diagnostic radiology department, the University Hospital, London, Ontario has seen a decline of 11% total (in vivo and in the laboratory) in the nuclear medicine workload between 1982 and 1985. The decline of in vivo work alone was 24%. This trend has already been noted in the U.S.. Nuclear medicine is no longer 'a large volume prosperous specialty of wide diagnostic application'

  1. Nuclear medicine

    International Nuclear Information System (INIS)

    Blanquet, Paul; Blanc, Daniel.

    1976-01-01

    The applications of radioisotopes in medical diagnostics are briefly reviewed. Each organ system is considered and the Nuclear medicine procedures pertinent to that system are discussed. This includes, the principle of the test, the detector and the radiopharmaceutical used, the procedure followed and the clinical results obtained. The various types of radiation detectors presently employed in Nuclear Medicine are surveyed, including scanners, gamma cameras, positron cameras and procedures for obtaining tomographic presentation of radionuclide distributions [fr

  2. Mercury and selenium binding biomolecules in terrestrial mammals (Cervus elaphus and Sus scrofa) from a mercury exposed area.

    Science.gov (United States)

    Ropero, M J Patiño; Fariñas, N Rodríguez; Krupp, E; Mateo, R; Nevado, J J Berzas; Martín-Doimeadios, R C Rodríguez

    2016-06-01

    Mercury (Hg) is likely bound to large biomolecules (e.g. proteins) in living organisms, and in order to assess Hg metabolic pathways and possible toxicological effects, it is essential to study these Hg containing biomolecules. However, the exact nature of most metal binding biomolecules is unknown. Such studies are still in their infancy and information on this topic is scarce because the analysis is challenging, mainly due to their lability upon digestion or extraction from the tissue. New analytical methods that allow complex Hg-biomolecules to be analysed intact are needed and only few very recent studies deal with this approach. Therefore, as an initial step towards the characterization of Hg containing biomolecules, an analytical procedure has been optimised using size-exclusion chromatography (SEC) with inductively coupled plasma mass spectrometry (ICP-MS) detection. We applied this technique to elucidate the distribution and elution profile of Hg and Se, and some physiological important elements such as Fe, Ni, Zn and Cu, to assess metal binding profiles in liver and kidney samples of red deer (Cervus elaphus) and wild boar (Sus scrofa) who roam freely within the largest Hg mining district on Earth, Almadén in Spain. Elemental fractionation profiles of the extracts from different tissues were obtained using two different SEC columns (BioSep-SEC-S2000 GL 300-1kDa and Superdex 75 10/300 GL 70-3kDa). Similar profiles of Hg were observed in red deer and wild boar; however, significant differences were evident for liver and kidney. Moreover, the profiles of Se showed a single peak at high-medium molecular weight in all investigated tissues, while co-elution of Hg with Fe, Ni, Zn and Cu was observed. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Dynamic membrane interactions of antibacterial and antifungal biomolecules, and amyloid peptides, revealed by solid-state NMR spectroscopy.

    Science.gov (United States)

    Naito, Akira; Matsumori, Nobuaki; Ramamoorthy, Ayyalusamy

    2018-02-01

    A variety of biomolecules acting on the cell membrane folds into a biologically active structure in the membrane environment. It is, therefore, important to determine the structures and dynamics of such biomolecules in a membrane environment. While several biophysical techniques are used to obtain low-resolution information, solid-state NMR spectroscopy is one of the most powerful means for determining the structure and dynamics of membrane bound biomolecules such as antibacterial biomolecules and amyloidogenic proteins; unlike X-ray crystallography and solution NMR spectroscopy, applications of solid-state NMR spectroscopy are not limited by non-crystalline, non-soluble nature or molecular size of membrane-associated biomolecules. This review article focuses on the applications of solid-state NMR techniques to study a few selected antibacterial and amyloid peptides. Solid-state NMR studies revealing the membrane inserted bent α-helical structure associated with the hemolytic activity of bee venom melittin and the chemical shift oscillation analysis used to determine the transmembrane structure (with α-helix and 3 10 -helix in the N- and C-termini, respectively) of antibiotic peptide alamethicin are discussed in detail. Oligomerization of an amyloidogenic islet amyloid polypeptide (IAPP, or also known as amylin) resulting from its aggregation in a membrane environment, molecular interactions of the antifungal natural product amphotericin B with ergosterol in lipid bilayers, and the mechanism of lipid raft formation by sphingomyelin studied using solid state NMR methods are also discussed in this review article. This article is part of a Special Issue entitled "Biophysical Exploration of Dynamical Ordering of Biomolecular Systems" edited by Dr. Koichi Kato. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. PET and PET/CT with radiolabeled choline in prostate cancer: a critical reappraisal of 20 years of clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Giovacchini, Giampiero; Giovannini, Elisabetta; Leoncini, Rossella; Riondato, Mattia; Ciarmiello, Andrea [S. Andrea Hospital, Nuclear Medicine Department, La Spezia (Italy)

    2017-09-15

    We here aim to provide a comprehensive and critical review of the literature concerning the clinical applications of positron emission tomography/computed tomography (PET/CT) with radiolabeled choline in patients with prostate cancer (PCa). We will initially briefly summarize the historical context that brought to the synthesis of [{sup 11}C]choline, which occurred exactly 20 years ago. We have arbitrarily grouped the clinical studies in three different periods, according to the year in which they were published and according to their relation with their applications in urology, radiotherapy and oncology. Studies at initial staging and, more extensively, studies in patients with biochemical failure, as well as factors predicting positive PET/CT will be reviewed. The capability of PET/CT with radiolabeled choline to provide prognostic information on PCa-specific survival will also be examined. The last sections will be devoted to the use of radiolabeled choline for monitoring the response to androgen deprivation therapy, radiotherapy, and chemotherapy. The accuracy and the limits of the technique will be discussed according to the information available from standard validation processes, including biopsy or histology. The clinical impact of the technique will be discussed on the basis of changes induced in the management of patients and in the evaluation of the response to therapy. Current indications to PET/CT, as officially endorsed by guidelines, or as routinely performed in the clinical practice will be illustrated. Emphasis will be made on methodological factors that might have influenced the results of the studies or their interpretation. Finally, we will briefly highlight the potential role of positron emission tomography/magnetic resonance and of new radiotracers for PCa imaging. (orig.)

  5. Properties of radiolabeled type I, II, and III collagens related to their use as substrates in collagenase assays

    International Nuclear Information System (INIS)

    Mookhtiar, K.A.; Mallya, S.K.; Van Wart, H.E.

    1986-01-01

    Calf skin and rat tendon type I, bovine cartilage type II, and human amnion type III collagens have been radiolabeled by reaction with [ 3 H]acetic anhydride, [ 3 H]formaldehyde, and succinimidyl 2,3-[3H]propionate. All three reactions produce collagens with high specific activities that are suitable for use as substrates in collagenase assays. The identity of the radiolabel and the labeling indices do not alter the molecular weights or thermal stabilities of the collagens or the solubilities of the collagens or gelatins in dioxane-water mixtures at 4 degrees C. However, in contrast to native or sparsely labeled collagens, those with 40 or more lysine + hydroxylysine residues labeled per molecule do not undergo fibrillogenesis in the presence of 0.2-0.4 M NaCl in the 4-35 degree C temperature range. Thus, the modification reactions not only serve to introduce the radiolabel, but also to keep the collagens soluble over a wide range of temperatures and concentrations. The TCA, TCB fragments produced on partial reaction of each collagen type with tissue collagenases can be selectively denatured by a 10-minute incubation under specific conditions and the intact collagens selectively precipitated by addition of 50% v/v dioxane. This serves as the basis for soluble collagenase assays. The effect of labeling index on the properties of the collagens has been investigated and the results establish the range of conditions over which these collagens can be used as substrates for soluble versus fibrillar collagenase assays

  6. Synthesis of new molecular probes radiolabelled with fluorine-18 for imaging neuro-inflammation with Positon Emission Tomography

    International Nuclear Information System (INIS)

    Medran-Navarrete, Vincent

    2014-01-01

    The work presented in this manuscript aims to describe the synthesis of new ligands of the translocation protein 18 kDa (TSPO), their in vitro evaluation and, for the most promising candidates, their isotopic radiolabelling with the short-lived positron emitter fluorine-18 (t 1/2 : 109.8 minutes). The ultimate goal of this work consists in developing new molecular probes, or bio-markers, for imaging neuro-inflammation in a non-invasive and atraumatic manor using Positron Emission Tomography (PET). Neuro-inflammatory processes have been identified in Alzheimer and Parkinson diseases, MS and various psychiatric pathologies. The radioligand of choice for imaging TSPO is currently [ 18 F]DPA-714, a pyr-azolo[1,5-a]pyrimidine radiolabelled with fluorine-18 which has been recently prepared in our laboratories. However, [ 18 F]DPA-714 undergoes a rapid in vivo loss of the radioactive fluorine by cleavage of the fluoro-alkoxy chain as demonstrated in metabolic studies. Therefore, my PhD project aimed to design and develop new structurally related analogues of DPA-714 where the linkage between the main backbone and the fluorine-18 would be reinforced. To this extent, nineteen compounds were prepared and their affinity towards the TSPO was evaluated. Two promising candidates, coded DPA-C5yne and CfO-DPA-714, were radiolabelled with fluorine-18 with good radiochemical yields (20-30 %) and high specific radioactivities (50-90 GBq/μmol). These radioligands were also evaluated by PET imaging at the preclinical stage and displayed equivalent or slightly improved results when compared to [ 18 F]DPA- 714. (author) [fr

  7. 99mTc-rituximab radiolabelled by photo-activation: a new non-Hodgkin's lymphoma imaging agent

    International Nuclear Information System (INIS)

    Gmeiner Stopar, T.; Fettich, J.; Hojker, S.; Mlinaric-Rascan, I.; Mather, S.J.

    2006-01-01

    Rituximab was the first chimeric monoclonal antibody to be approved for treatment of indolent B-cell non-Hodgkin's lymphoma (NHL). It is directed against the CD20 antigen, which is expressed by 95% of B-cell NHLs. The aim of this study was to explore the possibility of radiolabelling rituximab with 99m Tc for use as an imaging agent in NHL for early detection, staging, remission assessment, monitoring for metastatic spread and tumour recurrence, and assessment of CD20 expression prior to (radio)immunotherapy. Rituximab was purified from Mabthera solution (Roche), photo-activated at 302 nm by UV irradiation and radiolabelled with 99m Tc. The effectiveness of the labelling method was evaluated by determination of the number of free thiol groups per photoreduced antibody, radiochemical purity and in vitro stability of 99m Tc-rituximab. On average, 4.4 free thiol groups per photoreduced antibody were determined. Radiolabelling yields greater than 95% were routinely observed after storage of the photo-activated antibody at -80 C for 195 days. The direct binding assay showed preserved ability of 99m Tc-rituximab to bind to CD20, with an average immunoreactive fraction of 93.3%. The internalisation rate was proven to be low, with only 5.3% of bound 99m Tc-rituximab being internalised over 4 h at 37 C. Our results demonstrate that 99m Tc-rituximab of high radiochemical purity and with preserved binding affinity for the antigen can be prepared by photoreduction and that the method shows good reproducibility. 99m Tc-rituximab will be further explored as an imaging agent applicable in NHL for the purposes mentioned above. (orig.)

  8. Anti-CD20 Immunoglobulin G Radiolabeling with a 99mTc-Tricarbonyl Core: In Vitro and In Vivo Evaluations.

    Directory of Open Access Journals (Sweden)

    Hélène Carpenet

    Full Text Available In recent years, the diagnostic and therapeutic uses of radioisotopes have shown significant progress. Immunoglobulin (Ig appears to be a promising tracer, particularly due to its ability to target selected antigens. The main objective of this study is to optimize and assess an Ig radiolabeling method with Technetium 99m (99mTc, an attractive radioelement used widely for diagnostic imaging. Monoclonal anti-CD20 IgG was retained to study in vitro and in vivo radiolabeling impact. After IgG derivatization with 2-iminothiolane, IgG-SH was radiolabeled by an indirect method, using a 99mTc-tricarbonyl core. Radiolabeling stability was evaluated over 24h by thin-layer chromatography. IgG integrity was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis coupled with Western blot and autoradiography. The radiolabeled Ig's immunoaffinity was assessed in vitro by a radioimmunoassay method and binding experiments with cells (EL4-hCD20 and EL4-WT. Biodistribution studies were performed in normal BALB/c mice. Tumor uptake was assessed in mice bearing EL4-hCD20 and EL4-WT subcutaneous xenografts. With optimized method, high radiolabeling yields were obtained (95.9 ± 3.5%. 99mTc-IgG-SH was stable in phosphate-buffered saline (4°C and 25°C and in serum (37°C, even if important sensitivity to transchelation was observed. IgG was not degraded by derivatization and radiolabeling, as shown by Western blot and autoradiography results. 99mTc-anti-CD20 IgG-SH immunoaffinity was estimated with Kd = 35 nM by both methods. In vivo biodistribution studies for 48h showed significant accumulation of radioactivity in plasma, liver, spleen, lungs and kidneys. Planar scintigraphy of mice bearing tumors showed a significant uptake of 99mTc-anti-CD20 IgG-SH in CD20+ tumor versus CD20- tumor. Radiolabeling of derivatized IgG with 99mTc-tricarbonyl was effective, stable and required few antibody amounts. This attractive radiolabeling method is "antibody safe

  9. Travel medicine

    Science.gov (United States)

    Aw, Brian; Boraston, Suni; Botten, David; Cherniwchan, Darin; Fazal, Hyder; Kelton, Timothy; Libman, Michael; Saldanha, Colin; Scappatura, Philip; Stowe, Brian

    2014-01-01

    Abstract Objective To define the practice of travel medicine, provide the basics of a comprehensive pretravel consultation for international travelers, and assist in identifying patients who might require referral to travel medicine professionals. Sources of information Guidelines and recommendations on travel medicine and travel-related illnesses by national and international travel health authorities were reviewed. MEDLINE and EMBASE searches for related literature were also performed. Main message Travel medicine is a highly dynamic specialty that focuses on pretravel preventive care. A comprehensive risk assessment for each individual traveler is essential in order to accurately evaluate traveler-, itinerary-, and destination-specific risks, and to advise on the most appropriate risk management interventions to promote health and prevent adverse health outcomes during travel. Vaccinations might also be required and should be personalized according to the individual traveler’s immunization history, travel itinerary, and the amount of time available before departure. Conclusion A traveler’s health and safety depends on a practitioner’s level of expertise in providing pretravel counseling and vaccinations, if required. Those who advise travelers are encouraged to be aware of the extent of this responsibility and to refer all high-risk travelers to travel medicine professionals whenever possible. PMID:25500599

  10. Stable and high-yielding intrinsic 59Fe-radiolabeling of the intravenous iron preparations Monofer and Cosmofer

    DEFF Research Database (Denmark)

    Jensen, Andreas Tue Ingemann; Severin, Gregory; Andreasen, Hans B.

    2016-01-01

    Commercial iron supplements Monofer((R)) and Cosmofer((R)) were intrinsically radiolabeled with Fe-59 for the purpose of tracing iron absorption in vivo. Optimized procedures aimed at introducing Fe-59 into the macromolecular construct in a form that was as chemically equivalent to the matrix iron...... as possible. This was determined by challenging the labeled constructs with diethylenetriaminepentaacetic acid (DTPA) followed by separation by size-exclusion and measurements of radioactivity and iron in the eluted fractions. The final procedures were simple and involved heating aqueous dispersions...

  11. Indirect assay for serum free thyroxine (FT/sub 4/) using monoclonal antibody coated tubes and radiolabelled thyroxine

    Energy Technology Data Exchange (ETDEWEB)

    Ross, H.A.

    1985-11-01

    The most straightforward approach to assessment of antibody occupancy is by introducing a trace amount of radiolabelled T/sub 4/ into the sample and multiplying the fraction of total radioactivity that is bound by the antibody with the sample's total T/sub 4/ concentration. This latter approach was followed in the free T/sub 4/ test to be discussed in this paper, which was developed in cooperation with the research and development group of Mallinckrodt (Dietzenbach) and is now commercially available as 'SPAC ET'.

  12. Development and preclinical evaluation of radiolabelled somatostatin receptor agonists and αvβ3-integrin antagonists

    International Nuclear Information System (INIS)

    Stoecklin, G.; Wester, H.J.; Haubner, R.; Schottelius, M.

    2002-01-01

    Tumours express specific receptors for peptide ligands. This can be exploited for tumour targeting. New bioactive peptides are available, in particular new somatostatin analogs and RGD-Peptides for targeting the α V β 3 -integrin. The design and optimization of radiolabelled peptides with respect to their receptor affinity, tumour uptake, biodistribution, pharmacokinetics and stability may provide better tracers for tumour imaging and therapy. Based on two basic structures, new radioiodinated and carbohydrated somatostatin analogs and cyclic RGD-peptides were developed and evaluated. (author)

  13. In vivo and in vitro evaluation of dota-lanreotide radiolabelled with gallium-67; Avaliacao in vivo e in vitro do dota-lanreotideo radiomarcado com galio-67

    Energy Technology Data Exchange (ETDEWEB)

    Aldegheri, Eliane Bernardes

    2005-07-01

    One of the refinements of modern Nuclear Medicine is the capacity of providing dynamic and kinetics images of the administered radiopharmaceutical, reproducing its transport mechanism, action sites, receptor binding and excretion route. With the continues technological advances new radiopharmaceuticals have been developed in order to express higher specificity and with higher characters of affinity between receptor/complex. One radiopharmaceutical is formed by a reagent or bio molecule that has in its structure a radioisotope, that has the objectives of carrying it to the organs of affinity or to benign or malign tumoral process. Somatostatin inhibits the growing and proliferation of several tumoral cells. Somatostatin analogs bind to somatostatic receptors that are expressed in different kind of neoplasia DOTA-LANREOTIDE (DOTALAN) is an octapeptide analog to somatostatin. The interest of labeling the bio conjugate with gallium-67 in Nuclear Medicine comes from its physical, chemical and biological properties. Besides its gamma radiation, useful in the diagnosis of inflammation and infection foci, {sup 67}Ga emits Auger electrons (0.1 - 8 keV) and conversion electrons (80 - 90 keV), making it attractive to internal radiotherapy if the vectors used to lead the radionuclide to the tumoral cell are internalized. The objective of this work was to develop a methodology of labelling DOTA-LANREOTIDE with {sup 67}Ga, optimizing the labelling variables and its quality control. The novelty aspect was the comparison between labeling with national and imported {sup 67}Ga, in its original and purified forms. The purification of {sup 67}Ga was essential to reach yields higher than 90%. The radiolabelled bio conjugate peptides must be free of metallic contaminants that could compete in the labeling process. The following procedure was established after studying the labeling parameters: mass of peptide of 10 {mu}g (6nmol), pH5, final reaction volume of 170 {mu}L of the labelled

  14. PEG spacers of different length influence the biological profile of bombesin-based radiolabeled antagonists

    International Nuclear Information System (INIS)

    Jamous, Mazen; Tamma, Maria L.; Gourni, Eleni; Waser, Beatrice; Reubi, Jean C.; Maecke, Helmut R.; Mansi, Rosalba

    2014-01-01

    Introduction: The gastrin-releasing peptide receptor (GRPR) was shown to be expressed with high density on several types of cancers. Radiolabeled peptides for imaging and targeted radionuclide therapy have been developed. In this study, we evaluated the potential of statine-based bombesin antagonists, conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) through oligoethyleneglycol spacers, labeled with 177 Lu and we determined the effect of polyethyleneglycol (PEG) spacer length on in vitro and in vivo properties. Methods: The bombesin antagonists were synthesized on solid phase using Fmoc chemistry; the spacers Fmoc-dPEG x -OH (x = 2, 4, 6 and 12) and the DOTA(tBu) 3 were coupled using a standard procedure. The peptides were labeled with 177 Lu and evaluated in vitro (lipophilicity, serum stability, internalization and binding affinity assays). Biodistribution studies were performed in PC-3 tumor-bearing nude mice. Results: The solid-phase synthesis was straightforward with an overall yield ranging from 30% to 35% based on the first Fmoc cleavage. The hydrophilicity increased with spacer length (logD: − 1.95 vs − 2.22 of PEG 2 and PEG 12 analogs, respectively). There is a tendency of increased serum stability by increasing the spacer length (T 1/2 = 246 ± 4 and 584 ± 20 for PEG 2 and PEG 6 analogs, respectively) which seems to reverse with the PEG 12 analog. The IC 50 values are similar with the only significant difference of the PEG 12 analog. The 177 Lu-labeled PEG 4 and PEG 6 conjugates showed similar pharmacokinetic with high tumor uptake and excellent tumor-to-kidney ratios (7.8 and 9.7 at 4 h for the PEG 4 and PEG 6 derivatives, respectively). The pancreas uptake was relatively high at 1 h but it shows fast washout (0.46% ± 0.02% IA/g and 0.29% ± 0.08% IA/g already at 4 h). Conclusion: Among all the studied analogs the PEG 4 and PEG 6 showed significantly better properties. The very high tumor-to-non-target organ ratios, in

  15. WE-G-303-04: Intrinsically Radiolabeled Nanoparticles: An Emerging Paradigm

    International Nuclear Information System (INIS)

    Cai, W.

    2015-01-01

    Objectives: Understand the physical bases of gold nanoparticle applications for radiosensitization and x-ray fluorescence imaging Understand the parameters that define gold nanoparticle-mediated radiosensitization in biological systems Understand the potential of magnetic nanoparticle characterization of the microenvironment Understand the various strategies for radiolabeling of nanoparticles and their applications S.C. and S.K. acknowledge support from MD Anderson Cancer Center, NIH (R01CA155446 and P30CA16672) and DoD (W81XWH-12-1-0198); J.W. acknowledges support from NIH (U54CA151662-01); W.C. acknowledges support from the University of Wisconsin-Madison, NIH (R01CA169365, P30CA014520, and T32CA009206), DoD (W81XWH-11-1-0644 and W81XWH-11-1-0648), and ACS (125246-RSG-13-099-01-CCE)

  16. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... News Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging ... the limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch ...

  17. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Physician Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses ... limitations of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of ...

  18. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Resources Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small ... of Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical ...

  19. Children's (Pediatric) Nuclear Medicine

    Science.gov (United States)

    ... Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  20. General Nuclear Medicine

    Science.gov (United States)

    ... Resources Professions Site Index A-Z General Nuclear Medicine Nuclear medicine imaging uses small amounts of radioactive ... of General Nuclear Medicine? What is General Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  1. Children's (Pediatric) Nuclear Medicine

    Medline Plus

    Full Text Available ... Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  2. Nanotechnology: emerging tools for biology and medicine.

    Science.gov (United States)

    Wong, Ian Y; Bhatia, Sangeeta N; Toner, Mehmet

    2013-11-15

    Historically, biomedical research has been based on two paradigms. First, measurements of biological behaviors have been based on bulk assays that average over large populations. Second, these behaviors have then been crudely perturbed by systemic administration of therapeutic treatments. Nanotechnology has the potential to transform these paradigms by enabling exquisite structures comparable in size with biomolecules as well as unprecedented chemical and physical functionality at small length scales. Here, we review nanotechnology-based approaches for precisely measuring and perturbing living systems. Remarkably, nanotechnology can be used to characterize single molecules or cells at extraordinarily high throughput and deliver therapeutic payloads to specific locations as well as exhibit dynamic biomimetic behavior. These advances enable multimodal interfaces that may yield unexpected insights into systems biology as well as new therapeutic strategies for personalized medicine.

  3. Medicinal smokes.

    Science.gov (United States)

    Mohagheghzadeh, Abdolali; Faridi, Pouya; Shams-Ardakani, Mohammadreza; Ghasemi, Younes

    2006-11-24

    All through time, humans have used smoke of medicinal plants to cure illness. To the best of our knowledge, the ethnopharmacological aspects of natural products' smoke for therapy and health care have not been studied. Mono- and multi-ingredient herbal and non-herbal remedies administered as smoke from 50 countries across the 5 continents are reviewed. Most of the 265 plant species of mono-ingredient remedies studied belong to Asteraceae (10.6%), followed by Solanaceae (10.2%), Fabaceae (9.8%) and Apiaceae (5.3%). The most frequent medical indications for medicinal smoke are pulmonary (23.5%), neurological (21.8%) and dermatological (8.1%). Other uses of smoke are not exactly medical but beneficial to health, and include smoke as a preservative or a repellent and the social use of smoke. The three main methods for administering smoke are inhalation, which accounts for 71.5% of the indications; smoke directed at a specific organ or body part, which accounts for 24.5%; ambient smoke (passive smoking), which makes up the remaining 4.0%. Whereas inhalation is typically used in the treatment of pulmonary and neurological disorders and directed smoke in localized situations, such as dermatological and genito-urinary disorders, ambient smoke is not directed at the body at all but used as an air purifier. The advantages of smoke-based remedies are rapid delivery to the brain, more efficient absorption by the body and lower costs of production. This review highlights the fact that not enough is known about medicinal smoke and that a lot of natural products have potential for use as medicine in the smoke form. Furthermore, this review argues in favor of medicinal smoke extended use in modern medicine as a form of drug delivery and as a promising source of new active natural ingredients.

  4. Guidelines to develop interactive tutorials on 3D biomolecules: the case of DNA repair by photolyase

    Directory of Open Access Journals (Sweden)

    Larissa Assis Barony Valadares Fonseca

    2016-11-01

    Full Text Available INTRODUCTION: This work presents the following guidelines for developing interactive learning objects on the 3D biomolecules: i- identify a relevant educational need; ii-select an appropriate subject; iii- employ interactive 3D molecular structures; iv- simultaneously display animation with related textual information or 2D diagrams; v- integrating different modes of representation of chemical phenomena. Based on these, was constructed the "Photolyase Tutorial". Photolyase is an enzyme that repairs DNA. It recognizes the cyclobutane pyrimidine dimer lesion (CPD caused by exposure to ultraviolet light. Understanding the repair mechanism requires understanding the structure-activity relationships of the molecules involved. Therefore, this topic is a convenient subject for teaching key aspects of the structure of protein and nucleic acids. There are few interactive 3D DNA repair tutorials available and most of these are in english, therefore not acessible for students that do not domain this language. Besides, these tutorials generally focus only on displaying structural features without make foster correlations between the structure and chemical aspects of repair mechanisms. OBJECTIVES: In order to construct a interactive tutorial that fills these gaps, the 3D structures of a DNA molecule, a DNA with CPD lesion and the photolyase enzyme were manipulated focusing on structural and chemical explanation. MATERIALS AND METHODS: These structures were obtained from PDB (http://www.rcsb.org/pdb/home/home.do and manipulated to show biochemical and chemical concepts by using the resources from the LABIQ Platform (http://labiq.is.usp.br. DISCUSSION AND RESULTS: Several concepts are covered, i.e., H-bonding, active site, co-factors etc. The tutorial is organized in small conceptual blocks presenting, in a stepwise fashion, how the enzyme recognizes the DNA lesion and proceeds to repair. Each block comprises a trigger button that controls the interactive

  5. On-chip micro-electromagnets for magnetic-based bio-molecules separation

    International Nuclear Information System (INIS)

    Ramadan, Qasem; Samper, Victor; Poenar, Daniel; Yu Chen

    2004-01-01

    This paper reports a comprehensive theoretical, finite element and measurement analysis of different designs of planar micro-electromagnets for bio-molecular manipulation. The magnetic field due to current flowing in complex shapes of current-carrying conductors have been calculated analytically, simulated using finite-element analysis (FEA), and measured using the superconducting quantum interference device technique (SQUID). A comparison of the theoretical and measured magnetic field strength and patterns is presented. The planar electromagnets have been fabricated using patterned Al 2 μm thick. The aim of the study is to explore and optimize the geometrical and structural parameters of planar electromagnets that give rise to the highest magnetic fields and forces for magnetic micro-beads manipulation. Magnetic beads are often used in biochemical assays for separation of bio-molecules. Typical beads are 0.2-10 μm in diameter and have superparamagnetic properties. Increasing the intensity of the magnetic field generated by a coil by injection a larger current is not the most suitable solution as the maximum current is limited by Joule heating. Consequently, in order to maximize the field for a given current, one should optimize the geometry of the coil, as this is an extremely significant factor in determining the magnetic field intensity in 2D planar designs. The theoretical and measured results of this work show that the meander micro-electromagnet with mesh-shaped winding profile produces the strongest magnetic field (about 2.7 μT for a current intensity of 6 mA) compared with other meander designs, such as the serpentine and rosette-shaped ones. The magnetic fields of these three types of meander-shaped micro-electromagnets were compared theoretically with that produced by a spiral micro-electromagnet whose technological realization is more complicated and costly due to the fact that it requires an additional insulation layer with a contact window and a

  6. Distribution of biomolecules in porous nitrocellulose membrane pads using confocal laser scanning microscopy and high-speed cameras.

    Science.gov (United States)

    Mujawar, Liyakat Hamid; Maan, Abid Aslam; Khan, Muhammad Kashif Iqbal; Norde, Willem; van Amerongen, Aart

    2013-04-02

    The main focus of our research was to study the distribution of inkjet printed biomolecules in porous nitrocellulose membrane pads of different brands. We produced microarrays of fluorophore-labeled IgG and bovine serum albumin (BSA) on FAST, Unisart, and Oncyte-Avid slides and compared the spot morphology of the inkjet printed biomolecules. The distribution of these biomolecules within the spot embedded in the nitrocellulose membrane was analyzed by confocal laser scanning microscopy in the "Z" stack mode. By applying a "concentric ring" format, the distribution profile of the fluorescence intensity in each horizontal slice was measured and represented in a graphical color-coded way. Furthermore, a one-step diagnostic antibody assay was performed with a primary antibody, double-labeled amplicons, and fluorophore-labeled streptavidin in order to study the functionality and distribution of the immune complex in the nitrocellulose membrane slides. Under the conditions applied, the spot morphology and distribution of the primary labeled biomolecules was nonhomogenous and doughnut-like on the FAST and Unisart nitrocellulose slides, whereas a better spot morphology with more homogeneously distributed biomolecules was observed on the Oncyte-Avid slide. Similar morphologies and distribution patterns were observed when the diagnostic one-step nucleic acid microarray immunoassay was performed on these nitrocellulose slides. We also investigated possible reasons for the differences in the observed spot morphology by monitoring the dynamic behavior of a liquid droplet on and in these nitrocellulose slides. Using high speed cameras, we analyzed the wettability and fluid flow dynamics of a droplet on the various nitrocellulose substrates. The spreading of the liquid droplet was comparable for the FAST and Unisart slides but different, i.e., slower, for the Oncyte-Avid slide. The results of the spreading of the droplet and the penetration behavior of the liquid in the

  7. Medicinal Mushrooms

    NARCIS (Netherlands)

    Lindequist, U.; Won Kim, H.; Tiralongo, E.; Griensven, van L.J.L.D.

    2014-01-01

    Since beginning of mankind nature is the most important source of medicines. Bioactive compounds produced by living organisms can be used directly as drugs or as lead compounds for drug development. Besides, the natural material can be used as crude drug for preparation of powder or extracts. Plants

  8. Medicinal Plants.

    Science.gov (United States)

    Phillipson, J. David

    1997-01-01

    Highlights the demand for medicinal plants as pharmaceuticals and the demand for health care treatments worldwide and the issues that arise from this. Discusses new drugs from plants, anticancer drugs, antiviral drugs, antimalarial drugs, herbal remedies, quality, safety, efficacy, and conservation of plants. Contains 30 references. (JRH)

  9. Predictive medicine

    NARCIS (Netherlands)

    Boenink, Marianne; ten Have, Henk

    2015-01-01

    In the last part of the twentieth century, predictive medicine has gained currency as an important ideal in biomedical research and health care. Research in the genetic and molecular basis of disease suggested that the insights gained might be used to develop tests that predict the future health

  10. Bioenergetic medicine

    Science.gov (United States)

    Swerdlow, Russell H

    2014-01-01

    Here we discuss a specific therapeutic strategy we call ‘bioenergetic medicine’. Bioenergetic medicine refers to the manipulation of bioenergetic fluxes to positively affect health. Bioenergetic medicine approaches rely heavily on the law of mass action, and impact systems that monitor and respond to the manipulated flux. Since classically defined energy metabolism pathways intersect and intertwine, targeting one flux also tends to change other fluxes, which complicates treatment design. Such indirect effects, fortunately, are to some extent predictable, and from a therapeutic perspective may also be desirable. Bioenergetic medicine-based interventions already exist for some diseases, and because bioenergetic medicine interventions are presently feasible, new approaches to treat certain conditions, including some neurodegenerative conditions and cancers, are beginning to transition from the laboratory to the clinic. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24004341

  11. Personalized medicine

    DEFF Research Database (Denmark)

    Bendtzen, Klaus

    2013-01-01

    engineered anti-TNF-alpha antibody constructs now constitute one of the heaviest medicinal expenditures in many countries. All currently used TNF antagonists may dramatically lower disease activity and, in some patients, induce remission. Unfortunately, however, not all patients respond favorably, and safety...

  12. Cardiac lymphoscintigraphy following closed-chest catheter injection of radiolabeled colloid into the myocardium of dogs: concise communication

    International Nuclear Information System (INIS)

    Osbakken, M.D.; Kopiwoda, S.Y.; Swan, A.; Castronovo, F.P.; Strauss, H.W.

    1982-01-01

    A catheter technique for injection of radiolabeled colloids into the myocardium was developed and tested in a series of 15 dogs. A multipurpose angiographic catheter was modified to permit an inner core of PE-50 polyethylene tubing, tipped with a 23-gage needle, to pass through the lumen for intra-myocardial injection of the femoral artery: for the right ventricle, the femoral vein. The catheter advanced under fluoroscopy until the desired surface for injection is reached. The inner core is then extended to lodge the needle in the endocardium. A mixture of Renogratin (to confirm the endocardial injection site) and radiolabeled colloid was injected in up to 6 hr. In three dogs the procedure was repeated 3 or 4 times. From two to five nodes were visible in all animals, irrespective of whether the right or left ventricular myocardium was injected. In two animals the injection was given intravenously, and no nodes were seen. These data suggest that cardiac lymphatic drainage can be studied with a catheter injection method

  13. Cardiac lymphoscintigraphy following closed-chest catheter injection of radiolabeled colloid into the myocardium of dogs: concise communication

    International Nuclear Information System (INIS)

    Osbakken, M.D.; Kopiwoda, S.Y.; Swan, A.; Castronovo, F.P.; Strauss, H.W.

    1982-01-01

    A catheter technique for injection of radiolabeled colloids into the myocardium was developed and tested in a series of 15 dogs. A multipurpose angiographic catheter was modified to permit an inner core of PE-50 polyethylene tubing, tipped with a 23-gage needle, to pass through the lumen for intra-myocardial injection of radiocolloids. For injection of the left ventricle, the catheter is introduced through the femoral artery: for the right ventricle, the femoral vein. The catheter advanced under fluoroscopy until the desired surface for injection is reached. The inner core is then extended to lodge the needle in the endocardium. A mixture of Renografin (to confirm the endocardial injection site) and radiolabeled colloid was injected in 13 animals. Ten minutes after injection, scintigraphy was begun and continued for up to 6 hr. In three dogs the procedure was repeated 3 or 4 times. From two to five nodes were visible in all animals, irrespective of whether the right or left ventricular myocardium was injected. In two animals the injection was given intravenously, and no nodes were seen. These data suggest that cardiac lymphatic drainage can be studied with a catheter injection method

  14. The role of positron emission tomography/computed tomography imaging with radiolabeled choline analogues in prostate cancer.

    Science.gov (United States)

    Navarro-Pelayo Láinez, M M; Rodríguez-Fernández, A; Gómez-Río, M; Vázquez-Alonso, F; Cózar-Olmo, J M; Llamas-Elvira, J M

    2014-11-01

    prostate cancer is the most frequent solid malignant tumor in Western Countries. Positron emission tomography/x-ray computed tomography imaging with radiolabeled choline analogues is a useful tool for restaging prostate cancer in patients with rising prostate-specific antigen after radical treatment (in whom conventional imaging techniques have important limitations) as well as in the initial assessment of a selected group of prostate cancer patients. For this reason a literature review is necessary in order to evaluate the usefulness of this imaging test for the diagnosis and treatment of prostate cancer. a MEDLINE (PubMed way) literature search was performed using the search parameters: «Prostate cancer» and «Choline-PET/CT». Other search terms were «Biochemical failure» and/or «Staging» and/or «PSA kinetics». English and Spanish papers were selected; original articles, reviews, systematic reviews and clinical guidelines were included. according to available data, radiolabeled choline analogues plays an important role in the management of prostate cancer, especially in biochemical relapse because technique accuracy is properly correlated with prostate-specific antigen values and kinetics. Although is an emerging diagnostic technique useful in treatment planning of prostate cancer, final recommendations have not been submitted. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  15. Recent achievements in the development of radiolabeled monoclonal antibodies for diagnosis, therapy and biologic characterization of human tumors

    International Nuclear Information System (INIS)

    Larson, S.M.; Macapinlac, H.A.; Scott, A.M.; Divgi, C.R.

    1993-01-01

    Human tumors express antigenic sites that can serve as targets for radiolabeled monoclonal antibodies for diagnosis, therapy and biologic characterization of human tumors in vivo. Over the last decade, nearly 200 clinical trials have been performed which demonstrate that tumors can be detected with excellent sensitivity and specificity. Tumors which are otherwise occult, particularly for colorectal (anti-CEA and anti-TAG-72 antibodies) and ovarian cancer (anti-TAG-72 and anti-HMFG), are detected in a significant fraction of problem patients. Therapy using radiolabeled antibodies has been effective in lymphomas, leukemias and neuroblastomas, and is beginning to show promise in other solid tumors. Biologic characterization of tumors is likely to become more and more important in the future as monoclonal antibodies against oncogene products, such as her-2-neu, are developed. Development of new antibody forms through genetic engineering techniques, and the continual evolution toward higher resolution imaging instruments, such as PET and SPECT, will lead to further clinical improvements in cancer detection. (orig.)

  16. Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

    International Nuclear Information System (INIS)

    Araujo, Bortoleti de; Pujatti, Priscilla Brunelli; Barrio, Ofelia; Caldeira, Jose S.; Mengatti, Jair; Suzuki, Miriam F.

    2008-01-01

    Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 ( 177 Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177 Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177 Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

  17. Lipoxygenase- and cyclooxygenase-reaction products and incorporation into glycerolipids or radiolabeled arachidonic acid in the bovine retina

    International Nuclear Information System (INIS)

    Birkle, D.L.; Bazan, N.G.

    1984-01-01

    The metabolism of radiolabeled arachidonic acid (AA) by the intact bovine retina in vitro has been studied. Synthesis of prostaglandins (PGs) and hydroxyeicosatetraenoic acids (HETEs), and incorporation of AA into glycerolipids has been measured by reverse-phase and straight-phase high performance liquid chromatography with flow scintillation detection, and by thin-layer chromatography. AA was actively acylated into glycerolipids, particularly triglycerides, phosphatidylcholine and phosphatidylinositol. AA was also converted to the major PGs, PGF2 alpha, PGE2, PGD2, 6-keto-PGF1 alpha and TXB2, and to the lipoxygenase reaction products, 12-HETE, 5-HETE, and other monohydroxy isomers. Approximately 6% of the radiolabeled AA was converted to eicosanoids. The synthesis of HETEs was inhibited in a concentration-dependent manner (IC50 . 8.3 nM) by nordihydroguaiaretic acid (NDGA). PG synthesis was inhibited by aspirin (10 microM), indomethacin (1 microM) and NDGA (IC50 . 380 nM). Metabolism of AA via lipoxygenase, cyclooxygenase and activation-acylation was inhibited by boiling retinal tissue prior to incubation. These studies demonstrate an active system for the uptake and utilization of AA in the bovine retina, and provide the first evidence of lipoxygenase-mediated metabolism of AA, resulting in the synthesis of mono-hydroxyeicosatetraenoic acids, in the retina

  18. Synthesis, radiolabeling and quality control of {sup 111}In-DOTA-bevacizumab for radioimmunoscintigraphy of VEGF receptors

    Energy Technology Data Exchange (ETDEWEB)

    Khorami-Moghadam, A.; Jalilian, A.R.; Yavari, K.; Alirezapour, B.; Mazidi, M.; Mirzaii, M. [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of)

    2013-11-01

    In this study, bevacizumab was successively labeled with {sup 111}In-InCl{sub 3} after conjugation with DOTA-NHS-ester followed by molecular filtration and determination of the average number ofDOTAconjugated per mAb (6:1) by spectrophotometric method. Radiochemical purity (> 97%, measured by ITLC and HPLC), integrity of protein after radiolabeling (gel electrophoresis) and stability of {sup 111}In-DOTA-Bevacizumab (in final formulation, human serum, liver/kidney homogenates) were determined in 24-72 h as well as biodistribution studies in wild-type rats and human colon cancer (SW-480) bearing mice. The accumulation of the radiolabeled antibody was consistent with the former reported Bevacizumab conjugates. Significant tumor uptake (8%) was observed at 72 h p.i. Tumor/muscle uptake ratios were 2.6 (24 h), 9.74 (48 h) and 25 (72 h). {sup 111}In-DOTA-Bevacizumab was prepared as a SPECT molecular imaging agent for diagnosis and follow-up of vascular endothelial growth factor A (VEGF-A) expression in oncology. (orig.)

  19. Radiolabeled nanoceria probes may reduce oxidative damages and risk of cancer: a hypothesis for radioisotope-based imaging procedures.

    Science.gov (United States)

    Bakht, Mohamadreza K; Hosseini, Vahid; Honarpisheh, Hamid

    2013-12-01

    Low-dose ionizing radiations are commonly utilized in medical centers for diagnostic imaging procedures. Unfortunately, the absorption of ionizing radiation generates reactive chemical species that could damage cells. In diagnostic radioisotope-based imaging procedures, the radiological exposures by gamma emitter imaging probes such as radioactive technetium ((99m)Tc) could express low risk of cancer. Recently, many studies have documented cell protective, neuro-protective, anti-inflammatory and cardio-protective properties of cerium oxide nanoparticles (nanoceria) as a result of their antioxidant and free radical scavenger properties. Since there is no safe level of ionizing radiations, then we hypothesize that radiolabeled nanoceria might be an interesting probe to reduce cancer risk and other related oxidative stresses. We also provide a synthetic scheme of nanoceria functionalization with fluorine radiolabeled ligands as an exemplary approach. In conclusion, using nanoceria to combine radioisotope-based imaging probes with antioxidant activity might open new way to protect patient against radioactive emission of radioisotopes and ionizing radiations in several radioisotope-based imaging applications, in particular for patients who need frequent imaging procedures and children who are more susceptible to radiation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Metabolic labeling of cellular glycoproteins with glucosamine: potential for erroneous interpretations due to nonenzymatic radiolabeling of proteins

    International Nuclear Information System (INIS)

    Briles, E.I.B.; Updyke, T.V.

    1986-01-01

    Proteins, including serum proteins of culture media, become nonenzymatically radiolabeled under conditions used for metabolic labeling of cultured cells with glucosamine. This occurs even under sterile conditions in the absence of cells. Various commercial lots of 3 H or 14 C glcN gave similar results: ∼ 0.7% of total label was incorporated into 20% serum (14 mg/ml protein) in 48 h at 37 0 C. By SDS-PAGE fluorography, labeled serum bands correspond to Coomassie stained bands. Incorporation is linear with protein concentration and label input, shows biphasic kinetics (initial rapid rate within first 3 hr, followed by slower linear rate with no sign of saturation through 120 hr), and is temperature-dependent (no reaction at 0 0 C; incorporation at 20 0 C is ∼ 45% of that at 37 0 C). Poly-D-lysine is a better acceptor than protein: 0.5 mg/ml PL accepts as much label as 7 mg/ml protein. Incorporation is inhibited by excess unlabeled glcN and ethanolamine, but not by man, gal or glucose. However, when proteins were incubated with 160 mM glcN, SDS-PAGE bands were yellow-brown, suggesting the occurrence of Maillard-type reactions. Although the chemical mechanism(s) responsible for nonmetabolic radiolabeling by glcN are not clear at this point, the fact that it occurs represents a serious artifact which may lead to erroneous interpretation of data

  1. The detection of axillary lymph node metastases from breast cancer by radiolabelled monoclonal antibodies: a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Tjandra, J.J. (Melbourne Univ., Parkville (Australia) Royal Melbourne Hospital, Parkville (Australia)); Sacks, N.P.M.; Thompson, C.H. (Melbourne Univ., Parkville (Australia)) (and others)

    1989-02-01

    Two murine monoclonal antibodies that react with human breast cancer (3E1.2 and RCC-1) were labelled with {sup 131}iodine, and the radiolabelled antibody was injected into 40 patients, 36 of whom had breast cancer and the remaining four of whom had fibroadenoma (the normal, contralateral axilla was used as a control). Immunoscintigraphy had an overall sensitivity of 33% (23% with {sup 131}I-3E1.2 and 5% with {sup 131}I-RCC-1) for the detection of lymph node metastases and a specificity of 63% (67% with {sup 131}I-3E1.2 and 60% with {sup 131}I-RCC-1) with problems of non-specific uptake by presumably normal lymph nodes. The results of immunoscintigraphy obtained with {sup 131}I-RCC-1 (IgG) were superior to {sup 131}I-3E1.2 (IgM) although the accuracy of immunoscintigraphy using {sup 131}I-RCC-1 (56%) was not much better than preoperative clinical assessment (50%). However, there were cases when immunoscintigraphy using radiolabelled antibody (IgM or IgG) detected axillary lymph node metastases not suspected by clinical examination. Thus it appears that while immunoscintigraphy may be a useful adjunct to preoperative clinical assessment and is simple and safe, a major improvement in its accuracy is needed before it can replace axillary dissection and histological examination in the accurate staging of axilla in breast cancer. (author).

  2. Optimized Solid Phase-Assisted Synthesis of Dendrons Applicable as Scaffolds for Radiolabeled Bioactive Multivalent Compounds Intended for Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Gabriel Fischer

    2014-05-01

    Full Text Available Dendritic structures, being highly homogeneous and symmetric, represent ideal scaffolds for the multimerization of bioactive molecules and thus enable the synthesis of compounds of high valency which are e.g., applicable in radiolabeled form as multivalent radiotracers for in vivo imaging. As the commonly applied solution phase synthesis of dendritic scaffolds is cumbersome and time-consuming, a synthesis strategy was developed that allows for the efficient assembly of acid amide bond-based highly modular dendrons on solid support via standard Fmoc solid phase peptide synthesis protocols. The obtained dendritic structures comprised up to 16 maleimide functionalities and were derivatized on solid support with the chelating agent DOTA. The functionalized dendrons furthermore could be efficiently reacted with structurally variable model thiol-bearing bioactive molecules via click chemistry and finally radiolabeled with 68Ga. Thus, this solid phase-assisted dendron synthesis approach enables the fast and straightforward assembly of bioactive multivalent constructs for example applicable as radiotracers for in vivo imaging with Positron Emission Tomography (PET.

  3. Optimization of biomolecule separation by combining microscale filtration and design-of-experiment methods.

    Science.gov (United States)

    Kazemi, Amir S; Kawka, Karina; Latulippe, David R

    2016-10-01

    There is considerable interest in developing microscale (i.e., high-throughput) methods that enable multiple filtration experiments to be run in parallel with smaller sample amounts and thus reduce the overall required time and associated cost to run the filtration tests. Previous studies to date have focused on simply evaluating the filtration capacity, not the separation performance. In this work, the stirred-well filtration (SWF) method was used in combination with design-of-experiment (DOE) methods to optimize the separation performance for three binary mixtures of bio-molecules: protein-protein, protein-polysaccharide, and protein-DNA. Using the parallel based format of the SWF method, eight constant-flux ultrafiltration experiments were conducted at once to study the effects of stirring conditions, permeate flux, and/or solution conditions (pH, ionic strength). Four separate filtration tests were conducted for each combination of process variables; in total, over 100 separate tests were conducted. The sieving coefficient and selectivity results are presented to match the DOE design format and enable a greater understanding of the effects of the different process variables that were studied. The method described herein can be used to rapidly determine the optimal combination of process factors that give the best separation performance for a range of membrane-based separations applications and thus obviate the need to run a large number of traditional lab-scale tests. Biotechnol. Bioeng. 2016;113: 2131-2139. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  4. Automated astatination of biomolecules - a stepping stone towards multicenter clinical trials

    Science.gov (United States)

    Aneheim, Emma; Albertsson, Per; Bäck, Tom; Jensen, Holger; Palm, Stig; Lindegren, Sture

    2015-07-01

    To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform. This platform will standardize production of astatinated radiopharmaceuticals, and hence, it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies.

  5. Spatially controlled immobilisation of biomolecules: A complete approach in green chemistry

    Science.gov (United States)

    Grinenval, Eva; Nonglaton, Guillaume; Vinet, Françoise

    2014-01-01

    The development of 'green' sensors is a challenging task in the field of biomolecule sensing, for example in the detection of cardiac troponin-I (cTnI). In the present work a complete approach in green chemistry was developed to create chemically active patterns for the immobilisation of biological probes. This key technology is discussed on the basis of the twelve green chemistry principles, and is a combination of surface patterning by spotting and surface chemistries modified by molecular vapour deposition. The (1H,1H,2H,2H)-perfluorodecyltrichlorosilane (FDTS) was used as a novel anti-adsorption layer while the 3,4-epoxybutyltrimethoxysilane (EBTMOS) was used to immobilise probes. Oligonucleotides and the anti-cTnI antibody were studied. The spatially controlled immobilisation of probes was characterised by fluorescence. The demonstrated surface modification has broad applications in areas such as diagnostics and bio-chemical sensing. Moreover, the environmental impacts of surface patterning and surface chemistry were discussed from a 'greenness' point of view.

  6. Studies on mass deposition effect and energy effect of biomolecules implanted by N+ ion beam

    International Nuclear Information System (INIS)

    Shao Chunlin; Yu Zengliang

    1994-05-01

    By analyzing some spectrum of tyrosine sample implanted by N + ion beam, it is deduced that the implantation N + could react with the tyrosine molecule and substitute =C 5 H- group of benzene ring to produce a N-heterocyclic compound. This compound would notably affect the residual activity of the sample. Moreover, the percentage of the product molecules to the damaged tyrosine molecules is larger than the reciprocal of the proportion of their extinction coefficients. On the other hand, by comparing the release of inorganic phosphate, it is found that the radiation sensibility for four basic nucleotides is 5'-dTMP>5'-CMP>5'-GMP>5'-AMP. to implanted nucleotides, alkali treatment and heat treatment could increase the amount of inorganic phosphate. The amount of inorganic phosphate in the nucleotide samples directly implanted by ions beam is about 60% of the total amount of inorganic phosphate that could be released from the implanted samples heated at 90 degree C for 1.75 hours. Alkali treatment could damage and split the free bases released from the implanted nucleotides, but heat treatment might repair those damaged bases. Above results prove that ions implantation to biomolecules has the mass deposition effects and energy effects

  7. Modifications of a calcium phosphate cement with biomolecules--influence on nanostructure, material, and biological properties.

    Science.gov (United States)

    Vater, Corina; Lode, Anja; Bernhardt, Anne; Reinstorf, Antje; Nies, Berthold; Gelinsky, Michael

    2010-12-01

    Calcium phosphate cements (CPC), forming hydroxyapatite during the setting reaction, are characterized by good biocompatibility and osteoconductivity, however, their remodeling into native bone tissue is slow. One strategy to improve remodeling and bone regeneration is the directed modification of their nanostructure. In this study, a CPC was set in the presence of cocarboxylase, glucuronic acid, tartaric acid, α-glucose-1-phosphate, L-arginine, L-aspartic acid, and L-lysine, respectively, with the aim to influence formation and growth of hydroxyapatite crystals through the functional groups of these biomolecules. Except for glucuronic acid, all these modifications resulted in the formation of smaller and more agglomerated hydroxyapatite particles which had a positive impact on the biological performance indicated by first experiments with the human osteoblast cell line hFOB 1.19. Moreover, adhesion, proliferation, and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSC) as well as binding of the growth factors BMP-2 and VEGF was investigated on CPC modified with cocarboxylase, arginine, and aspartic acid. Initial adhesion of hBMSC was improved on these three modifications and proliferation was enhanced on CPC modified with cocarboxylase and arginine whereas osteogenic differentiation remained unaffected. Modification of the CPC with arginine and aspartic acid, but not with cocarboxylase, led to a higher BMP-2 binding. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.

  8. Biotin-Streptavidin Competition Mediates Sensitive Detection of Biomolecules in Enzyme Linked Immunosorbent Assay.

    Science.gov (United States)

    Lakshmipriya, Thangavel; Gopinath, Subash C B; Tang, Thean-Hock

    2016-01-01

    Enzyme Linked Immunosorbent Assay (ELISA) is the gold standard assay for detecting and identifying biomolecules using antibodies as the probe. Improving ELISA is crucial for detecting disease-causing agents and facilitating diagnosis at the early stages of disease. Biotinylated antibody and streptavidin-conjugated horse radish peroxide (streptavidin-HRP) often are used with ELISA to enhance the detection of various kinds of targets. In the present study, we used a competition-based strategy in which we pre-mixed free biotin with streptavidin-HRP to generate high-performance system, as free biotin occupies some of the biotin binding sites on streptavidin, thereby providing more chances for streptavidin-HRP to bind with biotinylated antibody. ESAT-6, which is a protein secreted early during tuberculosis infection, was used as the model target. We found that 8 fM of free biotin mixed with streptavidin-HRP anchored the higher detection level of ESAT-6 by four-fold compared with detection without free biotin (only streptavidin-HRP), and the limit of detection of the new method was 250 pM. These results suggest that biotin-streptavidin competition can be used to improve the diagnosis of analytes in other types of sensors.

  9. A Universal Method for Fishing Target Proteins from Mixtures of Biomolecules using Isothermal Titration Calorimetry

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, X.; Sun, Q; Kini, R; Sivaraman, J

    2008-01-01

    The most challenging tasks in biology include the identification of (1) the orphan receptor for a ligand, (2) the ligand for an orphan receptor protein, and (3) the target protein(s) for a given drug or a lead compound that are critical for the pharmacological or side effects. At present, several approaches are available, including cell- or animal-based assays, affinity labeling, solid-phase binding assays, surface plasmon resonance, and nuclear magnetic resonance. Most of these techniques are not easy to apply when the target protein is unknown and the compound is not amenable to labeling, chemical modification, or immobilization. Here we demonstrate a new universal method for fishing orphan target proteins from a complex mixture of biomolecules using isothermal titration calorimetry (ITC) as a tracking tool. We took snake venom, a crude mixture of several hundred proteins/peptides, as a model to demonstrate our proposed ITC method in tracking the isolation and purification of two distinct target proteins, a major component and a minor component. Identities of fished out target proteins were confirmed by amino acid sequencing and inhibition assays. This method has the potential to make a significant advancement in the area of identifying orphan target proteins and inhibitor screening in drug discovery and characterization.

  10. Charging effect in Au nanoparticle memory device with biomolecule binding mechanism.

    Science.gov (United States)

    Jung, Sung Mok; Kim, Hyung-Jun; Kim, Bong-Jin; Yoon, Tae-Sik; Kim, Yong-Sang; Lee, Hyun Ho

    2011-07-01

    Organic memory device having gold nanoparticle (Au NPs) has been introduced in the structure of metal-pentacene-insulator-silicon (MPIS) capacitor device, where the Au NPs layer was formed by a new bonding method. Biomolecule binding mechanism between streptavidin and biotin was used as a strong binding method for the formation of monolayered Au NPs on polymeric dielectric of poly vinyl alcohol (PVA). The self-assembled Au NPs was functioned to show storages of charge in the MPIS device. The binding by streptavidin and biotin was confirmed by AFM and UV-VIS. The UV-VIS absorption of the Au NPs was varied at 515 nm and 525 nm depending on the coating of streptavidin. The AFM image showed no formation of multi-stacked layers of the streptavidin-capped Au NPs on biotin-NHS layer. Capacitance-voltage (C-V) performance of the memory device was measured to investigate the charging effect from Au NPs. In addition, charge retention by the Au NPs storage was tested to show 10,000 s in the C-V curve.

  11. Effect of pore size on performance of monolithic tube chromatography of large biomolecules.

    Science.gov (United States)

    Podgornik, Ales; Hamachi, Masataka; Isakari, Yu; Yoshimoto, Noriko; Yamamoto, Shuichi

    2017-11-01

    Effect of pore size on the performance of ion-exchange monolith tube chromatography of large biomolecules was investigated. Radial flow 1 mL polymer based monolith tubes of different pore sizes (1.5, 2, and 6 μm) were tested with model samples such as 20 mer poly T-DNA, basic proteins, and acidic proteins (molecular weight 14 000-670 000). Pressure drop, pH transient, the number of binding site, dynamic binding capacity, and peak width were examined. Pressure drop-flow rate curves and dynamic binding capacity values were well correlated with the nominal pore size. While duration of the pH transient curves depends on the pore size, it was found that pH duration normalized on estimated surface area was constant, indicating that the ligand density is the same. This was also confirmed by the constant number of binding site values being independent of pore size. The peak width values were similar to those for axial flow monolith chromatography. These results showed that it is easy to scale up axial flow monolith chromatography to radial flow monolith tube chromatography by choosing the right pore size in terms of the pressure drop and capacity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. N-acetyl-L-histidine, a Prominent Biomolecule in Brain and Eye of Poikilothermic Vertebrates.

    Science.gov (United States)

    Baslow, Morris H; Guilfoyle, David N

    2015-04-24

    N-acetyl-L-histidine (NAH) is a prominent biomolecule in brain, retina and lens of poikilothermic vertebrates. In fish lens, NAH exhibits an unusual compartmentalized metabolism. It is synthesized from L-histidine (His) and acetyl Co-enzyme A. However, NAH cannot be catabolized by lens cells. For its hydrolysis, NAH is exported to ocular fluid where a specific acylase cleaves His which is then actively taken up by lens and re-synthesized into NAH. This energy-dependent cycling suggested a pump mechanism operating at the lens/ocular fluid interface. Additional studies led to the hypothesis that NAH functioned as a molecular water pump (MWP) to maintain a highly dehydrated lens and avoid cataract formation. In this process, each NAH molecule released to ocular fluid down its gradient carries with it 33 molecules of bound water, effectively transporting the water against a water gradient. In ocular fluid the bound water is released for removal from the eye by the action of NAH acylase. In this paper, we demonstrate for the first time the identification of NAH in fish brain using proton magnetic resonance spectroscopy (MRS) and describe recent evidence supporting the NAH MWP hypothesis. Using MRS, we also document a phylogenetic transition in brain metabolism between poikilothermic and homeothermic vertebrates.

  13. Differential fates of biomolecules delivered to target cells via extracellular vesicles.

    Science.gov (United States)

    Kanada, Masamitsu; Bachmann, Michael H; Hardy, Jonathan W; Frimannson, Daniel Omar; Bronsart, Laura; Wang, Andrew; Sylvester, Matthew D; Schmidt, Tobi L; Kaspar, Roger L; Butte, Manish J; Matin, A C; Contag, Christopher H

    2015-03-24

    Extracellular vesicles (EVs), specifically exosomes and microvesicles (MVs), are presumed to play key roles in cell-cell communication via transfer of biomolecules between cells. The biogenesis of these two types of EVs differs as they originate from either the endosomal (exosomes) or plasma (MVs) membranes. To elucidate the primary means through which EVs mediate intercellular communication, we characterized their ability to encapsulate and deliver different types of macromolecules from transiently transfected cells. Both EV types encapsulated reporter proteins and mRNA but only MVs transferred the reporter function to recipient cells. De novo reporter protein expression in recipient cells resulted only from plasmid DNA (pDNA) after delivery via MVs. Reporter mRNA was delivered to recipient cells by both EV types, but was rapidly degraded without being translated. MVs also mediated delivery of functional pDNA encoding Cre recombinase in vivo to tissues in transgenic Cre-lox reporter mice. Within the parameters of this study, MVs delivered functional pDNA, but not RNA, whereas exosomes from the same source did not deliver functional nucleic acids. These results have significant implications for understanding the role of EVs in cellular communication and for development of EVs as delivery tools. Moreover, studies using EVs from transiently transfected cells may be confounded by a predominance of pDNA transfer.

  14. Optimization of extraction conditions for secondary biomolecules from various plant species

    Directory of Open Access Journals (Sweden)

    Šibul Filip S.

    2016-01-01

    Full Text Available Extraction of plant secondary metabolites is an essential step in isolation of natural products. Non-optimized extraction conditions can lead to losses, degradation and modification of the biomolecules. In this paper, the influence of different solvent mixtures, solvent amounts, temperature, extraction time, and procedures for defatting on yield and profile of various classes of secondary metabolites was investigated. Rumex alpinus was used for the extraction of anthraquinones, Glycine max for isoflavonoids, Chaerophyllum bulbosum for flavonoids and phenolic acids, Anthriscus sylvestris for lignans and coumarins, alkaloids were extracted from Lupinus albus and sesquiterpene lactones from Artemisia absinthium. Extraction efficiency was evaluated by use of LC-DAD-ESI-MS/MS. The compromise extraction solvent for all of the examined compounds is 80 % methanol, mixed in ratio 13 : 1 with plant material. Maceration should last for six hours, repeated four times with fresh solvent. Defatting of the extracts does not lead to significant losses of the compounds of interest. It is acceptable to use extraction and evaporation temperature of 60ºC, while the extracts should be stored in the dark, on -20ºC. [Projekat Ministarstva nauke Republike Srbije, br. 172058

  15. A Practical Quantum Mechanics Molecular Mechanics Method for the Dynamical Study of Reactions in Biomolecules.

    Science.gov (United States)

    Mendieta-Moreno, Jesús I; Marcos-Alcalde, Iñigo; Trabada, Daniel G; Gómez-Puertas, Paulino; Ortega, José; Mendieta, Jesús

    2015-01-01

    Quantum mechanics/molecular mechanics (QM/MM) methods are excellent tools for the modeling of biomolecular reactions. Recently, we have implemented a new QM/MM method (Fireball/Amber), which combines an efficient density functional theory method (Fireball) and a well-recognized molecular dynamics package (Amber), offering an excellent balance between accuracy and sampling capabilities. Here, we present a detailed explanation of the Fireball method and Fireball/Amber implementation. We also discuss how this tool can be used to analyze reactions in biomolecules using steered molecular dynamics simulations. The potential of this approach is shown by the analysis of a reaction catalyzed by the enzyme triose-phosphate isomerase (TIM). The conformational space and energetic landscape for this reaction are analyzed without a priori assumptions about the protonation states of the different residues during the reaction. The results offer a detailed description of the reaction and reveal some new features of the catalytic mechanism. In particular, we find a new reaction mechanism that is characterized by the intramolecular proton transfer from O1 to O2 and the simultaneous proton transfer from Glu 165 to C2. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Radiolabeling optimization and characterization of 68Ga labeled DOTA–polyamido-amine dendrimer conjugate – Animal biodistribution and PET imaging results

    International Nuclear Information System (INIS)

    Ghai, Aanchal; Singh, Baljinder; Panwar Hazari, Puja; Schultz, Michael K.; Parmar, Ambika; Kumar, Pardeep; Sharma, Sarika; Dhawan, Devinder; Kumar Mishra, Anil

    2015-01-01

    The present study describes the optimization of 68 Ga radiolabeling with PAMAM dendrimer–DOTA conjugate. A conjugate (PAMAM–DOTA) concentration of 11.69 µM, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0 min and reaction temperature ranging between 90 and 100 °C. The decay corrected radiochemical yield was found to be 79.4±0.01%. The radiolabeled preparation ([ 68 Ga]-DOTA–PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0 h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 0.33% of the %ID/g accumulated in the tumor at 1 h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good ‘non-specific’ tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA–PAMAM-D conjugation with α V β 3 receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the 68 Ga labeled product for imaging and treating angiogenesis respectively. - Highlights: • Chemical conjugation of G-4 PAMAM dendrimers with DOTA-NHS carried out successfully. • Purification and characterization of the conjugate was done by SEC and MALDI-TOF. • Radiolabeling of PAMAM-DOTA-conjugate with 68Ga yielded high radiolabeling efficiency. • [ 68 Ga] DOTA–PAMAM-Dhas rapid blood clearance and excreted mainly through the kidneys. • No significant retention of the radiotracer was seen in any other organ.

  17. Proteopedia: a status report on the collaborative, 3D web-encyclopedia of proteins and other biomolecules.

    Science.gov (United States)

    Prilusky, Jaime; Hodis, Eran; Canner, David; Decatur, Wayne A; Oberholser, Karl; Martz, Eric; Berchanski, Alexander; Harel, Michal; Sussman, Joel L

    2011-08-01

    Proteopedia is a collaborative, 3D web-encyclopedia of protein, nucleic acid and other biomolecule structures. Created as a means for communicating biomolecule structures to a diverse scientific audience, Proteopedia (http://www.proteopedia.org) presents structural annotation in an intuitive, interactive format and allows members of the scientific community to easily contribute their own annotations. Here, we provide a status report on Proteopedia by describing advances in the web resource since its inception three and a half years ago, focusing on features of potential direct use to the scientific community. We discuss its progress as a collaborative 3D-encyclopedia of structures as well as its use as a complement to scientific publications and PowerPoint presentations. We also describe Proteopedia's use for 3D visualization in structure-related pedagogy. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Computational solvation analysis of biomolecules in aqueous ionic liquid mixtures : From large flexible proteins to small rigid drugs.

    Science.gov (United States)

    Zeindlhofer, Veronika; Schröder, Christian

    2018-04-23

    Based on their tunable properties, ionic liquids attracted significant interest to replace conventional, organic solvents in biomolecular applications. Following a Gartner cycle, the expectations on this new class of solvents dropped after the initial hype due to the high viscosity, hydrolysis, and toxicity problems as well as their high cost. Since not all possible combinations of cations and anions can be tested experimentally, fundamental knowledge on the interaction of the ionic liquid ions with water and with biomolecules is mandatory to optimize the solvation behavior, the biodegradability, and the costs of the ionic liquid. Here, we report on current computational approaches to characterize the impact of the ionic liquid ions on the structure and dynamics of the biomolecule and its solvation layer to explore the full potential of ionic liquids.

  19. Aequorin as a bioluminescent indicator for use in the determination of biomolecules in single cells. Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Sylvia Daunert

    2000-02-17

    During this funding period, the laboratories of Drs. Anderson and Daunert have performed a considerable amount of work toward addressing the issues associated with small volume analysis necessary for single cell studies. In that respect, their research has been focused on (1) developing new assays that can be miniaturized and are suitable for small volume and single cell analysis; (2) fabricating pL-vials that simulate the volume of single cells and setting up instrumentation capable of low-volume detection; (3) developing reproducible and reliable microinjection techniques; (4) developing methods of analysis for biomolecules in the pL-vials and employing these assays in the detection of biomolecules in single cells. The accomplishments attained in all these areas are described below. A total of 24 publications and 35 presentations have resulted from this work.

  20. PHOTOACTIVITY OF THE BIOMOLECULES AS A POSSIBLE FACTOR FOR CORRECTION OF TRGGER DEPENDENT SYSTEMS PROCESSES (FIRST REPORT

    Directory of Open Access Journals (Sweden)

    O. P. Mintser

    2015-12-01

    link create the conditions for accumulation and take into all of the known results of numerous studies. Using this approach were re-evaluated the targets of electromagnetic radiation of UV, visible and infrared spectra for correction of intracellular systems processes. The aim of this work was to create a concept of trigger biomolecules photoactivation of living cells as a correction factor of intracellular systems processes. Were used the content analysis, collocate analysis and the data obtained from the database of known and predicted biomolecules and interactions. It was developed the four resulting of light on trigger dependent systems processes of living cells: size; resonance; increasing of luminous flux power after polarization; asymmetric response of living systems. It was shown that physical and chemical properties of the biopolymers caused the possibilities for correction of trigger dependent processes and asymmetric response of living systems to the increase in total energy uptake to the system leads to activation of survival mechanisms.