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Sample records for antitumoral radiopharmaceutical 125i-crotoxin

  1. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical; Estudo do mecanismo de acao da crotoxina em tumores mamarios e avaliacao do seu potenctial radiofarmaceutico

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    Silveira, Marina Bicalho

    2010-07-01

    /cell high affinity binding sites; moreover, the radiolabeled polypeptide interaction showed low specificity toward to MCF-7 (37%). EGF reduced 20% of {sup 125}I-Crotoxin specific binding, so specific binding sites of Crotoxin on Ehrlich tumor cells partially overlap to EGFR. Crotoxin biodistribution studies showed significant uptake in the tumor paw (tumor/skeletal muscle ratio= 18.55), three hours after administration. SPECT imaging also showed tumor uptake confirming in vivo interaction with Ehrlich tumor cells. Crotoxin had an antitumoral effect on Ehrlich tumor cells and this action is due, at least partially, to the specific interaction with low and high affinity binding sites. Low affinity binding sites correlate EGFR and high affinity binding sites still need identification. These results confirm Crotoxin as a template for radiopharmaceutical design for cancer diagnosis and as a tool for cancer studies, increasing its biotechnological potential. (author)

  2. Biotechnological application of protein Leuc-B isolated from Bothrops leucurus venom as a prototype for antitumoral radiopharmaceutical;Aplicacao biotecnologica da proteina Leuc-B isolada da peconha de Bothrops leucurus como prototipo de radiofarmaco antitumoral

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    Gabriel, Lucilene Marcia

    2010-07-01

    solution and acridine/ethidium bromide indicate that the antitumoral effect of these substances occurs via apoptosis. Radioactive probes of Leuc-B ({sup 131}/{sup 125}I-Leuc-B) were synthesized with high specific activity and high radiochemical purity. Biodistribution studies, performed by intravenous injection and intratumoral flow in mice bearing Ehrlich tumor showed a significant tumor uptake Leuc-B ( p <0.05). These results show the potential of Leuc-B as a template for the development of drugs and radiopharmaceuticals for diagnosis and therapy of tumors. (author

  3. Organometallic Radiopharmaceuticals

    Science.gov (United States)

    Alberto, Roger

    Although molecular imaging agents have to be synthesized ultimately from aqueous solutions, organometallic complexes are becoming more and more important as flexible yet kinetically stable building blocks for radiopharmaceutical drug discovery. The diversity of ligands, targets, and targeting molecules related to these complexes is an essential base for finding novel, noninvasive imaging agents to diagnose and eventually treat widespread diseases such as cancer. This review article covers the most important findings toward these objectives accomplished during the past 3-4 years. The two major available organometallic building blocks will be discussed in the beginning together with constraints for market introduction as imposed by science and industry. Since targeting radiopharmaceuticals are a major focus of current research in molecular imaging, attempts toward so-called technetium essential radiopharmaceuticals will be briefly touched in the beginning followed by the main discussion about the labeling of targeting molecules such as folic acid, nucleosides, vitamins, carbohydrates, and fatty acids. At the end, some new strategies for drug discovery will be introduced together with results from organometallic chemistry in water. The majority of the new results have been achieved with the [99mTc(OH2)3(CO)3]+ complex which will, though not exclusively, be a focus of this review.

  4. Internal dosimetry of radiopharmaceuticals derived of antitumor polypeptide isolated from venoms: Crotalus durissus terrifucus and Scorpaena plumieri;Dosimetria interna de radiofarmacos derivados de polipeptideos antitumorais isolados dos venenos de: Crotalus durissus terrificus e Scorpaena plumieri

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    Andrade, Henrique Martins de

    2009-07-01

    The identification of new diagnostic and therapeutic agents capable of inhibiting tumor growth is essential for improving the prognosis of patients suffering from malignant tumors (glioma, breast and others). In this context, natural products (plants and animals) are a rich source of substances with potential antitumor. Despite knowledge of the etiology and pathology of tumors little progress has been observed in the area of diagnosis. Molecules of snake venoms have been shown to play an important role not only in the survival and proliferation of tumor cells but also in the process of tumor cell adhesion, migration and angiogenesis. Polypeptides isolated from the venom of the snake, Crotalus durissus terrificus, Crtx, and Scorpaena plumieri fish, SPGP, have antitumor activity against malignant tumors. It was shown that similar radio iodines Crtx and SPGP, {sup 125}I-Crtx and {sup 125}I-SPGP, can interact specifically with malignant tumors and induce cell death. Prototype-based radiopharmaceuticals Crtx and SPGP containing radioiodine 1311 were able to produce diagnostic images to accumulate specifically in the tumor site. The present study aimed at evaluating the potential radiological safety and diagnostic/therapeutic efficacy of {sup 131}I-Crtx {sup l31}I-SPGP and (evaluated from the biokinetic data in mice bearing Ehrlich tumor) were treated by the MIRD formalism to carry out internal dosimetry studies. Absorbed doses due to the uptake of {sup 131}I-Crtx and {sup 131}I-SPGP were determined in various organs of mice and implanted into the tumor. The results obtained for the animal model were extrapolated to humans by assuming a similar concentration ratio among the various tissues between mice and humans. In extrapolation, we used the masses of human organs of the phantom of Cristy/Eckerman. Both radiation penetrating and non penetrating of {sup 131}I on the tissue were considered in dose calculations. The absorbed dose in the bone marrow due to the

  5. Medicinal Radiopharmaceutical Chemistry of Metal Radiopharmaceuticals

    Science.gov (United States)

    Saw, Maung Maung

    2012-06-01

    Metal complexes have been used as medicinal compounds. Metals have advantageous features over organic compounds. Significant applications of metal complexes are in the field of nuclear medicine. Radiopharmaceuticals are drugs containing radioisotopes used for diagnostic and therapeutic purposes. The generalized targeting strategy for molecular imaging probe consists of three essential parts: (i) reporter unit or payload, (ii) carrier, and (iii) targeting system. Medicinal radiopharmaceutical chemistry pays special consideration to radioisotopes, as a reporter unit for diagnostic application or as a payload for therapeutic application. Targeting is achieved by a few approaches but the most common is the bifunctional chelator approach. While designing a radiopharmaceutical, a range of issues needs to be considered including properties of metal radioisotopes, bifunctional chelators, linkers, and targeting molecules. Designing radiopharmaceuticals requires consideration of two key words: "compounds of biological interest" and "fit for intended use." The ultimate goal is the development of new diagnostic methods and treatment. Diagnostic metal radiopharmaceuticals are used for SPECT and PET applications. Technetium chemistry constitutes a major portion of SPECT and gallium chemistry constitutes a major portion of PET. Therapeutic radiopharmaceuticals can be constructed by using alpha-, beta minus-, or Auger electron-emitting radiometals. Special uses of medicinal radiopharmaceuticals include internal radiation therapy, brachytherapy, immunoPET, radioimmunotherapy, and peptide receptor radionuclide imaging and therapy.

  6. Eleventh international symposium on radiopharmaceutical chemistry

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    NONE

    1995-12-31

    This document contains abstracts of papers which were presented at the Eleventh International Symposium on Radiopharmaceutical Chemistry. Sessions included: radiopharmaceuticals for the dopaminergic system, strategies for the production and use of labelled reactive small molecules, radiopharmaceuticals for measuring metabolism, radiopharmaceuticals for the serotonin and sigma receptor systems, labelled probes for molecular biology applications, radiopharmaceuticals for receptor systems, radiopharmaceuticals utilizing coordination chemistry, radiolabelled antibodies, radiolabelling methods for small molecules, analytical techniques in radiopharmaceutical chemistry, and analytical techniques in radiopharmaceutical chemistry.

  7. [Nuclear medicine and radiopharmaceuticals].

    Science.gov (United States)

    Sopena Novales, P; Plancha Mansanet, M C; Martinez Carsi, C; Sopena Monforte, R

    2014-06-01

    Nuclear Medicine is a medical specialty that allows modern diagnostics and treatments using radiopharmaceuticals original radiotracers (drugs linked to a radioactive isotope). In Europe, radiopharmaceuticals are considered a special group of drugs and thus their preparation and use are regulated by a set of policies that have been adopted by individual member countries. The radiopharmaceuticals used in diagnostic examinations are administered in very small doses. So, in general, they have no pharmacological action, side effects or serious adverse reactions. The biggest problem associated with their use are the alterations in their biodistribution that may cause diagnostic errors. Nuclear Medicine is growing considerably influenced by the appearance and development of new radiopharmaceuticals in both the diagnostic and therapeutic fields and primarily to the impact of new multimodality imaging techniques (SPECT-CT, PET-CT, PET-MRI, etc.). It's mandatory to know the limitations of these techniques, distribution and eventual physiological alterations of radiopharmaceuticals, contraindications and adverse reactions of radiological contrasts, and the possible interference of both.

  8. The development of cyclotron radiopharmaceuticals

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    Yang, Seung Dae; Chun, K. W.; Suh, Y. S.; Lee, J. D.; Ahn, S. H. and others

    1999-03-01

    The purpose of this project is to developthe radiopharmaceuticals and automatic synthetic unit for labelled compounds, and to establish mass production system of radiopharmaceuticals. These will contribute to the early diagnosis of the disease hard to cure. The contents of this project are as follows, the development of the radiopharmaceutical for imaging of cancer, the development of automatic synthesizer for the synthesis of radio-pharmaceuticals, the development of hormone derivatives labelled with {sup 12}'3I, the development of the radiopharmaceuticals for therapy of cancer labelled with cyclotron produced radionuclides, the development of radiopharmaceuticals for therapy of cancer labelled with cyclotron produced radionuclides, the development of radiopharmaceuticals for imaging of myocardial metabolism.

  9. Melanin-binding radiopharmaceuticals

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    Packer, S; Fairchild, R G; Watts, K P; Greenberg, D; Hannon, S J

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed. (PSB)

  10. Radiopharmaceuticals for diagnosis

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    Kuhl, D.E.

    1990-06-01

    During this grant period 1 January 1988--31 December 1990, we have successfully developed a number of new approaches to fluorine-18 labeled compounds, prepared several new radiotracers for both animal studies and eventual clinical trials, and explored the utility of a high-quality industrial robot in radiopharmaceutical applications. The progress during the last grant period is summarized briefly in the following sections. Publications arising from this research are listed below and can be found in Appendix I. 1 fig.

  11. Cyclotrons and positron emitting radiopharmaceuticals

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    Wolf, A.P.; Fowler, J.S.

    1984-01-01

    The state of the art of Positron Emission Tomography (PET) technology as related to cyclotron use and radiopharmaceutical production is reviewed. The paper discusses available small cyclotrons, the positron emitters which can be produced and the yields possible, target design, and radiopharmaceutical development and application. 97 refs., 12 tabs. (ACR)

  12. Nitroimidazole radiopharmaceuticals in bioimaging: part I: synthesis and imaging applications.

    Science.gov (United States)

    Sharma, Rakesh

    2011-10-01

    The paper is review on synthesis of nitroimidazole radiosensitizers useful in imaging of tumor cells. Nitroimidazole compounds are radiolabeled probes for specific use in imaging such as 18F for positron emission tomography; 99mTc for single photon emission computed tomography; 123I, or 131I for computer assisted tomography and 19F for magnetic resonance imaging. In synthesis of radiopharmaceutical compounds, parent nitroimidazole is modified to thiopyranosyl nucleosides, neuraminic acid derivatives followed by nitro group deprotection-substitution and radiolabeling by specific isotopes. Commercial attempts have been made to radiolabel the nitroimidazole by [18F]fluorine, [131I or 123I]iodine, [99mTc]technicium and [64Cu]copper on modified side chain of nitroimidazole compounds to design multimodal and multifunctional imaging techniques to detect and monitor the tumor hypoxia by measuring distribution of radiatiolabel or radiation. Nitroimidazole initially showed poor diffusion and poor stability in tissues with neurotoxicity concern limited its use as radiosensitizer. In last decade, several nitroimidazole derivatives were developed as potent less toxic and highly stable radiopharmaceuticals with optimized radiolabel concentration with high detectability of tumor oxygen or hypoxia. Currently, nitroimidazole based radiopharmaceuticals have emerged as multimodal and multifunctional hypoxia reporters with antitumor, anti-ischemic, anti-inflammatory and tumor targeting properties. In conclusion, nitroimidazole based radiopharmaceuticals are a new generation hypoxia biosensors for localized theradiagnostic utility in clinical medicine.

  13. PET radiopharmaceuticals for neuroreceptor imaging

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

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

  14. Development of radiopharmaceuticals

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    Park, Kyung Bae; Kim, J. R.; Shin, B. C.; Kim, Y. M.; Cho, U. K.; Han, K. H.; Chung, Y. J.; Shin, H. Y.; Hong, S. B.

    1997-09-01

    To overcome many problems caused by external radiation therapy, we have developed a new agent for internal radiation therapy, which is administered directly to the lesions and irradiate {beta}-rays resulting in maximized therapeutic effect and minimized radiation damage to normal tissues or organs to nearby. In the same reasons, we have also developed a new radioactive patch for the treatment of skin cancer using {beta}-emitting radionuclide. We prepared for {sup 166}Ho-chitosan complex ({sup 166}Ho-CHICO) which is potential radiopharmaceuticals for the treatment of liver cancer, peritoneal cancer metastasized from stomach cancer, ovarian cancer, and rheumatoid arthritis in knee joints. We carried out various experiments such as evaluation of absorbed dosimetry, studies on absorption, distribution, metabolism, and excretion (ADME) and clinical trials with {sup 166}Ho-CHICO. For commercialization of {sup 166}Ho-CHICO, we evaluated its toxicity, efficacy and safety, and then prepared documents for submission to the Mininstry of Health and Welfare to get license as an investigational new drug. {sup 166}Ho-Patch for skin cancer treatment was prepared by neutron irradiation of pre-made non-radioactive {sup 165}Ho-Patch. We evaluated the efficacy and safety of {sup 166}Ho-Patch in the treatment of skin cancer using an animal model and in clinical cases. (author). 49 refs., 15 tabs., 36 figs.

  15. Bone-seeking therapeutic radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Srivastava Suresh C.

    2002-01-01

    Full Text Available Bone-seeking therapeutic radiopharmaceuticals are utilized on the basis of the radionuclide?s particulate emissions (primarily low to intermediate beta emission. The requirements therefore are different from those of bone imaging agents that consist mainly of short-lived single photon emitters. Lately, the therapeutic bone seeking radiopharmaceuticals have attained increasing importance due to their potential role in alleviating pain from osseous metastases in cancer patients, for the treatment of joint pain resulting from inflamed synovium (radiosynoviorthesis, or radiosynovectomy, or from various other forms of arthritic disease. There is, however, a paucity of published data on the bio-pharmacokinetics of these agents when used following intravenous administration for bone pain palliation. This paper will briefly review and summarize the presently available chemical and biopharmacokinetic information on the various clinically approved as well as experimental bone-localizing therapeutic radiopharmaceuticals, and make projections on their clinical application for the treatment of primary/metastatic cancer in bone.

  16. Preparation of radiopharmaceuticals labeled with metal radionuclides

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    Welch, M.J.

    1992-06-01

    We recently developed a useful zinc-62/copper-62 generator and are presently evaluating copper-62 radiopharmaceuticals for clinical studies. While developing these copper-62 radiopharmaceuticals, in collaboration with the University of Missouri Research Reactor, Columbia we have also explored copper-64 radiopharmaceuticals. The PET images we obtained with copper-64 tracers were of such high quality that we have developed and evaluated copper-64 labeled antibodies for PET imaging. The major research activities described herein include: the development and assessment of gallium-68 radiopharmaceuticals; the development and evaluation of a new zinc-62/copper-62 generator and the assessment of copper-62 radiopharmaceuticals; mechanistic studies on proteins labeled with metal radionuclides.

  17. Bioinorganic Activity of Technetium Radiopharmaceuticals.

    Science.gov (United States)

    Pinkerton, Thomas C.; And Others

    1985-01-01

    Technetium radiopharmaceuticals are diagnostic imaging agents used in the field of nuclear medicine to visualize tissues, anatomical structures, and metabolic disorders. Bioavailability of technetium complexes, thyroid imaging, brain imaging, kidney imaging, imaging liver function, bone imaging, and heart imaging are the major areas discussed. (JN)

  18. Lymphoscintigraphy: radiopharmaceutical selection and methods

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    Kramer, E.L. (Memorial Sloan-Kettering Cancer Center, New York, NY (USA))

    1990-01-01

    The range of radiopharmaceuticals available for lymphoscintigraphy including radiocolloids, radiolabeled macromolecules and monoclonal antibodies are briefly discussed. The techniques used for tumour staging in internal mammary lymphoscintigraphy, iliopelvic lymphoscintigraphy, peripheral lymphoscintigraphy, localization of 'at risk' lymph nodes and lymphedema are also reviewed. (UK).

  19. Radiopharmaceuticals for diagnosis. Final report

    Energy Technology Data Exchange (ETDEWEB)

    1994-03-01

    In the period 1969-1986, this project was directed to the evolution of target-specific labeled chemicals useful for nuclear medical imaging, especially radioactive indicators suited to tracing adrenal functions and localizing tumors in the neuroendocrine system. Since 1986, this project research has focused on the chemistry of positron emission tomography (PET) ligands. This project has involved the evaluation of methods for radiochemical syntheses with fluorine-18, as well as the development and preliminary evaluation of new radiopharmaceuticals for positron emission tomography. In the radiochemistry area, the ability to predict fluorine-18 labeling yields for aromatic substitution reactions through the use of carbon-13 NMR analysis was studied. Radiochemical yields can be predicted for some structurally analogous aromatic compounds, but this correlation could not be generally applied to aromatic substrates for this reaction, particularly with changes in ring substituents or leaving groups. Importantly, certain aryl ring substituents, particularly methyl groups, appeared to have a negative effect on fluorination reactions. These observations are important in the future design of syntheses of complicated organic radiopharmaceuticals. In the radiopharmaceutical area, this project has supported the development of a new class of radiopharmaceuticals based on the monoamine vesicular uptake systems. The new radioligands, based on the tetrabenazine structure, offer a new approach to the quantification of monoaminergic neurons in the brain. Preliminary primate imaging studies support further development of these radioligands for PET studies in humans. If successful, such radiopharmaceuticals will find application in studies of the causes and treatment of neurodegenerative disorders such as Parkinson`s disease.

  20. Radiation dose estimates for radiopharmaceuticals

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    Stabin, M.G.; Stubbs, J.B.; Toohey, R.E. [Oak Ridge Inst. of Science and Education, TN (United States). Radiation Internal Dose Information Center

    1996-04-01

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.

  1. Radiopharmaceuticals drug interactions: a critical review

    Energy Technology Data Exchange (ETDEWEB)

    Santos-Oliveira, Ralph [Comissao Nacional de Energia Nuclear (CNEN/CRCN-NE), Recife, PE (Brazil). Centro Regional de Ciencias Nucleares. Servico de Controle de Qualidade]. E-mail: roliveira@cnen.gov.br; Smith, Sheila W. [University of Maryland, Baltimore, MF (United States). School of Pharmacy and Medicine. Dept. of Pharmaceutical Health Service Research; Carneiro-Leao, Ana Maria A. [Universidade Federal Rural de Pernambuco (UFRPE), Recife, PE (Brazil). Dept. de Morfologia e Fisiologia Animal

    2008-12-15

    Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance) or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here, we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions. (author)

  2. Radiopharmaceutical chemistry for positron emission tomography

    NARCIS (Netherlands)

    Elsinga, PH

    2002-01-01

    Radiopharmaceutical chemistry includes the selection, preparation, and preclinical evaluation of radiolabeled compounds. This paper describes selection criteria for candidates for positron emission tomography (PET) investigations. Practical aspects of nucleophilic and electrophilic F-18-fluorination

  3. Characterization of the anti tumoral activity of the thiosemicarbazones derived from N(4)-methyl-tolyl-2acetylpyridine And 2-pyridinoformamide and its metal complex: evaluation of the radiopharmaceutical potential; Caracterizacao da atividade antitumoral das tiossemicarbazonas derivadas de N(4)-metil-toluil-2-acetilpiridina e 2-piridinoformamida e seus complexos metalicos: avaliacao do potencial radiofarmaceutico

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Paulo Roberto Ornelas da

    2008-07-01

    Thiosemicarbazones have attracted great pharmacological interest because of their biological properties, such as cytotoxic activity against multiple strains of human tumors. The most studied compounds are pyridine-based because of their resemblance to pyridoxal metabolites that attach to co-enzyme B{sub 6}-dependant enzymes. This work aimed the characterization of the anti tumoral effect of N(4)-methyl-tolyl-2-acetylpyridine and 2-pyridinoformamide-derived thiosemicarbazones and the development of a radiopharmaceutical based on a thiosemicarbazone metal complex for positron emission tomography. In the first phase of this study were synthesized twenty-one thiosemicarbazones, derived from N(4)methyl-2 acetylpyridine and 2-pyridine formamide, as well as their metal complexes (Sn, Ga and Cu). Their cytotoxic potential were evaluated against brain and breast tumor cells in vitro. Our results showed all of them presented powerful cytotoxic and antiproliferative activities against glioblastoma multiform and breast adenocarcinoma at very low concentrations (nanomolar range). Morphological alterations characteristic of apoptosis, such as cell shrinkage, chromatin condensation were observed. Copper chloride was used as control and has presented IC50 at millimolar range suggesting that copper complexation with thiosemicarbazone significantly increases (more than 1 million) the anti tumoral effect of this metal. Due to the potent anti tumoral activity of N(4)-methyl-tolyl-2-acetylpyridine derived thiosemicarbazones and the excellent properties of {sup 64}Cu (T{sub 1/2} = 12.7 hours, {beta}{sup +}, {beta}{sup -}, and EC decay), at the second part for this work it was developed a new imaging agent (radiopharmaceutical) for tumor detection by positron emission tomography (PET). The radiopharmaceuticals were produced in the nuclear reactor TRIGA-IPR-R1 from CDTN, via neutron capture reaction {sup 63}Cu (n,{gamma}) {sup 64}Cu, of the copper complex N(4)-ortho-toluyl-2

  4. Radiopharmaceutical development of radiolabelled peptides

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    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  5. Applications of click chemistry in radiopharmaceutical development.

    Science.gov (United States)

    Walsh, Joseph C; Kolb, Hartmuth C

    2010-01-01

    Click chemistry, a concept that employs only practical and reliable transformations for compound synthesis, has made a significant impact in several areas of chemistry, including material sciences and drug discovery. The present article describes the use of click chemistry for the development of radiopharmaceuticals. Target templated in situ click chemistry was used for lead generation. The 1,2,3-triazole moiety was found to improve the pharmacokinetic properties of certain radiopharmaceuticals. The reliable Cu(I)-catalyzed click reaction was employed for radiolabeling of peptidic compounds without the need for protecting groups. In summary, the click chemistry approach for the discovery, optimization and labeling of new radiotracers, represents a very powerful tool for radiopharmaceutical development.

  6. Radiopharmaceuticals for imaging chronic lymphocytic inflammation

    NARCIS (Netherlands)

    Malviya, Gaurav; De Vries, Erik F. J.; Dierckx, Rudi A.; Signore, Alberto

    2007-01-01

    In the last few decades, a number of radiopharmaceuticals for imaging inflammation have been proposed that differ in their specificity and mechanism of uptake in inflamed foci as compared to the traditional inflammation imaging agents. Radiolabelled cytokines represent a reliable tool for the precli

  7. Radiopharmaceuticals in China. Current status and prospects

    Energy Technology Data Exchange (ETDEWEB)

    Jia, Hong-Mei; Liu, Bo-Li [Beijing Normal Univ. (China). Key Laboratory of Radiopharmaceuticals

    2014-04-01

    The review provides an overview of the current status of radiopharmaceuticals in China for in vivo clinical use and also describes some important advances in the past three decades. Development of the diagnostic and therapeutic radiopharmaceuticals as well as basic research on radiopharmaceutical chemistry are being introduced. The radiotracers developed in China include: (1) Brain perfusion imaging agents and CNS radiotracers for β-amyloid plaques, σ{sub 1} receptors, and dopamine D{sub 2} or D{sub 4} receptors; (2) {sup 99m}Tc- and {sup 18}F-labeled myocardial perfusion imaging agents; (3) tumor imaging agents including integrin-targeting radiotracer, novel sentinel lymph node imaging agents, hypoxia imaging agents, {sup 99m}Tc-labeled glucose derivatives, σ{sub 2} receptor imaging agents, folate receptor imaging agents, and potential radiotracers for imaging of human telomerase reverse transcriptase expression; (4) Potential infection imaging agents; (5) Potential asialoglycoprotein receptor imaging agents; (6) Other imaging agents. Moreover, some prospects of research and development of radiopharmaceuticals in the near future are discussed. (orig.)

  8. Simplification of Methods for PET Radiopharmaceutical Syntheses

    Energy Technology Data Exchange (ETDEWEB)

    Kilbourn, Michael, R.

    2011-12-27

    In an attempt to develop simplified methods for radiochemical synthesis of radiopharmaceuticals useful in Positron Emission Tomography (PET), current commercially available automated synthesis apparati were evaluated for use with solid phase synthesis, thin-film techniques, microwave-accelerated chemistry, and click chemistry approaches. Using combinations of these techniques, it was shown that these automated synthesis systems can be simply and effectively used to support the synthesis of a wide variety of carbon-11 and fluorine-18 labeled compounds, representing all of the major types of compounds synthesized and using all of the common radiochemical precursors available. These techniques are available for use to deliver clinically useful amounts of PET radiopharmaceuticals with chemical and radiochemical purities and high specific activities, suitable for human administration.

  9. Detection of sentinel nodes with radiopharmaceuticals

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    Yokoyama, Kunihiko; Michigishi, Takatoshi; Kinuya, Seigo; Konishi, Shota; Nakajima, Kenichi; Tonami, Norihisa [Kanazawa Univ. (Japan). School of Medicine

    2000-10-01

    Sentinel lymph nodes have been found to be an indicator of lymph node metastasis in breast cancer. In Japan, the theory and concept of sentinel lymph nodes in breast cancer have begun to be applied to carcinomas of the digestive system. Based on clinical experience in the detection of sentinel lymph nodes with radiopharmaceuticals, differences and similarities between the radiopharmaceuticals, methods, and techniques used to detect sentinel lymph nodes have been assessed in relation to breast cancer and carcinomas of the digestive system (including carcinomas of the esophagus and large intestine). The greatest difference between the methods used for breast and digestive cancers is the site of administration of the radiopharmaceutical. In breast cancer, the radiopharmaceutical is administered into a superficial organ (i.e., the mammary gland), whereas in carcinomas of the digestive system, it is administered into a deep organ (i.e., digestive tract). Another obvious difference is in lymph flow, i.e., the flow of the mammary glands is subcutaneous whereas lymph flow in the digestive tract is submucosal. Two radionuclide diagnostic methods are available to detect sentinel lymph nodes: sentinel lymphoscintigraphy with a gamma camera and a method that involves the use of a gamma probe intraoperatively. Radiopharmaceuticals used to detect sentinel lymph nodes must be smoothly transferred from the site of administration into the lymph, and uptake by the sentinel lymph node must continue for a long time without excessive flowing to lower reaches. The optimal particle size remains a matter of controversy, and no radiopharmaceuticals appropriate for lymphoscintigraphy have ever been approved in Japan. The authors compared the pharmacokinetics of three different radiopharmaceuticals used for sentinel lymphoscintigraphy in breast cancer ({sup 99m}Tc-labeled albumin, {sup 99m}Tc-labeled tin colloid, and {sup 99m}Tc-labeled phytic acid) and founded that the detection rate was

  10. Radiopharmaceuticals drug interactions: a critical review

    Directory of Open Access Journals (Sweden)

    Ralph Santos-Oliveira

    2008-12-01

    Full Text Available Radiopharmaceuticals play a critical role in modern medicine primarily for diagnostic purposes, but also for monitoring disease progression and response to treatment. As the use of image has been increased, so has the use of prescription medications. These trends increase the risk of interactions between medications and radiopharmaceuticals. These interactions which have an impact on image by competing with the radiopharmaceutical for binding sites for example can lead to false negative results. Drugs that accelerate the metabolism of the radiopharmaceutical can have a positive impact (i.e. speeding its clearance or, if repeating image is needed, a negative impact. In some cases, for example in cardiac image among patients taking doxirubacin, these interactions may have a therapeutic benefit. The incidence of drug-radiopharmaceuticals adverse reactions is unknown, since they may not be reported or even recognized. Here,we compiled the medical literature, using the criteria of a systematic review established by the Cochrane Collaboration, on pharmaceutical-drug interactions to provide a summary of documented interactions by organ system and radiopharmaceuticals. The purpose is to provide a reference on drug interactions that could inform the nuclear medicine staff in their daily routine. Efforts to increase adverse event reporting, and ideally consolidate reports worldwide, can provide a critically needed resource for prevention of drug-radiopharmaceuticals interactions.Os radiofármacos desempenham função crítica na medicina moderna, primariamente para fins diagnósticos, mas também no monitoramento da progressão de doenças assim como na avaliação de respostas ao tratamento. O uso da tecnologia por imagem tem crescido e conseqüentemente as prescrições de medicamentos (radiofármacos em especial com esse propósito. Este fato, aumenta o risco de interações entre medicamentos e radiofármacos. Interações que podem ter um impacto na

  11. Application of a small molecule radiopharmaceutical concept to improve kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min [Dept. of Nuclear Medicine, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    Recently, large molecules or nanoparticles are actively studied as radiopharmaceuticals. However, their kinetics is problematic because of a slow penetration through the capillaries and slow distribution to the target. To improve the kinetics, a two-step targeting method can be applied by using small molecules and very rapid copper-free click reaction. Although this method might have limitations such as internalization of the first targeted conjugate, it will provide high target-to-non-target ratio imaging of radiopharmaceuticals. The majority of radiopharmaceuticals belong to small molecules of which the molecular weight is less than 2000 Da, and the molecular size is smaller than 2 nm generally. The outstanding feature of the small molecule radiopharmaceuticals compared to large molecules is with their kinetics. Their distribution to target and clearance from non-target tissues are very rapid, which is the essential requirement of radiopharmaceuticals. In conclusion, the small molecule radiopharmaceuticals generally show excellent biodistribution properties; however, they show poor efficiency of radioisotope delivery. Large molecule or nanoparticle radiopharmaceuticals have advantages of multimodal and efficient delivery, but lower target-to-non-target ratio. Two-step targeting using a bio-orthogonal copper-free click reaction can be a solution of the problem of large molecule or nanoparticle radiopharmaceuticals. The majority of radiopharmaceuticals belong to small molecules of which the molecular weight is less than 2000 Da, and the molecular size is smaller than 2 nm generally. The outstanding feature of the small molecule radiopharmaceuticals compared to large molecules is with their kinetics. Their distribution to target and clearance from non-target tissues are very rapid, which is the essential requirement of radiopharmaceuticals.

  12. Preparation of Radiopharmaceuticals Labeled with Metal Radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    2012-02-16

    The overall goal of this project was to develop methods for the production of metal-based radionuclides, to develop metal-based radiopharmaceuticals and in a limited number of cases, to translate these agents to the clinical situation. Initial work concentrated on the application of the radionuclides of Cu, Cu-60, Cu-61 and Cu-64, as well as application of Ga-68 radiopharmaceuticals. Initially Cu-64 was produced at the Missouri University Research Reactor and experiments carried out at Washington University. A limited number of studies were carried out utilizing Cu-62, a generator produced radionuclide produced by Mallinckrodt Inc. (now Covidien). In these studies, copper-62-labeled pyruvaldehyde Bis(N{sup 4}-methylthiosemicarbazonato)-copper(II) was studied as an agent for cerebral myocardial perfusion. A remote system for the production of this radiopharmaceutical was developed and a limited number of patient studies carried out with this agent. Various other copper radiopharmaceuticals were investigated, these included copper labeled blood imaging agents as well as Cu-64 labeled antibodies. Cu-64 labeled antibodies targeting colon cancer were translated to the human situation. Cu-64 was also used to label peptides (Cu-64 octriatide) and this is one of the first applications of a peptide radiolabeled with a positron emitting metal radionuclide. Investigations were then pursued on the preparation of the copper radionuclides on a small biomedical cyclotron. A system for the production of high specific activity Cu-64 was developed and initially the Cu-64 was utilized to study the hypoxic imaging agent Cu-64 ATSM. Utilizing the same target system, other positron emitting metal radionuclides were produced, these were Y-86 and Ga-66. Radiopharmaceuticals were labeled utilizing both of these radionuclides. Many studies were carried out in animal models on the uptake of Cu-ATSM in hypoxic tissue. The hypothesis is that Cu-ATSM retention in vivo is dependent upon the

  13. Trends in radiopharmaceutical dispensing in a regional nuclear pharmacy

    Energy Technology Data Exchange (ETDEWEB)

    Basmadjian, G.P.; Johnston, J.; Barker, K.; Ice, R.D.

    1982-11-01

    Dispensing trends for radiopharmaceuticals at a regional nuclear pharmacy over a 51-month period were studied. dispensing records of a regional nuclear pharmacy were analyzed with a forecasting procedure that uses univariate time data to produce time trends and autoregressive models. The overall number of prescriptions increased from 3500 to 5500 per quarter. Radiopharmaceuticals used in nuclear cardiology studies increased from less than 0.1% to 17.5% of total prescriptions dispensed, while radiopharmaceuticals used for brain imaging showed a steady decline from 29% to 11% of total prescriptions dispensed. The demand for other radiopharmaceuticals increased in areas such as renal studies, bone studies, lung studies, liver-function studies, and /sup 67/Ga tumor-uptake studies, and declined slightly for static liver studies. Changes in dispensing trends for radiopharmaceuticals will continue as the practice of nuclear medicine concentrates more on functional studies and as newer imaging techniques become used for other purposes.

  14. Placental transfer of radiopharmaceuticals and dosimetry in pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Russell, J.R. [Univ. of Maryland, Baltimore, MD (United States); Stabin, M.G.; Sparks, R.B. [Oak Ridge Inst. for Science and Education, TN (United States)

    1999-01-01

    The calculation of radiation dose estimates to the fetus is often important in nuclear medicine. To obtain the best estimates of radiation dose to the fetus, the best biological and physical models should be employed. In this paper, after identification of radiopharmaceuticals often administered to women of childbearing age, the most recent data available on the placental crossover of these radiopharmaceuticals was used (with standard kinetic models describing the maternal distribution and retention and with the best available physical models) to obtain fetal dose estimates for these radiopharmaceuticals were identified as those most commonly administered to women of childbearing years. The literature yielded information on placental crossover of 15 radiopharmaceuticals, from animal or human data. Radiation dose estimates are presented in early pregnancy and at 3-, 6-, and 9-months gestation for these radiopharmaceuticals, as well as for many others used in nuclear medicine (the latter considering only maternal organ contributions to fetal dose). 46 refs., 1 fig., 5 tabs.

  15. Use of radiopharmaceuticals in Finland in 1997

    Energy Technology Data Exchange (ETDEWEB)

    Korpela, H

    1999-04-01

    The use of radiopharmaceuticals in diagnostics and therapy has been surveyed by STUK - Radiation and Nuclear Safety Authority. In 1997 the number of nuclear medicine examinations was 51,700, and the number of treatments 2,240. In 1994 the number of nuclear medicine examinations had been 50,900, and the number of treatments 2,150. In 1997 the collective effective dose received by patients was 207 manSv, and the mean effective dose received by the population was 0.04 mSv per person. In 1994 the collective effective dose had been 220 manSv. Numbers of nuclear medicine examinations and treatments have not changed much from 1994. The collective effective dose has slightly decreased. The main reason for the reduction is decreased use of the radionuclide {sup 131}I. (orig.) 4 refs.

  16. Production of bromine-75, a new radionuclide for marking radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Paans, A.M.J.; Wiegman, T.; Hoeve, W.; Vaalburg, W. (Rijksuniversiteit Groningen (Netherlands). Academisch Ziekenhuis)

    1982-01-01

    Bromine-75 is the most useful of all bromine isotopes for nuclear medicine. Its properties like half-life, nuclear reactions, production and chemical preparation, as well as the preparation of radiopharmaceuticals containing bromine-75 are presented.

  17. Preparation of radiopharmaceutical formulations; Fremstilling av radioaktive farmasoeytiske blandinger

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.; Garlich, J.R.; Frank, R.K.; McMillan, K

    1998-03-16

    Radiopharmaceutical formulations for complexes comprising at least one radionuclide complexed with a ligand, or its physiologically-acceptable salts thereof, especially {sup 153}samarium-ethylenediaminetetramethylenephosphonic acid, which optionally contains a divalent metal ion, e.g. calcium, and is frozen, thawed, and then administered by injection. Alternatively, the radiopharmaceutical formulations must contain the divalent metal and are frozen only if the time before administration is sufficiently long to cause concern for radiolysis of the ligand. 2 figs., 9 tabs.

  18. (Coordinated research of chemotherapeutic agents and radiopharmaceuticals)

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, P.C.

    1991-01-14

    The traveler received a United Nations Development Program (UNDP) Award for Distinguished Scientists to visit Indian Research Institutions including Central Drug Research Institute (CDRI), Lucknow, the host institution, in cooperation with the Council of Scientific and Industrial Research (CSIR) of India. At CDRI, the traveler had meetings to discuss progress and future directions of on-going collaborative research work on nucleosides and had the opportunity to initiate new projects with the divisions of pharmacology, biopolymers, and membrane biology. As a part of this program, the traveler also visited Sanjay Gandhi Post Graduate Institute (SGPI) of Medical Sciences, Lucknow; Board of Radiation and Isotope Technology (BRIT) and Bhabha Atomic Research Center (BARC), Bombay; Variable Energy Cyclotron Center (VECC) and Indian Institute of Chemical Biology, Calcutta. He also attended the Indo-American Society of Nuclear Medicine Meeting held in Calcutta. The traveler delivered five seminars describing various aspects of radiopharmaceutical development at the Oak Ridge National Laboratory (ORNL) and discussed the opportunities for exchange visits to ORNL by Indian scientists.

  19. Drug interaction with radiopharmaceuticals: a review

    Energy Technology Data Exchange (ETDEWEB)

    Bernardo-Filho, Mario; Santos-Filho, Sebastiao David; Moura, Egberto Gaspar de; Maiworm, Adalgisa Ieda; Bernardo, Luciana Camargo; Brito, Lavinia de Carvalho [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Orlando, Margarida Maria de Camoes [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Hospital Universitario Pedro Ernesto. Setor de Medicina Nuclear; Penas, Maria Exposito [Universidade Federal do Rio de Janeiro, RJ (Brazil). Hospital Universitario Clementino Fraga Filho. Setor de Medicina Nuclear; Cardoso, Valbert Nascimento [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Faculdade de Farmacia. Lab. de Radioisotopos

    2005-10-15

    Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99m T, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemo perfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.(author)

  20. Auger Emitting Radiopharmaceuticals for Cancer Therapy

    Science.gov (United States)

    Falzone, Nadia; Cornelissen, Bart; Vallis, Katherine A.

    Radionuclides that emit Auger electrons have been of particular interest as therapeutic agents. This is primarily due to the short range in tissue, controlled linear paths and high linear energy transfer of these particles. Taking into consideration that ionizations are clustered within several cubic nanometers around the point of decay the possibility of incorporating an Auger emitter in close proximity to the cancer cell DNA has immense therapeutic potential thus making nuclear targeted Auger-electron emitters ideal for precise targeting of cancer cells. Furthermore, many Auger-electron emitters also emit γ-radiation, this property makes Auger emitting radionuclides a very attractive option as therapeutic and diagnostic agents in the molecular imaging and management of tumors. The first requirement for the delivery of Auger emitting nuclides is the definition of suitable tumor-selective delivery vehicles to avoid normal tissue toxicity. One of the main challenges of targeted radionuclide therapy remains in matching the physical and chemical characteristics of the radionuclide and targeting moiety with the clinical character of the tumor. Molecules and molecular targets that have been used in the past can be classified according to the carrier molecule used to deliver the Auger-electron-emitting radionuclide. These include (1) antibodies, (2) peptides, (3) small molecules, (4) oligonucleotides and peptide nucleic acids (PNAs), (5) proteins, and (6) nanoparticles. The efficacy of targeted radionuclide therapy depends greatly on the ability to increase intranuclear incorporation of the radiopharmaceutical without compromising toxicity. Several strategies to achieve this goal have been proposed in literature. The possibility of transferring tumor therapy based on the emission of Auger electrons from experimental models to patients has vast therapeutic potential, and remains a field of intense research.

  1. Technetium-99m radiopharmaceuticals for in vivo diagnostics

    Directory of Open Access Journals (Sweden)

    Đokić Divna Đ.

    2005-01-01

    Full Text Available Technetiiim-99m is an ideal radionuclide with optimum decay characteristics. It can be obtained in sterile, pyrogen-free and carrier-free condition, as sodium pertechnetate (Na99mTcO4, from 99Mo/99Tc generator. Because of its six-hour physical half-life and monochromatic 140 keV photons free of -radiation, administration of small amounts of 99mTc solution is possible, without a significant radiation damage to the patient. Technetium eluted from the 99Mo/99mTc generator is in the highest oxidation form (+7. It can be used for diagnostic purposes alone, but it is often used for labeling different organic and inorganic compounds. As it is unreactive, reduction with a chemical reductant, (+1, (+3 and (+5 oxidation are necessary before use. Nowadays almost 80% of radiopharmaceuticals are based on 99mTc. Radiopharmaceuticals. Radiopharmaceuticals are radionuclides or radioactive compounds used in diagnosis and therapy of human diseases. A pharmaceutical is chosen based on its localization in the organ, or its participation in its physiological function. Radiation emitted from a radionuclide is detected by a radiation detector. The ability to incorporate available radionuclides into tracer molecules has been the main goal in developing radiopharmaceuticals. As radionuclides with nuclear characteristics used as either diagnostic or therapeutic radiopharmaceuticals, are predominantly metals, they can be designed as metal essential, whereby biological distribution is determined by coordination compound, or metal tagged, in which case the properties of the carrier molecule (ligand system determine the biological distribution. This paper reviews the development of 99mTc-radiopharmaceuticals. .

  2. Drug interaction with radiopharmaceuticals: a review

    Directory of Open Access Journals (Sweden)

    Mario Bernardo-Filho

    2005-10-01

    Full Text Available Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99mT, can also be modified. These factors include drugs (synthetic and natural and dietary conditions, as well as some medical procedures (invasive or non-invasive, such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemoperfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.Imagens clínicas são valiosas em Ciências da Saúde e a análise e a interpretação correta das mesmas auxiliam os profissionais, como médico, fisioterapeuta, terapeuta ocupacional, na tomada de decisões e subseqüentes ações terapêuticas e/ou de reabilitação. Além das doenças outros fatores podem interferir e afetar a biodisponibilidade dos radiofármacos (radiobiocomplexos e a qualidade das imagens (SPECT e PET. Além disso, a marcação de alguns desses radiobiocomplexos com Tc-99m, como proteínas plasmáticas, leucócitos e hemácias, também pode ser modificada. Entre esses fatores, estão drogas (sintéticas e naturais e condições alimentares, assim como alguns procedimentos médicos (invasivos e não invasivos, como a radioterapia, processos cirúrgicos, pr

  3. Preparation of radiopharmaceuticals labeled with metal radionuclides. Progress report, July 1, 1988--June 30, 1992

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1992-06-01

    We recently developed a useful zinc-62/copper-62 generator and are presently evaluating copper-62 radiopharmaceuticals for clinical studies. While developing these copper-62 radiopharmaceuticals, in collaboration with the University of Missouri Research Reactor, Columbia we have also explored copper-64 radiopharmaceuticals. The PET images we obtained with copper-64 tracers were of such high quality that we have developed and evaluated copper-64 labeled antibodies for PET imaging. The major research activities described herein include: the development and assessment of gallium-68 radiopharmaceuticals; the development and evaluation of a new zinc-62/copper-62 generator and the assessment of copper-62 radiopharmaceuticals; mechanistic studies on proteins labeled with metal radionuclides.

  4. Labeling radiopharmaceuticals with Se-75: using Se-75 selenious acid

    Energy Technology Data Exchange (ETDEWEB)

    Sadek, S.A.; Basmadjian, G.P.; Ice, R.D. (Oklahoma Univ., Oklahoma City (USA). Health Sciences Center)

    1982-08-01

    A cheap, easy method of introducing high specific activity Se-75 into radiopharmaceuticals is described. Se-75 selenious acid is reduced with NaBH/sub 4/ producing the nucleophile NaHSe. Using this method, a fatty acid, cholesterol, estrogen and phenethylamine are all labelled with Se-75.

  5. Harvard-MIT research program in short-lived radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J.

    1991-01-01

    This report presents research on radiopharmaceuticals. The following topics are discussed: antibody labeling with positron-emitting radionuclides; antibody modification for radioimmune imaging; labeling antibodies; evaluation of technetium acetlyacetonates as potential cerebral blood flow agents; and studies in technetium chemistry. (CBS)

  6. Infection imaging with radiopharmaceuticals in the 21st century

    Energy Technology Data Exchange (ETDEWEB)

    Das, Satya S.; Wareham, David W. [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Medical Microbiology; Britton, Keith E. [St. Bartholomew' s Hospital, London (United Kingdom). Dept. of Nuclear Medicine; Hall, Anne V. [Harefield Hospital, Middlesex (United Kingdom). Microbiology Dept.

    2002-09-01

    Infection continues to be a major cause of morbidity and mortality worldwide. Nuclear medicine has an important role in aiding the diagnosis of particularly deep-seated infections such as abscesses, osteomyelitis, septic arthritis, endocarditis, and infections of prosthetic devices. Established techniques such as radiolabelled leucocytes are sensitive and specific for inflammation but do not distinguish between infective and non-infective inflammation. The challenge for Nuclear Medicine in infection imaging in the 21st century is to build on the recent trend towards the development of more infection specific radiopharmaceuticals, such as radiolabelled anti-infectives (e.g. 99 m Tc ciprofloxacin). In addition to aiding early diagnosis of infection, through serial imaging these agents might prove very useful in monitoring the response to and determining the optimum duration of anti-infective therapy. This article reviews the current approach to infection imaging with radiopharmaceuticals nd the future direction it might take. (author)

  7. Pharmacokinetics of SPECT radiopharmaceuticals for imaging hypoxic tissues.

    Science.gov (United States)

    Wiebe, L I; Stypinski, D

    1996-09-01

    Although hypoxia has been known for decades to play an important role in the outcome of radiotherapy in oncology, and inspite of the contribution of hypoxia to a myriad of pathologies that involve vascular disease, the selective imaging of hypoxic tissue has attained prominence only within the past decade. Contemporary research in the hypoxia imaging field is based largely on radiosensitizer research of the 1960's and 1970's. Early sensitizer research identified a family of nitro-organic compounds, the N-1 substituted 2-nitroimidazoles as candidate drugs. The early champion, and still the reference standard for therapeutic radiosensitization of hypoxic tumor cells is misonidazole (MISO). Its peripheral neurotoxicity led to failure in clinical studies, but its biological, biophysical and biochemical properties have been investigated in detail and serve as a basis for further design, not only of sensitizers, but of diagnostic radiopharmaceuticals for imaging tissue hypoxia. Pharmacokinetic characterization of radiopharmaceuticals, specifically radiopharmaceuticals for imaging tissue hypoxia, has not been a central theme in their development. The advent of PET, through which quantitative determinations first became possible, opened the field for both descriptive and analytical radiopharmacokinetic studies. In SPECT, however, this approach is still undergoing refinement. This paper addresses some of the underlying issues in radiopharmaceutical pharmacokinetics. There is a paucity of published radiopharmacokinetic data for SPECT hypoxia imaging agents. Consequently, the pharmacokinetic issues for MISO are presented as a basis for development of pharmacokinetics for the chemically-related imaging agents. Properties of an hypoxia marker are described from a pharmacokinetic viewpoint, a theoretical model for descriptive pharmacokinetics is introduced and finally, recent pharmacokinetic studies from our laboratory are described.

  8. Radiopharmaceuticals and other compounds labelled with short-lived radionuclides

    CERN Document Server

    Welch, Michael J

    2013-01-01

    Radiopharmaceuticals and Other Compounds Labelled with Short-Lived Radionuclides covers through both review and contributed articles the potential applications and developments in labeling with short-lived radionuclides whose use is restricted to institutions with accelerators. The book discusses the current and potential use of generator-produced radionuclides as well as other short-lived radionuclides, and the problems of quality control of such labeled compounds. The book is useful to nuclear medicine physicians.

  9. Improving radiopharmaceutical supply chain safety by implementing bar code technology.

    Science.gov (United States)

    Matanza, David; Hallouard, François; Rioufol, Catherine; Fessi, Hatem; Fraysse, Marc

    2014-11-01

    The aim of this study was to describe and evaluate an approach for improving radiopharmaceutical supply chain safety by implementing bar code technology. We first evaluated the current situation of our radiopharmaceutical supply chain and, by means of the ALARM protocol, analysed two dispensing errors that occurred in our department. Thereafter, we implemented a bar code system to secure selected key stages of the radiopharmaceutical supply chain. Finally, we evaluated the cost of this implementation, from overtime, to overheads, to additional radiation exposure to workers. An analysis of the events that occurred revealed a lack of identification of prepared or dispensed drugs. Moreover, the evaluation of the current radiopharmaceutical supply chain showed that the dispensation and injection steps needed to be further secured. The bar code system was used to reinforce product identification at three selected key stages: at usable stock entry; at preparation-dispensation; and during administration, allowing to check conformity between the labelling of the delivered product (identity and activity) and the prescription. The extra time needed for all these steps had no impact on the number and successful conduct of examinations. The investment cost was reduced (2600 euros for new material and 30 euros a year for additional supplies) because of pre-existing computing equipment. With regard to the radiation exposure to workers there was an insignificant overexposure for hands with this new organization because of the labelling and scanning processes of radiolabelled preparation vials. Implementation of bar code technology is now an essential part of a global securing approach towards optimum patient management.

  10. GMP compliant radiosynthesis of11C and18F-labeled PET radiopharmaceuticals with a modular disposable cassette system

    NARCIS (Netherlands)

    Hessels-Scheper, J.G.; Maarsingh, P.; Kwizera, C.; Zijlma, R.; Maas, B.; De Vries, A.M.T.; Antunes, I.F.; Lub-de Hooge, M.N.; Boersma, H.H.; Dierckx, R.A.J.O.; De Vries, E.F.J.; Luurtsema, G.; Elsinga, P.H.

    2014-01-01

    Background Many nuclear medicine departments have an extensive radiopharmaceutical portfolio. Consequently, these multiple PET radiopharmaceuticals have to be produced with the same synthesis module. An important consideration in GMP-compliant PET production is to avoid potential cross-contamination

  11. Public exposure due to the transport of radiopharmaceuticals; Exposicao do publico devido ao transporte de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Demerval L.; Carneiro, Janete C.G.G.; Sanches, Matias P.; Sordi, Gian Maria A.A., E-mail: dlrodri@ipen.b, E-mail: janetegc@ipen.b, E-mail: msanches@ipen.b, E-mail: gsordi@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-10-26

    This paper estimate the radiological impact resulting from radiopharmaceuticals transport from the IPEN to some destinations defined a priori. So, doses were estimated in the public individuals, which are in the streets and vehicles that transit near the public transport, alongside the itinerary went through by packages, during the realization of radiopharmaceuticals transport

  12. In-vivo behavior of tin-radiopharmaceuticals

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Tin is an essential ingredient of most technetium-99m radiopharmaceuticals but its in-vivo distribution and long-term fate are not well understood. This work describes distribution in mice of several tin-117m labeled compounds. The results indicate that stannic-HEDTMP appears to be the best overall bone localizing agent with very low blood, muscle, kidney, or liver uptake, and its binding to bone is higher than that of tin-117m-DTPA, which make it potentially useful as an agent for skeletal scintigraphy and radiotherapy of bone tumors.

  13. Radiopharmaceuticals introduction to drug evaluation and dose estimation

    CERN Document Server

    Williams, Lawerence E

    2010-01-01

    Nanoengineering, energized by the desire to find specific targeting agents, is leading to dramatic acceleration in novel drug design. However, in this flurry of activity, some issues may be overlooked. This is especially true in the area of determining dosage and evaluating the effects of multiple agents designed to target more than one site of metastasis. Offering the unique perspective of a medical physicist who has worked directly with cancer patients for over three decades, Radiopharmaceuticals: Introduction to Drug Evaluation and Dose Estimation starts by exploring the recent history and

  14. Molecular Engineering of Technetium and Rhenium Based Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Zubieta, J.

    2003-06-30

    The research was based on the observation that despite the extraordinarily rich coordination chemistry of technetium and rhenium and several notable successes in reagent design, the extensive investigations by numerous research groups on a variety of N{sub 2}S{sub 2} and N{sub 3}S donor type ligands and on HYNIC have revealed that the chemistries of these ligands with Tc and Re are rather complex, giving rise to considerable difficulties in the development of reliable procedures for the development of radiopharmaceutical reagents.

  15. A Peltier thermal cycling unit for radiopharmaceutical synthesis

    Energy Technology Data Exchange (ETDEWEB)

    McKinney, C.J.; Nader, M.W

    2001-01-15

    We have investigated the use of Peltier devices to rapidly cycle the temperature of reaction vessels in a radiopharmaceutical synthesis system. Peltier devices have the advantage that they can be actively cooled as well as heated, allowing precise and rapid control of vessel temperatures. Reaction vessel temperatures of between -6 deg. C and 110 deg. C have been obtained with commercially available devices with reasonable cycle times. Two devices have been used as the basis for a general purpose, two-pot synthesis system for production of [{sup 11}C] compounds such as raclopride.

  16. A Peltier thermal cycling unit for radiopharmaceutical synthesis.

    Science.gov (United States)

    McKinney, C J; Nader, M W

    2001-01-01

    We have investigated the use of Peltier devices to rapidly cycle the temperature of reaction vessels in a radiopharmaceutical synthesis system. Peltier devices have the advantage that they can be actively cooled as well as heated, allowing precise and rapid control of vessel temperatures. Reaction vessel temperatures of between -6 degrees C and 110 degrees C have been obtained with commercially available devices with reasonable cycle times. Two devices have been used as the basis for a general purpose, two-pot synthesis system for production of [11C] compounds such as raclopride.

  17. 68Ga-Based Radiopharmaceuticals: Production and Application Relationship

    Directory of Open Access Journals (Sweden)

    Irina Velikyan

    2015-07-01

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

  18. Guidance for nuclear medicine staff on radiopharmaceuticals drug interaction

    Directory of Open Access Journals (Sweden)

    Ralph Santos-Oliveira

    2009-12-01

    Full Text Available Numerous drug interactions related to radiopharmaceuticals take place every day in hospitals many of which are not reported or detected. Information concerning this kind of reaction is not abundant, and nuclear medicine staff are usually overwhelmed by this information. To better understand this type of reaction, and to help nuclear medicine staff deal with it, a review of the literature was conducted. The results show that almost all of radiopharmaceuticals marketed around the world present drug interactions with a large variety of compounds. This suggests that a logical framework to make decisions based on reviews incorporating adverse reactions must be created. The review also showed that researchers undertaking a review of literature, or even a systematic review that incorporates drug interactions, must understand the rationale for the suggested methods and be able to implement them in their review. Additionally, a global effort should be made to report as many cases of drug interaction with radiopharmaceuticals as possible. With this, a complete picture of drug interactions with radiopharmaceuticals can be drawn.Diversos casos de interações medicamentosas com radiofármacos ocorrem diariamente na rotina hospitalar, contudo muitos deles não são notificados ou mesmo percebidos. Informações a respeito desse tipo de reação não é abundante e os profissionais da medicina nuclear muitas vezes estão assoberbados por essas informações. De modo a entender esse tipo de reação e auxiliar a medicina nuclear a lidar com essa situação uma revisão da literatura foi realizada. Os resultados mostraram que a totalidade dos radiofármacos comercializados no mundo apresentam interação medicamentosa com uma enorme variedade de outros medicamentos. Dessa forma sugere-se que revisões sobre radiofármacos inclua um capítulo sobre efeitos adversos. Além disso, um esforço mundial para notificar efeitos adversos deve ser realizado, pois somente

  19. Basics and principles of radiopharmaceuticals for PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Wadsak, W. [Department of Nuclear Medicine, Medical University of Vienna (Austria); Mitterhauser, M. [Department of Nuclear Medicine, Medical University of Vienna (Austria); Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

    2010-03-15

    The presented review provides general background on PET radiopharmaceuticals for oncological applications. Special emphasis is put on radiopharmacological, radiochemical and regulatory aspects. This review is not meant to give details on all different PET tracers in depth but to provide insights into the general principles coming along with their preparation and use. The PET tracer plays a pivotal role because it provides the basis both for image quality and clinical interpretation. It is composed of the radionuclide (signaller) and the molecular vehicle which determines the (bio-)chemical properties (e.g. binding characteristics, metabolism, elimination rate)

  20. HPLC-MS technique for radiopharmaceuticals analysis and quality control

    Science.gov (United States)

    Macášek, F.; Búriová, E.; Brúder, P.; Vera-Ruiz, H.

    2003-01-01

    Potentialities of liquid chromatography with mass spectrometric detector (MSD) were investigated with the objective of quality control of radiopharmaceuticals; 2-deoxy-2-[18F]fluoro-D-glucose (FDG) being an example. Screening of suitable MSD analytical lines is presented. Mass-spectrometric monitoring of acetonitrile— aqueous ammonium formate eluant by negatively charged FDG.HCO2 - ions enables isotope analysis (specific activity) of the radiopharmaceutical at m/z 227 and 226. Kryptofix® 222 provides an intense MSD signal of the positive ion associated with NH4 + at m/z 394. Expired FDG injection samples contain decomposition products from which at least one labelled by 18F and characterised by signal of negative ions at m/z 207 does not correspond to FDG fragments but to C5 decomposition products. A glucose chromatographic peak, characterised by m/z 225 negative ion is accompanied by a tail of a component giving a signal of m/z 227, which can belong to [18O]glucose; isobaric sorbitol signals were excluded but FDG-glucose association occurs in the co-elution of separation of model mixtures. The latter can actually lead to a convoluted chromatographic peak, but the absence of 18F makes this inconsistent. Quantification and validation of the FDG component analysis is under way.

  1. Stabilization of Tc-99m radiopharmaceuticals by chemical additives (NOTE

    Directory of Open Access Journals (Sweden)

    NADEZDA VUKICEVIC

    2001-09-01

    Full Text Available The reliability and applicability of the preparation of the three, for nuclear medicine very important, 99mTc-radiopharmaceuticals from the inactive (technetium-cold kit solutions were tested. Each examined commercial kit was dissolved in saline (0.9 % NaCl. The conditions of the storage of the inactive kit solutions till labeling were examined. The main problem is the stablity of the reductant stannous ions which is very difficult to predict. To stabilize and ensure a good quality of the labeled radiopharmaceuticals, ascorbic or gentisic acid were added. It was found that the best results were obtained by keeping the samples frozen at –20 ?C. Both stabilizers can be used but for an effective protection much lower concentrations of ascorbic acid are needed. Its concentrations of 12–60 mg/ml of the kit, stabilized dimercaptosuccinate (DMS and pyrophosphate (PyP for about 7–8 days. The solution of 2,3-dicarboxypropane-1,1-diphosphonate (DPD was found to be stable even without the stabilizer. This could be attributed probably to the chemical nature of this complex. However, in routine praxis the applied procedure demands great care and personel very experienced in radiopharmacy.

  2. Antitumor Peptides from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Mi Sun

    2011-10-01

    Full Text Available The biodiversity of the marine environment and the associated chemical diversity constitute a practically unlimited resource of new antitumor agents in the field of the development of marine bioactive substances. In this review, the progress on studies of antitumor peptides from marine sources is provided. The biological properties and mechanisms of action of different marine peptides are described; information about their molecular diversity is also presented. Novel peptides that induce apoptosis signal pathway, affect the tubulin-microtubule equilibrium and inhibit angiogenesis are presented in association with their pharmacological properties. It is intended to provide useful information for further research in the fields of marine antitumor peptides.

  3. Radiopharmaceuticals for the therapy of metastatic bone pain

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol [Kyungpook National University Medicine School, Daegu (Korea, Republic of)

    2006-04-15

    Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. It occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and is complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesion. {sup 32}P, {sup 89}SrCl, {sup 153}Sm-EDTMP, {sup 188}Re/{sup 186}Re-HEDP, and {sup 177}Lu-EDTMP can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic from of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and in some studies, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article

  4. A method to assess safety and resilience in radiopharmaceuticals production process.

    Science.gov (United States)

    Grecco, Cláudio H S; Vidal, Mario C R; Santos, Isaac J A L; Carvalho, Paulo V R

    2012-01-01

    Radiopharmaceuticals are radiation-emitting substances used in medicine for radiotherapy and imaging diagnosis. A Research Institute, located in Rio de Janeiro, produces three radiopharmaceuticals: the sodium iodate is used in the diagnosis of thyroid dysfunctions, the meta-iodo-benzylguanidine is used in the diagnosis of cardiac diseases, and the fluordesoxyglucose is used in diagnosis in cardiology, oncology, neurology and neuropsychiatry. This paper presents a method to access safety and resilience in radiopharmaceuticals production processes. The method uses resilience indicators in order to proactively evaluate and manage the safety.

  5. Leading safety performance indicators for resilience assessment of radiopharmaceuticals production process

    Energy Technology Data Exchange (ETDEWEB)

    Grecco, Claudio H.S.; Santos, Isaac J.A.L.; Carvalho, Paulo V.R., E-mail: grecco@ien.gov.b, E-mail: luquetti@ien.gov.b, E-mail: paulov@ien.gov.b [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Instrumentacao e Confiabilidade Humana; Vidal, Mario C.R., E-mail: mvidal@ergonomia.ufrj.b [Coordenacao dos Programas de Pos-Graduacao de Engenharia (PEP/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia de Producao. Grupo de Ergonomia e Novas Tecnologias (GENTE)

    2011-07-01

    Radiopharmaceuticals are radiation-emitting substances used in medicine for radiotherapy and imaging diagnosis. A Research Institute, located in Rio de Janeiro, produces three radiopharmaceuticals: the sodium iodate is used in the diagnosis of thyroid dysfunctions, the meta-iodo-benzyl guanidine is used in the diagnosis of cardiac diseases, and the fluorodeoxyglucose is used in diagnosis in cardiology, oncology, neurology and neuro psychiatry. This paper presents a leading safety performance indicators framework to assess the resilience of radiopharmaceuticals production processes. The organizations that use resilience indicators will be able to pro actively evaluate and manage safety. (author)

  6. Uncertainty sources in radiopharmaceuticals clinical studies; Fontes de incertezas em estudos clinicos com radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Degenhardt, Aemilie Louize; Oliveira, Silvia Maria Velasques de, E-mail: silvia@cnen.gov.br, E-mail: amilie@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    The radiopharmaceuticals should be approved for consumption by evaluating their quality, safety and efficacy. Clinical studies are designed to verify the pharmacodynamics, pharmacological and clinical effects in humans and are required for assuring safety and efficacy. The Bayesian analysis has been used for clinical studies effectiveness evaluation. This work aims to identify uncertainties associated with the process of production of the radionuclide and radiopharmaceutical labelling as well as the radiopharmaceutical administration and scintigraphy images acquisition and processing. For the development of clinical studies in the country, the metrological chain shall assure the traceability of the surveys performed in all phases. (author)

  7. 86Y based PET radiopharmaceuticals: radiochemistry and biological applications.

    Science.gov (United States)

    Nayak, Tapan K; Brechbiel, Martin W

    2011-09-01

    Development of targeted radionuclide therapy with (90)Y labeled antibodies and peptides has gained momentum in the past decade due to the successes of (90)Y-ibritumomab tiuxetan and (90)Y-DOTA-Phe(1)-Tyr(3)-octreotide in treatment of cancer. (90)Y is a pure β(-)-emitter and cannot be imaged for patient-specific dosimetry which is essential for pre-therapeutic treatment planning and accurate absorbed dose estimation in individual patients to mitigate radiation related risks. This review article describes the utility of (86)Y, a positron emitter (33%) with a 14.7-h half-life that can be imaged by positron emission tomography and used as an isotopically matched surrogate radionuclide for (90)Y radiation doses estimations. This review discusses various aspects involved in the development of (86)Y labeled radiopharmaceuticals with the specific emphasis on the radiochemistry and biological applications with antibodies and peptides.

  8. New selenium-75 labeled radiopharmaceuticals: selenonium analogues of dopamine

    Energy Technology Data Exchange (ETDEWEB)

    Sadek, S.A.; Basmadjian, G.P.; Hsu, P.M.; Rieger, J.A.

    1983-07-01

    Selenium-75 labeled selenonium analogues of dopamine, (2-(3,4-dimethoxyphenyl)ethyl)dimethylselenonium iodide and its dihydroxy analogue, were prepared by reducing (/sup 75/Se)selenious acid with sodium borohydride at pH 6.0 and reacting the NaSeH produced with 1-(3,4-dimethoxyphenyl)-2-(p-toluenesulfonyloxy)ethane. Tissue distribution studies in rats given the /sup 75/Se-labeled selenonium agents intravenously demonstrated high initial heart uptake. Prolonged adrenal retention and high adrenal to blood ratio of compound 4 were observed. The high uptake and adrenal to blood ratio suggest the potential use of compound 4 as a radiopharmaceutical for the adrenal gland.

  9. Receptor-binding radiotracers: a class of potential radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Eckelman, W.C.; Reba, R.C.; Gibson, R.E.; Rzeszotarski, W.J.; Vieras, F.; Mazaitis, J.K.; Francis, B.

    1979-04-01

    To date no radiopharmaceutical is routinely used to study changes in receptor concentration. Frequently changes in receptor concentration, or the appearance of receptors in tumors, indicates a specific pathologic state. With a receptor-binding radiotracer, in vivo studies of these changes will be possible. A reversible bimolecular model and in vitro tests were used to determine equilibrium constants and maximal target-to-blood ratios for new derivatives. Theoretical calculations showed that derivatives binding to the estrogen receptor, the beta adrenoceptor, or the cholinergic receptor are capable of achieving satisfactory target-to-blood ratios. Using in vitro tests, the apparent affinity constant was determined for five iodinated estrogen derivatives and five derivatives of beta blockers. Results of the in vitro study with derivatives of beta blockers. Results of the in vitro study with derivatives of beta blockers, and in vivo displacement studies using propranolol, indicated that the high heart-to-blood ratios (5 to 20) obtained with the new derivatives were not the result of a specific interaction with the receptor. In this instance factors other than receptor binding control the in vivo distribution. The in vitro assay using estrogen receptors showed that of the five derivatives, iodohexestrol and 17-alpha-iodoethynylestradiol bind to the receptor with the highest affinity. In vivo studies confirmed these results; iodohexestrol gave a uterus-to-blood ratio of 10 in immature rats when plasma-protein binding was blocked. With a tritiated muscarinic cholinergic blocking agent, heart-to-blood ratios near the theoretical maximum were obtained. This compound most closely follows the mechanism described by the model. Use of the theoretical model in conjunction with in vitro assays can greatly aid in the design of this new class of receptor-binding radiopharmaceuticals.

  10. Effect of blood activity on dosimetric calculations for radiopharmaceuticals

    Science.gov (United States)

    Zvereva, Alexandra; Petoussi-Henss, Nina; Li, Wei Bo; Schlattl, Helmut; Oeh, Uwe; Zankl, Maria; Graner, Frank Philipp; Hoeschen, Christoph; Nekolla, Stephan G.; Parodi, Katia; Schwaiger, Markus

    2016-11-01

    The objective of this work was to investigate the influence of the definition of blood as a distinct source on organ doses, associated with the administration of a novel radiopharmaceutical for positron emission tomography-computed tomography (PET/CT) imaging—(S)-4-(3-18F-fluoropropyl)-L-glutamic acid (18F-FSPG). Personalised pharmacokinetic models were constructed based on clinical PET/CT images from five healthy volunteers and blood samples from four of them. Following an identifiability analysis of the developed compartmental models, person-specific model parameters were estimated using the commercial program SAAM II. Organ doses were calculated in accordance to the formalism promulgated by the Committee on Medical Internal Radiation Dose (MIRD) and the International Commission on Radiological Protection (ICRP) using specific absorbed fractions for photons and electrons previously derived for the ICRP reference adult computational voxel phantoms. Organ doses for two concepts were compared: source organ activities in organs parenchyma with blood as a separate source (concept-1); aggregate activities in perfused source organs without blood as a distinct source (concept-2). Aggregate activities comprise the activities of organs parenchyma and the activity in the regional blood volumes (RBV). Concept-1 resulted in notably higher absorbed doses for most organs, especially non-source organs with substantial blood contents, e.g. lungs (92% maximum difference). Consequently, effective doses increased in concept-1 compared to concept-2 by 3-10%. Not considering the blood as a distinct source region leads to an underestimation of the organ absorbed doses and effective doses. The pronounced influence of the blood even for a radiopharmaceutical with a rapid clearance from the blood, such as 18F-FSPG, suggests that blood should be introduced as a separate compartment in most compartmental pharmacokinetic models and blood should be considered as a distinct source in

  11. UPLC®-RAD the new standard in quality control of PET radiopharmaceutical

    NARCIS (Netherlands)

    Maas, B.; Zijlma, R.; Bannink, A.; Lub-De Hooge, M.; Elsinga, P.H.; Dierckx, R.A.J.O.; Boersma, H.H.; Luurtsema, G.

    2013-01-01

    Objectives: Good Manufacturing Practice (GMP) compliant productions require validated, quality control procedures of the radiopharmaceutical. Quality control of the final product is conventionally performed by High Performance Liquid Chromatography (HPLC) with UV and radioactivity (RAD) detection. T

  12. VII. Boettstein Colloquium: PET-Radiopharmaceuticals at PSI: achievement and future prospects

    Energy Technology Data Exchange (ETDEWEB)

    Schubiger, P.A.; Beer, H.F.; Blaeuenstein, P.; Leenders, K.E.

    1993-12-31

    The three sessions of the 1993 Boettstein colloquium dealt with the following topics: - PET-radiopharmaceuticals, - PET-scanning: significance of tracer uptake, - clinical options using PET. 22 papers were presented. figs., refs.

  13. Metabolic radiopharmaceutical therapy in nuclear medicine; Terapia metabolica mediante radiofarmacos en medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Reguera, L.; Lozano, M. L.; Alonso, J. C.

    2016-08-01

    In 1986 the National Board of Medical Specialties defined the specialty of nuclear medicine as a medical specialty that uses radioisotopes for prevention, diagnosis, therapy and medical research. Nowadays, treatment with radiopharmaceuticals has reached a major importance within of nuclear medicine. The ability to treat tumors with radiopharmaceutical, Radiation selective therapy has become a first line alternative. In this paper, the current situation of the different therapies that are sued in nuclear medicine, is reviewed. (Author)

  14. Pharmaceuticals—Special Issue on Radiopharmaceutical Chemistry between Imaging and Endoradiotherapy

    Directory of Open Access Journals (Sweden)

    Klaus Kopka

    2014-07-01

    Full Text Available The fields of molecular biology, immunology and genetics have generated many important developments that advance the understanding of the induction and progression of oncological, cardiological and neurological diseases as well as the identification of disease-associated molecules and drugs that specifically target diseased cells during therapy. These insights have triggered the development of targeted radiopharmaceuticals which open up a new dimension of radiopharmaceutical sciences in nuclear medicine. Radiopharmaceuticals, also called radiotracers, are radiolabelled molecules, bearing a “radioactive lantern”, and used as molecular probes to address clinically relevant biological targets such as receptors, enzymes, transport systems and others. Positron emission tomography (PET and single photon emission computed tomography (SPECT realised in the en-vogue hybrid technologies PET/CT, SPECT/CT and PET/MRI represent the state-of-the-art diagnostic imaging technologies in nuclear medicine which are used to follow the trace of the administered radiopharmaceutical noninvasively thereby in vivo visualising and assessing biological processes at the subcellular and molecular level in a highly sensitive manner. In this connexion novel radiopharmaceuticals for the noninvasive molecular imaging of early disease states and monitoring of treatment responses in vivo by means of PET/CT, SPECT/CT and PET/MRI are indispensable prerequisites to further advance and strengthen the unique competence of radiopharmaceutical sciences. In the era of personalised medicine the diagnostic potential of radiopharmaceuticals is directly linked to a subsequent individual therapeutic approach called endoradiotherapy. Depending on the “radioactive lantern” (gamma or particle emitter used for radiolabelling of the respective tracer molecule, the field of Radiopharmaceutical Chemistry can contribute to the set-up of an “in vivo theranostic” approach especially in

  15. Pharmacokinetic properties of new antitumor radiopharmaceutical on the basis of diamond nanoporous composites labeled with rhenium-188

    Science.gov (United States)

    Petriev, V. M.; Tishchenko, V. K.; Kuril’chik, A. A.; Skvortsov, V. G.

    2017-01-01

    Today the development of address therapeutic radionuclide delivery systems directly to tumor tissue is of current interest. It can be achieved by the design of drug containers of specific sizes and shapes from carbon-based composite materials. It will be allowed to enhance the efficacy of anticancer therapy and avoid serious side effects. In this work we studied the pharmacokinetic properties of nanodiamond nanoporous composite labeled with rhenium-188 in rats with hepatocholangioma PC-1 after intratumoral injection. It was established that substantial part of injected radioactivity remained in tumor tissue. Within three hours after 188Re-nanoporous composites injection activity in tumor constituted 79.1–91.3% of injected dose (ID). Then activity level declined to 45.9% ID at 120 hours. No more than 1.34% ID entered the bloodstream. In soft organs and tissues, except thyroid gland, the content of compound didn’t exceed 0.3% ID/g. The highest activity in thyroid gland was 6.95% ID/g. In conclusion, received results suggest 188Re-nanoporous composites can be promising radionuclide delivery systems for cancer treatment.

  16. Calibration and qualification of equipment in the pharmaceutical industry: emphasis on radiopharmaceuticals production

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

    The calibration and qualification of equipment are listed items in RDC number 17 of 2010 which refers about the Good Manufacturing Practice (GMP) of medicaments and RDC number 63 of 2009 which refers about GMP of Radiopharmaceuticals. Both are essential requirements since they are involved in process control to attend the regulatory criteria and are a key part of the validation process. The aim of this work is presenting the importance of calibration and qualification, and the routine use of equipment and facilities in industrial scale production of radiopharmaceuticals in the IPEN/CNEN. The radiopharmacy of IPEN is a pharmaceutical industry that produces radiopharmaceuticals for diagnosis and therapy. It was the pioneer institute in production of radioisotopes and radiopharmaceuticals in Brazil. Currently, 38 products are distributed to the nuclear medicine centers, including primary radioisotopes, labeled molecules and lyophilized reagents for labeling with technetium-99m. To fulfill the GMP requirements for quality assurance of products, several factors must be considered including infrastructure, equipment and raw materials beyond, obviously, the whole production process should be controlled until the release of the final product. Therefore, the calibration and verification of equipment, instruments and other appliances used in the production and quality control should be performed. A program of calibration, qualification and requalification of equipment used in production and quality control of radiopharmaceuticals is necessary for the validation of production processes and analytical methods, and should be established for quality assurance of produced radiopharmaceuticals. (author)

  17. Use of radiopharmaceuticals in diagnostic nuclear medicine in the United States: 1960-2010.

    Science.gov (United States)

    Drozdovitch, Vladimir; Brill, Aaron B; Callahan, Ronald J; Clanton, Jeffrey A; DePietro, Allegra; Goldsmith, Stanley J; Greenspan, Bennett S; Gross, Milton D; Hays, Marguerite T; Moore, Stephen C; Ponto, James A; Shreeve, Walton W; Melo, Dunstana R; Linet, Martha S; Simon, Steven L

    2015-05-01

    To reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, the authors assessed which radiopharmaceuticals were used in different time periods, their relative frequency of use, and typical values of the administered activity. This paper presents data on the changing patterns of clinical use of radiopharmaceuticals and documents the range of activity administered to adult patients undergoing diagnostic nuclear medicine procedures in the U.S. between 1960 and 2010. Data are presented for 15 diagnostic imaging procedures that include thyroid scan and thyroid uptake; brain scan; brain blood flow; lung perfusion and ventilation; bone, liver, hepatobiliary, bone marrow, pancreas, and kidney scans; cardiac imaging procedures; tumor localization studies; localization of gastrointestinal bleeding; and non-imaging studies of blood volume and iron metabolism. Data on the relative use of radiopharmaceuticals were collected using key informant interviews and comprehensive literature reviews of typical administered activities of these diagnostic nuclear medicine studies. Responses of key informants on relative use of radiopharmaceuticals are in agreement with published literature. Results of this study will be used for retrospective reconstruction of occupational and personal medical radiation doses from diagnostic radiopharmaceuticals to members of the U.S. radiologic technologists' cohort and in reconstructing radiation doses from occupational or patient radiation exposures to other U.S. workers or patient populations.

  18. Radiopharmaceuticals for diagnosis of inflammation; Radiopharmaka fuer die Entzuendungsdiagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Meller, B.; Baehre, M. [Luebeck Univ. (Germany). Klinik fuer Radiologie und Nuklearmedizin

    2007-06-15

    Inflammations represent mediator-induced reactions of the hematopoetic-immunologic cell system resulting from exogenous or endogenous stimuli. On cellular level, an increased expression of inflammatory genes is followed by the release of several mediators. As inflammatory response vascular permeability increases and interstitial oedema develops. Additionally, white blood cells emigrate and several transduction cascades are activated. Radiopharmaceuticals for inflammation scintigraphy should specifically reflect one or several aspects of inflammation pathophysiology on molecular level. A group of elder tracers for this purpose comprised substances that are accumulated due to the permeability of physiological barriers. However, their property to accumulate in all processes with increased vascular permeability results in a comparably low specificity of these methods. In-vitro-labelled granulocytes were the method of choice for scintigraphic imaging of inflammation for years. Investigations with {sup 111}In-labelled granulocytes are still frequently considered as the gold standard to detect inflammation by scintigraphy. The use of antibodies or antibody fragments directed against leucocytes allowed in vivo labelling and substituted more complex techniques of in vitro labelling despite of several disadvantages. Due to the superior imaging quality of positron emission tomography, [{sup 18}F]FDG-labelled leucocytes might result in a renaissance of in vitro methods. In cases of cerebral inflammation, activated microglia was visualised by its increased expression of benzodiazepin receptors. An interesting approach to differentiate between infection and sterile inflammation could be the use of bacterial gyrase inhibitors labelled with radioactive compounds. At present, specificity of this method is still controversially discussed. In search of substances to visualise inflammatory transduction cascades selectively, several chemotactic and chemokinetic cytokines, metabolites

  19. Activities, procedures and doses in pediatric patients due to radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Silvia Maria Velasques de Oliveira

    2008-12-01

    Full Text Available An investigation performed between 2003 and 2005 in sixteen selected public and private institutions in Northeast, Southeast and South geographical regions of Brazil evaluated average organ doses and effective doses in 2,411 pediatric patients due to diagnostic procedures with radiopharmaceuticals. For 1 year, effective doses were greater than literature. For 5 years, differences were noticed between present work and literature for bone scintigraphy, thyroid scintigraphy and 67Ga citrate scintigraphy. These differences may be attributed to the uncertainties in internal dose calculations. High absorved doses in bone surfaces of children due to 67Ga citrate and bone scintigraphy should be evaluated accordingly. Current protocols used recommend standardized mean activities per mean weight for all ages. However, it was observed that the activities were not standardized and were higher for children with younger ages. Future studies are needed for optimising activities of radiopharmaceuticals to these patients in the country.Foi realizado no Brasil, no período 2003-2005, um estudo sobre doses absorvidas em órgãos e doses efetivas devido ao uso de radiofármacos em pacientes pediátricos. Foram estudadas 2.411 crianças e adolescentes menores de 18 anos. Foi observado que as atividades usadas não foram padronizadas, sendo maiores para crianças de menor idade, podendo ser otimizadas conforme apropriado. Para 1 ano, as doses efetivas foram maiores do que as publicadas na literatura e para 5 anos, foram observadas diferenças para cintilografias ósseas, cintilografias da tireóide, e pesquisas de corpo inteiro com citrato de 67G. Deve ser avaliado se doses absorvidas em órgãos, especialmente para superfície óssea devido a cintilografias ósseas com 99mTc MDP e pesquisa de corpo inteiro com citrato de 67Ga podem acarretar risco radiológico adicional aos pacientes, considerando-se as peculiaridades de seu estado clínico.

  20. AUTOMATION FOR THE SYNTHESIS AND APPLICATION OF PET RADIOPHARMACEUTICALS.

    Energy Technology Data Exchange (ETDEWEB)

    Alexoff, D.L.

    2001-09-21

    The development of automated systems supporting the production and application of PET radiopharmaceuticals has been an important focus of researchers since the first successes of using carbon-11 (Comar et al., 1979) and fluorine-18 (Reivich et al., 1979) labeled compounds to visualize functional activity of the human brain. These initial successes of imaging the human brain soon led to applications in the human heart (Schelbert et al., 1980), and quickly radiochemists began to see the importance of automation to support PET studies in humans (Lambrecht, 1982; Langstrom et al., 1983). Driven by the necessity of controlling processes emanating high fluxes of 511 KeV photons, and by the tedium of repetitive syntheses for carrying out these human PET investigations, academic and government scientists have designed, developed and tested many useful and novel automated systems in the past twenty years. These systems, originally designed primarily by radiochemists, not only carry out effectively the tasks they were designed for, but also demonstrate significant engineering innovation in the field of laboratory automation.

  1. The next generation of positron emission tomography radiopharmaceuticals in oncology.

    Science.gov (United States)

    Rice, Samuel L; Roney, Celeste A; Daumar, Pierre; Lewis, Jason S

    2011-07-01

    Although (18)F-fluorodeoxyglucose ((18)F-FDG) is still the most widely used positron emission tomography (PET) radiotracer, there are a few well-known limitations to its use. The last decade has seen the development of new PET probes for in vivo visualization of specific molecular targets, along with important technical advances in the production of positron-emitting radionuclides and their related labeling methods. As such, a broad range of new PET tracers are in preclinical development or have recently entered clinical trials. The topics covered in this review include labeling methods, biological targets, and the most recent preclinical or clinical data of some of the next generation of PET radiopharmaceuticals. This review, which is by no means exhaustive, has been separated into sections related to the PET radionuclide used for radiolabeling: fluorine-18, for the labeling of agents such as FACBC, FDHT, choline, and Galacto-RGD; carbon-11, for the labeling of choline; gallium-68, for the labeling of peptides such as DOTATOC and bombesin analogs; and the long-lived radionuclides iodine-124 and zirconium-89 for the labeling of monoclonal antibodies cG250, and J591 and trastuzumab, respectively.

  2. Uptake of SPECT radiopharmaceuticals in neocortical brain cultures

    Energy Technology Data Exchange (ETDEWEB)

    Jong, B.M. de; Royen, E.A. van

    1989-01-01

    The uptake, retention and uptake antagonism of /sup 201/Tl-DDC, /sup 201/Tl-Cl, /sup 123/I-IMP, /sup 99m/Tc-HMPAO and /sup 99m/Tc-O4/sup -/ were compared in rat neocortex cultures. /sup 201/Tl-DDC and /sup 123/I-IP revealed the highest uptake of radioactivity in the cultures. /sup 99m/Tc-HMPAO and /sup 123/I-IMP showed the highest retention of radioactivity within the tissue in washout experiments. Blocking of bioelectric activity by tetrodotoxin did not significantly affect the uptake of the radiopharmaceuticals (RPHA). Inhibition of Na K ATPase by ouabain inhibited the uptake of /sup 201/Tl-Cl (77%) and /sup 201/Tl-DDC (27%). Imipramine showed a significantly stronger inhibitory effect on /sup 123/I-IMP uptake in comparison with the effect on other RPHA. /sup 99m/Tc-O4/sup -/ was not concentrated within the cultured tissue. Under the in vitro conditions used in this study, the various RPHA were characterised by distinct differences in their interaction with cortical brain tissue.

  3. New SPECT and PET Radiopharmaceuticals for Imaging Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Oyebola O. Sogbein

    2014-01-01

    Full Text Available Nuclear cardiology has experienced exponential growth within the past four decades with converging capacity to diagnose and influence management of a variety of cardiovascular diseases. Single photon emission computed tomography (SPECT myocardial perfusion imaging (MPI with technetium-99m radiotracers or thallium-201 has dominated the field; however new hardware and software designs that optimize image quality with reduced radiation exposure are fuelling a resurgence of interest at the preclinical and clinical levels to expand beyond MPI. Other imaging modalities including positron emission tomography (PET and magnetic resonance imaging (MRI continue to emerge as powerful players with an expanded capacity to diagnose a variety of cardiac conditions. At the forefront of this resurgence is the development of novel target vectors based on an enhanced understanding of the underlying pathophysiological process in the subcellular domain. Molecular imaging with novel radiopharmaceuticals engineered to target a specific subcellular process has the capacity to improve diagnostic accuracy and deliver enhanced prognostic information to alter management. This paper, while not comprehensive, will review the recent advancements in radiotracer development for SPECT and PET MPI, autonomic dysfunction, apoptosis, atherosclerotic plaques, metabolism, and viability. The relevant radiochemistry and preclinical and clinical development in addition to molecular imaging with emerging modalities such as cardiac MRI and PET-MR will be discussed.

  4. In Vitro Assessment of the In Vivo Stability of Cu-64 Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Packard, Alan B

    2011-12-15

    Research Plans: The successful development of Cu-64 radiopharmaceuticals depends upon retention of the Cu-64 atom in the radiopharmaceutical. To date, the focus has been on the development of chelators that better retain Cu-64, but there has been no effort to develop an effective method by which improved retention may be measured. In the absence of a suitable analytical method, the stability of Cu-64 radiopharmaceuticals is estimated indirectly, with decreased liver uptake suggesting higher in vivo complex stability. But this approach is inadequate for radiopharmaceuticals, such as radiolabeled antibodies, that are expected to accumulate in the liver even when there is no free Cu-64 present. The absence of such a method has also hampered efforts to systematically evaluate the chemical factors that may give rise to improved retention. The objective of this project is to develop and validate such a method. Accomplishments: The two primary accomplishments of this project will be 1) the development and validation of a method to measure the stability of Cu-64 radiopharmaceuticals and 2) the determination of the chemical factors that define the in vivo stability of Cu 64 radiopharmaceuticals. Because Cu(II) is extremely labile, the in vivo stability of Cu-64 radiopharmaceuticals is not primarily determined by the amount of free Cu that is present at any given time or by the thermodynamic stability constants, but rather by the rate at which Cu is lost from the complex, the dissociation rate constant, kd. The dissociation rate constants of the Cu-64 complexes from a series of bifunctional chelators (BFCs) will be measured using Free Ion Selective Radiotracer Extraction (FISRE), a technique originally developed to measure bioavailable Cu in environmental samples. FISRE will also be applied to the determination of the kd's of a series of reference Cu-64 complexes to determine the chemical factors that define the in vivo stability of Cu-64 radiopharmaceuticals. Potential

  5. Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals : a concise overview and practical guidance for a risk-based approach

    NARCIS (Netherlands)

    Lange, Rogier; ter Heine, Rob; Decristoforo, Clemens; Penuelas, Ivan; Elsinga, Philip H.; van der Westerlaken, Monique M. L.; Hendrikse, N. Harry

    2015-01-01

    Radiopharmaceuticals are highly regulated, because they are controlled both as regular medicinal products and as radioactive substances. This can pose a hurdle for their development and clinical use. Radiopharmaceuticals are fundamentally different from other medicinal products and these regulations

  6. Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals: a concise overview and practical guidance for a risk-based approach

    NARCIS (Netherlands)

    Lange, R.; Heine, R. ter; Decristoforo, C.; Penuelas, I.; Elsinga, P.H.; Westerlaken, M.M. van der; Hendrikse, N.H.

    2015-01-01

    Radiopharmaceuticals are highly regulated, because they are controlled both as regular medicinal products and as radioactive substances. This can pose a hurdle for their development and clinical use. Radiopharmaceuticals are fundamentally different from other medicinal products and these regulations

  7. Incorporation of radiohalogens via versatile organometallic reactions: applications in radiopharmaceutical chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, P.C.; Goodman, M.M.; Knapp, F.F. Jr.

    1985-01-01

    Factors that must be considered for the design of radiohalogenated radio-pharmaceuticals include the stability and availability of the substrate, the physical half-life of the radiohalogen and the in vivo stability of the radiolabel. Vinyl and phenyl radiohalogen bonds show more in vivo stability than the alkyl radiohalogen bonds. Consequently, a variety of methods suitable for the synthesis of tissue specific radiopharmaceuticals bearing a vinyl or phenyl radiohalogen have been developed involving the synthesis and halogenation of metallovinyl and phenyl intermediates. The halogens and metallation reactions include iodine and bromine and alanation, boronation, mercuration, stannylation, and thallation, respectively. 19 refs., 1 fig., 1 tab.

  8. A 3D high-resolution gamma camera for radiopharmaceutical studies with small animals

    CERN Document Server

    Loudos, G K; Giokaris, N D; Styliaris, E; Archimandritis, S C; Varvarigou, A D; Papanicolas, C N; Majewski, S; Weisenberger, D; Pani, R; Scopinaro, F; Uzunoglu, N K; Maintas, D; Stefanis, K

    2003-01-01

    The results of studies conducted with a small field of view tomographic gamma camera based on a Position Sensitive Photomultiplier Tube are reported. The system has been used for the evaluation of radiopharmaceuticals in small animals. Phantom studies have shown a spatial resolution of 2 mm in planar and 2-3 mm in tomographic imaging. Imaging studies in mice have been carried out both in 2D and 3D. Conventional radiopharmaceuticals have been used and the results have been compared with images from a clinically used system.

  9. Radiopharmaceuticals for diagnosis. [Final] report, 1 January 1991--31 December 1993

    Energy Technology Data Exchange (ETDEWEB)

    Kuhl, D.E.

    1993-06-01

    Since 1987, this grant has supported the development of new radiochemical methods for use with short-lived, positron-emitting radionuclides; new laboratory techniques for radiochemical syntheses; and development of new radiopharmaceuticals which will be of use in Positron Emission Tomography. For the period 1 January 1991 to 31 December 1993, the authors have continued their efforts in all of these areas, as they feel that an integrated approach to the synthesis and characterization of new PET Radiopharmaceuticals is crucial to the continued growth and application of this imaging technique in modern medicine. Progress in a number of these areas is described in this report.

  10. Determination and reliability of dose coefficients for radiopharmaceuticals; Ermittlung der Zuverlaessigkeit von Dosiskoeffizienten fuer Radiopharmaka

    Energy Technology Data Exchange (ETDEWEB)

    Spielmann, V.; Li, W.B.; Zankl, M.; Oeh, U.

    2015-11-15

    The dose coefficients used in nuclear medicine for dose calculations of radiopharmaceuticals are based on recommendations by ICRP (International Commission on radiological protection) and the MIRD (Medical Internal Radiation Dose Committee) using mathematical models for the temporal activity distributions in organs and tissues (biokinetic models) and mathematical models of the human body. These models using an idealized human body do not include uncertainty estimations. The research project is aimed to determine the uncertainties and thus the reliability of the dose coefficients for radiopharmaceuticals and to identify the biokinetic and dosimetric parameters that contribute most of the uncertainties.

  11. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2015-07-01

    Full Text Available Objective(s: Peptide Receptor Radionuclide Therapy (PRRT with yttrium-90 (90Y and lutetium-177 (177Lu-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system.Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany. Sterile, GMP-certified, no-carrier added (NCA 177Lu was used with GMPcertifiedpeptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods.Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05% and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5% for this period.Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

  12. Studies on clinical standard. Studies on the standardization of clinical application of novel radiopharmaceuticals for circulation

    Energy Technology Data Exchange (ETDEWEB)

    Sugishita, Yasuro [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine; Kanbara, Hirofumi; Konishi, Junji [and others

    1998-08-01

    This paper is a summary guideline for the use of recent radiopharmaceuticals for circulation in various disease states, which is based on the studies to recognize the actual status of the use of radiopharmaceuticals by questionnaire, then to make the guideline for their use by authors and finally to evaluate its usefulness. The questionnaire to 339 facilities was performed in 1995 to obtained answers from 200 facilities, of which 96% had used at least one of the novel radiopharmaceuticals. Planar and SPECT imaging had been done under various conditions in those facilities. This guideline consists of three chapters. In the chapter for the tracer, use of radiopharmaceuticals, theory, apparatuses, technique, diagnostic criteria and notes for diagnosis were guided for {sup 123}I-BMIPP (myocardial imaging), {sup 123}I-MIBG (myocardial imaging) and {sup 99m}Tc-MIBI and -TF (blood flow imaging). In the chapter for disease states, pathophysiology of following diseases and significance of nuclear medicine in their diagnosis, therapy and prognosis were described: acute coronary diseases, myocardial infarction, angina pectoris, cardiomyopathy and others. In the additional chapter, {sup 111}In-labeled anti-myosin antibody was described for imaging of impaired myocardium. The present guideline was hoped to be useful. (K.H.). 315 refs.

  13. Obligations, precautions and pending issues in regulatory development for radiopharmaceuticals in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Gamboa, Maryelle Moreira Lima; Roesch, Heveline Rayane Moura; Lemos, Vanessa Pinheiro Amaral, E-mail: maryellelg@hotmail.com [PPG BioSaude, Universidade Luterana do Brasil, Canoas, RS (Brazil); Rocha, Bruna Oliveira [Faculty of Biology, Universidade Luterana do Brasil, Canoas, RS (Brazil); Santos-Oliveira, Ralph [Institute of Radiopharmacy Research, Universidade Estadual da Zona Oeste, Rio de Janeiro, RJ (Brazil)

    2014-04-15

    Radiopharmaceuticals are compounds that have a radionuclide and may be gamma-radiation emitter (γ) or positrons emitter (β+), linked to a molecule with specific diagnostic and therapeutic purposes. The progress in the use of radiopharmaceuticals has culminated to a sector in common with other types of drugs: regulation and surveillance. >From 2006 on, production, marketing and use of these drugs were open to the Brazilian market granting much more freedom due to the Constitutional Amendment 49, resulting from the previous Constitutional Amendment 199/03 which removes the Union monopoly for this kind of manipulation and granted this production to other nuclear medicine. From this date on, the amount of this type of sold product have been greatly increased, and the nucleus of surveillance and regulation in Brazil have also advanced in the legislative processes, creating documents that are now more focused on radiopharmaceuticals in the national territory (Resolutions No. 63 and No. 64). In international overview, there is too much to be done in regulatory terms in Brazil, such as adding mainly issues of drugs surveillance to pharmacovigilance practice in radiopharmaceuticals drugs. (author)

  14. SPECT radiopharmaceuticals for imaging chronic inflammatory diseases in the last decade

    NARCIS (Netherlands)

    Anzola Fuentes, Luz; Galli, F.; Dierckx, R. A.

    2015-01-01

    In the recent years, many radiopharmaceuticals have been described for the diagnosis of inflammatory chronic diseases. Several peptides receptor ligands and monoclonal antibodies have been radiolabelled, allowing in-vivo visualization of inflammatory processes at a cellular and molecular level. The

  15. Harvard-MIT research program in short-lived radiopharmaceuticals. Technical progress report, 1991

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J.

    1991-12-31

    This report presents research on radiopharmaceuticals. The following topics are discussed: antibody labeling with positron-emitting radionuclides; antibody modification for radioimmune imaging; labeling antibodies; evaluation of technetium acetlyacetonates as potential cerebral blood flow agents; and studies in technetium chemistry. (CBS)

  16. Implementation of a metrology programme to provide traceability for radionuclides activity measurements in the CNEN Radiopharmaceuticals Producers Centers

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Erica A.L. de; Braghirolli, Ana M.S.; Tauhata, Luiz; Gomes, Regio S.; Silva, Carlos J., E-mail: erica@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Delgado, Jose U.; Oliveira, Antonio E.; Iwahara, Akira, E-mail: ealima@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-07-01

    The commercialization and use of radiopharmaceuticals in Brazil are regulated by Agencia Nacional de Vigilancia Sanitaria (ANVISA) which require Good Manufacturing Practices (GMP) certification for Radiopharmaceuticals Producer Centers. Quality Assurance Program should implement the GMP standards to ensure radiopharmaceuticals have requirements quality to proving its efficiency. Several aspects should be controlled within the Quality Assurance Programs, and one of them is the traceability of the Radionuclides Activity Measurement in radiopharmaceuticals doses. The quality assurance of activity measurements is fundamental to maintain both the efficiency of the nuclear medicine procedures and patient and exposed occupationally individuals safety. The radiation doses received by patients, during the nuclear medicine procedures, is estimated according to administered radiopharmaceuticals quantity. Therefore it is very important either the activity measurements performed in radiopharmaceuticals producer centers (RPC) as the measurements performed in nuclear medicine services are traceable to national standards. This paper aims to present an implementation program to provide traceability to radionuclides activity measurements performed in the dose calibrators(well type ionization chambers) used in Radiopharmaceuticals Producer Center placed in different states in Brazil. The proposed program is based on the principles of GM Pand ISO 17025 standards. According to dose calibrator performance, the RPC will be able to provide consistent, safe and effective radioactivity measurement to the nuclear medicine services. (author)

  17. Current status of production and research of radioisotopes and radiopharmaceuticals in Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Soenarjo, Sunarhadijoso; Tamat, Swasono R. [Center for Development of Radioisotopes and Radiopharmaceuticals, National Nuclear Energy Agency (BATAN), Kawasan Puspiptek, Serpong, Tangerang (Indonesia)

    2000-10-01

    The use of radioactive preparation in Indonesia has sharply increased during the past years, indicated by increase of the number of companies utilizing radioisotopes during 1985 to 1999. It has been clearly stressed in the BATAN's Strategic Plan for 1994-2014 that the production of radioisotopes and radiopharmaceuticals is one of five main industrial fields within the platform of the Indonesian nuclear industry. Research programs supporting the production of radioisotopes and radiopharmaceuticals as well as development of production technology are undertaken by the Research Center for Nuclear Techniques (RCNT) in Bandung and by the Radioisotope Production Center (RPC) in Serpong, involving cooperation with other research center within BATAN, universities and hospitals as well as overseas nuclear research institution. The presented paper describes production and research status of radioisotopes and radiopharmaceuticals in Indonesia after the establishment of P.T. Batan Teknologi in 1996, a government company assigned for activities related to the commercial application of nuclear technology. The reviewed status is divided into two short periods, i.e. before and after the Chairman Decree No. 73/KA/IV/1999 declaring new BATAN organizational structure. Subsequent to the Decree, all commercial requests for radioisotopes and radiopharmaceuticals are fulfilled by P.T. Batan Teknologi, while demands on novel radioactive preparations or new processing technology, as well as research and development activities should be fulfilled by the Center for the Development of Radioisotopes and Radiopharmaceuticals (CDRR) through non-commercial arrangement. The near-future strategic research programs to response to dynamic public demand are also discussed. The status of research cooperation with JAERI (Japan) is also reported. (author)

  18. Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases.

    Science.gov (United States)

    Lange, Rogier; Ter Heine, Rob; Knapp, Russ Ff; de Klerk, John M H; Bloemendal, Haiko J; Hendrikse, N Harry

    2016-10-01

    Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents.

  19. The radiopharmaceuticals labelled with technetium-99m and the radiopharmacy; Les radiopharmaceutiques marques au technetium-99m et la radiopharmacie

    Energy Technology Data Exchange (ETDEWEB)

    Bodenant, V

    1998-10-01

    In less than fifty years, the place of nuclear medicine is become primordial. Among all the radiopharmaceuticals used in nuclear medicine, the technetium-99m is the most used because of its physico-chemical properties and its great availability with the molybdenum-99m - technetium-99m generator. Since 1992, the radiopharmaceuticals, the packages, the generators are included in the pharmaceutic monopole. They are now under the reliability of the radio-pharmacist. This thesis has for object to introduce these different radiopharmaceuticals labelled with technetium-99m and to show the primordial place of the radio-pharmacist in a service of nuclear medicine. (N.C.)

  20. Understanding radioxenon isotopical ratios originating from radiopharmaceutical facilities

    Science.gov (United States)

    Saey, P. R. J.; Ringbom, A.; Bowyer, T. W.; Becker, A.; de Geer, L.-E.; Nikkinen, M.; Payne, R. F.

    2009-04-01

    It was recently shown that radiopharmaceutical facilities (RPF) are major contributors to the general background of 133Xe and other xenon isotopes both in the northern and southern hemisphere. To distinguish a nuclear explosion signal from releases from civil nuclear facilities, not only the activity concentrations but also the ratios of the four different CTBT relevant radioxenon isotopes (131mXe, 133mXe, 133Xe and 135Xe) have to be well understood. First measurements taken recently in and around two of the world's largest RPF's: NTP at Pelindaba, South Africa and IRE at Fleurus, Belgium have been presented. At both sites, also stack samples were taken in close cooperation with the facility operators. The radioxenon in Belgium could be classified in four classes: the normal European background (133Xe activity between 0 - 5 mBq/m3) on one hand and then the samples where all four isotopes were detected with 133mXe/131mXe > 1. In northern South Africa the Pelindaba RPF is in practice the sole source of radioxenon. It generated a background of 133Xe at the measurement site some 230 km to the west of the RPF of 0 - 5 mBq/m3. In the cases where the air from the Pelindaba facility reached the measurement site directly and in a short time period, the 133Xe was higher, also 135Xe was present and in some samples 133mXe as well. The ratios of the activity concentrations of 135Xe/133Xe vs. 133mXe/131mXe (Multiple Isotope Ratio Plot - MIRC) have been analysed. For both facilities, the possible theoretical ratio's for different scenarios were calculated with the information available and compared with the measurements. It was found that there is an excess of 131mXe present in the European samples compared to theoretical calculations. A similar excess has also been seen in samples measured in northern America. In South Africa, neither the environmental samples nor the stack ones contained 131mXe at measurable levels. This can probably be explained by different processes and

  1. Sensitive determination of specific radioactivity of positron emission tomography radiopharmaceuticals by radio high-performance liquid chromatography with fluorescence detection

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Ryuji [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: nakaor@nirs.go.jp; Furutsuka, Kenji [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Sumitomo Accelerator Service, Tokyo 141-8686 (Japan); Yamaguchi, Masatoshi [Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180 (Japan); Suzuki, Kazutoshi [Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2008-10-15

    A sensitive quality control method is often required in positron emission tomography (PET) radiopharmaceutical analysis due to the high specific radioactivity of synthetic products. The applicability of a radio high-performance liquid chromatography (HPLC) method with fluorescence detection was evaluated for a wide variety of PET radiopharmaceuticals. In 29 different radiopharmaceuticals studied, 20 compounds exhibited native fluorescence. These properties enabled sensitive determination of their chemical masses by direct fluorimetric detection after separation by HPLC. For some substances, detection limits were below nanograms per milliliter level, at least 40 times better than current UV absorbance detection. Sufficient reproducibility and linearity were obtained for the analysis of pharmaceutical fluid. Post-column fluorimetric derivatization was also established for the quantitative determination of FDG and ClDG in [{sup 18}F]FDG samples. These methods could be applied successfully to the analysis of PET radiopharmaceuticals with ultra-high specific radioactivity.

  2. Preliminary study fo the interference of proteic compounds of radiopharmaceuticals in the test of lisadode amebocitos de limulus (LAL)

    CERN Document Server

    Aldana, C

    1997-01-01

    In this thesis the objective was evaluate the interference of proteic compounds of the radiopharmaceuticals in the test LAL (lisado of amebocitos de limulus) for this, macroagregates of albumina (MAA) was used with metilendifosfonato (MDP) as control that is the radiopharmaceutical more used in the nuclear medicine centers of the country. Initially preliminary test were carried out to assess if some of two radiopharmaceuticals would cause interference with LAL test, after the test was validated and finally routine tests were made. With the preliminary assays was concluded that proteic compounds did not cause interference (albumina with a concentration of 2 md/dl) with the MAA. However with the MDP cause interference with LAL test. The interference was eliminated with a dilution of 1:8 of the sample. Was concluded that the success of LAL test depends on conditions such as temperature, pH, constant incubation (no minimum variations) and that is a good test for quality control of the radiopharmaceuticals.

  3. A rapid and efficient preparation of [{sup 123}I]radiopharmaceuticals using a small HPLC Rocket[reg] column

    Energy Technology Data Exchange (ETDEWEB)

    Katsifis, Andrew [Radiopharmaceuticals Division R and D, Australian Nuclear Science and Technology, Organisation, Menai, NSW 2234, Sydney (Australia)]. E-mail: akx@ansto.gov.au; Papazian, Vahan [Radiopharmaceuticals Division R and D, Australian Nuclear Science and Technology, Organisation, Menai, NSW 2234, Sydney (Australia); Jackson, Timothy [Radiopharmaceuticals Division R and D, Australian Nuclear Science and Technology, Organisation, Menai, NSW 2234, Sydney (Australia); Loc' h, Christian [Radiopharmaceuticals Division R and D, Australian Nuclear Science and Technology, Organisation, Menai, NSW 2234, Sydney (Australia)

    2006-01-01

    A simplified method for the rapid and efficient preparation of [{sup 123}I]radiopharmaceuticals is described. Three radiopharmaceuticals, [{sup 123}I]{beta}-CIT, [{sup 123}I]MIBG and [{sup 123}I]clioquinol, were synthesised and purified as model compounds. The radiotracers were labelled with iodine-123 using electrophilic oxidative conditions and purified by a compact semi-preparative reverse phase column (C-18, 3 {mu}m, 7x53 mm, Alltima Rocket[reg, Alltech] using aqueous-ethanol as HPLC solvents that were directly used for radiopharmaceutical formulation. The radiochemical purity of the radioiodinated tracers as assessed by analytical HPLC was higher than 99% with specific activity higher than 3 GBq/nmol. The total preparation time of a radiotracer ranged from 40 to 60 min and, starting from 3.7 GBq of iodine-123, more than 2.5 GBq of formulated radiopharmaceuticals were available for clinical investigations.

  4. Preparações radiofarmacêuticas e suas aplicações Radiopharmaceuticals and applications

    Directory of Open Access Journals (Sweden)

    Rita Oliveira

    2006-06-01

    ármacos em uso clínico corresponde a agentes de perfusão. Atualmente, o esforço de investigação na área da química radiofarmacêutica centra-se no desenvolvimento de radiofármacos específicos que possam fornecer informação, ao nível molecular, relativa às alterações bioquímicas associadas às diferentes patologias.Radiopharmaceuticals are substances without pharmacological activity that are used in Nuclear Medicine for diagnosis and therapy for several diseases. Diagnosis radiopharmaceuticals generally emit gamma radiation or positrons (beta+, because their decay originates penetrating electromagnetic radiation that can cross the tissues and be externally detected. Therapeutic radiopharmaceuticals must include in their composition ionized particles emission nucleus (a, b- or Auger electrons, since their action is based in selective tissue destruction. There are two main methods for image acquisition: SPECT (Single Photon Emission Computerized Tomography that uses g emission radionuclides (99mTc, 123I, 67Ga, 201Tl and PET (Positron Emission Tomography that uses positron emission radionuclides like 11C, 13N, 15O, 18F. Radiopharmaceuticals can be classified into perfusion radiopharmaceuticals (first generation or specific radiopharmaceuticals (second generation. Perfusion radiopharmaceuticals are transported in the blood e reach the target organ in the direct proportion of the blood stream. Specific radiopharmaceuticals contain a biologically active molecule that binds to cellular receptors that must remain biospecific after binding to the radiopharmaceutical. For this type of radiopharmaceuticals, tissue or organ uptake is determined by the biomolecule capacity of recognizing receptors in those biological structures. Radiopharmaceuticals are produced ready to use, in cold kits or in autologal preparations. According to the preparation type there is a different quality control procedure. Most of the radiopharmaceuticals used nowadays are of the perfusion type

  5. Radiopharmaceutical: options to marketing authorization; Le medicament radiopharmaceutique: les alternatives a l'AMM

    Energy Technology Data Exchange (ETDEWEB)

    Guilloteau, D.; Valat, Ch. [Centre Hospitalier Regional Universitaire, Service Medecine Nucleaire In Vitro, INSERM U 619, 37 - Tours (France); Verbruggen, A. [University Hospital Gasthuisberg, Lab. of Radiopharmaceutical Chemistry, Leuven (Belgium)

    2005-04-15

    In France, since the law 92-1279 (December 1992) the tracer used in nuclear medicine are considered as medicines, and all the regulations applicable to general medicines have to be followed for radiopharmaceuticals. The best situation in order to use radiopharmaceutical in nuclear medicine center is to use a tracer with a marketing authorization. However due to the very high cost to obtain this authorization, many tracers validated by scientific community will never been sold by pharmaceutical companies. However in respect with legal rules, it is possible to prepare these tracers in the hospital radiopharmacy, under the responsibility of the radio-pharmacist. We discuss here these different possibilities (magistral preparation...) and the conditions for these preparations. (author)

  6. Potential synergistic implications for stromal-targeted radiopharmaceuticals in bone-metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor

    2011-01-01

    Genetic heterogeneity and chemotherapy-resistant 'stem cells' represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long been present for men with localized disease, metastatic prostate cancer is currently incurable. Though substantial improvements in outcomes are now possible through the utilization of newly approved therapies, novel combinations are clearly needed. Herein we describe potentially synergistic interactions between bone stromal-targeted radiopharmaceuticals and other therapies for treatment of bone-metastatic prostate cancer. Radiation has long been known to synergize with cytotoxic chemotherapies and recent data also suggest the possibility of synergy when combining radiation and immune-based strategies. Combination therapies will be required to substantially improve survival for men with castrate-resistant metastatic prostate cancer and we hypothesize that bone-targeted radiopharmaceuticals will play an important role in this process.

  7. Radiochemistry on chip: towards dose-on-demand synthesis of PET radiopharmaceuticals.

    Science.gov (United States)

    Arima, Valentina; Pascali, Giancarlo; Lade, Oliver; Kretschmer, Hans R; Bernsdorf, Ingo; Hammond, Victoria; Watts, Paul; De Leonardis, Francesco; Tarn, Mark D; Pamme, Nicole; Cvetkovic, Benjamin Z; Dittrich, Petra S; Vasovic, Nikola; Duane, Russell; Jaksic, Aleksandar; Zacheo, Antonella; Zizzari, Alessandra; Marra, Lucia; Perrone, Elisabetta; Salvadori, Piero A; Rinaldi, Rosaria

    2013-06-21

    We have developed an integrated microfluidic platform for producing 2-[(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) in continuous flow from a single bolus of radioactive isotope solution, with constant product yields achieved throughout the operation that were comparable to those reported for commercially available vessel-based synthesisers (40-80%). The system would allow researchers to obtain radiopharmaceuticals in a dose-on-demand setting within a few minutes. The flexible architecture of the platform, based on a modular design, can potentially be applied to the synthesis of other radiotracers that require a two-step synthetic approach, and may be adaptable to more complex synthetic routes by implementing additional modules. It can therefore be employed for standard synthesis protocols as well as for research and development of new radiopharmaceuticals.

  8. Structure biodistribution relationship of radiolabeled ergolines: search for brain imaging radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Basmadjian, G.P.; Sadek, S.A.; Mikhail, E.A.; Parikh, A.; Weaver, A.; Mills, S.L. (Oklahoma Univ., Oklahoma City, OK (USA). Medical Center)

    1989-08-01

    A series of ergoline derivatives, analogues of Pergolide and Lysergol were synthesized, radiolabeled with {sup 125}I or {sup 75}Se, and evaluated for their ability to cross the Blood Brain Barrier of rats, for potential use as radiopharmaceuticals for imaging the brain. Introduction of the radiolabel was either at the 17- position (attached to the 8{beta}-methylene) or at the 2- position of the indole portion of the ergoline moiety. Of the 8 radiolabeled compounds tested, two pergoline analogues, 8{beta}-(methyl-{sup 75}Se-seleno)-methyl-6-propyl ergoline and 8{beta}-({sup 125}I)-iodomethyl-6-propyl ergoline, showed the highest uptake in the brain, adrenal and heart with good organ to blood ratios. This work has shown that analogues of pergolide, a dopamine agonist, if labeled with {sup 123}I may yield a clinically useful brain imaging radiopharmaceutical. (author).

  9. Detection of sentinel lymphnode using radiopharmaceuticals methods, importance and safety handling

    Energy Technology Data Exchange (ETDEWEB)

    Yokoyama, Kunihiko; Nakajima, Kenichi; Tonami, Norihisa; Tugawa, Koichiro; Noguchi, Masakuni [Kanazawa Univ. (Japan). Hospital

    2000-04-01

    In our district, there is no approved radiopharmaceutical appropriate for lymphoscintigraphy. Thus, we have attempted to evaluate the three radiopharmaceuticals such as {sup 99m}Tc-human serum albumin (HSA), {sup 99m}Tc-tin colloid (TC) and {sup 99m}Tc-phytate for this application. HSA demonstrated the sentinel LNs in 35 out 49 cases. However, it traveled so rapid that LNs might tend to be visualized more than the sentinel LN. TC was so big in size that it could only visualize the sentinel LNs in 18 out of 33 cases. Although the number of patients who received phytate is limited, it seemed to detect sentinel LNs better that the other 2 compounds. (author)

  10. Radiopharmaceutical stannic Sn-117m chelate compositions and methods of use

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Suresh C. (Setauket, NY); Meinken, George E. (Middle Island, NY)

    2001-01-01

    Radiopharmaceutical compositions including .sup.117m Sn labeled stannic (Sn.sup.4+) chelates are provided. The chelates are preferably polyhydroxycarboxylate, such as oxalates, tartrates, citrates, malonates, gluconates, glucoheptonates and the like. Methods of making .sup.117m Sn-labeled (Sn.sup.4+) polyhydroxycarboxylic chelates are also provided. The foregoing pharmaceutical compositions can be used in methods of preparing bone for scintigraphical analysis, for radiopharmaceutical skeletal imaging, treatment of pain resulting from metastatic bone involvement, treatment of primary bone cancer, treatment of cancer resulting from metastatic spread to bone from other primary cancers, treatment of pain resulting from rheumatoid arthritis, treatment of bone/joint disorders and to monitor radioactively the skeletal system.

  11. Development of a modular system for the synthesis of PET [{sup 11}C]labelled radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Boschi, Stefano [PET Radiopharmacy, Nuclear Medicine, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna (Italy)], E-mail: stefano.boschi@aosp.bo.it; Lodi, Filippo [PET Radiopharmacy, Nuclear Medicine, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna (Italy); Cicoria, Gianfranco [Medical Physics, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi (Italy); Raul Ledesma, Jorge [Fundacion Escuela de Medicina Nuclear, Mendoza (Argentina); Knopp, Roger [Eckert Ziegler-Eurotope, Berlin (Germany); Rizzello, Anna; Di Pierro, Donato; Trespidi, Silvia [PET Radiopharmacy, Nuclear Medicine, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Via Massarenti 9, 40138 Bologna (Italy); Marengo, Mario [Medical Physics, Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi (Italy)

    2009-10-15

    [{sup 11}C]labelled radiopharmaceuticals as N-[{sup 11}C]methyl-choline ([{sup 11}C]choline), L-(S-methyl-[{sup 11}C])methionine ([{sup 11}C]methionine) and [{sup 11}C]acetate have gained increasing importance in clinical PET and for the routine production of these radiopharmaceuticals, simple and reliable modules are needed to produce clinically relevant radioactivity. On the other hand, flexible devices are needed not only for the routine synthesis but also for more complex applications as the development of new tracers. The aim of this work was the adaptation of an Eckert Ziegler modular system for easy routine synthesis of [{sup 11}C]choline, [{sup 11}C]methionine and [{sup 11}C]acetate using components that account for straightforward scaling up and upgrades.

  12. Options for shielding the hand during dispensing and administration of radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Whitby, M.; Martin, C. J.

    2002-07-01

    Hospital staff manipulating radiopharmaceuticals may receive significant radiation doses to their hands. A study of hand doses has been carried out in a large radionuclide dispensary and in nuclear medicine departments in the West of Scotland and the implications of different shielding options considered. Doses received for individual manipulation during many routine sessions have been measured with an electronic extremity dose monitor. Doses received from dispensing of radiopharmaceuticals in nuclear medicine were 4 mGy per 10 GBq handled, compared to 0.2 mGy per 10 GBq for radionuclide dispensary staff. There were a number of reasons for the large difference, with one of the most important being the speed with which the manipulations were performed. The actions performed in nuclear medicine consist of dispensing into a syringe and injection. Withdrawal of radiopharmaceuticals made up the higher dose component 5 to 500 {mu}Sv per procedure as a siring shield was not used for this part of the procedure. Doses received from individual injections for which syringe shields were used varied from 1.5 to 300 {mu}Sv depending on the degree of difficulty experienced during the injection. The study has shown the effectiveness of using local shielding in dose reduction. Tungsten vial shields limit the radiation dose and are useful for handling large activities during radiopharmaceutical preparation. Syringe shields substantially reduce doses for individual manipulations and should be used for procedures in which accurate reading of the syringe scale is not required. This includes higher dose manipulations in the radionuclide dispensary and injections in nuclear medicine. (Author)

  13. A Study on the Quality Control of {sup 18}F-FDG Radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ssang Tae [CareCamp Inc., Seoul (Korea, Republic of); Yong, Chul Soon [Yeungnam University, Gyeongsan (Korea, Republic of); Han, Eun Ok [Daegu Health College, Daegu (Korea, Republic of)

    2010-12-15

    The types of test items which were recorded in this test report of quality control domestic {sup 18}F-FDG radiopharmaceutical which consisted of 13 different types: appearance, half-life, radioactive heterokaryosis, radiochemical Confirmation (measure of Rf value), radiochemical Purity, Ethanol, Acetonitrile, Kryptofix, Aluminium, pH, Endotoxin, aseptic test, and radioactivity·ml-1. The record was fully recorded in 'appearance', 'radioactive heterokaryosis', 'pH', 'Endotoxin', and 'aseptic test'. In 'half-life', 'radiochemical Confirmation (measure of Rf value), 'radiochemical Purity', 'Ethanol', 'Acetonitrile', 'Kryptofix', 'Aluminium', 'radioactivity·ml-1', there were differences in records of each manufacturing business on radioactive medicine and medical supplies. The result of the test showed all 13 items of quality control test were 100% suitable on the basis of recorded data. There were more radiopharmaceutical made in the laboratory than in hospitals and businesses and in for result of suitability test, the laboratory showed higher suitability than did the hospitals or businesses. Domestically, there are differences of the test report items in the safety of radiopharmaceutical of each facility, and since it is not standardized, supplements are needed. To submit standardized test reports of quality guarantee in radiopharmaceutical, GMP of U.S. and CE Mark of Europe should be referred as well as receiving advice from professionals to standardize as suitable domestic standard.

  14. Novel diagnostic and therapeutic radionuclides for the development of innovative radiopharmaceuticals

    CERN Multimedia

    We propose the exploration of novel radionuclides with diagnostic or therapeutic properties from ISOLDE. Access to such unique isotopes will enable the fundamental research in radiopharmaceutical science towards superior treatment, e.g. in nuclear oncology. The systematic investigation of the biological response to the different characteristics of the decay radiation will be performed for a better understanding of therapeutic effects. The development of alternative diagnostic tools will be applied for the management and optimization of radionuclide therapy.

  15. Garcinia xanthones as orally active antitumor agents.

    Science.gov (United States)

    Zhang, Xiaojin; Li, Xiang; Sun, Haopeng; Wang, Xiaojian; Zhao, Li; Gao, Yuan; Liu, Xiaorong; Zhang, Shenglie; Wang, Yanyan; Yang, Yingrui; Zeng, Su; Guo, Qinglong; You, Qidong

    2013-01-10

    Using a newly developed strategy whose key step is the regioselective propargylation of hydroxyxanthone substrates, 99 structurally diverse Garcinia natural-product-like xanthones based on gambogic acid were designed and synthesized and their in vitro antitumor activity was evaluated. A set of 40 related compounds was chosen for determination of their physicochemical properties including polar surface area, log D₇.₄, aqueous solubility, and permeability at pH 7.4. In the light of the in vitro antitumor activity and the physicochemical properties, two compounds were advanced into in vivo efficacy experiments. The antitumor activity of compound 112, administered po, showed more potent in vivo oral antitumor activity than gambogic acid.

  16. Overview of internal dose evaluation in the radiopharmaceutical production plant at IPEN

    Energy Technology Data Exchange (ETDEWEB)

    Todo, Alberto S.; Gerulis, Eduardo; Cardoso, Joaquim C.S.; Rodrigues Junior, Orlando, E-mail: astodo@ipen.br, E-mail: rodrijr@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2015-07-01

    The internal dosimetry program at the Instituto de Pesquisas Energeticas e Nucleares, IPEN, is accomplished in two steps: the activity measurements are performed at the In Vivo Monitoring Laboratory and subsequently the data analysis and the dose evaluation are carried out by the Dose Calculation Group according to the ICRP models. The objective of this study is to take the whole body and thyroid monitoring results recorded from 2005 to 2015 to see whether the internal contamination control procedure for workers were suitable even with the increase in the radiopharmaceutical production. The study were based in a research called “Search of Variables” for the operations carried out in the restricted areas of radiopharmaceutical production plant, taking into account the dose distribution data for all the tasks recorded by the radioprotection service. This methodology aims to identify and determine the principal variables that impact on the worker's dose. The results were presented for the following variables: individual occupationally exposed, operation variable, area/cell, type of task of operation, which depend on the variable dose. In spite of growth rate in the production of radiopharmaceutical, this study has shown that the improvements in the plant have contributed to the dose reduction of the workers. (author)

  17. Synthetic techniques of radiopharmaceuticals production labeled with C-11 for PET in cardiology

    Science.gov (United States)

    Dyubkov, V. S.; Ekaeva, I. V.; Katunina, T. A.; Rumyantsev, A. S.; Silchenkov, A. V.; Tuflina, T. V.

    2017-01-01

    Positron emission tomography (PET) and PET-Computerised Tomography (CT) are unique, non-invasive diagnostic techniques, in which the local, temporal and quantitative distributions of radioactive labelled substances are measured to investigate physiological processes. It is well known that PET centre of Bakulev Scientific Centre for Cardiovascular Surgery is the oldest one in Moscow. During more than fifteen years a large number of patients have received PET scans. Due to main stream of Scientific Centre, emphasis is placed on examining the heart functioning. For the diagnosis innervation of the heart muscle a number of radiopharmaceuticals are used, including PET radiopharmaceuticals such as 11C-CGP 12177, 11C-meta-hydroxyephedrine as well as its synthetic analogues labelled with other PET radionuclides (18F, 68Ga). 11C-meta-hydroxyephedrine is one of the most perspective radiopharmaceutical for an investigation of cardiac receptors function due to required materials availability for a radio synthesis in Russia. The main advantage of proposed 11C-meta-hydroxyephedrine synthesis technique is the use of a catalyst which allows one decrease reaction time from 5 minutes to 30 seconds. Obtained results allow one decrease reaction time of methylation and increase radiochemical and technological yields.

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

    Energy Technology Data Exchange (ETDEWEB)

    Welch, M.J.

    1980-06-01

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

  19. Harvard-MIT research program in short-lived radiopharmaceuticals. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J. [Massachusetts Inst. of Tech., Cambridge, MA (United States). Office of Sponsored Programs

    1995-02-01

    The Harvard-MIT Research Program in Short-lived Radiopharmaceuticals was established in 1977 to foster interaction among groups working in radiopharmaceutical chemistry at Harvard Medical School, the Massachusetts Institute of Technology, and the Massachusetts General Hospital. To this was added a group at The Childrens Hospital. From these collaborations and building upon the special strengths of the participating individuals, laboratories and institutions, it was hoped that original approaches would be found for the design of new, clinically useful, radiolabeled compounds. The original thrust of this proposal included: (a) examination of the coordination chemistry of technetium as a basis for rational radiopharmaceutical design, (b) development of an ultrashort-lived radionuclide generator for the diagnosis of congenital heart disease in newborns, (c) synthesis of receptor-site-directed halopharmaceuticals, (d) improved facile labeling of complex molecules with positron-emitting radionuclides. The authors` 1986 proposal was oriented toward organs and disease, emphasizing radiolabeled agents that delineate specific functions and the distribution of receptors in brain, heart, and tumors. In 1989, they further refined their purposes and focused on two major aims: (a) synthesis and utilization of neutral technetium and rhenium complexes of high specific activity, and (b) development of new approaches to the radiolabeling of proteins, peptides, immunoglobulins, and their fragments. In 1992, the authors amended this proposal to concentrate their efforts on biologically active peptides and proteins for targeted radiodiagnosis and therapy.

  20. Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing.

    Science.gov (United States)

    Belanger, Anthony P; Byrne, John F; Paolino, Justin M; DeGrado, Timothy R

    2009-11-01

    The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [(18)F]FDG and [(11)C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells).

  1. Use of pressure-hold test for sterilizing filter membrane integrity in radiopharmaceutical manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Belanger, Anthony P.; Byrne, John F.; Paolino, Justin M. [Brigham and Women' s Hospital, Boston, MA 02115 (United States); DeGrado, Timothy R. [Brigham and Women' s Hospital, Boston, MA 02115 (United States)], E-mail: tdegrado@partners.org

    2009-11-15

    The bubble point test is the de facto standard for postproduction filter membrane integrity test in the radiopharmaceutical community. However, the bubble point test depends on a subjective visual assessment of bubbling rate that can be obscured by significant diffusive gas flows below the manufacturer's prescribed bubble point. To provide a more objective means to assess filter membrane integrity, this study evaluates the pressure-hold test as an alternative to the bubble point test. In our application of the pressure-hold test, the nonsterile side of the sterilizing filter is pressurized to 85% of the predetermined bubble point with nitrogen, the filter system is closed off from the pressurizing gas and the pressure is monitored over a prescribed time interval. The drop in pressure, which has a known relationship with diffusive gas flow, is used as a quantitative measure of membrane integrity. Characterization of the gas flow vs. pressure relationship of each filter/solution combination provides an objective and quantitative means for defining a critical value of pressure drop over which the membrane is indicated to be nonintegral. The method is applied to sterilizing filter integrity testing associated with the commonly produced radiopharmaceuticals, [{sup 18}F]FDG and [{sup 11}C]PIB. The method is shown to be robust, practical and amenable to automation in radiopharmaceutical manufacturing environments (e.g., hot cells)

  2. Introduction to the use of FRAM on the effectiveness assessment of a radiopharmaceutical dispatches process

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Ana G.A.A., E-mail: agaap@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-07-01

    This article aims to make an introduction to the use of Functional Resonance Analysis Method (FRAM) on the effectiveness assessment of a specific radiopharmaceutical dispatching process. The main purpose was to provide a didactic view of the method application to further in-depth analysis. The investigation also provided a relevant body of knowledge of radiopharmaceuticals dispatches processes. This work uses the term 'effectiveness assessment' instead of 'risk assessment' due to the broader meaning the former provide. The radiopharmaceutical dispatching process is the final task of a dynamic system designed to attend several medical facilities. It is comprised by functions involving mostly human activities, such as checking and packaging the product and measuring the radiopharmaceutical nuclear activity. Although the dispatch process has well-known steps for its completion, the human factor is the fundamental mechanism of work and control, being susceptible of irregular and instable performance. As a socio-technical system, the risk assessment provided by FRAM may be of importance for safety and quality improvements, even more if considered the nuclear nature of the product, which makes risk assessment critical and mandatory. A system is safe if it is resistant and resilient to perturbations. Identification and assessment of possible risks is, therefore, an essential prerequisite for system safety. Although this seems obvious, most risk assessments are conducted under relative ignorance of the full behavior of the system. Such condition has lead to an approach to assess the risks of intractable systems (i.e., systems that are incompletely described or under specified), namely Resilience Engineering. Into this area, the Functional Resonance Analysis Method has been developed in order to provide concepts, terminology and a set of methods capable of dealing with such systems. The study was conducted following the Functional Resonance Analysis

  3. SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

    Energy Technology Data Exchange (ETDEWEB)

    Fernandes, F [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil); Silva, D da [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Rodrigues, L [Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil)

    2015-06-15

    Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: {sup 18}F (109,7 min, 249,8 keV), {sup 89}Zr (78,4 hs, 395,5 keV), {sup 11}C (20,4 min, 385,7 keV) and {sup 68}Ga (67,8 min, 836 keV). {sup 68}Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ({sup 18}F-FDG), lipogenesis ({sup 11}C-Choline and {sup 11}C-Acetate), amino acid transport (Anti-{sup 18}F-FACBC), bone matrix ({sup 18}F-NaF), prostatespecific membrane antigen ({sup 68}Ga-PSMA and {sup 89}Zr-J591), CXCR receptors ({sup 89}Ga-Pentixafor), adrenal receptors ({sup 18}F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti-{sup 18}FFACBC (liver) and {sup 18}F-FBDC (stomach wall) are the exception. Higher effective dose was seen {sup 18}F-NaF (27 μSv/MBq) while the lowest was {sup 11}CAcetate (3,5 μSv/MBq). Conclusion: Even though {sup 18}F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when {sup 18}F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider {sup 11}C or {sup 18}F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for {sup 18}F labeling. Anti-{sup 18}F-FACBC, {sup 68}Ga-PSMA and {sup

  4. Efficiancy of hydrogen peroxide for cleaning production areas and equipments in the radiopharmaceutical production

    Energy Technology Data Exchange (ETDEWEB)

    Baptista, Tatyana S.; Batista, Vanessa; Gomes, Antonio; Matsuda, Margareth; Fukumori, Neuza; Araujo, Elaine B. de, E-mail: tsbaptista@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    A great challenge in the radiopharmaceuticals production is to fulfill the Good Manufacturing Practices (GMPs), involving the validation of process and of all supporting activities such as cleaning and sanitization. The increasingly strict requirements for quality assurance system, with several norms and normative resolutions has led to a constant concern with programs and cleaning validation in pharmaceutical production. The main goal of GMP is to reduce risks inherent to pharmaceutical production, that is to reduce product contamination with microorganisms and cross-contamination. The basic requirements to prevent contamination is the development and implementation of efficient cleaning programs. In the case of clean rooms for the production of injectable radiopharmaceuticals, the requirement for cleaning programs is evidently higher due to the characteristics of these areas with hot cells for radioactive materials, where sterile radiopharmaceuticals are manipulated and distributed before administration to patients just after minutes or hours of its preparation. In the Radiopharmacy Department at IPEN it was established a cleaning program for clean rooms and hot cells using a hydrogen peroxide solution (20% proxitane alfa). The objective of this work was to assess effectiveness of this cleaning agent in reducing and/or eliminating microbial load in the clean rooms and equipment to acceptable levels in accordance with the current legislation. The analysis was conducted using results of the environmental monitoring program with and settling contact plates in clean rooms after the cleaning procedures. Furthermore, it was possible to evaluate the action of the sanitizing agent on the microbial population on the surface of equipment and clean rooms. It was also evaluated the best way to accomplish the cleaning program considering the dosimetric factor in each production process, as the main concern of pharmaceutical companies is the microbiological contamination, in

  5. Antitumor effects of electrochemical treatment

    Institute of Scientific and Technical Information of China (English)

    Héctor Manuel Camué Ciria; Maraelys Morales González; Lisset Ortíz Zamora; Luis Enrique Bergues Cabrales; Gustavo Victoriano Sierra González; Luciana Oliveira de Oliveira; Rodrigo Zanella

    2013-01-01

    Electrochemical treatment is an alternative modality for tumor treatment based on the application of a low intensity direct electric current to the tumor tissue through two or more platinum electrodes placed within the tumor zone or in the surrounding areas.This treatment is noted for its great effectiveness,minimal invasiveness and local effect.Several studies have been conducted worldwide to evaluate the antitumoral effect of this therapy.In all these studies a variety of biochemical and physiological responses of tumors to the applied treatment have been obtained.By this reason,researchers have suggested various mechanisms to explain how direct electric current destroys tumor cells.Although,it is generally accepted this treatment induces electrolysis,electroosmosis and electroporation in tumoral tissues.However,action mechanism of this alternative modality on the tumor tissue is not well understood.Although the principle of Electrochemical treatment is simple,a standardized method is not yet available.The mechanism by which Electrochemical treatment affects tumor growth and survival may represent more complex process.The present work analyzes the latest and most important research done on the electrochemical treatment of tumors.We conclude with our point of view about the destruction mechanism features of this alternative therapy.Also,we suggest some mechanisms and strategies from the thermodynamic point of view for this therapy.In the area of Electrochemical treatment of cancer this tool has been exploited very little and much work remains to be done.Electrochemical treatment constitutes a good therapeutic option for patients that have failed the conventional oncology methods.

  6. Drug interaction with radiopharmaceuticals: effect on the labeling of red blood cells with technetium-99m and on the bioavailability of radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Maria Luisa Gomes

    2002-09-01

    Full Text Available The evidence that natural and synthetic drugs can affect radiolabeling or bioavailability of radiopharmaceuticals in setting of nuclear medicine clinic is already known. However, this drug interaction with radiopharmaceuticals (DIR is not completely understood. Several authors have described the effect of drugs on the labeling of blood elements with technetium-99m (99mTc and on the biodistribution of radiopharmaceuticals. When the DIR is known, if desirable or undesirable, the natural consequence is a correct diagnosis. However, when it is unknown, it is undesirable and the consequences are the possibility of misdiagnosis and/or the repetition of the examination with an increase of radiation dose to the patient. The possible explanation to the appearance of DIR are (a radiopharmaceutical modification, (b alteration of the labeling efficiency of the radiopharmaceutical, (c modification of the target, (d modification of no target and/or the (e alteration of the binding of the radiopharmaceutical on the blood proteins. The effect of drugs on the labeling of blood elements with 99mTc might be explained by (i a direct inhibition (chelating action of the stannous and pertechnetate ions, (ii damage induced in the plasma membrane, (iii competition of the cited ions for the same binding sites, (iv possible generation of reactive oxygen species that could oxidize the stannous ion and/or (v direct oxidation of the stannous ion. In conclusion, the development of biological models to study the DIR is highly relevant.A evidência de que drogas naturais ou sintéticas podem afetar a radiomarcação ou a biodisponibilidade de radiofármacos nos procedimentos de medicina nuclear já é bem conhecida. Entretanto, essa interação de droga com radiofármacos (IDR não está completamente compreendida. Vários autores têm descrito o efeito de drogas na marcação de elementos sanguíneos com tecnécio-99m (99mTce na biodistribuição de radiofármacos. Quando a

  7. The relationship between administered radiopharmaceutical activity in myocardial perfusion scintigraphy and imaging outcome

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, C.N.; Aswegen, A. van; Tout, D.A. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Julious, S.A. [University of Sheffield, Sheffield (United Kingdom); Nunan, T.O. [Guy' s and St Thomas' Hospital NHS Trust, London (United Kingdom); Thomson, W.H. [Sandwell and West Birmingham Hospitals NHS Trust, Birmingham (United Kingdom); Tindale, W.B. [Sheffield Teaching Hospitals, Sheffield (United Kingdom); Underwood, S.R. [Royal Brompton and Harefield NHS Trust, London (United Kingdom); Imperial College London, London (United Kingdom); Royal Brompton Hospital, London (United Kingdom)

    2008-02-15

    Lower radiopharmaceutical activities are used for myocardial perfusion scintigraphy (MPS) in the UK than in other countries. There is no evidence to suggest that higher activities improve imaging or clinical outcome. We undertook a multicentre study of the relationship between radiopharmaceutical activity and imaging outcome. Fifty-one patients with clinical referrals for MPS followed a 2-day protocol with an injection of 1,000 MBq {sup 99m}Tc-tetrofosmin for each of the stress and rest images. ECG-gated acquisition was performed in three rotations occupying 25, 35 and 40% of a standard acquisition, and rotations were summed to simulate administered activities of 250, 400, 750 and 1,000 MBq. Each set of images was reported by an experienced physician who was blinded to all clinical information and to the simulated activity. Scores were assigned for image quality, low count, attenuation and reconstruction artefact, segmental tracer uptake, segmental and global defect classification, and confidence in the global classification. The images were reported twice to assess intra-observer variability. Positive relationships were found between administered activity and overall image quality, observer confidence and intra-observer agreement of uptake score, and a negative relationship was found with low-count artefact. For the majority of comparisons, there was no additional improvement with increasing activity from 750 to 1,000 MBq. Intra-observer agreement was found to be better in female patients and in those below average body mass index. We conclude that higher administered radiopharmaceutical activities lead to better quality images and improved surrogate parameters for clinical outcome, but that activities above 750 MBq may be unnecessary in average patients. (orig.)

  8. Eye lens dosimetry in workers of a PET radiopharmaceutical production facility

    Energy Technology Data Exchange (ETDEWEB)

    Guimaraes, M. C.; Lacerda, M. A. S.; Da Silva, T. A. [Development Center of Nuclear Technology, Posgraduate Course in Science and Technology of Radiations, Minerals and Materials, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil); Meireles, L. S.; Teles, L. L. D., E-mail: margaretecristinag@gmail.com [Development Center of Nuclear Technology / CNEN, Av. Pte. Antonio Carlos 6627, 31270-901 Belo Horizonte, Minas Gerais (Brazil)

    2015-10-15

    Full text: A new regulatory statement was issued concerning the eye lens radiation protection of persons in some planned exposures. A debate was raised on the adequacy of the dosimetric quantity and on its method of measurement. The aim of this work was to establish the dosimetry procedure with the Eye-D{sup TM} holder with a MCP-N LiF:Mg,Cu,P thermoluminescent chip detector for measuring the personal dose equivalent Hp(3) in workers of the Development Center of Nuclear Technology (DCNT) Positron-Electron Tomography (PET) Radiopharmaceuticals Production Facility (RPF). The eye lens dosimeter was calibrated and its energy response was studied in terms Hp(3) on a ISO standard slab phantom and on a recent suggested cylindrical phantom. Irradiations were carried out at the DCNT Dosimeter Calibration Laboratory in ISO reference radiations of {sup 137}Cs gamma, narrow spectrum series X-ray beams, {sup 90}Sr/{sup 90}Y and {sup 85}Kr beta rays. Fifteen workers of the RPF/DCNT were monitored during radiopharmaceutical production activities (e.g. cyclotron operation, quality control tests, radiopharmaceutical production and radioprotection). Considering the predominant exposure to 511 keV photons, the energy dependence of the dosimeter of 30% in energies down to 33 keV should not be a concern. Calibration coefficient of the dosimeter in {sup 137}Cs beam showed that the use of the slab phantom will underestimate the Hp(3) in 8.8% related to the cylindrical phantom. The absorbed dose due to beta radiation exposure seems to be unfeasible to be assessed with the chosen dosimeter. Results showed that the workers responsible for quality control tests received the highest doses and that there is room for optimization. (Author)

  9. The Radiopharmaceuticals Production and Research Centre established by the Heavy Ion Laboratory of the University of Warsaw

    Directory of Open Access Journals (Sweden)

    Choiński J.

    2014-03-01

    Full Text Available The Radiopharmaceuticals Production and Research Centre was recently installed on the premises of the Heavy Ion Laboratory, University of Warsaw. Equipped with a medical PETtrace p/d cyclotron , radiochemistry synthesis and dispensing units and a modern quality control laboratory the Centre is intended to produce regularly for commercial purposes the classic PET radiopharmaceuticals ( such -as e.g. FDG- . Situated on the largest Warsaw scientific campus OCHOTA, an important part of the Centre’s activities will also be devoted to the production of known species for preclinical studies and research into innovative radiopharmaceuticals in collaboration with other scientific units of this Campus as well as with members of the Warsaw Consortium for PET Collaboration. Research into the accelerator production route of 99mTc will also begin shortly.

  10. Knowledge evaluation for knowledge management implementation: A case study of the radiopharmaceutical centre of IPEN

    Energy Technology Data Exchange (ETDEWEB)

    Ricciardi, R.I. [Instituto de Pesquisas Energeticas e Nucleares, Nuclear and Energy Research Institute, IPEN-Brazil, Cidade Universitaria, Sao Paulo, SP (Brazil)]. E-mail: rita@ipen.br; Barroso, A.C.O. [Instituto de Pesquisas Energeticas e Nucleares, Nuclear and Energy Research Institute, IPEN-Brazil, Cidade Universitaria, Sao Paulo, SP (Brazil)]. E-mail: barroso@ipen.br; Ermine, J.-L. [INT - Institut National des Telecommunications, Evry Cedex (France)]. E-mail: jean-louis.ermine@int-evry.fr

    2006-07-01

    In recent years, organisations have used multiple methods and approaches to design their strategic and action plans. In this context, resource-based view (RBV) and knowledge-based view (KBV) frameworks have received increased attention as being instrumental to strategy formulation. The synergy of these approaches with knowledge management initiatives is intuitive and their use in a common framework is discussed here to show the importance of methods and instruments to mapping and assessing the knowledge assets of an organisation. The application of such methods to the radiopharmaceutical centre of IPEN is described. (author)

  11. {sup 18}F-labeled radiopharmaceuticals for PET in oncology, excluding FDG

    Energy Technology Data Exchange (ETDEWEB)

    Varagnolo, L.; Stokkel, M.P.M.; Mazzi, U.; Pauwels, E.K.J

    2000-02-01

    This article reviews possible use of {sup 18}F-labelled radiopharmaceuticals in oncology with positron emission tomography. The characteristics of various {sup 18}F-labelled compounds are proteins and peptides, those that bind to {center_dot} receptors, agents to assess hypoxia, and agents to evaluate gene therapy are highlighted. Furthermore, different {sup 18}F-labelled tissue specific agents are indicated for the detection and monitoring of various malignancies: melanoma, brain tumours, breast cancer, prostate cancer and colorectal cancer. {sup 18}F-fluorodeoxyglucose has been excluded from this summary.

  12. Localization of placenta in scanning by /sup 113m/In radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Cho, O.K.; Oh, K.K.; Park, C.Y.; Choi, B.S.; Ha, C.H.; Chung, S.O.; Kwak, H.M.

    1975-01-01

    Placenta previa is a common grave complication of late pregnancy, usually manifestated clinically by painless antenatal vaginal bleeding. Digital and rectal examinations are dangerous, due to the possibility that profuse hemorrhage from the vagina may result. Various radiological examinations have been performed in placenta previa for diagnosis and localization. However radioisotopic methods are superior due to safety, simplicity and a lower radiation dose, both fetal and maternal, compared to plain radiography. Among radiopharmaceuticals, In/sup 113m/ (transferrin for blood pool scan) is useful, giving more satisfactory results without any complications or untoward reactions.

  13. USCEA/NIST measurement assurance programs for the radiopharmaceutical and nuclear power industries

    Energy Technology Data Exchange (ETDEWEB)

    Golas, D.B. [Council for Energy Awareness, Washington, DC (United States)

    1993-12-31

    In cooperation with the U.S. Council for Energy Awareness (USCEA), the National Institute of Standards and Technology (NIST) supervises and administers two measurement assurance programs for radioactivity measurement traceability. One, in existence since the mid 1970s, provides traceability to suppliers of radiochemicals and radiopharmaceuticals, dose calibrators, and nuclear pharmacy services. The second program, begun in 1987, provides traceability to the nuclear power industry for utilities, source suppliers, and service laboratories. Each program is described, and the results of measurements of samples of known, but undisclosed activity, prepared at NIST and measured by the participants are presented.

  14. Development of Holmium 166-chitosan complex as a radiopharmaceutical agent for liver cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jei Man; Nam, Soon Chul; Park, Sun Joo; Moon, Eun Yi; Lee, Won Yong; Shin, Dong Hyuk; Cho, Eun Hee [Korea Atomic Energy Research Instisute, Taejon (Korea, Republic of)

    1997-09-01

    Effective therapeutic methods for cancer disease should be developed because the frequency of cancer disease is being increased rapidly. But there is no effective therapeutic method for treating these disease until now. The purpose of this research is to gain the clinical approval of Holmium{sup 166}-Chitosan complex as a radiopharmaceutical agent for liver cancer. We finished the preclinical test of Holmium{sup 166}-Chitosan complex and got the approval for clinical trial of this agent. 12 refs., 11 tabs., 9 figs. (author)

  15. Evaluation of quality control of radiopharmaceuticals in Nuclear Medicine service; Avaliacao do controle de qualidade de radiofarmacos em servico de medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Tavares, Jamille A. Lopes; Lira, Renata F. de, E-mail: jam_alt@hotmail.com, E-mail: renatafariasdelira@hotmail.com [Universidade Federal de Pernambuco (UFPE), Recife (Brazil); Santos, Marcus Aurelio P. dos, E-mail: masantos@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2014-07-01

    Radiopharmaceuticals are a type of pharmaceutical preparation associated with radionuclides with purpose of diagnosis and therapy. Nuclear Medicine Services (NMS) should perform quality control of radiopharmaceuticals according to the recommendations of the manufacturer and scientific evidences accepted by the National Agency Sanitary Surveillance ( Brazilian ANVISA). This study evaluated the quality of the main radiopharmaceuticals in a NMS of the state of Pernambuco in relation to pH and radiochemical purity. The results showed that 96.8% of the radiopharmaceuticals showed radiochemical purity and all pH values were within the range recommended by the American pharmacopoeia. The study found that the quality control when inserted into the NMS, provides important data that allows exclusion of radiopharmaceuticals with low radiochemistry purity, favoring a reliable diagnosis and ensuring good radiation protection practices and biosecurity for patient and occupationally exposed individuals.

  16. Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

    Energy Technology Data Exchange (ETDEWEB)

    Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M. [Austin and Repatriation Medical Centre, Melbourne, VIC (Australia). Centre for Positron Emission Tomography

    1997-10-01

    Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient`s body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t,{sub 1/2}=2min), nitrogen-13 (t{sub 1/2}= 10 min), carbon-11 (t{sub 1/2}=20 min) and fluorine-18 (t{sub 1/2}= 110 min). These radiopharmaceuticals include [{sup 15}O]oxygen, [{sup 15}O]carbon monoxide, [{sup 15}O]carbon dioxide, [{sup 15}O]water, [{sup 13}N]ammonia, [{sup 11}C]flumazenil, [{sup 11}C]SCH23390, [{sup 18}F]fluoromisonidazole and [{sup 18}F]fluoro-deoxy-glucose ([{sup 18}F]FDG). In addition, since the half life of [{sup 18}F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [{sup 18}F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [{sup 18}F]thymidine analog to measure cell proliferation and a [{sup 11}C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors) 23 refs., 2 tabs.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-06-01

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

  18. European regulatory framework on the use and development of pharmaceuticals and radiopharmaceuticals for pediatrics.

    Science.gov (United States)

    Mensonides-Harsema, Marguérite; Otte, Andreas

    2011-01-01

    A survey in 2000 revealed that only about 30% of the prescriptions in the European pediatric population were on the basis of evidence-based medicine (EbM). Less for radiopharmaceuticals and principally for diagnostics, radiologists throughout Europe are referred to the pediatric guidelines of the European Association of Nuclear Medicine (EANM), as none of the frequently used tracers have been evaluated in clinical trials in the different pediatric subgroups. Following a resolution to address the lack of EbM in children, the European Commission published the Pediatric Regulation EC 1901/2006 and its amendment EC 1902/2006, effective from 2007. This regulation foresees the development of evidence-based medicine in the pediatric population. This is effected through a set of principles like the mandatory pediatric investigation plan (PIP) to be included with the market authorization application (MAA), and the pediatric use market authorization (PUMA) for off-patent pharmaceuticals, and to a very small part radiopharmaceuticals with funding possibilities for pediatric-specific research through the 7th Framework Programme (7FP) of the European Union.

  19. Direct Technetium radiopharmaceuticals production using a 30MeV Cyclotron

    Directory of Open Access Journals (Sweden)

    M Kamali Dehgan

    2011-07-01

    Full Text Available Background and purpose of the study: Technetium-99m is the major radionuclide used in the world and mainly is provided by fission product. However extensive research has been conducted on the use of accelerators for production of 99mTc. This investigation reports the production of 99mTc radioisotope using cyclotrons followed by the preparation, quality control and biodistribution studies of four major Tc-radiopharmaceuticals. Methods: The high purity molybdenum natural target (130mg/cm2 was irradiated in a Cyclone 30 accelerator using 160 µA of 25 MeV proton beam energy for 1000 µA-h. After dissolution, the technetium radionuclides were extracted using methyl ethyl ketone (MEK followed by preparation of Tc-MIBI, Tc-DTPA, Tc-DMSA and Tc-phytate as radiopharmaceutical samples. Results: The results of quality controls and animal biodistribution studies showed successful production of Tc radionuclides (including 99mTc in the bombarded target and subsequent labelling of the kit with Tc. Conclusion: The developed high power Mo target if constructed using enriched 100Mo, could be a practical method for large-scale production of 99mTc and promising as an alternative to fission product 99Mo-99mTc generators for local applications near cyclotron facilities.

  20. 18F-Labeled Silicon-Based Fluoride Acceptors: Potential Opportunities for Novel Positron Emitting Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Vadim Bernard-Gauthier

    2014-01-01

    Full Text Available Background. Over the recent years, radiopharmaceutical chemistry has experienced a wide variety of innovative pushes towards finding both novel and unconventional radiochemical methods to introduce fluorine-18 into radiotracers for positron emission tomography (PET. These “nonclassical” labeling methodologies based on silicon-, boron-, and aluminium-18F chemistry deviate from commonplace bonding of an [18F]fluorine atom (18F to either an aliphatic or aromatic carbon atom. One method in particular, the silicon-fluoride-acceptor isotopic exchange (SiFA-IE approach, invalidates a dogma in radiochemistry that has been widely accepted for many years: the inability to obtain radiopharmaceuticals of high specific activity (SA via simple IE. Methodology. The most advantageous feature of IE labeling in general is that labeling precursor and labeled radiotracer are chemically identical, eliminating the need to separate the radiotracer from its precursor. SiFA-IE chemistry proceeds in dipolar aprotic solvents at room temperature and below, entirely avoiding the formation of radioactive side products during the IE. Scope of Review. A great plethora of different SiFA species have been reported in the literature ranging from small prosthetic groups and other compounds of low molecular weight to labeled peptides and most recently affibody molecules. Conclusions. The literature over the last years (from 2006 to 2014 shows unambiguously that SiFA-IE and other silicon-based fluoride acceptor strategies relying on 18F− leaving group substitutions have the potential to become a valuable addition to radiochemistry.

  1. Evaluation of a measurement system for Uranium electrodeposition control to radiopharmaceuticals production

    Energy Technology Data Exchange (ETDEWEB)

    Tufic Madi Filho; Adonis Marcelo Saliba Silva; Jose Patricio Nahuel Cardenas; Maria da Conceicao Costa Pereira; Valdir Maciel Lopes; Alexandre, P. S.; Diogo, F. S.; Rafael, T. P.; Vitor, O. A; Anderson, F. L.; Lucas, R. S.; Brianna, S.; Eduardo, L. C. [Nuclear and Energy Research Institute, IPEN-CNEN/SP, Av. Prof. Lineu Prestes 2242 Cid Univers. CEP: 05508-000- Sao Paulo-SP, (Brazil)

    2015-07-01

    For 2016, studies by international bodies forecast a crisis in the supply of Molybdenum ({sup 99}Mo), which is the generator of {sup 99m}Tc, widely used for medical diagnoses and treatments. As a result, many countries are making efforts to prevent this crisis. Brazil is developing the Brazilian Multipurpose Reactor (RMB) project, under the responsibility of the National Nuclear Energy Commission (CNEN). The RMB is a nuclear reactor for research and production of radioisotopes used in the production of radiopharmaceuticals and radioactive sources, broadly used in industrial and research areas in Brazil. Electrodeposition of uranium is a common practice to create samples for alpha spectrometry and this methodology may be an alternative way to produce targets of low enriched uranium (LEU) to fabricate radiopharmaceuticals, as {sup 99}Mo, used for cancer diagnosis. To study the electrodeposition, a solution of 10 mM uranyl nitrate, in 2-propanol, containing uranium enriched to 2.4% in {sup 235}U, with pH = 1, was prepared and measurements with an alpha spectrometer were performed. These studies are justified by the need to produce {sup 99}Mo since, despite using molybdenum in bulk, Brazil is totally dependent on its import. In this project, we intend to obtain a process that may be technologically feasible to control the radiation targets for {sup 99}Mo production. (authors)

  2. 正电子放射性药物的点击合成%Click synthesis of PET radiopharmaceuticals

    Institute of Scientific and Technical Information of China (English)

    许梅; 匡春香

    2009-01-01

    Increasing attention has been focused on synthesis radiopharmaceuticals for positron emission tomography (PET).The recent years witnessed applications of click chemistry to PET radiopharmaceutical synthesis,because of its distinctive advantages including high speed,yield and stereospecificity under mild conditions.Synthesis of 18F-labeled and 11C-labeled radiopharmaceuticals and intermediates via click chemistry are reviewed.The future trend of click chemistry for the synthesis of PET radiopharmaceutical is prospected.%正电子放射性药物的合成是核技术应用领域的焦点之一.近年来点击化学因其高速、高收率、高选择性和条件温和等优点而应用于正电子放射性药物的合成.本文综述了近年来点击化学在PET药物合成中的研究进展(包括将18F和11C导入药物分子),并展望其发展前景.

  3. An in vitro approach to evaluate and develop potential Sn-117m based bone-seeking radiopharmaceuticals

    NARCIS (Netherlands)

    Jansen, D.R.

    2010-01-01

    It has become standard practice in the development of radiopharmaceuticals to evaluate/assess the efficacy of prospective therapeutic or diagnostic agents by animal models, which generally calls for subjecting a substantial number of animals to intensive test and retest measurements for obtaining re

  4. The good laboratory practice and good clinical practice requirements for the production of radiopharmaceuticals in clinical research

    NARCIS (Netherlands)

    De Vos, FJ; De Decker, M; Dierckx, RA

    2005-01-01

    Radiopharmaceuticals account for more than 95% of the group of sterile pharmaceutical products and should therefore be handled and produced with care. Since the introduction of the European directive, all pharmaceuticals used in clinical studies must be prepared under good manufacturing practice (GM

  5. A restricted access material for rapid analysis of [(11)C]-labeled radiopharmaceuticals and their metabolites in plasma

    DEFF Research Database (Denmark)

    Gillings, N.

    2009-01-01

    , sensitive and robust method for the measurement of plasma samples from PET studies using [(11)C]-labeled radiopharmaceuticals. METHODS: Unadulterated plasma samples were analyzed directly, following a simple filtration, by the use of a small extraction column, containing a restricted access material...

  6. Radiopharmaceuticals preparation following hygienic rule; Preparation des radiopharmaceutiques dans le respect des regles d'hygiene

    Energy Technology Data Exchange (ETDEWEB)

    Bertrand-Barat, J.; Rogues, A.M. [Hopital Pellegrin, 33 - Bordeaux (France); Brunet-Desruet, M.D. [Centre Hospitalier Universitaire, 38 - Grenoble (France); Couret, I. [Centre Hospitalier Universitaire, 34 - Montpellier (France). Hopital Lapeyronnie; Fraysse, M. [Hopital-CHG, 03 - Montlucon (France); Saurat, S.; Tafani, M. [Centre Hospitalier Universitaire Purpan, 31 - Toulouse (France); Bounaud, M.P. [Centre Hospitalier Universitaire, Jean Bernard, 86 - Poitiers (France); Fialdes, P. [Centre Hospitalier Universitaire, 59 - Lille (France). Hopital Salengro

    1999-03-01

    The rules of radiation protection are essential in a service of nuclear medicine. A sensitization to hygiene in hospital in front of the fresh outbreak of nosocomial infections is useful in order to optimize the quality approach. In this context, the preparation of radiopharmaceuticals in the structure of nuclear medicine deserves a specific reflection. (N.C.)

  7. Quality assessment of radiopharmaceuticals in nuclear medicine services at Northeast states, Brazil; Avaliacao da qualidade de radiofarmacos em servicos de medicina nuclear de estados da regiao nordeste

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Wellington Gomes de

    2012-07-01

    The radiopharmaceuticals are used in the field nuclear medicine services (NMS) as tracer in the diagnoses and treatment of many diseases. Radiopharmaceuticals used in nuclear medicine and usually have a minimum of pharmacological effect. The procedures for labelling Radiopharmaceuticals should be observed in order to minimize risks to patients, employees and individuals from the public, and to be administered in humans, must be sterile and free of pyrogens and possess elements all measures of quality controls required a conventional drug. The 'Agencia Nacional de Vigilancia Sanitaria (ANVISA)' in its 'Resolucao de Diretoria Colegiada' (RDC) No. 38 of June 4{sup th} 2008, decided that the NMS must perform quality control in the generators eluate and radiopharmaceuticals according to recommendations of manufacturers and scientific evidence accepted by ANVISA. Thus, this study proposes to evaluate the quality of the generator {sup 99M}o-{sup 99m}Tc eluate and radiopharmaceuticals labeled with {sup 99m}Tc used in most NMS of some states in the Northeast, in relation to radionuclide, chemical, radiochemical purity and pH and promote the inclusion of procedure for quality control of radiopharmaceuticals in routine NMS. The results show that 90% radionuclidic purity, 98.2% purity chemical and radiochemical purity of 46% and 100% of the eluates are in agreement with international pharmacopoeias; already radiopharmaceuticals showed 82.6% purity and all radiochemical pH values are also in accordance with international pharmacopoeias. Even with so many positive results, staff the majority of MNS was not able to perform the quality control of the eluates and radiopharmaceuticals. Showing the importance of implementing of quality control programs of the eluates and radiopharmaceuticals in nuclear medicine. (author)

  8. Determination of radiochemical yield of {sup 99m}Tc radiopharmaceutical preparations using gamma counter and linear radiochromatography scanner

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Patricia de A.; Moura, Rebeca G.; Shiki, Andressa M.; Fukumori, Neuza T.O.; Matsuda, Margareth M.N., E-mail: patyosborne@yahoo.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    The radiochemical purity (RCP) evaluation is a prerequisite for radiopharmaceuticals before the administration in patients. RCP is defined as the proportion of the total radioactivity in the product that is present in the specified chemical form. The most widely used techniques for RCP determination in radiopharmaceutical preparations are thin layer chromatography (TLC-Al), instant thin layer chromatography (ITLC-SG) and paper chromatography (PC). These techniques combined with radioactivity detection are one of the most important tools in the RCP of the radiopharmaceutical compounds. Several methods are used for the determination of the spatial distribution of radioactivity on the strips. The aim of this study was to compare two methods for radioactivity measurement in the determination of RCP in {sup 99m}Tc radiopharmaceuticals using gamma counter and linear radiochromatography scanner. Lyophilized radiopharmaceuticals were labeled with {sup 99m}Tc. The analysis was carried out using TLC-Al and high performance thin layer chromatography (HPTLC-Cellulose) sheets, ITLC-SG and 3MM Whatman PC. The radioactivity distribution was determined by counting each strip during 1 minute in a radiochromatography TLC scanner. For comparison, the strips were cut into small pieces and each one was separately measured in a gamma-counter during 0.20 minutes in 70-210 KeV {sup 99m}Tc window. USP 36 and FDA specify that not less than 90% of the total radioactivity must be in the spot corresponding to {sup 99m}Tc labeled compound. In conclusion, the procedure for RCP determination of ALBUMINA-TEC, DEX500-TEC, ECD-TEC, MACRO-TEC and MIBI-TEC can be faster using radiochromatography. (author)

  9. Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

    Science.gov (United States)

    Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

    2013-06-01

    In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less

  10. {sup 18}F-Fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type

    Energy Technology Data Exchange (ETDEWEB)

    Balogova, Sona [Comenius University and St. Elisabeth Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Talbot, Jean-Noel; Michaud, Laure; Huchet, Virginie; Kerrou, Khaldoun; Montravers, Francoise [Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Nataf, Valerie [Hopital Tenon, AP-HP, Department of Radiopharmacy, Paris (France)

    2013-06-15

    6-Fluoro-({sup 18}F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, {sup 123}I-metaiodobenzylguanidine (MIBG) and {sup 111}In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for {sup 123}I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as

  11. Enantiopure bifunctional chelators for copper radiopharmaceuticals--does chirality matter in radiotracer design?

    Science.gov (United States)

    Singh, Ajay N; Dakanali, Marianna; Hao, Guiyang; Ramezani, Saleh; Kumar, Amit; Sun, Xiankai

    2014-06-10

    It is well recognized that carbon chirality plays a critical role in the design of drug molecules. However, very little information is available regarding the effect of stereoisomerism of macrocyclic bifunctional chelators (BFC) on biological behaviors of the corresponding radiopharmaceuticals. To evaluate such effects, three enantiopure stereoisomers of a copper radiopharmaceutical BFC bearing two chiral carbon atoms were synthesized in forms of R,R-, S,S-, and R,S-. Their corresponding peptide conjugates were prepared by coupling with a model peptide sequence, c(RGDyK), which targets the αvβ3 integrin for in vitro and in vivo evaluation of their biological behaviors as compared to the racemic conjugate. Despite the chirality differences, all the conjugates showed a similar in vitro binding affinity profile to the αvβ3 integrin (106, 108, 85 and 100 nM for rac-H2-1, RR-H2-1, SS-H2-1, and RS-H2-1 respectively with all p values > 0.05) and a similar level of in vivo tumor uptake (2.72 ± 0.45, 2.60 ± 0.52, 2.45 ± 0.48 and 2.88 ± 0.59 for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 at 1 h p.i. respectively). Furthermore, they demonstrated a nearly identical biodistribution pattern in major organs (e.g. 2.07 ± 0.21, 2.13 ± 0.58, 1.70 ± 0.20 and 1.90 ± 0.46 %ID/g at 24 h p.i. in liver for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 respectively; 1.80 ± 0.46, 2.30 ± 1.49, 1.73 ± 0.31 and 2.23 ± 0.71 at 24 h p.i. in kidneys for rac-(64)Cu-1, RR-(64)Cu-1, SS-(64)Cu-1, and RS-(64)Cu-1 respectively). Therefore we conclude that the chirality of BFC plays a negligible role in αvβ3-targeted copper radiopharmaceuticals. However, we believe it is still worthwhile to consider the chirality effects of BFCs on other targeted imaging or therapeutic agents.

  12. Antitumor Activities of Kushen: Literature Review

    Directory of Open Access Journals (Sweden)

    Mingyu Sun

    2012-01-01

    Full Text Available To discover and develop novel natural compounds with therapeutic selectivity or that can preferentially kill cancer cells without significant toxicity to normal cells is an important area in cancer chemotherapy. Kushen, the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As and kushen flavonoids (KS-Fs are well-characterized components in kushen. KS-As containing oxymatrine, matrine, and total alkaloids have been developed in China as anticancer drugs. More potent antitumor activities were identified in KS-Fs than in KS-As in vitro and in vivo. KS-Fs may be developed as novel antitumor agents.

  13. Antitumor Activities of Metal Oxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Maria Pilar Vinardell

    2015-06-01

    Full Text Available Nanoparticles have received much attention recently due to their use in cancer therapy. Studies have shown that different metal oxide nanoparticles induce cytotoxicity in cancer cells, but not in normal cells. In some cases, such anticancer activity has been demonstrated to hold for the nanoparticle alone or in combination with different therapies, such as photocatalytic therapy or some anticancer drugs. Zinc oxide nanoparticles have been shown to have this activity alone or when loaded with an anticancer drug, such as doxorubicin. Other nanoparticles that show cytotoxic effects on cancer cells include cobalt oxide, iron oxide and copper oxide. The antitumor mechanism could work through the generation of reactive oxygen species or apoptosis and necrosis, among other possibilities. Here, we review the most significant antitumor results obtained with different metal oxide nanoparticles.

  14. The antitumor activity of the fungicide ciclopirox

    OpenAIRE

    Zhou, Hongyu; Shen, Tao; Luo, Yan; Lei LIU; Chen, Wenxing; Xu, Baoshan; Han, Xiuzhen; Pang, Jia; Rivera, Chantal A.; Huang, Shile

    2010-01-01

    Ciclopirox olamine (CPX) is a synthetic antifungal agent clinically used to treat mycoses of the skin and nails. Here we show that CPX inhibited tumor growth in human breast cancer MDA-MB-231 xenografts. To unveil the underlying mechanism, we further studied the antitumor activity of CPX in cell culture. The results indicate that CPX inhibited cell proliferation and induced apoptosis in human rhabdomyosarcoma (Rh30), breast carcinoma (MDA-MB231), and colon adenocarcinoma (HT-29) cells in a co...

  15. {sup 90}Y-oxine-ethiodol, a potential radiopharmaceutical for the treatment of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yu Junfeng; Haefeli, U.O. E-mail: hafeliu@ccf.org; Sands, Mark; Dong Yonghua

    2003-05-01

    Ethiodol (or lipiodol) is selectively retained in hepatocellular carcinoma and is used as a vehicle to deliver radioactive agents following intraarterial hepatic infusion. We prepared the lipophilic complex {sup 90}Y-oxine with a radiolabeling efficiency of 97.6{+-}1.1%. After extraction into ethiodol, a stability test in serum at 37 deg. C showed that 87.8% of the {sup 90}Y remained ethiodol-bound for 7 days. Bremsstrahlung imaging of a rabbit for 48 h confirmed that the homogeneous mixture of radiolabeled {sup 90}Y-oxine and ethiodol stayed in the targeted liver lobe. This radiopharmaceutical is thus a potential candidate for the treatment of non-resectable liver cancer.

  16. The growing impact of bioorthogonal click chemistry on the development of radiopharmaceuticals.

    Science.gov (United States)

    Zeng, Dexing; Zeglis, Brian M; Lewis, Jason S; Anderson, Carolyn J

    2013-06-01

    Click chemistry has become a ubiquitous chemical tool with applications in nearly all areas of modern chemistry, including drug discovery, bioconjugation, and nanoscience. Radiochemistry is no exception, as the canonical Cu(I)-catalyzed azide-alkyne cycloaddition, strain-promoted azide-alkyne cycloaddition, inverse electron demand Diels-Alder reaction, and other types of bioorthogonal click ligations have had a significant impact on the synthesis and development of radiopharmaceuticals. This review will focus on recent applications of click chemistry ligations in the preparation of imaging agents for SPECT and PET, including small molecules, peptides, and proteins labeled with radionuclides such as (18)F, (64)Cu, (111)In, and (99m)Tc.

  17. Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Thomas L. Mindt

    2013-03-01

    Full Text Available The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (biomolecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.

  18. Sentinel node biopsy using two kinds of radiopharmaceuticals in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hisamatsu, Kazutoshi; Ishine, Masahiro; Takiyama, Wataru [Hiroshima City Asa Hospital (Japan)] [and others

    2002-08-01

    Between June 2000 and May 2001, 37 consecutive patients with breast cancer received sentinel node biopsy (SNB) be the gamma-probe method using two kinds of radiopharmaceutical, Tin colloid in 11 patients (T-group) and Phytate in 26 patients (P-group). The differences in their clinical results were evaluated retrospectively. The identification rate of SN in the P-group was superior than that in the T-group (92% vs. 64%). Accuracy and false negative rates in the P-group vs. the T-group were 96% vs. 100% and 17% vs. 0%, respectively. From these results, Phytate was more useful than Tin colloid in the SNB using gamma-probe method for patients with breast cancer. (author)

  19. The role of coordination chemistry in the development of copper and rhenium radiopharmaceuticals.

    Science.gov (United States)

    Donnelly, Paul S

    2011-02-01

    There are several isotopes of copper and rhenium that are of interest in the development of new molecular imaging or radiotherapeutic agents. This perspective article highlights the role of coordination chemistry in the design of copper and rhenium radiopharmaceuticals engineered to selectively target tissue of interest such as cancer cells or pathological features associated with Alzheimer's disease. The coordination chemistry of copper bis(thiosemicarbazone) derivatives and copper macrocyclic complexes is discussed in terms of their potential application as targeted positron emission tomography tracers for non-invasive diagnostic imaging. A range of rhenium complexes with different ligands with rhenium in different oxidation states are introduced and their potential to be translated to new radiotherapeutic agents discussed.

  20. Influence of radiation on endotoxin test using the PTSTM for 18-FDG radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Santos-Oliveira, Ralph, E-mail: roliveira@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Radiofarmacia

    2010-07-15

    F-18 FDG (2-[18-F] fluoro-2-deoxy-D-glucose) is the most frequently used radiopharmaceutical for PET and PET CT imaging exams. The FDA recently approved the use of the PTS{sup TM} (Portable Test System) as an alternative to the standard test proposed by the United States Pharmacopeia using the LAL (Limulus Amebocyte Lysates), that takes longer to perform (about 1h) than the PTS{sup TM} (15 min). Recent studies have demonstrated that radiation could interfere with the PTS{sup TM} test. In order to study the effects of radiation on the PTS{sup TM} test and/or equipment, 27 batches of F-18 FDG produced in the Nuclear Engineering Institute were analyzed. The results showed that no direct correlation with radiation was found in any of the cases. (author)

  1. PET Radiopharmaceuticals for Imaging Integrin Expression: Tracers in Clinical Studies and Recent Developments

    Directory of Open Access Journals (Sweden)

    Roland Haubner

    2014-01-01

    Full Text Available Noninvasive determination of integrin expression has become an interesting approach in nuclear medicine. Since the discovery of the first 18F-labeled cyclic RGD peptide as radiotracer for imaging integrin αvβ3 expression in vivo, there have been carried out enormous efforts to develop RGD peptides for PET imaging. Moreover, in recent years, additional integrins, including α5β1 and αvβ6, came into the focus of pharmaceutical radiochemistry. This review will discuss the tracers already evaluated in clinical trials and summarize the preliminary outcome. It will also give an overview on recent developments to further optimize the first-generation compounds such as [18F]Galacto-RGD. This includes recently developed 18F-labeling strategies and also new approaches in 68Ga-complex chemistry. Furthermore, the approaches to develop radiopharmaceuticals targeting integrin α5β1 and αvβ6 will be summarized and discussed.

  2. Design Features Of Microfluidic Reactor For [18F]FDG Radiopharmaceutical Synthesis

    Science.gov (United States)

    Oh, J. H.; Lee, B. N.; Nam, K. R.; Attla, G. A.; Lee, K. C.; Cjai, J. S.

    2011-06-01

    Microfluidic reactor exhibits advantages for radiopharmaceutical synthesis. Microfluidic chips can reduce the time for radiosynthesis using tiny quantities of chemical compounds. It also has a good heat transfer, performance and provides an integrated system including synthesis, separation, and purification. These advantages make FDG production. So we have designed a microreactor chip which included the whole chemical processing; water evaporation, solvent exchange, radiofluorination and so on. It was designed by using a commercial 3D CAD modeling program CATIA V5, heat transfer performance was analyzed by ANSYS, and CFX was used for analyzing fluid performance. This paper described the design of FDG synthesis system on a microchip, the relevant locations of its parts, both heat and fluid performance efficiency analysis.

  3. Highway accident involving radiopharmaceuticals near Brookhaven, Mississippi on December 3, 1983

    Energy Technology Data Exchange (ETDEWEB)

    Mohr, P.B.; Mount, M.E.; Schwartz, M.W.

    1985-04-01

    A rear-end collision occurred between a passenger automobile and a luggage trailer carrying 84 packages, 76 of which contained radiopharmaceuticals, on US Highway 84 near Brookhaven, Mississippi on the afternoon of December 3, 1983. The purpose of this report is to document the mechanical circumstances of the accident, confirm the nature and quantity of radioactive materials involved, and assess the nature of the physical environment to which the packages were exposed and the response of the packages. The report consists of three major sections. The first deals wth the nature and circumstances of the accident and findings of fact. The second gives an accounting and description of the materials involved and the consequences of their exposure. The third gives an assessment and analysis of the mechanisms of damage and the conclusions which may be drawn from the investigation. 4 refs., 24 figs., 4 tabs.

  4. Development of specific radiopharmaceuticals for infection imaging by targeting infectious micro-organisms.

    Science.gov (United States)

    Ferro-Flores, Guillermina; Ocampo-Garcia, Blanca E; Melendez-Alafort, Laura

    2012-01-01

    Infectious diseases remain a major health problem and cause of death worldwide. A variety of radiopharmaceuticals are used for the imaging of infections and inflammation in the practice of nuclear medicine. Long-term clinical use has shown that the majority of radiolabeled probes cannot distinguish between inflammation and infection. Gallium-67-citrate binds to bacteria, but also to proteins accumulating at both sterile inflammation and bacterial infection sites. Other agents are used to interact with receptors or domains on circulating and infiltrating leukocytes or to label them directly. However, these probes cannot distinguish between infection and inflammation because they are not specific to infectious micro-organisms. This review examines the recent developments and applications of radiolabeled specific agents, such as antiviral drugs, antifungal, antibiotics and antimicrobial peptides, to visualize infectious foci by targeting viruses, fungi or bacteria.

  5. Overview and perspectives on automation strategies in (68)Ga radiopharmaceutical preparations.

    Science.gov (United States)

    Boschi, Stefano; Malizia, Claudio; Lodi, Filippo

    2013-01-01

    The renaissance of (68)Ga radiopharmacy has led to great advances in automation technology. The availability of a highly efficient, reliable, long-lived (68)Ge/(68)Ga generator system along with a well-established coordination chemistry based on bifunctional chelating agents have been the bases of this development in (68)Ga radiopharmacy. Syntheses of (68)Ga peptides were originally performed by manual or semiautomated systems, but increasing clinical demand, radioprotection, and regulatory issues have driven extensive automation of their production process. Several automated systems, based on different post-processing of the (68)Ga generator eluate, on different engineering, and on fixed tubing or disposable cassette approaches, have been developed and are discussed in this chapter. Since automatic systems for preparation of radiopharmaceuticals should comply with qualification and validation protocols established by regulations such as current Good Manufacturing Practices (cGMP) and local regulations, some regulatory issues and the more relevant qualification protocols are also discussed.

  6. Image quality and radiopharmaceutical parameters of Indium-111 granulocytes in scintigraphy of inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Arndt, J.W.; Blok, D.; Tjon, R.T.O.; Tham, A.; Pauwels, E.K.J.; Crama-Bohbouth, G.E.; Verspaget, H.W.; Pena, A.S.; Weterman, I.T.; Lamers, C.B.H.W.

    1989-04-01

    This study was undertaken to investigate the influence of various parameters of injected autologous /sup 111/In labelled granulocytes on scintigraphic image quality. Forty-two scintigrams of 37 patients with inflammatory bowel disease were evaluated. The images were divided into three groups according to quality: Good, intermediate and poor. The relationships between image quality and such radiopharmaceutical parameters as injected dose of /sup 111/In, number of injected cells and specific activity were investigated. It appeared that in order to obtain interpretable images, a specific activity of at least 85 kBq /sup 111/In/million cells was necessary. The activity of the injected dose must exceed 7 MBq if poor quality images and very long acquisition times are to be avoided.

  7. Cage-like bifunctional chelators, copper-64 radiopharmaceuticals and PET imaging using the same

    Energy Technology Data Exchange (ETDEWEB)

    Conti, Peter S.; Cai, Hancheng; Li, Zibo; Liu, Shuanglong

    2016-08-02

    Disclosed is a class of versatile Sarcophagine based bifunctional chelators (BFCs) containing a hexa-aza cage for labeling with metals having either imaging, therapeutic or contrast applications radiolabeling and one or more linkers (A) and (B). The compounds have the general formula ##STR00001## where A is a functional group selected from group consisting of an amine, a carboxylic acid, an ester, a carbonyl, a thiol, an azide and an alkene, and B is a functional group selected from the group consisting of hydrogen, an amine, a carboxylic acid, and ester, a carbonyl, a thiol, an azide and an alkene. Also disclosed are conjugate of the BFC and a targeting moiety, which may be a peptide or antibody. Also disclosed are metal complexes of the BFC/targeting moiety conjugates that are useful as radiopharmaceuticals, imaging agents or contrast agents.

  8. Advances in the production of isotopes and radiopharmaceuticals at the Atomic Energy Corporation of South Africa

    Energy Technology Data Exchange (ETDEWEB)

    Louw, P.A.; De Villiers, W.Y.Z.; Jarvis, N.V. [Atomic Energy Corporation of South Africa Ltd, Pretoria (South Africa)

    1997-10-01

    The Atomic Energy Corporation of South Africa Ltd (AEC) owns and operates the 20 MW research reactor, SAFARI-1. Utilisation of the reactor has in recent years changed from research and materials testing to the production of isotopes. The most important breakthrough achieved in recent years is the production of high quality fission 99Mo. This has been produced routinely since April 1993 and supplied to clients across the world. A capability for the reliable production of 1000 Ci of 99Mo per week (calibrated for six days after production) has been proven. The AEC has also established facilities to produce its own 99mTc generators together with a most of radiopharmaceutical kits for diagnostic nuclear medicine purposes. The production of {sup 153}Sm and {sup 131}I (tellurium oxide route) has been operational for many years. Applications include therapeutic radiopharmaceuticals such as {sup 153}Sm-EDTMP for bone cancer pain palliation, {sup 13`}I-Lipiodol for liver cancer and {sup 131}I capsules for thyroid treatment. Facilities for the production of other isotopes such as {sup 131}I (from fission), {sup 32}P and {sup 35}S are in various stages of completion. Extensive analytical methods and equipment have been developed and are routinely used to certify the quality of exported isotopes. Irradiation and encapsulation of {sup 192}Ir is also performed routinely at the AEC. Modern facilities allow for the production of isotopes such as {sup 131}Ba and {sup 140}La on an ad hoc basis. Quality assurance procedures based on ISO9000 were developed for all aspects of the production of the various isotopes. Documentation, such as Drug Master Files, required by authorities in various countries has also been submitted and accepted 15 refs., 1 tab., 2 figs.

  9. Radiopharmaceuticals to monitor the expression of transferred genes in gene transfer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, L. I. [University of Alberta, Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-10-01

    The development and application of radiopharmaceuticals has, in many instances, been based on the pharmacological properties of therapeutic agents. The molecular biology-biotechnology revolution has had an important impact on treatment of diseases, in part through the reduced toxicity of `biologicals`, in part because of their specificity for interaction at unique molecular sites and in part because of their selective delivery to the target site. Immunotherapeutic approaches include the use of monoclonal antibodies (MABs), MAB-fragments and chemotactic peptides. Such agents currently form the basis of both diagnostic and immunotherapeutic radiopharmaceuticals. More recently, gene transfer techniques have been advanced to the point that a new molecular approach, gene therapy, has become a reality. Gene therapy offers an opportunity to attack disease at its most fundamental level. The therapeutic mechanism is based on the expression of a specific gene or genes, the product of which will invoke immunological, receptor-based or enzyme-based therapeutic modalities. Several approaches to gene therapy of cancer have been envisioned, the most clinically-advanced concepts involving the introduction of genes that will encode for molecular targets nor normally found in healthy mammalian cells. A number of gene therapy clinical trials are based on the introduction of the Herpes simplex virus type-1 (HSV-1) gene that encodes for viral thymidine kinase (tk+). Once HSV-1 tk+ is expressed in the target (cancer) cell, therapy can be effected by the administration of a highly molecularly-targeted and systemically non-toxic antiviral drug such as ganciclovir. The development of radiodiagnostic imaging in gene therapy will be reviewed, using HSV-1 tk+ and radioiodinated IVFRU as a basis for development of the theme. Molecular targets that could be exploited in gene therapy, other than tk+, will be identified

  10. Advanced research on anti-tumor effects of amygdalin.

    Science.gov (United States)

    Song, Zuoqing; Xu, Xiaohong

    2014-08-01

    Malignant tumors are the major disease that cause serious damage to human health, and have been listed as the premier diseases which seriously threatened human health by World Health Organization (WHO). In recent years the development of antitumor drugs has been gradually transformed from cytotoxic drugs to improving the selectivity of drugs, overcoming multidrug resistance, development of new targeted drugs and low toxicity with high specificity drugs. Amygdalin is a natural product that owns antitumor activity, less side effects, widely sourced and relatively low priced. All these features make the amygdalin a promising antitumor drugs, if combined with conditional chemotherapy drugs, which can produce synergistic effect. In this paper, we summarized the pharmacological activity, toxicity and antitumor activity of amygdalin, mainly focused on the advanced research of amygdalin on its antitumor effects in recent years, providing new insights for the development of new anticancer drugs, new targets searching and natural antitumor mechanism investigations.

  11. Advanced research on anti-tumor effects of amygdalin

    Directory of Open Access Journals (Sweden)

    Zuoqing Song

    2014-01-01

    Full Text Available Malignant tumors are the major disease that cause serious damage to human health, and have been listed as the premier diseases which seriously threatened human health by World Health Organization (WHO. In recent years the development of antitumor drugs has been gradually transformed from cytotoxic drugs to improving the selectivity of drugs, overcoming multidrug resistance, development of new targeted drugs and low toxicity with high specificity drugs. Amygdalin is a natural product that owns antitumor activity, less side effects, widely sourced and relatively low priced. All these features make the amygdalin a promising antitumor drugs, if combined with conditional chemotherapy drugs, which can produce synergistic effect. In this paper, we summarized the pharmacological activity, toxicity and antitumor activity of amygdalin, mainly focused on the advanced research of amygdalin on its antitumor effects in recent years, providing new insights for the development of new anticancer drugs, new targets searching and natural antitumor mechanism investigations.

  12. Considerations of radiation protection by the use of a new radiopharmaceutical in metabolic therapy; Consideraciones de proteccion radiologica por la utilizacion de un nuevo radiofarmaco en terapia metabolica

    Energy Technology Data Exchange (ETDEWEB)

    Esteve, S.; Sanchez, K.; Prieto, D.; Rodriguez, P.; Diaz, E.; Barquero, R.; Ferrer, N.; Arranz, L.

    2013-07-01

    The use of high doses of radiopharmaceutical requires special measures for radiation protection and establishing protocols to minimize the dose of professionally exposed workers and family members who have to care for, or living with the patient treated. (Author)

  13. Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17. cap alpha. -methylestradiol in normal and tumor-bearing rats

    Energy Technology Data Exchange (ETDEWEB)

    Feenstra, A.; Vaalburg, W.; Nolten, G.M.J.; Reiffers, S.; Talma, A.G.; Wiegman, T.; van der Molen, H.D.; Woldring, M.G.

    1983-06-01

    Tritiated 17..cap alpha..-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17..cap alpha..-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (K/sub d/ = 1.96 x 10/sup -10/M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 h after injection. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23 to 30% of the uptake in the uterus. Tritiated 17..cap alpha..-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that a 17 ..cap alpha..-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical.

  14. Antitumor Immunity Induced after α Irradiation

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Gorin

    2014-04-01

    Full Text Available Radioimmunotherapy (RIT is a therapeutic modality that allows delivering of ionizing radiation directly to targeted cancer cells. Conventional RIT uses β-emitting radioisotopes, but recently, a growing interest has emerged for the clinical development of α particles. α emitters are ideal for killing isolated or small clusters of tumor cells, thanks to their specific characteristics (high linear energy transfer and short path in the tissue, and their effect is less dependent on dose rate, tissue oxygenation, or cell cycle status than γ and X rays. Several studies have been performed to describe α emitter radiobiology and cell death mechanisms induced after α irradiation. But so far, no investigation has been undertaken to analyze the impact of α particles on the immune system, when several studies have shown that external irradiation, using γ and X rays, can foster an antitumor immune response. Therefore, we decided to evaluate the immunogenicity of murine adenocarcinoma MC-38 after bismuth-213 (213Bi irradiation using a vaccination approach. In vivo studies performed in immunocompetent C57Bl/6 mice induced a protective antitumor response that is mediated by tumor-specific T cells. The molecular mechanisms potentially involved in the activation of adaptative immunity were also investigated by in vitro studies. We observed that 213Bi-treated MC-38 cells release “danger signals” and activate dendritic cells. Our results demonstrate that α irradiation can stimulate adaptive immunity, elicits an efficient antitumor protection, and therefore is an immunogenic cell death inducer, which provides an attractive complement to its direct cytolytic effect on tumor cells.

  15. Structural Antitumoral Activity Relationships of Synthetic Chalcones

    Science.gov (United States)

    Echeverria, Cesar; Santibañez, Juan Francisco; Donoso-Tauda, Oscar; Escobar, Carlos A.; Ramirez-Tagle, Rodrigo

    2009-01-01

    Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series. PMID:19333443

  16. Benzoylphenylurea sulfur analogues with potent antitumor activity.

    Science.gov (United States)

    Hallur, Gurulingappa; Jimeno, Antonio; Dalrymple, Susan; Zhu, Tao; Jung, M Katherine; Hidalgo, Manuel; Isaacs, John T; Sukumar, Saraswati; Hamel, Ernest; Khan, Saeed R

    2006-04-06

    A novel series of BPU analogues were synthesized and evaluated for antitumor activity. In particular, BPU sulfur analogues 6n and 7d were shown to possess up to 10-fold increased potency, when compared to 1 (NSC-639829), against cancer cell lines. 6n was more effective than 1 in causing apoptosis of MCF-7 cells. When compared to other drugs with a similar mechanism of action, 6n retained significant ability to inhibit tubulin assembly, with an IC(50) of 2.1 microM.

  17. (18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization.

    Science.gov (United States)

    Vallabhajosula, Shankar

    2007-11-01

    Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on

  18. Role of vasoactive amines in the antitumor activity of endotoxin

    NARCIS (Netherlands)

    Hofhuis, F.M.A.; Bloksma, N.; Kuper, C.F.; Willers, J.M.N.

    1984-01-01

    To estimate a possible role of vasoamines in the antitumor action of endotoxin, effects of isoproterenol, serotonin and adrenaline on subcutaneosly transplanted murine Meth A sarcoma and the capacity of these agents to elicit antitumor factors were studied. Macroscopically all agents induced tumor n

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

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2014-10-01

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

  20. Analysis of sup 99m Tc-labeled radiopharmaceuticals by high-performance liquid chromatography

    Energy Technology Data Exchange (ETDEWEB)

    Muto, Toshio (Tokyo Metropolitan Isotope Research Center (Japan))

    1990-02-01

    High-performance liquid chromatography (HPLC) equiped with on line radiometric and optical detectors (i.e. radio-HPLC) have been applied to the radiochemical analysis of commonly-used {sup 99m}Tc-radio pharma ceuticals with a view point to check the radiochemical purities of the compounds. Chromatographic conditions were determined by examination of the types of column, mobile phase and pH. An aqueous size-exclusion (Shim-pack Diol-300) and reversed-phase column (Zorbax-ODS) were found to be suitable for {sup 99m}Tc-HSA and the other {sup 99m}Tc-agents, respectively. The analysis of low molecular weight {sup 99m}Tc-agents (e.g. {sup 99m}Tc-DTPA, {sup 99m}Tc-DMSA, {sup 99m}Tc-pyrophosphate, {sup 99m}Tc-phytic acid, {sup 99m}Tc-MDS, {sup 99m}Tc-HMDP) were done by reversed-phaseion pairing chromatography using a optimized mobile phase consisted on a mixture of 50 mM phosphate buffer (pH 7.0) and 2 mM TBA (tetra nbutyl) ammonium hydroxide in 30 % methanol. The mobile phases for analysis of medium molecular weight {sup 99m}Tc-HSA were consisted of a mixture of 50 mM phosphate buffer (ph 7.0) in 30 % methanol, and a mixtures of 1 % SDS (sodium dodecyl sulfonate) in Tris buffer (pH. 7.0), respectively. It was apparent from the radio-chromatograms obtained from these chromatographic conditions, that impurity of {sup 99m}TcO{sub 4} was observed in {sup 99m}Tc-pyrophosphate, {sup 99m}Tc-phytic acid, {sup 99m}Tc-MDP, {sup 99m}Tc-HMDP, and impurities of {sup 99m}Tc-labeled species and {sup 99m}TcO{sub 4}, were observed in {sup 99m}Tc-HIDA, {sup 99m}Tc-HIDA, {sup 99m}Tc-HSA. The radiochemical impurities of the {sup 99m}Tc-radiopharmaceuticals were ranged between 90 and 100 %. From these results, radio-HPLC has been shown to be suitable method for analysis of {sup 99m}Tc-radiopharmaceuticals, with rapidity and excellent precision. (author).

  1. Experimental study of radiopharmaceuticals based on technetium-99m labeled derivative of glucose for tumor diagnosis

    Science.gov (United States)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.; Dergilev, A.

    2016-06-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 minutes at room temperature. After centrifugation of the vials with cells, the supernatant was removed. Radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B 1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 minutes. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D- glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3±0.15MBq and 1.07±0.6MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio- D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  2. Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

    Science.gov (United States)

    Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.

    2016-08-01

    Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio-D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

  3. Smart Mesoporous Nanomaterials for Antitumor Therapy

    Directory of Open Access Journals (Sweden)

    Marina Martínez-Carmona

    2015-11-01

    Full Text Available The use of nanomaterials for the treatment of solid tumours is receiving increasing attention by the scientific community. Among them, mesoporous silica nanoparticles (MSNs exhibit unique features that make them suitable nanocarriers to host, transport and protect drug molecules until the target is reached. It is possible to incorporate different targeting ligands to the outermost surface of MSNs to selectively drive the drugs to the tumour tissues. To prevent the premature release of the cargo entrapped in the mesopores, it is feasible to cap the pore entrances using stimuli-responsive nanogates. Therefore, upon exposure to internal (pH, enzymes, glutathione, etc. or external (temperature, light, magnetic field, etc. stimuli, the pore opening takes place and the release of the entrapped cargo occurs. These smart MSNs are capable of selectively reaching and accumulating at the target tissue and releasing the entrapped drug in a specific and controlled fashion, constituting a promising alternative to conventional chemotherapy, which is typically associated with undesired side effects. In this review, we overview the recent advances reported by the scientific community in developing MSNs for antitumor therapy. We highlight the possibility to design multifunctional nanosystems using different therapeutic approaches aimed at increasing the efficacy of the antitumor treatment.

  4. PARP1 Inhibitors: antitumor drug design.

    Science.gov (United States)

    Malyuchenko, N V; Kotova, E Yu; Kulaeva, O I; Kirpichnikov, M P; Studitskiy, V M

    2015-01-01

    The poly (ADP-ribose) polymerase 1 (PARP1) enzyme is one of the promising molecular targets for the discovery of antitumor drugs. PARP1 is a common nuclear protein (1-2 million molecules per cell) serving as a "sensor" for DNA strand breaks. Increased PARP1 expression is sometimes observed in melanomas, breast cancer, lung cancer, and other neoplastic diseases. The PARP1 expression level is a prognostic indicator and is associated with a poor survival prognosis. There is evidence that high PARP1 expression and treatment-resistance of tumors are correlated. PARP1 inhibitors are promising antitumor agents, since they act as chemo- and radiosensitizers in the conventional therapy of malignant tumors. Furthermore, PARP1 inhibitors can be used as independent, effective drugs against tumors with broken DNA repair mechanisms. Currently, third-generation PARP1 inhibitors are being developed, many of which are undergoing Phase II clinical trials. In this review, we focus on the properties and features of the PARP1 inhibitors identified in preclinical and clinical trials. We also describe some problems associated with the application of PARP1 inhibitors. The possibility of developing new PARP1 inhibitors aimed at DNA binding and transcriptional activity rather than the catalytic domain of the protein is discussed.

  5. Biodistribution of the radiopharmaceutical technetium-99m-sodium phytate in rats after splenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Kercia Regina Santos Gomes; Acucena, Maria Kadja Meneses Torres; Villarim Neto, Arthur; Rego, Amalia Cinthia Meneses [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Ciencias da Saude; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria; Azevedo, Italo Medeiros; Araujo Filho, Irami; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Cirurgia]. E-mail: aldo@ufrnet.br

    2008-12-15

    Drugs and surgery can interfere with the biodistribution of radiopharmaceuticals and data about the effect of splenectomy on the metabolism of phytate-Tc-99m are scarce. This study aimed at evaluating the interference of splenectomy on phytate-Tc-99m biodistribution and liver function in rats. The SP group rats (n=6) underwent splenectomy. In group C (control) the animals were not operated on. After 15 days, all rats were injected with 0.1 mL of Tc-99m-phytate via orbital plexus (0.66 MBq). After 30 minutes, liver samples were harvested, weighed and the percentage of radioactivity per gram (%ATI/g) was determined by a Wizard Perkin-Elme gamma counter. The ATI%/g in splenectomized rats (0.99{+-}0.02) was significantly higher than in controls (0.4{+-}0.02), (p=0.034). ALT, AST and HDL were significantly lower in SP rats (p= 0.001) and leucocytosis was observed in SP rats. In conclusion, splenectomy in rats changed the hepatic biodistribution of Tc-99m-phytate and liver enzymatic activity. (author)

  6. RADIONUCLIDE STUDIES USING TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS OF PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    N. I. Tarassov

    2009-01-01

    Full Text Available Object: to evaluate the efficiency of prostate scintigraphy in the prebioptic diagnosis of prostate cancer (PC.Subjects and methods. Two hundred and two patients with suspected PC underwent comprehensive examination, including 99mTc-technetril prostate scintigraphy and a morphometric study of biopsy material columns. A computer program (official registration certificate No. 2007614475 dated October 24, 2007 was worked out and patented to calculate the intensity of accumulation of radiopharmaceuticals in different portions of the right and left prostate lobes.Results and discussion. When the division index point «pathological focus/background», 1.5; ≤ 1.5, healthy; > 1.5 suspected prostate cancer was used, the sensitivity of prostate scintigraphy was 81.65%; its specificity was 87.1%; the diagnostic effectiveness was 84.37%.Conclusion: The application of prostate scintigraphy can improve indicators for early detection of PC, due to the purposeful detection of the points, enhance the effectiveness of biopsy, and, having more grounds than the early ones, to exclude this disease at the prebioptic stage. The method is noninvasive and can be used to monitor patients with suspected PC.

  7. RADIONUCLIDE STUDIES USING TUMOR-SEEKING RADIOPHARMACEUTICALS IN THE DIAGNOSIS OF PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    N. I. Tarassov

    2014-08-01

    Full Text Available Object: to evaluate the efficiency of prostate scintigraphy in the prebioptic diagnosis of prostate cancer (PC.Subjects and methods. Two hundred and two patients with suspected PC underwent comprehensive examination, including 99mTc-technetril prostate scintigraphy and a morphometric study of biopsy material columns. A computer program (official registration certificate No. 2007614475 dated October 24, 2007 was worked out and patented to calculate the intensity of accumulation of radiopharmaceuticals in different portions of the right and left prostate lobes.Results and discussion. When the division index point «pathological focus/background», 1.5; ≤ 1.5, healthy; > 1.5 suspected prostate cancer was used, the sensitivity of prostate scintigraphy was 81.65%; its specificity was 87.1%; the diagnostic effectiveness was 84.37%.Conclusion: The application of prostate scintigraphy can improve indicators for early detection of PC, due to the purposeful detection of the points, enhance the effectiveness of biopsy, and, having more grounds than the early ones, to exclude this disease at the prebioptic stage. The method is noninvasive and can be used to monitor patients with suspected PC.

  8. Development of dopamine receptor radiopharmaceuticals for the study of neurological and psychiatric disorders

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Jogeshwar Mukherjee

    2009-01-02

    Our goals in this grant application are directed towards the development of radiotracers that may allow the study of the high-affinity state (functional state) of the dopamine receptors. There have been numerous reports on the presence of two inter-convertible states of these (G-protein coupled) receptors in vitro. However, there is no report that establishes the presence of these separate affinity states in vivo. We have made efforts in this direction in order to provide such direct in vivo evidence about the presence of the high affinity state. This understanding of the functional state of the receptors is of critical significance in our overall diagnosis and treatment of diseases that implicate the G-protein coupled receptors. Four specific aims have been listed in the grant application: (1). Design and syntheses of agonists (2). Radiosyntheses of agonists (3). In vitro pharmacology of agonists (4). In vivo distribution and pharmacology of labeled derivatives. We have accomplished the syntheses and radiosyntheses of three agonist radiotracers labeled with carbon-11. In vitro and in vivo pharmacological experiments have been accomplished in rats and preliminary PET studies in non-human primates have been carried out. Various accomplishments during the funded years, briefly outlined in this document, have been disseminated by several publications in various journals and presentations in national and international meetings (Society of Nuclear Medicine, Society for Neuroscience and International Symposium on Radiopharmaceutical Chemistry).

  9. Development of anti β glucan aptamers for use as radiopharmaceutical in the identification of fungal Infections

    Energy Technology Data Exchange (ETDEWEB)

    Lacerda, Camila Maria de Sousa; Reis, Mariana Flister; Correa, Cristiane Rodrigues; Andrade, Antero S.R., E-mail: cmsl@cdtn.br, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEM-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    Invasive fungal infections caused by Candida albicans, are recognized as a major cause of morbidity and mortality in immuno compromised individuals. Patients may not show obvious clinical signs or symptoms, making it difficult to detect its origin or new focus that developed through hematogenous spread. Nuclear medicine could contribute to an early diagnosis of fungal infections, since specific markers are available. The aim of this study was to develop, through SELEX technique (Systematic Evolution of Ligands by Exponential Enrichment), aptamers for beta glucan for subsequent labeling with {sup 99}mTc and evaluation of this radiopharmaceutical in the diagnosis of invasive fungal infections, scintigraphy. To obtain aptamers were performed 15 cycles of SELEX technique, using centrifugation as separation method of oligonuclotideos linked to the beta-glucan is not connected. The DNA bands were observed in all 15 cycles. The oligonucleotides obtained after cycles were cloned using the standard protocol kit-Topo TA vector (Invitrogen), and subjected to sequencing Megabase. Three aptamers for yeast cells were selected for this study. Further, other studies should be performed to assess the specificity and affinity thereof for later use in the diagnosis of fungal infections. (author)

  10. A Concise Radiosynthesis of the Tau Radiopharmaceutical, [18F]T807

    Science.gov (United States)

    Shoup, Timothy M.; Yokell, Daniel L.; Rice, Peter A.; Jackson, Raul N.; Livni, Eli; Johnson, Keith A.; Brady, Thomas J.; Vasdev, Neil

    2014-01-01

    Fluorine-18 labelled 7-(6-fluoropyridin-3-yl)-5H-pyrido[4,3-b]indole ([18F]T807) is a potent and selective agent for imaging paired helical filaments of tau (PHF-tau) and is among the most promising PET radiopharmaceuticals for this target in early clinical trials. The present study reports a simplified one-step method for the synthesis of [18F]T807 that is broadly applicable for routine clinical production using a GE Tracerlab™ FXFN radiosynthesis module. Key facets of our optimized radiosynthesis include development and use of a more soluble protected precursor, tert-butyl 7-(6-nitropyridin-3-yl)-5H-pyrido[4,3-b]indole-5-carboxylate, as well as new HPLC separation conditions that enable a facile one-step synthesis. During the nucleophilic fluorinating reaction with potassium cryptand [18F]fluoride (K[18F]/K222) in DMSO at 130 °C over 10 min, the precursor is concurrently deprotected. Formulated [18F]T807 was prepared in an uncorrected radiochemical yield of 14 ± 3%, with a specific activity of 216 ± 60 GBq/μmol (5837 ± 1621 mCi/μmol) at the end of synthesis (60 min; n = 3) and validated for human use. This methodology offers the advantage of faster synthesis in fewer steps, with simpler automation which we anticipate will facilitate widespread clinical use of [18F]T807. PMID:24339014

  11. Laser stimulation of the acupoint 'Zusanli' (ST.36) on the radiopharmaceutical biodistribution in Wistar rats.

    Science.gov (United States)

    Frederico, Éric H F F; Santos, Ailton A; Sá-Caputo, Danubia C C; Neves, Rosane F; Guimarães, Carlos A S; Chang, Shyang; Bernardo-Filho, Mario

    2016-03-01

    Laser used to stimulate acupoints is called laser acupuncture (LA). It is generally believed that similar clinical responses to manual acupuncture can be achieved. Here we analysed the effects of the laser (904 nm) at the 'Zusanli' acupoint (ST.36) of the stomach meridian on the biodistribution of the radiopharmaceutical Na(99m)TcO4. Wistar rats were divided into control (CG) and experimental groups (EG). The EG were exposed daily to the laser (904 nm) at ST.36 with 1 joule/min (40 mW/cm(2)) for 1 min. The animals of the CG were not exposed to laser at all. On the 8th day after LA, the animals were sedated and Na(99m)TcO4 was administered. After 10 min, the animals were all sacrificed and the organs removed. The radioactivity was counted in each organ to calculate the percentage of radioactivity of the injected dose per gram (%ATI/ g). Comparison of the %ATI/g in EG and CG was performed by Mann-Whitney test. The %ATI/g was significantly increased in the thyroid due to the stimulation of the ST.36 by laser. It is possible to conclude that the stimulation of ST.36 does lead to biological phenomena that interfere with the metabolism of the thyroid.

  12. Tibial lead determination by 99Tcm radiopharmaceutical x-ray fluorescence.

    Science.gov (United States)

    Mountford, P J; Green, S; Bradley, D A; Lewis, A D; Morgan, W D

    1994-04-01

    The feasibility of measuring tibial lead concentration by x-ray fluorescence with an internal 99Tcm labelled bone-seeking radiopharmaceutical was investigated using phantoms containing known values of lead concentration and 99Tcm activity. The minimum detectable concentration (MDC) at two standard deviations based on the counts in the Kalpha1 peak of 10.9 microg Pb ml(-1) was estimated to correspond to an MDC for an individual within a range of approximately 8-15 microg Pb (g bone mineral)(-1) if the counts from all four K x-ray peaks were included. Due to its much greater dose compared to an external source, the MDC of this internal source technique would have to be reduced before it could be used for measurements of occupationally or environmentally exposed individuals other than as an adjunct for a patient undergoing a bone scan. Methods of achieving such a reduction include increasing the acquisition time and the number of HPGE detectors, and optimizing the design of their collimators.

  13. Present status of research on Re-186 radiopharmaceuticals at Radioisotope Production Center

    Energy Technology Data Exchange (ETDEWEB)

    Mutalib, A. [Radioisotope Production Center, National Atomic Energy Agency Kawasan PUSPIPTEK, Serpong (Indonesia)

    1998-10-01

    Rhenium shows a close chemical similarity to technetium and is suitable for radiotherapy because the {beta}-emitting radionuclides {sup 186}Re (t{sub 1/2} 90 h, E{sub {beta}} = 1.1 MeV, E{sub {gamma}} = 137 keV) and {sup 188}Re (t{sub 1/2} = 17 h, E{sub {beta}} = 2.1 MeV). The {gamma}-emission associated with decay of {sup 186}Re is also useful in scintigraphy. The research on {sup 186}Re radiopharmaceuticals at Radioisotope Production Center has been carried out since April 1997. Interest in radioimmunotherapy (RIT) led us to the development of labeling antibodies with rhenium isotopes. Although there are several methods for coupling radiometal to antibody, we prefer an indirect labeling method in which a bifunctional chelating agent is used for coupling of {sup 186}Re to monoclonal antibodies. In this report we outline the study on the preparation of {sup 186}Re DMSA-TFP as precursor for labeling with monoclonal antibody. (author)

  14. Structural Antitumoral Activity Relationships of Synthetic Chalcones

    Directory of Open Access Journals (Sweden)

    Cesar Echeverria

    2009-01-01

    Full Text Available Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series.

  15. Onconase: A ribonuclease with antitumor activity

    Directory of Open Access Journals (Sweden)

    Małgorzata Zwolińska

    2010-02-01

    Full Text Available Onconase (ranpirnase is a homologous protein obtained from [i]Rana pipiens [/i]frog eggs. The activity of onconase, and particularly its antitumor effect, is strictly connected with ribonuclease (RN-ase activity. Onconase induces cell death through the decomposition of inner cellular RNA, inhibition of protein synthesis, and inhibition of cell growth and proliferation and it also specifically triggers tumor cell apoptosis. A very important mechanisms of its cytotoxicity is also its antioxidant activity. The results of preclinical trials demonstrated a high activity of onconase against tumor cells, also those resistant to cytostatics. Moreover, onconase showed synergic activity with other commonly used anticancer drugs. Several clinical trials were performed on patients suffering from kidney, breast, and pancreatic cancers. Most recently a phase III study of onconase in patients with mesothelioma was completed. There are also ongoing phase I and II clinical trials with non-small-cell lung cancer (NSCLC.

  16. Calculation of the Dose of Samarium-153-Ethylene Diamine Tetramethylene Phosphonate (153Sm-EDTMP as a Radiopharmaceutical for Pain Relief of bone Metastasis

    Directory of Open Access Journals (Sweden)

    Fatemeh Razghandi

    2016-04-01

    Full Text Available Introduction One of the important applications of nuclear physics in medicine is the use of radioactive elements as radiopharmaceuticals. Metastatic bone disease is the most common form of malignant bone tumors. Samarium-153-ethylene diamine tetramethylene phosphonate (153Sm-EDTMP as a radiopharmaceutical is used for pain palliation. This radiopharmaceutical usually emits beta particles, which have a high uptake in bone tissues. The purpose of this study was to calculate the radiation dose distribution of 153Sm-EDTMP in bone and other tissues, using MCNPX Monte Carlo code in the particle transport model. Materials and Methods Dose delivery to the bone was simulated by seeking radiopharmaceuticals on the bone surface. The phantom model had a simple cylindrical geometry and included bone, bone marrow, and soft tissue. Results The simulation results showed that a significant amount of radiation dose was delivered to the bone by the use of this radiopharmaceutical. Conclusion Thebone acted as a fine protective shield against rays for the bone marrow. Therefore, the trivial absorbed dose by the bone marrow caused less damage to bone-making cells. Also, the high absorbed dose of the bone could destroy cancer cells and relieve the pain in the bone.

  17. Risk assessment and economic impact analysis of the implementation of new European legislation on radiopharmaceuticals in Italy: the case of the new monograph chapter Compounding of Radiopharmaceuticals (PHARMEUROPA, Vol. 23, No. 4, October 2011).

    Science.gov (United States)

    Chitto, Giuseppe; Di Domenico, Elvira; Gandolfo, Patrizia; Ria, Francesco; Tafuri, Chiara; Papa, Sergio

    2013-12-01

    An assessment of the new monograph chapter Compounding of Radiopharmaceuticals has been conducted on the basis of the first period of implementation of Italian legislation on Good Radiopharmaceuticals Practice (NBP) in the preparation of radiopharmaceuticals, in keeping with Decree by the Italian Ministry of Health dated March 30, 2005. This approach is well grounded in the several points of similarity between the two sets of regulations. The impact on patient risk, on staff risk, and on healthcare organization risk, has been assessed. At the same time, the actual costs of coming into compliance with regulations have been estimated. A change risk analysis has been performed through the identification of healthcare-associated risks, the analysis and measurement of the likelihood of occurrence and of the potential impact in terms of patient harm and staff harm, and the determination of the healthcare organization's controlling capability. In order to evaluate the economic impact, the expenses directly related to the implementation of the activities as per ministerial decree have been estimated after calculating the overall costs unrelated to NBP implementation. The resulting costs have then been averaged over the total number of patient services delivered. NBP implementation shows an extremely positive impact on risk management for both patients receiving Nuclear Medicine services and the healthcare organization. With regard to healthcare workers, instead, the implementation of these regulations has a negative effect on the risk for greater exposure and a positive effect on the defense against litigation. The economic impact analysis of NBP implementation shows a 34% increase in the costs for a single patient service. The implementation of the ministerial decree allows for greater detectability of and control over a number of critical elements, paving the way for risk management and minimization. We, therefore, believe that the proposed tool can provide basic

  18. Development of radiopharmaceuticals based on aptamers: selection and characterization of DNA aptamers for CEA

    Energy Technology Data Exchange (ETDEWEB)

    Correa, C.R.; Andrade, A.S.R., E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Augusto-Pinto, L. [BioAptus, Belo Horizonte, MG (Brazil); Goes, A.M., E-mail: goes@icb.ufmg.br [Departamento de Imunologia e Bioquimica. Instituto de Ciencias Biologicas. Universidade Federal de Minas Gerais. Belo Horizonte, MG (Brazil)

    2011-07-01

    Colorectal cancer is among the top four causes of cancer deaths worldwide. Carcinoembryonic antigen (CEA) is a complex intracellular glycoprotein produced by about 90% of colorectal cancers. CEA has been identified as an attractive target for cancer research because of its pattern of expression in the surface cell and its likely functional role in tumorigenesis. Research on the rapid selection of ligands based on the SELEX (systematic evolution of ligands by exponential enrichment) forms the basis for the development of high affinity and high specificity molecules, which can bind to surface determinants of tumour cells, like CEA. The oligonucleotides ligands generated in this technique are called aptamers. Aptamers can potentially find applications as therapeutic or diagnostic tools for many kind of diseases, like a tumor. Aptamers offer low immunogenicity, good tumour penetration, rapid uptake and fast systemic clearance, which favour their application as effective vehicles for radiotherapy. In addition aptamers can be labeled with different radioactive isotopes. The aim of this work was select aptamers binding to the CEA tumor marker. The aptamers are obtained through by SELEX, in which aptamers are selected from a library of random sequences of synthetic DNA by repetitive binding of the oligonucleotides to target molecule (CEA). Analyses of the secondary structure of the aptamers were determined using the m fold toll. Three aptamers were selected to binding assay with target cells. These aptamers were confirmed to have affinity and specific binding for T84 cell line (target cell), showed by confocal imaging. We are currently studying the potential efficacy of these aptamers as targeted radiopharmaceuticals, for use as imaging agents or therapeutic applications. The development of aptamers specific to CEA open new perspectives for colorectal cancer diagnosis and treatment. Acknowledgments: This investigation was supported by the Centro de Desenvolvimento da

  19. Clinical use of bone-targeting radiopharmaceuticals with focus on alpha-emitters

    Institute of Scientific and Technical Information of China (English)

    Hinrich; A; Wieder; Michael; Lassmann; Martin; S; Allen-Auerbach; Johannes; Czernin; Ken; Herrmann

    2014-01-01

    Various single or multi-modality therapeutic options are available to treat pain of bone metastasis in patients with prostate cancer.Different radionuclides that emitβ-rays such as 153Samarium and 89Strontium and achieve palliation are commercially available.In contrast toβ-emitters,223Radium as a a-emitter has a short path-length.The advantage of the a-emitter is thus a highly localized biological effect that is caused by radiation induced DNA double-strand breaks and subsequent cell killing and/or limited effectiveness of cellular repair mechanisms.Due to the limited range of the a-particles the bone surface to red bone marrow dose ratio is also lower for 223Radium which is expressed in a lower myelotoxicity.The a emitter 223Radium dichloride is the first radiopharmaceutical that significantly prolongslife in castrate resistant prostate cancer patients with wide-spread bone metastatic disease.In a phaseⅢ,randomized,double-blind,placebo-controlled study 921patients with castration-resistant prostate cancer and bone metastases were randomly assigned.The analysis confirmed the 223Radium survival benefit compared to the placebo(median,14.9 mo vs 11.3 mo;P<0.001).In addition,the treatment results in pain palliation and thus,improved quality of life and a delay of skeletal related events.At the same time the toxicity profile of223Radium was favourable.Since May 2013,223Radium dichloride(Xofigo?)is approved by the US Food and Drug Administration.

  20. Influence of Annona muricata (soursop) on biodistribution of radiopharmaceuticals in rats

    Energy Technology Data Exchange (ETDEWEB)

    Holanda, Cecilia Maria de Carvalho Xavier [Universidade Federal do Rio Grande do Norte (UFGN), Natal, RN (Brazil). Lab. de Radiobiologia Experimental e Ensaios Antiparasitarios; Barbosa, Delianne Azevedo; Demeda, Vanessa Favero; Bandeira, Flora Tamires Moura [Universidade Federal do Rio Grande do Norte (UFGN), Natal, RN (Brazil). Escola de Medicina; Medeiros, Hilkea Carla Souza de; Pereira, Kercia Regina Santos Gomes [Universidade Federal do Rio Grande do Norte (UFGN), Natal, RN (Brazil). Programa de Pos-Graduacao em Bioquimica; Barbosa, Vanessa Santos de Arruda [Universidade Federal de Campina Grande (UFCG), PB (Brazil); Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFGN), Natal, RN (Brazil). Nucleo de Cirurgia Experimental

    2014-03-01

    Purpose: to evaluate the effect of hydroalcoholic extract of A. muricata on biodistribution of two radiopharmaceuticals: sodium phytate and dimercaptosuccinic acid (DMSA), both labeled with {sup 99m}technetium. Methods: twenty four Wistar rats were divided into two treated groups and two controls groups. The controls received water and the treated received 25mg/kg/day of A. muricata by gavage for ten days. One hour after the last dose, the first treated group received {sup 99m}Tc-DMSA and the second sodium {sup 99m}Tc-phytate (0.66MBq each group), both via orbital plexus. Controls followed the same protocol. Forty min later, all groups were sacrificed and the blood, kidney and bladder were isolated from the first treated group and the blood, spleen and liver isolated from the second treated group. The percentage of radioactivity per gram of tissue (%ATI/g) was calculated using a gamma counter. Results: the statistical analysis showed that there was a statistically significant decrease (p<0.05) in the uptake of %ATI/g in bladder (0.11±0.01and1.60±0.08), kidney (3.52±0.51and11.84±1.57) and blood (0.15±0.01and 0.54±0.05) between the treated group and control group, respectively. Conclusion: the A. muricata hydroalcoholic extract negatively influenced the uptake of {sup 99m}Tc-DMSA in bladder, kidney and blood of rats (author)

  1. Analysis of radionuclide concentration in air released through the stack of a radiopharmaceutical production facility based on a medical cyclotron

    Science.gov (United States)

    Giardina, M.; Tomarchio, E.; Greco, D.

    2015-11-01

    Positron emitting radionuclides are increasingly used in medical diagnostics and the number of radiopharmaceutical production facilities have been estimated to be growing worldwide. During the process of production and/or patient administration of radiopharmaceuticals, an amount of these radionuclides might become airborne and escape into the environment. Therefore, the analysis of radionuclide concentration in the air released to the stack is a very important issue to evaluate the dose to the population living around the plant. To this end, sampling and measurement of radionuclide concentration in air released through the stack of a Nuclear Medicine Center (NMC), provided with a cyclotron for radiopharmaceuticals production, must be routinely carried out with an automatic measurement system. In this work is presented the air monitoring system realized at "San Gaetano" NMC at Bagheria (Italy) besides the analysis of the recorded stack relesead air concentration data. Sampling of air was carried out continuously and gamma-ray spectrometric measurement are made on-line and for a short time by using a shielded Marinelli beaker filled with sampled air and a gamma detector. The use of this system allows to have 1440 values of air concentration per day from 2002, year of the start of operation with the cyclotron. Therefore, the concentration values are very many and an analysis software is needed to determine the dose to the population. A comparison with the results of a simulation code based on a Gaussian Plume air dispersion modelling allow us to confirm the no-radiological significance of the stack effluent releases in terms of dose to population and to evaluate possible improvements in the plant devices to reduce the air concentration at stack.

  2. 177Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical

    Directory of Open Access Journals (Sweden)

    Héctor Mendoza-Nava

    2016-01-01

    Full Text Available 177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4-folate-bombesin with gold nanoparticles (AuNPs in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs and gastrin-releasing peptide receptors (GRPRs overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys1Lys3(DOTA-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS, particle size distribution (DLS, TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%. Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15±2.72%. 177Lu-dendrimer(AuNP-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.

  3. Cu(II) bis(thiosemicarbazone) radiopharmaceutical binding to serum albumin: further definition of species dependence and associated substituent effects

    Energy Technology Data Exchange (ETDEWEB)

    Basken, Nathan E. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States); Green, Mark A. [Division of Nuclear Pharmacy, Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907 (United States)], E-mail: magreen@purdue.edu

    2009-07-15

    Introduction: The pyruvaldehyde bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-PTSM) and diacetyl bis(N{sup 4}-methylthiosemicarbazonato)copper(II) (Cu-ATSM) radiopharmaceuticals exhibit strong, species-dependent binding to the IIA site of human serum albumin (HSA), while the related ethylglyoxal bis(thiosemicarbazonato)copper(II) (Cu-ETS) radiopharmaceutical appears to exhibit only nonspecific binding to HSA and animal serum albumins. Methods: To further probe the structural basis for the species dependence of this albumin binding interaction, we examined protein binding of these three radiopharmaceuticals in solutions of albumin and/or serum from a broader array of mammalian species (rat, sheep, donkey, rabbit, cow, pig, dog, baboon, mouse, cat and elephant). We also evaluated the albumin binding of several copper(II) bis(thiosemicarbazone) chelates offering more diverse substitution of the ligand backbone. Results: Cu-PTSM and Cu-ATSM exhibit a strong interaction with HSA that is not apparent with the albumins of other species, while the binding of Cu-ETS to albumin is much less species dependent. The strong interaction of Cu-PTSM with HSA does not appear to simply correlate with variation, relative to the animal albumins, of a single amino acid lining HSA's IIA site. Those agents that selectively interact with HSA share the common feature of only methyl or hydrogen substitution at the carbon atoms of the diimine fragment of the ligand backbone. Conclusions: The interspecies variations in albumin binding of Cu-PTSM and Cu-ATSM are not simply explained by unique amino acid substitutions in the IIA binding pocket of the serum albumins. However, the specific affinity for this region of HSA is disrupted when substituents bulkier than a methyl group appear on the imine carbons of the copper bis(thiosemicarbazone) chelate.

  4. Preclinical assessment of dopaminergic system in rats by MicroPET using three positron-emitting radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Lara-Camacho, V. M., E-mail: victormlc13@hotmail.com; Ávila-García, M. C., E-mail: victormlc13@hotmail.com; Ávila-Rodríguez, M. A., E-mail: victormlc13@hotmail.com [Unidad PET, Facultad de Medicina, Universidad Nacional Autónoma de México, 04510, México, D.F. (Mexico)

    2014-11-07

    Different diseases associated with dysfunction of dopaminergic system such as Parkinson, Alzheimer, and Schizophrenia are being widely studied with positron emission tomography (PET) which is a noninvasive method useful to assess the stage of these illnesses. In our facility we have recently implemented the production of [{sup 11}C]-DTBZ, [{sup 11}C]-RAC, and [{sup 18}F]-FDOPA, which are among the most common PET radiopharmaceuticals used in neurology applications to get information about the dopamine pathways. In this study two healthy rats were imaged with each of those radiotracers in order to confirm selective striatum uptake as a proof of principle before to release them for human use.

  5. Untangling the web of European regulations for the preparation of unlicensed radiopharmaceuticals: a concise overview and practical guidance for a risk-based approach.

    Science.gov (United States)

    Lange, Rogier; ter Heine, Rob; Decristoforo, Clemens; Peñuelas, Iván; Elsinga, Philip H; van der Westerlaken, Monique M L; Hendrikse, N Harry

    2015-05-01

    Radiopharmaceuticals are highly regulated, because they are controlled both as regular medicinal products and as radioactive substances. This can pose a hurdle for their development and clinical use. Radiopharmaceuticals are fundamentally different from other medicinal products and these regulations are not always adequate for their production. Strict compliance may have a huge resource impact, without further improving product quality. In this paper we give an overview of the applicable legislation and guidelines and propose a risk-based approach for their implementation. We focus on a few controversial Good Manufacturing Practice topics: cleanroom classification, air pressure regime, cleanroom qualification and microbiological monitoring. We have developed an algorithm to assess the combined risk of microbiological contamination of a radiopharmaceutical preparation process and propose corresponding Good Manufacturing Practice classification levels. In our opinion, the risk of carry-over of radiopharmaceuticals by individuals cannot be contained by pressure differences, and complicated regimes with underpressured rooms are not necessary in most situations. We propose a sterility assurance level of 10 for radiopharmaceuticals that are administered within a working day, irrespective of their use. We suggest the adoption of limits for environmental monitoring of microbial contamination, as proposed by Bruel and colleagues, on behalf of the French Society of Radiopharmacy. Recently launched regulatory documents seem to breathe a more liberal spirit than current legislation and recognize the need for the use of risk assessment. We argue that future legislation be further harmonized and state risk assessment as the gold standard for implementation of drug quality regulations for the preparation of unlicensed radiopharmaceuticals.

  6. Synthesis and Antitumor Activities In Vitro of Solanesylpiperazinotriamine

    Institute of Scientific and Technical Information of China (English)

    Chao Pie WANG; Jian Hong WANG; Ying GAN; Zhi Yong CHEN; Gang Jun DU; Jin ZHAO

    2006-01-01

    A series of novel antitumor agents-the solanesylpiperazinotriamine derivatives were designed and synthesized, their structures were confirmed by IR, 1H-NMR, MS, and element analysis. The preliminary tests showed that at low micromolar concentrations these compounds exhibited obvious toxicity on tumor cells in vitro, and the synergistic effect on clinical antitumor agent indicated that at noncytotoxic concentrations they also evidently enhanced the curative effect of vincristine.

  7. Progress of Research in Antitumor Mechanisms with Chinese Medicine

    Institute of Scientific and Technical Information of China (English)

    韩淑燕; 李萍萍

    2009-01-01

    The anti-tumor effects of Chinese herbal medicines and their prescription preparations attracted more and more attention at home and abroad.Thus,it is becoming a hot research topic to exploit the anti-tumor mechanisms of Chinese medicine,and some of them have been partly clarified with the improved research ability to date.In brief,the Chinese herbal medicines possess unique advantages on the treatment of tumors through their multiple actions on multiple targets.

  8. Harvard--MIT research program in short-lived radiopharmaceuticals. Progress report, September 1, 1977--April 30, 1978. [/sup 99m/Tc, positron-emitting radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Adelstein, S.J.; Brownell, G.L.

    1978-05-01

    Progress is reported on the following studies: chemistry studies designed to achieve a more complete understanding of the fundamental chemistry of technetium in order to facilitate the design of future radiopharmaceuticals incorporating the radionuclide /sup 99m/Tc; the development of new radiopharmaceuticals intended to improve image quality and lower radiation doses by the use of short-lived radionuclides and disease-specific agents; the development of short-lived positron-emitting radionuclides which offer advantages in transverse section imaging of regional physiological processes; and studies of the toxic effects of particulate radiation.

  9. Advanced nanocarriers for an antitumor peptide

    Energy Technology Data Exchange (ETDEWEB)

    Pippa, Natassa [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Pispas, Stergios [National Hellenic Research Foundation, Theoretical and Physical Chemistry Institute (Greece); Demetzos, Costas, E-mail: demetzos@pharm.uoa.gr [National and Kapodistrian University of Athens, Department of Pharmaceutical Technology, Faculty of Pharmacy (Greece); Sivolapenko, Gregory [University of Patras, Laboratory of Pharmacokinetics, Department of Pharmacy (Greece)

    2013-11-15

    In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic, and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Egg phosphatidylcholine (EggPC) and dipalmytoylphosphatidylcholine (DPPC) (EggPC:PCK3145 and DPPC:PCK3145, 9:0.2 molar ratio), into cationic liposomes composed of EggPC:SA:PCK3145 and DPPC:SA:PCK3145 (9:1:0.2 molar ratio) into complexes with the block polyelectrolyte (quaternized poly[3,5-bis(dimethylaminomethylene)hydroxystyrene]-b-poly(ethylene oxide) (QNPHOSEO) and finally into dendrimeric structures (i.e., PAMAM G4). Light scattering techniques are used in order to examine the size, the size distribution and the Z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules.

  10. [Biodegradable polyhydroxyalkanoates as carriers for antitumor agents].

    Science.gov (United States)

    Shishatskaia, E I; Zhemchugova, A V; Volova, T G

    2005-01-01

    The possible use of biodegradable polyethers of microbial origin (polyhydroxyalkanoates) as matrices for deposition of daunorubicin (rubomycin), an antitumor anthracycline, was studied. The tablet dosage form of various rubomycin load (from 1 to 60% w/w) was prepared by cold compaction under pressure. The in vitro kinetics of the rubomycin release from the polymer matrix was investigated. It was shown that the rubomycin release to the medium resulted from the drug solution and diffusion within various periods, from tens hours to several weeks and months depending on the load. When the rubomycin load was under 20% w/w the drug release was prolonged and directly proportional to the observation time. When the rubomycin concentration was under 5%, the drug release kinetics corresponded to the type of the zero order reaction with prolonged release without sharp efflux at the initial stage of the observation. The findings showed that the polyhydroxyalkanoates were applicable as matrices for deposition of rubomycin and preparation of drugs with prolonged action.

  11. Antitumor activity of chemical modified natural compounds

    Directory of Open Access Journals (Sweden)

    Marilda Meirelles de Oliveira

    1991-01-01

    Full Text Available Search of new activity substances starting from chemotherapeutic agents, continously appears in international literature. Perhaps this search has been done more frequently in the field of anti-tumor chemotherapy on account of the unsuccess in saving advanced stage patients. The new point in this matter during the last decade was computer aid in planning more rational drugs. In near future "the accessibility of supercomputers and emergence of computer net systems, willopen new avenues to rational drug design" (Portoghese, P. S. J. Med. Chem. 1989, 32, 1. Unknown pharmacological active compounds synthetized by plants can be found even without this eletronic devices, as tradicional medicine has pointed out in many contries, and give rise to a new drug. These compounds used as found in nature or after chemical modifications have produced successful experimental medicaments as FAA, "flavone acetic acid" with good results as inibitors of slow growing animal tumors currently in preclinical evaluation for human treatment. In this lecture some international contributions in the field of chemical modified compounds as antineoplasic drugs will be examined, particularly those done by Brazilian researches.

  12. The nineteenth report on survey of the adverse reaction to radiopharmaceuticals. The 22nd survey in 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    The report included cases of adverse reaction to radiopharmaceuticals and of drug defect which had occurred from April 1, 1996 to March 31, 1997. The survey was done by the questionnaire to 1,182 nuclear medicine facilities in Japan and 961 answers (81.3%) were obtained. Thirty one cases of adverse reactions were reported from 31 facilities in 1,264,865 cases to that radiopharmaceuticals had been administered and 7 cases of drug defect were reported from 7 facilities. Adverse reactions involved 8 vasovagal reactions, 14 allergic reactions and 9 others for {sup 99m}Tc-MAA (adverse reaction rate in %: 0.0025), -PYP (0.0352), -HM-PAO (0.0025), -MDP{center_dot}HMDP (0.0008), -DTPA (0.0189), -HSA (0.0086), -MIBI (0.0066), -tetrofosmin (0.0032), -MAG{sub 3} (0.0147), {sup 201}Tl-TlCl2 (0.0014), {sup 123}I-NaI capsule (0.0068), -IMP (0.0016), {sup 131}I-NaI capsule (0.0128) and -iodomethyl-norcholesterol (0.2752). Drug defects involved 1 incomplete radio-labeling, 3 broken or contaminated vials and 3 others. Relative to those hitherto, adverse reaction cases tended to be decreasing and drug defect cases clearly decreased. (K.H.)

  13. Influence of the Generator in-Growth Time on the Final Radiochemical Purity and Stability of Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    L. Uccelli

    2013-01-01

    Full Text Available At Legnaro laboratories of the Italian National Institute for Nuclear Physics (INFN, a feasibility study has started since 2011 related to accelerated-based direct production of by the 100Mo(p,2n reaction. Both theoretical investigations and some recent preliminary irradiation tests on 100Mo-enriched samples have pointed out that both the / ratio and the specific activity will be basically different in the final accelerator-produced Tc with respect to generator-produced one, which might affect the radiopharmaceutical procedures. The aim of this work was to evaluate the possible impact of different / isomeric ratios on the preparation of different Tc-labeled pharmaceutical kits. A set of measurements with , eluted from a standard 99Mo/ generator, was performed, and results on both radiochemical purity and stability studies (following the standard quality control procedures are reported for a set of widely used pharmaceuticals (i.e., -Sestamibi, -ECD, -MAG3, -DTPA, -MDP, -HMDP, -nanocolloids, and -DMSA. These pharmaceuticals have been all reconstituted with either the first [O4]− eluate obtained from a 99Mo/ generator (coming from two different companies or eluates after 24, 36, 48, and 72 hours from last elution. Results show that the radiochemical purity and stability of these radiopharmaceuticals were not affected up to the value of 11.84 for the / ratio.

  14. Effects of the variation of samples geometry on radionuclide calibrator response for radiopharmaceuticals used in nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Albuquerque, Antonio Morais de Sa; Fragoso, Maria Conceicao de Farias; Oliveira, Mercia L. [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-07-01

    In the nuclear medicine practice, the accurate knowledge of the activity of radiopharmaceuticals which will be administered to the subjects is an important factor to ensure the success of diagnosis or therapy. The instrument used for this purpose is the radionuclide calibrator. The radiopharmaceuticals are usually contained on glass vials or syringes. However, the radionuclide calibrators response is sensitive to the measurement geometry. In addition, the calibration factors supplied by manufactures are valid only for single sample geometry. To minimize the uncertainty associated with the activity measurements, it is important to use the appropriate corrections factors for the each radionuclide in the specific geometry in which the measurement is to be made. The aims of this work were to evaluate the behavior of radionuclide calibrators varying the geometry of radioactive sources and to determine experimentally the correction factors for different volumes and containers types commonly used in nuclear medicine practice. The measurements were made in two ionization chambers of different manufacturers (Capintec and Biodex), using four radionuclides with different photon energies: {sup 18}F, {sup 99m}Tc, {sup 131}I and {sup 201}Tl. The results confirm the significant dependence of radionuclide calibrators reading on the sample geometry, showing the need of use correction factors in order to minimize the errors which affect the activity measurements. (author)

  15. Radiopharmaceutical management in Brazil: the case of fluorodeoxyglucose production; Gestao de radiofarmacos no Brasil: o caso da producao de fluordesoxiglicose

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Vitor da Silva

    2016-07-01

    Nowadays, the combination of fluorodeoxyglucose tracer (FDG) and PET/CT equipment is the best technological condition for medical diagnosis, allowing the generation of images that associate anatomy and metabolic functions of tissues or organs. Constitutional Amendment (CA) No 49 of 2006, relaxed the state monopoly on the production of radioactive substances, allowing private investment in radioisotope area with half-life of less than or equal to two hours, as a way to increase the supply of these materials to national health sector. In order to reflect on the Brazilian production of radiopharmaceuticals, especially FDG was performed a theoretical study with a qualitative approach, substantiated by documentary research and data collection through a questionnaire sent to the producing private companies of this radiopharmaceutical. Initially, it sought to identify in the federal level the legal and regulatory parameters for the activity; then the existing competitive environment was observed, and, finally, were prospected the business perspectives on the behavior of domestic demand of this product. The results showed the growth of production and its largest geographical distribution in the country, beyond what would be possible only considering public investment; but short of expectations surrounding the enactment of Constitutional Amendment. Private entrepreneurs believe in market growth; since, most of the population has no access to the benefits that the medical imaging diagnostic with the use of FDG may allow. It was also noted that there is a need to improve the regulatory framework in relation to licensing procedures; as well as implementation of common marketing parameters. (author)

  16. In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements

    Directory of Open Access Journals (Sweden)

    Ripoll-Hamer E.

    1998-01-01

    Full Text Available In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99mTcO4, methylenediphosphonic acid (99mTc-MDP and glucoheptonate acid (99mTc-GHA to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P and blood cells (BC were isolated and precipitated with 5% trichloroacetic acid (TCA, and soluble (SF and insoluble fractions (IF were separated. Blood samples were prepared (0 and 24 h and coated with LM-1 radioautographic emulsions and percent radioactivity (%rad in P and BC was determined. The binding of Na 99mTcO4 (%rad to P was 61.2% (0 h and 46.0% (24 h, and radioautography showed 63.7% (0 h and 43.3% (24 h. The binding to BC was 38.8% (0 h and 54.0% (24 h, and radioautography showed 36.3% (0 h and 56.7% (24 h. 99mTc-MDP study presented 91.1% (0 h to P and 87.2% (24 h, and radioautography showed 67.9% (0 h and 67.4% (24 h. The binding to BC was 8.9% (0 h and 12.8% (24 h, and radioautography showed 32.1% (0 h and 32.6% (24 h. 99mTc-GHA study was 90.1% (0 h to P and 79.9% (24 h, and radioautography showed 67.2% (0 h and 60.1% (24 h. The binding to BC was 9.9% (0 h and 20.1% (24 h, and radioautography showed 32.8% (0 h and 39.9% (24 h. The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation is qualitatively in accordance

  17. Biokinetics and dosimetry of target-specific radiopharmaceuticals for molecular imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Torres G, E. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Gonzalez V, A. [UAEM, Facultad de Medicina, Toluca (Mexico); Murphy, C.A. de [INCMNSZ, Mexico D.F. (Mexico)

    2006-07-01

    Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. {sup 99m}Tc-HYNlC-TOC has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. Therapies using radiolabeled anti-CD20 have demonstrated their efficacy in patients with B-cell non Hodgkin's Iymphoma (NHL). The aim of this study was to establish biokinetic models for {sup 99m}Tc-HYNlC-TOC and {sup 188}Re-anti-CD20 prepared from Iyophilized kits, and to evaluate their dosimetry as target-specific radiopharmaceuticals. Whole-body images were acquired at different times after {sup 99m}Tc-HYNlC-TOC or {sup 188}Re-anti-CD20 administration obtained from instant freeze-dried kit formulations with radiochemical purities > 95 %. Regions of interest (ROls) were drawn around source organs on each time frame. The cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate time-activity curves in each organ, to adjust the biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. {sup 99m}Tc-HYNlC-TOC images showed an average tumor/blood (heart) ratio of 4.3 {+-} 0.7 in receptor-positive tumors at 1 h and the mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv. Results showed that after administration of 7 GBq of {sup 188}Re-anti-CD20 the absorbed dose to whole body would be 0.7 Gy (0.1 mGy/MBq) which is the indicated dose for non Hodgkin's Iymphome therapies. (Author)

  18. Evaluation of novel bifunctional chelates for the development of Cu-64-based radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Cara L. [MDS Nordion, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada)], E-mail: cara.ferreira@mdsinc.com; Yapp, Donald T. [British Columbia Cancer Agency Research Centre, Vancouver, BC, V5Z 1L3 (Canada); Lamsa, Eric [MDS Nordion, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Gleave, Martin [Prostrate Centre at Vancouver General Hospital, Vancouver, BC, V6H 3Z6 (Canada); Bensimon, Corinne [MDS Nordion, 4004 Wesbrook Mall, Vancouver, BC, V6T 2A3 (Canada); Jurek, Paul; Kiefer, Garry E. [Macrocylics Inc., Dallas, Texas, 75235 (United States)

    2008-11-15

    Background: Currently available bifunctional chelates (BFCs) for attaching Cu-64 to a targeting molecule are limited by either their radiolabeling conditions or in vivo stability. With the goal of identifying highly effective BFCs, we compared the properties of two novel BFCs, 1-oxa-4,7,10-triazacyclododecane-S-5-(4-nitrobenzyl)-4,7,10-triacetic acid (p-NO{sub 2}-Bn-Oxo) and 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-S-4- (4-nitrobenzyl)-3,6,9-triacetic acid (p-NO{sub 2}-Bn-PCTA), with the commonly used S-2-(4-nitrobenzyl)-1,4,7,10-tetraazacyclododecanetetraacetic acid (p-NO{sub 2}-Bn-DOTA). Methods: p-NO{sub 2}-Bn-DOTA, p-NO{sub 2}-Bn-Oxo and p-NO{sub 2}-Bn-PCTA were each radiolabeled with Cu-64 under various conditions to assess the reaction kinetics and robustness of the radiolabeling. Stability of each Cu-64 BFC complex was evaluated at low pH and in serum. Small animal positron emission tomography imaging and biodistribution studies in mice were undertaken. Results: p-NO{sub 2}-Bn-Oxo and p-NO{sub 2}-Bn-PCTA possessed superior reaction kinetics compared to p-NO{sub 2}-Bn-DOTA under all radiolabeling conditions; >98% radiochemical yields were achieved in <5 min at room temperature even when using near stoichiometric amounts of BFC. Under nonideal conditions, such as low or high pH, high radiochemical yields were still achievable with the novel BFCs. The radiolabeled compounds were stable in serum and at pH 2 for 48 h. The imaging and biodistribution of the Cu-64-radiolabeled BFCs illustrated differences between the BFCs, including preferential clearance via the kidneys for the p-NO{sub 2}-Bn-PCTA Cu-64 complex. Conclusions: The novel BFCs facilitated efficient Cu-64 radiolabeling under mild conditions to produce stable complexes at potentially high specific activities. These BFCs may find wide utility in the development of Cu-64-based radiopharmaceuticals.

  19. Selection of aptamers for use as radiopharmaceuticals in bacterial infection diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Ieda Mendes; Faria, Ligia Santana de; Correa, Cristiane Rodrigues; Andrade, Antero Silva Ribeiro de, E-mail: imendesf@yahoo.com.br, E-mail: antero@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2013-07-01

    The difficulty in early detection of specific foci in the bacterial infection caused by bacteria has raised the need to search for new techniques for this purpose, since these foci require prolonged treatment with antibiotics and in some cases even drainage or, if applicable, removal of prostheses or grafts. Detection of bacterial infections by scintigraphy has the advantage that an image of the whole body could be obtained. This study aims to obtain aptamers specific bacteria for future use as radiopharmaceutical. The SELEX (Systematic Evolution of Ligands by Exponential Enrichment) methodology can generate oligonucleotides (aptamers) that are able to bind with high affinity and specificity to a specific target, from small molecules to complex proteins, by using rounds of enrichment and amplification. Aptamers can be labeled with different radionucleotides such as {sup 99m}Tc, {sup 18}F and {sup 32}P. In this study aptamers anti-peptidoglycan, the main component of the outer cell wall of bacteria, were obtained through SELEX. The SELEX started with a pool of ssDNA that had 10{sup 15}different sequences (library), each oligo has two fixed regions merging a portion of 25 random nucleotides. Initially, the library of ssDNA was incubated with peptidoglycan, for 1h at 37 dec C with stirring. Subsequently, amplification of oligonucleotides that were able to bind to peptidoglycan was performed by PCR (Polymerase Chain Reaction). The amplified oligonucleotides were again incubated with peptidoglycan, amplified and purified. At the end of 15 rounds of selection the oligonucleotides were cloned using TOPO plasmid and Escherichia coli strain Top10F'. The plasmid DNA from 40 colonies were extracted and quantified. The plasmids were sequenced using the sequencing MegaBase, and two different aptamers sequences were obtained from all clones. The aptamers obtained were synthesized and subsequently labeled with {sup 32}P in the 5' end. The labeled aptamers were incubated

  20. In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain.

    Science.gov (United States)

    Báez, Roxana; Lopes, Miriam T; Salas, Carlos E; Hernández, Martha

    2007-10-01

    Stem bromelain (EC 3.4.22.32) is a major cysteine proteinase, isolated from pineapple ( Ananas comosus) stem. Its main medicinal use is recognized as digestive, in vaccine formulation, antitumoral and skin debrider for the treatment of burns. To verify the identity of the principle in stem fractions responsible for the antitumoral effect, we isolated bromelain to probe its pharmacological effects. The isolated bromelain was obtained from stems of adult pineapple plants by buffered aqueous extraction and cationic chromatography. The homogeneity of bromelain was confirmed by reverse phase HPLC, SDS-PAGE and N-terminal sequencing. The in vivo antitumoral/antileukemic activity was evaluated using the following panel of tumor lines: P-388 leukemia, sarcoma (S-37), Ehrlich ascitic tumor (EAT), Lewis lung carcinoma (LLC), MB-F10 melanoma and ADC-755 mammary adenocarcinoma. Intraperitoneal administration of bromelain (1, 12.5, 25 mg/kg), began 24 h after tumor cell inoculation in experiments in which 5-fluorouracil (5-FU, 20 mg/kg) was used as positive control. The antitumoral activity was assessed by the survival increase (% survival index) following various treatments. With the exception of MB-F10 melanoma, all other tumor-bearing animals had a significantly increased survival index after bromelain treatment. The largest increase ( approximately 318 %) was attained in mice bearing EAT ascites and receiving 12.5 mg/kg of bromelain. This antitumoral effect was superior to that of 5-FU, whose survival index was approximately 263 %, relative to the untreated control. Bromelain significantly reduced the number of lung metastasis induced by LLC transplantation, as observed with 5-FU. The antitumoral activity of bromelain against S-37 and EAT, which are tumor models sensitive to immune system mediators, and the unchanged tumor progression in the metastatic model suggests that the antimetastatic action results from a mechanism independent of the primary antitumoral effect.

  1. Positron emitting nuclides and their synthetic incorporation in radiopharmaceuticals. [Labeled with /sup 11/C, /sup 13/N, and /sup 18/F

    Energy Technology Data Exchange (ETDEWEB)

    Fowler, J.S.

    1976-01-01

    /sup 11/C, /sup 13/N, and /sup 15/O has potential applicability to the study of metabolism in humans. Problems in the synthesis of radiopharmaceuticals labeled with /sup 11/C, /sup 13/N, and /sup 18/F are described: quality control, radiation exposure, carboxylic acids, glucose, amines, amino acids, nitrosources, fluoroethanol. 54 references. (DLC)

  2. Metal-ion Speciation in Blood Plasma as a Tool in Predicting the "in vivo" Behaviour of Potential Bone-Seeking Radiopharmaceuticals

    NARCIS (Netherlands)

    Zeevaart, J.R.

    2001-01-01

    In a quest for more effective radiopharmaceuticals for palliation of pain experienced by metastatic bone cancer patients, results obtained with the therapeutic radionuclides 153 SM, 166 Ho and 117mSn complexed to bone-seeking phopsphate ligands are related. As phosphonates are known to enhance the r

  3. Dosimetric aspects of the treatment of metastatic bone pain with radiopharmaceuticals; Aspectos dosimetricos de los tratamientos del dolor oseo metastasico con radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, T.; Marti, J. F.; Olivas, C.; Vercher, J. L.; Repetto, R.; Bello, P.

    2014-02-01

    Within the context of treatment of metastatic bone pain with bone seeking radiopharmaceuticals, this paper expounds the results of an analysis of available molecules (both approved for clinical use or still under study) intended to obtain a detailed comparison of their dosimetric characteristics. These can be used to supplement the list of already know differences between them, such as efficacy, appearance and length of the palliative effect, eventual tumoricidal effect, myelotoxicity, sale price and availability. Seven radiopharmaceuticals have been analysed, five of them are based on beta emission radionuclides: {sup 3}2P, {sup 1}53Sm, {sup 1}86Re and {sup 1}88Re and the other two ones are based on high Linear energy Transference emission radionuclides: {sup 1}17mSn and {sup 2}23Ra a series of estimates of the main dosimetric parameters for each radiopharmaceutical analysed have been obtained. The values obtained might be worth being incorporated to the risk/benefit analysis that precedes every choice of the specific radiopharmaceutical to be used with an individual patient. In this way, we hope these results will be of some help for those Nuclear Medicine specialists interested in the treatment of oncological bone pathologies. (Author)

  4. Determination of Sn in 99{sup m}Tc Radiopharmaceutical Kits by Polarographic Methods; Determinacion de Estano en Radiofarmacos de 99{sup m}Tc mediante Metodos Polarograficos

    Energy Technology Data Exchange (ETDEWEB)

    Castro, M.; Cruz, J.; Sanchez, M.

    2009-07-01

    Kits of 99{sup m}Tc radiopharmaceuticals are used in nuclear medicine for diagnosis of different diseases. Sn (II) is one of the essential components in their formulations, which is used for reduction 99{sup m}Tc-pertechnetate in cold kits for on-site preparation 99{sup m}Tc-pertechnetate radiopharmaceuticals. Usually, these cold kits contain different additives (complexing agents, antioxidants, buffers, etc.) and the amount of Sn (II) varies from kit to kit. The determination of Sn in these products is essential in assessing their quality. We report here the development of a new polarographic method for the determination of Sn (II) and total Sn in representative radiopharmaceuticals kits (for the content of Sn and chemical composition) produced at the Center of Isotopes of Cuba (CENTIS). These methods were validated by analysis of variance and recovery techniques. From the results of the validation, the characteristic functions of uncertainties and fits are considered for the established methods, which give the necessary evidences to demonstrate the usefulness of these methods according to the current trends in Analytical Chemistry. This work provides practical results of great importance for CENTIS. After the speciation of Sn in the MAG3 radiopharmaceuticals kit is inferred that the production process is affected by uncontrolled factors that influence in the product stability, which demonstrates the necessity for analytical tools for the characterization of products and processes. (Author) 57 refs.

  5. First Human Use of a Radiopharmaceutical Prepared by Continuous-Flow Microfluidic Radiofluorination: Proof of Concept with the Tau Imaging Agent [18F]T807

    Directory of Open Access Journals (Sweden)

    Steven H. Liang

    2014-10-01

    Full Text Available Despite extensive preclinical imaging with radiotracers developed by continuous-flow microfluidics, a positron emission tomographic (PET radiopharmaceutical has not been reported for human imaging studies by this technology. The goal of this study was to validate the synthesis of the tau radiopharmaceutical 7-(6-fluoropyridin-3-yl-5H-pyrido[4,3-b]indole ([18F]T807 and perform first-in-human PET scanning enabled by microfluidic flow chemistry. [18F]T807 was synthesized by our modified one-step method and adapted to suit a commercial microfluidic flow chemistry module. For this proof of concept, the flow system was integrated to a GE Tracerlab FXFN unit for high-performance liquid chromatography purification and formulation. Three consecutive productions of [18F]T807 were conducted to validate this radiopharmaceutical. Uncorrected radiochemical yields of 17 ± 1% of crude [18F]T807 (≈ 500 mCi, radiochemical purity 95% were obtained from the microfluidic device. The crude material was then purified, and > 100 mCi of the final product was obtained in an overall uncorrected radiochemical yield of 5 ± 1% (n = 3, relative to starting [18F]fluoride (end of bombardment, with high radiochemical purity (≥ 99% and high specific activities (6 Ci/μmol in 100 minutes. A clinical research study was carried out with [18F]T807, representing the first reported human imaging study with a radiopharmaceutical prepared by this technology.

  6. Crotalus durissus terrificus venom as a source of antitumoral agents

    Directory of Open Access Journals (Sweden)

    MA Soares

    2010-01-01

    Full Text Available The basic knowledge on neoplasms is increasing quickly; however, few advances have been achieved in clinical therapy against tumors. For this reason, the development of alternative drugs is relevant in the attempt to improve prognosis and to increase patients' survival. Snake venoms are natural sources of bioactive substances with therapeutic potential. The objective of this work was to identify and characterize the antitumoral effect of Crotalus durissus terrificus venom (CV and its polypeptide, crotoxin, on benign and malignant tumors, respectively, pituitary adenoma and glioblastoma. The results demonstrated that CV possess a powerful antitumoral effect on benign (pituitary adenoma and malignant (glioblastoma multiforme tumors with IC50 values of 0.96 ± 0.11 µg/mL and 2.15 ± 0.2 µg/mL, respectively. This antitumoral effect is cell-cycle-specific and dependent on extracellular calcium, an important factor for crotoxin phospholipase A2 activity. The CV antitumoral effect can be ascribed, at least partially, to the polypeptide crotoxin that also induced brain tumor cell death. In spite of the known CV nephrotoxicity and neurotoxicity, acute treatment with its antitumoral dose established in vitro was not found to be toxic to the analyzed animals. These results indicate the biotechnological potential of CV as a source of pharmaceutical templates for cancer therapy.

  7. Antitumor activity of polyacrylates of noble metals in experiment

    Directory of Open Access Journals (Sweden)

    Larisa A. Ostrovskaya

    2014-08-01

    Full Text Available The aim of this research has been the study of the antitumor activity of polymetalacrylate derivatives containing in their structure noble metals. Metallic derivatives of polyacrylic acid were not previously tested as antitumor agents.The antitumor activity of polyacrylates, containing argentum (argacryl, aurum (auracryl and platinum (platacryl against experimental models of murine solid tumors (Lewis lung carcinoma and Acatol adenocarcinoma as well as acute toxicity have been studied. It is found that the polyacrylates of noble metals are able to inhibit tumor growth up to 50-90% in comparison with the control. Auracryl induced the inhibition of the Lewis lung carcinoma and Acatol adenocarcinoma by 80 and 90% in comparison with the control, results recommending it for further advanced preclinical studies.

  8. Interactions between inflammatory mediators in expression of antitumor cytostatic activity of macrophages

    NARCIS (Netherlands)

    I.L. Bonta; S. Ben-Efraim

    1990-01-01

    markdownabstractAbstract Antitumor properties and participation in inflammatory events are important characteristics of activated macrophages. We show here that both antitumor cytostatic function of macrophages and participation of these cells at inflammatory sites are controlled by two main group

  9. Synthesis and antitumor activity of novel 10-amino acids ester homocamptothecin analogues

    Institute of Scientific and Technical Information of China (English)

    Liang You; Wan Nian Zhang; Zhen Yuan Miao; Wei Guo; Xiao Ying Che; Wen Ya Wang; Chun Quan Sheng; Jiang Zhong Yao; Ting Zhou

    2008-01-01

    Nine racemic homocamptothecin derivatives were synthesized and in vitro antitumor activities were evaluated by standard MTT method.The results showed that some of the compound had higher antitumor activity than iritecan.

  10. Fractionated photothermal antitumor therapy with multidye nanoparticles

    Directory of Open Access Journals (Sweden)

    Gutwein LG

    2012-01-01

    Full Text Available Luke G Gutwein1, Amit K Singh2, Megan A Hahn2, Michael C Rule3, Jacquelyn A Knapik4, Brij M Moudgil2, Scott C Brown2, Stephen R Grobmyer11Division of Surgical Oncology, Department of Surgery, College of Medicine, 2Particle Engineering Research Center, 3Cell and Tissue Analysis Core, McKnight Brain Institute, 4Department of Pathology, University of Florida, Gainesville, FL, USAPurpose: Photothermal therapy is an emerging cancer treatment paradigm which involves highly localized heating and killing of tumor cells, due to the presence of nanomaterials that can strongly absorb near-infrared (NIR light. In addition to having deep penetration depths in tissue, NIR light is innocuous to normal cells. Little is known currently about the fate of nanomaterials post photothermal ablation and the implications thereof. The purpose of this investigation was to define the intratumoral fate of nanoparticles (NPs after photothermal therapy in vivo and characterize the use of novel multidye theranostic NPs (MDT-NPs for fractionated photothermal antitumor therapy.Methods: The photothermal and fluorescent properties of MDT-NPs were first characterized. To investigate the fate of nanomaterials following photothermal ablation in vivo, novel MDT-NPs and a murine mammary tumor model were used. Intratumoral injection of MDT-NPs and real-time fluorescence imaging before and after fractionated photothermal therapy was performed to study the intratumoral fate of MDT-NPs. Gross tumor and histological changes were made comparing MDT-NP treated and control tumor-bearing mice.Results: The dual dye-loaded mesoporous NPs (ie, MDT-NPs; circa 100 nm retained both their NIR absorbing and NIR fluorescent capabilities after photoactivation. In vivo MDT-NPs remained localized in the intratumoral position after photothermal ablation. With fractionated photothermal therapy, there was significant treatment effect observed macroscopically (P = 0.026 in experimental tumor-bearing mice

  11. Regional intracellular pH shift: a proposed new mechanism for radiopharmaceutical uptake in brain and other tissues.

    Science.gov (United States)

    Kung, H F; Blau, M

    1980-02-01

    This paper proposes a new mechanism for radiopharmaceutical uptake, which may be applicable to a variety of clinical studies. Many tissues and organs have low intracellular pH, either normally or as a result of various metabolic disturbances. We have developed a series of compounds that are neutral and lipid-soluble at blood pH. These molecules can diffuse freely into cells. In those regions where intracellular pH is low, they pick up a hydrogen ion and become charged. In this form they are no longer lipid-soluble and are trapped because they cannot diffuse out of the cell. Studies of the brain uptake of two compounds of this type, Se-75 labeled di-beta-(morpholinoethyl)-selenide (MOSE) and di-beta-(piperidinoethyl)-selenide (PIPSE), demonstrate the application of the principle.

  12. Interactive radiopharmaceutical facility between Yale Medical Center and Brookhaven National Laboratory. Progress report, October 1976-June 1979

    Energy Technology Data Exchange (ETDEWEB)

    Gottschalk, A.

    1979-01-01

    DOE Contract No. EY-76-S-02-4078 was started in October 1976 to set up an investigative radiochemical facility at the Yale Medical Center which would bridge the gap between current investigation with radionuclides at the Yale School of Medicine and the facilities in the Chemistry Department at the Brookhaven National Laboratory. To facilitate these goals, Dr. Mathew L. Thakur was recruited who joined the Yale University faculty in March of 1977. This report briefly summarizes our research accomplishments through the end of June 1979. These can be broadly classified into three categories: (1) research using indium-111 labelled cellular blood components; (2) development of new radiopharmaceuticals; and (3) interaction with Dr. Alfred Wolf and colleagues in the Chemistry Department of Brookhaven National Laboratory.

  13. Food and Drug Administration process for development and approval of drugs and radiopharmaceuticals: treatments in urologic oncology.

    Science.gov (United States)

    Ning, Yang-Min; Maher, V Ellen

    2015-03-01

    Regulatory advice and assessment play an important role in the successful development of new drugs and radiopharmaceuticals for the treatment of urologic malignancies. Cooperation between the US Food and Drug Administration (FDA) and the pharmaceutical industry has led to the approval of more than 20 new urologic oncology products in the last 2 decades. Despite these advances, more effective treatments need to be developed and approved for the treatment of urologic malignancies. This review provides general information about the FDA's role in the development of investigational new drugs, with an emphasis on the regulatory process and the requirements for marketing approval. In addition, this review summarizes the products for the treatment of urologic malignancies that were approved by the FDA in the last 30 years and the key issues concerning urologic oncology products that were discussed publicly at Oncologic Drug Advisory Committee meetings in the past 10 years.

  14. Evaluation of different detection systems to determine the radiochemical purity of the technetium eluate and the radiopharmaceutical sestamibi

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Poliane Angelo de L.; Andrade, Wellington G., E-mail: polianeangelo@gmail.com, E-mail: wandrade@cnen.gov.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear; Santos, Luiz Antonio P.; Lima, Fabiana Farias de, E-mail: luanps@uol.com.br, E-mail: fflima@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN/CNEN-PE), Recife, PE (Brazil)

    2013-07-01

    Since 2008 the Brazilian Health Surveillance Agency (ANVISA) has imposed some rules requiring that Nuclear Medicine Services (NMS) perform a minimum of tests with the radiopharmaceuticals before they are administered to their patients according to the Resolution n. 38 (RDC 38). Among the tests, the radiochemical purity is very important because the effectiveness for the use in vivo, and the fact radiochemical impurities may increase the radiation dose beyond to cause some damage in the diagnostic images. Radiochemical Purity is determined by ascendant chromatography technique and when it is used by NMS, the strips are analyzed in dose calibrator. Furthermore, the low activity on the strips can produce errors due to the low detection of this equipment type. Therefore, the aim of this paper is to compare different methods for determining the radiochemical purity of {sup 99m}Tc eluate and {sup 99m}Tc-MIBI radiopharmaceutical; gamma camera, and dose calibrator. The study was developed in three clinics in Recife-PE, and 15 analyses were performed to determine radiochemical purity of technetium eluate and {sup 99m}Tc-MIBI. For evaluating technetium eluate it was used Whatman® 3MM paper in 1cmx8cm strips. On the other hand, for analyzing MIBI radiopharmaceutical it was used 3 Whatman® 3MM paper strips and 3 with silica gel in 1cmx6.5cm format. According to the manufactures, an 1cm point from the base of the strip was labeled. It was dropped 50μ1 of sodium pertechnetate and {sup 99m}Tc-MIBI and, then, the strips were put in the glass tank, with solvent, according to the pharmacopoeia and inserts of the drug manufacturers. After the solvent front reached the end point, the strips were removed and allowed to dry. Firstly, the radioactivity count was made with a gamma camera. After that, the strips were cut in half (eluate) and in 2.5 cm from the base (MIBI) and measured with a dose calibrator. The results of the average radiochemical purity of the eluate in clinics A, B

  15. Sucralose sweetener in vivo effects on blood constituents radiolabeling, red blood cell morphology and radiopharmaceutical biodistribution in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, G.S.; Pereira, M.O. [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Universidade Federal do Rio Grande do Norte, Programa de Pos-Graduacao em Ciencias da Saude, Avenida General Gustavo Cordeiro de Farias, s/n, 59010180 Natal, Rio Grande do Norte (Brazil); Benarroz, M.O.; Frydman, J.N.G.; Rocha, V.C. [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Pereira, M.J. [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Fisiologia, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Fonseca, A.S., E-mail: adnfonseca@ig.com.b [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Universidade Federal do Estado do Rio de Janeiro, Instituto Biomedico, Departamento de Ciencias Fisiologicas, Rua Frei Caneca, 94, Rio de Janeiro 20211040 (Brazil); Medeiros, A.C. [Universidade Federal do Rio Grande do Norte, Programa de Pos-Graduacao em Ciencias da Saude, Avenida General Gustavo Cordeiro de Farias, s/n, 59010180 Natal, Rio Grande do Norte (Brazil); Bernardo-Filho, M. [Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofisica e Biometria, Avenida 28 de Setembro, 87, Vila Isabel, 20551030 Rio de Janeiro (Brazil); Instituto Nacional do Cancer, Coordenadoria de Pesquisa Basica, Praca Cruz Vermelha, 23, 20230130 Rio de Janeiro (Brazil)

    2011-01-15

    Effects of sucralose sweetener on blood constituents labelled with technetium-99m ({sup 99m}Tc) on red blood cell (RBC) morphology, sodium pertechnetate (Na{sup 99m}TcO{sub 4}) and diethylenetriaminepentaacetic acid labeled with {sup 99m}Tc ({sup 99m}Tc-DTPA) biodistribution in rats were evaluated. Radiolabeling on blood constituents from Wistar rats was undertaken for determining the activity percentage (%ATI) on blood constituents. RBC morphology was also evaluated. Na{sup 99m}TcO{sub 4} and {sup 99m}Tc-DTPA biodistribution was used to determine %ATI/g in organs. There was no alteration on RBC blood constituents and morphology %ATI. Sucralose sweetener was capable of altering %ATI/g of the radiopharmaceuticals in different organs. These findings are associated to the sucralose sweetener in specific organs.

  16. Jacalin-Activated Macrophages Exhibit an Antitumor Phenotype

    Science.gov (United States)

    Danella Polli, Cláudia; Pereira Ruas, Luciana; Chain Veronez, Luciana; Herrero Geraldino, Thais; Rossetto de Morais, Fabiana; Roque-Barreira, Maria Cristina; Pereira-da-Silva, Gabriela

    2016-01-01

    Tumor-associated macrophages (TAMs) have an ambiguous and complex role in the carcinogenic process, since these cells can be polarized into different phenotypes (proinflammatory, antitumor cells or anti-inflammatory, protumor cells) by the tumor microenvironment. Given that the interactions between tumor cells and TAMs involve several players, a better understanding of the function and regulation of TAMs is crucial to interfere with their differentiation in attempts to skew TAM polarization into cells with a proinflammatory antitumor phenotype. In this study, we investigated the modulation of macrophage tumoricidal activities by the lectin jacalin. Jacalin bound to macrophage surface and induced the expression and/or release of mainly proinflammatory cytokines via NF-κB signaling, as well as increased iNOS mRNA expression, suggesting that the lectin polarizes macrophages toward the antitumor phenotype. Therefore, tumoricidal activities of jacalin-stimulated macrophages were evaluated. High rates of tumor cell (human colon, HT-29, and breast, MCF-7, cells) apoptosis were observed upon incubation with supernatants from jacalin-stimulated macrophages. Taken together, these results indicate that jacalin, by exerting a proinflammatory activity, can direct macrophages to an antitumor phenotype. Deep knowledge of the regulation of TAM functions is essential for the development of innovative anticancer strategies. PMID:27119077

  17. An antitumor compound julibroside J28 from Albizia julibrissin.

    Science.gov (United States)

    Liang, Hong; Tong, Wen-yong; Zhao, Yu-ying; Cui, Jing-rong; Tu, Guang-zhong

    2005-10-15

    A new triterpenoid saponin, julibroside J(28) (1), was isolated from the stem bark of Albizia julibrissin Durazz (Leguminosae) by using chromatographic method. The structure of 1 was established by spectroscopic methods. 1 displayed significant antitumor activity in vitro against PC-3M-1E8, Bel-7402, and HeLa cancer cell lines at 10 microM assayed by SRB method.

  18. Synthesis and anti-tumor activity of alkenyl camptothecin esters

    Institute of Scientific and Technical Information of China (English)

    Zhi-song CAO; John MENDOZA; Albert DEJESUS; Beppino GIOVANELLA

    2005-01-01

    Aim: To study the degrees of influence of changing side ester chains at position C20 of camptothecin on the anti-tumor activity of the molecules. Methods: The esterification reaction of camptothecin 1 and 9-nitrocamptothecin 2 with crotonic anhydride in pyridine gave the corresponding esters 3 and 4, respectively. The acylation of 1 and 2 with cinnamoyl chloride gave products 7 and 8. Epoxidation reaction of 3 and 4 with m-chloroperoxybenzoic acid in benzene solvent gave the products 5 and 6. Esters 3, 4, and 5 were tested for anti-tumor activity against 14 human cancer cell lines. Results: Both in vitro and in vivo anti-tumor activity studies for these esters were conducted and the data demonstrated positive results, that is, these esters were active against the tested tumor lines. Conclusion: Alkenyl esters 3 and 4 showed strong anti-tumor activity in vitro against 14 different cancer cell lines. Ester 3 was active against human breast carcinoma in mice and the toxicity of the agent was not observed in mice during the treatment, implying that this agent is effective for treatment with low toxicity.

  19. The early antitumor immune response is necessary for tumor growth

    OpenAIRE

    Parmiani, Giorgio; Maccalli, Cristina

    2012-01-01

    Early events responsible of tumor growth in patients with a normal immune system are poorly understood. Here, we discuss, in the context of human melanoma, the Prehn hypothesis according to which a weak antitumor immune response may be required for tumor growth before weakly or non-immunogenic tumor cell subpopulations are selected by the immune system.

  20. Fully automatic, microprocessor-controlled system for the production of /sup 11/CO/sub 2/, /sup 11/CH/sub 3/I and /sup 11/C-labeled radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Vandewalle, T.; Vandecasteele, C.; Guchteneire, F. de; Meulewaeter, L.; Haver, D. van; Denutte, H.; Goethals, P.; Slegers, G. (Ghent Rijksuniversiteit (Belgium))

    1985-06-01

    An automated system for the production of /sup 11/C-labeled radiopharmaceuticals, using /sup 11/C-CH/sub 3/I as a precursor, has been developed. The whole procedure, including irradiation, production of /sup 11/C-CH/sub 3/I, synthesis of the labeled molecule and isolation of the final product is controlled by a microprocessor. Between 30 and 80 mCi of 5 different radiopharmaceuticals are produced routinely with this system.

  1. Difficulties and aspects to take into account in the production, use and distribution of new radiopharmaceuticals PET; Difficultes et aspects a prendre en compte dans la production, l'utilisation et la distribution des nouveaux radiopharmaceutiques TEP

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez, R.; Rayo, J.I.; Serrano, J.; Infante, J.; Luz Dominguez, M.; Garcia, L.; Duran, C. [Hospital Infanta Cristina, Servicio de Medicina Nuclear, Badajoz (Spain)

    2008-10-15

    This article seeks to describe the requirements, legal and technical, for the production, distribution and use of new radiopharmaceuticals PET (other than the {sup 18}F.D.G.), describing the legislative framework in which we find ourselves, the characteristics of a production and types of synthesis and existing modules. A list of susceptible radiopharmaceuticals is presented that are being currently used in nuclear medicine by specifying the real possibilities of their production and use and which are the difficulties we face.

  2. Antitumor effect of seaweeds. II. Fractionation and partial characterization of the polysaccharide with antitumor activity from Sargassum fulvellum.

    Science.gov (United States)

    Yamamoto, I; Nagumo, T; Fujihara, M; Takahashi, M; Ando, Y

    1977-06-01

    An almost purified antitumor polysaccharide fraction (SFPP) was obtained by fractional precipitation with ethanol from hot-water extract of Sargassum fulvellum. The fraction showed remarkable tumor-inhibiting effect against sarcoma-180 implanted subcutaneously in mice. The results of chemical and physical analyses suggested that the active substance may be either a sulphated peptidoglycuronoglycan or a sulphated glycuronoglycan.

  3. Investigation using an advanced extremity gamma instrumentation system of options for shielding the hand during the preparation and injection of radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Whitby, M; Martin, C J [Health Physics, Department of Clinical Physics and Bio-Engineering, Western Infirmary, Glasgow G11 6NY (United Kingdom)

    2003-03-01

    Staff preparing and injecting radiopharmaceuticals in hospitals may receive significant radiation doses to their hands. These doses may be high enough to warrant that they be classified as radiation workers. The influence of local shielding on finger doses has been investigated. Staff preparing radioactive liquids in a radionuclide dispensary and drawing up and injecting radiopharmaceuticals in a nuclear medicine department have been studied. Measurements have been recorded with an electronic extremity dose monitor, an advanced extremity gamma instrumentation system (AEGIS), worn near to the finger tip. The electronic dosimeter allows the pattern of doses received during different procedures to be determined. Doses received for individual manipulations during many routine sessions have been recorded for different staff members. Dose distributions around shielded vials and syringes have also been measured using AEGIS. In the radionuclide dispensary the vials from which radioactive liquids are dispensed are held in tungsten shields, whereas in nuclear medicine simple lead pots are used. Syringe shields are employed for some parts of dispensing and patient injections. Data on dose distributions have been used in interpretation of results from monitoring. Use of syringe shields during dispensing reduced the finger dose by 75-85%. The peaks in dose rate were 60% lower, and periods of exposure to high dose rates were reduced in length by a third because of the restriction in the region of high dose rate. The extremity doses to staff dispensing and injecting radiopharmaceuticals in nuclear medicine were of similar magnitude. Doses received during dispensing varied from 10 to 555 {mu}Gy depending upon whether the vial containing the radiopharmaceutical was directly handled or not. Dose received from individual injections varied from 1 to 150 {mu}Gy depending on the degree of difficulty experienced during the injection.

  4. A simple low-cost of liquid I-131 dispenser for routine radiopharmaceutical dispensing at nuclear medicine department, Institut Kanser Negara

    Energy Technology Data Exchange (ETDEWEB)

    Said, M. A.; Suhaimi, N. E. F. [Fakulti Sains dan Teknologi, Universiti Kebangsaan Malaysia, 43600 UKM, Bangi Selangor (Malaysia); Ashhar, Z. N., E-mail: aminhpj@gmail.com [Institut Kanser Negara, No 4, Jalan P7, Presint 7, 62250 Putrajaya (Malaysia); Zainon, R. [Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, 13200, Kepala Batas, Pulau Pinang (Malaysia)

    2016-01-22

    In routine radiopharmaceutical Iodine-131 ({sup 131}I) dispensing, the amount of radiation dose received by the personnel depends on the distance between the personnel and the source, the time spent manipulating the source and the amount of shielding used to reduce the dose rate from the source. The novel iRAD-I131 dispenser using recycle {sup 131}I liquid lead pot will lead into low cost production, less maintenance and low dose received by the personnel that prepared the {sup 131}I. The new fabricated of low cost {sup 131}I dispenser was tested and the dose received by personnel were evaluated. The body of lead material is made from 2.5 cm lead shielded coated with epoxy paint to absorb the radiation dose up to 7.4 GBq of {sup 131} I. The lead pot was supported with two stainless steel rod. The Optically Stimulated Luminescence (OSL) nanodot was used in this study to measure the dose rate at both extremities for every personnel who prepared the {sup 131}I. Each OSL nanodot was attached at the fingertip. Three different personnel (experienced between one to ten years above in preparing the radiopharmaceuticals) were participated in this study. The average equivalent dose at right and left hand were 122.694 ± 121.637 µSv/GBq and 77.281 ± 62.146 µSv/GBq respectively. This study found that the dose exposure received using iRAD-I131 was less up to seven times compared to the conventional method. The comparison of experimental data using iRAD-I131 and established radiopharmaceutical dispenser was also discussed. The innovation of {sup 131}I dispenser is highly recommended in a small radiopharmaceutical facility with limited budget. The novel iRAD-I131 enables implementation of higher output liquid dispensing with low radiation dose to the personnel.

  5. Radiation risk in pediatric patients: the need for criteria using radiopharmaceuticals activities;Risco radiologico em pacientes pediatricos: a necessidade de criterios para o uso de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Simas, Felipe [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. de Fisica; Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Servico de Monitoracao Individual Interna; Velasques, Silvia M. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Servico de Monitoracao Individual Interna

    2009-07-01

    The administration of radionuclides to children for diagnostic procedures should be carried out only if there is a strong clinical indication. The amount of activity administered may be reduced according to body weight, body surface area or other appropriate criteria. In Brazil, activities used for pediatric patients were evaluated (2003-2005) in sixteen selected public and private institutions in Northeast, Southeast and South geographical regions. The present work presents radiopharmaceuticals activities used in Brazil compared with international surveys performed in USA in 2005 and in the European Union in 2007. The activities per patient weight and minimum and maximum activities used per Brazilian installations were compared with those used in USA installations. Per patients, it was calculated the ideal minimum administered activity for each type of radiopharmaceutical by body weight according the Pediatric Dosage Card (PDC) criteria. It was not possible to compare activities for all radiopharmaceuticals used in Brazil because some are not more used outside, e.g. {sup 131}I-NaI, which is replaced by {sup 123}I-NaI for thyroid imaging. The discrepancy between activities used in Brazil compared with those used in USA and Europe may be attributed to the heterogeneity of Brazilian imaging equipment and lack for specific children protocols. The disadvantages for using fractions of adult activities are: necessity of minimum statistical counting for assurance of image quality and dependence upon equipment calibration. It was concluded that is necessary to establish standard criteria for radiopharmaceuticals activities applied to pediatric patients in Brazil and the risks due to additional activities should be estimated individually. (author)

  6. Investigation using an advanced extremity gamma instrumentation system of options for shielding the hand during the preparation and injection of radiopharmaceuticals.

    Science.gov (United States)

    Whitby, M; Martin, C J

    2003-03-01

    Staff preparing and injecting radiopharmaceuticals in hospitals may receive significant radiation doses to their hands. These doses may be high enough to warrant that they be classified as radiation workers. The influence of local shielding on finger doses has been investigated. Staff preparing radioactive liquids in a radionuclide dispensary and drawing up and injecting radiopharmaceuticals in a nuclear medicine department have been studied. Measurements have been recorded with an electronic extremity dose monitor, an advanced extremity gamma instrumentation system (AEGIS), worn near to the finger tip. The electronic dosimeter allows the pattern of doses received during different procedures to be determined. Doses received for individual manipulations during many routine sessions have been recorded for different staff members. Dose distributions around shielded vials and syringes have also been measured using AEGIS. In the radionuclide dispensary the vials from which radioactive liquids are dispensed are held in tungsten shields, whereas in nuclear medicine simple lead pots are used. Syringe shields are employed for some parts of dispensing and patient injections. Data on dose distributions have been used in interpretation of results from monitoring. Use of syringe shields during dispensing reduced the finger dose by 75-85%. The peaks in dose rate were 60% lower, and periods of exposure to high dose rates were reduced in length by a third because of the restriction in the region of high dose rate. The extremity doses to staff dispensing and injecting radiopharmaceuticals in nuclear medicine were of similar magnitude. Doses received during dispensing varied from 10 to 555 microGy depending upon whether the vial containing the radiopharmaceutical was directly handled or not. Dose received from individual injections varied from 1 to 150 microGy depending on the degree of difficulty experienced during the injection.

  7. Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [{sup 99m}Tc(MIBI){sub 6}]{sup +}

    Energy Technology Data Exchange (ETDEWEB)

    Faria, D.P.; Buchpiguel, C.A.; Marques, F.L.N., E-mail: danielefaria1@gmail.com [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Faculdade de Medicina. Departamento de Radiologia. Servico de Medicina Nuclear

    2015-10-15

    Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [{sup 99m}Tc(MIBI){sub 6}]{sup +} as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol: chloroform (25:75), Whatman 3MM paper and ethanol:chloroform (25:75), and the more expensive ITLC-SG and 1-propanol: chloroform (10:90) were suitable systems for the direct determination of radiochemical purity of [{sup 99m}Tc(MIBI){sub 6}]{sup +} since impurities such as {sup 99m}Tc-reduced-hydrolyzed (RH), {sup 99m}TcO4{sup -} and [{sup 99m}Tc(cysteine){sub 2}]{sup -} complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines. (author)

  8. Effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis

    Institute of Scientific and Technical Information of China (English)

    Jia-Lun Zhu; Zhi-Yong Deng; Chuan-Zhou Yang

    2016-01-01

    Objective:To find the effect of zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy on the growth and clinical symptoms of lung cancer bone metastasis.Methods: A total of 102 lung cancer patients with bone metastases were included in the study and randomly divided into observation group and control group (n=51) according to different treatment they received. Control group received zoledronic acid injection therapy alone, observation group received zoledronic acid injection combined with radiopharmaceutical 89SrCI2 therapy, and then differences in the growth of lung cancer bone metastasis, bone metabolism, tumor markers and alkaline phosphatase, pain score and pain-related mediator levels,etc. were compared between two groups.Results: Number of metastases of observation group after treatment was less than that of control group, and serum bone metabolism indexes OPG, BSP, TRACP-5b, ICTP and BAP levels, serum tumor markers CYFRA21-1, CEA, NSE, CA125 and BALP levels as well as serum pain-related mediators PGE2, ET-1 and TNF-α levels were lower than those of control group (P<0.05).Conclusions:Zoledronic acid injection combined with radiopharmaceutical89SrCI2 therapy can contain the growth of lung cancer bone metastasis, optimize bone metabolism state while alleviate patients’ perception of pain.

  9. Alternative chromatographic system for the quality control of lipophilic technetium-99m radiopharmaceuticals such as [99mTc(MIBI6]+

    Directory of Open Access Journals (Sweden)

    D.P. Faria

    2015-01-01

    Full Text Available Knowledge of the radiochemical purity of radiopharmaceuticals is mandatory and can be evaluated by several methods and techniques. Planar chromatography is the technique normally employed in nuclear medicine since it is simple, rapid and usually of low cost. There is no standard system for the chromatographic technique, but price, separation efficiency and short time for execution must be considered. We have studied an alternative system using common chromatographic stationary phase and alcohol or alcohol:chloroform mixtures as the mobile phase, using the lipophilic radiopharmaceutical [99mTc(MIBI6]+ as a model. Whatman 1 modified phase paper and absolute ethanol, Whatman 1 paper and methanol:chloroform (25:75, Whatman 3MM paper and ethanol:chloroform (25:75, and the more expensive ITLC-SG and 1-propanol:chloroform (10:90 were suitable systems for the direct determination of radiochemical purity of [99mTc(MIBI6]+ since impurities such as 99mTc-reduced-hydrolyzed (RH, 99mTcO4 - and [99mTc(cysteine2]- complex were completely separated from the radiopharmaceutical, which moved toward the front of chromatographic systems while impurities were retained at the origin. The time required for analysis was 4 to 15 min, which is appropriate for nuclear medicine routines.

  10. Detection of active alveolar bone destruction in human periodontal disease by analysis of radiopharmaceutical uptake after a single injection of 99m-Tc-methylene diphosphonate

    Energy Technology Data Exchange (ETDEWEB)

    Jeffcoat, M.K.; Williams, R.C.; Holman, B.L.; English, R.; Goldhaber, P.

    1986-01-01

    Previous studies have shown that, following a single injection of 99m-Tc-MDP, measurement of bone-seeking radiopharmaceutical uptake can detect ''active'' alveolar bone loss due to periodontal disease in beagle dogs, as determined by radiographs taken at the time of, and several months after, the nuclear medicine procedure. The efficacy of this diagnostic test, however, had not been assessed in human periodontal disease. The ability of a single boneseeking radiopharmaceutical uptake examination to detect ''active'' alveolar bone loss due to periodontal disease in human patients was assessed by comparing a single uptake measurement to the rate of bone loss determined from serial radiographs taken over a 6-month period. Uptake was expressed as a ratio of the cpm from the alveolar bone divided by the cpm from the non-tooth supporting bone of the nuchal crest. High uptake ratios were associated with ''active'' loss and low uptake ratios were associated with little if any change in alveolar bone height (p<0.001). The nuclear medicine examination was an accurate detector of periodontal disease activity in nearly 80% of the individual teeth studied. These data indicate that high bone-seeking radiopharmaceutical uptake ratios may be pathognomonic of active bone loss in human periodontal disease.

  11. State of the art and perspectives in radiopharmaceutical field since ACOMEN 8. International Conference (Bordeaux May 11-13, 2005); Le radiopharmaceutique: situation et perspectives depuis la 8. conference internationale de l'ACOMEN (Bordeaux, 11-12-13 mai 2005)

    Energy Technology Data Exchange (ETDEWEB)

    Vuillez, J.P.; Desruet, M.D. [CHU de Grenoble, Pole d' Imagerie, Clinique de Medecine Nucleaire, 38 (France); Desruet, M.D. [CHU de Grenoble, Service de Radiopharmacie, Clinique de Medecine Nucleaire, 38 (France); Mundler, O. [CHU La Timone, Service de Medecine Nucleaire, 13 - Marseille (France); Karcher, G. [CHU de Nancy, Service de Medecine Nucleaire, 54 (France)

    2009-02-15

    Since previous ACOMEN conference in 2005 on radiopharmaceuticals, many improvements have been encountered: active research has allowed the development of numerous new tracers of interest, with a large part dedicated for PET; clinical applications of radiopharmaceuticals have resulted in patients care improvement, both for management and survival; therapeutic applications are now fully recognized, as internal targeted radiotherapy could be considered as efficient in several cancer diseases; and regulation, despite remaining difficulties, will certainly become more favourable for radiopharmaceuticals. Thus we could make sure that radiopharmaceuticals use will be even more established in the next years. (authors)

  12. Antitumor activity of two gelsemine metabolites in rat liver microsomes.

    Science.gov (United States)

    Zhao, Qing-Chun; Hua, Wei; Zhang, Lin; Guo, Tao; Zhao, Ming-Hong; Yan, Ming; Shi, Guo-Bing; Wu, Li-Jun

    2010-09-01

    Gelsemine is one of the major alkaloids from Gelsemium elegans Benth., which has been used as an antitumor remedy in clinic. In this paper, metabolism of gelsemine has been investigated in vitro in phenobarbital-treated rat liver microsomes. The metabolites of gelsemine were separated and evaluated using the flash silica gel column, preparative HPLC, using NMR and MS methods. According to the spectral data, two metabolites, M1 and M2, were identified as 4-N-demethylgelsemine and 21-oxogelsemine, respectively. By the MTT method in vitro, the antitumor activities between gelsemine and its metabolites were compared in the HepG2 and HeLa cell lines. Moreover, the main metabolic pathway was further proposed.

  13. Mucin-like peptides from Echinococcus granulosus induce antitumor activity.

    Science.gov (United States)

    Noya, Verónica; Bay, Sylvie; Festari, María Florencia; García, Enrique P; Rodriguez, Ernesto; Chiale, Carolina; Ganneau, Christelle; Baleux, Françoise; Astrada, Soledad; Bollati-Fogolín, Mariela; Osinaga, Eduardo; Freire, Teresa

    2013-09-01

    There is substantial evidence suggesting that certain parasites can have antitumor properties. We evaluated mucin peptides derived from the helminth Echinococcus granulosus (denominated Egmuc) as potential inducers of antitumor activity. We present data showing that Egmuc peptides were capable of inducing an increase of activated NK cells in the spleen of immunized mice, a fact that was correlated with the capacity of splenocytes to mediate killing of tumor cells. We demonstrated that Egmuc peptides enhance LPS-induced maturation of dendritic cells in vitro by increasing the production of IL-12p40p70 and IL-6 and that Egmuc-treated DCs may activate NK cells, as judged by an increased expression of CD69. This evidence may contribute to the design of tumor vaccines and open new horizons in the use of parasite-derived molecules in the fight against cancer.

  14. Antitumoral Potential of Tunisian Snake Venoms Secreted Phospholipases A2

    Directory of Open Access Journals (Sweden)

    Raoudha Zouari-Kessentini

    2013-01-01

    Full Text Available Phospholipases type A2 (PLA2s are the most abundant proteins found in Viperidae snake venom. They are quite fascinating from both a biological and structural point of view. Despite similarity in their structures and common catalytic properties, they exhibit a wide spectrum of pharmacological activities. Besides being hydrolases, secreted phospholipases A2 (sPLA2 are an important group of toxins, whose action at the molecular level is still a matter of debate. These proteins can display toxic effects by different mechanisms. In addition to neurotoxicity, myotoxicity, hemolytic activity, antibacterial, anticoagulant, and antiplatelet effects, some venom PLA2s show antitumor and antiangiogenic activities by mechanisms independent of their enzymatic activity. This paper aims to discuss original finding against anti-tumor and anti-angiogenic activities of sPLA2 isolated from Tunisian vipers: Cerastes cerastes and Macrovipera lebetina, representing new tools to target specific integrins, mainly, and integrins.

  15. Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents.

    Science.gov (United States)

    Liu, Jia-Jia; Zhao, Meng-Yue; Zhang, Xin; Zhao, Xin; Zhu, Hai-Liang

    2013-11-01

    Within the past years, many researches on the synthesis, structure-activity relationships (SAR), antitumor, antiinflammatory and anti-bacterial activities of the pyrazole derivatives have been reported. Several pyrazole derivatives possess important pharmacological activities and they have been proved useful materials in drug research. Pyrazole derivatives play an important role in antitumor agents because of their good inhibitory activity against BRAF(V600E), EGFR, telomerase, ROS Receptor Tyrosine Kinase and Aurora-A kinase. In addition, pyrazole derivatives also show good antiinflammatory and anti-bacterial activities. In this review, the bioactivities of the pyrazole derivatives mentioned above will be summarized in detail. We sincerely hope that increasing knowledge of the SAR and cellular processes underlying the bioactivity of pyrazole derivatives will be beneficial to the rational design of new generation of small molecule drugs.

  16. Antitumor Activity of Monoterpenes Found in Essential Oils

    Directory of Open Access Journals (Sweden)

    Marianna Vieira Sobral

    2014-01-01

    Full Text Available Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented.

  17. Anti-tumor Action and Clinical Application of Proteasome Inhibitor

    Institute of Scientific and Technical Information of China (English)

    ZHOU Yong-ming; YU Mei-xia; LONG Hui; HUANG Shi-ang

    2008-01-01

    Ubiquitin-proteasome pathway mediates the degradation of cell protein,and cell cycle,gene translation and expression,antigen presentation and inflammatory development.Proteasome inhibitor Call inhibit growth and proliferation of tumor cell,induce apoptosis and reverse multipledrug resistance of tumor cell,increase the sensitivity of other chemomerapeutic drugs and radiotherapy,and is a novel class of potent anti-tumor agents.

  18. Synthesis and antitumor activity of 9-methyl-10-hydroxycamptothecin

    Institute of Scientific and Technical Information of China (English)

    Sheng Wang; Yu Yan Li; Qi Dong You

    2008-01-01

    A novel camptothecin analogue, 9-methyl-10-hydroxycamptothecin (4), was unexpectedly synthesized from 10-hydroxycamptothecin in two steps. The key step included an efficient Mannich-type reaction. The overall yield was 47.2%. An ether analogue of 4, 9-methyl-10-benzylaminomethoxycamptothecin (5), was also prepared. These new camptothecin analogues were evaluated for in vitro cytotoxicity against four human cancer cell lines, and exhibited more potent antitumor activities than contrals camptothecin and topotecan against several cancer cells.

  19. Antitumor mechanisms of metformin: Signaling, metabolism, immunity and beyond

    Directory of Open Access Journals (Sweden)

    Ismael Samudio

    2010-08-01

    Full Text Available Metformin is a synthetic biguanide first described in the 1920´s as a side product of the synthesis of N,N-dimethylguanidine. Like otherrelated biguanides, metformin displays antihyperglycemic properties, and has become the most widely prescribed oral antidiabetic medicinearound the world. Intriguing recent evidence suggests that metformin has chemopreventive and direct antitumor properties, and severalongoing clinical studies around the world are using this agent alone or in combination with chemotherapeutic schemes to determineprospectively its safety and efficacy in the treatment of human cancer. Notably, immune activating effects of metformin have recently beendescribed, and may support a notion put forth in the 1950s that this agent possessed antiviral and antimalarial effects. However, how theseeffects may contribute to its observed antitumor effects in retrospective studies has not been discussed. Mechanistically, metformin has beenshown to activate liver kinase B1 (LKB1 and its downstream target AMP-activated kinase (AMPK. The activation of AMPK has beenproposed to mediate metformin´s glucose lowering effect, although recent evidence suggests that this agent can inhibit electron transport inhepatocyte mitochondria resulting in AMPK-independent inhibition of hepatic gluconeogenesis. Likewise, albeit activation of AMPK andthe resulting inhibition of the mammalian target of rapamycin (mTOR signaling have been suggested to mediate the antitumor effects ofmetformin, AMPK-independent growth inhibitory properties of this agent in tumor cells have also been described. Here we present a briefreview of the signaling, metabolic, and immune effects of metformin and discuss how their interplay may orchestrate the antitumor effectsof this agent. In addition, we provide the rationale for a compassionate use study of metformin in combination with metronomic chemotherapy.

  20. Three anti-tumor saponins from Albizia julibrissin.

    Science.gov (United States)

    Zheng, Lu; Zheng, Jian; Zhao, Yuying; Wang, Bin; Wu, Lijun; Liang, Hong

    2006-05-15

    Three new triterpenoid saponins, julibroside J(29) (1), julibroside J(30) (2), and julibroside J(31) (3), were isolated from the stem bark of Albizia julibrissin Durazz. (Leguminosae) by using chromatographic method. Their structures were established by spectroscopic methods. Compounds 1, 2, and 3 displayed significant anti-tumor activities in vitro against PC-3M-1E8, HeLa, and MDA-MB-435 cancer cell lines at 10microM assayed by SRB and MTT methods.

  1. Jungle Honey Enhances Immune Function and Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Miki Fukuda

    2011-01-01

    Full Text Available Jungle honey (JH is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal. After seven injections, peritoneal cells (PC were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2 cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261.

  2. Separation and nanoencapsulation of antitumor polypeptide from Spirulina platensis.

    Science.gov (United States)

    Zhang, Bochao; Zhang, Xuewu

    2013-01-01

    Spirulina platensis is a multicellular edible blue-green alga with abundant proteins (∼ 60%). No report is available on the antitumor polypeptides from the whole proteins of S. platensis. In this study, for the first time, an antitumor polypeptide Y2 from trypsin digest of S. platensis proteins was obtained by using freeze-thawing plus ultrasonication extraction, hydrolysis with four enzymes (trypsin, alcalase, papain, and pepsin), and gel filtration chromatography. The results showed that the degree of hydrolysis can be ordered as: trypsin (38.5%) > alcalase (31.2%) > papain (27.8%) > pepsin (7.1%). For MCF-7 and HepG2 cells, at 250 µg/mL, the maximum inhibitory rate of Y2 was 97%, while standard drug 5-FU was 55 and 97%, respectively. Furthermore, the nanoencapsulation of Y2 with chitosan (CS) was also investigated. After nanoencapsulation, the maximum encapsulation efficiency and polypeptides contents are 49 and 15%, respectively; and the antitumor activity is basically not lost. These data demonstrated the potential of nanopolypeptides (Y2-CS) in food and pharmaceutical applications.

  3. Piper betle extracts exhibit antitumor activity by augmenting antioxidant potential.

    Science.gov (United States)

    Alam, Badrul; Majumder, Rajib; Akter, Shahina; Lee, Sang-Han

    2015-02-01

    The present study was conducted to evaluate the methanolic extract of Piper betle leaves (MPBL) and its organic fractions with regard to antitumor activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice and to confirm their antioxidant activities. At 24 h post-intraperitoneal inoculation of tumor cells into mice, extracts were administered at 25, 50 and 100 mg/kg body weight for nine consecutive days. The antitumor effects of the extracts were then assessed according to tumor volume, packed cell count, viable and non-viable tumor cell count, median survival time and increase in life span of EAC-bearing mice. Next, hematological profiles and serum biochemical parameters were calculated, and antioxidant properties were assessed by estimating lipid peroxidation, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. MPBL and the ethylacetate fraction (EPBL) at a dose of 100 mg/kg induced a significant decrease in tumor volume, packed cell volume and viable cell count and increased the life span of the EAC-bearing mice (PPiper betle extracts exhibit significant antitumor activity, which may be attributed to the augmentation of endogenous antioxidant potential.

  4. Synergistic antitumor efficiency of docetaxel and curcumin against lung cancer

    Institute of Scientific and Technical Information of China (English)

    Haitao Yin; Rui Guo; Yong Xu; Yulong Zheng; Zhibo Hou; Xinzheng Dai; Zhengdong Zhang; Donghui Zheng; Hua'e Xu

    2012-01-01

    Curcumin (Cum),the principal polyphenolic curcuminoid,obtained from the turmeric rhizome Curcuma longa,is recently reported to have potential antitumor effects in vitro and in vivo.Docetaxel (Doc) is considered as first-line chemotherapy for the treatment of non-small cell lung cancer.Here we report for the first time that Cum could synergistically enhance the in vitro and in vivo antitumor efficacy of Doc against lung cancer.In the current study,combination index (CI) is calculated in both in vitro and in vivo studies to determine the interaction between Cum and Doc.In the in vitro cytotoxicity test,media-effect analysis clearly indicated a synergistic interaction between Cum and Doc in certain concentrations.Moreover,in vivo evaluation further demonstrated the superior anticancer efficacy of Cum + Doc compared with Doc alone by intravenous delivery in an established A549 transplanted xenograft model.Results showed that Cum synergistically increased the efficacy of Doc immediately after 4 days of the initial treatment.Additionally,simultaneous administration of Cum and Doc showed little toxicity to normal tissues including bone marrow and liver at the therapeutic doses.Therefore,in vitro and in vivo evaluations demonstrated the satisfying synergistic antitumor efficacy of Cum and Doc against lung cancer and the introduction of Cum in traditional chemotherapy is a most promising way to counter the spread of nonsmall cell lung cancer.

  5. Antitumor effects of the benzophenanthridine alkaloidsanguinarine: Evidence and perspectives

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Historically, natural products have represented a significantsource of anticancer agents, with plant-deriveddrugs becoming increasingly explored. In particular,sanguinarine is a benzophenanthridine alkaloid obtainedfrom the root of Sanguinaria canadensis , and from otherpoppy Fumaria species, with recognized anti-microbial,anti-oxidant and anti-inflammatory properties. Recently,increasing evidence that sanguinarine exibits anticancerpotential through its capability of inducing apoptosisand/or antiproliferative effects on tumor cells, has beenproved. Moreover, its antitumor seems to be due notonly to its pro-apoptotic and inhibitory effects on tumorgrowth, but also to its antiangiogenic and anti-invasiveproperties. Although the precise mechanisms underlyingthe antitumor activity of this compound remain notfully understood, in this review we will focus on themost recent findings about the cellular and molecularpathways affected by sanguinarine, together withthe rationale of its potential application in clinic. Thecomplex of data currently available suggest the potentialapplication of sanguinarine as an adjuvant in the therapyof cancer, but further pre-clinical studies are neededbefore such an antitumor strategy can be effectivelytranslated in the clinical practice.

  6. Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds.

    Science.gov (United States)

    Chen, Ling; Zhang, Qiao-Yan; Jia, Min; Ming, Qian-Liang; Yue, Wei; Rahman, Khalid; Qin, Lu-Ping; Han, Ting

    2016-05-01

    Plant endophytic fungi have been recognized as an important and novel resource of natural bioactive products, especially in anticancer application. This review mainly deals with the research progress on the production of anticancer compounds by endophytic fungi between 1990 and 2013. Anticancer activity is generally associated with the cytotoxicity of the compounds present in the endophytic fungi. All strains of endophytes producing antitumor chemicals were classified taxonomically and the genera of Pestalotiopsis and Aspergillus as well as the taxol producing endophytes were focused on. Classification of endophytic fungi producing antitumor compounds has received more attention from mycologists, and it can also lead to the discovery of novel compounds with antitumor activity due to phylogenetic relationships. In this review, the structures of the anticancer compounds isolated from the newly reported endophytes between 2010 and 2013 are discussed including strategies for the efficient production of the desired compounds. The purpose of this review is to provide new directions in endophytic fungi research including integrated information relating to its anticancer compounds.

  7. Antioxidant, antimutagenic, and antitumor effects of pine needles (Pinus densiflora).

    Science.gov (United States)

    Kwak, Chung Shil; Moon, Sung Chae; Lee, Mee Sook

    2006-01-01

    Pine needles (Pinus densiflora Siebold et Zuccarini) have long been used as a traditional health-promoting medicinal food in Korea. To investigate their potential anticancer effects, antioxidant, antimutagenic, and antitumor activities were assessed in vitro and/or in vivo. Pine needle ethanol extract (PNE) significantly inhibited Fe(2+)-induced lipid peroxidation and scavenged 1,1-diphenyl- 2-picrylhydrazyl radical in vitro. PNE markedly inhibited mutagenicity of 2-anthramine, 2-nitrofluorene, or sodium azide in Salmonella typhimurium TA98 or TA100 in Ames tests. PNE exposure effectively inhibited the growth of cancer cells (MCF-7, SNU-638, and HL-60) compared with normal cell (HDF) in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In in vivo antitumor studies, freeze-dried pine needle powder supplemented (5%, wt/wt) diet was fed to mice inoculated with Sarcoma-180 cells or rats treated with mammary carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA, 50 mg/kg body weight). Tumorigenesis was suppressed by pine needle supplementation in the two model systems. Moreover, blood urea nitrogen and aspartate aminotransferase levels were significantly lower in pine needle-supplemented rats in the DMBA-induced mammary tumor model. These results demonstrate that pine needles exhibit strong antioxidant, antimutagenic, and antiproliferative effects on cancer cells and also antitumor effects in vivo and point to their potential usefulness in cancer prevention.

  8. Characterization and antitumor activity of a polysaccharide from Sarcodia ceylonensis.

    Science.gov (United States)

    Fan, Yijun; Lin, Mengchuan; Luo, Aoshuang; Chun, Ze; Luo, Aoxue

    2014-07-25

    A water-soluble polysaccharide from Sarcodia ceylonensis was obtained by using the method of water-extraction and ethanol-precipitation. The polysaccharide was further purified by chromatography on AB-8 and ADS-7 columns, yielding a pure polysaccharide termed SCP-60. The molecular weight (Mw) of SCP-60 was calculated to be 50.0 kDa, based on the calibration curve obtained with a series of Dextran T standards. The results of FT-IR indicated that the polysaccharide contains the α-configuration of sugar units. GC-MS analysis revealed that SCP-60 was mainly composed of galactose and glucose. NMR spectroscopy revealed SCP-60 had the backbone consisting of → 6)-α-Manp-(1 →, α-D-Glcp-(1 →, → 6)-α-D-Glcp-(1 → and → 6)-α-Galp-(1 →. In order to evaluate the antitumor activity in vivo of the polysaccharide, a sarcoma 180 model was used. The results showed SCP-60 had strong antitumor ability, meanwhile, SCP-60 at a high dose (100 mg/kg) could significantly increase the thymic and splenic indices of S180 mice, and strongly promote the secretion of IL-2, TNF-α and IFN-γ, increase the SOD activities and reduce the concentrations of MDA in blood. Therefore the polysaccharide SCP-60 should be explored as a novel potential antitumor drug.

  9. In Vitro Antitumor Activity of Sesquiterpene Lactones from Lychnophora trichocarpha

    Directory of Open Access Journals (Sweden)

    D.A. Saúde-Guimarães

    2014-06-01

    Full Text Available The sesquiterpene lactones lychnopholide and eremantholide C were isolated from Lychnophora trichocarpha Spreng. (Asteraceae, which is a plant species native to the Brazilian Savannah or Cerrado and popularly known as arnica. Sesquiterpene lactones are known to present a variety of biological activities including antitumor activity. The present paper reports on the evaluation of the in vitro antitumor activity of lychnopholide and eremantholide C, in the National Cancer Institute, USA (NCI, USA, against a panel of 52 human tumor cell lines of major human tumors derived from nine cancer types. Lychnopholide disclosed significant activity against 30 cell lines of seven cancer types with IC100 (total growth concentration inhibition values between 0.41 µM and 2.82 µM. Eremantholide C showed significant activity against 30 cell lines of eight cancer types with IC100 values between 21.40 µM and 53.70 µM. Lychnopholide showed values of lethal concentration 50% (LC50 for 30 human tumor cell lines between 0.72 and 10.00 µM, whereas eremantholide C presented values of LC50 for 21 human tumor cell lines between 52.50 and 91.20 µM. Lychnopholide showed an interesting profile of antitumor activity. The α-methylene-γ-lactone present in the structure of lychnopholide, besides two α,β- unsaturated carbonyl groups, might be responsible for the better activity and higher cytotoxicity of this compound in relation to eremantholide C.

  10. Laser stimulation of the acupoint ‘Zusanli’ (ST.36) on the radiopharmaceutical biodistribution in Wistar rats

    Indian Academy of Sciences (India)

    Eric Hff Frederico; Ailton A Santos; Danubia C Sa-Caputo; Rosane F Neves; Carlos As Guimaraes; Shyang Chang; Mario Bernardo-Filho

    2016-03-01

    Laser used to stimulate acupoints is called laser acupuncture (LA). It is generally believed that similar clinical responses to manual acupuncture can be achieved. Here we analysed the effects of the laser (904 nm) at the ‘Zusanli’ acupoint (ST.36) of the stomach meridian on the biodistribution of the radiopharmaceutical Na 99mTcO4. Wistar rats were divided into control (CG) and experimental groups (EG). The EG were exposed daily to the laser (904 nm) at ST.36 with 1 joule/min (40 mW/cm2) for 1 min. The animals of the CG were not exposed to laser at all. On the 8th day after LA, the animals were sedated and Na 99mTcO4 was administered. After 10 min, the animals were all sacrificed and the organs removed. The radioactivity was counted in each organ to calculate the percentage of radioactivity of the injected dose per gram (%ATI/g). Comparison of the %ATI/g in EG and CG was performed by Mann-Whitney test. The %ATI/g was significantly increased in the thyroid due to the stimulation of the ST.36 by laser. It is possible to conclude that the stimulation of ST.36 does lead to biological phenomena that interfere with the metabolism of the thyroid.

  11. New pathways to medicare coverage for innovative PET radiopharmaceuticals: report of a medical imaging & technology alliance (MITA) workshop.

    Science.gov (United States)

    Hillman, Bruce J; Frank, Richard A; Rodriguez, Gail M

    2012-02-01

    PET and PET/CT have revolutionized the diagnosis, staging, and monitoring of treatment effect or recurrence for a wide range of cancers and shown promise for improving health outcomes for patients with cardiovascular and central nervous system diseases. However, this technology is challenged by insurance coverage policies that hinder patients' access to PET and discourage technologic innovation. Recently, the Medical Imaging & Technology Alliance (MITA), a Washington-based industry association, convened a workshop to consider new pathways for making decisions on Medicare coverage of new PET radiopharmaceuticals and imaging procedures that are currently subject to a national noncoverage decision, or "exclusionary rule." Stakeholders from the government, medical professional societies, academia, patient groups, and industry gathered to brainstorm alternatives to the national noncoverage decision and evaluate their potential to improve access and enhance innovation. Ultimately, MITA, on behalf of the PET community, expects to use the outcomes of the workshop to propose that the Centers for Medicare and Medicaid Services reconsider this current national noncoverage decision for PET and adopt a new framework for coverage.

  12. Comparison of four technetium-99m radiopharmaceuticals for detection and localization of gastrointestinal bleeding in a sheep model

    Energy Technology Data Exchange (ETDEWEB)

    Owunwanne, A.; Al-Wafai, I.; Vallgren, S.; Sadek, S.; Abdel-Dayem, H.M.; Yacoub, T.

    1988-01-01

    Four Tc-99 radiopharmaceuticals, Tc-99m sulphur colloid, Tc-99m red blood cells (RBCs), Tc-99m mercaptoacetyltriglycine (MAG3), and Tc-99m DTPA, were studied in an experimental animal model for detection and localization of gastrointestinal (GI) bleeding site in both the upper and lower abdomen. With Tc-99m sulphur colloid and Tc-99m RBCs, it was possible to detect and localize the GI bleeding site in the lower abdomen. With Tc-99m MAG3, it was possible to visualize the bleeding site in both the upper and lower abdomen. However, Tc-99m MAG3 is partially excreted by the liver into the bile, hence it will be difficult to use Tc-99m MAG3 to localize the GI bleeding site in the lower abdomen. With Tc-99m DTPA, it was possible to detect and localize the GI bleeding site simultaneously in both upper and lower abdomen. The overall background radioactivity was reduced considerably by diuresis with frusemide and catheterization of the urinary bladder.

  13. Bone-seeking radiopharmaceuticals for treatment of osseous metastases, Part 1: α therapy with 223Ra-dichloride.

    Science.gov (United States)

    Pandit-Taskar, Neeta; Larson, Steven M; Carrasquillo, Jorge A

    2014-02-01

    Metastatic disease to bone is commonly seen in the advanced stages of many cancers. The cardinal symptom, pain, is often the cause of significant morbidity and reduced quality of life. Treatment of bone pain includes nonsteroidal analgesics and opiates; however, long-term use of these drugs is commonly associated with significant side effects, and tolerance is common. External-beam radiation therapy is effective mainly in localized disease sites. Bone-targeting radiopharmaceuticals are beneficial in the management of patients with multiple metastatic lesions. This article focuses on the 3 most commonly used agents: the Food and Drug Administration-approved (89)Sr-chloride, (153)Sm-ethylenediaminetetramethylene phosphonic acid (EDTMP), and (223)Ra-dichloride. We will discuss the physical characteristics, clinical data, dosage, and administration of these agents, including optimal patient selection and toxicity associated with their use. These radioactive agents have proven efficacy in the treatment of painful osseous metastases from prostate cancer and breast cancer. Significant recent advances include use of these agents in combination with chemotherapy and the use of the α emitter (223)Ra-dichloride in prostate cancer, primarily to improve survival and skeletal related events. The review is presented in 2 parts. The first will discuss the characteristics and clinical use of (223)Ra-dichloride, and the second will discuss the β emitters (89)Sr and (153)Sm-EDTMP.

  14. Molecular modeling in the development of metal radiopharmaceuticals. Final progress report, July 15, 1989--July 14, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Green, M.A.

    1993-10-01

    We began this project with a compilation of a structural library to serve as a data base containing descriptions of the molecular features of metal-labeled radiopharmaceuticals known to efficiently cross the blood-brain barrier. Such a data base is needed in order to identify structural features (size, shape, molecular surface areas and volumes) that are critical in allowing blood-brain barrier penetration. Nine metal complexes have been added to this structural library. We have completed a detailed comparison of four molecular mechanics computer programs QUANTA, SYBYL, BOYD, and MM2DREW to assess their applicability to modeling the structures of low molecular weight metal complexes. We tested the ability of each program to reproduce the crystallographic structures of 38 complexes between nickel(II) and saturated N-donor ligands. The programs were evaluated in terns of their ability to reproduce structural features such as bond lengths, bond angles, and torsion angles. Recently, we investigated the synthesis and characterization of lipophilic cationic gallium complexes with hexadentate bis(salicylaldimine) ligands. This work identified the first gallium-68 radiopharrnaceuticals that can be injected intravenously and that subsequently exhibit significant myocardial uptake followed by prolonged myocardial retention of {sup 68}Ga radioactivity. Tracers of this type remain under investigation as agents for evaluation of myocardial perfusion with positron emission tomography.

  15. Environmental effects on the structure of metal ion-DOTA complexes: An ab initio study of radiopharmaceutical metals.

    Energy Technology Data Exchange (ETDEWEB)

    Lau, E Y; Lightstone, F C; Colvin, M E

    2006-02-10

    Quantum mechanical calculations were performed to study the differences between the important radiopharmaceutical metals yttrium (Y) and indium (In) bound by DOTA and modified DOTA molecules. Energies were calculated at the MP2/6-31+G(d)//HF/6-31G(d) levels, using effective core potentials on the Y and In ions. Although the minimum energy structures obtained are similar for both metal ion-DOTA complexes, changes in coordination and local environment significantly affect the geometries and energies of these complexes. Coordination by a single water molecule causes a change in the coordination number and a change in the position of the metal ion in In-DOTA; but, Y-DOTA is hardly affected by water coordination. When one of the DOTA carboxylates is replaced by an amide, the coordination energy for the amide arm shows a large variation between the Y and In ions. Optimizations including water and guandinium moieties to approximate the effects of antibody binding indicate a large energy cost for the DOTA-chelated In to adopt the ideal conformation for antibody binding.

  16. Performance of the radionuclide calibrators used at Division of Radiopharmaceuticals Production of the CRCN-NE, Recife, PE, Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Fragoso, Maria Conceicao de Farias; Albuquerque, Antonio Morais de Sa; Oliveira, Mercia L.; Lima, Fernando Roberto de Andrade [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-07-01

    The radionuclide calibrators are essential instruments in nuclear medicine services to determine the activity of radiopharmaceuticals which will be administered to the patients. Essentially, it consists of a well-type ionization chamber coupled to a special displaying electronic circuit which allows one visualize the instrument response in activity units. Inappropriate performance of these equipment may lead to underestimation or overestimation of the activity, compromising the success of diagnosis or therapy. Quality control describes the procedures by which one can assure quality of activity measurement, providing efficacy of nuclear medicine procedures that employ unsealed sources of radioactivity. Several guides of national and international organizations summarize the recommended tests for the quality control of the radionuclide calibrators: accuracy, precision, reproducibility, linearity and geometry. The aim of this work was to establish a quality control program on the radionuclide calibrators from Divisao de Producao de Radiofarmacos (DIPRA) of the Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE), Brazil, utilized as reference instruments on comparison of activities measurements.. The results were determined and compared to the references values recommended by national and international guides. Besides, the geometry test provided the correction factors to be applied in activity measurements in different containers, in different volumes and in different positions. (author)

  17. Technetium-99m d,l-HM-PAO: a new radiopharmaceutical for SPECT imaging of regional cerebral blood perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Neirinckx, R.D.; Canning, L.R.; Piper, I.M.; Nowotnik, D.P.; Pickett, R.D.; Holmes, R.A.; Volkert, W.A.; Forster, A.M.; Weisner, P.S.; Marriott, J.A.

    1987-02-01

    Following investigation of a large number of new ligands based upon propylene amine oxime (PnAO) the d,l-diastereoisomer of hexamethyl propyleneamine oxime (HM-PAO) was selected as the preferred ligand for 99mTc as a tracer for cerebral perfusion imaging. The neutral, lipophilic 99mTc complex of d,l-HM-PAO was formed in high yield by stannous reduction of 99Mo/99mTc generator eluate using a kit formulation of the ligand. Two minutes following i.v. administration of this complex in rats, 2.25% of the injected dose appears in the brain. Little washout of the tracer is observed up to 24 hr postinjection. By qualitative autoradiographic comparison with iodoantipyrine this new radiopharmaceutical displays blood flow dependent brain uptake with little redistribution of the tracer over time. The lipophilic 99mTc complex converts slowly in vitro to a secondary complex. This conversion process may account for the ability of (99mTc)d,l-HM-PAO to be retained within the brain without redistribution.

  18. SU-C-303-03: Dosimetric Model of the Beagle Needed for Pre-Clinical Testing of Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Shang, M; Sands, M; Bolch, W [University of Florida, Gainesville, FL (United States)

    2015-06-15

    Purpose: Large animal models, most popularly beagles, have been crucial surrogates to humans in determining radiation safety levels of radiopharmaceuticals. This study aims to develop a detailed beagle phantom to accurately approximate organ absorbed doses for therapy nuclear medicine preclinical studies. Methods: A 3D NURBS model was created subordinate to a whole body CT of an adult beagle. Bones were harvested and CT imaged to offer macroscopic skeletal detail. Samples of trabecular spongiosa were cored and imaged to offer microscopic skeletal detail for bone trabeculae and marrow volume fractions. Results: Organ masses in the model are typical of an adult beagle. Trends in volume fractions for skeletal dosimetry are fundamentally similar to those found in existing models of other canine species. Conclusion: This work warrants its use in further investigations of radiation transport calculation for electron and photon dosimetry. This model accurately represents the anatomy of a beagle, and can be directly translated into a useable geometry for a voxel-based Monte Carlo radiation transport program such as MCNP6. Work supported by a grant from the Hyundai Hope on Wheels Foundation for Pediatric Cancer Research.

  19. A radiopharmaceutical for imaging areas of lymphocytic infiltration: [sup 123]I-interleukin-2. Labelling procedure and animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Signore, A.; Chianelli, M.; Toscano, A.; Monetini, L.; Ronga, G.; Pozzilli, P.; Negri, M. (Policlinico Umberto, Rome (Italy). Clinica Medica 2); Nimmon, C.C.; Britton, K.E. (Saint Bartholomew' s Hospital, London (United Kingdom). Dept. of Nuclear Medicine)

    1992-10-01

    The labelling of interleukin-2 (IL-2) with [sup 123]I and its in vivo application for imaging chronic pathological lymphocytic infiltrations are described. The lactoperoxidase/glucoseoxidase technique was the labelling method of choice leading to immunoreactive IL-2 with high specific activity. Labelled IL-2 was injected in diabetes-prone non-obese diabetic (NOD) mice with pancreatic lymphocytic infiltration. As control animals, Balb/c mice were used. As specificity control, monoclonal antibodies AMT13 and UCHT1, bovine serum albumin and [alpha]-lactalbumin were radioiodinated and injected in mice. Eighteen NOD mice and four control Balb/c mice were used for gamma camera imaging experiments. Fifty-four NOD and 20 Balb/c mice were used for time course single organ counting and autoradiography. Gamma camera images showed that radioactivity accumulated in the pancreatic region from the 10th minute onwards in NOD mice injected with [sup 123]I-IL-2 but not in Balb/c mice, or in NOD mice injected with control radiopharmaceuticals. These findings were confirmed by counting the radioactivity present in single organs. Autoradiography of NOD pancreas, after injection of labelled IL-2, showed that radioactivity was specifically associated with infiltrating lymphocytes. In conclusion, this technique is highly specific and easy to perform and we suggest its application in humans for in vivo detection of areas of lymphocytic infiltration. (Author).

  20. Curative effect of HF10 on liver and peritoneal metastasis mediated by host antitumor immunity

    Science.gov (United States)

    Hotta, Yoshihiro; Kasuya, Hideki; Bustos, Itzel; Naoe, Yoshinori; Ichinose, Toru; Tanaka, Maki; Kodera, Yasuhiro

    2017-01-01

    Background HF10 is a highly attenuated type 1 herpes simplex virus (HSV) with proven effective oncolytic effect. Previous investigations have demonstrated that colon cancer mice model treated with HF10 not only had better survival but were also resistant to the reimplantation of the antitumor effect mediated by host antitumor immunity. Importantly, it has also been noted that in mice with antitumors implanted on both sides of the back, an injection of HF10 on only one side strongly restrains not only the injected antitumor but also the non-injected ones. Materials and methods MC26 colon cancer cells were injected subcutaneously into the back, spleen, and intraperitoneal region of metastasis model mice. Antitumor volume and survival rate were monitored. To measure cytotoxic T lymphocytes (CTL) cytotoxicity against MC26, lymphocytes were extracted from the spleens of the peritoneal metastasis model mice as well as from the thymus of the liver metastasis model mice. The expression of interferon gamma was examined by enzyme-linked immunospot assay. Samples from the liver metastasis model mice were subjected to polymerase chain reaction to quantify the level of HSV genomes. Results HF10 was injected only on the back antitumor; however, a antitumor-suppressor effect was observed against liver and peritoneal metastases. When HF10 genome was measured, we observed lower genome on liver metastases compared to back antitumor genome quantity. CTL activity against MC26 was also observed. These results indicate that local administration of HF10 exerts a curative effect on systemic disease, mediated by host antitumor immunity. Conclusion HF10 local administration stimulates antitumor immunity to recognize antitumor-specific antigen, which then improves systemic disease. Metastatic antitumors lysis, on the other hand, appears to be mediated by the host immune system, rather than by virus-mediated direct oncolysis. PMID:28331843

  1. Interaction between antitumor drug and silver nanoparticles:combined fluorscence and surface enhanced Raman scattering study

    Institute of Scientific and Technical Information of China (English)

    Jing Yang; Hong Wang; Zhuyuan Wang; Xuebin Tan; Chunyuan Song; Ruohu Zhang; Jin Li; Yiping Cui

    2009-01-01

    Optical methods and MTT method are used to characterize the antiproliferation effect of antitumor drug 9-aminoacridine (9AA) with and without silver nanoparticles.Intracellular surface enhanced Raman scat tering (SERS) spectra and fluorescent spectra of 9AA indicate the form of 9AA adsorbed on the surface of silver nanoparticles.Although both silver nanoparticles and antitumor drug can inhibit the growth of Hela cells,silver nanoparticles can slow down the antiproliferation effect on Hela cells at low concentration of antitumor drugs.Our experimental results suggest that silver nanoparticles may serve as slow-release drug carriers,which is important in antitumor drug delivery.

  2. Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Melendez-Alafort, Laura [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)], E-mail: laura.melendez@unipd.it; Nadali, Anna; Zangoni, Elena [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy); Banzato, Alessandra; Rondina, Maria [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Rosato, Antonio [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Istituto Oncologico Veneto, IOV, Padova, Padua (Italy); Mazzi, Ulderico [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)

    2009-08-15

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of {sup 188}Re-HA was determined. Results: A stable complex of {sup 188}Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T{sub 1/2}{alpha}=21 min). Four hours after administration, {sup 188}Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47{+-}5.11% of the injected dose). The liver MTD in mice was {approx}40 Gy after 7.4 MBq of {sup 188}Re-HA injection. Conclusions: {sup 188}Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

  3. {sup 177}Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Rajabi, Hossein, E-mail: hrajabi@modares.ac.i [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Babaei, Mohammad Hossein; Daha, Fariba Johari [Department of Radioisotope, Nuclear Science and Technology Research Institute, 14115-331 Tehran (Iran, Islamic Republic of)

    2010-11-15

    Introduction: In the present study, Herceptin was labeled with lutetium-177 via DOTA, and the necessary preclinical quality control tests (in vitro and in vivo) were performed to evaluate its use as a radioimmunotherapy agent. Material and Methods: Herceptin was conjugated to DOTA as a chelator in three different conjugation buffers (ammonium acetate, carbonate and HEPES buffer); each of the resulting conjugates was compared with respect to in vitro characteristics such as number of chelates per antibody, incorporated activity, immunoreactivity and in vitro stability in PBS buffer and blood serum. The biodistribution study and gamma camera imaging were performed in mice bearing breast tumors. To assess the therapeutic effects of {sup 177}Lu-Herceptin, cytotoxicity was investigated for 7 days in a SKBr3 breast cancer cell line. Results: Carbonate buffer was the best conjugation buffer (number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81%, after 4 days). The efficient tumor uptake observed in the biodistribution studies was consistent with the gamma camera image results. At a concentration of 4 {mu}g ml{sup -1}, {sup 177}Lu-Herceptin (surviving cells: 5{+-}0.6% of the total cells) of the total cells corresponded to an approximately eightfold increase in cytotoxicity in comparison to unmodified Herceptin (surviving cells: 43{+-}3.9%). Conclusion: The new complex described herein could be considered for further evaluation in animals and potentially in humans as a radiopharmaceutical for use in the radioimmunotherapy of breast cancer. These results may be important for patients who cannot tolerate the therapeutic dosage of Herceptin currently used because of heart problems.

  4. Non invasive scintigraphic method for biodistribution study of radiopharmaceuticals; Metodo cintilografico nao invasivo para estudo de biodistribuicao de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Erika V.; Silva, Natanael G.; Freire, Antonio C.; Monteiro, Elisiane de G.; Benedetti, Stella; Muramoto, Emiko; Fukumori, Neuza T.O.; Matsuda, Margareth M.N., E-mail: erikavieira@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia; Vasconcellos, Marina B.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisa

    2011-07-01

    Biodistribution studies can be done by invasive or noninvasive methods. The aim of this study was to evaluate the percentage of retained dose (RD) in the organs of interest in noninvasive and invasive study of biodistribution of {sup 99m}Tc-DMSA (dimercaptosuccinic acid), {sup 99m}Tc-MAA (macro aggregated human serum albumin) and {sup 99m}Tc-MDP (methylene diphosphonate) and to compare with the invasive method described in the United States Pharmacopoeia (USP). Lyophilized reagents (DMSA, MAA and MDP) and sodium pertechnetate was obtained from IPEN-CNEN/SP. The radioactive concentration was 123 MBq mL{sup -1} ({sup 99m}Tc-DMSA and {sup 99m}Tc-MAA) and 617 MBq mL{sup -1} ({sup 99m}Tc-MDP). {sup 99m}Tc-DMSA and {sup 99m}Tc-MDP were injected via the tail vein and {sup 99m}Tc-MAA in the penile vein of rats. The scintigraphic images were obtained in a Nucline TH/22 Mediso gamma camera. The animals were sacrificed after the acquisition of images. The organs were removed and the activity of each organ of interest was measured in an ionization chamber. The renal uptake of {sup 99m}Tc-DMSA by noninvasive method was (47,02 +- 2,87)% up to (49,37 +- 3,41)%. By the invasive method it was observed RD (49.27 +- 1.88)%. The %RD of {sup 99m}Tc-MAA in the lungs by non-invasive method varied from (94,22 +- 0,17)% to (94,67 +- 0,25)%. Bone scintigraphy with {sup 99m}Tc-MDP showed significant uptake in the skeleton. The method proposed for noninvasive scintigraphic study biodistribution of radiopharmaceuticals was feasible, with results comparable to those obtained by invasive method described in USP. (author)

  5. Non invasive scintigraphic method for biodistribution study of radiopharmaceuticals; Metodo cintilografico nao invasivo para estudo de biodistribuicao de radiofarmacos

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, Erika V.; Silva, Natanael G.; Freire, Antonio C.; Monteiro, Elisiane de G.; Benedetti, Stella; Muramoto, Emiko; Fukumori, Neuza T.O.; Matsuda, Margareth M.N., E-mail: erikavieira@usp.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia; Vasconcellos, Marina B.A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro do Reator de Pesquisa

    2010-07-01

    Biodistribution studies can be done by invasive or noninvasive methods. The aim of this study was to evaluate the percentage of retained dose (RD) in the organs of interest in noninvasive and invasive study of biodistribution of {sup 99m}Tc-DMSA (dimercaptosuccinic acid), {sup 99m}Tc-MAA (macro aggregated human serum albumin) and {sup 99m}Tc-MDP (methylene diphosphonate) and to compare with the invasive method described in the United States Pharmacopoeia (USP). Lyophilized reagents (DMSA, MAA and MDP) and sodium pertechnetate was obtained from IPEN-CNEN/SP. The radioactive concentration was 123 MBq mL{sup -1} ({sup 99m}Tc-DMSA and {sup 99m}Tc-MAA) and 617 MBq mL{sup -1} ({sup 99m}Tc-MDP). {sup 99m}Tc-DMSA and {sup 99m}Tc-MDP were injected via the tail vein and {sup 99m}Tc-MAA in the penile vein of rats. The scintigraphic images were obtained in a Nucline TH/22 Mediso gamma camera. The animals were sacrificed after the acquisition of images. The organs were removed and the activity of each organ of interest was measured in an ionization chamber. The renal uptake of {sup 99m}Tc-DMSA by noninvasive method was (47,02 {+-} b 2,87)% up to (49,37 {+-} b 3,41)%. By the invasive method it was observed RD (49.27 {+-} b 1.88)%. The %RD of {sup 99}mTc-MAA in the lungs by non-invasive method varied from (94,22 {+-} b 0,17)% to (94,67 {+-} b 0,25)%. Bone scintigraphy with {sup 99}mTc-MDP showed significant uptake in the skeleton. The method proposed for noninvasive scintigraphic study biodistribution of radiopharmaceuticals was feasible, with results comparable to those obtained by invasive method described in USP. (author)

  6. A new monoclonal antibody radiopharmaceutical for radioimmunoscintigraphy of breast cancer: direct labeling of antibody and its quality control

    Directory of Open Access Journals (Sweden)

    Mojtaba Salouti

    2006-03-01

    Full Text Available Radioimmunoscintigraphy (RIS has found widespread clinical application in tumor diagnosis. The antibody (Ab PR81 is a new murine anti-MUC1 monoclonal antibody (MAb against human breast carcinoma. In this study a very simple, rapid and efficient method for labeling of this MAb with 99mTc, particularly suitable for development of a ‘kit’is described. The reduction of Ab was performed with 2-mercaptoethanol (2-ME at a molar ratio of 2000:1 (2-ME:MAb and the reduced Ab was labeled with 99mTc via methylene diphosphonate (MDP as a transchelator. The labeling efficiency which was determined by instant thin layer chromatography (ITLC was 94.2%±2.3. Radiocolloides measured by cellulose nitrate electrophoresis were 2.5%±1.7. In vitro stability of the labeled product in human serum which was measured by gel filtration chromatography (FPLC was 70%±5.7 over 24 hr. The integrity of labeled MAb was checked by means of SDS-PAGE and no significant fragmentation was observed. The results of the cell-binding studies showed that both labeled and unlabeled PR81 were able to compete for binding to MCF 7 cells. Biodistribution studies were performed in normal BALB/c mice at 4 and 24 hrs post-injection and no important accumulation was observed in vital organs. These results show that the new radiopharmaceutical may be considered as a promising candidate for imaging of breast cancer.

  7. Synergistic Antitumor Efficacy of Oncolytic Adenovirus Combined with Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    LI Yue-min; QIAN Qi-jun; SONG San-tai; JIANG Ze-fei; ZHANG Qi; QU Yi-mei; SU Chang-qing; ZHAO Chuan-hua; LI Zhi-qiang; GE Fei-jiao

    2007-01-01

    Objective: Chemotherapy is an effective means of treating breast cancer, and cancer-specific replicative adenovirus is also a promising antitumor agent in recent years. Our investigation aims to demonstrate that CNHK300 can mediate selective antitumor efficacy and produce synergistic cytotoxicity with chemotherapy on HER-2 over-expressing breast cancer. Methods: We engineered the telomerase-dependent replicative adenovirus CNHK300 by placing the E1A gene under the control of the human hTERT promoter. By analysis of E1A expression, we proved the fidelity of hTERT promoter in adenovirus genome and the selective expression of E1A in telomerase-positive breast cancer cells but not in normal fibroblast cells. By proliferation test, we further showed efficient replication of CNHK300 in breast cancer cells with apparently attenuated proliferation in normal fibroblast cells. Finally, we demonstrated by MTT methods that CNHK300 virus caused potent cytolysis and produced synergistic cytotoxicity with chemotherapy in breast cancer cells with attenuated cytotoxicity on normal cells. Results: In this virus, the E1A gene is successfully placed under the control of the human hTERT promoter. CNHK300 virus replicated as efficiently as the wild-type adenovirus and caused intensive cell killing in HER-2 over-expressing breast cancer cells in vitro. In contrast, telomerase-negative normal fibroblast cells, which expressed no hTERT activity, were not able to support CNHK300 replication. Combined treatment of CNHK300 with paclitaxel improved cytotoxicity on cancer cells. Conclusion: We conclude that CNHK300 can produce selective antitumor efficacy and enhance the in vitro response of chemotherapy on HER-2 overexpressing breast cancer.

  8. IL-12 induces T helper 1-directed antitumor response.

    Science.gov (United States)

    Tsung, K; Meko, J B; Peplinski, G R; Tsung, Y L; Norton, J A

    1997-04-01

    Although IL-12 possesses the most potent single-cytokine antitumor efficacy, the mechanism by which IL-12 exerts its antitumor activities remains unclear. Using a complete tumor regression model induced by IL-12 treatment, we demonstrate that the antitumor response induced by IL-12 is mediated by a Th1 cell-directed process, with the macrophage as the effector cell and nitric oxide produced by the activated macrophage as the effector molecule. The induction of the Th1 response by IL-12 depends on the existence of a host T cell response to the tumor before IL-12 administration. IL-12 treatment causes the complete regression of 10-day established s.c. tumors (4-8 mm). Associated with the induction of tumor necrosis, activated macrophages expressing high levels of inducible nitric oxide synthase were found surrounding the tumor. The importance of nitric oxide as the effector molecule was further confirmed by the delay and loss of tumor regression in the presence of a nitric oxide synthase inhibitor in vivo. Examination of tumor-associated T cells indicates that IL-12 induces production of the Th1 cytokine IFN-gamma and suppresses production of IL-2, IL-4, and IL-10 at the tumor site, where these are found to be the predominant cytokines produced by tumor-associated T cells before IL-12 treatment. These findings demonstrate that IL-12 plays an essential role in the induction of an effective Th1 type of cell-mediated immune response against established tumors.

  9. In vivo toxicity and antitumor activity of mangosteen extract.

    Science.gov (United States)

    Kosem, Nuttavut; Ichikawa, Kazuhiro; Utsumi, Hideo; Moongkarndi, Primchanien

    2013-04-01

    Mangosteen (Garcinia mangostana) has been widely used in the traditional medicine of Thailand to treat various ailments, especially diseases of the digestive system and infections. Many reports show antiproliferation of crude extracts and active constituents from mangosteen against many cancer cell lines. Therefore, the current study is proposed to demonstrate in vivo evidence on the antitumor activity of mangosteen. Crude methanolic extract (CME) from mangosteen pericarp including 25.19 % α-mangostin as an active xanthone was used in this study. The inhibition on tumor cell proliferation of CME was preliminarily evaluated against the murine colon cancer cell line NL-17 with an IC50 value of 17 and 84 μg/ml based on WST-1 and LDH assays, respectively. The safety dose for animal application was assessed by in vivo toxicity studies using female BALB/c mice. Acute toxicity showed an LD50 value and approximate lethal dose at 1,000 mg/kg, whereas the suitable dose for short-term study should be ≤200 mg/kg. The effective dose for antitumor activity of CME was found to be between 100 and 200 mg/kg, with a tumor size reduction of 50-70 %. Histological staining clearly illustrated a decrease of tumor cell density in the footpad in a dose-dependent manner. The median survival time and life span significantly increased in tumor-bearing mice with CME treatment. This study suggests that CME possesses a powerful antitumor activity. Therefore, it is worth undertaking further investigation to identify active compounds and obtain a deeper understanding of their mechanism, in order to acquire novel effective anticancer drugs.

  10. THEORETICAL STUDY OF PODOPHYLLOTOXIN AND QUINOLONE ANALOGUES AS ANTITUMOR DRUGS

    Institute of Scientific and Technical Information of China (English)

    何峰; 戴颖仪; 朱孝峰; 黄爱东; 张翎; 颜少平; 刘宗潮

    2002-01-01

    Objective: To study the active sites of podophyllotoxin derivatives. Methods: Some podophyllotoxin derivatives were analyzed by quantum and mechanics method. Results: Some information was given according to the calculation results about HOMO and LUMO electron density. The C-4 position is the position for effective modification. The B ring and E ring are important active centers. Conclusion: The hole of positive charge in B ring easily combines with an acceptor within the molecular. Some quinolones with similar electronic construction to podophyllotoxin may have antitumor activity.

  11. Arginine Deiminase Enzyme Evolving As A Potential Antitumor Agent.

    Science.gov (United States)

    Somani, Rakesh; Chaskar, Pratip K

    2016-08-17

    Some melanomas and hepatocellular carcinomas have been shown to be auxotrophic for arginine. Arginine deiminase (ADI), an arginine degrading enzyme isolated from Mycoplasma, can inhibit the growth of these tumors. It is a catabolizing enzyme which catabolizes arginine to citrulline. Tumor cells do not express an enzyme called arginosuccinate synthetase (ASS) and hence, these cells becomes auxotrophic for arginine. It is found that ADI is specific for arginine and did not degrade other amino acid. This review covers various aspects of ADIs like origin, properties and chemical modifications for better antitumor activity.

  12. NMR studies on antitumor drug candidates, berberine and berberrubine

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Young Wook; Jung, Jin Won; Kang, Mi Ran; Chung, In Kwon; Lee, Weon Tae [Yonsei Univ., Seoul (Korea, Republic of)

    2002-03-01

    Berberine and berberrubine, which display antitumor activity, have also demonstrated distinct enzyme-poisoning activities by stabilizing topoisomerase II-DNA cleavable complexes. The protoberberine berberrubine differs in chemical structure with berberine at only one position, however, it shows a prominent activity different from berberine. Solution structures of berberine and berberrubine determined by NMR spectroscopy are similar, however, the minor structural rearrangement has been observed near 19 methoxy or hydroxyl group. We suggest that the DNA cleavage activities of topoisomerase II poisons could be correlated with both chemical environments and minor structural change together with hydrophobicity of interacting side chains of drugs with DNA molecules.

  13. Evaluation of Deoxyribonucleic Acid Toxicity Induced by the Radiopharmaceutical 99mTechnetium-Methylenediphosphonic Acid and by Stannous Chloride in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Adriano Caldeira-de-Araujo

    2012-11-01

    Full Text Available Radiopharmaceuticals are employed in patient diagnostics and disease treatments. Concerning the diagnosis aspect, technetium-99m (99mTc is utilized to label radiopharmaceuticals for single photon computed emission tomography (SPECT due to its physical and chemical characteristics. 99mTc fixation on pharmaceuticals depends on a reducing agent, stannous chloride (SnCl2 being the most widely-utilized. The genotoxic, clastogenic and anegenic properties of the 99mTc-MDP(methylene diphosphonate used for bone SPECT and SnCl2 were evaluated in Wistar rat blood cells using the Comet assay and micronucleus test. The experimental approach was to endovenously administer NaCl 0.9% (negative control, cyclophosphamide 50 mg/kg b.w. (positive control, SnCl2 500 μg/mL or 99mTc-MDP to animals and blood samples taken immediately before the injection, 3, and 24 h after (in the Comet assay and 36 h after, for micronucleus test. The data showed that both SnCl2 and 99mTc-MDP-induced deoxyribonucleic acid (DNA strand breaks in rat total blood cells, suggesting genotoxic potential. The 99mTc-MDP was not able to induce a significant DNA strand breaks increase in in vivo assays. Taken together, the data presented here points to the formation of a complex between SnCl2 in the radiopharmaceutical 99mTc-MDP, responsible for the decrease in cell damage, compared to both isolated chemical agents. These findings are important for the practice of nuclear medicine.

  14. Control flow of radiopharmaceuticals in nuclear medicine by means of an E-service; Control flujo de radiofarmacos en medicine nuclear por medio de un E-servicio

    Energy Technology Data Exchange (ETDEWEB)

    Nunez Martin, L.; Gonzalez de Mingo, M. A.; Fragua Redondo, J. A.; Martinez Ortega, J.; Gutierrez Camunas, S.; Redondo Miguel, A. B.

    2013-07-01

    The almost generalized use of single-dose Nuclear Medicine for performing diagnostic tests or treatments, and the consequent complexity that accompanies its management, has resulted in the need to control the flow of material radioisotopic tools. An e-service is designed to manage the flow of radiopharmaceuticals and control its use and spending. This control does not only affect the efficiency in the use and cost of material, but in the radioactive waste associated with the non-use and waste reduction and a more effective organization of the Department. (Author)

  15. Identification of anti-tumoral effect of a polypeptide isolated from Scorpionfish Scorpaena plumieri venom and assessment of its potential use for tumor diagnosis; Identificacao do efeito antitumoral de um polipeptidio isolado da peconha do peixe-escorpiao Scorpaena plumieri e avaliacao do seu potencial uso no diagnostico de tumores

    Energy Technology Data Exchange (ETDEWEB)

    Soprani, Juliana

    2008-07-01

    Cancer has killed millions of people worldwide. Despite the increasing knowledge about the molecular basis of tumor development, few advances have been reached in clinical therapy and diagnoses, which shows the importance of new drugs development for therapeutic and diagnosis purpose. Venomous creatures have been studied as potential sources of pharmacological agents and physiological tools. A lot of work has been done about biological activity of terrestrial animals, but comparatively less research has been undertaken on venomous marine creature, particularly fish, which means that marine toxins represent a vast and unexplored source of novel molecules with therapeutical potential. In this work, the scorpion fish Scorpaena plumieri crude venom (SPB) and a gelatinolytic protease purified from this venom (SPGP) were evaluated for their applicability for in vivo tumor detection. In vitro results showed that both. SPB and SPGP, possess a powerful antitumor effects on p53-wild-type glioblastoma cells (LD{sub 50}= 3,9 {+-} 0,98{mu}g/mL and 8,00 x 10{sup -12} {+-} 2,94 x 10{sup -12}M, respectively) and Ehrlich ascites carcinoma cells (LD{sub 50}=14,05 {+-} 2,95 {mu}g/mL and 1,22 x 10{sup -11} {+-} 6,56 x 10{sup -12}M, respectively). P53 mutant glioblastoma cells were more resistant to both, SPB and SPGP treatment (LD{sub 50} > 125 {mu}g/mL and LD{sub 50} > 1,39 x 10{sup -9}M, respectively). The morphological changes observed in the cell lines treated with SPB and SPGP, and the data of DAPI staining, indicate that the antitumor effect of these substances occurs via apoptosis. Radioactive probes of SPB ([{sup 99m}Tc] SPB) and SPGP ([{sup 125}I] SPGP) with high specific activity and high radiochemical purity were synthesized. Data of biodistribution studies, performed by intravenous injections in Swiss mice bearing Ehrlich carcinoma cells, showed that SPB has poor uptake in tumor region. On the other hand, SPGP had a substantial uptake in tumor at ali analyzed times

  16. Purification and Crystallization of Flammulin, a Basic Protein with Anti-tumor Activities from Flammulina Velutipes

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Flammulin, an anti-tumor protein, was purified from the aqueous extract of basidiomes of Flammulina Velutipes to electrophoretic homogeneity and crystallized by microdialysis against a polyethylene glycol- sodium phosphate buffer. The purified product was found to have marked antitumor effects and be able to affect the tumor cells directly.

  17. Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma

    Directory of Open Access Journals (Sweden)

    Yu Wang

    2015-01-01

    Conclusions: Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors. This mHSP/P vaccine exerted greater antitumor effects than did HSP70, HSP60, or tumor lysates alone.

  18. Evaluation of radiochemistry purity and p H of radiopharmaceuticals in nuclear medicine services at Pernambuco, Brazil; Avaliacao da pureza radioquimica e pH de radiofarmacos em servicos de medicina nuclear de Pernambuco, Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Wellington; Lima, Fabiana Farias de, E-mail: falima@cnen.gov.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Santos, Poliane A.L.; Lima, Fernando Roberto de Andrade; Lima, Fabiana Farias de, E-mail: fflima@cnen.gov.b [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2011-07-01

    Radiopharmaceuticals are cellular or molecular structures that have a radionuclide in its composition and they are used for diagnosing or treating diseases. The evaluation of the radiochemical purity of radiopharmaceuticals is essential to produce images with artifacts free, as well as avoid unnecessary absorbed dose to the patient. Since they are administered in humans is important and necessary that they undergo rigorous quality control. Due to this fact, the norm in ANVISA RDC 38/2008 declaring the mandatory completion of a minimum of tests in routine nuclear medicine services before human administration. (author)

  19. Study of the influence of the protective covering from contamination on the radiopharmaceutical bottle in measurement of activity; Estudo da influencia do involucro protetor de contaminacao no frasco de radiofarmacos na medicao da atividade

    Energy Technology Data Exchange (ETDEWEB)

    Kuahara, L.T.; Correa, E.L.; Potiens, M.P.A, E-mail: lilian547@hotmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2014-07-01

    This study aims to determine the influence of the use of a plastic covering on the bottle used to supply radiopharmaceuticals to analyze the feasibility of its use at the time of manufacture, in order to avoid contamination in the activity meter well chamber. For that were held several measured with liquid {sup 137}Cs source with and without this envelope and the activity meters of the calibration laboratory. Tests showed a small variation in the percentage of measures with the plastic covering, value considerably low, which will not cause injury in providing radiopharmaceuticals for the Service Nuclear Medicine.

  20. Synthesis of [1-{sup 11}C]octanoic acid, [{sup 11}C]raclopride and [{sup 11}C]nicergoline with a general-purpose automated synthesis apparatus of {sup 11}C-labeled radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Yajima, Kazuyosi; Kawashima, Hidefumi; Cui, Ying-she; Hashimoto, Naoto; Miyake, Yoshihiro [National Cardiovascular Center, Suita, Osaka (Japan)

    1997-06-01

    We have developed a general-purpose automated synthesis apparatus of {sup 11}C-labeled radiopharmaceuticals for PET, which can be adopted to both one-pot and two-or-more-pot reactions. The features of the apparatus were shown in the successful preparation of [(1-{sup 11})C]octanoic acid in a one-pot reaction and [{sup 11}C]raclopride and [{sup 11}C]nicergoline in two-pot reactions, the latter being a novel radiopharmaceutical. (author).

  1. Antitumor activities of D-glucosamine and its derivatives

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li; LIU Wan-shun; HAN Bao-qin; PENG Yan-fei; WANG Dong-feng

    2006-01-01

    The growth inhibitory effects of D-glucosamine hydrochloride (GlcNH2·HCl), D-glucosamine (GlcNH2) and N-acetyl glucosamine (NAG) on human hepatoma SMMC-7721 cells in vitro were investigated. The results showed that GlcNH2·HCl and GlcNH2 resulted in a concentration-dependent reduction in hepatoma cell growth as measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. This effect was accompanied by a marked increase in the proportion of S cells as analyzed by flow cytometry. In addition, human hepatoma SMMC-7721 cells treated with GlcNH2·HCl resulted in the induction of apoptosis as assayed qualitatively by agarose gel electrophoresis. NAG could not inhibit the proliferation of SMMC-7721 cells.GlcNH2·HCl exhibited antitumor activity against Sarcoma 180 in Kunming mice at dosage of 125~500 mg/kg, dose of 250 mg/kg being the best. GlcNH2·HCl at dose of 250 mg/kg could enhance significantly the thymus index, and spleen index and could promote T lymphocyte proliferation induced by ConA. The antitumor effect of GlcNH2·HCl is probably host-mediated and cytocidal.

  2. ANTITUMOR EFFECTS OF MONOCLONAL ANTIBODY FAB′ FRAGMENT CONTAINING IMMUNOCONJUGATES

    Institute of Scientific and Technical Information of China (English)

    刘小云; 甄永苏

    2002-01-01

    Objective.Using monoclonal antibody (mAb) Fab′ fragment to develop mAb immunoconjugates for cancer. Methods.Fab′ fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DTT),while Fab′ fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by β mercaptoethanol.The conjugation between Fab′ fragment and pingyangmycin (PYM),an antitumor antibiotic,was mediated by dextran T 40.Immunoreactivity of Fab′ PYM conjugates with cancer cells was determined by ELISA,and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay.Antitumor effects of the Fab′ PYM conjugates were evaluated by subcutaneously transplanted tumors in mice. Results.The molecular weight of Fab′ fragment was approximately 53 kD,while the average molecular weight of Fab′ PYM conjugate was 170 kD.The Fab′ PYM conjugates showed immunoreactivity with antigen relevant cancer cells and selective cytotoxicity against target cells.Administered intravenously,Fab′ PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb. Conclusion.Fab′ PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth,suggesting its therapeutic potential in cancer treatment.

  3. Antitumor effect of sonodynamically activated pyrrolidine tris-acid fullerene

    Science.gov (United States)

    Iwase, Yumiko; Nishi, Koji; Fujimori, Junya; Fukai, Toshio; Yumita, Nagahiko; Ikeda, Toshihiko; Chen, Fu-shin; Momose, Yasunori; Umemura, Shin-ichiro

    2016-07-01

    In this study, the sonodynamically induced antitumor effect of pyrrolidine tris-acid fullerene (PTF) was investigated. Sonodynamically induced antitumor effects of PTF by focused ultrasound were investigated using isolated sarcoma-180 cells and mice bearing ectopically-implanted colon 26 carcinoma. Cell damage induced by ultrasonic exposure was enhanced by 5-fold in the presence of 80 µM PTF. The combined treatment of ultrasound and PTF suppressed the growth of the implanted colon 26 carcinoma. Ultrasonically induced 2,2,6,6-tetramethyl-4-piperidone-1-oxyl (4oxoTEMPO) production in the presence and absence of PTF was assessed, and it was shown that 80 µM PTF enhanced 4oxoTEMPO production as measured by ESR spectroscopy. Histidine, a reactive oxygen scavenger, significantly reduced cell damage and 4oxoTEMPO generation caused by ultrasonic exposure in the presence of PTF. These results suggest that singlet oxygen is likely to be involved in the ultrasonically induced cell damage enhanced by PTF.

  4. [Immunomodulatory and antitumor properties of polysaccharide peptide (PSP)].

    Science.gov (United States)

    Piotrowski, Jakub; Jędrzejewski, Tomasz; Kozak, Wiesław

    2015-01-21

    Modern medicine successfully uses multiple immunomodulators of natural origin, that can affect biological reactions and support body's natural defense mechanisms including antitumor activities. Among them is a group of products derived from fungi, including schizophyllan, lentinan, polysaccharide Krestin (PSK), and polysaccharidepeptide (PSP). Present paper is focused on polysaccharidepeptide, which due to the negligible toxicity and numerous benefits for health, is increasingly used in China and Japan as an adjuvant in the treatment of cancer. PSP is a protein-polisaccharide complex with a molecular weight 100 kDa derived from Coriolus versicolor mushroom. The results of numerous studies and clinical trials confirm that it inhibits the growth of cancer cells in in vitro and in vivo settings as well as decreases cancer treatment-related adverse side effects such as fatigue, loss of appetite, nausea, vomiting, and pain. PSP is able to restore weakened immune response observed in patients with cancer during chemotherapy. Its anti-tumor effects seemed to be mediated through immunomodulatory regulation. PSP stimulates cells of the immune system, induces synthesis of cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), eicosanoids including prostaglandin E2 (PGE2), histamine, reactive oxygen species and nitrogen mediators. There is a growing interest in understanding the mechanisms of PSP action. Because of its unique properties and safety, PSP may become a widely used therapeutic agent in the near future.

  5. Electroporation: A New Approach Enhancing Antitumor Effects of Cytoxan

    Institute of Scientific and Technical Information of China (English)

    Yang Kong(杨孔); Yue Bisong; Wang Zishu; Zou Fangdong; Zhao Ermi; Wang Baoyi; Zhang Hong

    2003-01-01

    Electrochemotherapy (ECT) is a novel cancer treatment in which electric pulses (Eps) inducing cell membrane pored (electroporation) are used as a means of delivering antitumor drugs to the cytoplasm of cancer cells. In vitro, with scan electromicroscope (SEM) and Trypan blue staining examination, the best parameter of Eps of electroporation is studied by the S-180 cells exposed to EP with various voltages, pulses , capacitance. The best parameter of EP of electroporation is 600V/cm, 6 pulses, 10 μF. In the in vivo study, ECT is studied with the Cytoxan (CTX) injected directly into the tumor followed immediately by a local EP at the tumor site. Four parameters, which include the tumor inhibitory ratio, the curing ratio and the vas capillare of tumor, the tumor's histopathological characteristics are determined and compared among the ECT group, the control group, the EP-only group and the drug-only group. The results indicate that the antitumor effect of CTX is significantly enhanced by electroporation.

  6. Proteomic Study to Survey the CIGB-552 Antitumor Effect

    Directory of Open Access Journals (Sweden)

    Arielis Rodríguez-Ulloa

    2015-01-01

    Full Text Available CIGB-552 is a cell-penetrating peptide that exerts in vitro and in vivo antitumor effect on cancer cells. In the present work, the mechanism involved in such anticancer activity was studied using chemical proteomics and expression-based proteomics in culture cancer cell lines. CIGB-552 interacts with at least 55 proteins, as determined by chemical proteomics. A temporal differential proteomics based on iTRAQ quantification method was performed to identify CIGB-552 modulated proteins. The proteomic profile includes 72 differentially expressed proteins in response to CIGB-552 treatment. Proteins related to cell proliferation and apoptosis were identified by both approaches. In line with previous findings, proteomic data revealed that CIGB-552 triggers the inhibition of NF-κB signaling pathway. Furthermore, proteins related to cell invasion were differentially modulated by CIGB-552 treatment suggesting new potentialities of CIGB-552 as anticancer agent. Overall, the current study contributes to a better understanding of the antitumor action mechanism of CIGB-552.

  7. Antitumor activity of C-phycocyanin from Arthronema africanum (Cyanophyceae

    Directory of Open Access Journals (Sweden)

    Elena Gardeva

    2014-10-01

    Full Text Available Pure C-phycocyanin (C-PC was isolated from Arthronema africanumto evaluate its potential antitumor effects in vivo and in vitro. Experimental myeloid Graffi tumor in hamsters was used as a model. The cell proliferation assay showed that C-PC treatment, at concentration of 100 µg mL-1 for 24 h, significantly inhibited the growth of Graffi tumor cells (51.4% viability. Agarose gel electrophoresis of the genomic DNA of treated cells displayed time-and concentration-dependent fragmentation pattern, typical for apoptosis. Apoptotic process was related to the increase in cellular manganese and copper/zinc superoxide dismutases and glutathione reductase activities, coupled with a low catalase activity. In vivo C-PC administration (5.0 mg kg-1 body weight suppressed the tumor transplantability and growth, while the mean survival time of the tumor-bearing hamsters was increased. The results revealed promising antitumor activities of A. africanum C-PC and suggested the potential of this natural biliprotein pigment for future pharmacological and medical applications. The study provided new data on the mechanism of the C-PC induced apoptosis in which the imbalance of antioxidant enzymes that favoured hydrogen peroxide accumulation might play a leading role.

  8. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos, E-mail: marciaoliveira.13@terra.com.b [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Lab. de Radiofarmacia Experimental; Fonseca, Adenilson de Souza da [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. Biomedico. Dept. de Ciencias Fisiologicas; Bernardo-Filho, Mario [Instituto Nacional do Cancer (INCA), Rio de Janeiro, RJ (Brazil). Coordenadoria de Pesquisa

    2011-07-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m ({sup 99m}Tc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na{sup 99m}TcO{sub 4}) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na{sup 99m}TcO{sub 4} and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na{sup 99m}TcO{sub 4} in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na{sup 99m}TcO{sub 4} are conducted in patients who are using senna extract. (author)

  9. A rapid kinetic chromogenic method for quantification of bacterial endotoxins in lyophilized reagents for labeling with {sup 99m}Tc radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Fukumori, Neuza T.O.; Campos, Domingos G.; Silva, Laercio; Fernandes, Adriana V.; Mengatti, Jair; Silva, Constancia P.G.; Matsuda, Margareth M.N. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    A rapid quantitative kinetic chromogenic test in an automated Portable Test System (PTS) has been developed for determination of bacterial endotoxins in water, in-process and end-products using the Limulus amebocyte lysate (LAL). The aim of this work was to validate the method for lyophilized reagents for labeling with {sup 99m}Tc radiopharmaceuticals with no interfering factors. Experiments were performed in three consecutive batches of the lyophilized reagents Methylenediphosphonic Acid (MDP) and Pyrophosphate (PYRO) produced at IPEN-CNEN/ SP using the PTS from Endosafe, Inc.{sup TM}, Charleston, SC. The Maximum Valid Dilution (MVD) was calculated to establish the extent of dilution to avoid interfering test conditions (MVD=500). Better results were obtained above 1:20 dilution factor for MDP and 1:100 for PYRO. The parameters of coefficient correlation (R) -0.980, RPPC between 50 - 200% and coefficient variation (CV) of the samples less than 25% were satisfied and the endotoxin concentration was lower than the lowest concentration of the standard curve (0.05 EU mL{sup -1}), therefore less than the established limit in pharmacopoeias. The PTS is a rapid, simple and accurate technique using the quantitative kinetic chromogenic method for bacterial endotoxin determination. For this reason, it is very practical in the radiopharmaceutical area and it trends to be the method of choice for the pyrogen test. For MDP and PYRO, the validation was successfully performed. (author)

  10. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    Directory of Open Access Journals (Sweden)

    Deise Elizabeth Souza

    2011-01-01

    Full Text Available Cassia angustifolia Vahl (senna is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract.

  11. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats.

    Science.gov (United States)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

    2011-01-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-⁹⁹m (⁹⁹mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na⁹⁹mTcO₄)in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na⁹⁹mTcO₄ and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na⁹⁹mTcO₄ in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na⁹⁹mTcO₄ are conducted in patients who are using senna extract.

  12. Beyond current guidelines: reduction in minimum administered radiopharmaceutical activity with preserved diagnostic image quality in pediatric hepatobiliary scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Fahey, Frederic; Markelewicz, Robert; Grant, Frederick; Drubach, Laura; Treves, S. Ted [Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Boston Children' s Hospital, Boston, MA (United States); Harvard Medical School, Joint Program in Nuclear Medicine, Boston (United States); Zukotynski, Katherine [University of Toronto, Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto (Canada); Harvard Medical School, Joint Program in Nuclear Medicine, Boston (United States); Zurakowski, David [Boston Children' s Hospital, Departments of Anesthesia and Surgery, Boston (United States); Falone, Anthony; Vitello, Marie; Cao, Xinhua [Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging, Boston Children' s Hospital, Boston, MA (United States); Vija, A.H.; Bhattacharya, Manojeet; Ding, Xinhong [Siemens Medical Solutions USA, Inc., Molecular Imaging, Malvern, PA (United States); Bar-Sever, Zvi [Schneider Children' s Medical Center, Petach Tikvah (Israel); Tel-Aviv University, Tel-Aviv (Israel); Gelfand, Michael [Cincinnati Children' s Hospital, Cincinnati, OH (United States)

    2014-12-15

    To determine if the minimum administered radiopharmaceutical activity for hepatobiliary scintigraphy can be reduced while preserving diagnostic image quality using enhanced planar processing (EPP). A total of 40 infants between 10 and 270 days old (body mass 2.2 - 6.5 kg) had hepatobiliary scintigraphy during the period 2004 - 2010 following the intravenous administration of either {sup 99m}Tc-mebrofenin (18 patients) or {sup 99m}Tc-disofenin (22 patients). Due to the small size of these patients, they all received the minimum administered activity of 18.5 MBq consistent with the North American Consensus Guidelines. Six nuclear medicine physicians subjectively graded the acceptability of the image quality for clinical interpretation using a four-point scale (not acceptable, fair, good, excellent). Each physician independently graded seven image sets including the original study (full activity) and simulated reduced activity studies using binomial subsampling (50 % of full activity, 25 % of full activity and activity reduced by weight), with and without EPP. For full-activity studies, 98 % were deemed acceptable by the six physicians for clinical interpretation. The percentages of acceptable 50 % reduced activity studies with and without EPP were not significantly different from the percentage of acceptable full-activity studies (P = 0.193 and P = 0.998, respectively). The percentage of acceptable 25 % reduced activity studies without EPP was significantly different from the percentage of acceptable full-activity studies (P < 0.001); however, this difference vanished when EPP was applied (P = 0.482). The activity reduced by weight ranged from 1.85 to 4.81 MBq (10 % to 26 % of full dose) and the percentages of acceptable studies with and without EPP were significantly different from the percentage of acceptable full-activity studies (P < 0.001 and P = 0.02, respectively). Clinically interpretable hepatobiliary scintigraphy images can be obtained in infants when the

  13. Toward the definition of immunosuppressive regimens with antitumor activity.

    Science.gov (United States)

    Casadio, F; Croci, S; D'Errico Grigioni, A; Corti, B; Grigioni, W F; Landuzzi, L; Lollini, P-L

    2005-06-01

    Immunosuppressive therapies associated with organ transplantation produce an increased risk of cancer development. Malignancies are increased in transplant recipients because of the impaired immune system. Moreover, experimental data point to a tumor-promoting activity of various immunosuppressive agents. In this study, we compared the effects of 4 immunosuppressive agents with different mechanisms of action (cyclosporine, rapamycin, mycophenolic acid, and leflunomide) on the in vitro growth of various tumor cell lines and umbilical vein endothelial cells. To varying degrees rapamycin (10 ng/mL), mycophenolic acid (300 nmol/L), and leflunomide (30 micromol/L) highly inhibited the growth of human rhabdomyosarcoma, hepatocellular carcinoma, colorectal carcinoma, and endothelial cells. In contrast, cyclosporine (100 ng/mL) did not affect their growth. Our data suggest that regimens containing rapamycin, mycophenolic acid, or leflunomide, which have both immunosuppressive and antitumor activities, should be preferred in transplant recipients to minimize the risk of tumors.

  14. Telomerase:a novel target of antitumor agents

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Telomerase activity was found to be high in various human cancers, but absent in most normal tissues. Its expression pattern made it a novel target for antitumor agents. Several strategies against telomerase were presented in this review. Targeting the telomerase RNA component by oligonucleotide/ribozyme was considered to be one of the most hopeful approaches. Some progresses were made in this area, such as the use of PANs and 2- 5A antisense compounds. The relationships among telomerase activity and cell differentiation, signal transduction, oncogene, tumor suppressor gene as well as cell cycle modulation also provided a series of valuable ideas in designing anti-telomerase drugs for cancer therapy. In conclusion, although there is still a long way in understanding the mechanism and regulation of telomerase, the advance of studies on telomerase has allowed the development of numerous strategies for the treatment of cancer.

  15. Vaccines against Human Carcinomas: Strategies to Improve Antitumor Immune Responses

    Directory of Open Access Journals (Sweden)

    Claudia Palena

    2010-01-01

    Full Text Available Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultimately will reduce tumor burden by tipping the balance from a protumor to an antitumor immune environment. This review discusses common mechanisms that govern immune cell activation and tumor immune escape, and some of the current strategies employed in the field of cancer vaccines aimed at enhancing activation of tumor-specific T-cells with concurrent reduction of immunosuppression.

  16. Gene Therapy of Cancer: Induction of Anti-Tumor Immunity

    Institute of Scientific and Technical Information of China (English)

    ChengQian; JesusPrieto

    2004-01-01

    Many malignancies lack satisfactory treatment and new therapeutic options are urgently needed. Gene therapy is a new modality to treat both inherited and acquired diseases based on the transfer of genetic material to the tissues. Different gene therapy strategies against cancers have been developed. A considerable number of preclinical studies indicate that a great variety of cancers are amenable to gene therapy. Among these strategies, induction of anti-tumor immunity is the most promising approach. Gene therapy with cytokines has reached unprecedented success in preclinical models of cancer. Synergistic rather than additive effects have been demonstrated by combination of gene transfer of cytokines/chemokines, costimulatory molecules or adoptive cell therapy. Recent progress in vector technology and in imaging techniques allowing in vivo assessment of gene expression will facilitate the development of clinical applications of gene therapy, a procedure which may have a notorious impact in the management of cancers lacking effective treatment. Cellular & Molecular Immunology. 2004;1(2):105-111.

  17. Expression, Purification and Anti-tumor Activity of Curcin

    Institute of Scientific and Technical Information of China (English)

    Meng-Jun LUO; Xin-Yu YANG; Wei-Xin LIU; Ying XU; Ping HUANG; Fang YAN; Fang CHEN

    2006-01-01

    Curcin, purified from the seeds of Jatropha curcas, can be used as a cell-killing agent. Understanding the anti-tumor activity of the recombinant protein of curcin is important for its application in clinical medicine.The segment encoding the mature protein of curcin was inserted into Escherichia coli strain M15, and the recombinant strain was induced to express by isopropyl-β-D-thiogalactopyranoside at concentration of 0.5 mM. The recombinant protein was expressed in the form of inclusion bodies and purified by Ni-NTA affinity chromatography. The target protein was incubated with the tumor cells at different concentrations for different times and the results demonstrated that the target protein could inhibit the growth of tumor cells (NCL-H446, SGC-7901 and S180) at 5 μg/ml.

  18. Antitumor Effects of Laminaria Extract Fucoxanthin on Lung Cancer

    Directory of Open Access Journals (Sweden)

    ChengHan Mei

    2017-02-01

    Full Text Available Lung cancer is the leading cause of cancer mortality worldwide and non-small-cell lung cancer (NSCLC is the most common type. Marine plants provide rich resources for anticancer drug discovery. Fucoxanthin (FX, a Laminaria japonica extract, has attracted great research interest for its antitumor activities. Accumulating evidence suggests anti-proliferative effects of FX on many cancer cell lines including NSCLCs, but the detailed mechanisms remain unclear. In the present investigation, we confirmed molecular mechanisms and in vivo anti-lung cancer effect of FX at the first time. Flow cytometry, real-time PCR, western blotting and immunohistochemistry revealed that FX arrested cell cycle and induced apoptosis by modulating expression of p53, p21, Fas, PUMA, Bcl-2 and caspase-3/8. These results show that FX is a potent marine drug for human non-small-cell lung cancer treatment.

  19. Study on the Interaction between Antitumor Drug Daunomycin and DNA

    Institute of Scientific and Technical Information of China (English)

    CHENG Gui-Fang; ZHAO Jie; TU Yong-Hua; HE Pin-Gang; FANG Yu-Zhi

    2005-01-01

    A detection of anthracycline antitumor drug daunomycin (DNR) reacting with DNA in simulate metabolism in vitro has been made. It was found that DNR could react with DNA to form DNR-DNA adducts. The adduct compositions of DNR with fish sperm DNA and thermally denaturated DNA were determined. The equilibrium association constant K of DNR with fish sperm DNA is 1.98 × 105 L/mol and that of DNR with denaturated DNA is 2.29 × 104 L/mol. Semiquinone free radicals, metabolic products of DNR, can destroy both fish sperm DNA and its thermally denaturated DNA. It is verified by hyperchromic effect increase observed in UV spectrum and AFM experiments. The mechanism of DNA degradation has also been investigated. Results obtained allow one to explain the reason of side effect of anthracycline drug and give the way to depress, which were of clinical significance.

  20. OFFICIAL MEDICATIONS FOR ANTI-TUMOR GENE THERAPY

    Directory of Open Access Journals (Sweden)

    E. R. Nemtsova

    2016-01-01

    Full Text Available This is a review of modern literature data of official medications for anti-tumor gene therapy as well as of medications that finished clinical trials.The article discusses the concept of gene therapy, the statistical analysis results of initiated clinical trials of gene products, the most actively developing directions of anticancer gene therapy, and the characteristics of anti-tumor gene medications.Various delivery systems for gene material are being examined, including viruses that are defective in  replication (Gendicine™ and Advexin and oncolytic (tumor specific conditionally replicating viruses (Oncorine™, ONYX-015, Imlygic®.By now three preparations for intra-tumor injection have been introduced into oncology clinical practice: two of them – Gendicine™ and Oncorine™ have been registered in China, and one of them – Imlygic® has been registered in the USA. Gendicine™ and Oncorine™ are based on the wild type p53 gene and are designed for treatment of patients with head and neck malignancies. Replicating adenovirus is the delivery system in Gendicine™, whereas oncolytic adenovirus is the vector for gene material in Oncorine™. Imlygic® is based on the  recombinant replicating HSV1 virus with an introduced GM–CSF gene and is designed for treatment of  melanoma patients. These medications are well tolerated and do not cause any serious adverse events. Gendicine™ and Oncorine™ are not effective in monotherapy but demonstrate pronounced synergism with chemoand radiation therapy. Imlygic® has just started the post marketing trials.

  1. Cancer vaccines: harnessing the potential of anti-tumor immunity.

    Science.gov (United States)

    Suckow, Mark A

    2013-10-01

    Although the presence of cancer suggests failure of the immune system to protect against development of tumors, the possibility that immunity can be redirected and focused to generate an anti-tumor response offers great translational possibility. The key to this is identifying antigens likely to be present in any given tumor and functionally critical to tumor survival and growth. Such tumor-associated antigens (TAAs) are varied and optimally should be absent from normal tissue. Of particular interest are TAAs associated with the tumor stroma, as immunity directed against the stroma may restrict the ability of the tumor to grow and metastasize. Important to directing the immune system toward an effect anti-tumor response is the understanding of how TAAs are processed and how the tumor is able to evade immune elimination. The process of immunoediting happens in response to the selective pressure that the immune system places upon tumor cell populations and allows for emergence of tumor cells capable of escaping immune destruction. Efforts to harness the immune system for clinical application has been aided by vaccines based on purified recombinant protein or nucleic acid TAAs. For example, a vaccine for canine melanoma has been developed and approved based on immunization with DNA components of tyrosinase, a glycoprotein essential to melanin synthesis. The performance of cancer vaccines has been aided in some cases when supplemented with immunostimulatory molecules such as interleukin 2 or a novel extracellular matrix vaccine adjuvant. Vaccines with the broadest menu of antigenic targets may be those most likely to succeed against cancer. For this reason, tissue vaccines produced from harvested tumor material may offer significant benefit. With several cancer vaccines on the veterinary and human markets, efforts to understand basic tumor immunology are soon to yield great dividends.

  2. Antitumor immunomodulatory activity of allogenic bone marrow cells on TiNi scaffold

    Science.gov (United States)

    Kokorev, O. V.; Hodorenko, V. N.; Cherdyntseva, N. V.; Gunther, V. E.

    2016-08-01

    The present study was undertaken to evaluate the feasibility of modulation of anti-tumor response by allogenic bone marrow cell transplantation into porous TiNi-based scaffold. Transplantation of bone marrow cells into porous TiNi-based scaffold leads to antitumor (35%) and antimetastatic (55%) effects. The lifetime of tumor-bearing animals and implanted allogenic bone marrow cells in incubator of TiNi increases up to 60%. The possible mechanisms of the effect of allogenic cells on tumor process are the stimulation of endogenous effectors of antitumor immunity.

  3. Synthesis and Biological Evaluation of Novel Tricyclic Oximino Derivatives as Antitumor Agents

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A series of novel alkylthio/sulfinyl-8H-thieno[2,3-b]pyrrolizin-8-oximino derivatives Ⅴ1-Ⅷ15 were designed and synthesized as antitumor agents. Their structures were confirmed using IR, 1H NMR, elemental analysis,and MS. The antitumor activities of all the target compounds were tested by the MTT method in vitro against Bel-7402,HT-1080, SGC-7901, and A549 Cell Lines. Among them, compound Ⅵ9 displayed a promising antitumor activity superior to that of Cisplatin.

  4. Survey or quality for radiopharmaceuticals and activimeters available in services of nuclear medicine from Recife, Pernambuco State, Brazil; Estudo da qualidade dos radiofarmacos e dos activimetros utilizados nos servicos de medicina nuclear do Recife

    Energy Technology Data Exchange (ETDEWEB)

    Nogueira, Fernanda Maria Dornellas Camara

    2001-08-01

    The radiopharmaceutical used in Nuclear Medicine must present high chemical and radiochemical purities in order to obtain images with contrast and clearness adequate for the diagnosis. Test should be made by the Nuclear Medicine institutes to evaluate the presence of molybdenum, aluminium and the free Tc O{sub 4}{sup -}/TC-HR in the radiopharmaceutical before they use it. On the other hand, the activity to be administered to the patient is determined by the activimeters available in the Nuclear Medicine institutions. So it is necessary to perform tests to verify operating conditions of the activimeter to guarantee that the dose received by patient is the prescribed by the physician. In Brazil, few clinics of Nuclear Medicine are implanting the tests of the radiopharmaceutical and of the activimeters. The objective of this work is to establish the procedures for the radiopharmaceutical tests and to evaluate the quality of the radiopharmaceutical used at the clinics of Recife, as well as the operation conditions of the activemeters in these institutions. The results show that all the activimeters analyzed present a good performance and that the equipment with Geiger-Muller detectors present larger instability than the ones that use ionization chamber. Concerning the Mo/Tc generators, it was observed that only one presented Mo in the generator eluate with concentration over the acceptable limits and that the concentration of Al found in the samples analyzed were below the limits. On the other hand, in 73% of the MIBI analyzed samples were observed problems with its preparation that were caused by the procedures adopted at the clinics, which do not follow the manufacturers recommendations. (author)

  5. Formulation of an inhibitor radiopharmaceutical of prostatic antigen of {sup 177}Lu-Glu-Nh-CO-Nh-Lys membrane; Formulacion de un radiofarmaco inhibidor del antigeno prostatico de membrana {sup 177}Lu-Glu-NH-CO-NH-Lys

    Energy Technology Data Exchange (ETDEWEB)

    Ortega S, D.

    2015-07-01

    The prostate specific membrane antigen (PSMA) is a zinc metalloenzyme that is expressed on the cell membrane and highly expressed in prostate cancer. Recently, it has been demonstrated that the peptide sequence Glu-Nh-CO-Nh-Lys inhibit PSMA activity through an electrostatic interaction with the Zn. Several theragnostic radiopharmaceuticals with base in {sup 177}Lu have been developed for radiotherapy of specific molecular targets because gamma and beta emissions of the radionuclide (β = 0.498 MeV and γ= 0.133 MeV). However, there is currently no label a formulation for preparing a radiopharmaceutical of {sup 177}Lu-Glu-Nh-CO-Nh-Lys useful treatment of prostate cancer. The aim of this research was to optimize and document the process of production of the radiopharmaceutical {sup 177}Lu-Glu-Nh-CO-Nh-Lys for sanitary registration application before the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). The optimization of the production process was assessed a factorial design of three variables with mixed levels (3 x 3 x 2) where the dependent variable is the radiochemical purity, the analytical method was validated by UV-Vis spectrophotometry. Next, process validation was carried out by labeling 3 lots of the optimized formulation of the radiopharmaceutical (5.55 GBq (2.16 μg) of {sup 177}LuCl{sub 3}, 90 mg peptide PSMA, 50 mg ascorbic acid and 150 μL of acetate buffer 1 M ph 5), long-term stability was performed by high resolution liquid chromatography) to determine its useful shelf life. 3 validation batches were prepared under protocols of Good Manufacturing Practice (GMP) in the Production Plant of Radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ), meet specifications preset by obtaining a sterile and free development of bacterial endotoxin yields of labeled 100% and which retains its quality characteristics radiochemical purity greater than 90% for at least 15 days. (Author)

  6. Determination of radiochemistry purity and pH of radiopharmaceutical in Northeast nuclear medicine services; Determinacao da pureza radioquimica e pH de radiofarmacos em servicos de medicina nuclear do Nordeste

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Wellington; Santos, Poliane, E-mail: wellington.gandrade@gmail.com, E-mail: polianeangelo@gmail.com [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Lima, Fernando de Andrade; Lima, Fabiana Farias de, E-mail: falima@cnen.gov.br, E-mail: ffmima@cnen.gov.br [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2013-07-01

    The radiopharmaceutical is a chemical compound associated with a radionuclide, which is selected so that meets the need cf diagnosis and capable of producing quality images. Drugs labeled with {sup 99m}Tc radionuclide kits consist of lyophilized, and be handled by the nuclear medicine services (NMS) must pass tests as the resolution of ANVISA (RDC 38) published in 2008. Among these tests are those of radiochemical purity and pH determination. This study evaluated the radiochemical purity of radiopharmaceuticals and pH SMN manipulated in the Northeast. The radiochemical purity (RCP) was determined by thin layer chromatography, which were used Whatman Registered-Sign and silica gel, with dimensions of 1 x 10 cm, as stationary phase, and solvents indicated in the inserts of manufacturers. The chromatographic strips were placed in sealed containers so as not to touch the walls thereof. After the chromatographic run, the tape was cut every centimeter and the activities determined in doses of each calibrator NMS. The pH of the radiopharmaceutical was assessed through the use of universal pH paper (Merck Registered-Sign ) and obtained staining compared with its color scale. The results showed (hat 82.6% and 100% of the radiopharmaceuticals of the samples were within the limits recommended by international pharmacopoeias for radiochemical purity and pl-l, respectively. There is then the need to include in routine tests indicated SMN by ANVISA. Well, they can detect possible problems in the marking of radiopharmaceuticals administered to the patient and avoid inappropriate material. (author)

  7. Rapid brain scanning radiopharmaceutical

    Science.gov (United States)

    Sargent, III, Thornton W.; Shulgin, Alexander T.; Mathis, Chester A.

    1987-01-01

    A method for detecting the blood flow in animals, particularly in the brain, is provided wherein a detectable amount of a novel radioactive compound of the formula I is administered to one animal: ##STR1## wherein R.sub.1 and R.sub.2 are independently alkyl of 1 to 6 carbon atoms or benzyl; R.sub.3 is alkyl of 1 to 6 carbon atoms, benzyl, cyclopropylalkyl of 4 to 6 carbon atoms, or cyanoalkyl of 2 to 6 carbon atoms; R.sub.4 is hydrogen, benzyl or alkyl of 1 to 6 carbon atoms; with the provisos that R.sub.4 is not isopropyl and when R.sub.4 is methyl, R.sub.3 is not benzyl; and X is a radioactive halogen.

  8. Paediatric radiopharmaceutical administration

    DEFF Research Database (Denmark)

    Lassmann, Michael; Treves, S Ted; Borgwardt, Lise

    2014-01-01

    In 2008 the EANM published their paediatric dosage card. In 2011 the North American consensus guidelines recommended a set of administered activities for paediatric nuclear medicine. During the EANM congress in 2012 a working group of the EANM and the SNMMI met to study the possibility of harmoni...

  9. 中国放射性药物的现状与展望%Current Status and Prospects of Radiopharmaceuticals in China

    Institute of Scientific and Technical Information of China (English)

    贾红梅; 刘伯里

    2011-01-01

    放射性药物不仅可以作为有效的诊断和治疗手段,而且结合单光子断层扫描仪(SPECT)或正电子断层扫描仪(PET),还可以在分子水平上直接研究它们在正常人体(活体)内的功能和代谢过程,实现人体内生理和病理过程的快速、无损和实时成像,为真正意义上的早诊断、早治疗提供新方法和新手段,为预防医学、转化医学、个性化医学的实现提供可能的途径.本文概述了体内放射性药物的最新进展,分析了我国放射性药物的研究现状,提出大力加强医用放射性核素的研制、加强基础放射性药物化学研究、系统开展受体分子显像剂的研究以及开展多模式多功能复合分子探针的研究等建议.%Radiopharmaceuticals could not only serve as effective diagnostic and therapeutic tools in human diseases, but also allow the assessment of metabolism and functional processes by providing quick, non-invasive and real-time visualization of physiological and pathological processes in the living humans at the molecular level together with PET (positron e-mission tomography) and SPECT (single photon emission computed tomography) imaging modalities. They could provide new methods and new approaches of truly early diagnosis and therapy and possible pathways for the preventative medicine, translational medicine and personalized medicine. The present review provides an overview of current status of in vivo radiopharmaceuticals in China. Moreover, some prospects of research and development of radiopharmaceuticals in the near future was discussed. The addressed future trends include the following aspects. (1) Production of medical radioisotopes including 99Mo, 131I, 188/186Re and 123I. (2) Investigation on the basic radiopharmaceutical chemistry. (3) Development of receptor-based imaging agents. (4) Development of multi-modality imaging probes.

  10. Determination of bacterial endotoxin (pyrogen) in radiopharmaceuticals by the gel clot method. Validation; Determinacao de endotoxina bacteriana (pirogenio) em radiofarmacos pelo metodo de formacao de gel. Validacao

    Energy Technology Data Exchange (ETDEWEB)

    Fukumori, Neuza Taeko Okasaki

    2008-07-01

    Before the Limulus amebocyte lysate (LAL) test, the only available means of pirogenicity testing for parenteral drugs and medical devices was the United States Pharmacopoeia (USP) rabbit pyrogen test. Especially for radiopharmaceuticals, the LAL assay is the elective way to determine bacterial endotoxin. The aim of this work was to validate the gel clot method for some radiopharmaceuticals without measurable interference. The FDA's LALTest guideline defines interference as a condition that causes a significant difference between the endpoints of a positive water control and positive product control series using a standard endotoxin. Experiments were performed in accordance to the USP bacterial endotoxins test in the {sup 131}I- m-iodobenzylguanidine; the radioisotopes Gallium-67 and Thallium-201; the lyophilized reagents DTPA, Phytate, GHA, HSA and Colloidal Tin. The Maximum Valid Dilution (MVD) was calculated for each product based upon the clinical dose of the material and a twofold serial dilution below the MVD was performed in duplicate to detect interferences. The labeled sensitivity of the used LAL reagent was 0.125 EU mL{sup -1} (Endotoxin Units per milliliter). For validation, a dilution series was performed, a twofold dilution of control standard endotoxin (CSE) from 0.5 to 0.03 EU mL{sup -1}, to confirm the labeled sensitivity of the LAL reagent being tested in sterile and non pyrogenic water, in quadruplicate. The same dilution series was performed with the CSE and the product in the 1:100 dilution factor, in three consecutive batches of each radiopharmaceutical. The products {sup 131}I-m-iodobenzylguanidine, Gallium-67, Thallium-201, DTPA, HSA and Colloidal Tin were found compatible with the LAL test at a 1:100 dilution factor. Phytate and GHA showed some interference in the gel clot test. Other techniques to determine endotoxins as the chromogenic (color development) and the turbidimetric test (turbidity development), were also assessed to get

  11. Synthesis and in vitro antitumor activities of lupeol dicarboxylic acid monoester derivatives.

    Science.gov (United States)

    Li, Weijie; Hao, Jing; Xiao, Yeyu

    2013-12-01

    Ten lupeol dicarboxylic acid monoester derivatives as new potent antitumor agents were synthesized and evaluated for in vitro antitumor activities against A549, LAC, HepG2 and HeLa cell lines. Among them, compounds 1-5 showed excellent antitumor activities against all tested tumor cell lines and compounds 6-10 exhibited high activities against A549, HepG2 and HeLa cells, exceeded lupeol, lupanol and doxorubicin. Compound 2 displayed the highest potent antitumor activities with IC50 values of 5.78 μM against A549 cell, 2.38 μM against LAC cell, 6.14 μM against HepG2 cell and 0.00842 μM against HeLa cell.

  12. Synthesis and Antitumor Activity of C-2/C-10 Modified Analogues of Docetaxel

    Institute of Scientific and Technical Information of China (English)

    Wei Shuo FANG; Hong Yan LIU; Qi Cheng FANG

    2005-01-01

    Four 10-propionyl docetaxel analogues (11a-d) with 2α-amido substituents were prepared, and their antitumor activity against three solid tumor cell lines and their drug-resistant counterparts were determined.

  13. [Antitumor Activity of Polysaccharides from Ganoderma lucidum Mycelium: in vivo Comparative Study].

    Science.gov (United States)

    Krasnopolskaya, L M; Yarina, M S; Avtonomova, A V; Usov, A I; Isakova, E B; Bukchman, V M

    2015-01-01

    Fractions of water soluble and alkali soluble polysaccharides, as well as fucogalactan, a water soluble polysaccharide, and xylomannan, an alkali soluble polysaccharide, were isolated from the Ganoderma lucidum submerged mycelium. When administered orally, the polysaccharides showed antitumor activity in vivo on murine models of solid tumors. Xylomannan and fucogalactan showed the highest antitumor activity. Sensitivity to xylomannan was more pronounced in adenocarcinoma Ca755 as compared to the T-cell lymphocytic leukemia P388. The antitumor activity of the water soluble polysaccharides total fractions from the mycelium and fruiting bodies of the G. lucidum strain was almost identical. The maximum antitumor effect of the mycelium water soluble polysaccharides total fraction was observed with the use of the daily dose of 2 mg/kg.

  14. Anti-tumor and immunoregulatory activities of Ganoderma lucidum and its possible mechanisms

    Institute of Scientific and Technical Information of China (English)

    Zhi-binLIN; Hui-naZHANG

    2004-01-01

    Ganoderma lucidum (G lucidum) is a medicinal fungus with a variety of biological activities. It has long been used as a folk remedy for promotion of health and longevity in China and other oriental countries. The most attractive character of this kind of medicinal fungus is its immunomodulatory and anti-tumor activities. Large numbers of studies have shown that G lucidum modulate many components of the immune system such as the antigen-presenting cells, NK cells, T and B lymphocytes. The water extract and the polysaccharides fraction of G lucidum exhibited significant anti-tumor effect in several tumor-bearing animals mainly through its immunoenhancing activity. Recent studies also showed that the alcohol extract or the triterpene fraction of G lucidum possessed antitumor effect, which seemed to be related to the cytotoxic activity against tumor cells directly. Preliminary study indicated that antiangiogenic effect may be involved antitumor activity of G lucidum.

  15. Carboxylate groups play a major role in antitumor activity of Ganoderma applanatum polysaccharide.

    Science.gov (United States)

    Sun, Xiaobo; Zhao, Chen; Pan, Wei; Wang, Jinping; Wang, Weijun

    2015-06-05

    In this paper, the structure difference between the polysaccharides isolated from fruit bodies (FGAP) and submerged fermentation system (SGAP) of Ganoderma applanatum was investigated by means of GPC, HPLC and IR, respectively. And their antitumor activities were evaluated against Sarcoma 180 in vivo. The results showed that FGAP and SGAP were typical polysaccharides with different molecular weights, monosaccharide components, and functional groups. Closely related to the distinct structures, FGAP exhibited a better antitumor activity than SGAP. Moreover, since FGAP contained carboxylate groups rather than SGAP, such groups were chemically introduced into SGAP (CSGAP) by carboxymethylation in order to identify their contribution to antitumor activity. The results demonstrated that the inhibition of CSGAP against Sarcoma 180 in vivo was significantly enhanced by comparison to the native SGAP and even higher than that of FGAP, suggesting that the carboxylate groups played a major role in antitumor activity of G. applanatum polysaccharide.

  16. A review about the development of fucoidan in antitumor activity: Progress and challenges.

    Science.gov (United States)

    Wu, Lei; Sun, Jing; Su, Xitong; Yu, Qiuli; Yu, Qiuyang; Zhang, Peng

    2016-12-10

    Fucoidan is composed of l-fucose, sulfate groups and one or more small proportions of d-xylose, d-mannose, d-galactose, l-rhamnose, arabinose, glucose, d-glucuronic acid and acetyl groups in different kinds of brown seaweeds. Many reports have demonstrated that fucoidan has antitumor activities on various cancers. However, until now, few reviews have discussed the antitumor activity of fucoidan and few reports have summarized detailed molecular mechanisms of its actions and antitumor challenges of fucoidan specially. In this review, the antitumor signaling pathway mechanisms related to fucoidan are elucidated as much detail as possible. Besides, the factors affecting the anticancer effects of fucoidan, the structural characteristics of fucoidan with anticancer activities and the challenges for the further development of fucoidan are also summarized and evaluated. The existing similar and different conclusions are summarized in an attempt to provide guidelines to help further research, and finally contribute to go into market as chemotherapeumtics.

  17. Efficient microwave irradiation enhanced stereoselective synthesis and antitumor activity of indolylchalcones and their pyrazoline analogs

    Indian Academy of Sciences (India)

    Magdy A H Zahran; Hanan F Salama; Yasmin G Abdin; Amira M Gamal-Eldeen

    2010-07-01

    2-Aryl-1-indole-3-carbaldehyde derivatives underwent Claisen-Schmidt condensation with acetophenone derivatives under microwave irradiation condition compared with the conventional heating to afford excellent yields of trans substituted indolylchalcones which subjected to condensation reaction with phenylhydrazine to afford their indolylpyrazoline analogs. The antitumor activity of the synthesized compounds was examined and evaluated against human hepatocellular carcinoma cell line (Hep-G2) as well as the half maximal inhibitory concentration (IC50). Most of them showed high potent antitumor activity.

  18. Synthesis and Antitumor Activities of 26-O-tert-Butyldimethylsiliyl Protodisogenyl β-D-Glucopyranoside

    Institute of Scientific and Technical Information of China (English)

    Liang ZHOU; Shu Jie HOU; Peng XU; De Quan YU; Ping Sheng LEI; Chuan Chun ZOU

    2006-01-01

    New saponin 26-O-tert-butyldimethylsiliyl protodiosgenyl β-D-glucopyranoside 1 was synthesized and its cytotoxicity activity in vitro was evaluated by MTT. It showed potent antitumor activity to human cancer cells. E ring and C22-OH play important roles in the antitumor activity of 1. A method to selective removal of acetyl group in the presence of benzoyl group was reported.

  19. Determination of {sup 125}I impurities in [{sup 123}I]labelled radiopharmaceuticals, by liquid scintillation counting: sensitivity of the method

    Energy Technology Data Exchange (ETDEWEB)

    Bonardi, M.L. E-mail: mauro.bonardi@mi.infn.itmauro.bonari@mi.infn.it; Birattari, C.; Groppi, F.; Gini, L.; Mainardi, C.H.S.; Menapace, E

    2004-01-01

    Iodine-125 is a radioisotopic impurity 'always' present in iodine-123, produced by nuclear reactions induced either on natural or 'highly' enriched targets. Liquid scintillation counting is a very sensitive tool to determine low level impurities of both low energy electrons and photons in aqueous and organic solutions of radiopharmaceutical compounds. With this technique it was possible to determine, on commercial samples, that the content of {sup 125}I was of the order of not less than 0.1% for {sup 123}I produced via {sup 127}I(p,5n) reactions and not less than 0.01% for {sup 123}I produced via 'highly' enriched {sup 124}Xe(p,X) nuclear reactions.

  20. Radiation protection optimization in practices for radiopharmaceuticals production at IEN; Otimizacao da protecao radiologica nas praticas para a producao de radiofarmaco no IEN

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Osvaldir Paulo dos

    2004-06-15

    This works has arisen from the need of updating radiological protection procedures, creating new ones and training qualified personnel to perform radiological protection duties in a nuclear facility. The main purpose of the research was to assess and minimize gamma and neutron dose rates emitted during the production and handling of radiopharmaceuticals at IEN/DIRA. A mobile measurements system (SMMG-N) was developed for on-site measurements. This system has proven to be more handy than the equipment formerly used for for this task. It has also proven to reduce the measurements uncertainties and to allow for the standardization of assessment procedures. He dose rates calculated using the data provided by this system have been compared with results obtained otherwise and good agreement was observed between them. This study has confirmed the need to improve the radiation shielding of KIPROS target-chamber and target vault in order to meet the radiological principles of dose rate limitation and optimization. (author)

  1. Preparation of the radiopharmaceutical {sup 99m} Tc-HYNIC-[Lys{sup 3}]-BN; Preparacion del radiofarmaco {sup 99m} Tc-HYNIC-[Lys{sup 3}]-BN

    Energy Technology Data Exchange (ETDEWEB)

    Conde S, E. [Universidad Autonoma del Estado de Mexico, Facultad de Quimica, 50000 Toluca, Estado de Mexico (Mexico)

    2007-07-01

    In accordance with their design, the radiopharmaceuticals can be divided in three generations. The radiopharmaceuticals of third generation are used in nuclear medicine to obtain images of specific molecular targets, and they are only in their capacity to detect in vivo such specific biochemical places as receivers and enzymes. The receivers of regulator peptides are over expressed in numerous carcinogenic cells. Those receivers have been used as molecular targets of radiolabelled peptides to locate cancerous tumors. The small peptide bombesin (BN, 14 amino acids) it was isolated of the frog skin and it belongs to a wide neuropeptides group with many biological functions. The equivalent human is the liberator peptide of the gastrin (GRP, 27 amino acids) and his receivers (r-GRP) that are on expressed in the membranes of the tumor cells. The receiving subtype 2 of bombesin (receiving GRP) it is on expressed in several human tumors including breast, prostate, lung cells and pancreatic cancer. Some radiopharmaceuticals similar of BN has been developed that were prepared to be used in nuclear medicine for the detection of wicked tumors and to evidence prostate cancers, breast and of lymphatic nodules. A technique was developed to allow the conjugation of HYNIC-[Lys3]-BN that allowed to obtain this product with a high purity. The identity was determined by HPLC chromatography. It was necessary the validation of the method and the HPLC system, to assure that the results were reliable. Linearity, specificity, accuracy and precision parameters were analyzed, that are those required by the Mexican pharmacopoeia for chromatographic methods. With this conjugated a formulation for lyophilized kits were analyzed, with the purpose of obtaining a radiochemical purity, after the labelled one with {sup 99m}Tc, bigger to 95%; the components used in the nucleus-equipment should favor the conjugation of the {sup 99m}Tc by means of a ligands exchange between the tricine and the

  2. Formulation, radiopharmaceutical kinetics and dosimetry of the {sup 188}Re(V)-DMSA complex; Formulacion, radiofarmacocinetica y dosimetria del complejo {sup 188}Re(V)-DMSA

    Energy Technology Data Exchange (ETDEWEB)

    Garcia S, L.; Ferro F, G. [Departamento de Materiales Radiactivos. Instituto Nacional de Investigaciones Nucleares, C.P. 52045 Salazar, Estado de Mexico (Mexico); Murphy, C.A. de; Pedraza L, M. [Departamento de Medicina Nuclear, Instituto Nacional de la Nutricion, Salvador Zubiran, Mexico D.F. (Mexico); Azorin N, J. [Departamento de Fisica, Universidad Autonoma Metropolitana Iztapalapa, Mexico D.F. (Mexico)

    1999-07-01

    It was developed through experimental design (ANOVA), a formulation to prepare the {sup 188} Re(V)-Dmsa complex. Likewise, there were realized studies of radiopharmaceutical kinetics and internal dosimetry in animals, its normal and with induced tumors, considering an open bi compartmental model using the MIRD methodology. The {sup 188} Re(V)-Dmsa complex was obtained with a radiochemical purity greater than 95% incubating 30 min at 90 Centigrade under the following formulation: [SnCl{sub 2}] = 1.4 mg/ml, [ascorbic acid] = 0.5 mg/ml, p H = 2.0 - 3.0. The stability test of the formulation, shows that after 48 h of its preparation, does not produce radiolytic degradation neither chemical decomposition. The radiopharmaceutical kinetics data show an average residence time 7.2h, velocity constant {alpha} = 0.6508h{sup -1} and {beta} = 0.1046 h{sup -1} with an apparent distribution volume 6.9 l. The main elimination via was renal and it was observed osseous caption with an accumulated activity 522.049 {+-} 62 MBq h (residence time 14.1094 {+-} 1.69h). In according with the dosimetric calculations, by each 37 MBq injected, the equivalent dose at the tumor was 9.67{+-} 0.33 Sv/g, for an effective dose 0.292 {+-} 0.0017 mSv/MBq. The images obtained in the gamma camera of the mice with induced tumors, show that do not have significant accumulation in the metabolic organs. The caption in bone and in tumors induced of the {sup 188} Re(V)-Dmsa complex, show its potential for be used as a palliative agent for pain in patients with osseous metastasis and in the treatment of tumors of soft tissue. (Author)

  3. Modular syntheses of H₄octapa and H₂dedpa, and yttrium coordination chemistry relevant to ⁸⁶Y/⁹⁰Y radiopharmaceuticals.

    Science.gov (United States)

    Price, Eric W; Cawthray, Jacqueline F; Adam, Michael J; Orvig, Chris

    2014-05-21

    The ligands H2dedpa, H4octapa, p-SCN-Bn-H2dedpa, and p-SCN-Bn-H4octapa were synthesized using a new protection chemistry approach, with labile tert-butyl esters replacing the previously used methyl esters as protecting groups for picolinic acid moieties. Additionally, the ligands H2dedpa and p-SCN-Bn-H2dedpa were synthesized using nosyl protection chemistry for the first time. The use of tert-butyl esters allows for deprotection at room temperature in trifluoroacetic acid (TFA), which compares favorably to the harsh conditions of refluxing HCl (6 M) or LiOH that were previously required for methyl ester cleavage. H4octapa has recently been shown to be a very promising (111)In and (177)Lu ligand for radiopharmaceutical applications; therefore, coordination chemistry studies with Y(3+) are described to assess its potential for use with (86)Y/(90)Y. The solution chemistry of H4octapa with Y(3+) is shown to be suitable via solution NMR studies of the [Y(octapa)](-) complex and density functional theory (DFT) calculations of the predicted structure, suggesting properties similar to those of the analogous In(3+) and Lu(3+) complexes. The molecular electrostatic potential (MEP) was mapped onto the molecular surface of the DFT-calculated coordination structures, suggesting very similar and even charge distributions between both the Lu(3+) and Y(3+) complexes of octapa(4-), and coordinate structures between 8 (ligand only) and 9 (ligand and one H2O). Potentiometric titrations determined H4octapa to have a formation constant (log K(ML)) with Y(3+) of 18.3 ± 0.1, revealing high thermodynamic stability. This preliminary work suggests that H4octapa may be a competent ligand for future (86)Y/(90)Y radiopharmaceutical applications.

  4. Comparative evaluation of glutamate-sensitive radiopharmaceuticals: Technetium-99m-glutamic acid and technetium-99m-diethylenetriaminepentaacetic acid-bis(glutamate) conjugate for tumor imaging.

    Science.gov (United States)

    Kakkar, Dipti; Tiwari, Anjani K; Chuttani, Krishna; Kaul, Ankur; Singh, Harpal; Mishra, Anil K

    2010-12-01

    Single-photon emission computed tomography has become a significant imaging modality with huge potential to visualize and provide information of anatomic dysfunctions that are predictive of future diseases. This imaging tool is complimented by radiopharmaceuticals/radiosubstrates that help in imaging specific physiological aspects of the human body. The present study was undertaken to explore the utility of technetium-99m (⁹⁹(m)Tc)-labeled glutamate conjugates for tumor scintigraphy. As part of our efforts to further utilize the application of chelating agents, glutamic acid was conjugated with a multidentate ligand, diethylenetriaminepentaacetic acid (DTPA). The DTPA-glutamate conjugate [DTPA-bis(Glu)] was well characterized by IR, NMR, and mass spectroscopy. The biological activity of glutamic acid was compared with its DTPA conjugate by radiocomplexation with ⁹⁹(m)Tc (labeling efficiency ≥98%). In vivo studies of both the radiolabeled complexes ⁹⁹(m)Tc-Glu and ⁹⁹(m)Tc-DTPA-bis(Glu) were then carried out, followed by gamma scintigraphy in New Zealand albino rabbits. Improved serum stability of ⁹⁹(m)Tc-labeled DTPA conjugate indicated that ⁹⁹(m)Tc remained bound to the conjugate up to 24 hours. Blood clearance showed a relatively slow washout of the DTPA conjugate when compared with the labeled glutamate. Biodistribution characteristics of the conjugate in Balb/c mice revealed that DTPA conjugation of glutamic acid favors less accumulation in the liver and bone and rapid renal clearance. Tumor scintigraphy in mice showed increasing tumor accumulation, stable up to 4 hours. These preliminary studies show that ⁹⁹(m)Tc-DTPA-bis(Glu) can be a useful radiopharmaceutical for diagnostic applications in single-photon emission computed tomography imaging.

  5. Synthesis and Primary Research on Antitumor Activity of Three New Panaxadiol Fatty Acid Esters

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    For making use of Ginseng resources that exhibit an antitumor activity and for finding new anticancer drugs,three new fatty acid ester compounds: 3β-acetoxy panaxadiol ( Ⅰ ), 3β-palmitic acid aceloxy panaxadiol ( Ⅱ ), and 3β-octadecanoic acid aceloxy panaxadiol( Ⅰ , Ⅱ , and Ⅲ ) were synthesized with panaxadiol, diacetyl oxide, palmityl chloride and stearyl chloride, and their structures were determined via MS, 13C NMR, IR, TLC, and so on. The molar yields of the three compounds are 75.14%, 79. 08%, and 72. 57%, respectively. Meanwhile, the antitumor activity of the three new panaxadiol fatty acid ester derivatives and panaxadiol was compared by using the method of MTT. Tumor cell used was Vero cell line. Positive control was 5-FU, blank was an RPMI1640 culture medium, negative control was an RPMI1640 culture medium and the solvent for drugs to be tested. Compound Ⅰ has the strongest antitumor activity followed by panaxadiol; compounds Ⅱ and Ⅲ have similar and weakest antitumor activities.Furthermore, the antitumor activities of the panaxadiol fatty acid ester derivatives show positive correlation with the concentration of the test group, but show no relationship with the molecular weight of fatty acid. The methods that are used to synthesize the three compounds with high yields and strong antitumor activities are simple and show a great potential for meeting the needs of industrial manufacture of these drugs.

  6. Synthesis and docking studies of novel antitumor benzimidazoles.

    Science.gov (United States)

    Omar, Mohamed A; Shaker, Yasser M; Galal, Shadia A; Ali, Mamdouh M; Kerwin, Sean M; Li, Jing; Tokuda, Harukuni; Ramadan, Raghda A; El Diwani, Hoda I

    2012-12-15

    In this work, the benzimidazole-pyrrole conjugates 6a-h and benzimidazole-tetracycles conjugates 12-14 were prepared. The cytotoxicity of the compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 was tested against lung cancer cell line A549. Compound 6b exhibited higher activity than the bis-benzoxazole natural product (UK-1), the standard. The tested 4g,h, 6a-h, 10 and 12-14 exhibited remarkable cytotoxicity activity against breast cancer cell line MCF-7 with higher activity than tamoxifen. Furthermore, compound 4h was found to be also more potent than doxurubicin. The antitumor promotion activity of synthesized compounds 4g,h, 6a-h, 10 and 12-14 has been estimated by studying their possible inhibitory effects on EBV-EA activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds, the inhibitory activities of compounds 8, 13 and 14 demonstrated strong inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation without showing any cytotoxicity on the Raji cells and their effects being stronger than that of a representative control, oleanolic acid. Moreover, the molecular docking of the new compounds into plasminogen activator (uPA) receptor has been in correlation with the antitumor activity. All synthesized compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 were docked into same groove of the binding site of the native co-crystalized (4-iodobenzo[b]thiophene-2-carboxamidine) ligand (PDB code:1c5x) for activity explaination. Compounds 4h, 6b and 13, giving the best docking results, were further studied to estimate their effect on the level of uPA using AssayMax human urokinase (uPA) ELISA kit. In case of A549 cell line, compound 6 exhibited similar activity to MMC, and for MCF-7 cell line, compound 4h exhibited similar activity to doxorubicin, in inhibiting the expression of uPA.

  7. Antitumor effects of the combination of cholesterol reducing drugs.

    Science.gov (United States)

    Issat, Tadeusz; Nowis, Dominika; Bil, Jacek; Winiarska, Magdalena; Jakobisiak, Marek; Golab, Jakub

    2011-07-01

    There are a number of potential mechanisms linking cholesterol homeostasis to processes that are tightly linked with carcinogenesis. Statins, which are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAR), the rate-limiting enzyme in the mevalonic acid synthesis pathway, exert cytostatic and cytotoxic effects towards tumor cells. It seems that the cytostatic and cytotoxic effects of statins result from blocking protein prenylation, leading to inhibition of isoprenoid compound synthesis. Another compound which affects cholesterol metabolism is the plant alkaloid berberine. The aim of this study was to investigate potential antitumor effects of lovastatin combined with berberine. Combined with berberine, lovastatin appeared to exert potentiated cytostatic and/or cytotoxic effects against human MDA-MB231 breast cancer and murine Panc 02 pancreatic cancer cells. The obtained results indicated that the effect of berberine is not dependent on blocking protein prenylation in cells, and the toxic effect of lovastatin combined with berberine is reversed by addition of the substrates of this pathway to the level brought out by lovastatin alone. Lovastatin-berberine combination caused cell cycle inhibition in G1 phase after 48 h of incubation with drugs. In a Panc 02 pancreatic cancer model in mice, lovastatin-berberine combination slightly, but significantly, slowed down tumor growth. Taking into account the number of patients treated with the investigated drugs one may suppose that the described interactions may be of clinical value.

  8. Pharmacokinetic evaluation and antitumor activity of 2-methoxyestradiol nanosuspension.

    Science.gov (United States)

    Du, Shuzhang; Zhu, Ling; Du, Bin; Shi, Xiufang; Zhang, Zhenzhong; Wang, Shuyu; Zhang, Chaofeng

    2012-04-01

    The aim of the present study was to evaluate the pharmacokinetic and antitumor activity of 2-methoxyestradiol (2-ME) nanosuspension relative to 2-ME solution both in vitro and in vivo. The pharmacokinetics of 2-ME administered either as a nanosuspension or as a solution were compared after I.V. administration to rats. In plasma, 2-ME nanosuspension exhibited a significantly (p nanosuspension could significantly enhance the cytotoxicity of 2-ME on EC9706 cells in vitro. After 72 h exposure, the IC(50) value of 2-ME nanosuspension was much lower than that of 2-ME solution (1.81 ± 0.15 μmol/L versus 4.14 ± 0.30 μmol/L). Studies on BALB/c mice with EC9706 solid tumors demonstrated significantly greater inhibition of tumor growth following treatment with 2-ME nanosuspension than 2-ME solution at the same dosage. These results suggest that the delivery of 2-ME nanosuspension is a promising approach for the treatment of tumors.

  9. In vitro and in vivo antitumor activity of oridonin nanosuspension.

    Science.gov (United States)

    Lou, Haiyan; Zhang, Xiumei; Gao, Lei; Feng, Feifei; Wang, Juying; Wei, Xinbing; Yu, Zongqin; Zhang, Dianrui; Zhang, Qiang

    2009-09-08

    The aim of the present study was to evaluate the antitumor activity of an oridonin (ORI) nanosuspension relative to ORI solution both in vitro and in vivo. ORI nanosuspension with a particle size of 897.2+/-14.2 nm was prepared by the high pressure homogenization method (HPH). MTT assay showed that ORI nanosuspension could significantly enhance the in vitro cytotoxicity against K562 cells compared to the ORI solution, the IC(50) value at 36 h was reduced from 12.85 micromol/L for ORI solution to 8.11 micromol/L for ORI nanosuspension. Flow cytometric analysis demonstrated that the ORI nanosuspension also induced a higher apoptotic rate in K562 cells compared to ORI solution. In vivo studies in a mouse model of sarcoma-180 solid tumors demonstrated significantly greater inhibition of tumor growth following treatment with ORI nanosuspension than ORI solution at the same dosage. The mice injected with ORI nanosuspension showed a higher reduction in tumor volume and tumor weight at the dose of 20mg/kg compared to the ORI solution (Pnanosuspension. Taken together, these results suggest that the delivery of ORI in nanosuspension is a promising approach for the treatment of the tumor.

  10. Antitumor and Antiviral Activity of Colombian Medicinal Plant Extracts

    Directory of Open Access Journals (Sweden)

    Betancur-Galvis LA

    1999-01-01

    Full Text Available Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity and antiherpetic activity. MTT (Tetrazolium blue and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2. The 50% cytotoxic concentration (CC50 and the 50% inhibitory concentration of the viral effect (EC50 for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x103mg/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50. These species are good candidates for further activity-monitored fractionation to identify active principles.

  11. [Procedure for determination of individual sensitivity to antitumor drugs].

    Science.gov (United States)

    Abduvaliev, A A; Gil'dieva, M S; Tatarskiĭ, V P

    2006-05-01

    The present paper proposes to employ the cultured tumor cells of the breast and chick fibroblasts after long-term cultivation (for above 24 days) to determine their individual drug sensitivity and, as a criterion of cell damage, to use the percent of destruction of the cell layer formed in the wells 24 hours after drug insertion. It also presents the comparative results of tests of 2 cellular models that have been used to determine the in vitro sensitivity of the cells of breast cancer and chick fibroblasts to melfalan and its complex compound with copper acetylacetonate - MOK*M. At the same time, the cytotoxic activity of MOK*M and melfalan against tumor cells has been not shown to differ greatly (16.02+/-1.85 and 15.71+/-0.65% cell layer destruction, respectively), but the same activity of MOK*M against the model of intact cells (chick fibroblasts) was much less (15.23+/-1.97%) than that of melfalan (95.39+/-1.11%). The test system proposed by the authors is of certain informative value and it may be used for the determination of the individual sensitivity of tumor cells to antitumor drugs.

  12. [Progress of anti-tumor study based on BRAF].

    Science.gov (United States)

    Yan, Gui-Rui; Xu, Zhi-Jian; Wang, He-Yao; Zhu, Wei-Liang

    2012-12-01

    BRAF is one of the most important pro-oncogenes, which is mutated in approximately 8% of human tumors. The most common BRAF mutation is a valine-to-glutamate transition (V600E) that is expressed primarily in melanoma, colorectal cancer and thyroid carcinoma. MEK/ERK is constitutively activated in the cells expressing BRAFV600E, leading to tumor development, invasion, and metastasis. Therefore, BRAFV600E is a therapeutic target for melanoma and some other BRAFV600E tumors. Vemurafenib, a BRAFV600E inhibitor, which was approved by FDA for the treatment of late-stage melanoma in 2011, produces improved rates of overall and progression-free survival in patients with the BRAFV600E mutation, making a dramatic breakthrough in melanoma treatment. Vemurafenib is also an individual target drug based on genetic diagnosis. However, its therapeutic success is limited by the emergence of drug resistance. Therefore, it is important to explore the mechanisms underlying the resistance for developing new inhibitor drugs and for preventing or delaying the resistance evolution to BRAF inhibitor drugs. In this review, we described the role of BRAFV600E as an anti-tumor drug target and the development of BRAF inhibitors. We also discussed the mechanisms leading to resistance of BRAFV600E inhibitors. Furthermore, therapeutic strategies that might be employed to overcome acquired resistance were proposed.

  13. Antitumor Lipids--Structure, Functions, and Medical Applications.

    Science.gov (United States)

    Kostadinova, Aneliya; Topouzova-Hristova, Tanya; Momchilova, Albena; Tzoneva, Rumiana; Berger, Martin R

    2015-01-01

    Cell proliferation and metastasis are considered hallmarks of tumor progression. Therefore, efforts have been made to develop novel anticancer drugs that inhibit both the proliferation and the motility of tumor cells. Synthetic antitumor lipids (ATLs), which are chemically divided into two main classes, comprise (i) alkylphospholipids (APLs) and (ii) alkylphosphocholines (APCs). They represent a new entity of drugs with distinct antiproliferative properties in tumor cells. These compounds do not interfere with the DNA or mitotic spindle apparatus of the cell, instead, they incorporate into cell membranes, where they accumulate and interfere with lipid metabolism and lipid-dependent signaling pathways. Recently, it has been shown that the most commonly studied APLs inhibit proliferation by inducing apoptosis in malignant cells while leaving normal cells unaffected and are potent sensitizers of conventional chemo- and radiotherapy, as well as of electrical field therapy. APLs resist catabolic degradation to a large extent, therefore accumulate in the cell and interfere with lipid-dependent survival signaling pathways, notably PI3K-Akt and Raf-Erk1/2, and de novo phospholipid biosynthesis. They are internalized in the cell membrane via raft domains and cause downstream reactions as inhibition of cell growth and migration, cell cycle arrest, actin stress fibers collapse, and apoptosis. This review summarizes the in vitro, in vivo, and clinical trials of most common ATLs and their mode of action at molecular and biochemical levels.

  14. Organo-platinum complexes as antitumor agents (review).

    Science.gov (United States)

    Hill, J M; Speer, R J

    1982-01-01

    Rosenberg et al discovered in the coordination complexes of platinum a new, novel type of potential antitumor agent. Cisplatin [cis-dichlorodiammine platinum (II)4 proved active against a variety of rodent tumors and acted synergistically when combined with other chemotherapeutic agents. Initial clinical tests by Hill et al in 1971, showed cisplatin to be active against malignant lymphoma, Hodgkin's disease, and certain other malignancies. Significant nephrotoxicity, nausea, and vomiting were noted. Since then, cisplatin has been tested alone and in combination chemotherapy and has proven an efficacious anticancer agent in squamous cell carcinoma of head and neck, ovarian carcinoma, disseminated testicular cancer, and others. Its therapeutic value was acknowledged when approved in 1978 by the U.S. FDA for treatment of the latter cancer. The current clinical literature indicates clearly that the full potential of this drug has not yet been realized. Hydration and diuresis have served to mitigate much of the nephrotoxicity, while significant strides toward amelioration of the nausea and vomiting have also been achieved. Literally, thousands of chemically-related congeners have been synthesized, and many have shown marked potency against rodent tumors. Very few, however, have been evaluated clinically, vis-a-vis malonato trans(-)-1,2-diaminocyclohexane platinum(II); this appears a most promising and fertile area of future investigation.

  15. GMCSF-armed vaccinia virus induces an antitumor immune response.

    Science.gov (United States)

    Parviainen, Suvi; Ahonen, Marko; Diaconu, Iulia; Kipar, Anja; Siurala, Mikko; Vähä-Koskela, Markus; Kanerva, Anna; Cerullo, Vincenzo; Hemminki, Akseli

    2015-03-01

    Oncolytic Western Reserve strain vaccinia virus selective for epidermal growth factor receptor pathway mutations and tumor-associated hypermetabolism was armed with human granulocyte-macrophage colony-stimulating factor (GMCSF) and a tdTomato fluorophore. As the assessment of immunological responses to human transgenes is challenging in the most commonly used animal models, we used immunocompetent Syrian golden hamsters, known to be sensitive to human GMCSF and semipermissive to vaccinia virus. Efficacy was initially tested in vitro on various human and hamster cell lines and oncolytic potency of transgene-carrying viruses was similar to unarmed virus. The hGMCSF-encoding virus was able to completely eradicate subcutaneous pancreatic tumors in hamsters, and to fully protect the animals from subsequent rechallenge with the same tumor. Induction of specific antitumor immunity was also shown by ex vivo co-culture experiments with hamster splenocytes. In addition, histological examination revealed increased infiltration of neutrophils and macrophages in GMCSF-virus-treated tumors. These findings help clarify the mechanism of action of GMCSF-armed vaccinia viruses undergoing clinical trials.

  16. Mechanisms of selective antitumor action of cold atmospheric plasma

    Science.gov (United States)

    Graves, David; Bauer, Georg

    2016-09-01

    Transformed (precancerous) cells are known to be subject to elimination through intercellular RONS-dependent apoptosis-inducing signaling. It is a remarkable fact that the chemical species utilized by apoptosis induction in transformed cells are essentially identical to chemical species created by cold atmospheric plasma (CAP) in aqueous solutions. The association between CAP-induced biochemistry and natural cell anti-tumor mechanisms offers the opportunity to establish a rationale for the observed successes of CAP in selectively eliminating tumor cells in vitro and in vivo. In particular, 1O2 appears to act to selectively induce apoptosis in tumor cells, and can also result in self-perpetuating, cell-to-cell apoptotic signaling. Various CAP-generated liquid phase species can react to form 1O2, thus providing a hypothetical mechanism to explain how CAP can trigger therapeutic apoptosis in tumors. The analysis of model experiments performed with defined RONS in vitro implies that CAP-derived 1O2 induces the mechanism through which CAP acts selectively against cancer cells in vitro and tumors in vivo. This hypothesis needs to be tested experimentally in order to establish its validity.

  17. Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Paraskar, Abhimanyu; Soni, Shivani; Basu, Sudipta; Srivats, Shyam; Roy, Rituparna Sinha; Sengupta, Shiladitya [BWH-HST Center for Biomedical Engineering, Harvard Medical School, 65 Landsdowne street, Cambridge, MA 02139 (United States); Amarasiriwardena, Chitra J; Lupoli, Nicola, E-mail: ssengupta2@partners.org [Channing Laboratory, Department of Medicine, Brigham and Women' s Hospital, Harvard Medical School, 65 Landsdowne street, Cambridge, MA 02139 (United States)

    2011-07-01

    The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) copolymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibits an IC{sub 50} = 0.77 {+-} 0.11 {mu}M comparable to that of free cisplatin (IC{sub 50} = 0.44 {+-} 0.09 {mu}M). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and release cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibit significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo, with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.

  18. Design and synthesis of modified quinolones as antitumoral acridones.

    Science.gov (United States)

    Tabarrini, O; Cecchetti, V; Fravolini, A; Nocentini, G; Barzi, A; Sabatini, S; Miao, H; Sissi, C

    1999-06-17

    The bacterial topoisomerase II (DNA gyrase) and the mammalian topoisomerase II represent the cellular targets for quinolone antibacterials and a wide variety of anticancer drugs, respectively. In view of the mechanistic similarities and sequence homologies exhibited by the two enzymes, tentative efforts to selectively shift from an antibacterial to an antitumoral activity was made by synthesizing a series of modified tricyclic quinolones, in which the essential 3-carboxylic function is surrogated by phenolic OH and the classic C-6 fluorine atom is replaced by a NH2 group. The resulting 7-amino-9-acridone derivatives were assayed for their antibacterial as well as cytotoxic activities. No antibacterial activity was found. On the other hand, many derivatives showed significant cytotoxic activity against both HL-60 and P388 leukemias and a wide panel of human and rodent solid tumor cells, derivatives 25 and 26 displaying the best overall antiproliferative activity. Against the LoVo cell line, derivative 25 exhibited higher cytotoxic effects than etoposide.

  19. Development of an injectable formulation for the preparation of radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin; Desarrollo de una formulacion inyectable para la preparacion del radiofarmaco {sup 68}Ga-DOTA-Sargastrina

    Energy Technology Data Exchange (ETDEWEB)

    Castillo P, M.

    2015-07-01

    The CCK2 receptor (cholecystokinin) is located in areas of the central and peripheral nervous system and is over expressed in several types of human cancer, as medullar thyroid, lung and ovarian carcinomas. One of the endogenous ligands for the CCK2 receptor is the gastrin, so that radiolabeled peptides analogues to gastrin as Sar gastrin (Gln-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Nle-Asp-Phe-NH{sub 2}) have been proposed as potential diagnostic radiopharmaceuticals for obtaining tumors images with CCK2 receptors over expressed. The {sup 68}Ga is an ideal candidate for the peptides radiolabelled and has favorable characteristics to be used for diagnostic purposes by imaging with Positron emission tomography (PET). This work aimed to verify the technical documentation of the production process of radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin for its sanitary registration before the Comision Federal contra Riesgos Sanitarios (COFEPRIS) in Mexico. For optimization of the production process was assessed a factorial design of two variables with mixed levels (27 combinations), where the dependent variable was the radiochemical purity. The analytical method used for evaluating the content of Sar gastrin peptide in the injectable formulation was also validated by High-performance liquid chromatography. Subsequently the validation of the production process was carried out by manufacturing of lots in single-dose of the optimized injectable formulation of the radiopharmaceutical {sup 68}Ga-DOTA-Sar gastrin and the stability study was conducted at different times to determine the useful life time. The following was established as the optimal pharmaceutical formulation: 185 MBq of {sup 68}Ga, 50 μg de DOTA-Sar gastrin, 14 mg of sodium acetate and 0.5 m L of buffer acetates, 1.0 M, ph 4.22 in 2.5 m L of the vehicle. The analytical method used to determine the radiochemical purity of the formulation satisfied the requirements for the intended analytical

  20. In vivo and in vitro study of the 9{sup 9mT}c-DMSA radiopharmaceutical connection to blood elements; Estudo in vivo e in vitro da ligacao do radiofarmaco 99mTc-DMSA aos elementos sanquineos

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, Rosimeire de S. [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria]|[Hospital Universitario Clementino Fraga Filho, Rio de Janeiro (Brazil); Gomes, Maria L.; Mattos, Deise M.M.; Moreno, Silvana R.F.; Dire, Glaucio F.; Lima, Elaine A.; Lima-Filho, Guilherme L.; Aleixo, Luiz Claudio [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Bernardo-Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria]|[Instituto Nacional do Cancer, Rio de Janeiro (Brazil). Centro de Pesquisa Basica] E-mail: rosfreitas@hotmail.com

    2002-07-01

    Radiopharmaceuticals are widely used in nuclear medicine. The comprehension of their uptake mechanism in target organs, as well as their clearance may depend on the elucidation of their biochemical characteristics, for instance, their binding to blood elements. The reported precipitating studies of blood with radiopharmaceuticals have shown that the results can not be easily compared. Then, we decide evaluate of the binding proteins on the blood elements using trichloroacetic acid (TCA) to determine the radioactivity of the dimercaptosuccinic acid with technetium-99m (99mTc-DMSA) present in precipitating plasma (P) and blood cells (BC). Depending on the TCA concentration we have determined different values in the insoluble fractions of the plasma when the in vivo and in vitro evaluations were carried out. (author)

  1. The Synthesis and Antitumor Activity of Twelve Galloyl Glucosides

    Directory of Open Access Journals (Sweden)

    Chang-Wei Li

    2015-01-01

    Full Text Available Twelve galloyl glucosides 1–12, showing diverse substitution patterns with two or three galloyl groups, were synthesized using commercially available, low-cost D-glucose and gallic acid as starting materials. Among them, three compounds, methyl 3,6-di-O-galloyl-α-D-glucopyranoside (9, ethyl 2,3-di-O-galloyl-α-D-glucopyranoside (11 and ethyl 2,3-di-O-galloyl-β-D-glucopyranoside (12, are new compounds and other six, 1,6-di-O-galloyl-β-D-glucopyranose (1, 1,4,6-tri-O-galloyl-β-D-glucopyranose (2, 1,2-di-O-galloyl-β-D-glucopyranose (3, 1,3-di-O-galloyl-β-D-glucopyranose (4, 1,2,3-tri-O-galloyl-α-D-glucopyranose (6 and methyl 3,4,6-tri-O-galloyl-α-D-glucopyranoside (10, were synthesized for the first time in the present study. In in vitro MTT assay, 1–12 inhibited human cancer K562, HL-60 and HeLa cells with inhibition rates ranging from 64.2% to 92.9% at 100 μg/mL, and their IC50 values were determined to be varied in 17.2–124.7 μM on the tested three human cancer cell lines. In addition, compounds 1–12 inhibited murine sarcoma S180 cells with inhibition rates ranging from 38.7% to 52.8% at 100 μg/mL in the in vitro MTT assay, and in vivo antitumor activity of 1 and 2 was also detected in murine sarcoma S180 tumor-bearing Kunming mice using taxol as positive control.

  2. Potent and specific antitumor effect of CEA-targeted photoimmunotherapy.

    Science.gov (United States)

    Shirasu, Naoto; Yamada, Hiromi; Shibaguchi, Hirotomo; Kuroki, Motomu; Kuroki, Masahide

    2014-12-01

    Conventional photodynamic therapy (PDT) for cancer is limited by the insufficient efficacy and specificity of photosensitizers. We herein describe a highly effective and selective tumor-targeted PDT using a near-infrared (NIR) photosensitizer, IRDye700DX, conjugated to a human monoclonal antibody (Ab) specific for carcinoembryonic antigen (CEA). The antitumor effects of this Ab-assisted PDT, called photoimmunotherapy (PIT), were investigated in vitro and in vivo. The Ab-IRDye conjugate induced potent cytotoxicity against CEA-positive tumor cells after NIR-irradiation, whereas CEA-negative cells were not affected at all, even in the presence of excess photoimmunoconjugate. We found an equivalent phototoxicity and a predominant plasma membrane localization of Ab-IRDye after both one and six hours of incubation. Either no or little caspase activation and membrane peroxidation were observed in PIT-treated cells and a panel of scavengers for reactive oxygen species showed only partial inhibition of the phototoxic effect. Strikingly, Ab-IRDye retained significant phototoxicity even under hypoxia. We established a xenograft model, which allowed us to sensitively investigate the therapeutic efficacy of PIT by non-invasive bioluminescence imaging. Luciferase-expressing MKN-45-luc human gastric carcinoma cells were subcutaneously implanted into both flanks of nude mice. NIR-irradiation was performed for only the tumor on one side. In vivo imaging and measurement of the tumor size revealed that a single PIT treatment, with intraperitoneal administration of Ab-IRDye and subsequent NIR-irradiation, caused rapid cell death and significant inhibition of tumor growth, but only on the irradiated side. Together, these data suggest that Ab-IRDye-mediated PIT has great potential as an anticancer therapeutics targeting CEA-positive tumors.

  3. Comparative antitumor and anti-proliferative activities ofHippophae rhamnoidesL. leaves extracts

    Institute of Scientific and Technical Information of China (English)

    Javid Ali; Bashir Ahmad

    2015-01-01

    Objective:To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform andn-hexane extracts ofHippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens) with three different concentrations of test samples (10, 100 and 1 000 mg/L). Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8%) was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated inn-hexane extract. The difference in tumor and cell inhibition (%) may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions:Our finding showed thatHippophae rhamnoidesleaves are a potent natural source of antitumor and antiproliferative agent.

  4. Paracetamol Supplementation Does Not Alter The Antitumor Activity and Lung Toxicity of Bleomycin

    Directory of Open Access Journals (Sweden)

    Ghada M. Suddek

    2014-01-01

    Full Text Available Bleomycin (BLM is well known by its antitumor activity both in vitro and in vivo. However, pulmonary fibrosis has been considered the dose limiting toxicity of the drug. Hyperpyrexia following injection of BLM was reported thus, paracetamol is sometimes administered with BLM as antipyretic drug. Actually, paracetamol was found to interfere with cytotoxicity of some drugs. This study was conducted to investigate the effect of paracetamol administration on the antitumor and lung toxicity of BLM. The antitumor activity was evaluated both in vitro and in vivo using Ehrlich ascites carcinoma (EAC cells. Paracetamol did not alter the antitumor effect of BLM in vitro or in vivo. The lung toxicity of BLM was evidenced by decrease in the body weight, increase in the lung/body weight ratio, decrease in the response of pulmonary arterial rings to 5-hydroxytryptamine (5-HT and increase in the contractility of tracheal smooth muscles induced by acetylcholine (ACh. The toxicity was also confirmed biochemically by marked increases in hydroxyproline and lipid peroxidation in rat lung and the decrease in reduced glutathione (GSH level. Pretreatment with paracetamol did not significantly change lipid peroxidation, GSH level, percent survival of rats or the response of pulmonary arterial rings and tracheal smooth muscles to 5-HT and ACh respectively. The results of the present study indicated that paracetamol neither modified the antitumor effect of BLM nor changed drug-induced lung toxicity.

  5. Oncolytic Immunotherapy: Dying the Right Way is a Key to Eliciting Potent Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Zong Sheng eGuo

    2014-04-01

    Full Text Available Oncolytic viruses (OVs are novel immunotherapeutic agents whose anticancer effects come from both oncolysis and elicited antitumor immunity. OVs induce mostly immunogenic cancer cell death (ICD, including immunogenic apoptosis, necrosis/necroptosis, pyroptosis and autophagic cell death, leading to exposure of calreticulin and heat-shock proteins to the cell surface, and/or released ATP, high mobility group box-1 [HMGB1], uric acid, and other DAMPs as well as PAMPs as danger signals, along with tumor-associated antigens, to activate dendritic cells (DCs and elicit adaptive antitumor immunity. Dying the right way may greatly potentiate adaptive antitumor immunity. The mode of cancer cell death may be modulated by individual OVs and cancer cells as they often encode and express genes that inhibit/promote apoptosis, necroptosis or autophagic cell death. We can genetically engineer OVs with death-pathway-modulating genes and thus skew the infected cancer cells towards certain death pathways for the enhanced immunogenicity. Strategies combining with some standard therapeutic regimens may also change the immunological consequence of cancer cell death. In this review, we discuss recent advances in our understanding of danger signals, modes of cancer cell death induced by OVs, the induced danger signals and functions in eliciting subsequent antitumor immunity. We also discuss potential combination strategies to target cells into specific modes of ICD and enhance cancer immunogenicity, including blockade of immune checkpoints, in order to break immune tolerance, improve antitumor immunity and thus the overall therapeutic efficacy.

  6. ANTITUMOR EFFECT OF SARCNU IN A 06-METHYLGUANINE-DNA METHYLTRANSFERASE POSITIVE HUMAN GLIOMA XENOGRAFT MODEL

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To assess whether novel analogue of nitrosoureas, 2-chloroethyl-3-sarcosinamide-1-nitrosourea (SarCNU), has antitumor effect to 06-methylguanine-DNA methyltransferase (MGMT) positive tumors in vivo. Methods: MGMT positive human glioma cell line SF-767 xenografts in nude mice were treated with SarCNU. The antitumor efficacy of SarCNU was compared with the results of 1, 3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment with or without 06-benzylguanine (06-BG) preadministration. Results: Since the SF-767 is MGMT strongly positive, BCNU treatment alone did not result in a satisfactory anticancer effect. As expected, 06-BG by depleting MGMT activity, significantly enhanced BCNU antitumor efficacy (p<0.001). More interestingly, SarCNU treatment alone had a better antitumor effect than 06-BG plus BCNU treatment (F=51.7, p=0.00036). Conclusion: Since SarCNU enters cells via extraneuronal monoamine transporter (EMT), the enhanced antitumor activity of SarCNU in this MGMT positive human tumor xenograft model may be due to the presence of EMT in SF-767.SarCNU may be used as an alternative treatment for MGMT positive tumors, specifically for tumors expressing EMT.

  7. Lead optimization through VLAK protocol: new annelated pyrrolo-pyrimidine derivatives as antitumor agents.

    Science.gov (United States)

    Lauria, Antonino; Patella, Chiara; Abbate, Ilenia; Martorana, Annamaria; Almerico, Anna Maria

    2012-09-01

    The chemometric protocol VLAK was applied to predict improvement of the biological activity of pyrrolo-pyrimidine derivatives as anticancer agents, by using the NCI ACAM Database as depository of antitumor drugs with a known mechanism of action. Among the selected compounds two of these showed a good increase in the antitumor activity. These new pyrrolo-pyrimidine compounds were demonstrated effective against the full panels of NCI DTP tumour human cell lines. The derivative 8-[3-(piperidino)propyl]-4,10-dimethyl-9-phenyl-6-(methylsulfanyl)-3,4-dihydropyrimido[1,2-c]pyrrolo[3,2-e]pyrimidin-2(8H)-one reveled efficacious against the leukemia subpanel, in particular the RPMI cell line resulted the most sensitive (pGI(50) = 6.68). Moreover the derivative 7-(3-Chloropropyl)-9-methyl-5-(methylsulfanyl)-8-phenyl-3H-imidazo[1,2-c]pyrrolo[3,2-e]pyrimidin-2(7H)-one showed a good antitumor activity against the leukemia subpanel with a low cytotoxic activity, above all against the HCT11 human tumour cell line. The VLAK protocol revealed a good method to design new molecules with good antitumor activity, starting from low active compounds. Moreover this protocol focused on the pyrrolo-pyrimidine derivatives as useful starting point for further development to obtain more potent antitumor agents.

  8. Development of additive [{sup 11}C]CO{sub 2} target system in the KOTRON-13 cyclotron and its application for [{sup 11}C]radiopharmaceutical production

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Byung Seok; Lee, Hong Jin [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 463-707 (Korea, Republic of); Lee, Won Kyung [Technical Support Team, Duchembio, Seoul 121-844 (Korea, Republic of); Hur, Min Goo; Yang, Seung Dae [Radiation Instrumentation Research Division, Korea Atomic Energy Research Institute, Jeongeup 580-185 (Korea, Republic of); Lee, Byung Chul, E-mail: leebc2001@gmail.com [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 463-707 (Korea, Republic of); Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 443-270 (Korea, Republic of); Kim, Sang Eun [Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 463-707 (Korea, Republic of); Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 443-270 (Korea, Republic of); Smart Humanity Convergence Center, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 443-270 (Korea, Republic of)

    2015-08-01

    The KOTRON-13 cyclotron, which was developed in South Korea for the production of medical radioisotopes, has the structural limitation of only one beam-output port, restricting the production of the carbon-11 isotope. In the present study, we investigate the design of a switchable target system and develop an effective carbon-11 target in the KOTRON-13 cyclotron, for combination with the fluorine-18 target. The target system was designed by introducing a sliding-type element between the fluorine-18 and carbon-11 targets, a tailor-made C-11 target and its cooling system. For the efficient production of [{sup 11}C]CO{sub 2}, the desirable target shape and internal volume were determined by a Stopping and Range of Ions in Matter (SRIM) simulation program, and the target grid was modified to resist the cavity pressure during beam irradiation. We evaluated the [{sup 11}C]CO{sub 2} production while varying the material and thickness of the target foil, oxygen content of the nitrogen gas, and target loading pressure. Using sliding-type equipment including an additional gate valve and a high vacuum in a beam line, the bi-directional conversion between the fluorine-18 and carbon-11 targets was efficient regarding the accurate beam irradiation on both targets. The optimal [{sup 11}C]CO{sub 2} production for 30 min irradiation at 60 μA (86.6 ± 1.7 GBq in the target at EOB) was observed at a thickness of 19 μm with HAVAR® material as a target foil and a target loading pressure of 24 bar with nitrogen plus 300 ppb of oxygen gas. Additionally, the coolant cavity system in the target grid and target chamber is useful to remove the heat transferred to the target body by the internal convection of water and thereby ensure the stability of the [{sup 11}C]CO{sub 2} production under a high beam current. In the application of C-11 labeled radiopharmaceuticals such as [{sup 11}C]PIB, [{sup 11}C]DASB, [{sup 11}C]PBR28, [{sup 11}C]Methionine and [{sup 11}C]Clozapine, the radiochemical

  9. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice

    Science.gov (United States)

    Barakat, Waleed; Elshazly, Shimaa M.; Mahmoud, Amr A. A.

    2015-01-01

    Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive. PMID:26366170

  10. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice

    Directory of Open Access Journals (Sweden)

    Waleed Barakat

    2015-01-01

    Full Text Available Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg. Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive.

  11. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice.

    Science.gov (United States)

    Barakat, Waleed; Elshazly, Shimaa M; Mahmoud, Amr A A

    2015-01-01

    Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels failed to exert any protective effect. In addition, spirulina did not potentiate the antitumor effect of fluorouracil when they were administered concurrently. Interestingly, their combined administration resulted in a dose-dependent increase in mortality. The present study demonstrates that spirulina lacks antitumor effect against this model of solid Ehrlich carcinoma and increased mortality when combined with fluorouracil. However, the implicated mechanism is still elusive.

  12. ANTITUMOR AQCTIVITY OF REGIONAL ADMINISTRATION OF A-NK CELLS IN VIVO

    Institute of Scientific and Technical Information of China (English)

    GAO Jun; WANG Zhi-hua; ZHANG Zhi-bin; YANG Hong

    2006-01-01

    Objective: To observe the proliferation of A-NK in vitro and antitumor activity in vivo. Methods: The growth curve of A-NK and NA-NK cells was drawn in vitro. In the rat model, we compared the regional administration of A-NK-/IL-2 with the systemic administration. Results: The expansion of A-NK cells reached to climax on day 10 in the culture, increased 16.08 folds compared with the only 3.36 folds for NA-NK cells. In the rat model, we found that the regional administration of A-NK/IL-2 was better than systemic administration or administration of NA-NK/IL-2 not only in tumor infiltration and antitumor response, but also in the survival rate of rats (P<0.05). Conclusion: A-NK cells is a new immune effecter cells with high expansibility and high antitumor activity in vivo and in vitro.

  13. Tick salivary gland as potential natural source for the discovery of promising antitumor drug candidates.

    Science.gov (United States)

    Chudzinski-Tavassi, Ana Marisa; Morais, Katia L P; Pacheco, Mário Thiego Fernandes; Pasqualoto, Kerly Fernanda Mesquita; de Souza, Jean Gabriel

    2016-02-01

    Nowadays, the relationship between cancer blood coagulation is well established. Regarding biodiversity and bioprospection, the tick biology has become quite attractive natural source for coagulation inhibitors, since its saliva has a very rich variety of bioactive molecules. For instance, a Kunitz-type FXa inhibitor, named Amblyomin-X, was found through transcriptome of the salivary gland of the Amblyomma cajennense. tick. This TFPI-like inhibitor, after obtained as recombinant protein, has presented anticoagulant, antigionenic, and antitumor properties. Although its effects on blood coagulation could be relevant for antitumor effect, Amblyomin-X acts by non-hemostatic mechanisms, such as proteasome inhibition and autophagy inhibition. Notably, cytotoxicity was not observed on non-tumor cells treated with this protein, suggesting some selectivity for tumor cells. Considering the current efforts in order to develop effective anticancer therapies, the findings presented in this review strongly suggest Amblyomin-X as a promising novel antitumor drug candidate.

  14. Antitumor Effect of Water Decoctions of Taxus Cuspidate on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Chao Qu

    2014-01-01

    Full Text Available The Taxus cuspidate has been used as a traditional Chinese medicinal herb and considered to affect various physiological functions in the body for thousands of years. As we know that taxol isolated from the Taxus cuspidate has been approved for the treatment of ovarian cancer, it has also shown its antitumor abilities against other kinds of cancers. But the antitumor activity of other components which are free of paclitaxel and hydrophilic paclitaxel derivatives from Taxus cuspidate has not been fully understood. In this study, we investigated the effect of the water decoctions from the leaves of Taxus cuspidate on pancreatic cancer cell proliferation and the potential mechanism(s; though its antitumor activity and mechanism in vitro remain to be elucidated, the water soluble constituents from Taxus cuspidate could be used in clinical for cancer patients.

  15. Novel natural-product-like caged xanthones with improved druglike properties and in vivo antitumor potency.

    Science.gov (United States)

    Wu, Yue; Hu, Mingyang; Yang, Li; Li, Xiang; Bian, Jinlei; Jiang, Fen; Sun, Haopeng; You, Qidong; Zhang, Xiaojin

    2015-06-15

    DDO-6101, a natural-product-like caged xanthone discovered previously in our laboratory based on the pharmacophoric scaffold of Garcinia natural product gambogic acid (GA), shows potent cytotoxicity in vitro but poor efficacy in vivo due to its poor druglike properties. In order to improve the druglike properties and in vivo cytotoxic potency, a novel series of 19 prenyl group-modified derivatives of DDO-6101 was synthesized and evaluated for their in vitro antitumor activity and druglike properties. The SAR and SPR information of these compounds was also obtained. In the light of the in vitro antitumor activity and druglike properties such as aqueous solubility and permeability, compound 6f (named as DDO-6306) was advanced into in vivo efficacy experiment. The results showed that DDO-6306 is more potent than DDO-6101 in vivo and is a promising antitumor candidate for further evaluation.

  16. Design, synthesis and biological evaluation of new rhodacyanine analogues as potential antitumor agents

    Institute of Scientific and Technical Information of China (English)

    Yang Xiong Li; Xin Zhai; Wei Ke Liao; Wu Fu Zhu; Ying He; Ping Gong

    2012-01-01

    In an attempt to develop potent antitumor agents,new rhodacyanine analogues containing the pyridinium ring (5a-5h),the isoquinolinium ring (6a-6c) and the quinolinium ring (7a-7e) linked to the rhodanine ring via N-N covalent bond were designed,synthesized and evaluated for antitumor activity against human lung cancer cell line (H460) by MTT assay in vitro.Most of the tested compounds showed enhanced antitumor activity with IC50 values ranging from 0.006 to 9.2 μmol/L as compared to the lead compound MKT-077.Among them,the most promising compound 7d (IC50 =0.006 μmol/L) was 216.7 times more active than MKT-077 (IC50 =1.3 μmol/L).The preliminary structure-activity relationship of the target compounds was discussed.

  17. Enhancement of Antitumor Effect of Tegafur/Uracil (UFT) plus Leucovorin by Combined Treatment with Protein-Bound Polysaccharide, PSK, in Mouse Models

    Institute of Scientific and Technical Information of China (English)

    Ryoji Katoh; Mitsuru Ooshiro

    2007-01-01

    We evaluated the antitumor effect of combined therapy with tegafur/uracil (UFT) plus leucovorin (LV) (UFT/LV)and protein-bound polysaccharide, PSK, in three mouse models of transplantable tumors. UFT/LV showed antitumor effect against Meth A sarcoma, and the antitumor effect was enhanced when PSK given concomitantly.UFT/LV showed antitumor effect to Lewis lung carcinoma and PSK alone also showed antitumor effect at high dose, but a combination of UFT/LV and PSK resulted in no enhanced antitumor effect. Colon 26 carcinoma was weakly responsive to UFT/LV, and no enhancement of antitumor effect was found even PSK was used in combination. In conclusion, while the effect of PSK varies depending on tumor, combined use of UFT/LV and PSK may be expected to augment the antitumor effect.

  18. Intermittent Metronomic Drug Schedule Is Essential for Activating Antitumor Innate Immunity and Tumor Xenograft Regression

    Directory of Open Access Journals (Sweden)

    Chong-Sheng Chen

    2014-01-01

    Full Text Available Metronomic chemotherapy using cyclophosphamide (CPA is widely associated with antiangiogenesis; however, recent studies implicate other immune-based mechanisms, including antitumor innate immunity, which can induce major tumor regression in implanted brain tumor models. This study demonstrates the critical importance of drug schedule: CPA induced a potent antitumor innate immune response and tumor regression when administered intermittently on a 6-day repeating metronomic schedule but not with the same total exposure to activated CPA administered on an every 3-day schedule or using a daily oral regimen that serves as the basis for many clinical trials of metronomic chemotherapy. Notably, the more frequent metronomic CPA schedules abrogated the antitumor innate immune and therapeutic responses. Further, the innate immune response and antitumor activity both displayed an unusually steep dose-response curve and were not accompanied by antiangiogenesis. The strong recruitment of innate immune cells by the 6-day repeating CPA schedule was not sustained, and tumor regression was abolished, by a moderate (25% reduction in CPA dose. Moreover, an ~20% increase in CPA dose eliminated the partial tumor regression and weak innate immune cell recruitment seen in a subset of the every 6-day treated tumors. Thus, metronomic drug treatment must be at a sufficiently high dose but also sufficiently well spaced in time to induce strong sustained antitumor immune cell recruitment. Many current clinical metronomic chemotherapeutic protocols employ oral daily low-dose schedules that do not meet these requirements, suggesting that they may benefit from optimization designed to maximize antitumor immune responses.

  19. Silencing invariant chains of dendritic cells enhances anti-tumor immunity using small-interfering RNA

    Institute of Scientific and Technical Information of China (English)

    KE Shan; CHEN Xue-hua; ZHU Zheng-gang; LI Jian-fang; YU Bei-qin; GU Qin-long; LIU Bing-ya

    2010-01-01

    Background Genetic modification of dendritic cells (DCs) has been used as an effective approach to enhance anti-tumor immunity. RNA interference (RNAi), which can cause the degradation of any RNA in a sequence-specific manner, is a post-transcriptional gene silencing mechanism. In this study, small-interfering RNA (siRNA) specific for the Ii gene was transfected into DCs, and the anti-tumor immunity of Ii-silenced DCs was assessed.Methods The silencing effect of siRNA was evaluated by Western blotting and real-time PCR analyses. In vitro cytotoxic activity of T cells was evaluated using a Cytotox 96(R) non-radioactive cytotoxicity assay kit. The time to tumor onset and the tumor volumes were used as reliable indices to assess the anti-tumor immunity in vivo. To further examine the mechanisms underlying the anti-tumor immunity, flow cytometry analysis was used.Results The Ii expression of DCs was significantly reduced after Ii siRNA transfection. Significant in vitro anti-tumor ability was exhibited when DCs were co-transfected with Ii siRNA plus endogenous tumor antigen (P <0.05). Furthermore,tumor growth was greatly inhibited when mice were immunized with DCs transfected with Ii siRNA plus tumor antigen prior to or subsequent to tumor implantation. Flow cytometry analysis in vitro and in vivo indicated that both CD4+ and CD8+ T cells were significantly activated in the Ii siRNA group (P <0.05).Conclusion Silencing of the Ii gene of DCs may offer a potential approach to enhance DC-based anti-tumor immunity.

  20. STING activation of tumor endothelial cells initiates spontaneous and therapeutic antitumor immunity.

    Science.gov (United States)

    Demaria, Olivier; De Gassart, Aude; Coso, Sanja; Gestermann, Nicolas; Di Domizio, Jeremy; Flatz, Lukas; Gaide, Olivier; Michielin, Olivier; Hwu, Patrick; Petrova, Tatiana V; Martinon, Fabio; Modlin, Robert L; Speiser, Daniel E; Gilliet, Michel

    2015-12-15

    Spontaneous CD8 T-cell responses occur in growing tumors but are usually poorly effective. Understanding the molecular and cellular mechanisms that drive these responses is of major interest as they could be exploited to generate a more efficacious antitumor immunity. As such, stimulator of IFN genes (STING), an adaptor molecule involved in cytosolic DNA sensing, is required for the induction of antitumor CD8 T responses in mouse models of cancer. Here, we find that enforced activation of STING by intratumoral injection of cyclic dinucleotide GMP-AMP (cGAMP), potently enhanced antitumor CD8 T responses leading to growth control of injected and contralateral tumors in mouse models of melanoma and colon cancer. The ability of cGAMP to trigger antitumor immunity was further enhanced by the blockade of both PD1 and CTLA4. The STING-dependent antitumor immunity, either induced spontaneously in growing tumors or induced by intratumoral cGAMP injection was dependent on type I IFNs produced in the tumor microenvironment. In response to cGAMP injection, both in the mouse melanoma model and an ex vivo model of cultured human melanoma explants, the principal source of type I IFN was not dendritic cells, but instead endothelial cells. Similarly, endothelial cells but not dendritic cells were found to be the principal source of spontaneously induced type I IFNs in growing tumors. These data identify an unexpected role of the tumor vasculature in the initiation of CD8 T-cell antitumor immunity and demonstrate that tumor endothelial cells can be targeted for immunotherapy of melanoma.

  1. Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

    Science.gov (United States)

    Qi, Quan; Li, Rui; Li, Hui-ying; Cao, Yu-bing; Bai, Ming; Fan, Xiao-jing; Wang, Shu-yan; Zhang, Bo; Li, Shao

    2016-01-01

    Aim: Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods: The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The anti-tumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results: The nuciferine target profile was enriched with signaling pathways and biological functions, including “regulation of lipase activity”, “response to nicotine” and “regulation of cell proliferation”. Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion: By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels. PMID:27180984

  2. Anti-tumor immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  3. Evaluation of cytotoxic and anti-tumor activity of partially purified serine protease isolate from the Indian earthworm Pheretima posthuma

    Directory of Open Access Journals (Sweden)

    Mahendra Kumar Verma

    2013-11-01

    Conclusions: Exact molecular mechanism of the cytotoxic and antitumor activities is yet to be explored and currently we are working on ultra-purification and biophysical characterization of this fraction. Further investigation into the mechanism(s of cytotoxic and antitumor activities at molecular level would be useful in treatment of various classes of cancer and viral infections in future.

  4. The effect of anti-tumor necrosis factor alpha agents on postoperative anastomotic complications in Crohn's disease

    DEFF Research Database (Denmark)

    El-Hussuna, Alaa Abdul-Hussein H; Krag, Aleksander; Olaison, Gunnar

    2013-01-01

    Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications.......Patients with Crohn's disease treated with anti-tumor necrosis factor alpha agents may have an increased risk of surgical complications....

  5. Development of more efficacious Tc-99m organ imaging agents for use in nuclear medicine by analytical characterization of radiopharmaceutical mixtures. Progress report, May 1, 1981-April 30, 1982

    Energy Technology Data Exchange (ETDEWEB)

    Heineman, W.R.; Deutsch, E.A.

    1981-12-01

    The objectives of this year's research were to develop a method for rapidly determining TcO/sub 4//sup -/ in /sup 99/Mo//sup 99m/Tc generator eluates, to improve the ability to chromatographically determine individual Tc-HEDP complexes in radiopharmaceuticals, and to investigate the effects of TcO/sub 4//sup -/ concentration and electrochemical reduction on the types and relative amounts of Tc-HEDP complexes present in a radiopharmaceutical formulation. A rapid and sensitive high performance liquid chromatographic (HPLC) method for the quantitative determination of pertechnetate (TcO/sub 4//sup -/) was developed. This HPLC-based analysis may be of considerable utility in assessing the history and function of /sup 99/MO/sup 99m/Tc generators as well as in the routine analysis of reduced technetium radiopharmaceuticals for the presence of undesired TcO/sub 4//sup -/. Encouraging results were obtained on a dimethyl amine column using aqueous (NH/sub 4/)/sub 2/SO/sub 4/ as the mobile phase. The preparation of Tc(NaBH/sub 4/) HEDP radiopharmaceutical analogues using varying concentrations of total TcO/sub 4//sup -/ shows a dramatic effect in the number and distribution of Tc-HEDP complexes over a TcO/sub 4//sup -/ concentration range of 10/sup -2/ to 10/sup -8/M. These results suggest that total TcO/sub 4//sup -/ concentration is an important parameter to be considered in the preparation of a specific Tc-HEDP complex to improve skeletal imaging. The preparation of Tc(electrode) HEDP radiopharmaceutical analogues by using electrochemical reduction was explored. The resulting solutions contain Tc-HEDP complexes that are tentatively identified as being the same complexes formed by NaBH/sub 4/ reduction, although the relative concentrations of these complexes are quite different with the two modes of reduction. Thus, electrochemical reduction shows promise as a viable route to the preparation of specific Tc-HEDP complexes for improved skeletal imaging.

  6. Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized w...

  7. The application of antitumor drug-targeting models on liver cancer.

    Science.gov (United States)

    Yan, Yan; Chen, Ningbo; Wang, Yunbing; Wang, Ke

    2016-06-01

    Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future.

  8. [Research advances of anti-tumor immune response induced by pulse electric field ablation].

    Science.gov (United States)

    Cui, Guang-ying; Diao, Hong-yan

    2015-11-01

    As a novel tumor therapy, pulse electric field has shown a clinical perspective. This paper reviews the characteristics of tumor ablation by microsecond pulse and nanosecond pulse electric field, and the research advances of anti-tumor immune response induced by pulse electric field ablation. Recent researches indicate that the pulse electric field not only leads to a complete ablation of local tumor, but also stimulates a protective immune response, thereby inhibiting tumor recurrence and metastasis. These unique advantages will show an extensive clinical application in the future. However, the mechanism of anti-tumor immune response and the development of related tumor vaccine need further studies.

  9. Purification, Characterization and Antitumor Activities of a New Protein from Syngnathus acus, an Officinal Marine Fish

    OpenAIRE

    Ying Peng; Fen He; Mengyue Wang; Chunfu Wu; Jingyu Yang; Yuxiao Nie; Xiaobo Li

    2011-01-01

    Discovery and development of new antitumor agents from abundant marine fish are attracting an increasing interest. In the present study, we extracted and purified a novel antitumor protein Syngnathusin from the whole body of Syngnathus acus L., a precious marine fish traditionally used for tumors. Syngnathusin was comprised of 16 kinds of amino acids, mainly acidic amino acids. Its molecular weight was 67.3 kDa and its isoelectric point was 4.57. The N-terminal amino acid sequence of Syngnath...

  10. Antitumoral effects of vasoactive intestinal peptide in human renal cell carcinoma xenografts in athymic nude mice.

    Science.gov (United States)

    Vacas, Eva; Arenas, M Isabel; Muñoz-Moreno, Laura; Bajo, Ana M; Sánchez-Chapado, Manuel; Prieto, Juan C; Carmena, María J

    2013-08-01

    We studied antitumor effect of VIP in human renal cell carcinoma (RCC) (A498 cells xenografted in immunosuppressed mice). VIP-treated cells gave resulted in p53 upregulation and decreased nuclear β-catenin translocation and NFκB expression, MMP-2 and MMP-9 activities, VEGF levels and CD-34 expression. VIP led to a more differentiated tubular organization in tumours and less metastatic areas. Thus, VIP inhibits growth of A498-cell tumours acting on the major issues involved in RCC progression such as cell proliferation, microenvironment remodelling, tumour invasion, angiogenesis and metastatic ability. These antitumoral effects of VIP offer new therapeutical possibilities in RCC treatment.

  11. Synthesis and antitumor evaluation of fluoroquinolone C3 fused heterocycles (Ⅱ): From triazolothiadiazines to pyrazolotriazoles

    Institute of Scientific and Technical Information of China (English)

    Guo Qiang Hu; Wen Long Huang; Li Li Hou; Yong Yang; Lei Yi; Song Qiang Xie; Guo Qiang Wang; Nan Nan Duan; Tie Yao Chao; Xiao Yi Wen

    2011-01-01

    To further expand an effective modified route for the shift from an antibacterial fluoroquinolone (FQ) to an antitumor FQ, two series of title compounds based on an isostere of the FQ C3 carboxylic group with two fused heterocyclic rings, [l,2,4]triazolo[3,4-6][l,3,4]thiadiazine and pyrazolo[5,l-c][l,2,4]triazole, respectively, were designed and synthesized starting from the current antibacterial FQs, and their in vitro antitumor activity against L1210, CHO cell lines were evaluated via their respective IC50 values.

  12. Ecteinascidins. A review of the chemistry, biology and clinical utility of potent tetrahydroisoquinoline antitumor antibiotics.

    Science.gov (United States)

    Le, V H; Inai, M; Williams, R M; Kan, T

    2015-02-01

    The ecteinascidin family comprises a number of biologically active compounds, containing two to three tetrahydroisoquinoline subunits. Although isolated from marine tunicates, these compounds share a common pentacyclic core with several antimicrobial compounds found in terrestrial bacteria. Among the tetrahydroisoquinoline natural products, ecteinascidin 743 (Et-743) stands out as the most potent antitumor antibiotics that it is recently approved for treatment of a number of soft tissue sarcomas. In this article, we will review the backgrounds, the mechanism of action, the biosynthesis, and the synthetic studies of Et-743. Also, the development of Et-743 as an antitumor drug is discussed.

  13. Antitumor effect of humus extract on murine transplantable L1210 leukemia.

    Science.gov (United States)

    Kodama, Hiroshi

    2007-10-01

    Humic substances are formed during the decomposition of organic matter in humus that found in many natural environments in which organic materials and microorganisms have been present. In the present study, humus extract exhibited antitumor effect on L1210 tumor development in isogeneic DBA/2 mice with the delay of tumor formation and a significant smaller tumor mass that infer a significant increase of life span of mice. The antitumor effect was not due to direct killing of L1210 or induction of apoptosis in tumor cells by humus extract.

  14. Synthesis of sulfadimethoxine based surfactants and their evaluation as antitumor agents

    Directory of Open Access Journals (Sweden)

    Manal Mohmed Khowdiary

    2016-01-01

    Summary: The main goal of cancer therapy is to attain the maximum therapeutic damage of tumor cells in combination with a minimum concentration of the drug. This can be achieved in principle via selective antitumor preparations, the cytostatic effects of which would be restricted within tumor tissue. While 100% selectivity may be impractical, the achievement of reasonably high selectivity seems to be a feasible aim. Platinum and cobalt complex surfactants in our research affect tumor tissue at a very low concentration at values lower than their CMC values; this indicate that the sulfadimethoxine complexes merit further investigation as potential antitumor drugs.

  15. Synthesis, in vitro and in vivo antitumor activity of pyrazole-fused 23-hydroxybetulinic acid derivatives.

    Science.gov (United States)

    Zhang, Hengyuan; Zhu, Peiqing; Liu, Jie; Lin, Yan; Yao, Hequan; Jiang, Jieyun; Ye, Wencai; Wu, Xiaoming; Xu, Jinyi

    2015-02-01

    A collection of pyrazole-fused 23-hydroxybetulinic acid derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited significant antiproliferative activity. Especially compound 15e displayed the most potent activity with the IC50 values of 5.58 and 6.13μM against B16 and SF763 cancer cell lines, respectively. Furthermore, the significant in vivo antitumor activity of 15e was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

  16. The role of radiotherapy for the induction of antitumor immune responses; Die Rolle der Strahlentherapie bei der Induktion von Antitumor-Immunantworten

    Energy Technology Data Exchange (ETDEWEB)

    Multhoff, G. [Technische Univ. Muenchen, Klinikum rechts der Isar (Germany). Klinik fuer Strahlentherapie und Radiologische Onkologie, Experimentelle Radioonkologie; Helmholtz-Zentrum Muenchen (HMGU) (Germany). Klinische Kooperationsgruppe: ' Angeborene Immunantwort in der Tumorbiologie' ; Gaipl, U.S. [Universitaetsklinikum Erlangen (Germany). Strahlenklinik/Radioonkologie, Strahlen-Immunbiologie; Niedermann, G. [Universitaetsklinikum Freiburg (Germany). Klinik fuer Strahlenheilkunde, Sektion fuer Klinische und Experimentelle Strahlenbiologie

    2012-11-15

    Effective radiotherapy is aimed to control the growth of the primary carcinoma and to induce a long-term specific antitumor immune response against the primary tumor, recurrence and metastases. The contribution covers the following issues: T cells and tumor specific immune responses, dendritic cells (DCs) start adaptive immune responses, NK (natural killer) cells for HLA independent tumor control, abscopal effects of radiotherapy, combination of radiotherapy and immune therapy, radiotherapy contribution to the induction of immunogenic cell death, combinability of radiotherapy and DC activation, combinability of radiotherapy and NK cell therapy. It turns out that the combination of radio-chemotherapy and immune therapy can change the microenvironment initiating antitumor immune reactions that inhibit the recurrence risk and the development of metastases.

  17. Tumoral fibrosis effect on the radiation absorbed dose of {sup 177}Lu-Tyr{sup 3}-octreotate-gold nanoparticles and {sup 177}Lu-Tyr{sup 3}-octreotate radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Zambrano R, O. D.

    2015-07-01

    In this work was comparatively evaluated the effect of tumoral fibrosis in the radiation absorbed dose of the radiopharmaceutical {sup 177}Lu-Tyr{sup 3}-octreotate with and without gold nanoparticles. For this, was used an experimental array of tumoral fibrosis and computer models based on Monte Carlo calculations to simulate tumoral micro environments without fibrosis and with fibrosis. The computer simulation code Penelope (Penetration Energy Loss of Positron and Electrons) and MCNP (Monte Carlo N-particle Transport Code System) which are based on the Monte Carlo methodology were used to create the computer models for the simulation of the transport of particles (emitted by {sup 177}Lu) in the micro environments (without fibrosis and with fibrosis) with the purpose of calculating the radiation absorbed dose in the interstitial space and in the nucleus of cancer cells. The first computational model consisted of multiple concentric spheres (as onion shells) with the radioactive source homogeneously distributed in the shell between 5 and 10 μm in diameter which represents the internalization of the radioactive source into the cell cytoplasm as it occurs in target specific radiotherapy. The concentric spheres were useful to calculate the radiation absorbed dose in depth in the models without fibrosis and with fibrosis. Furthermore, there were constructed other computer models using two different codes that simulate the transport of radiation (Penelope and MCNP). These models consist of seven spheres that represent cancer cells (HeLa cells) of 10 μm in diameter and each one of them contain another smaller sphere in the center that represents the cell nucleus. A comparison was done of the radiation absorbed dose in the nucleus of the cells, calculated with both codes, Penelope and MCNP. The radioactive source ({sup 177}Lu) used for the simulations was given to the codes by means of a convoluted spectrum of the most important beta particles (high percentage emission

  18. The first experience of using 99mTc-Al2O3-based radiopharmaceutical for the detection of sentinel lymph nodes in cervical cancer patients

    Science.gov (United States)

    Sinilkin, I. G.; Chernov, V. I.; Lyapunov, A. Yu.; Medvedeva, A. A.; Zelchan, R. V.; Chernyshova, A. L.; Kolomiets, L. A.

    2016-08-01

    The purpose of the study was to evaluate the feasibility of using 99mTc-Al2O3-based radiopharmaceutical, a novel molecular imaging agent for sentinel lymph node detection in patients with invasive cervical cancer. The study included 23 cervical cancer patients (T1aNxMx-T2bNxMx) treated at the Tomsk Cancer Research Institute. In the 18 hours before surgery, 80 MBq of the 99mTc-Al2O3 in peritumoral injected, followed by single-photon emission computed tomography (SPECT) of the pelvis and intraoperative SLN identification. Twenty-seven SLNs were detected by SPECT, and 34 SLNs were identified by intraoperative gamma probe. The total number of identified SLNs per patient ranged from 1 to 3 (the mean number of SLNs was 1.4 per patient). The most common site for SLN detection was the external iliac region (57.2%), followed by the internal iliac (14%), obturator (14%), presacral and retrosacral regions (14%), and the parametrial region (1%). Sensitivity in detecting SLNs was 100% for intraoperative SLN identification and 79% for SPECT image.

  19. Evaluation of Acridine Orange Derivatives as DNA-Targeted Radiopharmaceuticals for Auger Therapy: Influence of the Radionuclide and Distance to DNA

    Science.gov (United States)

    Pereira, Edgar; Do Quental, Letícia; Palma, Elisa; Oliveira, Maria Cristina; Mendes, Filipa; Raposinho, Paula; Correia, Isabel; Lavrado, João; di Maria, Salvatore; Belchior, Ana; Vaz, Pedro; Santos, Isabel; Paulo, António

    2017-02-01

    A new family of 99mTc(I)- tricarbonyl complexes and 125I-heteroaromatic compounds bearing an acridine orange (AO) DNA targeting unit was evaluated for Auger therapy. Characterization of the DNA interaction, performed with the non-radioactive Re and 127I congeners, confirmed that all compounds act as DNA intercalators. Both classes of compounds induce double strand breaks (DSB) in plasmid DNA but the extent of DNA damage is strongly dependent on the linker between the Auger emitter (99mTc or 125I) and the AO moiety. The in vitro evaluation was complemented with molecular docking studies and Monte Carlo simulations of the energy deposited at the nanometric scale, which corroborated the experimental data. Two of the tested compounds, 125I-C5 and 99mTc-C3, place the corresponding radionuclide at similar distances to DNA and produce comparable DSB yields in plasmid and cellular DNA. These results provide the first evidence that 99mTc can induce DNA damage with similar efficiency to that of 125I, when both are positioned at comparable distances to the double helix. Furthermore, the high nuclear retention of 99mTc-C3 in tumoral cells suggests that 99mTc-labelled AO derivatives are more promising for the design of Auger-emitting radiopharmaceuticals than the 125I-labelled congeners.

  20. A comparative analysis of pharmacokinetics properties of diagnostic bone-seeking radiopharmaceuticals on the basis of phosphonic acids and technetium-99m

    Science.gov (United States)

    Tishchenko, V. K.; Petriev, V. M.; Smoryzanova, O. A.; Zavestovskaya, I. N.

    2017-01-01

    This work is devoted to comparative research of pharmacokinetics properties of four bone-seeking radiopharmaceuticals (RPP) on the basis of bi- tetra- and penta-phosphonic acids. Biodistribution studies were performed in intact rats after intravenous injections of 99mTc-hydroxyethylidenediphosphonic acid (99mTc-HEDP), 99mTc-oxabiphor (99mTc-OXB), 99mTc-ethylenediaminetetramethylenephosphonic acid (99mTc-EDTMP) or 99mTc-diethylenetriaminopentakis(methylphosphonic acid) (99mTc-PPA). In the structure of the HEDP contains two phosphonic groups, OENTMP and EDTMP – four phosphonic groups, PPA – five phosphonic groups. Radiochemical yield of labeled 99mTc HEDP, OENTMP, EDTMP, PPA is not less than 95%, the radiochemical impurities does not exceed 5%. The investigated compounds have high stability in vivo and selective accumulation in osseous tissue. The highest concentrations of labeled compounds is reached in 3–24 hours after their intravenous injections. The investigated compounds are rapidly excreted from blood and soft organs and tissues mainly through the urinary routes. So present study has showed that these RPP have properties, which making them promising candidates as a diagnostic pharmaceuticals of bone metastases.

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

    Directory of Open Access Journals (Sweden)

    Matthias Eder

    2014-06-01

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

  2. Study of the temperature distribution on welded thin plates of duplex steel to be used for the external clad of a cask for transportation of radiopharmaceuticals products

    Energy Technology Data Exchange (ETDEWEB)

    Betini, Evandro G.; Ceoni, Francisco C.; Mucsi, Cristiano S.; Politano, Rodolfo; Rossi, Jesualdo L., E-mail: egbetini@ipen.br, E-mail: fceoni@hotmail.com, E-mail: csmucsi@ipen.br, E-mail: politano@ipen.br, E-mail: jelrossi@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Orlando, Marcos T.D., E-mail: mtdorlando@gmail.com [Universidade Federal do Espirito Santo (CCE/DFIS/UFES), Vitoria, ES (Brazil). Centro de Ciencias Exatas. Departamento de Fisica

    2015-07-01

    The clad material for a proprietary transport device for radiopharmaceutical products is the main focus of the present work. The production of {sup 99}Mo-{sup 99m}Tc transport cask requires a receptacle or cask where the UNS S32304 duplex steel sheet has shown that it meets high demands as the required mechanical strength and the spread of impact or shock waves mitigation. This work reports the experimental efforts in recording the thermal distribution on autogenous thin plates of UNS S32304 steel during welding. The UNS S32304 duplex steel is the most probable candidate for the external clad of the containment package for the transport of radioactive substances so it is highly relevant the understanding of all its physical parameters and its behavior under the thermal cycle imposed by a welding process. For the welding of the UNS S32304 autogenous plates the GTAW (gas tungsten arc welding) process was used with a pure argon arc protection atmosphere in order to simulate a butt joint weld on a thin duplex steel plate without filler metal. The thermal cycles were recorded by means of K-type thermocouples embedded by electrical spot welding near the weld region and connected to a multi-channel data acquisition system. The obtained results validate the reliability of the experimental apparatus for the future complete analysis of the welding experiment and further comparison to numerical analysis. (author)

  3. Snake venoms components with antitumor activity in murine melanoma cells; Componentes derivados de venenos de serpentes com acao antitumoral em celulas de melanoma murino

    Energy Technology Data Exchange (ETDEWEB)

    Queiroz, Rodrigo Guimaraes

    2012-07-01

    Despite the constant advances in the treatment of cancer, this disease remains one of the main causes of mortality worldwide. So, the development of new treatment modalities is imperative. Snake venom causes a variety of biological effects because they constitute a complex mixture of substances as disintegrins, proteases (serine and metalo), phospholipases A2, L-amino acid oxidases and others. The goal of the present work is to evaluate a anti-tumor activity of some snake venoms fractions. There are several studies of components derived from snake venoms with this kind of activity. After fractionation of snake venoms of the families Viperidae and Elapidae, the fractions were assayed towards murine melanoma cell line B16-F10 and fibroblasts L929. The results showed that the fractions of venom of the snake Notechis ater niger had higher specificity and potential antitumor activity on B16-F10 cell line than the other studied venoms. Since the components of this venom are not explored yet coupled with the potential activity showed in this work, we decided to choose this venom to develop further studies. The cytotoxic fractions were evaluated to identify and characterize the components that showed antitumoral activity. Western blot assays and zymography suggests that these proteins do not belong to the class of metallo and serine proteinases. (author)

  4. Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity.

    Science.gov (United States)

    Miyashita, Michiko; Sadzuka, Yasuyuki

    2013-03-01

    As malignant neoplasm is a major public health problem, there is a need for the development of a novel modulator that enhances antitumor activity and reduces adverse reactions to antitumor agents. In this study, the effects of some volatile oil components in Humulus lupulus on doxorubicin (DOX) permeability in tumor cells and DOX-induced antitumor activity were examined. In vitro, DOX levels in tumor cells by combined linalool as its component significantly increased in the DOX influx system, and the increased effect by linalool on DOX cytotoxicity was shown. In vivo, the combination of DOX with linalool significantly decreased tumor weight compared with that of DOX alone treated group. The promotion of DOX influx level by combined linalool did not depend on energy, whereas it was suppressed by the absence of Na(+). This promoting effect was suppressed by the presence of S-(4-nitrobenzyl)-6-thioinosine and inhibited dependently on phlorizin concentration. It is considered that linalool promoted DOX influx in tumor cells because of its action on DOX transport through concentrative Na(+)-dependent nucleoside transporter 3, which increased DOX concentration in tumor cells and thus enhanced the antitumor activity of DOX. Therefore, linalool as a food component is anticipated to be an effective DOX modulator.

  5. Mycalamides, pederin and psymberin as natural carbohydrates and potential antitumor agents: past and future perspectives.

    Science.gov (United States)

    Witczak, Zbigniew J; Rampulla, Ricky M; Bommareddy, Ajay

    2012-12-01

    The mycalamide class of potent antiviral and antitumor natural compounds originally isolated from marine sponges in 1988 is a new interdisciplinary approach to molecular recognition. We review new synthetic approaches to this new family of natural products with remarkable biological activity. Some biological evaluation data are compiled and compared to other structurally similar molecular targets.

  6. Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication.

    Science.gov (United States)

    Chaoul, Nada; Fayolle, Catherine; Desrues, Belinda; Oberkampf, Marine; Tang, Alexandre; Ladant, Daniel; Leclerc, Claude

    2015-08-15

    The metabolic sensor mTOR broadly regulates cell growth and division in cancer cells, leading to a significant focus on studies of rapamycin and its analogues as candidate anticancer drugs. However, mTOR inhibitors have failed to produce useful clinical efficacy, potentially because mTOR is also critical in T cells implicated in immunosurveillance. Indeed, recent studies using rapamycin have demonstrated the important role of mTOR in differentiation and induction of the CD8+ memory in T-cell responses associated with antitumor properties. In this study, we demonstrate that rapamycin harms antitumor immune responses mediated by T cells in the setting of cancer vaccine therapy. Specifically, we analyzed how rapamycin affects the antitumor efficacy of a human papilloma virus E7 peptide vaccine (CyaA-E7) capable of eradicating tumors in the TC-1 mouse model of cervical cancer. In animals vaccinated with CyaA-E7, rapamycin administration completely abolished recruitment of CD8+ T cells into TC-1 tumors along with the ability of the vaccine to reduce infiltration of T regulatory cells and myeloid-derived suppressor cells. Moreover, rapamycin completely abolished vaccine-induced cytotoxic T-cell responses and therapeutic activity. Taken together, our results demonstrate the powerful effects of mTOR inhibition in abolishing T-cell-mediated antitumor immune responses essential for the therapeutic efficacy of cancer vaccines.

  7. Colloidally stable surface-modified iron oxide nanoparticles: Preparation, characterization and anti-tumor activity

    Energy Technology Data Exchange (ETDEWEB)

    Macková, Hana [Institute of Macromolecular Chemistry, AS CR, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Horák, Daniel, E-mail: horak@imc.cas.cz [Institute of Macromolecular Chemistry, AS CR, Heyrovsky Sq. 2, 162 06 Prague 6 (Czech Republic); Donchenko, Georgiy Viktorovich; Andriyaka, Vadim Ivanovich; Palyvoda, Olga Mikhailovna; Chernishov, Vladimir Ivanovich [Palladin Institute of Biochemistry, NASU, 9 Leontovich St., 01601 Kiev (Ukraine); Chekhun, Vasyl Fedorovich; Todor, Igor Nikolaevich [R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, 45 Vasylkivska St., 03022 Kiev (Ukraine); Kuzmenko, Oleksandr Ivanovich [Palladin Institute of Biochemistry, NASU, 9 Leontovich St., 01601 Kiev (Ukraine)

    2015-04-15

    Maghemite (γ-Fe{sub 2}O{sub 3}) nanoparticles were obtained by co-precipitation of Fe(II) and Fe(III) chlorides and subsequent oxidation with sodium hypochlorite and coated with poly(N,N-dimethylacrylamide-co-acrylic acid) [P(DMAAm-AA)]. They were characterized by a range of methods including transmission electron microscopy (TEM), elemental analysis, dynamic light scattering (DLS) and zeta potential measurements. The effect of superparamagnetic P(DMAAm-AA)-γ-Fe{sub 2}O{sub 3} nanoparticles on oxidation of blood lipids, glutathione and proteins in blood serum was detected using 2-thiobarbituric acid and the ThioGlo fluorophore. Finally, mice received magnetic nanoparticles administered per os and the antitumor activity of the particles was tested on Lewis lung carcinoma (LLC) in male mice line C57BL/6 as an experimental in vivo metastatic tumor model; the tumor size was measured and the number of metastases in lungs was determined. Surface-modified γ-Fe{sub 2}O{sub 3} nanoparticles showed higher antitumor and antimetastatic activities than commercial CuFe{sub 2}O{sub 4} particles and the conventional antitumor agent cisplatin. - Highlights: • Maghemite nanoparticles were prepared and characterized. • Poly(N,N-dimethylacrylamide-co-acrylic acid) coating was synthetized. • Blood lipid, glutathione and protein peroxidation/oxidation was determined. • Antitumor effect of coated particles on Lewis lung carcinoma in mice was observed.

  8. Medicinal Plants and Other Living Organisms with Antitumor Potential against Lung Cancer

    Directory of Open Access Journals (Sweden)

    Luara de Sousa Monteiro

    2014-01-01

    Full Text Available Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer.

  9. QSAR analysis for some β-carboline derivatives as anti-tumor

    Directory of Open Access Journals (Sweden)

    Ravindra Kumar Chourasiya

    2016-09-01

    Full Text Available β-Carboline moieties are important structural subunits which occur as components of many biologically interesting molecules for antitumor activity. Quantitative structure–activity relationship (QSAR studies have been performed on β-carboline derivatives to explore the structural necessities for antitumor activity. 3D QSAR studies were done using V-Life Sciences MDS 3.0 drug designing module to explain the structural requirements for the anti-tumor activity. The 3D-QSAR was performed using the Step Wise K Nearest Neighbour Molecular Field Analysis [(SW kNN MFA] technique with the partial least-square (PLS method on a database. Obtained best 3D-QSAR model having high predictive ability with q2 = 0.743, r2 = 0.721, pred_r2 = 0.708 and standard error = 0.346, explaining the majority of the variance in the data with partial least square (PLS components. The results of the present study may be useful on the designing of more potent compounds as antitumor drugs.

  10. PLASMID VACCINE ENCODING HN GENE FROM NEWCASTLE DISEASE VIRUS HAS MARKED ANTITUMORAL EFFECT IN VITRO

    Institute of Scientific and Technical Information of China (English)

    薛立娟; 金宁一; 龚伟; 王宏伟; 李萍

    2003-01-01

    Objective: To explore the antitumor effects of hemaagglutinin-neuraminase gene (HN gene) from Newcastle disease virus. Methods: Plasmid vaccine of pIRHN was constructed and transfected into HeLa cells. The expression of HN was analyzed by Western blot analysis, and the mode of cell death was detected by fluorescence microscope, gel electrophoresis and TUNEL assay and the expression of p53 and bcl-2 was also analyzed in transfected Hela cells. The effect of pIRHN on sialic acid contents in the Hela cell was examined. Results: pIRHN nucleic acid vaccines could be expressed in eukaryotic cell. pIRHN could induce apoptosis after HeLa cells were transfected. The effect of antitumor responses of pIRHN was correlated with the contents of sialic acid in tumor cells, and there was no prominent evidence for the relatedness of the antitumor effect with the expression of p53 and bcl-2. Conclusion: pIRHN may become a new antitumor biological agent.

  11. MAPLE-based method to obtain biodegradable hybrid polymeric thin films with embedded antitumoral agents.

    Science.gov (United States)

    Dinca, Valentina; Florian, Paula E; Sima, Livia E; Rusen, Laurentiu; Constantinescu, Catalin; Evans, Robert W; Dinescu, Maria; Roseanu, Anca

    2014-02-01

    In this work, antitumor compounds, lactoferrin [recombinant iron-free (Apo-rLf)], cisplatin (Cis) or their combination were embedded within a biodegradable polycaprolactone (PCL) polymer thin film, by a modified approach of a laser-based technique, matrix-assisted pulsed laser evaporation (MAPLE). The structural and morphological properties of the deposited hybrid films were analyzed by Fourier-transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). The in vitro effect on the cells' morphology and proliferation of murine melanoma B16-F10 cells was investigated and correlated with the films' surface chemistry and topography. Biological assays revealed decreased viability and proliferation, lower adherence, and morphological modifications in the case of melanoma cells cultured on both Apo-rLf and Cis thin films. The antitumor effect was enhanced by deposition of Apo-rLf with Cis within the same film. The unique capability of the new approach, based on MAPLE, to embed antitumor active factors within a biodegradable matrix for obtaining novel biodegradable hybrid platform with increased antitumor efficiency has been demonstrated.

  12. Stereospecific Synthesis of the Skeleton of the Antitumor Marine Natural Product Et-743

    Institute of Scientific and Technical Information of China (English)

    LIU Zhan-Zhu; TANG Ye-Feng; WANG Ye; CHEN Shi-Zhi

    2003-01-01

    @@ Ecteinascidin 743 (Et-743) is an exceedingly potent antitumor agent isolated from the marine tunicate Ecteinascidia turbinate. As its structurally simplified version, Phthalascidin was found to retain the cytotoxicity of the natural product. Their novel structures, impressive biological activities and difficult availabilities conspire to render the attractive targets for total synthesis.

  13. Antitumor effects of traditional Chinese medicine targeting the cellular apoptotic pathway

    Directory of Open Access Journals (Sweden)

    Xu HL

    2015-05-01

    Full Text Available Huanli Xu,1 Xin Zhao,2 Xiaohui Liu,1 Pingxiang Xu,1 Keming Zhang,2 Xiukun Lin11Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, 2Department of Hepatobiliary Surgery, 302 Hospital of Chinese People’s Liberation Army, Beijing, People’s Republic of ChinaAbstract: Defects in apoptosis are common phenomena in many types of cancer and are also a critical step in tumorigenesis. Targeting the apoptotic pathway has been considered an intriguing strategy for cancer therapy. Traditional Chinese medicine (TCM has been used in the People’s Republic of China for thousands of years, and many of the medicines have been confirmed to be effective in the treatment of a number of tumors. With increasing cancer rates worldwide, the antitumor effects of TCMs have attracted more and more attention globally. Many of the TCMs have been shown to have antitumor activity through multiple targets, and apoptosis pathway-related targets have been extensively studied and defined to be promising. This review focuses on several antitumor TCMs, especially those with clinical efficacy, based on their effects on the apoptotic signaling pathway. The problems with and prospects of development of TCMs as anticancer agents are also presented.Keywords: traditional Chinese medicine, antitumor effects, apoptotic pathway

  14. Function of Helper T Cells in the Memory CTL-mediated Anti-tumor Immunity

    Institute of Scientific and Technical Information of China (English)

    高丰光; GermainJ.P.Fernendo; 刘文军

    2004-01-01

    Abstract To investigate the role of CD4+ helper T (Th) cells in the memory CTL-mediated anti-tumor immunity, the RAG-1 gene knock out mice were adoptively transferred with OT-1 cells to generate the memory CTL, the C57B1/6 mice immunized with the epitope peptide of OVA specific Th cells and with different adjuvants were adopfively transferred with these memory-CTLs, and then the animals were challenged with tumor cells EGT. It was found that although the simple immunization of mice with the epitope peptide of the OVA specific Th cells could generate more effect CTL, but this effect was not so strong enough to resist completely the challenges with tumor cells. Nevertheless, the memory CTL-mediated anti-tumor immune effect required the helps of Th1 and Th2 cells. The cross-regulation between Thl and Th2 cells seemed to be beneficial for the host to generate more effector CTL for mounting an efficient anti-tumor response. It concluded that the interaction between Thl and Th2 cells might be more important than the single subset of Th cells in the memory CTL-mediated anti-tumor immune response. More attention should be paid in this regard for the future studies.

  15. ER Stress Sensor XBP1 Controls Anti-tumor Immunity by Disrupting Dendritic Cell Homeostasis.

    Science.gov (United States)

    Cubillos-Ruiz, Juan R; Silberman, Pedro C; Rutkowski, Melanie R; Chopra, Sahil; Perales-Puchalt, Alfredo; Song, Minkyung; Zhang, Sheng; Bettigole, Sarah E; Gupta, Divya; Holcomb, Kevin; Ellenson, Lora H; Caputo, Thomas; Lee, Ann-Hwee; Conejo-Garcia, Jose R; Glimcher, Laurie H

    2015-06-18

    Dendritic cells (DCs) are required to initiate and sustain T cell-dependent anti-cancer immunity. However, tumors often evade immune control by crippling normal DC function. The endoplasmic reticulum (ER) stress response factor XBP1 promotes intrinsic tumor growth directly, but whether it also regulates the host anti-tumor immune response is not known. Here we show that constitutive activation of XBP1 in tumor-associated DCs (tDCs) drives ovarian cancer (OvCa) progression by blunting anti-tumor immunity. XBP1 activation, fueled by lipid peroxidation byproducts, induced a triglyceride biosynthetic program in tDCs leading to abnormal lipid accumulation and subsequent inhibition of tDC capacity to support anti-tumor T cells. Accordingly, DC-specific XBP1 deletion or selective nanoparticle-mediated XBP1 silencing in tDCs restored their immunostimulatory activity in situ and extended survival by evoking protective type 1 anti-tumor responses. Targeting the ER stress response should concomitantly inhibit tumor growth and enhance anti-cancer immunity, thus offering a unique approach to cancer immunotherapy.

  16. Antitumoral materials with regenerative function obtained using a layer-by-layer technique

    Directory of Open Access Journals (Sweden)

    Ficai D

    2015-03-01

    Full Text Available Denisa Ficai,1 Maria Sonmez,1,2 Madalina Georgiana Albu,2 Dan Eduard Mihaiescu,1 Anton Ficai,1 Coralia Bleotu3 1Faculty of Applied Chemistry and Material Science, Politehnica University of Bucharest, 2Leather and Footwear Research Institute, National Research and Development Institute for Textiles and Leather, 3Stefan S Nicolau Institute of Virology, Romanian Academy, Bucharest, Romania Abstract: A layer-by layer technique was successfully used to obtain collagen/hydroxyapatite-magnetite-cisplatin (COLL/HAn-Fe3O4-CisPt, n=1–7 composite materials with a variable content of hydroxyapatite intended for use in the treatment of bone cancer. The main advantages of this system are the possibility of controlling the rate of delivery of cytostatic agents, the presence of collagen and hydroxyapatite to ensure more rapid healing of the injured bone tissue, and the potential for magnetite to be a passive antitumoral component that can be activated when an appropriate external electromagnetic field is applied. In vitro cytotoxicity assays performed on the COLL/HAn-Fe3O4-CisPt materials obtained using a layer-by layer method confirmed their antitumoral activity. Samples with a higher content of hydroxyapatite had more antitumoral activity because of their better absorption of cisplatin and consequently a higher amount of cisplatin being present in the matrices. Keywords: multifunctional materials, antitumoral activity, scaffold, bone grafts

  17. Genome Sequence of Streptomyces olindensis DAUFPE 5622, Producer of the Antitumoral Anthracycline Cosmomycin D

    Science.gov (United States)

    Rojas, Juan D.; Starcevic, Antonio; Baranas̆ić, Damir; Ferreira-Torres, Maria A.; Contreras, Camilo A.; Garrido, Leandro M.; Araújo, Welington L.; de Souza, Robson F.; Zucko, Jurica; Hranueli, Daslav; Long, Paul F.; Cullum, John

    2014-01-01

    Streptomyces olindensis DAUFPE 5622, which was isolated from a Brazilian soil sample, produces the antitumor anthracycline cosmomycin D. The genome sequence is 9.4 Mb in length, with a G+C content of 71%. Thirty-four putative secondary metabolite biosynthetic gene clusters were identified, including the cosmomycin D cluster. PMID:24970824

  18. Comparison of the fibronectin-binding ability and antitumor efficacy of various mycobacteria.

    Science.gov (United States)

    Hudson, M A; Ritchey, J K; Catalona, W J; Brown, E J; Ratliff, T L

    1990-07-01

    Although the mechanism by which Bacillus Calmette-Guerin (BCG) exerts an antitumor effect on superficial bladder tumors is not fully understood, recent evidence has implicated binding of BCG organisms to fibronectin (FN) as requisite for this antitumor efficacy. Various substrains of BCG and other mycobacteria were tested in vitro for their relative capacities to bind both matrix and soluble FN. A substrain of Mycobacterium kansasii, designated the "high-binding strain," was found to bind FN more readily (P less than 0.05) in in vitro studies, when compared to commercially available substrains of BCG (Tice, Connaught, and Armand Frappier). The binding by the three commercial strains of BCG to FN in vitro appeared to be equivalent. The high-binding strain was further demonstrated to attach more readily in vivo to the acutely injured murine bladder (P less than 0.005) than the Armand Frappier substrain. Finally, using the MB49 murine bladder tumor model, an enhanced antitumor effect (P less than 0.05) was noted in mice treated with intravesical high-binding strain, in comparison to the Armand Frappier substrain, during five weekly treatments. It appears not only that the commercial substrains of BCG bind FN in an equivalent manner but also that the relative binding capacities of the substrains correlate directly with antitumor activity. A substrain of M. kansasii appears to have been identified which may prove more clinically effective than the currently available strains of BCG.

  19. Antitumor activity and antioxident role of Bauhinia racemosa against Ehrlich ascites carcinoma in Swiss albino mice

    Institute of Scientific and Technical Information of China (English)

    Malaya GUPTA; Upal Kanti MAZUMDER; Ramanathan Sambath KUMAR; Thangavel Siva KUMAR

    2004-01-01

    AIM: To study the antitumor effect and antioxidant role of Bauhinia racemosa. METHODS: Antitumor activity and antioxidant status of methanol extract (50, 100, and 200 mg/kg) of Bauhinia racemosa stem bark was evaluated against Ehrlich ascites carcinoma (EAC) tumor in mice. Acute and short-term toxicity studies were performed initially in order to ascertain the safety of methanol extract of Bauhinia racemosa (MEBR). After 24 h of tumor inoculation, the extract was administered daily for 14 d. After administration of the last dose followed by 18 h fasting, mice were then sacrificed for observation of antitumor activity. The effect of MEBR on the growth of transplantable murine tumor, life span of EAC bearing hosts and simultaneous alterations in the hematological profile and liver biochemical parameters (lipid peroxidation, antioxidant enzymes) were estimated. RESULTS: The MEBR showed decrease in tumor volume, packed cell volume and viable cell count, and increased the nonviable cell count and mean survival time thereby increasing life span of EAC tumor bearing mice. Hematological profile reverted to more or less normal levels in extract treated mice. Treatment with MEBR decreased the levels of lipid peroxidation and increased the levels of glutathione, superoxide dismutase and catalase. CONCLUSION: The methanol extract of Bauhinia racemosa stem bark exhibited antitumor effect by modulating lipid peroxidation and augmenting antioxidant defense system in EAC bearing mice.

  20. Curcuma increasing antitumor effect of Rhizoma paridis saponins through absorptive enhancement of paridis saponins.

    Science.gov (United States)

    Man, Shuli; Li, Yuanyuan; Fan, Wei; Gao, Wenyuan; Liu, Zhen; Li, Nan; Zhang, Yao; Liu, Changxiao

    2013-09-15

    Rhizoma paridis saponins (RPS) played a good antitumor role in many clinical applications. However, low oral bioavailability limited its application. In this research, water extract of Curcuma (CW) significantly increased antitumor effect of Rhizoma paridis saponins (RPS). GC-MS was used to identify its polar composition. HPLC was applied for determination of the content of curcuminoids in CW. As a result, 47 analytes with 0.65% of curcuminoids were identified in CW. According to the in vivo anti-tumor data, the best proportion of curcuminoids in CW with RPS was 16:500 (w/w). Using this ratio, curcuminoids significantly increased absorption of RPS in the everted rat duodenum sac system. In addition, curcuminoids decreased the promotion of RPS on rhodamine 123 efflux. The effect of curcuminoids was similar to that of the P-gp inhibitor, cyclosporin A in combination with RPS. In conclusion, drug combination of water extract of Curcuma with RPS was a good method to increase the antitumor effect of RPS. This combination would be a potent anticancer agent used in the prospective application.

  1. Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn.

    Science.gov (United States)

    Wu, Yuanhao; He, Guanping; Zhang, Yu; Liu, Yang; Li, Mei; Wang, Xiaolan; Li, Nan; Li, Kang; Zheng, Guan; Zheng, Yufeng; Yin, Qingshui

    2016-02-24

    In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg-1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis.

  2. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility.

    NARCIS (Netherlands)

    Horssen, R. van; Hagen, T.L.M. ten; Eggermont, A.M.M.

    2006-01-01

    Tumor necrosis factor alpha (TNF-alpha), isolated 30 years ago, is a multifunctional cytokine playing a key role in apoptosis and cell survival as well as in inflammation and immunity. Although named for its antitumor properties, TNF has been implicated in a wide spectrum of other diseases. The curr

  3. Agaricus subrufescens: substratum nitrogen concentration and mycelial extraction method on antitumor activity

    Directory of Open Access Journals (Sweden)

    MÍRIA B.D. BERTÉLI

    Full Text Available ABSTRACT Antitumor activity of Agaricus subrufescens has been shown on vegetative mycelium and basidiocarp. However, few studies have assessed the effect of A. subrufescens cultivation conditions and extraction methods on antitumor activity. This study evaluated the effect of nitrogen concentration on the cultivation medium of A. subrufescens and the extraction method of mycelial antineoplastic actives against sarcoma 180 cells implanted in mice. Two nitrogen sources (isolated soybean protein and NaNO3 and 10 nitrogen concentrations (0.25 to 8.0 g/L were used. Dried mycelium extract was obtained by hot water infusion (1:10 mass:volume; 90 °C or by aqueous mixture (1:10 mass:volume, ambient temperature in ultrapure water. The doses were administered daily by gavage to mice implanted with sarcoma 180 cells. Isolated soy protein is more efficient to mycelial biomass production than NaNO3. The mycelial biomass production increases when the cultivation medium is added with high nitrogen concentrations as well as the splenic index and the antitumor activity of the moistened mycelial powder. Hot water extract is more effective than the moistened mycelial powder to reduce tumor. The antitumor activity of hot water mycelial extract is similar to the one of basidiocarps, presenting lower metabolic demand on the spleen, keeping blood parameters normal and promoting animal wellness.

  4. Use of thin layer chromatography for the determination of radiochemical purity of radiopharmaceuticals in nuclear medicine services of Paraiba and Rio Grande do Norte, Brazil; Utilizacao da cromatografia em camada delgada para determinacao da pureza radioquimica de radiofarmacos em servicos de medicina nuclear da Paraiba e Rio Grande do Norte, Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, W.G.; Santos, P.A.L.; Lima, F.R.A. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Programa de Pos-Graduacao em Tecnologia Energetica; Lima, F.F., E-mail: wellington.gandrade@gmail.com [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil)

    2012-07-01

    The paper chromatography and the thin layer chromatography are separation techniques in which the radioactive components migrate because of their affinity with the eluent (mobile phase) or stationary phase, respectively. In radiopharmaceuticals labeled with {sup 99m}Tc, besides its own radiopharmaceutical, {sup 99m}TcO{sup 4-} free and TcO{sub 2} can be identified and quantified. The evaluation of radiochemical purity of radiopharmaceuticals is essential to produce images free of artifacts as well as avoid unnecessary absorbed dose to the patient. Once they are managed in humans it is important and necessary that they undergo to strict quality control. Because of this, ANVISA in its 'Resolucao da Diretoria Colegiada (RDC) 38 of June 4th, 2008 states the obligation of performing a minimum of tests in nuclear medicine services routine prior to human administration. This work evaluated, by the method of thin layer chromatography (TLC), radiochemical purity, determined the pH of the radiopharmaceutical DEXTRAN- 500, DMSA, DTPA, PHYTATE, MDP, MIBI and Sn-Col used in nuclear medicine services in the states of Paraiba and Rio Grande do Norte - Brazil. The results show that the use of thin layer chromatography (TLC) as a standard method in routine of nuclear medicine services is possible, because it provides important data for the evaluation of radiochemical purity, allowing the exclusion of a radiopharmaceutical poorly marked. (author)

  5. Silybin-mediated inhibition of Notch signaling exerts antitumor activity in human hepatocellular carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Song Zhang

    Full Text Available Hepatocellular carcinoma (HCC is a global health burden that is associated with limited treatment options and poor patient prognoses. Silybin (SIL, an antioxidant derived from the milk thistle plant (Silybum marianum, has been reported to exert hepatoprotective and antitumorigenic effects both in vitro and in vivo. While SIL has been shown to have potent antitumor activity against various types of cancer, including HCC, the molecular mechanisms underlying the effects of SIL remain largely unknown. The Notch signaling pathway plays crucial roles in tumorigenesis and immune development. In the present study, we assessed the antitumor activity of SIL in human HCC HepG2 cells in vitro and in vivo and explored the roles of the Notch pathway and of the apoptosis-related signaling pathway on the activity of SIL. SIL treatment resulted in a dose- and time-dependent inhibition of HCC cell viability. Additionally, SIL exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration, intracellular glutathione (GSH levels and total antioxidant capability (T-AOC but also by increases in the apoptotic index, caspase3 activity, and reactive oxygen species (ROS. Furthermore, SIL treatment decreased the expression of the Notch1 intracellular domain (NICD, RBP-Jκ, and Hes1 proteins, upregulated the apoptosis pathway-related protein Bax, and downregulated Bcl2, survivin, and cyclin D1. Notch1 siRNA (in vitro or DAPT (a known Notch1 inhibitor, in vivo further enhanced the antitumor activity of SIL, and recombinant Jagged1 protein (a known Notch ligand in vitro attenuated the antitumor activity of SIL. Taken together, these data indicate that SIL is a potent inhibitor of HCC cell growth that targets the Notch signaling pathway and suggest that the inhibition of Notch signaling may be a novel therapeutic intervention for HCC.

  6. The in vitro sustained release profile and antitumor effect of etoposide-layered double hydroxide nanohybrids

    Directory of Open Access Journals (Sweden)

    Qin LL

    2013-05-01

    Full Text Available Lili Qin,1 Mei Wang,2 Rongrong Zhu,3 Songhui You,1 Ping Zhou,1 Shilong Wang31Department of Physical Education, Tongji University, Shanghai, People's Republic of China; 2Department of Chemistry, Tongji University, Shanghai, People's Republic of China; 3School of Life Science and Technology, Tongji University, Shanghai, People's Republic of ChinaAbstract: Magnesium-aluminum layered double hydroxides intercalated with antitumor drug etoposide (VP16 were prepared for the first time using a two-step procedure. The X-ray powder diffraction data suggested the intercalation of VP16 into layers with the increased basal spacing from 0.84–1.18 nm was successful. Then, it was characterized by X-ray powder diffraction, Fourier transform infrared spectroscopy, thermogravimetry and differential thermal analysis, and transmission electron microscopy. The prepared nanoparticles, VP16-LDH, showed an average diameter of 62.5 nm with a zeta potential of 20.5 mV. Evaluation of the buffering effect of VP16-LDH indicated that the nanohybrids were ideal for administration of the drugs that treat human stomach irritation. The loading amount of intercalated VP16 was 21.94% and possessed a profile of sustained release. The mechanism of VP16-LDH release in the phosphate buffered saline solution at pH 7.4 is likely controlled by the diffusion of VP16 anions from inside to the surface of LDH particles. The in vitro cytotoxicity and antitumor assays indicated that VP16-LDH hybrids were less toxic to GES-1 cells while exhibiting better antitumor efficacy on MKN45 and SGC-7901 cells. These results imply that VP16-LDH is a potential antitumor drug for a broad range of gastric cancer therapeutic applications.Keywords: layered double hydroxides, etoposide, drug delivery, antitumor effect, sustained release

  7. Tumor-altered dendritic cell function: implications for anti-tumor immunity

    Directory of Open Access Journals (Sweden)

    Kristian Michael Hargadon

    2013-07-01

    Full Text Available Dendritic cells are key regulators of both innate and adaptive immunity, and the array of immunoregulatory functions exhibited by these cells is dictated by their differentiation, maturation, and activation status. Although a major role for these cells in the induction of immunity to pathogens has long been appreciated, data accumulated over the last several years has demonstrated that DC are also critical regulators of anti-tumor immune responses. However, despite the potential for stimulation of robust anti-tumor immunity by DC, tumor-altered DC function has been observed in many cancer patients and tumor-bearing animals and is often associated with tumor immune escape. Such dysfunction has significant implications for both the induction of natural anti-tumor immune responses as well as the efficacy of immunotherapeutic strategies that target endogenous DC in situ or that employ exogenous DC as part of anti-cancer immunization maneuvers. In this review, the major types of tumor-altered DC function will be described, with emphasis on recent insights into the mechanistic bases for the inhibition of DC differentiation from hematopoietic precursors, the altered programming of DC precursors to differentiate into myeloid-derived suppressor cells or tumor-associated macrophages, the suppression of DC maturation and activation, and the induction of immunoregulatory DC by tumors, tumor-derived factors, and tumor-associated cells within the milieu of the tumor microenvironment. The impact of these tumor-altered cells on the quality of the overall anti-tumor immune response will also be discussed. Finally, this review will also highlight questions concerning tumor-altered DC function that remain unanswered, and it will address factors that have limited advances in the study of this phenomenon in order to focus future research efforts in the field on identifying strategies for interfering with tumor-associated DC dysfunction and improving DC-mediated anti-tumor

  8. Antitumor activity of Bulgarian herb Tribulus terrestris L. on human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Svetla Angelova

    2013-01-01

    Full Text Available Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction of Bulgarian Tribulus terrestris L. on human breast cancer (MCF7 and normal (MCF10A cell lines. Antitumor effect was established by МТТ cell viability assay and assessment of apoptotic potential was done through analysis of genomic integrity (DNA fragmentation assay and analysis of morphological cell changes (Fluorescence microscopy. The results showed that total extract of the herb has a marked dose-dependent inhibitory effect on viability of MCF7 cells (half maximal inhibitory concentration is 15 μg/ml. Cell viability of MCF10A was moderately decreased without visible dose-dependent effect. The saponin fraction has increased inhibitory effect on breast cancer cells compared to total extract. Morphological changes and DNA fragmentation were observed as markers for early and late apoptosis predominantly in tumor cells after treatment. Apoptotic processes were intensified with the increase of treatment duration.The obtained results are the first showing selective antitumor activity of Bulgarian Tribulus terrestris L. on human cancer cells in vitro. Apoptotic processes are involved in the antitumor mechanisms induced by the herb. This results give directions for future investigations concerning detailed assessment of its pharmacological potential.

  9. Study on fluorouracil–chitosan nanoparticle preparation and its antitumor effect

    Directory of Open Access Journals (Sweden)

    Gaimin Chen

    2016-05-01

    Full Text Available To successfully prepare fluorouracil–chitosan nanoparticles, and further analyze its anti-tumor activity mechanism, this paper makes a comprehensive study of existing preparation prescription and makes a detailed analysis of fluorouracil–chitosan in vitro release and pharmacodynamic behavior of animals. Two-step synthesis method is adopted to prepare 5-FU–CS–mPEG prodrugs, and infrared, 1H NMR and differential thermal analysis are adopted to analyze characterization synthetic products of prepared drugs. To ensure clinical efficacy of prepared drugs, UV spectrophotometry is adopted for determination of drug loading capacity of prepared drugs, transmission electron microscopy is adopted to observe the appearance, dynamic dialysis method is used to observe in vitro drug release of prepared drugs and fitting of various release models is done. Anti-tumor effect is studied via level of animal pharmacodynamics. After the end of the experiment, tumor inhibition rate, spleen index and thymus index of drugs are calculated. Experimental results show that the prepared drugs are qualified in terms of regular shape, dispersion, drug content, etc. Animal pharmacodynamics experiments have shown that concentration level of drug loading capacity of prepared drugs has a direct impact on anti-tumor rate. The higher the concentration, the higher the anti-tumor rate. Results of pathological tissue sections of mice show that the prepared drugs cause varying degrees of damage to receptor cells, resulting in cell necrosis or apoptosis problem. It can thus be concluded that ion gel method is an effective method to prepare drug-loading nanoparticles, with prepared nanoparticles evenly distributed in regular shape which demonstrate good slow-release characteristics in receptor vitro and vivo. At the same time, after completion of drug preparation, relatively strong anti-tumor activity can be generated for the receptor, so this mode of preparation enjoys broad

  10. Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis

    Directory of Open Access Journals (Sweden)

    Lindhofer Horst

    2009-02-01

    Full Text Available Abstract Peritoneal carcinomatosis (PC from epithelial tumors is a fatal diagnosis without efficient treatment. Trifunctional antibodies (trAb are novel therapeutic approaches leading to a concerted anti-tumor activity resulting in tumor cell destruction. In addition, preclinical data in mouse tumor models demonstrated the induction of long lasting tumor immunity after treatment with trAb. We describe the induction of anti-tumor specific T-lymphocytes after intraperitoneal administration of trAb in patients with PC. 9 patients with progressive PC from gastric (n = 6 and ovarian cancer (n = 2, and cancer of unknown primary (n = 1 received 3 escalating doses of trAb after surgery and/or ineffective chemotherapy. The trAb EpCAM × CD3 (10, 20, 40 μg or HER2/neu × CD3 (10, 40, 80 μg were applicated by intraperitoneal infusion. Four weeks after the last trAb application, all patients were restimulated by subdermal injection of trAb + autologous PBMC + irradiated autologous tumor cells. Immunological reactivity was tested by analyzing PBMC for specific tumor reactive CD4+/CD8+ T lymphocytes using an IFN-γ secretion assay. In 5 of 9 patients, tumor reactive CD4+/CD8+ T-lymphocytes increased significantly, indicating specific anti-tumor immunity. A clinical response (stable disease, partial regression has been observed in 5 of 9 patients, with a mean time to progression of 3.6 months. Follow-up showed a mean survival of 11.8 months (median 8.0 months after trAb therapy. TrAb are able to induce anti-tumor immunity after intraperitoneal application and restimulation. The induction of long-lasting anti-tumor immunity may provide an additional benefit of the intraperitoneal therapy with trAb and should be further elevated in larger clinical trials.

  11. Comparative efficacy, tolerability, and survival outcomes of various radiopharmaceuticals in castration-resistant prostate cancer with bone metastasis: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Tunio M

    2015-09-01

    Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Abdulrehman Al Hadab,1 Yasser Bayoumi2 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2Radiation Oncology, National Cancer Institute, Cairo University, Cairo, Egypt Background: A meta-analysis was conducted to assess the impact of radiopharmaceuticals (RPs in castration-resistant prostate cancer (CRPC on pain control, symptomatic skeletal events (SSEs, toxicity profile, quality of life (QoL, and overall survival (OS.Materials and methods: The PubMed/MEDLINE, CANCERLIT, EMBASE, Cochrane Library database, and other search engines were searched to identify randomized controlled trials (RCTs comparing RPs with control (placebo or radiation therapy in metastatic CRPC. Data were extracted and assessed for the risk of bias (Cochrane’s risk of bias tool. Pooled data were expressed as odds ratio (OR, with 95% confidence intervals (CIs; Mantel–Haenszel fixed-effects model.Results: Eight RCTs with a total patient population of 1,877 patients were identified. The use of RP was associated with significant reduction in pain intensity and SSE (OR: 0.63, 95% CI: 0.51–0.78, I2=27%, P<0.0001, improved QoL (OR: 0.71, 95% CI: 0.55–0.91, I2=65%, three trials, 1,178 patients, P=0.006, and a minimal improved OS (OR: 0.84, 95% CI: 0.64–1.04, I2=47%, seven trials, 1,845 patients, P=0.11. A subgroup analysis suggested an improved OS with radium-223 (OR: 0.68, 95% CI: 0.51–0.90, one trial, 921 patients and strontium-89 (OR: 0.21, 95% CI: 0.05–0.91, one trial, 49 patients. Strontium-89 (five trials was associated with increased rates of grade 3 and 4 thrombocytopenia (OR: 4.26, 95% CI: 2.22–8.18, P=0.01, leucopenia (OR: 7.98, 95% CI: 1.82–34.95, P=0.02, pain flare (OR: 6.82, 95% CI: 3.42–13.55, P=0.04, and emesis (OR: 3.61, 95% CI: 1.76–7.40, P=0.02.Conclusion: The use of RPs was associated with significant reduction in SSEs and improved QoL, while the radium-223

  12. Antitumor activities and interaction with DNA of oxaliplatin-type platinum complexes with linear or branched alkoxyacetates as leaving groups.

    Science.gov (United States)

    Yin, Runting; Gou, Shaohua; Liu, Xia; Lou, Liguang

    2011-08-01

    Five oxaliplatin-typed platinum complexes containing trans-1R, 2R-diaminocyclohexane chelating platinum cores, characteristic of linear or branched alkoxycarboxylates as leaving groups, were biologically evaluated. These compounds showed higher antitumor activity, lower toxicity in vivo than cisplatin or oxaliplatin. And the results revealed that the antitumor activity and interaction with DNA of these compounds were highly related to the nature of leaving groups. Among these complexes, 5a, cis-(trans-1R, 2R-diaminocyclohexane) bis (2-tert-butoxyacetate) platinum(II), showed the highest antitumor activity and the lowest toxicity.

  13. Enhancement of intrinsic antitumor activity in spore-endotoxin mixtures of Bacillus thuringiensis by exposure to ultraviolet radiation

    Energy Technology Data Exchange (ETDEWEB)

    Zamola, B.; Karminski-Zamola, G.; Fuks, Z.; Kubovic, M. (Zagreb Univ. (Yugoslavia)); Wrishcer, M. (Institut Rudjer Boskovic, Zagreb (Yugoslavia))

    1985-03-01

    Irradiation of spore-endotoxin mixtures from Bacillus thuringiensis cultures at 254 nm (60 ..mu..W cm/sup -2/) enhances their intrinsic antitumor potency as well as that of either component. The extent of enhancement depends on the length of exposure (optimum: 35 min) and may thus be due to photochemical changes of the endotoxin protein or/and to photoproduction of additional compounds with antitumor activity. Antitumor effects, expressed as survival rates of C57BL/6 mice inoculated with Lewis' mouse lung carcinoma and subjected to treatments 24 h later, depended on the number of doses of preparations administered (mixture, separated components).

  14. Synthesis, labeling with {sup 99m}Tc and biokinetics of brains scintigraphy diaminodithiol perfusion radiopharmaceuticals; Sintese, marcacao com {sup 99m}Tc e biocinetica de radiofarmacos perfusorios diaminoditiolicos para cintilografias cerebrais

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, Marcos Moises

    1999-07-01

    The recent tomography status using radiopharmaceuticals have been contributing greatly with the 'age of certainty' in the diagnosis examination of syndromes, pathologies and clinical signs, because they can evidence some phenomena occurring in a molecular manner. The purpose of this work have had the development of new diaminodithiol (DADT) perfusion radiopharmaceuticals to be used in brain diagnosis using S.P.E.T. (Single Photon Emission Tomography). Initially, the rational planning had been performed with the new DADT molecular structures as radiopharmaceutical candidates. Using of Q.S.A.R. (Quantitative Structure Activity Relationship) techniques, the molecular descriptors such as partition coefficient and effective polarizability, have been studied in order to increase the blood brain barrier transport and the brain uptake respectively. Applying the Q.S.P.R. (Quantitative Structure Property Relationship) concepts to perform drug latentiation, based on bio-labile functional groups, the congener DADT derivative has been transformed into a pro-drug that works as a DADT moiety carrier, allowing the increasing of brain radiopharmaceutical uptake. Later on, synthetic routes and chemical purifications have been developed allowing the creation of the proposed chemical structure. Each new DADT derivative has been synthesized and analyzed in terms of elemental analysis, infrared and NMR spectra, in order to confirm its proposed chemical structure. Then, the new derivative has been labeled with {sup 99m}Tc, radiochemically purified, intravenously injected in Swiss mice, allowing its biodistribution to evidence its brain transport and uptake. The rational planning studies have been re-evaluated after each biodistribution had been performed, to see what kind of molecular descriptor was responsible for causing a stronger optimization in the brain perfusion characteristics and then, new DADT derivatives have been prepared. Three new DADT derivatives have been

  15. The shielding against radiation produced by powder metallurgy with tungsten copper alloy applied on transport equipment for radio-pharmaceutical products

    Energy Technology Data Exchange (ETDEWEB)

    Cione, Francisco C.; Sene, Frank F.; Souza, Armando C. de; Betini, Evandro G.; Rossi, Jesualdo L., E-mail: fceoni@hotmail.com, E-mail: ffsene@hotmail.com, E-mail: armandocirilo@yahoo.com, E-mail: evandrobetini@gmail.com, E-mail: jelrossi@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Rizzuto, Marcia A., E-mail: marizzutto@if.usp.br [Universidade de Sao Paulo (IF/USP), SP (Brazil). Instituto de Fisica

    2015-07-01

    Safety is mandatory on medicine radiopharmaceutical transportation and dependent on radiation shielding material. The focus of the present work is to minimize the use of harmful materials as lead and depleted uranium usually used in packages transportation. The tungsten-copper composite obtained by powder metallurgy (PM) is non-toxic. In powder metallurgy the density and the porosity of the compacted parts depends basically upon particle size distribution of each component, mixture, compacting pressure and sintering temperature cycle. The tungsten-copper composite, when used for shielding charged particles, X-rays, gamma photons or other photons of lower energy require proper interpretation of the radiation transport phenomena. The radioactive energy reduction varies according to the porosity and density of the materials used as shielding. The main factor for radiation attenuation is the cross section value for tungsten. The motivation research factor is an optimization of the tungsten and cooper composition in order to achieve the best linear absorption coefficient given by equation I{sub (x)} = I{sub 0}e{sup (-ux)}. Experiments were conducted to quantify the effective radiation shielding properties of tungsten-copper composite produced by PM, varying the cooper amount in the composite. The studied compositions were 15%, 20% and 25% copper in mass. The Compaction pressure was 270 MPa and the sintering atmosphere was in 1.1 atm in N{sub 2}+H{sub 2}. The sintering temperature was 980 deg C for 2 h. The linear absorption coefficient factor was similar either for the green and the sintered compacts, due the amount of porosity did not affect the radiation attenuation. Thus the sintered was meant for size reduction and mechanical properties enhancement. (author)

  16. Binding of ReO4(-) with an engineered MoO4(2-)-binding protein: towards a new approach in radiopharmaceutical applications.

    Science.gov (United States)

    Aryal, Baikuntha P; Brugarolas, Pedro; He, Chuan

    2012-01-01

    Radiolabeled biomolecules are routinely used for clinical diagnostics. (99m)Tc is the most commonly used radioactive tracer in radiopharmaceuticals. (188)Re and (186)Re are also commonly used as radioactive tracers in medicine. However, currently available methods for radiolabeling are lengthy and involve several steps in bioconjugation processes. In this work we present a strategy to engineer proteins that may selectively recognize the perrhenate (ReO(4)(-)) ion as a new way to label proteins. We found that a molybdate (MoO(4)(2-))-binding protein (ModA) from Escherichia coli can bind perrhenate with high affinity. Using fluorescence and isothermal titration calorimetry measurements, we determined the dissociation constant of ModA for ReO(4)(-) to be 541 nM and we solved a crystal structure of ModA with a bound ReO(4)(-). On the basis of the structure we created a mutant protein containing a disulfide linkage, which exhibited increased affinity for perrhenate (K(d) = 104 nM). High-resolution crystal structures of ModA (1.7 Å) and A11C/R153C mutant (2.0 Å) were solved with bound perrhenate. Both structures show that a perrhenate ion occupies the molybdate binding site using the same amino acid residues that are involved in molybdate binding. The overall structure of the perrhenate-bound ModA is unchanged compared with that of the molybdate-bound form. In the mutant protein, the bound perrhenate is further stabilized by the engineered disulfide bond.

  17. Synthesis, quality control and dosimetry of the radiopharmaceutical 18F-sodium fluoride produced at the Center for Development of Nuclear Technology - CDTN

    Energy Technology Data Exchange (ETDEWEB)

    Silveira, Marina Bicalho; Soares, Marcella Araugio; Valente, Eduardo Sarmento; Waquil, Samira Soares; Santos, Raquel Gouvea dos; Silva, Juliana Batista da, E-mail: silvajb@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Serv. de Aplicacao das Radiacoes na Saude; Ferreira, Andrea Vidal [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Serv. de Reator e Irradiacoes

    2010-07-15

    {sup 18}F-Sodium fluoride (Na{sup 18}F) is a radiopharmaceutical used for diagnosis in nuclear medicine by positron emission tomography (PET) imaging. Bone scintigraphy is normally performed using {sup 99m}Tc- MDP. However, {sup 18}F PET scans promise high quality imaging with increased resolution and improved sensitivity and specificity. In order to make available a tool for more specific studies of tumors and non oncological diseases of bone tissue, the UPPR/CDTN team undertook the production and quality control of Na{sup 18}F injectable solution with the physical-chemical, microbiological and biological characteristics recommended in the U.S. Pharmacopeia. Na{sup 18}F radiochemical purity was 96.7 {+-} 1.3 %, with Rf= 0.026 {+-} 0.006. The product presented a pH of 5.3 {+-} 0.6, half life of 109.0 {+-} 0.8 minutes, endotoxin limit < 5.0 EU.mL{sup -1} and no microbial contaminants. The biodistribution of Na{sup 18}F was similar to that described in the literature, with a clearance of 0.19 mL.min{sup -1} and distribution volume of 18.76 mL. The highest bone concentration (5.0 {+-} 0.5 %ID.g{sup -1}) was observed 20 minutes after injection. Na{sup 18}F produced at the UPPR presented all the quality assurance requirements of the U.S. Pharmacopeia and can be safely used for clinical bone imaging. (author)

  18. Radiolabeling of new generation magnetic poly(HEMA-MAPA) nanoparticles with (131) I and preliminary investigation of its radiopharmaceutical potential using albino Wistar rats.

    Science.gov (United States)

    Avcıbaşı, Uğur; Demiroğlu, Hasan; Ediz, Melis; Akalın, Hilmi Arkut; Özçalışkan, Emir; Şenay, Hilal; Türkcan, Ceren; Özcan, Yeşim; Akgöl, Sinan; Avcıbaşı, Nesibe

    2013-12-01

    In this study, N-methacryloyl-l-phenylalanine (MAPA) containing poly(2-hydroxyethylmethacrylate) (HEMA)-based magnetic poly(HEMA-MAPA) nanobeads [mag-poly(HEMA-MAPA)] were radiolabeled with (131) I [(131) I-mag-poly(HEMA-MAPA)], and the radiopharmaceutical potential of (131) I-mag-poly(HEMA-MAPA) was investigated. Quality control studies were carried out by radiochromatographic method to be sure that (131) I binded to mag-poly(HEMA-MAPA) efficiently. In this sense, binding yield of (131) I-mag-poly(HEMA-MAPA) was found to be about 95-100%. In addition to this, optimum radiodination conditions for (131) I-mag-poly(HEMA-MAPA) were determined by thin-layer radiochromatography studies. In addition to thin-layer radiochromatography studies, lipophilicity (partition coefficient) and stability studies for (131) I-mag-poly(HEMA-MAPA) were realized. It was determined that lipophilicities of mag-poly(HEMA-MAPA) and (131) I-mag-poly(HEMA-MAPA) were 0.12 ± 0.01 and 1.79 ± 0.76 according to ACD/logP algorithm program, respectively. Stability of the radiolabeled compound was investigated in time intervals given as 0, 30, 60, 180, and 1440 min. It was found that (131) I-mag-poly(HEMA-MAPA) existed as a stable complex in rat serum within 60 min. After that, biodistribution and scintigraphy studies were carried out by using albino Wistar rats. It was determined that the most important (131) I activity uptake was observed in the breast, the ovary, and the pancreas. Scintigraphy studies well supported biodistribution results.

  19. Kinetic and allometric models for dosimetry using radiopharmaceuticals labeled with lanthanides; Proposicao de modelos cineticos e alometricos para a dosimetria de radiofarmacos marcados com lantanideos

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Marina Ferreira

    2012-07-01

    This work proposes two models based in compartmental analyses: Animal model and Human model, using images from gamma camera measurements to determinate the kinetic constants of the {sup 177}Lu-DOTATATE to three animal species (rat Wistar, Armenian hamster and Syrian hamster) and to the human in biodistribution studies split in two phases: Phase 1 governed by uptake from the blood and Phase 2 governed by the real excretion. The kinetic constants obtained from the animals' data ere used to build allometric scaling to predict radiopharmaceutical biodistribution in the human employing relations by mass, metabolism, by life span and by physiological parameters. These extrapolation results were compared with the PRRT (Peptide receptor radiotherapy) patients kinetic data calculated using the Human model. The kinetic constants obtained from humans were used in dose assessment to PRRT patients considering MIRD 26 organs and tissues. Dosimetry results were in agreement with available results from literature. For the Phase 1 allometric scaling from kinetic data from the blood to the organs straight responsible for the {sup 177}Lu-DOTATATE metabolism and excretion - liver, kidneys and urinary bladder -show good correlation in the scaling by mass, metabolism and physiological and parameters. For the Phase 2, only the kinetic data from blood to the liver and to the kidneys show good correlation. Based in the anaesthetics inhibitory action over the renal excretion, there is not empirical basis to allow measurement times over 40 minutes in in vivo studies with small animals. Consequently, the Phase 1 results seem enough to make allometric scaling to assessment dose in PRRT. (author)

  20. 99mTc complex conjugated to insulin: CNS radio-pharmaceuticals design based on principles of blood-brain barrier transport vector

    Institute of Scientific and Technical Information of China (English)

    LIU Fei; FAN Caiyun; ZHANG Jinming; WANG Wushang; LIU Boli

    2005-01-01

    Hydrophilic 99mTc-EC and nonlipophilic 99mTc- MAMA′-BA complexes, owing to the existing of intact blood-brain barrier (BBB) in vivo, cannot cross from blood to brain. Previous studies showed that insulin is selectively transported by receptor-mediated transcytosis through the brain capillary endothelial wall that makes up the BBB. In this paper, based on the characteristic of the insulin receptor enriched in brain capillary, the complexes of hydrophilic 99mTc-EC and nonlipophilic 99mTc-MAMA′-BA are conjugated to insulin respectively. After purification, the radiochemical purity of 99mTc-EC-insulin and 99mTc-MAMA′- BA-insulin was > 90% and the stability in vitro was good. Expectation for the special formulation can be internalized and endocytosed into the capillary membrane by the vector-mediated brain delivery system, and transported 99mTc-labeled conjugate through the BBB in vivo, thus enhancing brain uptake in mice. The biodistribution results of 99mTc-EC-insulin and 99mTc-MAMA′-BA-insulin in mice indicated that the brain uptake was higher than 99mTc-EC and 99mTc-MAMA′-BA to some extent. The ratios of brain uptake of 99mTc-EC-insulin to 99mTc-EC, 99mTc-MAMA′-BA-insulin to 99mTc-MAMA′-BA were 4―6 at 2 and 3 h post-injection respectively. In conclusion, the given results have illustrated a new way of brain uptake enhancing for nonlipophilic like complexes that have BBB delivery problems. It has a potential value for the ongoing development of 99mTc-labeled radiopharmaceuticals for CNS receptors imaging.

  1. Preparation and stability of the {sup 99m} Tc-HNE{sub 2} radiopharmaceutical; Preparacion y estabilidad del radiofarmaco {sup 99m} TC-HNE{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Estrada T, J

    2002-07-01

    A radiopharmaceutical is all substance containing a radioactive atom inside of its structure and what because of its pharmaceutical form, quantity and quality of radiation can be administered in the human beings with diagnostic or therapeutic aims. With the purpose to developing effective radiopharmaceuticals it is necessary to pick carefully the appropriate radionuclide in combination with the In vivo localization and the pharmacon kinetic properties of the carrier molecule. The peptides are designed by the nature to stimulate, regulate or inhibit numerous life functions, they act mainly as information transmitters and activity coordinators of several tissues in the body; it has been found that such substances are present in cells and in the body fluids in quantities extremely small, therefore the peptides have been considered as ideal agents for therapeutic applications. Elastase of human neutrophylls is a 29 kDa protease which is produced in high levels inside the neutrophyll and it is released as response for an inflammatory stimulus in infection/inflammation places. Once it liberated is quickly inhibited by the anti elastase {alpha} tripsine (HNE-2) peptide. Therefore, the neutrophylls elastase is considered as a target to obtain In vivo images of inflammatory/infectious processes by the intravenous application of {sup 99m} Tc-HNE-2. The objective of this work was to develop a labelling method with {sup 99m} Tc for the inhibitor peptide of the human neutrophyll elastase (HNE-2). Likewise, for evaluating its In vivo and In vitro stabilities. The methodology which was followed as first step to conjugate the (HNE-2) peptide with the bi chelating agents HYNIC and DTPA capable to chelate the {sup 99m} Tc metal. Therefore the attachment reactions to the peptide were realized starting from the NHS and HYNIC and the DTPA anhydride in buffer of 0.1 M, pH= 9.0/DMF (10:1) bicarbonates with a molar relation peptide/bi chelating agent 1:5. For the purification of the

  2. Synthesis and evaluation of Lys{sup 1}(α, γ-Folate)Lys{sup 3}({sup 177}Lu-DOTA)-Bombesin(1-14) as a potential theranostic radiopharmaceutical for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aranda L, L.; Ferro F, G.; Azorin V, E.; Ramirez, F. M.; Ocampo G, B.; Santos C, C.; Jimenez M, N. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Issac O, K. [Universidad Autonoma del Estado de Mexico, Facultad de Medicina, 50180 Toluca, Estado de Mexico (Mexico)

    2015-10-15

    Full text: Lutetium-177 labeled hetero bivalent molecules that interact with different targets on tumor cells have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this work was to synthesize Lys{sup 1} (α,γ-Folate)-Lys{sup 3}({sup 177}Lu-DOTA)-Bombesin (1-14) ({sup 177}LuFolate-Bn), as well as to assess its in vitro and in vivo potential for molecular imaging and targeted radiotherapy of breast tumors expressing folate receptors (Fr) and gastrin releasing peptide receptors (GRPR). Lys{sup 1} Lys{sup 3} (DOTA)-Bombesin (1-14) was conjugated to the terminal carboxylic group of the folic acid and the product purified by size-exclusion HPLC. Chemical characterization was carried out by UV-vis, Ft-IR spectroscopies and MALDI-TOF mass spectrometry. {sup 177}Lu labeling was performed by reaction of {sup 177}LuCl{sub 3} with the Lys{sup 1} (α,γ-Folate)-Lys{sup 3} (DOTA)-Bombesin (Folate-Bn) conjugate. In vitro binding studies were carried out in T47D breast cancer cells (positive to Fr and GRPR). Biokinetic studies and micro-SPECT/CT images were obtained using athymic mice with T47D induced tumors. Spectroscopic studies and HPLC analyses indicated that the conjugate was obtained with high chemical and radiochemical purity (98 ± 1.3%). T47D-tumors were clearly visible with high contrast at 2 h after radiopharmaceutical administration. The {sup 177}Lu-absorbed dose delivered to tumors was 23.9 ± 2.1 Gy (74 MBq, intravenously administered) {sup 177}Lu-Folate-Bn demonstrated properties suitable as a theranostic radiopharmaceutical for breast tumors expressing Fr s and GRPR s. (Author)

  3. Study of the production of the radiopharmaceutical {sup 18}F-FLT in automated system: contribution for process validation; Estudo da producao do radiofarmaco FLT-{sup 18}F em sistema automatizado: contribuicao para a validacao do processo

    Energy Technology Data Exchange (ETDEWEB)

    Zanette, Camila

    2013-07-01

    Radiopharmaceutical {sup 18}F-FLT is a thymidine nucleoside analogue and a promising tumor proliferation marker for PET images. The synthesis of this radiopharmaceutical is not simple, and often has low yields. This radiopharmaceutical has already been studied for some years; however, there is no production, nor are there clinical studies in Brazil. The study of the production process and its compliance with the guidelines of Good Manufacturing Practices (ANVISA) are of extreme importance. This study aimed to investigate the synthesis of this radiopharmaceutical, evaluate methods of quality control that will be used in future production routines, perform cytotoxicity studies, biodistribution studies and PET imaging in animals, thereby contributing to the development and elaboration of the process validation protocol and to the establishment of analytical methods to be used during production routines. Initially, we studied the synthesis and production of {sup 18}F-FLT, with the evaluation of three different temperatures of radiolabeling to check the behavior of the radiochemical yield and stability of the nal product. Studies of analytical methodology comprised the analysis of radionuclide identification, determination of chromatographic profiles, radiochemical purity, residual solvents, and pH. In vitro studies of internalization and cytotoxicity were also carried out. In in vivo studies, we evaluated the pharmacokinetics, biodistribution in healthy animals and in animals with tumor models, in addition to PET/CT images in animals with melanomas. The final product had high radiochemical purity and was stable for up to 10 hours after the synthesis, but got a relatively low radiochemical yield, as described in the literature. The tested analytical methods proved suitable for use in the quality control of {sup 18}F-FLT. In in vitro studies, {sup 18}F-FLT showed a significant percentage of binding to tumor cells, and the nonradiolabeled molecule was not considered toxic

  4. Development of nano radiopharmaceutical based on Bevacizumab labelled with Technetium-99m for early diagnosis of gastrointestinal stromal tumor; Desenvolvimento de nanorradiofarmaco a base de Bevacizumabe marcado com tecnecio-99m para diagnostico precoce do tumor estromal gastrointestinal

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Thais Ligiero

    2015-06-01

    The development of new radiopharmaceuticals is an essential activity to improve nuclear medicine, and essential for the early and effective diagnosis of oncological diseases. Among the various possibilities current research in the world, the radiopharmaceuticals to chemotherapeutic base may be the most effective in detecting tumors, particularly Gastrointestinal Stromal Tumor (GIST), the Metastatic Renal Cell Carcinoma and neuroendocrine pancreatic tumors. However, difficulties in directing, as well as adhesion of the radiopharmaceutical in the desired location, are currently the main problems in the early detection and treatment of some of these tumors. Advances in the field of nanotechnology, particularly in recent years, indicate significant contribution to overcoming these obstacles, particularly in the implementation of molecular barriers as well as the functionalization of the nanoparticles, thereby improving targeting by the use of surface nucleotides, and the increased adhesion, which facilitates the release of the drug and therefore increases the chances of early diagnosis and more effective treatment. This study aimed to the production, characterization and evaluation of cytotoxicity, as well as in vivo biodistribution test Bevacizumab nanoparticles labeled with Technetium-99m radionuclide for detection of type GIST tumors. Bevacizumab was encapsulated in the form of nanoparticles by the emulsification method using double poly-acetic acid and polyvinyl alcohol polymers (PLA / PVA) at a concentration of 2% of the monoclonal antibody. The characterization of the nanoparticles was performed by the technique of scanning electron microscopy (SEM). The cytotoxicity assessment was performed by XTT assay with various cell lines of solid tumor cells. The labeling with technetium-99m was done by the direct method, and its yield determined by paper chromatography using paper Whatmam 1 as the stationary phase and acetone as mobile phase. In the biodistribution study

  5. Therapeutical radiopharmaceuticals based In vivo generator system [{sup 166} Dy] Dy/{sup 166} Ho; Radiofarmacos terapeuticos basados en un sistema de generador In vivo [{sup 166}Dy] Dy/{sup 166}Ho

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Garcia S, L.; Monroy G, F.; Tendilla, J.I. [Gerencia de Aplicaciones Nucleares en la Salud, ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico); Pedraza L, M.; Murphy, C.A. de [Departamento de Medicina Nuclear, Instituto Nacional de Pediatria, Mexico D.F. (Mexico)

    2002-07-01

    At the idea to administer to a patient a molecule containing in it structure a father radionuclide, with a half life enough large which allows to the radiolabelled molecule to take up position specifically in a white tissue and decaying In vivo to the daughter radionuclide with properties potentially therapeutic, it is known as In vivo generator system. In this work the preparation and the preliminary dosimetric valuations of radiopharmaceuticals based In vivo generator system {sup 166} Dy Dy/{sup 166} Ho for applications in radioimmunotherapy, in the treatment of the rheumatoid arthritis and in the bone marrow ablation (m.o.) for candidates patients to bone marrow transplant are presented. (Author)

  6. Impurity radionuclide analysis for the radiopharmaceutical Na[{sup 123}I] using gamma spectrometry; Analise de impurezas radionuclidicas para o radiofarmaco Na[{sup 123}I] utilizando a espectrometria gama

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Miriam Taina Ferreira de; Silva, Ronaldo Lins da; Poledna, Roberto; Delgado, Jose Ubiratan; Andrade, Erica de Araujo Lima de; Oliveira, Antonio Eduardo de; Laranjeiras, Adilson Silva, E-mail: miriam@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Braghirolli, Ana Maria Silveira [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    During the process of manufacturing a radiopharmaceutical radionuclide impurities nature can be generated. With the need to meet the standards of ANVISA recommends that applications of doses as low as feasible in patients, the concern comes with a 'boost' that can come from these radionuclidic impurities generated in the production process and or manipulation. For Na[¹²³I] provided by IEN is important to quantify its major impurity, ¹²¹Te as well as gaining a better understanding of the parameters related to the decay scheme, since the data in the literature show discrepancies. (author)

  7. Synthesis of 2-methoxy-6-oxo-1, 4, 2-diazaphosphorinane-2-oxide, A New Potential Antitumor Phosphorus Heterocycle Compound

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    2-methoxy-6-oxo-1, 4, 2-diazaphosphorinane-2-oxide 8, phosphorus counterpart of 2, 6-dioxopiperazine, was synthesized as antitumor agent. The new phosphorus heterocycle compound 8 is the key intermediate in the synthesis of phosphorus counterpart of bisdioxopiperazine.

  8. In vitro and in vivo antitumor activity of Bulbus Fritillariae Cirrhosae and preliminary investigation of its mechanism.

    Science.gov (United States)

    Wang, Dong-Dong; Feng, Yong; Li, Zu; Zhang, Li; Wang, Shu; Zhang, Chao-Yang; Wang, Xiao-Xia; Liu, Zi-Yu

    2014-01-01

    Bulbus Fritillariae Cirrhosae (BFC) is widely used in China both for food and folk medicine because of its powerful biological activities. Firstly, this study was designed to examine the antiproliferative activities of the different fractions from BFC in vitro by MTT assay. The results showed that chloroform extracts (CE) and the purified total alkaloids of BFC (TAF) exhibited stronger antiproliferative activity than the other fractions. We further determined the total alkaloids and 3 main alkaloids monomers content of CE and TAF by UV and HPLC-ELSD methods, respectively. Moreover, we assessed the antitumor activity of TAF in vivo and made preliminary investigation of its antitumor mechanism by histological and immunohistochemical staining technique. These results demonstrate that TAF showed significant antitumor activity and low toxicity in vivo. Meanwhile, TAF significantly inhibited tumor angiogenesis and induced apoptosis by improvement of expression level of caspase-3. These results suggest that alkaloids of BFC could hold a good potential for use as an antitumor drug.

  9. UCH9, a new antitumor antibiotic produced by Streptomyces: I. Producing organism, fermentation, isolation and biological activities.

    Science.gov (United States)

    Ogawa, H; Yamashita, Y; Katahira, R; Chiba, S; Iwasaki, T; Ashizawa, T; Nakano, H

    1998-03-01

    We developed a microbial prescreen using Bacillus stearothermophilus NUB3620 and bacteriophage TP-68 to detect potential antitumor compounds acting on DNA or topoisomerases. During the course of screening microbial cultures for their antibacteriophage activities, we found that Streptomyces sp. isolated from a soil sample collected in Iwakuni city, Yamaguchi prefecture, Japan, produced a new antitumor antibiotic, UCH9. UCH9 was isolated from culture broth by a combination of EtOAc extraction and column chromatography. UCH9 has a new structure related to the antitumor antibiotic chromomycins. It exhibited antimicrobial activity against Gram-positive organisms. UCH9 also showed cytotoxic activity against HeLa S3 cells with an IC50 value of 13 nM and exhibited antitumor activity in vivo against mouse leukemia P388.

  10. Antitumor Activity of KW-2450 Against Triple-Negative Breast Cancer by Inhibiting Aurora A and B Kinases

    OpenAIRE

    Kai, Kazuharu; Kondo, Kimie; Wang, Xiaoping; Xie, Xuemei; Pitner, Mary K.; Reyes, Monica E.; Torres-Adorno, Angie M.; Masuda,Hiroko; Hortobagyi, Gabriel N.; Bartholomeusz, Chandra; Saya, Hideyuki; Tripathy, Debu; Sen, Subrata; Ueno, Naoto T

    2015-01-01

    Currently, no targeted drug is available for triple-negative breast cancer (TNBC), an aggressive breast cancer that does not express estrogen receptor, progesterone receptor, or HER2. TNBC has high mitotic activity, and since Aurora A and B mitotic kinases drive cell division and are overexpressed in tumors with a high mitotic index, we hypothesized that inhibiting Aurora A and B produces a significant antitumor effect in TNBC. We tested this hypothesis by determining the antitumor effects of...

  11. Synthesis and biological evaluation of novel benzo[b]xanthone derivatives as potential antitumor agents

    Directory of Open Access Journals (Sweden)

    Luo Lin

    2013-01-01

    Full Text Available Nine novel aminoalkoxy substituted benzoxanthones (3a-3i were synthesized. Their antitumor activities were evaluated in five human solid tumor cell lines including Hep-G2, BEL-7402, HeLa, MGC-803 and CNE by MTT method. The results showed that most of the compounds displayed moderate to good inhibitory activities on the tested cancer cell lines in vitro, among them compounds 3a and 3h showed higher antitumor activity than other tested compounds against most cell lines. The influence of two kinds of structural factors including the terminal amino group and length of carbon spacers on the anticancer activities were explored to discuss the preliminary structure-activity relationships.

  12. Synthesis of PEGylated fullerene-5-fluorouracil conjugates to enhance the antitumor effect of 5-fluorouracil

    Science.gov (United States)

    Dou, Zengpei; Xu, Yingying; Sun, Hongfang; Liu, Yuanfang

    2012-07-01

    Many drugs have been delivered by different types of nanoscale vehicles to enhance their therapeutic efficacy. 5-Fluorouracil (5FU) is a widely used antitumor drug, however its bioavailability still needs to be improved. Herein we synthesized a polyethylene glycol monomethylether-C60-5FU conjugate (mPEG-C60-5FU) and evaluated its antitumor efficacy in vitro. The results show that the inhibition abilities of mPEG-C60-5FU to the human breast cancer cell line MCF-7 and the human gastric carcinoma cell line BGC-823 are significantly higher than that of 5FU. The conjugate has good stability in murine serum for at least 24 h. Moreover, the PEGylated fullerene (mPEG-C60) vehicle is non-toxic to MCF-7 cells. These results demonstrate that mPEG-C60 is an efficient vehicle for the delivery of 5FU.

  13. Green synthesis and characterization of gold nanoparticles using extract of anti-tumor potent Crocus sativus

    Science.gov (United States)

    Vijayakumar, R.; Devi, V.; Adavallan, K.; Saranya, D.

    2011-12-01

    In the present study, we have explored anti-tumor potent Crocus sativus (saffron) as a reducing agent for one pot size controlled green synthesis of gold nanoparticles (AuNps) at ambient conditions. The nanoparticles were characterized using UV-vis, scanning electron microscope (SEM), high resolution transmission electron microscopy (HRTEM), X-ray diffraction (XRD) and FTIR analysis. The prepared AuNPs showed surface Plasmon resonance centered at 549 nm with average particle size of 15±5 nm. Stable, spherical and triangular crystalline AuNPs with well-defined dimensions were synthesized using anti-tumor potent Crocus sativus (saffron). Crystalline nature of the nanoparticles is confirmed from the HR-TEM, SAED and SEM images, and XRD patterns. From the FTIR spectra it is found that the biomolecules are responsible for capping in gold nanoparticles.

  14. Self-Assembled Peptide- and Protein-Based Nanomaterials for Antitumor Photodynamic and Photothermal Therapy.

    Science.gov (United States)

    Abbas, Manzar; Zou, Qianli; Li, Shukun; Yan, Xuehai

    2017-01-06

    Tremendous interest in self-assembly of peptides and proteins towards functional nanomaterials has been inspired by naturally evolving self-assembly in biological construction of multiple and sophisticated protein architectures in organisms. Self-assembled peptide and protein nanoarchitectures are excellent promising candidates for facilitating biomedical applications due to their advantages of structural, mechanical, and functional diversity and high biocompability and biodegradability. Here, this review focuses on the self-assembly of peptides and proteins for fabrication of phototherapeutic nanomaterials for antitumor photodynamic and photothermal therapy, with emphasis on building blocks, non-covalent interactions, strategies, and the nanoarchitectures of self-assembly. The exciting antitumor activities achieved by these phototherapeutic nanomaterials are also discussed in-depth, along with the relationships between their specific nanoarchitectures and their unique properties, providing an increased understanding of the role of peptide and protein self-assembly in improving the efficiency of photodynamic and photothermal therapy.

  15. Recent advances in understanding antitumor immunity [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Rodrigo Ramella Munhoz

    2016-10-01

    Full Text Available The term “antitumor immunity” refers to innate and adaptive immune responses which lead to tumor control. Turning the immune system into a destructive force against tumors has been achieved in a broad range of human cancers with the use of non-specific immunotherapies, vaccines, adoptive-cell therapy, and, more recently with significant success, through blockade of immune checkpoints. Nevertheless, the efficacy of these approaches is not universal, and tools to identify long-term responders and primarily refractory patients are warranted. In this article, we review recent advances in understanding the complex mechanisms of antitumor immunity and how these developments can be used to address open questions in a setting of growing clinical indications for the use of immunotherapy.

  16. Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: search for anticancer agent.

    Science.gov (United States)

    Noolvi, Malleshappa N; Patel, Harun M; Bhardwaj, Varun; Chauhan, Ankit

    2011-06-01

    The synthesis of some 2-furano-4(3H)-quinazolinones, diamides (open ring quinazolines), quinoxalines and their biological evaluation as antitumor agents using National Cancer Institute (NCI) disease oriented antitumor screen protocol are investigated. Among the synthesize compounds, seventeen compounds were granted NSC code and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10(-5) M) in full NCI 60 cell panel. Among the selected compounds, 3-(2-chloro benzylideneamine)-2-(furan-2-yl) quinazoline-4(3h)-one 21 was found to be the most active candidate of the series at five dose level screening against Ovarian OVCAR-4 and Non-small cell lung cancer NCI-H522 with GI50 1.82 & 2.14 μM respectively. Rational approach and QSAR techniques enabled the understanding of the pharmacophoric requirement for quinazoline, diamides and quinoxaline derivatives.

  17. Role of CD1A and HSP60 in the antitumoral response of oesophageal cancer

    Directory of Open Access Journals (Sweden)

    Simona Corrao

    2011-12-01

    Full Text Available Oesophageal cancer (OC is one of the most common and severe forms of tumor. A wider knowledge of molecular mechanisms which lead to a normal epithelium becoming a neoplasm may reveal new strategies to improve treatment and outcome of this disease. In this review, we report recent findings concerning molecular events which take place during carcinogenesis of the oesophagus. In particular, we focus on the role of two molecules, CD1a and Hsp60, which are overexpressed in oesophageal and many other types of tumor. Both molecules may present tumor antigens and promote in situ the stimulation of an antitumoral immune activity. We suggest there is a synergistic action between these molecules. Further knowledge about their intracellular pathways and extracellular roles may help develop new antitumoral tools for OC.

  18. Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides

    Directory of Open Access Journals (Sweden)

    Kelly eMulder

    2013-10-01

    Full Text Available Cationic antimicrobial peptides (AMPs and host defense peptides (HDPs show vast potential as peptide-based drugs. Great effort has been made in order to exploit their mechanisms of action, aiming to identify their targets as well as to enhance their activity and bioavailability. In this review, we will focus on both naturally occurring and designed antiviral and antitumor cationic peptides, including those here called promiscuous, in which multiple targets are associated with a single peptide structure. Emphasis will be given to their bio-chemical features, selectivity against extra targets and molecular mechanisms. Peptides which possess antitumor activity against different cancer cell lines will be discussed, as well as peptides which inhibit virus replication, focusing on their applications for human health, animal health and agriculture, and their potential as new therapeutic drugs. Moreover, the development of production and nano-delivery systems for both classes of cationic peptides and perspectives on improving them will be considered.

  19. Synthesis and antitumor activity of 1,2-diaminocyclohexane platinum(IV) complexes.

    Science.gov (United States)

    Khokhar, A R; al-Baker, S; Siddik, Z H

    1994-04-01

    The synthesis, characterization, and antitumor activity of a series of platinum(IV) complexes of the type DACH-PtIV(X)2Y (where DACH = trans-dl, or trans-l-1,2-diaminocyclohexane, X = OH or Cl, and Y = oxalato, malonato, methylmalonato, tartronato, ketomalonato, 1,1-cyclopropanedicarboxylato, or 1,1-cyclobutanedicarboxylato, are described. These complexes have been characterized by elemental analysis, HPLC, and infrared and 195Pt NMR spectroscopic techniques. The complexes had good in vitro cytotoxic activity (IC50 = 0.14-7.6 micrograms/ml) and were highly active in vivo against leukemia L1210 cells (%T/C = 152- > 600, cisplatin = 218). In addition, excellent in vivo antitumor activities against B16 melanoma (%T/C = 309), M5076 reticulosarcoma (100% cures) and cisplatin-resistant L1210/DDP (%T/C = 217) cell lines were also exhibited by an analog selected for further evaluation.

  20. [Antitumor components screening of Stellera chamaejasme L. under the case of discrete distribution of active data].

    Science.gov (United States)

    Yang, Qian-Xu; Cheng, Meng-Chun; Wang, Li; Kan, Xiao-Xi; Zhu, Xiao-Xin; Xiao, Hong-Bin

    2014-06-01

    This is to report the screening, extracting and validating antitumor components and compounds from Stellera chamaejasme L. under the case of discrete distribution of active data. In this work, different components from Stellera chamaejasme L. were collected by HPD macroporous resin and polyamide resin column, and their antitumor activity on A549 were tested by MTT assay. Activity results indicate that activity of components at 30-39 min is more potent than that of Stellera chamaejasme L. extract, and the activity of components at 33.97 min is equivalent to positive drug, cis-platinum at 100 microg x mL(-1), but with totally different mode of action. Under the case of discrete activity, the weight analysis is capable of screening active components and compounds from natural products.

  1. Antitumor mechanisms when pRb and p53 are genetically inactivated.

    Science.gov (United States)

    Zhu, L; Lu, Z; Zhao, H

    2015-08-27

    pRb and p53 are the two major tumor suppressors. Their inactivation is frequent when cancers develop and their reactivation is rationale of most cancer therapeutics. When pRb and p53 are genetically inactivated, cells irreparably lose the antitumor mechanisms afforded by them. Cancer genome studies document recurrent genetic inactivation of RB1 and TP53, and the inactivation becomes more frequent in more advanced cancers. These findings may explain why more advanced cancers are more likely to resist current therapies. Finding successful treatments for more advanced and multi-therapy-resistant cancers will depend on finding antitumor mechanisms that remain effective when pRb and p53 are genetically inactivated. Here, we review studies that have begun to make progress in this direction.

  2. Antioxidant and Antitumor Effect of Different Fractions of Ethyl Acetate Part from Elaeagnus angustifolia L.

    Directory of Open Access Journals (Sweden)

    Wang Ya

    2014-05-01

    Full Text Available To determine antitumor and antioxidant activities of the different fractions of ethyl acetate of Elaeagnus angustifolia L. extract, the MTT assay, the DPPH scavenging assay and the reducing power method were used. The results showed that as the concentration and the polarity were increasing, the antioxidant activity of the different fractions of ethyl acetate of Elaeagnus angustifolia L. extract was increased. The DPPH scavenging of the E and F fractions was 94.9%. The antitumor assay showed that the different fractions of ethyl acetate of Elaeagnus angustifolia L. exhibited the inhibition of the in vitro cultured Hela cell proliferation properties. During the first 48 h, there was a dependant relation of inhibition effect and the concentration and the polarity. The higher the concentration and the polarity, the stronger the inhibition effect was. The inhibition rate was 74.34% when the concentration of F faction was 2.5 mg/mL.

  3. Evaluation of In-vivo Antitumor Activity of Annona crassiflora Wood Extract

    Directory of Open Access Journals (Sweden)

    L. P. S. Pimenta

    2011-07-01

    Full Text Available Annona crassiflora is a native tree from Brazilian savanna area of the state of Minas Gerais. The ethanolic extract of A. crassiflora wood was obtained and purified, and an annonaceous acetogenins-rich fraction was obtained and characterized. The in vivo antitumor activity and toxicity of this fraction were evaluated in Ehrlich solid tumor-bearing Swiss mice. The annonaceous acetogenins showed a pronounced in vivo antitumor effect, with a reduction in the Ehrlich’s tumor growth of 38% and 20% after single intratumoral and intravenous administration, respectively, at a dose of 1.25 mg/kg, as compared to the control group. Concerning toxicological studies, the absence of clinical signs and renal toxicity could be observed, and all animals survive throughout the entire experimental period (14 days. By contrast, mielotoxicity and hepatotoxicity could be detected in mice treated with the A. crassiflora wood extract.

  4. Purification, characterization and antitumor activity of polysaccharides from Pleurotus eryngii residue.

    Science.gov (United States)

    Ma, Gaoxing; Yang, Wenjian; Mariga, Alfred Mugambi; Fang, Yong; Ma, Ning; Pei, Fei; Hu, Qiuhui

    2014-12-19

    A novel water-soluble polysaccharide from Pleurotus eryngii residue was isolated and further purified by DEAE cellulose-52 chromatography and Sephadex G-100 size-exclusion chromatography to yield PEPE-1, PEPE-2 and PEPE-3. Molecular weights were determined by high-performance size-exclusion chromatography (HPSEC). Gas chromatography (GC) analysis of monosaccharide composition confirmed that PEPE-1, PEPE-2 and PEPE-3 were heteropolysaccharides and mainly composed of glucose. Sulfate and uronic acid content, ultraviolet and infrared spectrum were also evaluated. The antitumor activities of the polysaccharides against HepG-2 cells were studied in vitro. Results showed that the three polysaccharides could suppress the proliferation and enhance lactate dehydrogenase (LDH) release of HepG-2 cells in a dose- and time-dependent manner. The effect increased in the order of PEPE-1polysaccharides extracted from P. eryngii residue might be suitable for functional foods and natural antitumor drugs development.

  5. Sulfated modification of the polysaccharides obtained from defatted rice bran and their antitumor activities.

    Science.gov (United States)

    Wang, Li; Li, Xiaoxuan; Chen, Zhengxing

    2009-03-01

    Nine sulfated defatted rice bran polysaccharides (sRBPS), with various degrees of sulfation (DS) and carbohydrate content, were prepared by chlorosulfonic acid-pyridine (CSA-Pyr) method according to orthogonal test. Nine sulfated derivatives sRBPS were obtained and their antitumor activities were compared by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results showed that when DS within the scope of 0.81-1.29, carbohydrate content in the range of 41.41-78.56%, sulfated derivatives exhibit relatively strong antitumor activity in vitro. The optimum modification conditions were reaction temperature of 70 degrees C, the ratio of chlorosulfonic acid to pyridine of 1:4 and the reaction time of 2h.

  6. Antitumor Metallothiosemicarbazonate:Synthesis,Crystal Structure,Spectra and Antitumor Studies of Co(Ⅲ) Complex with Thiosemicarbazone Derivative of 2-Benzoylpyridine

    Institute of Scientific and Technical Information of China (English)

    LI Ming-Xue; ZHOU Jing; WANG Zi-Liang; WANG Jing-Ping

    2008-01-01

    The title complex[Co(L)2]Cl·4H2O I has been achieved via self-assembly by incorporating cobalt into 2-benzoylpyridine thiosemicarbazonate ligand,and characterized by elemental analysis,infrared spectra,mass spectra and single-crystal X-ray diffraction study.The crystal crystallizes in monoclinic,space group P21/n,with a=10.227(3),b=17.363(4),c=17.459(4)(A),β=100.408(4)°,V=3049.2(13)(A)3,z=4,Mr=677.08,Dc=1.475 g/cm3,μ(MoKα)=0.834 mm-1,F(000)=1400,the final R=0.0747 and wR=0.0896 for 1663 observed reflections with Ⅰ>2σ(Ⅰ).The complex contains one six-coordinated cobalt ion connected by two thiosemicarbazone ligands which act as a tridentate ligand to coordinate with the center metal atoms via two pyridyl nitrogen atoms,two imine nitrogen atoms and two sulfur atoms giving rise to a mononuclear structure.Hydrogen bonds existing in the complex link the different components to stabilize the crystal structure.The antitumor activity of the title complex Was tested against A549 lung cancer cell line.Complex Ⅰ exhibits antitumor activity.

  7. Synthesis of Dithiocarbamate Derivatives of Quinazolinone and Their in vitro Antitumor Activity

    Institute of Scientific and Technical Information of China (English)

    CAO Sheng-Li; FENG Yu-Ping; WAN Rong; LI Run-Tao

    2003-01-01

    @@ Because of the essential role of thymidylate synthase (TS) in DNA biosynthesis, [1] many TS inhibitors have been designed for the treatment of cancer, [2] of which Raltitrexed has been successfully used for the first-line treat ment of advanced colorectal cancer. [3]Acknowledgements We thank National Center for pharmaceutical screening, Institute of Materia Medica, Chi-nese Academy of Medical Sciences, for in vitro antitumor activity screening.

  8. The Study of Anti-tumor Activity of Trichosanthin by Cyclic Voltammogram

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The anti-tumor activity of Trichosanthin (TCS) has been frequently reported in recent years. In our experiments, electrochemical methods were applied to detect the effects of TCS on human leukemia cells U937. 50m g/ml TCS treatment for 40 hours can cause irreversible negative effects on the viability of U937 cells. This effect largely depends on the concentration of TCS and the time period of treatment.

  9. Spirulina platensis Lacks Antitumor Effect against Solid Ehrlich Carcinoma in Female Mice

    OpenAIRE

    Waleed Barakat; Elshazly, Shimaa M.; Amr A A Mahmoud

    2015-01-01

    Spirulina is a blue-green alga used as a dietary supplement. It has been shown to possess anti-inflammatory, antioxidant, and hepatoprotective properties. This study was designed to evaluate the antitumor effect of spirulina (200 and 800 mg/kg) against a murine model of solid Ehrlich carcinoma compared to a standard chemotherapeutic drug, 5-fluorouracil (20 mg/kg). Untreated mice developed a palpable solid tumor after 13 days. Unlike fluorouracil, spirulina at the investigated two dose levels...

  10. Anti-tumor activity of calcitriol: pre-clinical and clinical studies.

    Science.gov (United States)

    Trump, Donald L; Hershberger, Pamela A; Bernardi, Ronald J; Ahmed, Sharmilla; Muindi, Josephia; Fakih, Marwan; Yu, Wei-Dong; Johnson, Candace S

    2004-05-01

    1,25-Dihydroxycholecalciferol (calcitriol) is recognized widely for its effects on bone and mineral metabolism. Epidemiological data suggest that low Vitamin D levels may play a role in the genesis of prostate cancer and perhaps other tumors. Calcitriol is a potent anti-proliferative agent in a wide variety of malignant cell types. In prostate, breast, colorectal, head/neck and lung cancer as well as lymphoma, leukemia and myeloma model systems calcitriol has significant anti-tumor activity in vitro and in vivo. Calcitriol effects are associated with an increase in G0/G1 arrest, induction of apoptosis and differentiation, modulation of expression of growth factor receptors. Glucocorticoids potentiate the anti-tumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. Calcitriol potentiates the antitumor effects of many cytotoxic agents and inhibits motility and invasiveness of tumor cells and formation of new blood vessels. Phase I and II trials of calcitriol either alone or in combination with carboplatin, taxanes or dexamethasone have been initiated in patients with androgen dependent and independent prostate cancer and advanced cancer. Data indicate that high-dose calcitriol is feasible on an intermittent schedule, no dose-limiting toxicity has been encountered and optimal dose and schedule are being delineated. Clinical responses have been seen with the combination of high dose calcitriol+dexamethasone in androgen independent prostate cancer (AIPC) and apparent potentiation of the antitumor effects of docetaxel have been seen in AIPC. These results demonstrate that high intermittent doses of calcitriol can be administered to patients without toxicity, that the MTD is yet to be determined and that calcitriol has potential as an anti-cancer agent.

  11. Antitumor activity and pharmacokinetics of podophyllotoxin incorporated into solid lipid nanoparticles

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    To evaluate the antitumor activity and pharmacokinetics of podophyllotoxin(PPT) incorporated into solid lipid nanoparticles(SLN),Kunming mice inoculated with flesh tumor were used as animal model.The mice received a single daily intraperitoneal injection of PPT in 20% ethanol(5 mg/kg) and PPT-SLN(5 mg/kg in PPT) for 3 weeks.Gross tumor volumes,body weight and clinical observations were recorded daily.The mice were sacrificed for 24 h after the last administration,and the tumor inhibition rate was calculated with the tumor weight.For the pharmacokinetics research,the mice were treated with intraperitoneal injection of PPT(10 mg/kg) and PPT-SLN(10 mg/kg in PPT).Blood samples were collected at different time to determine the PPT concentration in plasma by HPLC.Blood drug level-time curve was made and pharmacokinetic parameters were calculated.As a result of drug administration,the tumor volume and weight of the mice injected with PPT-SLN were significantly restrained compared with mice treated with PPT or negative control.The tumor inhibition rate of 58.13% showed a significant antitumor activity of PPT-SLN.At the same time,the increased weight gain of the mice injected with PPT-SLN suggested a reduced toxicity of PPT in SLN.Pharmacokinetics study displayed a higher blood concentration,a prolonged circulation time,and an increased bioavailability of PPT-SLN compared with those of PPT.Our results demonstrated that PPT-SLN could optimize pharmacokinetics,enhance antitumor activity and attenuate toxicity,so it has a promising prospect for the application in anti-tumor treatment.

  12. Antitumor activity and pharmacokinetics of podophyllotoxin incorporated into solid lipid nanoparticles

    Institute of Scientific and Technical Information of China (English)

    XUE Meng; ZHU RongRong; QIN LiLi; LI FaJie; LIU ZhiXue; SUN XiaoYu; WANG ShiLong

    2009-01-01

    To evaluate the antitumor activity and pharmacokinetics of podophyllotoxin (PPT) incorporated into solid lipid nanoparticles (SLN),Kunming mice inoculated with flesh tumor were used as animal model.The mice received a single daily intraperitoneal injection of PPT in 20% ethanol (5 mg/kg) and PPT-SLN (5 mg/kg in PPT) for 3 weeks.Gross tumor volumes,body weight and clinical observations were recorded daily.The mice were sacrificed for 24 h after the last administration,and the tumor inhibition rate was calculated with the tumor weight.For the pharmacokinetics research,the mice were treated with intraperitoneal injection of PPT (10 mg/kg) and PPT-SLN (10 mg/kg in PPT).Blood samples were collected at different time to determine the PPT concentration in plasma by HPLC.Blood drug level-time curve was made and pharmacokinetic parameters were calculated.As a result of drug administration,the tumor volume and weight of the mice injected with PPT-SLN were significantly restrained compared with mice treated with PPT or negative control.The tumor inhibition rate of 58.13% showed a significant antitumor activity of PPT-SLN.At the same time,the increased weight gain of the mice injected with PPT-SLN suggested a reduced toxicity of PPT in SLN.Pharmacokinetics study displayed a higher blood concentration,a prolonged circulation time,and an increased bioavailability of PPT-SLN compared with those of PPT.Our results demonstrated that PPT-SLN could optimize pharmacokinetics,enhance antitumor activity and attenuate toxicity,so it has a promising prospect for the application in anti-tumor treatment.

  13. Antitumor activity and biodistribution of cisplatin nanocapsules in nude mice bearing human ovarian carcinoma xenografts

    OpenAIRE

    Staffhorst, R.W.H.M.; Born, K.; Erkelens, C.A.M.; Hamelers, I.H.L.; Peters, G J; Boven, E.; de Kroon, A.I.P.M.

    2008-01-01

    Cisplatin nanocapsules represent a novel lipid formulation of the anticancer drug cis-diamminedichloridoplatinum(II) (cisplatin), characterized by an unprecedented cisplatin-tolipid molar ratio, and exhibiting strongly increased in-vitro cytotoxicity compared with the free drug. In this study, antitumor efficacy and biodistribution of PEGylated cisplatin nanocapsules were compared with those of the free drug in a mouse tumor model. Nude mice bearing human ovarian carcinoma OVCAR-3 xenografts ...

  14. Prophylactic Antitumor Effect of Mixed Heat Shock Proteins/Peptides in Mouse Sarcoma

    Institute of Scientific and Technical Information of China (English)

    Yu Wang; Shu-Yun Liu; Mei Yuan; Yu Tang; Quan-Yi Guo; Xue-Mei Cui; Xiang Sui

    2015-01-01

    Background:To develop a vaccine-based immunotherapy for sarcoma,we evaluated a mixture of heat shock proteins (mHSPs) as a vaccine for sarcoma treatment in a mouse model.Heat shock protein/peptides (HSP/Ps) are autoimmune factors that can induce both adaptive and innate immune responses;HSP/Ps isolated from tumors can induce antitumor immune activity when used as vaccines.Methods:In this study,we evaluated the effects of mHSP/Ps on prophylactic antitumor immunity.We extracted mHSP/Ps,including HSP60,HSP70,GP96,and HSP l 10,from the mouse sarcoma cell lines S 180 and MCA207 using chromatography.The immunity induced by mHSP/Ps was assessed using flow cytometry,ELISPOT,lactate dehydrogenase release,and enzyme-linked immunosorbent assay.Results:Of S180 sarcoma-beating mice immunized with mHSP/Ps isolated from S180 cells,41.2% showed tumor regression and long-term survival,with a tumor growth inhibition rate of 82.3% at 30 days.Of MCA207 sarcoma-bearing mice immunized with mHSP/Ps isolated from MCA207 cells,50% showed tumor regression and long-term survival with a tumor growth inhibition rate of 79.3%.All control mice died within 40 days.The proportions of natural killer cells,CD8+,and interferon-γ-secreting cells and tumor-specific cytotoxic T-lymphocyte activity were increased in the immunized group.Conclusions:Vaccination with a polyvalent mHSP/P cancer vaccine can induce an immunological response and a marked antitumor response to autologous tumors.This mHSP/P vaccine exerted greater antitumor effects than did HSPT0,HSP60,or tumor lysates alone.

  15. Antitumor and antiparasitic activity of novel ruthenium compounds with polycyclic aromatic ligands.

    Science.gov (United States)

    Miserachs, Helena Guiset; Cipriani, Micaella; Grau, Jordi; Vilaseca, Marta; Lorenzo, Julia; Medeiros, Andrea; Comini, Marcelo A; Gambino, Dinorah; Otero, Lucía; Moreno, Virtudes

    2015-09-01

    Five novel ruthenium(II)-arene complexes with polycyclic aromatic ligands were synthesized, comprising three compounds of the formula [RuCl(η(6)-p-cym)(L)][PF6], where p-cym = 1-isopropyl-4-methylbenzene and L are the bidentate aromatic ligands 1,10-phenanthroline-5,6-dione, 1, 5-amine-1,10-phenanthroline, 4, or 5,6-epoxy-5,6-dihydro-phenanthroline, 5. In the other two complexes [RuCl2(η(6)-p-cym)(L')], the metal is coordinated to a monodentate ligand L', where L' is phenanthridine, 2, or 9-carbonylanthracene, 3. All compounds were fully characterized by mass spectrometry and elemental analysis, as well as NMR and IR spectroscopic techniques. Obtained ruthenium compounds as well as their respective ligands were tested for their antiparasitic and antitumoral activities. Even though all compounds showed lower Trypanosoma brucei activity than the free ligands, they also resulted less toxic on mammalian cells. Cytotoxicity assays on HL60 cells showed a moderate antitumoral activity for all ruthenium compounds. Compound 1 was the most potent antitumoral (IC50 = 1.26±0.78 μM) and antiparasitic (IC50 = 0.19 ± 0.05 μM) agent, showing high selectivity towards the parasites (selectivity index >100). As complex 1 was the most promising antitumoral compound, its interaction with ubiquitin as potential target was also studied. In addition, obtained ruthenium compounds were found to bind DNA, and they are thought to interact with this macromolecule mainly through intercalation of the aromatic ligand.

  16. Improved antitumor activity of immunotherapy with BRAF and MEK inhibitors in BRAFV600E melanoma

    OpenAIRE

    Hu-Lieskovan, Siwen; Mok, Stephen; Moreno, Blanca Homet; Tsoi, Jennifer; Faja, Lidia Robert; Goedert, Lucas; Pinheiro, Elaine M.; Koya, Richard C; Graeber, Thomas; Comin-Anduix, Begoña; Ribas, Antoni

    2015-01-01

    Combining immunotherapy and BRAF targeted therapy may result in improved antitumor activity with the high response rates of targeted therapy and the durability of responses with immunotherapy. However, the first clinical trial testing the combination of the BRAF inhibitor vemurafenib and the CTLA-4 antibody ipilimumab was terminated early due to substantial liver toxicities. MEK inhibitors can potentiate the MAPK inhibition in BRAF mutant cells, while potentially alleviating the unwanted para...

  17. Synthesis and antitumor activities of rare earth substituted phosphotungstates containing 5-fluorouracil

    Institute of Scientific and Technical Information of China (English)

    FENG Changgen; GAN Qiang; LIU Xia; HE Hongyou

    2012-01-01

    Two novel rare earth substituted phosphotungstates containing 5-fluorouracil,K9(C4H4FN2O2)2Nd(PW11O39)2·25H2O (FNdPW)and K9(C4H4FN2O2)2Ce(PW11O39)2·23H2O (FCePW),were synthesized and characterized by elementary analysis,FT-IR spectra,X-ray powder diffraction and 1H NMR.The thermal analysis showed that FNdPW decomposed at 210 and 493℃,and FCePW decomposed at 223 and 471 ℃,both of which had good thermal stabilities.MTT tests were performed to study the antitumor activities against HeLa cells and HepG-2 cells of FNdPW,FCePW,5-fluorouracil,C4H4FN2O2H2PW12O40·8H2O and K11Ln(PW11O39)2·xH2O (Ln=Nd,Ce).and their cytotoxicities against HEK 293 cells.The results showed that FNdPW and FCePW possessed higher antitumor activities and lower cytotoxicities than those of 5- fluorouracil and C4H4FN2O2H2PW12O40·8H2O,of which FNdPW exhibited the highest antitumor activates against HeLa cells (EC50=3.41 × 10-6 mol/L) and HepG-2 cells (EC50=6.24× 10-6 mol/L).Thus the introduction of rare earth elements and 5-fluorouracil could significantly enhance antitumor effect of polyoxometalates.

  18. Enhanced antitumoral activity of doxorubicin against lung cancer cells using biodegradable poly(butylcyanoacrylate nanoparticles

    Directory of Open Access Journals (Sweden)

    Melguizo C

    2015-12-01

    Full Text Available Consolación Melguizo1,2,* Laura Cabeza,1,* Jose Prados,1,2 Raúl Ortiz,1,3 Octavio Caba,1,3 Ana R Rama,1,3 Ángel V Delgado,4 José L Arias1,2,5 1Institute of Biopathology and Regenerative Medicine (IBIMER, Biomedical Research Center, 2Biosanitary Institute of Granada (IBS Granada, SAS Universidad de Granada, Granada, 3Department of Health Science, University of Jaén, Jaén, 4Department of Applied Physics, 5Department of Pharmacy and Pharmaceutical Technology, University of Granada, Granada, Spain *These authors contributed equally to this work Abstract: Doxorubicin (Dox is widely used for the combined chemotherapy of solid tumors. However, the use of these drug associations in lung cancer has low antitumor efficacy. To improve its efficacious delivery and activity in lung adenocarcinoma cells, we developed a biodegradable and noncytotoxic nanoplatform based on biodegradable poly(butylcyanoacrylate (PBCA. The reproducible formulation method was based on an anionic polymerization process of the PBCA monomer, with the antitumor drug being entrapped within the nanoparticle (NP matrix during its formation. Improved drug-entrapment efficiencies and sustained (biphasic drug-release properties were made possible by taking advantage of the synthesis conditions (drug, monomer, and surfactant-agent concentrations. Dox-loaded NPs significantly enhanced cellular uptake of the drug in the A549 and LL/2 lung cancer cell lines, leading to a significant improvement of the drug’s antitumoral activity. In vivo studies demonstrated that Dox-loaded NPs clearly reduced tumor volumes and increased mouse-survival rates compared to the free drug. These results demonstrated that PBCA NPs may be used to optimize the antitumor activity of Dox, thus exhibiting a potential application in chemotherapy against lung adenocarcinoma. Keywords: lung cancer, cancer chemotherapy, PBCA, polymeric nanoparticles, drug carrier

  19. Synthesis and antitumor activity of nitric oxide releasing derivatives of AT1 antagonist

    Institute of Scientific and Technical Information of China (English)

    Yan Chun Zhang; Jin Pei Zhou; Xiao Ming Wu; Wei Hong Pan

    2009-01-01

    A series of novel nitric oxide-donating derivatives (7a-e, 8a-e) were synthesized by coupling furoxan and nitric oxide with irbesartan analogue and their cytotoxicity against BEL7402 cells in vitro were evaluated by MTI" method. It was found that 8c exhibits the most cytotoxic activities with IC.so value of 12.5 umol/L. The hybrids of ATI antagonist and nitric oxide donor appear to have beneficial effects on antitumor.

  20. Studies on Antitumor Activity of Bryophyllum calycinum Salisb. against Ehrlich Ascites Carcinoma in Swiss Albino Mice

    OpenAIRE

    Devbhuti D1,*; Gupta JK; Devbhuti P*,1

    2012-01-01

    The aim of the present study is to evaluate the antitumor effect of Bryophyllum calycinum Salisb. (Family: Crassulaceae) against Ehrlich Ascites Carcinoma (EAC) bearing Swiss albino mice. The effect of methanol and aqueous extracts of Bryophyllum calycinum Salisb. on tumor growth was studied by the following parameters: percentage inhibition of ascetic cells and percentage inhibition of tumor weight. Methanol and aqueous extracts were administered at doses of 100,200 and 400 mg/kg body weight...

  1. In Vitro and In Vivo Antitumor Activity of Scutellaria Barbate Extract on Murine Liver Cancer

    Directory of Open Access Journals (Sweden)

    Bao-Feng Wang

    2011-05-01

    Full Text Available In the present study, we investigated the in vitro and in vivo antitumor effects of crude extract of Scutellaria Barbate (CE-SB on mouse hepatoma H22 cells. The MTT assay was used to determine the growth inhibition of H22 cells in vitro. The in vivo therapeutic effects of CE-SB were determined using H22 tumor bearing mice. Besides, the body weight, tumor weight, thymus index and spleen index of H22 bearing mice were also measured. The tumor inhibitory rate (IR was calculated according to the mean weight of tumor (MWT. The phagocytotic function of macrophages was examined by observing peritoneal macrophages phagocytize chicken RBC. The results showed that CE-SB could inhibit the growth of hepatoma H22 Cells in vitro and in vivo. Furthermore, CE-SB could improve immune function of H22 tumor bearing mice. Together these results indicate that CE-SB has antitumor activity and seems to be safe and effective for the use of anti-tumor therapy.

  2. USING OF C60 FULLERENE COMPLEXES WITH ANTITUMOR DRUGS IN CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    S. V. Prylutska

    2014-06-01

    Full Text Available The literature data and own research results concerning antitumor effect in vitro and in vivo of C60 fullerene and its derivatives, cytostatics, and conjugated systems on their basis, which enable the practical application of C60 in combined chemotherapy for treatment efficacy improving of malignant tumors are generalized. The mechanism of antitumor action of C60 fullerene in combined treatment with cytostatics is based on antioxidant properties of its molecule, thereby reducing toxic side effects of traditional drugs in a body and ability to their transport purposefully into the target cells. The unique structure of C60 enables to modify its surface with chemotherapeutic drugs. Under combined action of the "fullerene C60-chemotherapy drug" conjugate the anti-tumor effects enhancement is observed both in vitro and in vivo, namely quantity reduction of viable tumor cells, tumor reduction etc. Furthermore, protective effects of fullerene C60 and derivatives relatively toxic effects of chemotherapeutic agents in a body were observed. Conjugate auxesis empowers it to be kept longer in a cell and prolong the duration of drug action. Ability of fullerene C60 to selective accumulation provides its using for target drug delivery.

  3. Toxicity and antitumor efficacy of Croton polyandrus oil against Ehrlich ascites carcinoma cells

    Directory of Open Access Journals (Sweden)

    Déborah R.P. Meireles

    Full Text Available ABSTRACT The essential oil from Croton polyandrus Spreng., Euphorbiaceae, leaves was tested for the toxicity and antitumor activity. The concentration producing 50% hemolysis was 141 µg/ml on mice erythrocytes. In the acute toxicological study, the estimated LD50 was 447.18 mg/kg. The essential oil did not induce increase in number of micronucleated erythrocytes, suggesting low genotoxicity. Essential oil (100 or 150 mg/kg showed significant antitumor activity in Ehrlich ascitic carcinoma model. We observed that essential oil induces cell-cycle arrest at the G0/G1 phase, and increases the sub-G1 peak, which represents a marker of cell death by apoptosis. Survival also increased for the treated animals. The toxicological analyses revealed reduction in body weight, increased aspartate aminotransferase and alanine aminotransferase activity, hematological changes, and a thymus index reduction. These data suggest gastrointestinal and liver toxicity, anemia, leukopenia/lymphocytopenia, and immunosuppressive effects. Histopathological analysis revealed the weak hepatotoxicity of essential oil. In summary, essential oil of C. polyandrus displays in vivo antitumor activity and moderate toxicity.

  4. Antitumor Activity and Immune Enhancement of Murine Interleukin-23 Expressed in Murine Colon Carcinoma Cells

    Institute of Scientific and Technical Information of China (English)

    Baoen Shan; Jingsheng Hao; Qiaoxia Li; Masatoshi Tagawa

    2006-01-01

    Interleukin (IL)-23, a cytokine composed of p19 and the p40 subunit of IL-12, can enhance the proliferation of memory T cells and production of IFN-γ from activated T cells. It can also induce antitumor effects in murine model. To further evaluate the antitumor activity and immune enhancement of IL-23 in vivo, murine colon carcinoma cells retrovirally transduced with mIL-23 gene were injected subcutaneously (s.c.) into BALB/c mice.Survival time and tumor volume were observed. LDH release assay, [3H]-TdR incorporation assay and ELISA were used to determine CTL activity, proliferation of splenocytes and level of cytokines, respectively. Number of dendritic cells (DCs) was analyzed by flow cytometry (FCM). IL-23 secreted by Colon26/IL-23 cells suppressed the growth of tumor and prolonged the survival time of mice, enhanced proliferation of splenocytes, CTL activity, and number of DCs. IL-23 also promoted the production of Th1 cytokines such as IFN-γ, IL-12 and TNF-o. However,the level of IL-4 was not enhanced significantly. These data suggested that IL-23 secreted by tumor cells can induce antitumor activity by enhancing immune response.

  5. Epistasis between microRNAs 155 and 146a during T cell-mediated antitumor immunity

    Science.gov (United States)

    Huffaker, Thomas B.; Hu, Ruozhen; Runtsch, Marah C.; Bake, Erin; Chen, Xinjian; Zhao, Jimmy; Round, June L.; Baltimore, David; O’Connell, Ryan M.

    2012-01-01

    SUMMARY An increased understanding of antitumor immunity is necessary to improve cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs), miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits IFNγ responses by T cells and reduced solid tumor growth in vivo. Using a novel double knockout (DKO) mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155−/− mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4+ and CD8+ T cell-mediated antitumor immunity, and demonstrates the dominant nature of miR-155 during its promotion of immune responses. PMID:23200854

  6. Epistasis between MicroRNAs 155 and 146a during T Cell-Mediated Antitumor Immunity

    Directory of Open Access Journals (Sweden)

    Thomas B. Huffaker

    2012-12-01

    Full Text Available An increased understanding of antitumor immunity is necessary for improving cell-based immunotherapies against human cancers. Here, we investigated the roles of two immune system-expressed microRNAs (miRNAs, miR-155 and miR-146a, in the regulation of antitumor immune responses. Our results indicate that miR-155 promotes and miR-146a inhibits interferon γ (IFNγ responses by T cells and reduces solid tumor growth in vivo. Using a double-knockout (DKO mouse strain deficient in both miR-155 and miR-146a, we have also identified an epistatic relationship between these two miRNAs. DKO mice had defective T cell responses and tumor growth phenotypes similar to miR-155−/− mice. Further analysis of the T cell compartment revealed that miR-155 modulates IFNγ expression through a mechanism involving repression of Ship1. Our work reveals critical roles for miRNAs in the reciprocal regulation of CD4+ and CD8+ T cell-mediated antitumor immunity and demonstrates the dominant nature of miR-155 during its promotion of immune responses.

  7. Antimicrobial and antitumor activities of chitosan from shiitake stipes, compared to commercial chitosan from crab shells.

    Science.gov (United States)

    Chien, Rao-Chi; Yen, Ming-Tsung; Mau, Jeng-Leun

    2016-03-15

    Chitosan was prepared by alkaline N-deacetylation of chitin obtained from shiitake stipes and crab shells and its antimicrobial and antitumor activities were studied. Chitosan from shiitake stipes and crab shells exhibited excellent antimicrobial activities against eight species of Gram positive and negative pathogenic bacteria with inhibition zones of 11.4-26.8mm at 0.5mg/ml. Among chitosan samples, shiitake chitosan C120 was the most effective with inhibition zones of 16.4-26.8mm at 0.5mg/ml. In addition, shiitake and crab chitosan showed a moderate anti-proliferative effect on IMR 32 and Hep G2 cells. At 5mg/ml, the viability of IMR 32 cells incubated with chitosan was 68.8-85.0% whereas that of Hep G2 cells with chitosan was 60.4-82.9%. Overall, shiitake chitosan showed slightly better antimicrobial and antitumor activities than crab chitosan. Based on the results obtained, shiitake and crab chitosan were strong antimicrobial agents and moderate antitumor agents.

  8. Predicting Antitumor Activity of Peptides by Consensus of Regression Models Trained on a Small Data Sample

    Directory of Open Access Journals (Sweden)

    Ivanka Jerić

    2011-11-01

    Full Text Available Predicting antitumor activity of compounds using regression models trained on a small number of compounds with measured biological activity is an ill-posed inverse problem. Yet, it occurs very often within the academic community. To counteract, up to some extent, overfitting problems caused by a small training data, we propose to use consensus of six regression models for prediction of biological activity of virtual library of compounds. The QSAR descriptors of 22 compounds related to the opioid growth factor (OGF, Tyr-Gly-Gly-Phe-Met with known antitumor activity were used to train regression models: the feed-forward artificial neural network, the k-nearest neighbor, sparseness constrained linear regression, the linear and nonlinear (with polynomial and Gaussian kernel support vector machine. Regression models were applied on a virtual library of 429 compounds that resulted in six lists with candidate compounds ranked by predicted antitumor activity. The highly ranked candidate compounds were synthesized, characterized and tested for an antiproliferative activity. Some of prepared peptides showed more pronounced activity compared with the native OGF; however, they were less active than highly ranked compounds selected previously by the radial basis function support vector machine (RBF SVM regression model. The ill-posedness of the related inverse problem causes unstable behavior of trained regression models on test data. These results point to high complexity of prediction based on the regression models trained on a small data sample.

  9. Antitumor and antimicrobial activities of endophytic fungi from medicinal parts of Aquilaria sinensis

    Institute of Scientific and Technical Information of China (English)

    Jin-long CUI; Shun-xing GUO; Pei-gen XIAO

    2011-01-01

    The purpose of this study was to isolate and characterize endophytic fungi from the stem tissue which can produce fragrant ingredients in Aquilaria sinensis (also called agarwood) to determine their antitumor and antimicrobial activities. Twenty-eight fungal endophytes were isolated from agarwood by strict sterile sample preparation and were classified into 14 genera and 4 taxonomic classes (Sordariomycetes, Dothideomycetes, Saccharomycetes, and Zygomycetes) based on molecular identification. Of the 28 isolates, 13 (46.4%) showed antimicrobial activity against at least one of the test strains by the agar well diffusion method, and 23 isolates (82.1%) displayed antitumor activity against at least one of five cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay. The diameters of inhibition zones of YNAS07, YNAS14, HNAS04, HNAS05, HNAS08, and HNAS11 were equal to or higher than 14.0 mm against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, B. subtilis, Aspergillus fumigatus, and B. subtilis, respectively. The inhibition rates of YNAS06, YNAS08, and HNAS06 were not less than 60% to 293-T, 293-T, and SKVO3 cells, respectively. These results suggest that the endophytic fungi associated with agarwood will provide us with not only useful micro-ecological information, but also potential antimicrobial and antitumor agents.

  10. Effects of cultural medium on the formation and antitumor activity of polysaccharides by Cordyceps gunnii.

    Science.gov (United States)

    Zhu, Zhen-Yuan; Liu, Xiao-Cui; Tang, Ya-Li; Dong, Feng-Ying; Sun, Hui-Qing; Chen, Lu; Zhang, Yong-Min

    2016-10-01

    The effects of culture medium composition (i.e., carbon and nitrogen sources) on the growth of mycelia, molecular weight distribution and antitumor activity of intracellular polysaccharides (IPS) from Cordyceps gunnii were investigated. Sucrose and peptone were proved to be the best carbon and nitrogen sources for mycelia growth and remarkably improved IPS production. When the sucrose concentration was 2.0%, the mycelium yield reached up to 15.94±1.26 g/L, but with lower IPS yield; whereas the sucrose concentration was 4.5%, IPS yield reached to a maximum of 138.78±3.89 mg/100 mL. The effects of different carbon/nitrogen (C/N) ratios with equal amounts of carbon source matter on the mycelia and IPS formation were optimized. It found that the yield of mycelia and IPS were both reached to the highest at a C/N ratio of 10:3. In addition, the IPS had the highest macro molecular polysaccharide content and antitumor activity when sucrose concentration was 3.5% and the C/N ratio was 10:1.5. Thus, there was a positive correlation between molecular weight distribution and antitumor activity of IPS by C. gunnii.

  11. Immunosuppression enhances oncolytic adenovirus replication and antitumor efficacy in the Syrian hamster model.

    Science.gov (United States)

    Thomas, Maria A; Spencer, Jacqueline F; Toth, Karoly; Sagartz, John E; Phillips, Nancy J; Wold, William S M

    2008-10-01

    We recently described an immunocompetent Syrian hamster model for oncolytic adenoviruses (Ads) that permits virus replication in tumor cells as well as some normal tissues. This model allows exploration of interactions between the virus, tumor, normal organs, and host immune system that could not be examined in the immunodeficient or nonpermissive animal models previously used in the oncolytic Ad field. Here we asked whether the immune response to oncolytic Ad enhances or limits antitumor efficacy. We first determined that cyclophosphamide (CP) is a potent immunosuppressive agent in the Syrian hamster and that CP alone had no effect on tumor growth. Importantly, we found that the antitumor efficacy of oncolytic Ads was significantly enhanced in immunosuppressed animals. In animals that received virus therapy plus immunosuppression, significant differences were observed in tumor histology, and in many cases little viable tumor remained. Notably, we also determined that immunosuppression allowed intratumoral virus levels to remain elevated for prolonged periods. Although favorable tumor responses can be achieved in immunocompetent animals, the rate of virus clearance from the tumor may lead to varied antitumor efficacy. Immunosuppression, therefore, allows sustained Ad replication and oncolysis, which leads to substantially improved suppression of tumor growth.

  12. Antitumor and antiangiogenic activity of Schisandra chinensis polysaccharide in a renal cell carcinoma model.

    Science.gov (United States)

    Qu, Hai-Ming; Liu, Shi-Jian; Zhang, Chun-Ying

    2014-05-01

    The aim of this study was to determine the antitumor and antiangiogenic effects of the Schisandra chinensis polysaccharides (SCP) in selected renal cell carcinoma (RCC) cells and evaluate its potential mechanism of action. In vitro, endothelial growth factor (VEGF) secretion by Caki-1 was blockaded in response to SCP treatment for 48h. In vivo, a significant tumor growth inhibition effect was observed after SCP administration for 4 weeks. Moreover, SCP treatment decreased the level of VEGF, CD31 and CD34 in RCC tumor tissues. Further analysis of the tumor inhibition mechanism indicated that the number of apoptotic tumor cells increased significantly; the expression of Bax and p53 increased; and the expression of Bcl-2 decreased dramatically in transplanted tumor tissues following SCP administration. These results indicated that the potential mechanisms involved by which SCP exerted its antitumor and antiangiogenic activity might be associated with the up-regulation of Bax and p53, downregulation of Bcl-2, as well as the reduction of VEGF, CD31 and CD34 in xenografted tumors. These findings demonstrated that the SCP is a potential antitumor agent for RCC treatment.

  13. Antitumor activity of a 2-pyridinecarboxaldehyde 2-pyridinecarboxylic acid hydrazone copper complex and the related mechanism.

    Science.gov (United States)

    Yang, Yingli; Huang, Tengfei; Zhou, Sufeng; Fu, Yun; Liu, Youxun; Yuan, Yanbin; Zhang, Qiongqing; Li, Shaoshan; Li, Changzheng

    2015-09-01

    In the present study, 2-pyridinecarboxaldehyde 2-pyridinecarboxylic acid hydrazone (PPAH) was prepared and its antitumor activity was evaluated. The inhibition of proliferation of PPAH against the HepG2 and HCT-116 cell lines was less effective, yet in the presence of copper ions, the mixture demonstrated excellent antitumor activity (IC50 at 2.75±0.30 µM for the HepG2 cell line, and 1.90±0.20 µM for the HCT-116 cell line, respectively) and the new active species was confirmed to be a PPAH copper complex with a 1:1 ratio by spectral analysis. The excellent antitumor activity of the copper complex prompted us to investigate the underlying mechanism. RT-PCR was performed to detect the changes in the expression of apoptotic genes induced by PPAH and its copper complex. However, no changes were observed when the cells were treated by the agents for 24 or 48 h, indicating that ROS were unlikely involved. Cell cycle analysis showed that both PPAH and its copper complex led to S phase arrest of the cells. The sDNA relaxation assay revealed that the PPAH-copper complex displayed dual topoisomerase inhibition for type I and II. The data suggest that the inhibition of proliferation exhibited by the PPAH copper complex may stem from its dual topoisomerase inhibition, which is rarely observed for a metal complex.

  14. Preparation of novel ferrocene-based shell cross-linked thermoresponsive hybrid micelles with antitumor efficacy.

    Science.gov (United States)

    Wei, Hua; Quan, Chang-Yun; Chang, Cong; Zhang, Xian-Zheng; Zhuo, Ren-Xi

    2010-04-29

    The shell cross-linked (SCL) thermoresponsive hybrid poly(N-isopropylacrylamide-co-aminoethyl methacrylate)-b-polymethyl methacrylate (P(NIPAAm-co-AMA)-b-PMMA) micelle consisting of a cross-linked thermoresponsive hybrid shell and a hydrophobic core domain was fabricated via a two-step process: micellization of P(NIPAAm-co-AMA)-b-PMMA in aqueous solution followed by cross-linking of the hydrophilic shell layer via the amidation reaction between the amine groups of AMA units and the carboxylic acid functions of 1,1'-ferrocenedicarboxylic acid. The SCL micelle showed reversible dispersion/aggregation in response to the temperature cycles through the lower critical solution temperature (LCST) of the thermoresponsive hybrid shell at around 36 degrees C, observed by turbidity measurements and dynamic light scattering (DLS). Besides the usage as an inorganic difunctional cross-linker, the inorganic ferrocene segment further endowed the SCL hybrid micelle with the antitumor efficacy, namely, the resulting SCL micelle exhibited a remarkable cytotoxic effect for HeLa cells with a very low IC50. The results showed that the SCL hybrid micelle developed in this study could be potentially used as an antitumor agent, which is unique compared to the conventional tumor therapy by using the antitumor drug loaded in the micellar core.

  15. Synthesis and anti-tumor activity evaluation of gallic acid-mangiferin hybrid molecule.

    Science.gov (United States)

    Hu, Xiang-yu; Deng, Jia-gang; Wang, Lin; Yuan, Ye-fei

    2013-12-01

    To improve the anti-tumor effects of gallic acid and mangiferin, a gallic acid-mangiferin hybrid molecule (GAMA) was synthesized from gallic acid with mangiferin in the presence of ionic liquid ChC1(choline chloride)·2SnC12. Chemical and spectroscopic methods, such as (1)H and (13)C NMR spectroscopy, and HR-ESIMS were used for the structure identification of GA-MA. Using the cell counting kit-8 (CCK-8) assay, the in vitro anti-tumor effects were compared between GA-MA, gallic acid and mangiferin on human hepatoma HepG2, human nasopharyngeal carcinoma CNE, human lung cancer NCI-H460, human ovarian cancer SK-OV-3, and human cervical cancer Hela cells. The results showed that the half inhibitory concentration (IC50) of GA-MA on HepG2, CNE, NCI-H460, SK-OV-3, and Hela cells was significantly lower than that of gallic acid or mangiferin. This showed that GA-MA has a better in vitro anti-tumor effect than gallic acid and mangi-ferin.

  16. In vitro and in vivo antitumor activity of crude extracts obtained from Brazilian Chromobacterium sp isolates

    Energy Technology Data Exchange (ETDEWEB)

    Menezes, C.B.A.; Silva, B.P. [Universidade Estadual de Campinas, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Campinas, SP (Brazil); Universidade de São Paulo, Interunidades em Biotecnologia, São Paulo, SP (Brazil); Sousa, I.M.O.; Ruiz, A.L.T.G.; Spindola, H.M. [Universidade Estadual de Campinas, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Campinas, SP (Brazil); Cabral, E.; Eberlin, M.N. [Instituto de Química, Universidade Estadual de Campinas, Laboratório Thomson Mass Spectrometry, Campinas, SP (Brazil); Tinti, S.V.; Carvalho, J.E. [Universidade Estadual de Campinas, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Campinas, SP (Brazil); Foglio, M.A.; Fantinatti-Garboggini, F. [Universidade Estadual de Campinas, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Campinas, SP (Brazil); Universidade de São Paulo, Interunidades em Biotecnologia, São Paulo, SP (Brazil)

    2012-10-23

    Natural products produced by microorganisms have been an important source of new substances and lead compounds for the pharmaceutical industry. Chromobacterium violaceum is a Gram-negative β-proteobacterium, abundant in water and soil in tropical and subtropical regions and it produces violacein, a pigment that has shown great pharmaceutical potential. Crude extracts of five Brazilian isolates of Chromobacterium sp (0.25, 2.5, 25, and 250 µg/mL) were evaluated in an in vitro antitumor activity assay with nine human tumor cells. Secondary metabolic profiles were analyzed by liquid chromatography and electrospray ionization mass spectrometry resulting in the identification of violacein in all extracts, whereas FK228 was detected only in EtCE 308 and EtCE 592 extracts. AcCE and EtCE 310 extracts showed selectivity for NCI/ADR-RES cells in the in vitro assay and were evaluated in vivo in the solid Ehrlich tumor model, resulting in 50.3 and 54.6% growth inhibition, respectively. The crude extracts of Chromobacterium sp isolates showed potential and selective antitumor activities for certain human tumor cells, making them a potential source of lead compounds. Furthermore, the results suggest that other compounds, in addition to violacein, deoxyviolacein and FK228, may be involved in the antitumor effect observed.

  17. Adenovirus with p16 gene exerts antitumor effect on laryngeal carcinoma Hep2 cells.

    Science.gov (United States)

    Yang, Zhengang; Hu, Jingxia; Li, Dajun; Pan, Xinliang

    2016-08-01

    Laryngeal cancer is an uncommon form of cancer. The tumor suppressor P16, known to be mutated or deleted in various types of human tumor, including laryngeal carcinoma, is involved in the formation and development of laryngeal carcinoma. It has been previously reported that the inactivation or loss of P16 is associated with the acquisition of malignant characteristics. The current study hypothesized that restoring wild‑type P16 activity into P16‑null malignant Hep2 cells may exert an antitumor effect. A recombinant adenovirus carrying the P16 gene (Ad‑P16) was used to infect and express high levels of P16 protein in P16‑null Hep2 cells. Cell proliferation and invasion assays and polymerase chain reaction were performed to evaluate the effects of the P16 gene on cell proliferation and the antitumor effect on Hep2 cells. The results demonstrated that the Hep2 cells infected with Ad‑P16 exhibited significantly reduced cell proliferation, invasion and tumor volume compared with untreated or control adenovirus cells. Furthermore, the expression of laryngeal carcinoma‑associated genes, EGFR, survivin and cyclin D1, were measured in Ad‑P16‑infected cells and were significantly reduced compared with control groups. The results of the current study demonstrate that restoring wild‑type P16 activity into P16-null Hep2 cells exerts an antitumor effect.

  18. Can we consider zoledronic acid a new antitumor agent? Recent evidence in clinical setting.

    Science.gov (United States)

    Santini, Daniele; Virzi, Vladimir; Fratto, Maria Elisabetta; Bertoldo, Francesco; Sabbatini, Roberto; Berardi, Rossana; Calipari, Nicola; Ottaviani, Davide; Ibrahim, Toni

    2010-02-01

    New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies.

  19. The programmed death-1 immune-suppressive pathway: barrier to antitumor immunity.

    Science.gov (United States)

    Ostrand-Rosenberg, Suzanne; Horn, Lucas A; Haile, Samuel T

    2014-10-15

    Programmed death ligand 1 (PD-L1, also known a