WorldWideScience

Sample records for inactivation molecular imaging

  1. Progress on molecular imaging

    International Nuclear Information System (INIS)

    Chen Quan; Zhang Yongxue

    2011-01-01

    Molecular imaging is a new era of medical imaging,which can non-invasively monitor biological processes at the cellular and molecular level in vivo, including molecular imaging of nuclear medicine, magnetic resonance molecular imaging, ultrasound molecular imaging,optical molecular imaging and molecular imaging with X-ray. Recently, with the development of multi-subjects amalgamation, multimodal molecular imaging technology has been applied in clinical imaging, such as PET-CT and PET-MRI. We believe that with development of molecular probe and multi-modal imaging, more and more molecular imaging techniques will be applied in clinical diagnosis and treatment. (authors)

  2. Molecular MR Imaging Probes

    OpenAIRE

    MAHMOOD, UMAR; JOSEPHSON, LEE

    2005-01-01

    Magnetic resonance imaging (MRI) has been successfully applied to many of the applications of molecular imaging. This review discusses by example some of the advances in areas such as multimodality MR-optical agents, receptor imaging, apoptosis imaging, angiogenesis imaging, noninvasive cell tracking, and imaging of MR marker genes.

  3. Targeted molecular imaging

    International Nuclear Information System (INIS)

    Kim, E. Edmund

    2003-01-01

    Molecular imaging aims to visualize the cellular and molecular processes occurring in living tissues, and for the imaging of specific molecules in vivo, the development of reporter probes and dedicated imaging equipment is most important. Reporter genes can be used to monitor the delivery and magnitude of therapeutic gene transfer, and the time variation involved. Imaging technologies such as micro-PET, SPECT, MRI and CT, as well as optical imaging systems, are able to non-invasively detect, measure, and report the simultaneous expression of multiple meaningful genes. It is believed that recent advances in reporter probes, imaging technologies and gene transfer strategies will enhance the effectiveness of gene therapy trials

  4. Molecular imaging in oncology

    Energy Technology Data Exchange (ETDEWEB)

    Schober, Otmar; Riemann, Burkhard (eds.) [Universitaetsklinikum Muenster (Germany). Klinik fuer Nuklearmedizin

    2013-02-01

    Considers in detail all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. Examines technological issues and probe design. Discusses preclinical studies in detail, with particular attention to multimodality imaging. Presents current clinical use of PET/CT, SPECT/CT, and optical imagingWritten by acknowledged experts. The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing significantly. The process of molecular imaging includes key biotarget identification, design of specific molecular imaging probes, and their preclinical evaluation, e.g., in vivo using small animal studies. A multitude of such innovative molecular imaging probes have already entered clinical diagnostics in oncology. There is no doubt that in future the emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation that will optimize diagnostic processes. This handbook addresses all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. The first section is devoted to technology and probe design, and examines a variety of PET and SPECT tracers as well as multimodality probes. Preclinical studies are then discussed in detail, with particular attention to multimodality imaging. In the third section, diverse clinical applications are presented, and the book closes by looking at future challenges. This handbook will be of value to all who are interested in the revolution in diagnostic oncology that is being brought about by molecular imaging.

  5. Molecular imaging in oncology

    International Nuclear Information System (INIS)

    Schober, Otmar; Riemann, Burkhard

    2013-01-01

    Considers in detail all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. Examines technological issues and probe design. Discusses preclinical studies in detail, with particular attention to multimodality imaging. Presents current clinical use of PET/CT, SPECT/CT, and optical imagingWritten by acknowledged experts. The impact of molecular imaging on diagnostics, therapy, and follow-up in oncology is increasing significantly. The process of molecular imaging includes key biotarget identification, design of specific molecular imaging probes, and their preclinical evaluation, e.g., in vivo using small animal studies. A multitude of such innovative molecular imaging probes have already entered clinical diagnostics in oncology. There is no doubt that in future the emphasis will be on multimodality imaging in which morphological, functional, and molecular imaging techniques are combined in a single clinical investigation that will optimize diagnostic processes. This handbook addresses all aspects of molecular imaging in oncology, ranging from basic research to clinical applications in the era of evidence-based medicine. The first section is devoted to technology and probe design, and examines a variety of PET and SPECT tracers as well as multimodality probes. Preclinical studies are then discussed in detail, with particular attention to multimodality imaging. In the third section, diverse clinical applications are presented, and the book closes by looking at future challenges. This handbook will be of value to all who are interested in the revolution in diagnostic oncology that is being brought about by molecular imaging.

  6. EDITORIAL: Molecular Imaging Technology

    Science.gov (United States)

    Asai, Keisuke; Okamoto, Koji

    2006-06-01

    'Molecular Imaging Technology' focuses on image-based techniques using nanoscale molecules as sensor probes to measure spatial variations of various species (molecular oxygen, singlet oxygen, carbon dioxide, nitric monoxide, etc) and physical properties (pressure, temperature, skin friction, velocity, mechanical stress, etc). This special feature, starting on page 1237, contains selected papers from The International Workshop on Molecular Imaging for Interdisciplinary Research, sponsored by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, which was held at the Sendai Mediatheque, Sendai, Japan, on 8 9 November 2004. The workshop was held as a sequel to the MOSAIC International Workshop that was held in Tokyo in 2003, to summarize the outcome of the 'MOSAIC Project', a five-year interdisciplinary project supported by Techno-Infrastructure Program, the Special Coordination Fund for Promotion of Science Technology to develop molecular sensor technology for aero-thermodynamic research. The workshop focused on molecular imaging technology and its applications to interdisciplinary research areas. More than 110 people attended this workshop from various research fields such as aerospace engineering, automotive engineering, radiotechnology, fluid dynamics, bio-science/engineering and medical engineering. The purpose of this workshop is to stimulate intermixing of these interdisciplinary fields for further development of molecular sensor and imaging technology. It is our pleasure to publish the seven papers selected from our workshop as a special feature in Measurement and Science Technology. We will be happy if this issue inspires people to explore the future direction of molecular imaging technology for interdisciplinary research.

  7. Nanoplatform-based molecular imaging

    National Research Council Canada - National Science Library

    Chen, Xiaoyuan

    2011-01-01

    "Nanoplathform-Based Molecular Imaging provides rationale for using nanoparticle-based probes for molecular imaging, then discusses general strategies for this underutilized, yet promising, technology...

  8. Cardiovascular Molecular Imaging

    International Nuclear Information System (INIS)

    Lee, Kyung Han

    2009-01-01

    Molecular imaging strives to visualize processes in living subjects at the molecular level. Monitoring biochemical processes at this level will allow us to directly track biological processes and signaling events that lead to pathophysiological abnormalities, and help make personalized medicine a reality by allowing evaluation of therapeutic efficacies on an individual basis. Although most molecular imaging techniques emerged from the field of oncology, they have now gradually gained acceptance by the cardiovascular community. Hence, the availability of dedicated high-resolution small animal imaging systems and specific targeting imaging probes is now enhancing our understanding of cardiovascular diseases and expediting the development of newer therapies. Examples include imaging approaches to evaluate and track the progress of recent genetic and cellular therapies for treatment of myocardial ischemia. Other areas include in vivo monitoring of such key molecular processes as angiogenesis and apoptosis. Cardiovascular molecular imaging is already an important research tool in preclinical experiments. The challenge that lies ahead is to implement these techniques into the clinics so that they may help fulfill the promise of molecular therapies and personalized medicine, as well as to resolve disappointments and controversies surrounding the field

  9. Molecular cardiovascular imaging

    International Nuclear Information System (INIS)

    Schaefers, M.

    2007-01-01

    Although huge and long-lasting research efforts have been spent on the development of new diagnostic techniques investigating cardiovascular diseases, still fundamental challenges exist; the main challenge being the diagnosis of a suspected or known coronary artery disease or its consequences (myocardial infarction, heart failure etc.). Beside morphological techniques, functional imaging modalities are available in clinical diagnostic algorithms, whereas molecular cardiovascular imaging techniques are still under development. This review summarizes clinical-diagnostical challenges of modern cardiovascular medicine as well as the potential of new molecular imaging techniques to face these. (orig.)

  10. Molecular imaging in oncology

    International Nuclear Information System (INIS)

    Weber, W.A.

    2007-01-01

    Molecular imaging is generally defined as noninvasive and quantitative imaging of targeted macromolecules and biological processes in living organisms. A characteristic of molecular imaging is the ability to perform repeated studies and assess changes in biological processes over time. Thus molecular imaging lends itself well for monitoring the effectiveness of tumor therapy. In animal models a variety of techniques can be used for molecular imaging. These include optical imaging (bioluminescence and fluorescence imaging), magnetic resonance imaging (MRI) and nuclear medicine techniques. In the clinical setting, however, nuclear medicine techniques predominate, because so far only radioactive tracers provide the necessary sensitivity to study expression and function of macromolecules non-invasively in patients. Nuclear medicine techniques allows to study a variety of biological processes in patients. These include the expression of various receptors (estrogen, androgen, somatostatin receptors and integrins). In addition, tracers are available to study tumor cell proliferation and hypoxia. The by far most commonly used molecular imaging technique in oncology is, however, positron emission tomography (PET) with the glucose analog [ 18 F]fluorodeoxyglucose (FDG-PET). FDG-PET permits non-invasive quantitative assessment of the accelerated exogenous glucose use of malignant tumors. Numerous studies have now shown that reduction of tumor FDG-uptake during therapy allows early prediction of tumor response and patient survival. Clinical studies are currently underway to determine whether FDG-PET can be used to individualize tumor therapy by signaling early in the course of therapy the need for therapeutic adjustments in patients with likely non-responding tumors. (orig.)

  11. Molecular MR imaging

    International Nuclear Information System (INIS)

    Fleige, G.; Hamm, B.

    2000-01-01

    Basic medicobiological research in recent years has made rapid advances in the functional understanding of normal and pathological processes down to the molecular level. At the same time, various imaging modalities have developed from the depiction of organs to approaching the depiction of the cellular level and are about to make the visualization of molecular processes an established procedure. Besides other modalities like PET and near-infrared fluorescence, MR imaging offers some promising options for molecular imaging as well as some applications that have already been tested such as the visualization of enzyme activity, the depiction of the expression of certain genes, the visualization of surface receptors, or the specific demonstration of cells involved in the body's immune response. A major advantage of molecular magnetic resonance imaging (mMRI) over other more sensitive modalities is its high spatial resolution. However, the establishment of mMRI crucially relies on further improvements in resolution and the development of molecular markers for improving its sensitivity and specificity. The state of the art of mMRI is presented by giving a survey of the literature on experimental studies and reporting the results our study group obtained during investigation on gliomas. (orig.) [de

  12. Molecular imaging II

    International Nuclear Information System (INIS)

    Semmler, Wolfhard; Schwaiger, Markus

    2008-01-01

    The aim of this textbook of molecular imaging is to provide an up to date review of this rapidly growing field and to discuss basic methodological aspects necessary for the interpretation of experimental and clinical results. Emphasis is placed on the interplay of imaging technology and probe development, since the physical properties of the imaging approach need to be closely linked with the biologic application of the probe (i.e. nanoparticles and microbubbles). Various chemical strategies are discussed and related to the biologic applications. Reporter-gene imaging is being addressed not only in experimental protocols, but also first clinical applications are discussed. Finally, strategies of imaging to characterize apoptosis and angiogenesis are described and discussed in the context of possible clinical translation. (orig.)

  13. Computational methods for molecular imaging

    CERN Document Server

    Shi, Kuangyu; Li, Shuo

    2015-01-01

    This volume contains original submissions on the development and application of molecular imaging computing. The editors invited authors to submit high-quality contributions on a wide range of topics including, but not limited to: • Image Synthesis & Reconstruction of Emission Tomography (PET, SPECT) and other Molecular Imaging Modalities • Molecular Imaging Enhancement • Data Analysis of Clinical & Pre-clinical Molecular Imaging • Multi-Modal Image Processing (PET/CT, PET/MR, SPECT/CT, etc.) • Machine Learning and Data Mining in Molecular Imaging. Molecular imaging is an evolving clinical and research discipline enabling the visualization, characterization and quantification of biological processes taking place at the cellular and subcellular levels within intact living subjects. Computational methods play an important role in the development of molecular imaging, from image synthesis to data analysis and from clinical diagnosis to therapy individualization. This work will bring readers fro...

  14. Molecular Biomedical Imaging Laboratory (MBIL)

    Data.gov (United States)

    Federal Laboratory Consortium — The Molecular Biomedical Imaging Laboratory (MBIL) is adjacent-a nd has access-to the Department of Radiology and Imaging Sciences clinical imaging facilities. MBIL...

  15. Nuclear medicine imaging instrumentations for molecular imaging

    International Nuclear Information System (INIS)

    Chung, Yong Hyun; Song, Tae Yong; Choi, Yong

    2004-01-01

    Small animal models are extensively utilized in the study of biomedical sciences. Current animal experiments and analysis are largely restricted to in vitro measurements and need to sacrifice animals to perform tissue or molecular analysis. This prevents researchers from observing in vivo the natural evolution of the process under study. Imaging techniques can provide repeatedly in vivo anatomic and molecular information noninvasively. Small animal imaging systems have been developed to assess biological process in experimental animals and increasingly employed in the field of molecular imaging studies. This review outlines the current developments in nuclear medicine imaging instrumentations including fused multi-modality imaging systems for small animal imaging

  16. Molecular nuclear cardiac imaging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soo; Paeng, Jin Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2004-04-01

    Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect.

  17. Molecular nuclear cardiac imaging

    International Nuclear Information System (INIS)

    Lee, Dong Soo; Paeng, Jin Chul

    2004-01-01

    Molecular nuclear cardiac imaging has included Tc-99m Annexin imaging to visualize myocardial apoptosis, but is now usually associated with gene therapy and cell-based therapy. Cardiac gene therapy was not successful so far but cardiac reporter gene imaging was made possible using HSV-TK (herpes simplex virus thymidine kinase) and F-18 FHBG (fluoro-hydroxymethylbutyl guanine) or I-124 FIAU (fluoro-deoxyiodo-arabino-furanosyluracil). Gene delivery was performed by needle injection with or without catheter guidance. TK expression did not last longer than 2 weeks in myocardium. Cell-based therapy of ischemic heart or failing heart looks promising, but biodistribution and differentiation of transplanted cells are not known. Reporter genes can be transfected to the stem/progenitor cells and cells containing these genes can be transplanted to the recipients using catheter-based purging or injection. Repeated imaging should be available and if promoter are varied to let express reporter transgenes, cellular (trans)differentiation can be studied. NIS (sodium iodide symporter) or D2R receptor genes are promising in this aspect

  18. A molecular switch driving inactivation in the cardiac K+ channel HERG.

    Directory of Open Access Journals (Sweden)

    David A Köpfer

    Full Text Available K(+ channels control transmembrane action potentials by gating open or closed in response to external stimuli. Inactivation gating, involving a conformational change at the K(+ selectivity filter, has recently been recognized as a major K(+ channel regulatory mechanism. In the K(+ channel hERG, inactivation controls the length of the human cardiac action potential. Mutations impairing hERG inactivation cause life-threatening cardiac arrhythmia, which also occur as undesired side effects of drugs. In this paper, we report atomistic molecular dynamics simulations, complemented by mutational and electrophysiological studies, which suggest that the selectivity filter adopts a collapsed conformation in the inactivated state of hERG. The selectivity filter is gated by an intricate hydrogen bond network around residues S620 and N629. Mutations of this hydrogen bond network are shown to cause inactivation deficiency in electrophysiological measurements. In addition, drug-related conformational changes around the central cavity and pore helix provide a functional mechanism for newly discovered hERG activators.

  19. Cardiovascular molecular imaging of apoptosis

    International Nuclear Information System (INIS)

    Wolters, S.L.; Reutelingsperger, C.P.M.; Corsten, M.F.; Hofstra, L.; Narula, J.

    2007-01-01

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  20. Cardiovascular molecular imaging of apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wolters, S.L.; Reutelingsperger, C.P.M. [Maastricht University, Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht (Netherlands); Corsten, M.F.; Hofstra, L. [Maastricht University, Department of Cardiology, Cardiovascular Research Institute Maastricht, P.O. Box 616, Maastricht (Netherlands); Narula, J. [University of California Irvine, Department of Cardiology, Irvine (United States)

    2007-06-15

    Molecular imaging strives to visualise processes at the molecular and cellular level in vivo. Understanding these processes supports diagnosis and evaluation of therapeutic efficacy on an individual basis and thereby makes personalised medicine possible. Apoptosis is a well-organised mode of cell suicide that plays a role in cardiovascular diseases (CVD). Apoptosis is associated with loss of cardiomyocytes following myocardial infarction, atherosclerotic plaque instability, congestive heart failure and allograft rejection of the transplanted heart. Thus, apoptosis constitutes an attractive target for molecular imaging of CVD. Our current knowledge about the molecular players and mechanisms underlying apoptosis offers a rich palette of potential molecular targets for molecular imaging. However, only a few have been successfully developed so far. This review highlights aspects of the molecular machinery and biochemistry of apoptosis relevant to the development of molecular imaging probes. It surveys the role of apoptosis in four major areas of CVD and portrays the importance and future perspectives of apoptosis imaging. The annexin A5 imaging protocol is emphasised since it is the most advanced protocol to measure apoptosis in both preclinical and clinical studies. (orig.)

  1. Molecular photoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Frogh Jafarian Dehkordi

    2015-04-01

    Full Text Available Background: Hybrid imaging modalities which simultaneously benefit from capabilities of combined modalities provides an opportunity to modify quality of the images which can be obtained by each of the combined imaging systems. One of the imaging modalities, emerged in medical research area as a hybrid of ultrasound imaging and optical imaging, is photoacoustic imaging which apply ultrasound wave generated by tissue, after receiving laser pulse, to produce medical images. Materials and Methods: In this review, using keywords such as photoacoustic, optoacoustic, laser-ultrasound, thermoacoustic at databases such as PubMed and ISI, studies performed in the field of photoacoustic and related findings were evaluated. Results: Photoacoustic imaging, acquiring images with high contrast and desired resolution, provides an opportunity to perform physiologic and anatomic studies. Because this technique does not use ionizing radiation, it is not restricted by the limitation of the ionizing-based imaging systems therefore it can be used noninvasively to make images from cell, vessels, whole body imaging of the animal and distinguish tumor from normal tissue. Conclusion: Photoacoustic imaging is a new method in preclinical researches which can be used in various physiologic and anatomic studies. This method, because of application of non-ionizing radiation, may resolve limitation of radiation based method in diagnostic assessments.

  2. Molecular sizes of lichen ice nucleation sites determined by gamma radiation inactivation analysis

    International Nuclear Information System (INIS)

    Kieft, T.L.; Ruscetti, T.

    1992-01-01

    It has previously been shown that some species of lichen fungi contain proteinaceous ice nuclei which are active at temperatures as warm as −2 °C. This experiment was undertaken to determine the molecular sizes of ice nuclei in the lichen fungus Rhizoplaca chrysoleuca and to compare them to bacterial ice nuclei from Pseudomonas syringae. Gamma radiation inactivation analysis was used to determine molecular weights. Radiation inactivation analysis is based on target theory, which states that the likelihood of a molecule being inactivated by gamma rays increases as its size increases. Three different sources of ice nuclei from the lichen R. chrysoleuca were tested: field-collected lichens, extract of lichen fungus, and a pure culture of the fungus R. chrysoleuca. P. syringae strain Cit7 was used as a source of bacterial ice nuclei. Samples were lyophilized, irradiated with gamma doses ranging from 0 to 10.4 Mrads, and then tested for ice nucleation activity using a droplet-freezing assay. Data for all four types of samples were in rough agreement; sizes of nucleation sites increased logarithmically with increasing temperatures of ice nucleation activity. Molecular weights of nucleation sites active between −3 and −4 °C from the bacteria and from the field-collected lichens were approximately 1.0 × 10 6 Da. Nuclei from the lichen fungus and in the lichen extract appeared to be slightly smaller but followed the same log-normal pattern with temperature of ice nucleation activity. The data for both the bacterial and lichen ice nuclei are in agreement with ice nucleation theory which states that the size of ice nucleation sites increases logarithmically as the temperature of nucleation increases linearly. This suggests that although some differences exist between bacterial and lichen ice nucleation sites, their molecular sizes are quite similar

  3. Molecular imaging in cardiovascular diseases

    International Nuclear Information System (INIS)

    Botnar, R.M.; Ebersberger, H.; Noerenberg, D.

    2015-01-01

    Cardiovascular diseases remain the leading cause of morbidity and mortality in industrialized and developing countries. In clinical practice, the in-vivo identification of atherosclerotic lesions, which can lead to complications such as heart attack or stroke, remains difficult. Imaging techniques provide the reference standard for the detection of clinically significant atherosclerotic changes in the coronary and carotid arteries. The assessment of the luminal narrowing is feasible, while the differentiation of stable and potentially unstable or vulnerable atherosclerotic plaques is currently not possible using non-invasive imaging. With high spatial resolution and high soft tissue contrast, magnetic resonance imaging (MRI) is a suitable method for the evaluation of the thin arterial wall. In clinical practice, native MRI of the vessel wall already allows the differentiation and characterization of components of atherosclerotic plaques in the carotid arteries and the aorta. Additional diagnostic information can be gained by the use of non-specific MRI contrast agents. With the development of targeted molecular probes, that highlight specific molecules or cells, pathological processes can be visualized at a molecular level with high spatial resolution. In this review article, the development of pathophysiological changes leading to the development of the arterial wall are introduced and discussed. Additionally, principles of contrast enhanced imaging with non-specific contrast agents and molecular probes will be discussed and latest developments in the field of molecular imaging of the vascular wall will be introduced.

  4. Molecular imaging. Fundamentals and applications

    International Nuclear Information System (INIS)

    Tian, Jie

    2013-01-01

    Covers a wide range of new theory, new techniques and new applications. Contributed by many experts in China. The editor has obtained the National Science and Technology Progress Award twice. ''Molecular Imaging: Fundamentals and Applications'' is a comprehensive monograph which describes not only the theory of the underlying algorithms and key technologies but also introduces a prototype system and its applications, bringing together theory, technology and applications. By explaining the basic concepts and principles of molecular imaging, imaging techniques, as well as research and applications in detail, the book provides both detailed theoretical background information and technical methods for researchers working in medical imaging and the life sciences. Clinical doctors and graduate students will also benefit from this book.

  5. General perspectives for molecular nuclear imaging

    International Nuclear Information System (INIS)

    Chung, June Key

    2004-01-01

    Molecular imaging provides a visualization of normal as well as abnormal cellular processes at a molecular or genetic level rather than at an anatomical level. Conventional medical imaging methods utilize the imaging signals produced by nonspecific physico-chemical interaction. However, molecular imaging methods utilize the imaging signals derived from specific cellular or molecular events. Because molecular and genetic changes precede anatomical change in the course of disease development, molecular imaging can detect early events in disease progression. In the near future, through molecular imaging we can understand basic mechanisms of disease, and diagnose earlier and, subsequently, treat earlier intractable disease such as cancer, neuro-degenerative diseases, and immunologic disorders. In beginning period, nuclear medicine started as a molecular imaging, and has had a leading role in the field of molecular imaging. But recently molecular imaging has been rapidly developed. Besides nuclear imaging, molecular imaging methods such as optical imaging, magnetic resonance imaging are emerging. Each imaging modalities have their advantages and weaknesses. The opportunities from molecular imaging look bright. We should try nuclear medicine continues to have a leading role in molecular imaging

  6. Molecular imaging by cardiovascular MR.

    Science.gov (United States)

    Cyrus, Tillmann; Lanza, Gregory M; Wickline, Samuel A

    2007-01-01

    Do molecularly-targeted contrast agents have what it takes to usher in a paradigm shift as to how we will image cardiovascular disease in the near future? Moreover, are non-invasive vulnerable plaque detection and preemptive treatments with these novel nanoparticulate agents within reach for clinical applications? In this article, we attempt to make a compelling case for how the advent of molecularly-targeted nanoparticle technology may change the way we detect atherosclerotic lesions, determine their clinical significance and even provide non-invasive treatments. Focusing on imaging with cardiovascular MR, an overview of the latest developments in this rapidly evolving field of so-called "intelligent" contrast agents that are able to interrogate the vascular wall and various complementary advanced imaging technologies are presented.

  7. Molecular imaging in cervical cancer

    International Nuclear Information System (INIS)

    KHAN, Sairah R.; ROCKALL, Andrea G.; BARWICK, Tara D.

    2016-01-01

    Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed.

  8. 3D molecular imaging SIMS

    Energy Technology Data Exchange (ETDEWEB)

    Gillen, Greg [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States)]. E-mail: Greg.gillen@nist.gov; Fahey, Albert [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States); Wagner, Matt [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States); Mahoney, Christine [Surface and Microanalysis Science Division, National Institute of Standards and Technology, Gaithersburg, MD 20899-8371 (United States)

    2006-07-30

    Thin monolayer and bilayer films of spin cast poly(methyl methacrylate) (PMMA), poly(2-hydroxyethyl methacrylate) (PHEMA), poly(lactic) acid (PLA) and PLA doped with several pharmaceuticals have been analyzed by dynamic SIMS using SF{sub 5} {sup +} polyatomic primary ion bombardment. Each of these systems exhibited minimal primary beam-induced degradation under cluster ion bombardment allowing molecular depth profiles to be obtained through the film. By combing secondary ion imaging with depth profiling, three-dimensional molecular image depth profiles have been obtained from these systems. In another approach, bevel cross-sections are cut in the samples with the SF{sub 5} {sup +} primary ion beam to produce a laterally magnified cross-section of the sample that does not contain the beam-induced damage that would be induced by conventional focussed ion beam (FIB) cross-sectioning. The bevel surface can then be examined using cluster SIMS imaging or other appropriate microanalysis technique.

  9. Molecular Imaging Challenges With PET

    CERN Document Server

    Lecoq, P

    2010-01-01

    The future trends in molecular imaging and associated challenges for in-vivo functional imaging are illustrated on the basis of a few examples, such as atherosclerosis vulnerable plaques imaging or stem cells tracking. A set of parameters are derived to define the specifications of a new generation of in-vivo imaging devices in terms of sensitivity, spatial resolution and signal-to-noise ratio. The limitations of strategies used in present PET scanners are discussed and new approaches are proposed taking advantage of recent progress on materials, photodetectors and readout electronics. A special focus is put on metamaterials, as a new approach to bring more functionality to detection devices. It is shown that the route is now open towards a fully digital detector head with very high photon counting capability over a large energy range, excellent timing precision and possibility of imaging the energy deposition process.

  10. Cancer Stratification by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Justus Weber

    2015-03-01

    Full Text Available The lack of specificity of traditional cytotoxic drugs has triggered the development of anticancer agents that selectively address specific molecular targets. An intrinsic property of these specialized drugs is their limited applicability for specific patient subgroups. Consequently, the generation of information about tumor characteristics is the key to exploit the potential of these drugs. Currently, cancer stratification relies on three approaches: Gene expression analysis and cancer proteomics, immunohistochemistry and molecular imaging. In order to enable the precise localization of functionally expressed targets, molecular imaging combines highly selective biomarkers and intense signal sources. Thus, cancer stratification and localization are performed simultaneously. Many cancer types are characterized by altered receptor expression, such as somatostatin receptors, folate receptors or Her2 (human epidermal growth factor receptor 2. Similar correlations are also known for a multitude of transporters, such as glucose transporters, amino acid transporters or hNIS (human sodium iodide symporter, as well as cell specific proteins, such as the prostate specific membrane antigen, integrins, and CD20. This review provides a comprehensive description of the methods, targets and agents used in molecular imaging, to outline their application for cancer stratification. Emphasis is placed on radiotracers which are used to identify altered expression patterns of cancer associated markers.

  11. Molecular imaging in neurology and neuroscience

    International Nuclear Information System (INIS)

    Schreckenberger, M.

    2007-01-01

    Molecular imaging in neurology and neuroscience is a suspenseful and fast developing tool in order to quantitatively image genomics and proteomics by means of direct and indirect markers. Because of its high-sensitive tracer principle, nuclear medicine imaging has the pioneering task for the methodical progression of molecular imaging. The current development of molecular imaging in neurology changes from the use of indirect markers of gene and protein expression to the direct imaging of the molecular mechanisms. It is the aim of this article to give a short review on the status quo of molecular imaging in neurology with emphasis on clinically relevant aspects. (orig.)

  12. Molecular imaging in biomedical research

    International Nuclear Information System (INIS)

    Jagannathan, N.R.

    2007-01-01

    Molecular imaging (MI) is a diverse technology that revolutionized preclinical, clinical and drug-discovery research. It integrates biology and medicine, and the technique presents a unique opportunity to examine living systems in vivo as a dynamic biological system. It is a hybrid technology that combines PET, SPECT, ultrasound, optical imaging and MR. Several MI methodologies are developed to examine the integrative functions of molecules, cells, organ systems and whole organisms. MI is superior to conventional diagnostic techniques in allowing better staging as well as to monitor the response of cancer/tumour to treatment. In addition, it helps visualization of specific molecular targets or pathways and cells in living systems and ultimately in the clinic. (author)

  13. Introduction to basic molecular biologic techniques for molecular imaging researches

    International Nuclear Information System (INIS)

    Kang, Joo Hyun

    2004-01-01

    Molecular imaging is a rapidly growing field due to the advances in molecular biology and imaging technologies. With the introduction of imaging reporter genes into the cell, diverse cellular processes can be monitored, quantified and imaged non-invasively in vivo. These processes include the gene expression, protein-protein interactions, signal transduction pathways, and monitoring of cells such as cancer cells, immune cells, and stem cells. In the near future, molecular imaging analysis will allow us to observe the incipience and progression of the disease. These will make us easier to give a diagnosis in the early stage of intractable diseases such as cancer, neuro-degenerative disease, and immunological disorders. Additionally, molecular imaging method will be a valuable tool for the real-time evaluation of cells in molecular biology and the basic biological studies. As newer and more powerful molecular imaging tools become available, it will be necessary to corporate clinicians, molecular biologists and biochemists for the planning, interpretation, and application of these techniques to their fullest potential. In order for such a multidisciplinary team to be effective, it is essential that a common understanding of basic biochemical and molecular biologic techniques is achieved. Basic molecular techniques for molecular imaging methods are presented in this paper

  14. Molecular imaging: current status and emerging strategies

    International Nuclear Information System (INIS)

    Pysz, M.A.; Gambhir, S.S.; Willmann, J.K.

    2010-01-01

    In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (SPECT)-based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly-targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future.

  15. Molecular imaging of transcriptional regulation during inflammation

    Directory of Open Access Journals (Sweden)

    Carlsen Harald

    2010-04-01

    Full Text Available Abstract Molecular imaging enables non-invasive visualization of the dynamics of molecular processes within living organisms in vivo. Different imaging modalities as MRI, SPECT, PET and optic imaging are used together with molecular probes specific for the biological process of interest. Molecular imaging of transcription factor activity is done in animal models and mostly in transgenic reporter mice, where the transgene essentially consists of a promoter that regulates a reporter gene. During inflammation, the transcription factor NF-κB is widely involved in orchestration and regulation of the immune system and almost all imaging studies in this field has revolved around the role and regulation of NF-κB. We here present a brief introduction to experimental use and design of transgenic reporter mice and a more extensive review of the various studies where molecular imaging of transcriptional regulation has been applied during inflammation.

  16. Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative.

    Directory of Open Access Journals (Sweden)

    Martina Loibner

    Full Text Available Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene, was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples.Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV. Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays.All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity.PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment.

  17. Pathogen Inactivating Properties and Increased Sensitivity in Molecular Diagnostics by PAXgene, a Novel Non-Crosslinking Tissue Fixative.

    Science.gov (United States)

    Loibner, Martina; Buzina, Walter; Viertler, Christian; Groelz, Daniel; Hausleitner, Anja; Siaulyte, Gintare; Kufferath, Iris; Kölli, Bettina; Zatloukal, Kurt

    2016-01-01

    Requirements on tissue fixatives are getting more demanding as molecular analysis becomes increasingly relevant for routine diagnostics. Buffered formaldehyde in pathology laboratories for tissue fixation is known to cause chemical modifications of biomolecules which affect molecular testing. A novel non-crosslinking tissue preservation technology, PAXgene Tissue (PAXgene), was developed to preserve the integrity of nucleic acids in a comparable way to cryopreservation and also to preserve morphological features comparable to those of formalin fixed samples. Because of the excellent preservation of biomolecules by PAXgene we investigated its pathogen inactivation ability and biosafety in comparison to formalin by in-vitro testing of bacteria, human relevant fungi and human cytomegalovirus (CMV). Guidelines for testing disinfectants served as reference for inactivation assays. Furthermore, we tested the properties of PAXgene for detection of pathogens by PCR based assays. All microorganisms tested were similarly inactivated by PAXgene and formalin except Clostridium sporogenes, which remained viable in seven out of ten assays after PAXgene treatment and in three out of ten assays after formalin fixation. The findings suggest that similar biosafety measures can be applied for PAXgene and formalin fixed samples. Detection of pathogens in PCR-based diagnostics using two CMV assays resulted in a reduction of four to ten quantification cycles of PAXgene treated samples which is a remarkable increase of sensitivity. PAXgene fixation might be superior to formalin fixation when molecular diagnostics and highly sensitive detection of pathogens is required in parallel to morphology assessment.

  18. Molecular imaging promotes progress in orthopedic research.

    Science.gov (United States)

    Mayer-Kuckuk, Philipp; Boskey, Adele L

    2006-11-01

    Modern orthopedic research is directed towards the understanding of molecular mechanisms that determine development, maintenance and health of musculoskeletal tissues. In recent years, many genetic and proteomic discoveries have been made which necessitate investigation under physiological conditions in intact, living tissues. Molecular imaging can meet this demand and is, in fact, the only strategy currently available for noninvasive, quantitative, real-time biology studies in living subjects. In this review, techniques of molecular imaging are summarized, and applications to bone and joint biology are presented. The imaging modality most frequently used in the past was optical imaging, particularly bioluminescence and near-infrared fluorescence imaging. Alternate technologies including nuclear and magnetic resonance imaging were also employed. Orthopedic researchers have applied molecular imaging to murine models including transgenic mice to monitor gene expression, protein degradation, cell migration and cell death. Within the bone compartment, osteoblasts and their stem cells have been investigated, and the organic and mineral bone phases have been assessed. These studies addressed malignancy and injury as well as repair, including fracture healing and cell/gene therapy for skeletal defects. In the joints, molecular imaging has focused on the inflammatory and tissue destructive processes that cause arthritis. As described in this review, the feasibility of applying molecular imaging to numerous areas of orthopedic research has been demonstrated and will likely result in an increase in research dedicated to this powerful strategy. Molecular imaging holds great promise in the future for preclinical orthopedic research as well as next-generation clinical musculoskeletal diagnostics.

  19. Molecular imaging of mental disorders

    International Nuclear Information System (INIS)

    Takahashi, Hidehiko; Suhara, Tetsuya

    2005-01-01

    Positron emission tomography (PET) techniques have made it possible to measure changes in neurochemical components in living human brain. PET can be used to investigate various brain functions such as receptors, transporters, enzymes and various biochemical pathways; therefore, it could be a powerful tool for molecular imaging of mental disorders. Since the pathophysiology of schizophrenia has been discussed with a functional alteration of dopaminergic transmission in the brain, we have focused the dopaminergic components for the research target of schizophrenia using PET. Using high affinity ligand [ 11 C]FLB 457, we found reduced D 2 receptor binding in the anterior cingulate cortex of patients with schizophrenia, and a significant negative correlation was observed between D 2 receptor binding and the positive symptom score. Subregions of interest were defined on the thalamus using individual magnetic resonance images. D 2 receptor binding was also lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. Alterations in D 2 receptor function in the extrastriatal region may underlie the positive symptoms of schizophrenia. On the other hand D 1 receptor binding was found to be lower in the prefrontal cortex and a significant negative correlation was observed between D 1 receptor binding and the negative symptom score. Abnormality of D 1 receptor function would be at the bottom of the negative symptoms and cognitive impairment of schizophrenia. Regarding the effect of antipsychotics on dopamine D 2 receptor, occupancy and it's time-course have been measured in a living body using PET. This approach can provide in vivo pharmacological evidences of antipsychotics and establish the rational therapeutic strategy. PET is a powerful tool not only in the field of brain research but also drug discovery. (author)

  20. Molecular imaging of oncolytic viral therapy

    Directory of Open Access Journals (Sweden)

    Dana Haddad

    2014-01-01

    Full Text Available Oncolytic viruses have made their mark on the cancer world as a potential therapeutic option, with the possible advantages of reduced side effects and strengthened treatment efficacy due to higher tumor selectivity. Results have been so promising, that oncolytic viral treatments have now been approved for clinical trials in several countries. However, clinical studies may benefit from the ability to noninvasively and serially identify sites of viral targeting via molecular imaging in order to provide safety, efficacy, and toxicity information. Furthermore, molecular imaging of oncolytic viral therapy may provide a more sensitive and specific diagnostic technique to detect tumor origin and, more importantly, presence of metastases. Several strategies have been investigated for molecular imaging of viral replication broadly categorized into optical and deep tissue imaging, utilizing several reporter genes encoding for fluorescence proteins, conditional enzymes, and membrane protein and transporters. Various imaging methods facilitate molecular imaging, including computer tomography, magnetic resonance imaging, positron emission tomography, single photon emission CT, gamma-scintigraphy, and photoacoustic imaging. In addition, several molecular probes are used for medical imaging, which act as targeting moieties or signaling agents. This review will explore the preclinical and clinical use of in vivo molecular imaging of replication-competent oncolytic viral therapy.

  1. Inorganic Nanoparticles for Multimodal Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Magdalena Swierczewska

    2011-01-01

    Full Text Available Multimodal molecular imaging can offer a synergistic improvement of diagnostic ability over a single imaging modality. Recent development of hybrid imaging systems has profoundly impacted the pool of available multimodal imaging probes. In particular, much interest has been focused on biocompatible, inorganic nanoparticle-based multimodal probes. Inorganic nanoparticles offer exceptional advantages to the field of multimodal imaging owing to their unique characteristics, such as nanometer dimensions, tunable imaging properties, and multifunctionality. Nanoparticles mainly based on iron oxide, quantum dots, gold, and silica have been applied to various imaging modalities to characterize and image specific biologic processes on a molecular level. A combination of nanoparticles and other materials such as biomolecules, polymers, and radiometals continue to increase functionality for in vivo multimodal imaging and therapeutic agents. In this review, we discuss the unique concepts, characteristics, and applications of the various multimodal imaging probes based on inorganic nanoparticles.

  2. Thermodynamic coupling between activation and inactivation gating in potassium channels revealed by free energy molecular dynamics simulations.

    Science.gov (United States)

    Pan, Albert C; Cuello, Luis G; Perozo, Eduardo; Roux, Benoît

    2011-12-01

    The amount of ionic current flowing through K(+) channels is determined by the interplay between two separate time-dependent processes: activation and inactivation gating. Activation is concerned with the stimulus-dependent opening of the main intracellular gate, whereas inactivation is a spontaneous conformational transition of the selectivity filter toward a nonconductive state occurring on a variety of timescales. A recent analysis of multiple x-ray structures of open and partially open KcsA channels revealed the mechanism by which movements of the inner activation gate, formed by the inner helices from the four subunits of the pore domain, bias the conformational changes at the selectivity filter toward a nonconductive inactivated state. This analysis highlighted the important role of Phe103, a residue located along the inner helix, near the hinge position associated with the opening of the intracellular gate. In the present study, we use free energy perturbation molecular dynamics simulations (FEP/MD) to quantitatively elucidate the thermodynamic basis for the coupling between the intracellular gate and the selectivity filter. The results of the FEP/MD calculations are in good agreement with experiments, and further analysis of the repulsive, van der Waals dispersive, and electrostatic free energy contributions reveals that the energetic basis underlying the absence of inactivation in the F103A mutation in KcsA is the absence of the unfavorable steric interaction occurring with the large Ile100 side chain in a neighboring subunit when the intracellular gate is open and the selectivity filter is in a conductive conformation. Macroscopic current analysis shows that the I100A mutant indeed relieves inactivation in KcsA, but to a lesser extent than the F103A mutant.

  3. Current state of molecular imaging research

    International Nuclear Information System (INIS)

    Grimm, J.; Wunder, A.

    2005-01-01

    The recent years have seen significant advances in both molecular biology, allowing the identification of genes and pathways related to disease, and imaging technologies that allow for improved spatial and temporal resolution, enhanced sensitivity, better depth penetration, improved image processing, and beneficial combinations of different imaging modalities. These advances have led to a paradigm shift in the scope of diagnostic imaging. The traditional role of radiological diagnostic imaging is to define gross anatomy and structure in order to detect pathological abnormalities. Available contrast agents are mostly non-specific and can be used to image physiological processes such as changes in blood volume, flow, and perfusion but not to demonstrate pathological alterations at molecular levels. However, alterations at the anatomical-morphological level are relatively late manifestations of underlying molecular changes. Using molecular probes or markers that bind specifically to molecular targets allows for the non-invasive visualization and quantitation of biological processes such as gene expression, apoptosis, or angiogenesis at the molecular level within intact living organisms. This rapidly evolving, multidisciplinary approach, referred to as molecular imaging, promises to enable early diagnosis, can provide improved classification of stage and severity of disease, an objective assessment of treatment efficacy, and a reliable prognosis. Furthermore, molecular imaging is an important tool for the evaluation of physiological and pathophysiological processes, and for the development of new therapies. This article comprises a review of current technologies of molecular imaging, describes the development of contrast agents and various imaging modalities, new applications in specific disease models, and potential future developments. (orig.)

  4. PET-based molecular imaging in neuroscience

    International Nuclear Information System (INIS)

    Jacobs, A.H.; Heiss, W.D.; Li, H.; Knoess, C.; Schaller, B.; Kracht, L.; Monfared, P.; Vollmar, S.; Bauer, B.; Wagner, R.; Graf, R.; Wienhard, K.; Winkeler, A.; Rueger, A.; Klein, M.; Hilker, R.; Galldiks, N.; Herholz, K.; Sobesky, J.

    2003-01-01

    Positron emission tomography (PET) allows non-invasive assessment of physiological, metabolic and molecular processes in humans and animals in vivo. Advances in detector technology have led to a considerable improvement in the spatial resolution of PET (1-2 mm), enabling for the first time investigations in small experimental animals such as mice. With the developments in radiochemistry and tracer technology, a variety of endogenously expressed and exogenously introduced genes can be analysed by PET. This opens up the exciting and rapidly evolving field of molecular imaging, aiming at the non-invasive localisation of a biological process of interest in normal and diseased cells in animal models and humans in vivo. The main and most intriguing advantage of molecular imaging is the kinetic analysis of a given molecular event in the same experimental subject over time. This will allow non-invasive characterisation and ''phenotyping'' of animal models of human disease at various disease stages, under certain pathophysiological stimuli and after therapeutic intervention. The potential broad applications of imaging molecular events in vivo lie in the study of cell biology, biochemistry, gene/protein function and regulation, signal transduction, transcriptional regulation and characterisation of transgenic animals. Most importantly, molecular imaging will have great implications for the identification of potential molecular therapeutic targets, in the development of new treatment strategies, and in their successful implementation into clinical application. Here, the potential impact of molecular imaging by PET in applications in neuroscience research with a special focus on neurodegeneration and neuro-oncology is reviewed. (orig.)

  5. Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation

    International Nuclear Information System (INIS)

    Mohandas, T.; Geller, R.L.; Yen, P.H.; Rosendorff, J.; Bernstein, R.; Yoshida, A.; Shapiro, L.J.

    1987-01-01

    A pericentric inversion of human X chromosome and a recombinant X chromosome [rec(X)] derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3 → Xqter and a deletion of Xp22.3 → Xpter and was interpreted to be Xqter → Xq26.3::Xp22.3 → Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) wee duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3 → qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state

  6. Nanobody: the "magic bullet" for molecular imaging?

    Science.gov (United States)

    Chakravarty, Rubel; Goel, Shreya; Cai, Weibo

    2014-01-01

    Molecular imaging involves the non-invasive investigation of biological processes in vivo at the cellular and molecular level, which can play diverse roles in better understanding and treatment of various diseases. Recently, single domain antigen-binding fragments known as 'nanobodies' were bioengineered and tested for molecular imaging applications. Small molecular size (~15 kDa) and suitable configuration of the complementarity determining regions (CDRs) of nanobodies offer many desirable features suitable for imaging applications, such as rapid targeting and fast blood clearance, high solubility, high stability, easy cloning, modular nature, and the capability of binding to cavities and difficult-to-access antigens. Using nanobody-based probes, several imaging techniques such as radionuclide-based, optical and ultrasound have been employed for visualization of target expression in various disease models. This review summarizes the recent developments in the use of nanobody-based probes for molecular imaging applications. The preclinical data reported to date are quite promising, and it is expected that nanobody-based molecular imaging agents will play an important role in the diagnosis and management of various diseases.

  7. Hydrogen bonds as molecular timers for slow inactivation in voltage-gated potassium channels

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Galpin, Jason D; Niciforovic, Ana P

    2013-01-01

    Voltage-gated potassium (Kv) channels enable potassium efflux and membrane repolarization in excitable tissues. Many Kv channels undergo a progressive loss of ion conductance in the presence of a prolonged voltage stimulus, termed slow inactivation, but the atomic determinants that regulate the k...... subunit(s). DOI: http://dx.doi.org/10.7554/eLife.01289.001....

  8. Fluorescence based molecular in vivo imaging

    International Nuclear Information System (INIS)

    Ebert, Bernd

    2008-01-01

    Molecular imaging represents a modern research area that allows the in vivo study of molecular biological process kinetics using appropriate probes and visualization methods. This methodology may be defined- apart from the contrast media injection - as non-abrasive. In order to reach an in vivo molecular process imaging as accurate as possible the effects of the used probes on the biological should not be too large. The contrast media as important part of the molecular imaging can significantly contribute to the understanding of molecular processes and to the development of tailored diagnostics and therapy. Since more than 15 years PTB is developing optic imaging systems that may be used for fluorescence based visualization of tissue phantoms, small animal models and the localization of tumors and their predecessors, and for the early recognition of inflammatory processes in clinical trials. Cellular changes occur during many diseases, thus the molecular imaging might be of importance for the early diagnosis of chronic inflammatory diseases. Fluorescent dyes can be used as unspecific or also as specific contrast media, which allow enhanced detection sensitivity

  9. Molecular and parametric imaging with iron oxides

    International Nuclear Information System (INIS)

    Matuszewski, L.; Bremer, C.; Tombach, B.; Heindel, W.

    2007-01-01

    Superparamagnetic iron oxide (SPIO) contrast agents, clinically established for high resolution magnetic resonance imaging of reticuloendothelial system containing anatomical structures, can additionally be exploited for the non-invasive characterization and quantification of pathology down to the molecular level. In this context, SPIOs can be applied for non-invasive cell tracking, quantification of tissue perfusion and target specific imaging, as well as for the detection of gene expression. This article provides an overview of new applications for clinically approved iron oxides as well of new, modified SPIO contrast agents for parametric and molecular imaging. (orig.) [de

  10. Molecular Imaging of Inflammation in Atherosclerosis

    Science.gov (United States)

    Wildgruber, Moritz; Swirski, Filip K.; Zernecke, Alma

    2013-01-01

    Acute rupture of vulnerable plaques frequently leads to myocardial infarction and stroke. Within the last decades, several cellular and molecular players have been identified that promote atherosclerotic lesion formation, maturation and plaque rupture. It is now widely recognized that inflammation of the vessel wall and distinct leukocyte subsets are involved throughout all phases of atherosclerotic lesion development. The mechanisms that render a stable plaque unstable and prone to rupture, however, remain unknown and the identification of the vulnerable plaque remains a major challenge in cardiovascular medicine. Imaging technologies used in the clinic offer minimal information about the underlying biology and potential risk for rupture. New imaging technologies are therefore being developed, and in the preclinical setting have enabled new and dynamic insights into the vessel wall for a better understanding of this complex disease. Molecular imaging has the potential to track biological processes, such as the activity of cellular and molecular biomarkers in vivo and over time. Similarly, novel imaging technologies specifically detect effects of therapies that aim to stabilize vulnerable plaques and silence vascular inflammation. Here we will review the potential of established and new molecular imaging technologies in the setting of atherosclerosis, and discuss the cumbersome steps required for translating molecular imaging approaches into the clinic. PMID:24312156

  11. Molecular Imaging Probe Development using Microfluidics

    Science.gov (United States)

    Liu, Kan; Wang, Ming-Wei; Lin, Wei-Yu; Phung, Duy Linh; Girgis, Mark D.; Wu, Anna M.; Tomlinson, James S.; Shen, Clifton K.-F.

    2012-01-01

    In this manuscript, we review the latest advancement of microfluidics in molecular imaging probe development. Due to increasing needs for medical imaging, high demand for many types of molecular imaging probes will have to be met by exploiting novel chemistry/radiochemistry and engineering technologies to improve the production and development of suitable probes. The microfluidic-based probe synthesis is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional systems. Numerous chemical reactions have been successfully performed in micro-reactors and the results convincingly demonstrate with great benefits to aid synthetic procedures, such as purer products, higher yields, shorter reaction times compared to the corresponding batch/macroscale reactions, and more benign reaction conditions. Several ‘proof-of-principle’ examples of molecular imaging probe syntheses using microfluidics, along with basics of device architecture and operation, and their potential limitations are discussed here. PMID:22977436

  12. High sensitivity optical molecular imaging system

    Science.gov (United States)

    An, Yu; Yuan, Gao; Huang, Chao; Jiang, Shixin; Zhang, Peng; Wang, Kun; Tian, Jie

    2018-02-01

    Optical Molecular Imaging (OMI) has the advantages of high sensitivity, low cost and ease of use. By labeling the regions of interest with fluorescent or bioluminescence probes, OMI can noninvasively obtain the distribution of the probes in vivo, which play the key role in cancer research, pharmacokinetics and other biological studies. In preclinical and clinical application, the image depth, resolution and sensitivity are the key factors for researchers to use OMI. In this paper, we report a high sensitivity optical molecular imaging system developed by our group, which can improve the imaging depth in phantom to nearly 5cm, high resolution at 2cm depth, and high image sensitivity. To validate the performance of the system, special designed phantom experiments and weak light detection experiment were implemented. The results shows that cooperated with high performance electron-multiplying charge coupled device (EMCCD) camera, precision design of light path system and high efficient image techniques, our OMI system can simultaneously collect the light-emitted signals generated by fluorescence molecular imaging, bioluminescence imaging, Cherenkov luminance and other optical imaging modality, and observe the internal distribution of light-emitting agents fast and accurately.

  13. Has molecular imaging delivered to drug development?

    Science.gov (United States)

    Murphy, Philip S.; Patel, Neel; McCarthy, Timothy J.

    2017-10-01

    Pharmaceutical research and development requires a systematic interrogation of a candidate molecule through clinical studies. To ensure resources are spent on only the most promising molecules, early clinical studies must understand fundamental attributes of the drug candidate, including exposure at the target site, target binding and pharmacological response in disease. Molecular imaging has the potential to quantitatively characterize these properties in small, efficient clinical studies. Specific benefits of molecular imaging in this setting (compared to blood and tissue sampling) include non-invasiveness and the ability to survey the whole body temporally. These methods have been adopted primarily for neuroscience drug development, catalysed by the inability to access the brain compartment by other means. If we believe molecular imaging is a technology platform able to underpin clinical drug development, why is it not adopted further to enable earlier decisions? This article considers current drug development needs, progress towards integration of molecular imaging into studies, current impediments and proposed models to broaden use and increase impact. This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.

  14. Molecular nuclear imaging for targeting and trafficking

    International Nuclear Information System (INIS)

    Bom, Hee Seung; Min, Jung Jun; Jeong, Hwan-Jeong

    2006-01-01

    Noninvasive molecular targeting in living subjects is highly demanded for better understanding of such diverse topics as the efficient delivery of drugs, genes, or radionuclides for the diagnosis or treatment of diseases. Progress in molecular biology, genetic engineering and polymer chemistry provides various tools to target molecules and cells in vivo. We used chitosan as a polymer, and 99m Tc as a radionuclide. We developed 99m Tc-galactosylated chitosan to target asialoglycoprotein receptors for nuclear imaging. We also developed 99m Tc-HYNIC-chitosan-transferrin to target inflammatory cells, which was more effective than 67 Ga-citrate for imaging inflammatory lesions. For an effective delivery of molecules, a longer circulation time is needed. We found that around 10% PEGylation was most effective to prolong the circulation time of liposomes for nuclear imaging of 99m Tc-HMPAO-labeled liposomes in rats. Using various characteristics of molecules, we can deliver drugs into targets more effectively. We found that 99m Tc-labeled biodegradable pullulan-derivatives are retained in tumor tissue in response to extracellular ion-strength. For the trafficking of various cells or bacteria in an intact animal, we used optical imaging techniques or radiolabeled cells. We monitored tumor-targeting bacteria by bioluminescent imaging techniques, dentritic cells by radiolabeling and neuronal stem cells by sodium-iodide symporter reporter gene imaging. In summary, we introduced recent achievements of molecular nuclear imaging technologies in targeting receptors for hepatocyte or inflammatory cells and in trafficking bacterial, immune and stem cells using molecular nuclear imaging techniques

  15. A review of molecular imaging studies reaching the clinical stage

    International Nuclear Information System (INIS)

    Wong, Franklin C.; Kim, E. Edmund

    2009-01-01

    The practice of molecular imaging in the clinics is examined across various imaging modalities to assess the current status of clinical molecular imaging. The various physiologic and scientific bases of clinical molecular imaging are surveyed to assess the possibilities and opportunities for the deployment of the different imaging modalities in the near future. The requisites for successful candidate(s) of clinical molecular imaging are reviewed for future development.

  16. In Vivo Imaging of Molecularly Targeted Phage

    Directory of Open Access Journals (Sweden)

    Kimberly A. Kelly

    2006-12-01

    Full Text Available Rapid identification of in vivo affinity ligands would have far-reaching applications for imaging specific molecular targets, in vivo systems imaging, and medical use. We have developed a high-throughput method for identifying and optimizing ligands to map and image biologic targets of interest in vivo. We directly labeled viable phage clones with far-red fluorochromes and comparatively imaged them in vivo by multichannel fluorescence ratio imaging. Using Secreted Protein Acidic and Rich in Cysteine (osteonectin and vascular cell adhesion molecule-1 as model targets, we show that: 1 fluorescently labeled phage retains target specificity on labeling; 2 in vivo distribution can be quantitated (detection thresholds of ~ 300 phage/mm3 tissue throughout the entire depth of the tumor using fluorescent tomographic imaging; and 3 fluorescently labeled phage itself can serve as a replenishable molecular imaging agent. The described method should find widespread application in the rapid in vivo discovery and validation of affinity ligands and, importantly, in the use of fluorochrome-labeled phage clones as in vivo imaging agents.

  17. Molecular Imaging in Nanotechnology and Theranostics.

    Science.gov (United States)

    Andreou, Chrysafis; Pal, Suchetan; Rotter, Lara; Yang, Jiang; Kircher, Moritz F

    2017-06-01

    The fields of biomedical nanotechnology and theranostics have enjoyed exponential growth in recent years. The "Molecular Imaging in Nanotechnology and Theranostics" (MINT) Interest Group of the World Molecular Imaging Society (WMIS) was created in order to provide a more organized and focused forum on these topics within the WMIS and at the World Molecular Imaging Conference (WMIC). The interest group was founded in 2015 and was officially inaugurated during the 2016 WMIC. The overarching goal of MINT is to bring together the many scientists who work on molecular imaging approaches using nanotechnology and those that work on theranostic agents. MINT therefore represents scientists, labs, and institutes that are very diverse in their scientific backgrounds and areas of expertise, reflecting the wide array of materials and approaches that drive these fields. In this short review, we attempt to provide a condensed overview over some of the key areas covered by MINT. Given the breadth of the fields and the given space constraints, we have limited the coverage to the realm of nanoconstructs, although theranostics is certainly not limited to this domain. We will also focus only on the most recent developments of the last 3-5 years, in order to provide the reader with an intuition of what is "in the pipeline" and has potential for clinical translation in the near future.

  18. Towards molecular imaging by means of MRI

    NARCIS (Netherlands)

    Norek, M.

    2008-01-01

    The work presented in the thesis is focused on the design of highly efficient contrast agents for molecular imaging by means of MRI based on the detailed physical characterization of the given material. Specifically, attention is paid on the development of contrast agents for magnetic fields higher

  19. Molecular Imaging in Schizophrenia Spectrum Disorders

    NARCIS (Netherlands)

    Klein, H.C.; Doorduin, J.; van Berckel, B.N.M.

    2014-01-01

    In this chapter, we aim to shed light on the schizophrenia spectrum disorders using molecular imaging. Schizophrenia spectrum disorders consist primarily of the disorders with full-blown psychosis in their course and are grouped in the DSM-IV category of schizophrenia and other psychotic disorders.

  20. Distinct molecular sites of anaesthetic action: pentobarbital block of human brain sodium channels is alleviated by removal of fast inactivation

    NARCIS (Netherlands)

    Wartenberg, H. C.; Urban, B. W.; Duch, D. S.

    1999-01-01

    Fast inactivation of sodium channel function is modified by anaesthetics. Its quantitative contribution to the overall anaesthetic effect is assessed by removing the fast inactivation mechanism enzymatically. Sodium channels from human brain cortex were incorporated into planar lipid bilayers. After

  1. Connotation and category of functional-molecular imaging

    International Nuclear Information System (INIS)

    Li Tianran; Tian Jiahe

    2007-01-01

    Function and molecular lmaging represent medical imaging' s direction. The review article introduce function and molecular's concept and category and its characteristic. Comparing with traditionary classics radiology, function and molecular imaging have many features, such as micro-mount and specificity and quantitative. There are many technology about function and molecular imaging. Function and molecular imaging is important ingredient of modern medical and play a considerable role. (authors)

  2. Molecular photoacoustic imaging of follicular thyroid carcinoma

    DEFF Research Database (Denmark)

    Levi, Jelena; Kothapalli, Sri-Rajashekar; Bohndiek, Sarah

    2013-01-01

    in living mice optically, observing the increase in Alexa750 fluorescence, and photoacoustically, using a dual wavelength imaging method. Results Active forms of both MMP2 and MMP-9 enzymes were found in FTC133 tumor homogenates, with MMP-9 detected in greater amounts. The molecular imaging agent......Purpose To evaluate the potential of targeted photoacoustic imaging as a non-invasive method for detection of follicular thyroid carcinoma. Experimental Design We determined the presence and activity of two members of matrix metalloproteinase family (MMP), MMP-2 and MMP-9, suggested as biomarkers...... for malignant thyroid lesions, in FTC133 thyroid tumors subcutaneously implanted in nude mice. The imaging agent used to visualize tumors was MMP activatable photoacoustic probe, Alexa750-CXeeeeXPLGLAGrrrrrXK-BHQ3. Cleavage of the MMP activatable agent was imaged after intratumoral and intravenous injections...

  3. Molecular Imaging and nuclear medicine: expectations and requirements

    International Nuclear Information System (INIS)

    Rollo, F.D.

    2003-01-01

    Molecular Imaging with Nuclear Medicine offers earlier, more accurate and more specific diagnosis, as well as targeted molecular therapy, providing significant improvements in clinical outcomes. (orig.)

  4. Functional and physical molecular size of the chicken hepatic lectin determined by radiation inactivation and sedimentation equilibrium analysis

    International Nuclear Information System (INIS)

    Steer, C.J.; Osborne, J.C. Jr.; Kempner, E.S.

    1990-01-01

    Radiation inactivation and sedimentation equilibrium analysis were used to determine the functional and physical size of the chicken hepatic membrane receptor that binds N-acetylglucosamine-terminated glycoproteins. Purified plasma membranes from chicken liver were irradiated with high energy electrons and assayed for 125I-agalactoorosomucoid binding. Increasing the dose of ionizing radiation resulted in a monoexponential decay in binding activity due to a progressive loss of binding sites. The molecular mass of the chicken lectin, determined in situ by target analysis, was 69,000 +/- 9,000 Da. When the same irradiated membranes were solubilized in Brij 58 and assayed, the binding protein exhibited a target size of 62,000 +/- 4,000 Da; in Triton X-100, the functional size of the receptor was 85,000 +/- 10,000 Da. Sedimentation equilibrium measurements of the purified binding protein yielded a lower limit molecular weight of 79,000 +/- 7,000. However, the solubilized lectin was detected as a heterogeneous population of oligomers with molecular weights as high as 450,000. Addition of calcium or calcium plus N-acetylglucosamine decreased the higher molecular weight species, but the lower limit molecular weights remained invariant. Similar results were determined when the chicken lectin was solubilized in Brij 58, C12E9, or 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonic acid (CHAPS). Results from the present study suggest that in the plasma membrane, the functional species of the chicken hepatic lectin exists as a trimer. However, in detergent solution, the purified receptor forms a heterogeneous population of irreversible oligomers that exhibit binding activity proportional to size

  5. Ethical and regulatory problems of molecular imaging

    International Nuclear Information System (INIS)

    Jeong, Jae Min

    2004-01-01

    As a molecular imaging is the most up-to-date technology in nuclear medicine, it has complicate ethical and regulatory problems. For animal experiment, we have to follow institutional animal care committee. For clinical experiment, we have to get approval of Institutional Review Board according to Helsinki declaration. In addition, approval from Korea Food and Drug Administration (KFDA) is essential for manufacturing and commercialization. However, too much regulation would suppress development of new technology, which would result in the loss of national competitive power. In addition, most new radioactive ligands for molecular imaging are administered to human at sub-pharmacological and sub-toxicological level. In conclusion, a balanced regulation is essential for the safety of clinical application and development of new technology

  6. Inactivation of Neurospora crassa conidia by singlet molecular oxygen generated by a photosensitized reaction

    International Nuclear Information System (INIS)

    Shimizu, M.; Egashira, T.; Takahama, U.

    1979-01-01

    Photodynamic damage of Neurospora crassa conidia was studied in the presence of the photosensitizing dye, toluidine blue O. Conidia which germinated to form colonies decreased in number as irradiation time became longer. The photoinactivation of conidia was suppressed by azide, bovine serum albumin, and histidine, and was stimulated in deuterium oxide. Wild-type conidia were less sensitive to the irradiation that albino conidia. In the wild type, carotenoid-enriched conidia were more resistant against the lethal damage than the conidia which contained small amounts of carotenoids. These results suggest that singlet molecular oxygen causes photodynamic lethal damage to N. crassa conidia and that singlet molecular oxygen is quenched by endogenous carotenoids

  7. Molecular Imaging in Synthetic Biology, and Synthetic Biology in Molecular Imaging.

    Science.gov (United States)

    Gilad, Assaf A; Shapiro, Mikhail G

    2017-06-01

    Biomedical synthetic biology is an emerging field in which cells are engineered at the genetic level to carry out novel functions with relevance to biomedical and industrial applications. This approach promises new treatments, imaging tools, and diagnostics for diseases ranging from gastrointestinal inflammatory syndromes to cancer, diabetes, and neurodegeneration. As these cellular technologies undergo pre-clinical and clinical development, it is becoming essential to monitor their location and function in vivo, necessitating appropriate molecular imaging strategies, and therefore, we have created an interest group within the World Molecular Imaging Society focusing on synthetic biology and reporter gene technologies. Here, we highlight recent advances in biomedical synthetic biology, including bacterial therapy, immunotherapy, and regenerative medicine. We then discuss emerging molecular imaging approaches to facilitate in vivo applications, focusing on reporter genes for noninvasive modalities such as magnetic resonance, ultrasound, photoacoustic imaging, bioluminescence, and radionuclear imaging. Because reporter genes can be incorporated directly into engineered genetic circuits, they are particularly well suited to imaging synthetic biological constructs, and developing them provides opportunities for creative molecular and genetic engineering.

  8. Molecular Imaging with Activatable Reporter Systems

    Directory of Open Access Journals (Sweden)

    Gang Niu, Xiaoyuan Chen

    2012-01-01

    Full Text Available Molecular imaging is a newly emerged multiple disciplinary field that aims to visualize, characterize and quantitatively measure biological processes at cellular and molecular levels in humans and other living systems. A reporter gene is a piece of DNA encoding reporter protein, which presents as a readily measurable phenotype that can be distinguished easily from the background of endogenous protein. After being transferred into cells of organ systems (transgenes, the reporter gene can be utilized to visualize transcriptional and posttranscriptional regulation of gene expression, protein-protein interactions, or trafficking of proteins or cells in living subjects. Herein, we review previous classification of reporter genes and regroup the reporter gene based imaging as basic, inducible and activatable, based on the regulation of reporter gene transcription and post-translational modification of reporter proteins. We then focus on activatable reporters, in which the signal can be activated at the posttranslational level for visualizing protein-protein interactions, protein phosphorylation or tertiary structure changes. The applications of several types of activatable reporters will also be summarized. We conclude that activatable reporter imaging can benefit both basic biomedical research and drug development.

  9. Neutron imaging for inertial confinement fusion and molecular optic imaging

    International Nuclear Information System (INIS)

    Delage, O.

    2010-01-01

    Scientific domains that require imaging of micrometric/nano-metric objects are dramatically increasing (Plasma Physics, Astrophysics, Biotechnology, Earth Sciences...). Difficulties encountered in imaging smaller and smaller objects make this research area more and more challenging and in constant evolution. The two scientific domains, through which this study has been led, are the neutron imaging in the context of the inertial confinement fusion and the fluorescence molecular imaging. Work presented in this thesis has two main objectives. The first one is to describe the instrumentation characteristics that require such imagery and, relatively to the scientific domains considered, identify parameters likely to optimize the imaging system accuracy. The second one is to present the developed data analysis and reconstruction methods able to provide spatial resolution adapted to the size of the observed object. Similarities of numerical algorithms used in these two scientific domains, which goals are quiet different, show how micrometric/nano-metric object imaging is a research area at the border of a large number of scientific disciplines. (author)

  10. Molecular imaging with targeted contrast ultrasound.

    Science.gov (United States)

    Piedra, Mark; Allroggen, Achim; Lindner, Jonathan R

    2009-01-01

    Molecular imaging with contrast-enhanced ultrasound uses targeted microbubbles that are retained in diseased tissue. The resonant properties of these microbubbles produce acoustic signals in an ultrasound field. The microbubbles are targeted to diseased tissue by using certain chemical constituents in the microbubble shell or by attaching disease-specific ligands such as antibodies to the microbubble. In this review, we discuss the applications of this technique to pathological states in the cerebrovascular system including atherosclerosis, tumor angiogenesis, ischemia, intravascular thrombus, and inflammation. Copyright 2009 S. Karger AG, Basel.

  11. Molecular imaging in Libman-Sacks endocarditis

    DEFF Research Database (Denmark)

    Dahl, Anders; Schaadt, Bente K; Santoni-Rugiu, Eric

    2015-01-01

    cardiothoracic surgery and pathologic examinations showed characteristic morphology of Libman-Sacks vegetations. All microbiological examinations including blood cultures, microscopy, culture and 16s PCR of the valve were negative and the diagnosis of Libman-Sacks endocarditis was convincing. It is difficult...... to distinguish Libman-Sacks endocarditis from culture-negative infective endocarditis (IE). Molecular imaging techniques are being used increasingly in cases of suspected IE but no studies have previously reported the use in patients with Libman-Sacks endocarditis. In the present case, (18)F-FDG-PET-CT clearly...

  12. Molecular imaging of apoptosis in cancer

    International Nuclear Information System (INIS)

    Hakumaeki, Juhana M.; Liimatainen, Timo

    2005-01-01

    Apoptosis plays an important role in cancer. Mechanisms hindering its action are implicated in a number of malignancies. Also, the induction of apoptosis plays a pivotal role in non-surgical cancer treatment regimes such as irradiation, chemotherapy, or hormones. Recent advanced in imaging science have made it now possible for us to detect and visualize previously inaccessible and even unrecognized biological phenomena in cells and tissue undergoing apoptosis in vivo. Not only are these imaging techniques painting an intriguing picture of the spatiotemporal characteristics and metabolic and biophysical of apoptosis in situ, but they are expected to have an ever increasing impact in preclinical testing and design of new anticancer agents as well. Rapid and accurate visualization of apoptotic response in the clinical settings can also be of significant diagnostic and prognostic worth. With the advent of molecular medicine and patient-tailored treatment options and therapeutic agents, such monitoring techniques are becoming paramount

  13. Bioresponsive probes for molecular imaging: concepts and in vivo applications

    NARCIS (Netherlands)

    Duijnhoven, S.M. van; Robillard, M.S.; Langereis, S.; Grull, H.

    2015-01-01

    Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of

  14. Bioresponsive probes for molecular imaging : Concepts and in vivo applications

    NARCIS (Netherlands)

    van Duijnhoven, S.M.J.; Robillard, M.S.; Langereis, S.; Grüll, H.

    2015-01-01

    Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of

  15. [Molecular imaging; current status and future prospects in USA].

    Science.gov (United States)

    Kobayashi, Hisataka

    2007-02-01

    The goal of this review is to introduce the definition, current status, and future prospects of the molecular imaging, which has recently been a hot topic in medicine and the biological science in USA. In vivo imaging methods to visualize the molecular events and functions in organs or animals/humans are overviewed and discussed especially in combinations of imaging modalities (machines) and contrast agents(chemicals) used in the molecular imaging. Next, the close relationship between the molecular imaging and the nanotechnology, an important part of nanomedicine, is stressed from the aspect of united multidisciplinary sciences such as physics, chemistry, biology, and medicine.

  16. The research progress of nuclear medicine on cardiovascular molecular imaging

    International Nuclear Information System (INIS)

    Yin Xiaohua; Zhang Yongxue

    2007-01-01

    Cardiovascular molecular imaging is a rapidly evolving discipline and its clinical application is promising. Nuclear medicine is playing a leading role in this field with its special superiority of noninvasive, quantifiability, high sensitivity and specificity. It provides broad opportunities for exploring the pathophysiologic process of cardiovascular diseases and monitoring its gene therapy in the molecular level. In this review, we mainly discuss some basic knowledge on cardiovascular molecular imaging, and then focus on the applied research prospect of nuclear medicine radionuclide imaging. (authors)

  17. Molecular ultrasound imaging: current status and future directions

    International Nuclear Information System (INIS)

    Deshpande, N.; Needles, A.; Willmann, J.K.

    2010-01-01

    Targeted contrast-enhanced ultrasound (molecular ultrasound) is an emerging imaging strategy that combines ultrasound technology with novel molecularly-targeted ultrasound contrast agents for assessing biological processes at the molecular level. Molecular ultrasound contrast agents are nano- or micro-sized particles that are targeted to specific molecular markers by adding high-affinity binding ligands onto the surface of the particles. Following intravenous administration, these targeted ultrasound contrast agents accumulate at tissue sites overexpressing specific molecular markers, thereby enhancing the ultrasound imaging signal. High spatial and temporal resolution, real-time imaging, non-invasiveness, relatively low costs, lack of ionising irradiation and wide availability of ultrasound systems are advantages compared to other molecular imaging modalities. In this article we review current concepts and future directions of molecular ultrasound imaging, including different classes of molecular ultrasound contrast agents, ongoing technical developments of pre-clinical and clinical ultrasound systems, the potential of molecular ultrasound for imaging different diseases at the molecular level, and the translation of molecular ultrasound into the clinic.

  18. Molecular imaging in the era of personalized medicine.

    Science.gov (United States)

    Jung, Kyung-Ho; Lee, Kyung-Han

    2015-01-01

    Clinical imaging creates visual representations of the body interior for disease assessment. The role of clinical imaging significantly overlaps with that of pathology, and diagnostic workflows largely depend on both fields. The field of clinical imaging is presently undergoing a radical change through the emergence of a new field called molecular imaging. This new technology, which lies at the intersection between imaging and molecular biology, enables noninvasive visualization of biochemical processes at the molecular level within living bodies. Molecular imaging differs from traditional anatomical imaging in that biomarkers known as imaging probes are used to visualize target molecules-of-interest. This ability opens up exciting new possibilities for applications in oncologic, neurological and cardiovascular diseases. Molecular imaging is expected to make major contributions to personalized medicine by allowing earlier diagnosis and predicting treatment response. The technique is also making a huge impact on pharmaceutical development by optimizing preclinical and clinical tests for new drug candidates. This review will describe the basic principles of molecular imaging and will briefly touch on three examples (from an immense list of new techniques) that may contribute to personalized medicine: receptor imaging, angiogenesis imaging, and apoptosis imaging.

  19. Magnetic resonance imaging of vulnerable atherosclerotic plaques: current imaging strategies and molecular imaging probes

    NARCIS (Netherlands)

    Briley-Saebo, Karen C.; Mulder, Willem J. M.; Mani, Venkatesh; Hyafil, Fabien; Amirbekian, Vardan; Aguinaldo, Juan Gilberto S.; Fisher, Edward A.; Fayad, Zahi A.

    2007-01-01

    The vulnerability or destabilization of atherosclerotic plaques has been directly linked to plaque composition. Imaging modalities, such as magnetic resonance (MR) imaging, that allow for evaluation of plaque composition at a cellular and molecular level, could further improve the detection of

  20. Translational research of optical molecular imaging for personalized medicine.

    Science.gov (United States)

    Qin, C; Ma, X; Tian, J

    2013-12-01

    In the medical imaging field, molecular imaging is a rapidly developing discipline and forms many imaging modalities, providing us effective tools to visualize, characterize, and measure molecular and cellular mechanisms in complex biological processes of living organisms, which can deepen our understanding of biology and accelerate preclinical research including cancer study and medicine discovery. Among many molecular imaging modalities, although the penetration depth of optical imaging and the approved optical probes used for clinics are limited, it has evolved considerably and has seen spectacular advances in basic biomedical research and new drug development. With the completion of human genome sequencing and the emergence of personalized medicine, the specific drug should be matched to not only the right disease but also to the right person, and optical molecular imaging should serve as a strong adjunct to develop personalized medicine by finding the optimal drug based on an individual's proteome and genome. In this process, the computational methodology and imaging system as well as the biomedical application regarding optical molecular imaging will play a crucial role. This review will focus on recent typical translational studies of optical molecular imaging for personalized medicine followed by a concise introduction. Finally, the current challenges and the future development of optical molecular imaging are given according to the understanding of the authors, and the review is then concluded.

  1. Molecular Imaging and Therapy of Merkel Cell Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Beylergil, Volkan, E-mail: beylergv@mskcc.org [Molecular and Imaging Therapy Service, Department of Radiology Box 77, Memorial Sloan-Kettering Cancer Center 1275 York Ave, New York, NY 10065 (United States); Carrasquillo, Jorge A. [Molecular and Imaging Therapy Service, Department of Radiology Box 77, Memorial Sloan-Kettering Cancer Center 1275 York Ave, New York, NY 10065 (United States); Department of Radiology, Weill Cornell Medical Center, New York, NY 10065 (United States)

    2014-04-29

    Several molecular imaging modalities have been evaluated in the management of Merkel cell carcinoma (MCC), a rare and aggressive tumor with a high tendency to metastasize. Continuous progress in the field of molecular imaging might improve management in these patients. The authors review the current modalities and their impact on MCC in this brief review article.

  2. Molecular Imaging and Therapy of Merkel Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Volkan Beylergil

    2014-04-01

    Full Text Available Several molecular imaging modalities have been evaluated in the management of Merkel cell carcinoma (MCC, a rare and aggressive tumor with a high tendency to metastasize. Continuous progress in the field of molecular imaging might improve management in these patients. The authors review the current modalities and their impact on MCC in this brief review article.

  3. Molecular Imaging and Precision Medicine in Prostate Cancer.

    Science.gov (United States)

    Ceci, Francesco; Fiorentino, Michelangelo; Castellucci, Paolo; Fanti, Stefano

    2017-01-01

    The aim of the present review is to discuss about the role of new probes for molecular imaging in the evaluation of prostate cancer (PCa). This review focuses particularly on the role of new promising radiotracers for the molecular imaging with PET/computed tomography in the detection of PCa recurrence. The role of these new imaging techniques to guide lesion-target therapies and the potential application of these molecular probes as theranostics agents is discussed. Finally, the molecular mechanisms underlying resistance to castration in PCa and the maintenance of active androgen receptor are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. DNA aptamer functionalized gold nanostructures for molecular recognition and photothermal inactivation of methicillin-Resistant Staphylococcus aureus.

    Science.gov (United States)

    Ocsoy, Ismail; Yusufbeyoglu, Sadi; Yılmaz, Vedat; McLamore, Eric S; Ildız, Nilay; Ülgen, Ahmet

    2017-11-01

    In this work, we report the development of DNA aptamer-functionalized gold nanoparticles (Apt@Au NPs) and gold nanorods (Apt@Au NRs) for inactivation of Methicillin-resistant Staphylococcus aureus (MRSA) with targeted photothermal therapy (PTT). Although both Apt@Au NPs and Apt@Au NRs specifically bind to MRSA cells, Apt@Au NPs and Apt@Au NRs inactivated ∼5% and over 95% of the cells,respectively through PTT. This difference in inactivation was based on the relatively high longitudinal absorption of near-infrared (NIR) radiation and strong photothermal conversion capability for the Apt@Au NRs compared to the Apt@Au NPs. The Au NRs served as a nanoplatform for the loading of thiolated aptamer and also provided multivalent effects for increasing binding strength and affinity to MRSA. Our results indicate that the type of aptamer and the degree of multivalent effect(s) are important factors for MRSA inactivation efficiency in PTT. We show that the Apt@Au NRs are a very effective and promising nanosystem for specific cell recognition and in vitro PTT. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Resonance Energy Transfer Molecular Imaging Application in Biomedicine

    Directory of Open Access Journals (Sweden)

    NIE Da-hong1,2;TANG Gang-hua1,3

    2016-11-01

    Full Text Available Resonance energy transfer molecular imaging (RETI can markedly improve signal intensity and tissue penetrating capacity of optical imaging, and have huge potential application in the deep-tissue optical imaging in vivo. Resonance energy transfer (RET is an energy transition from the donor to an acceptor that is in close proximity, including non-radiative resonance energy transfer and radiative resonance energy transfer. RETI is an optical imaging technology that is based on RET. RETI mainly contains fluorescence resonance energy transfer imaging (FRETI, bioluminescence resonance energy transfer imaging (BRETI, chemiluminescence resonance energy transfer imaging (CRETI, and radiative resonance energy transfer imaging (RRETI. RETI is the hot field of molecular imaging research and has been widely used in the fields of biology and medicine. This review mainly focuses on RETI principle and application in biomedicine.

  6. Computational methods in molecular imaging technologies

    CERN Document Server

    Gunjan, Vinit Kumar; Venkatesh, C; Amarnath, M

    2017-01-01

    This book highlights the experimental investigations that have been carried out on magnetic resonance imaging and computed tomography (MRI & CT) images using state-of-the-art Computational Image processing techniques, and tabulates the statistical values wherever necessary. In a very simple and straightforward way, it explains how image processing methods are used to improve the quality of medical images and facilitate analysis. It offers a valuable resource for researchers, engineers, medical doctors and bioinformatics experts alike.

  7. Nanomedicine: Perspective and promises with ligand-directed molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pan Dipanjan [Department of Medicine, Washington University Medical School, St. Louis, MO (United States)], E-mail: dipanjan@wustl.edu; Lanza, Gregory M.; Wickline, Samuel A. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Caruthers, Shelton D. [Department of Medicine, Washington University Medical School, St. Louis, MO (United States); Philips Healthcare, Andover, MA (United States)], E-mail: scaruthers@cmrl.wustl.edu

    2009-05-15

    Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

  8. Nanomedicine: Perspective and promises with ligand-directed molecular imaging

    International Nuclear Information System (INIS)

    Pan Dipanjan; Lanza, Gregory M.; Wickline, Samuel A.; Caruthers, Shelton D.

    2009-01-01

    Molecular imaging and targeted drug delivery play an important role toward personalized medicine, which is the future of patient management. Of late, nanoparticle-based molecular imaging has emerged as an interdisciplinary area, which shows promises to understand the components, processes, dynamics and therapies of a disease at a molecular level. The unprecedented potential of nanoplatforms for early detection, diagnosis and personalized treatment of diseases, have found application in every biomedical imaging modality. Biological and biophysical barriers are overcome by the integration of targeting ligands, imaging agents and therapeutics into the nanoplatform which allow for theranostic applications. In this article, we have discussed the opportunities and potential of targeted molecular imaging with various modalities putting a particular emphasis on perfluorocarbon nanoemulsion-based platform technology.

  9. Molecular imaging in the framework of personalized cancer medicine.

    Science.gov (United States)

    Belkić, Dzevad; Belkić, Karen

    2013-11-01

    With our increased understanding of cancer cell biology, molecular imaging offers a strategic bridge to oncology. This complements anatomic imaging, particularly magnetic resonance (MR) imaging, which is sensitive but not specific. Among the potential harms of false positive findings is lowered adherence to recommended surveillance post-therapy and by persons at increased cancer risk. Positron emission tomography (PET) plus computerized tomography (CT) is the molecular imaging modality most widely used in oncology. In up to 40% of cases, PET-CT leads to changes in therapeutic management. Newer PET tracers can detect tumor hypoxia, bone metastases in androgen-sensitive prostate cancer, and human epidermal growth factor receptor type 2 (HER2)-expressive tumors. Magnetic resonance spectroscopy provides insight into several metabolites at the same time. Combined with MRI, this yields magnetic resonance spectroscopic imaging (MRSI), which does not entail ionizing radiation and is thus suitable for repeated monitoring. Using advanced signal processing, quantitative information can be gleaned about molecular markers of brain, breast, prostate and other cancers. Radiation oncology has benefited from molecular imaging via PET-CT and MRSI. Advanced mathematical approaches can improve dose planning in stereotactic radiosurgery, stereotactic body radiotherapy and high dose-rate brachytherapy. Molecular imaging will likely impact profoundly on clinical decision making in oncology. Molecular imaging via MR could facilitate early detection especially in persons at high risk for specific cancers.

  10. Luminescence imaging using radionuclides: a potential application in molecular imaging

    International Nuclear Information System (INIS)

    Park, Jeong Chan; Il An, Gwang; Park, Se-Il; Oh, Jungmin; Kim, Hong Joo; Su Ha, Yeong; Wang, Eun Kyung; Min Kim, Kyeong; Kim, Jung Young; Lee, Jaetae; Welch, Michael J.; Yoo, Jeongsoo

    2011-01-01

    Introduction: Nuclear and optical imaging are complementary in many aspects and there would be many advantages when optical imaging probes are prepared using radionuclides rather than classic fluorophores, and when nuclear and optical dual images are obtained using single imaging probe. Methods: The luminescence intensities of various radionuclides having different decay modes have been assayed using luminescence imaging and in vitro luminometer. Radioiodinated Herceptin was injected into a tumor-bearing mouse, and luminescence and microPET images were obtained. The plant dipped in [ 32 P]phosphate solution was scanned in luminescence mode. Radio-TLC plate was also imaged in the same imaging mode. Results: Radionuclides emitting high energy β + /β - particles showed higher luminescence signals. NIH3T6.7 tumors were detected in both optical and nuclear imaging. The uptake of [ 32 P]phosphate in plant was easily followed by luminescence imaging. Radio-TLC plate was visualized and radiochemical purity was quantified using luminescence imaging. Conclusion: Many radionuclides with high energetic β + or β - particles during decay were found to be imaged in luminescence mode due mainly to Cerenkov radiation. 'Cerenkov imaging' provides a new optical imaging platform and an invaluable bridge between optical and nuclear imaging. New optical imaging probes could be easily prepared using well-established radioiodination methods. Cerenkov imaging will have more applications in the research field of plant science and autoradiography.

  11. Translational Applications of Molecular Imaging and Radionuclide Therapy

    International Nuclear Information System (INIS)

    Welch, Michael J.; Eckelman, William C.; Vera, David

    2005-01-01

    Molecular imaging is becoming a larger part of imaging research and practice. The Office of Biological and Environmental Research of the Department of Energy funds a significant number of researchers in this area. The proposal is to partially fund a workshop to inform scientists working in nuclear medicine and nuclear medicine practitioners of the recent advances of molecular imaging in nuclear medicine as well as other imaging modalities. A limited number of topics related to radionuclide therapy will also be discussed. The proposal is to request partial funds for the workshop entitled ''Translational Applications of Molecular Imaging and Radionuclide Therapy'' to be held prior to the Society of Nuclear Medicine Annual Meeting in Toronto, Canada in June 2005. The meeting will be held on June 17-18. This will allow scientists interested in all aspects of nuclear medicine imaging to attend. The chair of the organizing group is Dr. Michael J. Welch. The organizing committee consists of Dr. Welch, Dr. William C. Eckelman and Dr. David Vera. The goal is to invite speakers to discuss the most recent advances of modern molecular imaging and therapy. Speakers will present advances made in in vivo tagging imaging assays, technical aspects of small animal imaging, in vivo imaging and bench to bedside translational study; and the role of a diagnostic scan on therapy selection. This latter topic will include discussions on therapy and new approaches to dosimetry. Several of these topics are those funded by the Department of Energy Office of Biological and Environmental Research

  12. Quantitative Methods for Molecular Diagnostic and Therapeutic Imaging

    OpenAIRE

    Li, Quanzheng

    2013-01-01

    This theme issue provides an overview on the basic quantitative methods, an in-depth discussion on the cutting-edge quantitative analysis approaches as well as their applications for both static and dynamic molecular diagnostic and therapeutic imaging.

  13. Molecular-resolution imaging of pentacene on KCl(001

    Directory of Open Access Journals (Sweden)

    Julia L. Neff

    2012-02-01

    Full Text Available The growth of pentacene on KCl(001 at submonolayer coverage was studied by dynamic scanning force microscopy. At coverages below one monolayer pentacene was found to arrange in islands with an upright configuration. The molecular arrangement was resolved in high-resolution images. In these images two different types of patterns were observed, which switch repeatedly. In addition, defects were found, such as a molecular vacancy and domain boundaries.

  14. Nanobody: The “Magic Bullet” for Molecular Imaging?

    Science.gov (United States)

    Chakravarty, Rubel; Goel, Shreya; Cai, Weibo

    2014-01-01

    Molecular imaging involves the non-invasive investigation of biological processes in vivo at the cellular and molecular level, which can play diverse roles in better understanding and treatment of various diseases. Recently, single domain antigen-binding fragments known as 'nanobodies' were bioengineered and tested for molecular imaging applications. Small molecular size (~15 kDa) and suitable configuration of the complementarity determining regions (CDRs) of nanobodies offer many desirable features suitable for imaging applications, such as rapid targeting and fast blood clearance, high solubility, high stability, easy cloning, modular nature, and the capability of binding to cavities and difficult-to-access antigens. Using nanobody-based probes, several imaging techniques such as radionuclide-based, optical and ultrasound have been employed for visualization of target expression in various disease models. This review summarizes the recent developments in the use of nanobody-based probes for molecular imaging applications. The preclinical data reported to date are quite promising, and it is expected that nanobody-based molecular imaging agents will play an important role in the diagnosis and management of various diseases. PMID:24578722

  15. MRI Reporter Genes for Noninvasive Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Caixia Yang

    2016-05-01

    Full Text Available Magnetic resonance imaging (MRI is one of the most important imaging technologies used in clinical diagnosis. Reporter genes for MRI can be applied to accurately track the delivery of cell in cell therapy, evaluate the therapy effect of gene delivery, and monitor tissue/cell-specific microenvironments. Commonly used reporter genes for MRI usually include genes encoding the enzyme (e.g., tyrosinase and β-galactosidase, the receptor on the cells (e.g., transferrin receptor, and endogenous reporter genes (e.g., ferritin reporter gene. However, low sensitivity limits the application of MRI and reporter gene-based multimodal imaging strategies are common including optical imaging and radionuclide imaging. These can significantly improve diagnostic efficiency and accelerate the development of new therapies.

  16. Molecular imaging of cancer using PET and SPECT

    DEFF Research Database (Denmark)

    Kjaer, Andreas

    2006-01-01

    for molecular imaging of cancer. Especially the possibility of a quick transfer of methods developed in animals to patients (translational research) is an important strength. This article will briefly discuss the newest applications and their importance and perspective in relation to the shift in paradigm......Molecular imaging allows for the study of molecular and cellular events in the living intact organism. The nuclear medicine methodologies of positron emission tomography (PET) and single photon emission computer tomography (SPECT) posses several advantages, which make them particularly suited...

  17. Molecular Imaging and Precision Medicine in Dementia and Movement Disorders.

    Science.gov (United States)

    Mallik, Atul K; Drzezga, Alexander; Minoshima, Satoshi

    2017-01-01

    Precision medicine (PM) has been defined as "prevention and treatment strategies that take individual variability into account." Molecular imaging (MI) is an ideally suited tool for PM approaches to neurodegenerative dementia and movement disorders (MD). Here we review PM approaches and discuss how they may be applied to other associated neurodegenerative dementia and MD. With ongoing major therapeutic research initiatives that include the use of molecular imaging, we look forward to established interventions targeted to specific molecular pathophysiology and expect the potential benefit of MI PM approaches in neurodegenerative dementia and MD will only increase. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Nuclear Molecular Imaging Strategies in Immune Checkpoint Inhibitor Therapy

    DEFF Research Database (Denmark)

    Guldbrandsen, Kasper F; Hendel, Helle W; Langer, Seppo W

    2017-01-01

    this, new response criteria for evaluating these patients with morphologic imaging have been proposed. The aim of this paper is to review and discuss the current evidence for the use of molecular imaging, e.g., PET/CT (Positron Emission Tomography/Computer Tomography) with18F-Fluorodeoxyglucoes (FDG...

  19. Molecular mass spectrometry imaging in biomedical and life science research

    Czech Academy of Sciences Publication Activity Database

    Pól, Jaroslav; Strohalm, Martin; Havlíček, Vladimír; Volný, Michael

    2010-01-01

    Roč. 134, č. 5 (2010), s. 423-443 ISSN 0948-6143 R&D Projects: GA MŠk LC545; GA ČR GPP206/10/P018 Institutional research plan: CEZ:AV0Z50200510 Keywords : Mass spectrometry * Chemical imaging * Molecular imaging Subject RIV: EE - Microbiology, Virology Impact factor: 4.727, year: 2010

  20. Novel approach to improve molecular imaging research: Correlation between macroscopic and molecular pathological findings in patients

    Energy Technology Data Exchange (ETDEWEB)

    Boehm, Ingrid, E-mail: i.boehm@uni-bonn.de [Department of Diagnostic Radiology, ZARF Project, Center for Molecular Imaging Research MBMB, Philipps University of Marburg, Baldingerstrasse, 35039 Marburg (Germany)

    2011-09-15

    Purpose: Currently, clinical research approaches are sparse in molecular imaging studies. Moreover, possible links between imaging features and pathological laboratory parameters are unknown, so far. Therefore, the goal was to find a possible relationship between imaging features and peripheral blood cell apoptosis, and thereby to present a novel way to complement molecular imaging research. Materials and methods: The investigation has been done in systemic lupus erythematosus (SLE), a prototype of an autoimmune disease characterized by multiorgan involvement, autoantibody production, and disturbed apoptosis. Retrospectively, radiological findings have been compared to both autoantibody findings and percentage apoptotic blood cells. Results: Two SLE groups could be identified: patients with normal (annexin V binding < 20%), and with increased apoptosis (annexin V binding > 20%) of peripheral blood cells. The frequency of radiological examinations in SLE patients significantly correlated with an increased percentage of apoptotic cells (p < 0.005). In patients with characteristic imaging findings (e.g. lymph node swelling, pleural effusion) an elevated percentage of apoptotic cells was present. In contrast SLE-patients with normal imaging findings or uncharacteristic results of minimal severity had normal percentages of apoptotic blood cells. Conclusion: This correlation between radiographic findings and percentage of apoptotic blood cells provides (1) further insight into pathological mechanisms of SLE, (2) will offer the possibility to introduce apoptotic biomarkers as molecular probes for clinical molecular imaging approaches in future to early diagnose organ complaints in patients with SLE, and (3) is a plea to complement molecular imaging research by this clinical approach.

  1. The development of nanobody probes for molecular imaging

    International Nuclear Information System (INIS)

    Ding Zhiling; Lan Xiaoli; Zhang Yongxue

    2014-01-01

    The nanobody is a novel antibody fragment, which has beneficial biophysical and pharmacokinetic properties, such as the small molecular weight, high affinity and specificity for antigen. Nanobody is ideally suitable for molecular imaging as a targeting probe that could label antigen at nmol level in vitro. In animal models of xenografted tumor, atherosclerotic plaques and brain disorders, the target tissues were specifically and clearly detected and the high tumor-to-blood (T/B) ratios were obtained. Structural or chemical modified nanobodies will have higher affinity and retention to target tissues, and be convenient for the application of molecular imaging. With the development of the related research, nanobody-based molecular imaging will be gradually transformed into the clinical applications, and play an important role in early diagnosis and therapeutic assessment. (authors)

  2. Mechanically magnified imaging of molecular interferograms

    International Nuclear Information System (INIS)

    Stibor, A.; Stefanov, A.; Goldfarb, F.; Reiger, E.; Arndt, M.

    2005-01-01

    Full text: Imaging of surface adsorbed molecules is presented as a valuable detection method for matter interferometry with fluorescent particles. A mechanical magnification scheme is implemented to circumvent the optical resolution limit. Mechanically magnified fluorescence imaging turns out to be an excellent tool for recording quantum interference patterns with high visibility. A unique advantage of this technique is its scalability: for certain classes of nanosized objects, the detection sensitivity will even increase significantly with increasing size of the particle. (author)

  3. Cancerology: to see and to treat with molecular imaging

    International Nuclear Information System (INIS)

    2004-01-01

    By allowing to visualize, beyond the organs and tissues structure, the molecules present inside cells and their action in cell functioning, to the genome level, the molecular imaging opens a new era in biology and medicine and creates the conditions for the perfecting of targeting and personalised treatments of cancers. The E.M.I.L. network is the only European network in molecular imaging for the cancer. It has been initiated and is coordinated by 'the genes expression in vivo imaging group' of the Cea at Orsay. The E.M.I.L network represents 43 organisms of 13 european countries with 6 technological platforms. (N.C.)

  4. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun Ki; Herbst, Roy

    2006-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  5. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2008-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  6. IMPACT (Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets and Complementary, Innovative and Therapeutic Modalities)

    National Research Council Canada - National Science Library

    Hong, Waun K; Herbst, Roy

    2007-01-01

    .... These projects combine targeted approaches using molecular and imaging techniques to validate activity against a target and monitor response using imaging modalities specific to the receptor using...

  7. [Future perspectives for diagnostic imaging in urology: from anatomic and functional to molecular imaging].

    Science.gov (United States)

    Macis, Giuseppe; Di Giovanni, Silvia; Di Franco, Davide; Bonomo, Lorenzo

    2013-01-01

    The future approach of diagnostic imaging in urology follows the technological progress, which made the visualization of in vivo molecular processes possible. From anatomo-morphological diagnostic imaging and through functional imaging molecular radiology is reached. Based on molecular probes, imaging is aimed at assessing the in vivo molecular processes, their physiology and function at cellular level. The future imaging will investigate the complex tumor functioning as metabolism, aerobic glycolysis in particular, angiogenesis, cell proliferation, metastatic potential, hypoxia, apoptosis and receptors expressed by neoplastic cells. Methods for performing molecular radiology are CT, MRI, PET-CT, PET-MRI, SPECT and optical imaging. Molecular ultrasound combines technological advancement with targeted contrast media based on microbubbles, this allowing the selective registration of microbubble signal while that of stationary tissues is suppressed. An experimental study was carried out where the ultrasound molecular probe BR55 strictly bound to prostate tumor results in strong enhancement in the early phase after contrast, this contrast being maintained in the late phase. This late enhancement is markedly significant for the detection of prostatic cancer foci and to guide the biopsy sampling. The 124I-cG250 molecular antibody which is strictly linked to cellular carbonic anhydrase IX of clear cell renal carcinoma, allows the acquisition of diagnostic PET images of clear cell renal carcinoma without biopsy. This WG-250 (RENCAREX) antibody was used as a therapy in metastatic clear cell renal carcinoma. Future advancements and applications will result in early cancer diagnosis, personalized therapy that will be specific according to the molecular features of cancer and leading to the development of catheter-based multichannel molecular imaging devices for cystoscopy-based molecular imaging diagnosis and intervention.

  8. Thermoacoustic Molecular Imaging of Small Animals

    Directory of Open Access Journals (Sweden)

    Robert A. Kruger

    2003-04-01

    Full Text Available We have designed, constructed, and tested a thermoacoustic computed tomography (TCT scanner for imaging optical absorption in small animals in three dimensions. The device utilizes pulsed laser irradiation (680–1064 nm and a unique, 128-element transducer array. We quantified the isotropic spatial resolution of this scanner to be 0.35 mm. We describe a dual-wavelength subtraction technique for isolating optical dyes with TCT. Phantom experiments demonstrate that we can detect 5 fmol of a near-infrared dye (indocyanine green, ICG in a 1-ML volume using dual-wavelength subtraction. Initial TCT imaging in phantoms and in two sacrificed mice suggests that three-dimensional, optical absorption patterns in small animals can be detected with an order of magnitude better spatial resolution and an order of magnitude better low-contrast detectability in small animals when compared to fluorescence imaging or diffusion optical tomography.

  9. Molecular Imaging in Stem Cell Therapy for Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    Fahuan Song

    2014-01-01

    Full Text Available Spinal cord injury (SCI is a serious disease of the center nervous system (CNS. It is a devastating injury with sudden loss of motor, sensory, and autonomic function distal to the level of trauma and produces great personal and societal costs. Currently, there are no remarkable effective therapies for the treatment of SCI. Compared to traditional treatment methods, stem cell transplantation therapy holds potential for repair and functional plasticity after SCI. However, the mechanism of stem cell therapy for SCI remains largely unknown and obscure partly due to the lack of efficient stem cell trafficking methods. Molecular imaging technology including positron emission tomography (PET, magnetic resonance imaging (MRI, optical imaging (i.e., bioluminescence imaging (BLI gives the hope to complete the knowledge concerning basic stem cell biology survival, migration, differentiation, and integration in real time when transplanted into damaged spinal cord. In this paper, we mainly review the molecular imaging technology in stem cell therapy for SCI.

  10. Magnetic nanoparticles as contrast agents for molecular imaging in medicine

    Science.gov (United States)

    O'Donnell, Matthew

    2018-05-01

    For over twenty years, superparamagnetic nanoparticles have been developed for a number of medical applications ranging from bioseparations, magnetic drug targeting, hyperthermia and imaging. Recent studies have shown that they can be functionalized for in vivo biological targeting, potentially enabling nanoagents for molecular imaging and site-localized drug delivery. Here we review several imaging technologies developed using functionalized superparamagnetic iron oxide nanoparticles (SPIONs) as targeted molecular agents. Several imaging modalities have exploited the large induced magnetic moment of SPIONs to create local mechanical force. Magnetic force microscopy can probe nanoparticle uptake in single cells. For in vivo applications, magnetomotive modulation of primary images in ultrasound (US), photoacoustics (PA), and optical coherence tomography (OCT) can help identify very small concentrations of nanoagents while simultaneously suppressing intrinsic background signals from tissue.

  11. Multi-target molecular imaging and its progress in research and application

    International Nuclear Information System (INIS)

    Tang Ganghua

    2011-01-01

    Multi-target molecular imaging (MMI) is an important field of research in molecular imaging. It includes multi-tracer multi-target molecular imaging(MTMI), fusion-molecule multi-target imaging (FMMI), coupling-molecule multi-target imaging (CMMI), and multi-target multifunctional molecular imaging(MMMI). In this paper,imaging modes of MMI are reviewed, and potential applications of positron emission tomography MMI in near future are discussed. (author)

  12. Molecular imaging: a new approach to nuclear cardiology

    International Nuclear Information System (INIS)

    Dobrucki, L.W.; Sinusas, A.J.

    2005-01-01

    Nuclear cardiology has historically played an important role in detection of cardiovascular disease as well as risk statification. With the growth of molecular biology have come new therapeutic interventions and the requirement for new diagnostic imaging approaches. Noninvasive targeted radiotracer based as well as transporter gene imaging strategies are evolving to meet these new needs, but require the development of an interdisciplinary approach which focuses on molecular processes, as well as the pathogenesis and progression of disease. This progress has been made possible with the availability of transgenic animal models along with many technological advances. Future adaptations of the developing experimental procedures and instrumentations will allow for the smooth translation and application to clinical practice. This review is intended as a brief overview on the subject molecular imaging. Basic concepts and historical perspective of molecular imaging will be reviewed first, followed by description of current technology, and concluding with current applications in cardiology. The emphasis will be on the use of both single photon emission computed tomography (SPECT) and positron emission tomography (PET) radiotracers, although other imaging modalities will be also briefly discussed. The specific approaches presented here will include receptor-based and reporter gene imaging of natural and therapeutical angiogenesis

  13. Online molecular image repository and analysis system: A multicenter collaborative open-source infrastructure for molecular imaging research and application.

    Science.gov (United States)

    Rahman, Mahabubur; Watabe, Hiroshi

    2018-05-01

    Molecular imaging serves as an important tool for researchers and clinicians to visualize and investigate complex biochemical phenomena using specialized instruments; these instruments are either used individually or in combination with targeted imaging agents to obtain images related to specific diseases with high sensitivity, specificity, and signal-to-noise ratios. However, molecular imaging, which is a multidisciplinary research field, faces several challenges, including the integration of imaging informatics with bioinformatics and medical informatics, requirement of reliable and robust image analysis algorithms, effective quality control of imaging facilities, and those related to individualized disease mapping, data sharing, software architecture, and knowledge management. As a cost-effective and open-source approach to address these challenges related to molecular imaging, we develop a flexible, transparent, and secure infrastructure, named MIRA, which stands for Molecular Imaging Repository and Analysis, primarily using the Python programming language, and a MySQL relational database system deployed on a Linux server. MIRA is designed with a centralized image archiving infrastructure and information database so that a multicenter collaborative informatics platform can be built. The capability of dealing with metadata, image file format normalization, and storing and viewing different types of documents and multimedia files make MIRA considerably flexible. With features like logging, auditing, commenting, sharing, and searching, MIRA is useful as an Electronic Laboratory Notebook for effective knowledge management. In addition, the centralized approach for MIRA facilitates on-the-fly access to all its features remotely through any web browser. Furthermore, the open-source approach provides the opportunity for sustainable continued development. MIRA offers an infrastructure that can be used as cross-boundary collaborative MI research platform for the rapid

  14. Molecular Imaging of Ovarian Carcinoma Angiogenesis

    Science.gov (United States)

    2007-03-01

    specifically taken up by several benign conditions such as inflammatory disease, pneumonia, brown fat, muscle, bowel uptake, and granulomatous disease...demonstrated in vivo imaging of vascular cell proliferation- associated states, whether focal, as in postangioplasty re- stenosis , or diffuse, as in pulmonary...limitations. The tracer can be nonspecifically taken up by several benign condi- tions such as inflammatory disease, pneumonia, brown fat, muscle

  15. Molecular Imaging of Breast Cancer: Present and future directions

    Directory of Open Access Journals (Sweden)

    David eAlcantara

    2014-12-01

    Full Text Available Medical imaging technologies have undergone explosive growth over the past few decades and now play a central role in clinical oncology. But the truly transformative power of imaging in the clinical management of cancer patients lies ahead. Today, imaging is at a crossroads, with molecularly targeted imaging agents expected to broadly expand the capabilities of conventional anatomical imaging methods. Molecular imaging will allow clinicians to not only see where a tumour is located in the body, but also to visualize the expression and activity of specific molecules (e.g. proteases and protein kinases and biological processes (e.g. apoptosis, angiogenesis, and metastasis that influence tumour behavior and/or response to therapy. Breast cancer, the most common cancer among women and a research area where our group is actively involved, is a very heterogeneous disease with diverse patterns of development and response to treatment. Hence, molecular imaging is expected to have a major impact on this type of cancer, leading to important improvements in diagnosis, individualized treatment, and drug development, as well as our understanding of how breast cancer arises.

  16. Molecular imaging of prostate cancer: translating molecular biology approaches into the clinical realm.

    Science.gov (United States)

    Vargas, Hebert Alberto; Grimm, Jan; F Donati, Olivio; Sala, Evis; Hricak, Hedvig

    2015-05-01

    The epidemiology of prostate cancer has dramatically changed since the introduction of prostate-specific antigen (PSA) screening in the 1980's. Most prostate cancers today are detected at early stages of the disease and are considered 'indolent'; however, some patients' prostate cancers demonstrate a more aggressive behaviour which leads to rapid progression and death. Increasing understanding of the biology underlying the heterogeneity that characterises this disease has led to a continuously evolving role of imaging in the management of prostate cancer. Functional and metabolic imaging techniques are gaining importance as the impact on the therapeutic paradigm has shifted from structural tumour detection alone to distinguishing patients with indolent tumours that can be managed conservatively (e.g., by active surveillance) from patients with more aggressive tumours that may require definitive treatment with surgery or radiation. In this review, we discuss advanced imaging techniques that allow direct visualisation of molecular interactions relevant to prostate cancer and their potential for translation to the clinical setting in the near future. The potential use of imaging to follow molecular events during drug therapy as well as the use of imaging agents for therapeutic purposes will also be discussed. • Advanced imaging techniques allow direct visualisation of molecular interactions in prostate cancer. • MRI/PET, optical and Cerenkov imaging facilitate the translation of molecular biology. • Multiple compounds targeting PSMA expression are currently undergoing clinical translation. • Other targets (e.g., PSA, prostate-stem cell antigen, GRPR) are in development.

  17. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    Energy Technology Data Exchange (ETDEWEB)

    Noerenberg, Dominik [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); University of Munich - Grosshadern, Department of Clinical Radiology, Munich (Germany); Ebersberger, Hans U. [Heart Center Munich-Bogenhausen, Department of Cardiology and Intensive Care Medicine, Munich (Germany); Diederichs, Gerd; Hamm, Bernd [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); Botnar, Rene M. [King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Makowski, Marcus R. [Charite - University Medicine Berlin, Department of Radiology, Berlin (Germany); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2016-03-15

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  18. Molecular magnetic resonance imaging of atherosclerotic vessel wall disease

    International Nuclear Information System (INIS)

    Noerenberg, Dominik; Ebersberger, Hans U.; Diederichs, Gerd; Hamm, Bernd; Botnar, Rene M.; Makowski, Marcus R.

    2016-01-01

    Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. (orig.)

  19. Multimodality molecular imaging - from target description to clinical studies

    International Nuclear Information System (INIS)

    Schober, O.; Rahbar, K.; Riemann, B.

    2009-01-01

    This highlight lecture was presented at the closing session of the Annual Congress of the European Association of Nuclear Medicine (EANM) in Munich on 15 October 2008. The Congress was a great success: there were more than 4,000 participants, and 1,597 abstracts were submitted. Of these, 1,387 were accepted for oral or poster presentation, with a rejection rate of 14%. In this article a choice was made from 100 of the 500 lectures which received the highest scores by the scientific review panel. This article outlines the major findings and trends at the EANM 2008, and is only a brief summary of the large number of outstanding abstracts presented. Among the great number of oral and poster presentations covering nearly all fields of nuclear medicine some headlines have to be defined highlighting the development of nuclear medicine in the 21st century. This review focuses on the increasing impact of molecular and multimodality imaging in the field of nuclear medicine. In addition, the question may be asked as to whether the whole spectrum of nuclear medicine is nothing other than molecular imaging and therapy. Furthermore, molecular imaging will and has to go ahead to multimodality imaging. In view of this background the review was structured according to the single steps of molecular imaging, i.e. from target description to clinical studies. The following topics are addressed: targets, radiochemistry and radiopharmacy, devices and computer science, animals and preclinical evaluations, and patients and clinical evaluations. (orig.)

  20. Ultrafast molecular imaging by laser-induced electron diffraction

    International Nuclear Information System (INIS)

    Peters, M.; Nguyen-Dang, T. T.; Cornaggia, C.; Saugout, S.; Charron, E.; Keller, A.; Atabek, O.

    2011-01-01

    We address the feasibility of imaging geometric and orbital structures of a polyatomic molecule on an attosecond time scale using the laser-induced electron diffraction (LIED) technique. We present numerical results for the highest molecular orbitals of the CO 2 molecule excited by a near-infrared few-cycle laser pulse. The molecular geometry (bond lengths) is determined within 3% of accuracy from a diffraction pattern which also reflects the nodal properties of the initial molecular orbital. Robustness of the structure determination is discussed with respect to vibrational and rotational motions with a complete interpretation of the laser-induced mechanisms.

  1. Advances in study of molecular imaging reporte gene systems

    International Nuclear Information System (INIS)

    Wu Tao; An Rui

    2010-01-01

    The use of molecular imaging reporter gene systems has allowed gene therapy to move from the laboratory to the clinical application, which provides methodology to monitor the expression of therapeutic gene noninvasively and achieve quantitative outcome in vivo. Recently, the radionuclide reporter gene still is the focus many studies, but MRI and optical reporter gene have gradually played a important part in reporter gene systems. On the basis of combination of multi-subject, for example applied chemistry and molecular biology, more and more new modified reporter genes and molecular probes have spread out. This paper mainly introduces the advantages and disadvantages of reporter gene system and development trends. (authors)

  2. Development of molecular imaging in the European radiological community

    International Nuclear Information System (INIS)

    Grenier, Nicolas; Sardanelli, Francesco; Becker, Christoph D.; Walecki, Jerzy; Sebag, Guy; Lomas, David John; Krestin, Gabriel P.

    2009-01-01

    The recent and concomitant advances in molecular biology and imaging for diagnosis and therapy will place in vivo imaging techniques at the centre of their clinical transfer. Before that, a wide range of multidisciplinary preclinical research is already taking place. The involvement of radiologists in this new field of imaging sciences is therefore absolutely mandatory during these two phases of development. Achievement of such objectives requires the refinement of strategy within the European radiological community and the European Society of Radiology (ESR) will have to drive a number of actions to stimulate the younger generation of radiologists and to facilitate their access to knowledge. For that purpose, a molecular imaging (MI) subcommittee of the ESR Research Committee based on a group of involved radiologists will be constituted to develop contacts with other constitutive committees and associated societies to provide proposals to our community. (orig.)

  3. Molecular Imaging with Small Animal PET/CT

    DEFF Research Database (Denmark)

    Binderup, T.; El-Ali, H.H.; Skovgaard, D.

    2011-01-01

    is also described. In addition, the non-invasive nature of molecular imaging and the targets of these promising new tracers are attractive for other research areas as well, although these fields are much less explored. We present an example of an interesting research field with the application of small......Small animal positron emission tomography (PET) and computer tomography (CT) is an emerging field in pre-clinical imaging. High quality, state-of-the-art instruments are required for full optimization of the translational value of the small animal studies with PET and CT. However...... in this field of small animal molecular imaging with special emphasis on the targets for tissue characterization in tumor biology such as hypoxia, proliferation and cancer specific over-expression of receptors. The added value of applying CT imaging for anatomical localization and tumor volume measurements...

  4. [Microdose clinical trial--impact of PET molecular imaging].

    Science.gov (United States)

    Yano, Tsuneo; Watanabe, Yasuyoshi

    2010-10-01

    Microdose (MD) clinical trial and exploratory IND study including sub-therapeutic dose and therapeutic dose which are higher than microdoses are expected to bring about innovations in drug development. The outlines of guidances for microdose clinical trial and ICH-M3 (R2) issued by the MHLW in June, 2008, and February, 2010, are first explained, respectively, and some examples of their application to clinical developments of therapeutic drugs in the infection and cancer fields are introduced. Especially, thanks to the progress of molecular imaging research, a new field of drug development is explored by using imaging biomarkers for efficacy or safety evaluation which visualize biomarkers by PET imaging agents. Finally, the roadmap for drug development in infection and cancer fields utilizing PET molecular imaging is discussed.

  5. Molecular Imaging: A Promising Tool to Monitor Islet Transplantation

    Directory of Open Access Journals (Sweden)

    Ping Wang

    2011-01-01

    Full Text Available Replacement of insulin production by pancreatic islet transplantation has great potential as a therapy for type 1 diabetes mellitus. At present, the lack of an effective approach to islet grafts assessment limits the success of this treatment. The development of molecular imaging techniques has the potential to fulfill the goal of real-time noninvasive monitoring of the functional status and viability of the islet grafts. We review the application of a variety of imaging modalities for detecting endogenous and transplanted beta-cell mass. The review also explores the various molecular imaging strategies for assessing islet delivery, the metabolic effects on the islet grafts as well as detection of immunorejection. Here, we highlight the use of combined imaging and therapeutic interventions in islet transplantation and the in vivo monitoring of stem cells differentiation into insulin-producing cells.

  6. Simultaneous molecular and anatomical imaging of the mouse in vivo

    International Nuclear Information System (INIS)

    Goertzen, Andrew L; Meadors, A Ken; Silverman, Robert W; Cherry, Simon R

    2002-01-01

    Non-invasive imaging technologies are opening up new windows into mouse biology. We have developed a mouse imaging system that integrates positron emission tomography (PET) with x-ray computed tomography (CT), allowing simultaneous anatomic and molecular imaging in vivo with the potential for precise registration of the two image volumes. The x-ray system consists of a compact mini-focal x-ray tube and an amorphous selenium flat panel x-ray detector with a low-noise CMOS readout. The PET system uses planar arrays of lutetium oxyorthosilicate scintillator coupled to position-sensitive photomultiplier tubes. We describe the design of this dual-modality imaging system and show, for the first time, simultaneously acquired PET and CT images in a phantom and in mice

  7. Simultaneous molecular and anatomical imaging of the mouse in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Goertzen, Andrew L [Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Meadors, A Ken [Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Silverman, Robert W [Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Cherry, Simon R [Department of Biomedical Engineering, University of California, Davis, Davis, CA (United States)

    2002-12-21

    Non-invasive imaging technologies are opening up new windows into mouse biology. We have developed a mouse imaging system that integrates positron emission tomography (PET) with x-ray computed tomography (CT), allowing simultaneous anatomic and molecular imaging in vivo with the potential for precise registration of the two image volumes. The x-ray system consists of a compact mini-focal x-ray tube and an amorphous selenium flat panel x-ray detector with a low-noise CMOS readout. The PET system uses planar arrays of lutetium oxyorthosilicate scintillator coupled to position-sensitive photomultiplier tubes. We describe the design of this dual-modality imaging system and show, for the first time, simultaneously acquired PET and CT images in a phantom and in mice.

  8. Molecular imaging of small animals with dedicated PET tomographs

    International Nuclear Information System (INIS)

    Chatziioannou, A.F.

    2002-01-01

    Biological discovery has moved at an accelerated pace in recent years, with a considerable focus on the transition from in vitro to in vivo models. As a result, there has been a significant increase in the need to adapt clinical imaging methods, as well as for novel imaging technologies for biological research. Positron emission tomography (PET) is a clinical imaging modality that permits the use of positron-labeled molecular imaging probes for non-invasive assays of biochemical processes. The imaging procedure can be repeatedly performed before and after interventions, thereby allowing each animal to be used as its own control. Positron-labeled compounds that target a range of molecular targets have been and continue to be synthesized, with examples of biological processes ranging from receptors and synthesis of transmitters in cell communication, to metabolic processes and gene expression. In animal research, PET has been used extensively in the past for studies of non-human primates and other larger animals. New detector technology has improved spatial resolution, and has made possible PET scanning for the study of the most important modern molecular biology model, the laboratory mouse. This paper presents the challenges facing PET technology as applied to small animal imaging, provides a historical overview of the development of small animal PET systems, and discusses the current state of the art in small animal PET technology. (orig.)

  9. Therapeutic Implications of Black Seed and Its Constituent Thymoquinone in the Prevention of Cancer through Inactivation and Activation of Molecular Pathways

    Directory of Open Access Journals (Sweden)

    Arshad H. Rahmani

    2014-01-01

    Full Text Available The cancer is probably the most dreaded disease in both men and women and also major health problem worldwide. Despite its high prevalence, the exact molecular mechanisms of the development and progression are not fully understood. The current chemotherapy/radiotherapy regime used to treat cancer shows adverse side effect and may alter gene functions. Natural products are generally safe, effective, and less expensive substitutes of anticancer chemotherapeutics. Based on previous studies of their potential therapeutic uses, Nigella sativa and its constituents may be proved as good therapeutic options in the prevention of cancer. Black seeds are used as staple food in the Middle Eastern Countries for thousands of years and also in the treatment of diseases. Earlier studies have shown that N. sativa and its constituent thymoquinone (TQ have important roles in the prevention and treatment of cancer by modulating cell signaling pathways. In this review, we summarize the role of N. sativa and its constituents TQ in the prevention of cancer through the activation or inactivation of molecular cell signaling pathways.

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

    Energy Technology Data Exchange (ETDEWEB)

    Malviya, G.; Dierckx, R.A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Conti, F. [Rheumatology Unit, I Faculty of Medicine and Surgery, Sapienza University of Rome (Italy); Chianelli, M. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Unit of Nuclear Medicine, Regina apostolorum Hospital, Albano, Rome (Italy); Scopinaro, F. [Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy); Signore, A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy)

    2010-02-15

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  12. Molecular cloning and functional analysis of a recombinant ribosome-inactivating protein (alpha-momorcharin) from Momordica charantia.

    Science.gov (United States)

    Wang, Shuzhen; Zhang, Yubo; Liu, Honggao; He, Ying; Yan, Junjie; Wu, Zhihua; Ding, Yi

    2012-11-01

    Alpha-momorcharin (α-MC), a member of the ribosome-inactivating protein (RIP) family, has been used not only as antiviral, antimicrobial, and antitumor agents, but also as toxicant to protozoa, insects, and fungi. In this study, we expressed the protein in Escherichia coli Rosetta (DE3) pLysS strain and purified it by nickel-nitrilotriacetic acid affinity chromatography. A total of 85 mg of homogeneous protein was obtained from 1 l culture supernatant of Rosetta (DE3) pLysS, showing a high recovery rate of 73.9%. Protein activity assay indicated that α-MC had both N-glycosidase activity and DNA-nuclease activity, the former releasing RIP diagnostic RNA fragment (Endo's fragment) from rice rRNAs and the latter converting supercoiled circular DNA of plasmid pET-32a(+) into linear conformations in a concentration-dependent manner. Specially, we found that α-MC could inhibit the mycelial growth of Fusarium solani and Fusarium oxysporum with IC(50) values of 6.23 and 4.15 μM, respectively. Results of optical microscopy and transmission electron microscopy demonstrated that α-MC caused extensive septum formation, loss of integrity of the cell wall, separation of the cytoplasm from the cell wall, deformation of cells with irregular budding sites, and apoptosis in F. solani. Moreover, α-MC was active against Pseudomonas aeruginosa with an IC(50) value of 0.59 μM. The α-MC protein carries a high potential for the design of new antifungal drugs or the development of transgenic crops resistant to pathogens.

  13. Bench to bedside molecular functional imaging in translational cancer medicine: to image or to imagine?

    International Nuclear Information System (INIS)

    Mahajan, A.; Goh, V.; Basu, S.; Vaish, R.; Weeks, A.J.; Thakur, M.H.; Cook, G.J.

    2015-01-01

    Ongoing research on malignant and normal cell biology has substantially enhanced the understanding of the biology of cancer and carcinogenesis. This has led to the development of methods to image the evolution of cancer, target specific biological molecules, and study the anti-tumour effects of novel therapeutic agents. At the same time, there has been a paradigm shift in the field of oncological imaging from purely structural or functional imaging to combined multimodal structure–function approaches that enable the assessment of malignancy from all aspects (including molecular and functional level) in a single examination. The evolving molecular functional imaging using specific molecular targets (especially with combined positron-emission tomography [PET] computed tomography [CT] using 2- [ 18 F]-fluoro-2-deoxy-D-glucose [FDG] and other novel PET tracers) has great potential in translational research, giving specific quantitative information with regard to tumour activity, and has been of pivotal importance in diagnoses and therapy tailoring. Furthermore, molecular functional imaging has taken a key place in the present era of translational cancer research, producing an important tool to study and evolve newer receptor-targeted therapies, gene therapies, and in cancer stem cell research, which could form the basis to translate these agents into clinical practice, popularly termed “theranostics”. Targeted molecular imaging needs to be developed in close association with biotechnology, information technology, and basic translational scientists for its best utility. This article reviews the current role of molecular functional imaging as one of the main pillars of translational research. -- Highlights: •Molecular functional imaging (MFI) gives insight into the tumor biology and intratumoral heterogeneity. •It has potential role in identifying radiomic signatures associated with underlying gene-expression. •Radiomics can be used to create a road map

  14. Proceedings of II Molecular Imaging Symposium Cuba - Japan

    International Nuclear Information System (INIS)

    2016-01-01

    In the Central Theater, University Hospital 'General Calixto Garcia' took place the II Symposium on Molecular Imaging Cuba Japan in the framework of the Scientific Convention for the 120th anniversary of the hospital. The event was organized by the hospital itself with the support of the Society of Medical Physics (medical physics section), CEADEN, the Embassy of Japan and the Theragnostic Compounds R&D Center Neuroscience Research Institute Gachon University, Incheon Korea. It was attended by 80 national scientific leaders and with the invaluable presence of Dr. Tatsuo IDO, Emeritus professor of Tohoku University (Sendai, Japan) who presented the results of the scientific papers presented this year in national and international events , referring to the new technologies of molecular imaging and the importance of medical physics in its development. During the meeting the importance of the new technologies of molecular imaging, its undisputed diagnosis intake and medical treatment and the value of human capital struggled to deal with the new technologies, the view that these are only used best when it is understood that they are multidisciplinary systems where each specialist and technical personnel plays an indispensable role. The challenge has medical physics to address these new technologies and the need for changes in the theoretical and practical training in the specialty. These analyzes will be given continuity in the next symposia molecular imaging. (author)

  15. Molecular imaging of tumor blood vessels in prostate cancer.

    Science.gov (United States)

    Tilki, Derya; Seitz, Michael; Singer, Bernhard B; Irmak, Ster; Stief, Christian G; Reich, Oliver; Ergün, Süleyman

    2009-05-01

    In the past three decades many efforts have been undertaken to understand the mechanisms of tumor angiogenesis. The introduction of anti-angiogenic drugs in tumor therapy during the last few years necessitates the establishment of new techniques enabling molecular imaging of tumor vascular remodelling. The determination of tumor size as commonly used is not appropriate since the extended necrosis under anti-angiogenic therapy does not necessarily result in the reduction of tumor diameter. The basis for the molecular imaging of tumor blood vessels is the remodelling of the tumor vessels under anti-angiogenic therapy which obviously occurs at an early stage and seems to be a convincing parameter. Beside the enormous progress in this field during the last few years the resolution is still not high enough to evaluate the remodelling of the micro tumor vessels. New imaging approaches combining specific molecular markers for tumor vessels with the different imaging techniques are needed to overcome this issue as exemplarily discussed for prostate cancer in this review. Molecular contrast agents targeting the vasculature will allow clinicians the visualization of vascular remodelling processes taking place under anti-angiogenic therapy and improve tumor diagnosis and follow-up.

  16. PET-MRI: the likely future of molecular imaging

    International Nuclear Information System (INIS)

    Chen Xiang; Zhao Jinhua; Zhao Jun

    2008-01-01

    PET-CT is a successful combination of functional and morphologic information, and it has already been shown to have great value both in clinics and in scientific research. MRI is another kind of morphologic imaging method, in contrast to CT, MRI can yield images with higher soft-tissue contrast and better spatial resolution. The combination of PET and MRI for simultaneous data acquisition should have far- reaching consequences for molecular imaging. This review will talk about the problems met in the development of PET-MRI and describe the progress to date and look forward to its potential application. (authors)

  17. Molecular Imaging and Precision Medicine in Uterine and Ovarian Cancers.

    Science.gov (United States)

    Zukotynski, Katherine A; Kim, Chun K

    2017-10-01

    Gynecologic cancer is a heterogeneous group of diseases both functionally and morphologically. Today, PET coupled with computed tomography (PET/CT) or PET/MR imaging play a central role in the precision medicine algorithm of patients with gynecologic malignancy. In particular, PET/CT and PET/MR imaging are molecular imaging techniques that not only are useful tools for initial staging and restaging but provide anatomofunctional insight and can serve as predictive and prognostic biomarkers of response in patients with gynecologic malignancy. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Molecular Imaging and Precision Medicine in Breast Cancer.

    Science.gov (United States)

    Chudgar, Amy V; Mankoff, David A

    2017-01-01

    Precision medicine, basing treatment approaches on patient traits and specific molecular features of disease processes, has an important role in the management of patients with breast cancer as targeted therapies continue to improve. PET imaging offers noninvasive information that is complementary to traditional tissue biomarkers, including information about tumor burden, tumor metabolism, receptor status, and proliferation. Several PET agents that image breast cancer receptors can visually demonstrate the extent and heterogeneity of receptor-positive disease and help predict which tumors are likely to respond to targeted treatments. This review presents applications of PET imaging in the targeted treatment of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Molecular subtypes and imaging phenotypes of breast cancer

    International Nuclear Information System (INIS)

    Cho, Nariya

    2016-01-01

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics

  20. Molecular subtypes and imaging phenotypes of breast cancer

    Directory of Open Access Journals (Sweden)

    Nariya Cho

    2016-10-01

    Full Text Available During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2, and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  1. Molecular subtypes and imaging phenotypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Nariya [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2016-08-15

    During the last 15 years, traditional breast cancer classifications based on histopathology have been reorganized into the luminal A, luminal B, human epidermal growth factor receptor 2 (HER2), and basal-like subtypes based on gene expression profiling. Each molecular subtype has shown varying risk for progression, response to treatment, and survival outcomes. Research linking the imaging phenotype with the molecular subtype has revealed that non-calcified, relatively circumscribed masses with posterior acoustic enhancement are common in the basal-like subtype, spiculated masses with a poorly circumscribed margin and posterior acoustic shadowing in the luminal subtype, and pleomorphic calcifications in the HER2-enriched subtype. Understanding the clinical implications of the molecular subtypes and imaging phenotypes could help radiologists guide precision medicine, tailoring medical treatment to patients and their tumor characteristics.

  2. Molecular Ultrasound Imaging for the Detection of Neural Inflammation

    Science.gov (United States)

    Volz, Kevin R.

    Molecular imaging is a form of nanotechnology that enables the noninvasive examination of biological processes in vivo. Radiopharmaceutical agents are used to selectively target biochemical markers, which permits their detection and evaluation. Early visualization of molecular variations indicative of pathophysiological processes can aid in patient diagnoses and management decisions. Molecular imaging is performed by introducing molecular probes into the body. Molecular probes are often contrast agents that have been nanoengineered to selectively target and tether to molecules, enabling their radiologic identification. Ultrasound contrast agents have been demonstrated as an effective method of detecting perfusion at the tissue level. Through a nanoengineering process, ultrasound contrast agents can be targeted to specific molecules, thereby extending ultrasound's capabilities from the tissue to molecular level. Molecular ultrasound, or targeted contrast enhanced ultrasound (TCEUS), has recently emerged as a popular molecular imaging technique due to its ability to provide real-time anatomical and functional information in the absence of ionizing radiation. However, molecular ultrasound represents a novel form of molecular imaging, and consequently remains largely preclinical. A review of the TCEUS literature revealed multiple preclinical studies demonstrating its success in detecting inflammation in a variety of tissues. Although, a gap was identified in the existing evidence, as TCEUS effectiveness for detection of neural inflammation in the spinal cord was unable to be uncovered. This gap in knowledge, coupled with the profound impacts that this TCEUS application could have clinically, provided rationale for its exploration, and use as contributory evidence for the molecular ultrasound body of literature. An animal model that underwent a contusive spinal cord injury was used to establish preclinical evidence of TCEUS to detect neural inflammation. Imaging was

  3. Current Molecular Imaging Positron Emitting Radiotracers in Oncology

    International Nuclear Information System (INIS)

    Zhu, Aizhi; Shim, Hyunsuk

    2011-01-01

    Molecular imaging is one of the fastest growing areas of medical imaging. Positron emission tomography has been widely used in the clinical management of patients with cancer. Nuclear imaging provides biological information at the cellular, subcellular, and molecular level in living subjects with noninvasive procedures. In particular, PET imaging takes advantage of traditional diagnostic imaging techniques and introduces positron emitting probes to determine the expression of indicative molecular targets at different stages of cancer. 18F fluorodeoxyglucose ( 18F FDG), the only FDA approved oncological PET tracer, has been widely utilized in cancer diagnosis, staging, restaging, and even monitoring response to therapy; however, 18F FDG is not a tumor specific PET tracer. Over the last decade, many promising tumor specific PET tracer. Over the last decade, many promising tumor specific PET tracers have been developed and evaluated in preclinical and clinical studies. This review provides an overview of the current non 18F FDG PET tracers in oncology that have been developed based on tumor characteristics such as increased metabolism, hyperproliferation, angiogenesis, hypoxia, apoptosis, and tumor specific antigens and surface receptors

  4. Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

    International Nuclear Information System (INIS)

    Joshi, Bishnu P.; Wang, Thomas D.

    2010-01-01

    Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research

  5. PET molecular imaging in stem cell therapy for neurological diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiachuan; Zhang, Hong [Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Institute of Nuclear Medicine and Molecular Imaging of Zhejiang University, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [University of Texas, M.D. Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2011-10-15

    Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases. (orig.)

  6. Molecular Imaging of Apoptosis: From Micro to Macro

    Science.gov (United States)

    Zeng, Wenbin; Wang, Xiaobo; Xu, Pengfei; Liu, Gang; Eden, Henry S.; Chen, Xiaoyuan

    2015-01-01

    Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death. Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies. In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features. Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies. In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes. Their clinical translation will also be our focus. PMID:25825597

  7. In vivo molecular and genomic imaging: new challenges for imaging physics.

    Science.gov (United States)

    Cherry, Simon R

    2004-02-07

    The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field.

  8. In vivo molecular and genomic imaging: new challenges for imaging physics

    Energy Technology Data Exchange (ETDEWEB)

    Cherry, Simon R [Department of Biomedical Engineering, University of California, Davis, CA (United States)

    2004-02-07

    The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field. (topical review)

  9. In vivo molecular and genomic imaging: new challenges for imaging physics

    International Nuclear Information System (INIS)

    Cherry, Simon R

    2004-01-01

    The emerging and rapidly growing field of molecular and genomic imaging is providing new opportunities to directly visualize the biology of living organisms. By combining our growing knowledge regarding the role of specific genes and proteins in human health and disease, with novel ways to target these entities in a manner that produces an externally detectable signal, it is becoming increasingly possible to visualize and quantify specific biological processes in a non-invasive manner. All the major imaging modalities are contributing to this new field, each with its unique mechanisms for generating contrast and trade-offs in spatial resolution, temporal resolution and sensitivity with respect to the biological process of interest. Much of the development in molecular imaging is currently being carried out in animal models of disease, but as the field matures and with the development of more individualized medicine and the molecular targeting of new therapeutics, clinical translation is inevitable and will likely forever change our approach to diagnostic imaging. This review provides an introduction to the field of molecular imaging for readers who are not experts in the biological sciences and discusses the opportunities to apply a broad range of imaging technologies to better understand the biology of human health and disease. It also provides a brief review of the imaging technology (particularly for x-ray, nuclear and optical imaging) that is being developed to support this new field. (topical review)

  10. Multi-modality molecular imaging: pre-clinical laboratory configuration

    Science.gov (United States)

    Wu, Yanjun; Wellen, Jeremy W.; Sarkar, Susanta K.

    2006-02-01

    In recent years, the prevalence of in vivo molecular imaging applications has rapidly increased. Here we report on the construction of a multi-modality imaging facility in a pharmaceutical setting that is expected to further advance existing capabilities for in vivo imaging of drug distribution and the interaction with their target. The imaging instrumentation in our facility includes a microPET scanner, a four wavelength time-domain optical imaging scanner, a 9.4T/30cm MRI scanner and a SPECT/X-ray CT scanner. An electronics shop and a computer room dedicated to image analysis are additional features of the facility. The layout of the facility was designed with a central animal preparation room surrounded by separate laboratory rooms for each of the major imaging modalities to accommodate the work-flow of simultaneous in vivo imaging experiments. This report will focus on the design of and anticipated applications for our microPET and optical imaging laboratory spaces. Additionally, we will discuss efforts to maximize the daily throughput of animal scans through development of efficient experimental work-flows and the use of multiple animals in a single scanning session.

  11. Molecular imaging of brown adipose tissue in health and disease

    International Nuclear Information System (INIS)

    Bauwens, Matthias; Wierts, Roel; Brans, Boudewijn; Royen, Bart van; Backes, Walter; Bucerius, Jan; Mottaghy, Felix

    2014-01-01

    Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, 18 F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to 18 F-FDG, other radiopharmaceuticals such as 99m Tc-sestamibi, 123 I-metaiodobenzylguanidine (MIBG), 18 F-fluorodopa and 18 F-14(R,S)-[ 18 F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

  12. Molecular imaging of brown adipose tissue in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Bauwens, Matthias [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Maastricht University, Research School NUTRIM, Maastricht (Netherlands); Wierts, Roel; Brans, Boudewijn [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Royen, Bart van; Backes, Walter [MUMC, Department of Medical Imaging, Division of Radiology, Maastricht (Netherlands); Bucerius, Jan [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany); Maastricht University, Research School CARIM, Maastricht (Netherlands); Mottaghy, Felix [MUMC, Department of Medical Imaging, Division of Nuclear Medicine, Maastricht (Netherlands); Uniklinikum Aachen, Division of Nuclear Medicine, Aachen (Germany)

    2014-04-15

    Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological {sup 18}F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, {sup 18}F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to {sup 18}F-FDG, other radiopharmaceuticals such as {sup 99m}Tc-sestamibi, {sup 123}I-metaiodobenzylguanidine (MIBG), {sup 18}F-fluorodopa and {sup 18}F-14(R,S)-[{sup 18}F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

  13. Progress in Molecular Imaging in Endoscopy and Endomicroscopy for Cancer Imaging

    Directory of Open Access Journals (Sweden)

    Supang Khondee

    2013-01-01

    Full Text Available Imaging is an essential tool for effective cancer management. Endoscopes are important medical instruments for performing in vivo imaging in hollow organs. Early detection of cancer can be achieved with surveillance using endoscopy, and has been shown to reduce mortality and to improve outcomes. Recently, great advancements have been made in endoscopic instruments, including new developments in optical designs, light sources, optical fibers, miniature scanners, and multimodal systems, allowing for improved resolution, greater tissue penetration, and multispectral imaging. In addition, progress has been made in the development of highly-specific optical probes, allowing for improved specificity for molecular targets. Integration of these new endoscopic instruments with molecular probes provides a unique opportunity for significantly improving patient outcomes and has potential to further improve early detection, image guided therapy, targeted therapy, and personalized medicine. This work summarizes current and evolving endoscopic technologies, and provides an overview of various promising optical molecular probes.

  14. Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

    Science.gov (United States)

    Qin, Zhengtao

    Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and

  15. Optimisation in X-ray and Molecular Imaging 2015

    International Nuclear Information System (INIS)

    Baath, Magnus; Hoeschen, Christoph; Mattsson, Soeren; Mansson, Lars Gunnar

    2016-01-01

    This issue of Radiation Protection Dosimetry is based on contributions to Optimisation in X-ray and Molecular Imaging 2015 - the 4. Malmoe Conference on Medical Imaging (OXMI 2015). The conference was jointly organised by members of former and current research projects supported by the European Commission EURATOM Radiation Protection Research Programme, in cooperation with the Swedish Society for Radiation Physics. The conference brought together over 150 researchers and other professionals from hospitals, universities and industries with interests in different aspects of the optimisation of medical imaging. More than 100 presentations were given at this international gathering of medical physicists, radiologists, engineers, technicians, nurses and educational researchers. Additionally, invited talks were offered by world-renowned experts on radiation protection, spectral imaging and medical image perception, thus covering several important aspects of the generation and interpretation of medical images. The conference consisted of 13 oral sessions and a poster session, as reflected by the conference title connected by their focus on the optimisation of the use ionising radiation in medical imaging. The conference included technology-specific topics such as computed tomography and tomosynthesis, but also generic issues of interest for the optimisation of all medical imaging, such as image perception and quality assurance. Radiation protection was covered by e.g. sessions on patient dose benchmarking and occupational exposure. Technically-advanced topics such as modelling, Monte Carlo simulation, reconstruction, classification, and segmentation were seen taking advantage of recent developments of hardware and software, showing that the optimisation community is at the forefront of technology and adapts well to new requirements. These peer-reviewed proceedings, representing a continuation of a series of selected reports from meetings in the field of medical imaging

  16. Molecular imaging and the neuropathologies of Parkinson's disease

    DEFF Research Database (Denmark)

    Cumming, Paul; Borghammer, Per

    2012-01-01

    The main motor symptoms of Parkinson's disease (PD) are linked to degeneration of the nigrostriatal dopamine (DA) fibers, especially those innervating the putamen. This degeneration can be assessed in molecular imaging studies with presynaptic tracers such as [(18)F]-fluoro-L-DOPA (FDOPA...... with denervation upregulation, but there is an accelerated rate of DA receptor loss as the disease advances. Animal studies and post mortem investigations reveal changes in brain opioid peptide systems, but these are poorly documented in imaging studies of PD. Relatively minor changes in the binding sites for GABA...

  17. Molecular Imaging and Precision Medicine in Head and Neck Cancer.

    Science.gov (United States)

    Mena, Esther; Thippsandra, Shwetha; Yanamadala, Anusha; Redy, Siddaling; Pattanayak, Puskar; Subramaniam, Rathan M

    2017-01-01

    The concept of using tumor genomic profiling information has revolutionized personalized cancer treatment. Head and neck (HN) cancer management is being influenced by recent discoveries of activating mutations in epidermal growth factor receptor and related targeted therapies with tyrosine kinase inhibitors, targeted therapies for Kristen Rat Sarcoma, and MET proto-oncogenes. Molecular imaging using PET plays an important role in assessing the biologic behavior of HN cancer with the goal of delivering individualized cancer treatment. This review summarizes recent genomic discoveries in HN cancer and their implications for functional PET imaging in assessing response to targeted therapies, and drug resistance mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. The Center for Integrated Molecular Brain Imaging (Cimbi) database

    DEFF Research Database (Denmark)

    Knudsen, Gitte M.; Jensen, Peter S.; Erritzoe, David

    2016-01-01

    We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions rela...... currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank....

  19. Molecular imaging of retinal endothelial injury in diabetic animals

    Directory of Open Access Journals (Sweden)

    Sonja Frimmel

    2017-01-01

    Conclusion: Results indicate that molecular imaging can be used to detect subtle changes in the diabetic retina prior to the occurrence of irreversible pathology. Thus, ICAM-1 could serve as a diagnostic target in patients with diabetes. This study provides a proof of principle for non-invasive subclinical diagnosis in experimental diabetic retinopathy. Further development of this technology could improve management of diabetic complications.

  20. Intelligent Design of Nano-Scale Molecular Imaging Agents

    Directory of Open Access Journals (Sweden)

    Takeaki Ozawa

    2012-12-01

    Full Text Available Visual representation and quantification of biological processes at the cellular and subcellular levels within living subjects are gaining great interest in life science to address frontier issues in pathology and physiology. As intact living subjects do not emit any optical signature, visual representation usually exploits nano-scale imaging agents as the source of image contrast. Many imaging agents have been developed for this purpose, some of which exert nonspecific, passive, and physical interaction with a target. Current research interest in molecular imaging has mainly shifted to fabrication of smartly integrated, specific, and versatile agents that emit fluorescence or luminescence as an optical readout. These agents include luminescent quantum dots (QDs, biofunctional antibodies, and multifunctional nanoparticles. Furthermore, genetically encoded nano-imaging agents embedding fluorescent proteins or luciferases are now gaining popularity. These agents are generated by integrative design of the components, such as luciferase, flexible linker, and receptor to exert a specific on–off switching in the complex context of living subjects. In the present review, we provide an overview of the basic concepts, smart design, and practical contribution of recent nano-scale imaging agents, especially with respect to genetically encoded imaging agents.

  1. Bioresponsive probes for molecular imaging:Concepts and in vivo applications

    OpenAIRE

    Duijnhoven, van, SMJ Sander; Robillard, MS Marc; Langereis, S Sander; Grüll, H Holger

    2015-01-01

    Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecular imaging probes, known as bioresponsive molecular probes, has been developed. These probes generally benefit from signal enhancement at the site of interaction with its target. There are mainly ...

  2. Featured Image: A Molecular Cloud Outside Our Galaxy

    Science.gov (United States)

    Kohler, Susanna

    2018-06-01

    What do molecular clouds look like outside of our own galaxy? See for yourself in the images above and below of N55, a molecular cloud located in the Large Magellanic Cloud (LMC). In a recent study led by Naslim Neelamkodan (Academia Sinica Institute of Astronomy and Astrophysics, Taiwan), a team of scientists explore N55 to determine how its cloud properties differ from clouds within the Milky Way. The image above reveals the distribution of infrared-emitting gas and dust observed in three bands by the Spitzer Space Telescope. Overplotted in cyan are observations from the Atacama Submillimeter Telescope Experiment tracing the clumpy, warm molecular gas. Below, new observations from the Atacama Large Millimeter/submillimeter Array (ALMA) reveal the sub-parsec-scale molecular clumps in greater detail, showing the correlation of massive clumps with Spitzer-identified young stellar objects (crosses). The study presented here indicates that this cloud in the LMC is the site of massive star formation, with properties similar to equivalent clouds in the Milky Way. To learn more about the authors findings, check out the article linked below.CitationNaslim N. et al 2018 ApJ 853 175. doi:10.3847/1538-4357/aaa5b0

  3. UPAR targeted molecular imaging of cancers with small molecule-based probes.

    Science.gov (United States)

    Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

    2017-10-15

    Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Advancing Molecular Therapies through In Vivo Bioluminescent Imaging

    Directory of Open Access Journals (Sweden)

    Anton McCaffrey

    2003-04-01

    Full Text Available Effective development of therapeutics that target the molecular basis of disease is dependent on testing new therapeutic moieties and delivery strategies in animal models of human disease. Accelerating the analyses of these models and improving their predictive value through whole animal imaging methods, which provide data in real time and are sensitive to the subtle changes, are crucial for rapid advancement of these approaches. Modalities based on optics are rapid, sensitive, and accessible methods for in vivo analyses with relatively low instrumentation costs. In vivo bioluminescent imaging (BLI is one of these optically based imaging methods that enable rapid in vivo analyses of a variety of cellular and molecular events with extreme sensitivity. BLI is based on the use of light-emitting enzymes as internal biological light sources that can be detected externally as biological indicators. BLI has been used to test spatio-temporal expression patterns of both target and therapeutic genes in living laboratory animals where the contextual influences of whole biological systems are preserved. BLI has also been used to analyze gene delivery, immune cell therapies, and the in vivo efficacy of inhibitory RNAs. New tools for BLI are being developed that will offer greater flexibility in detection and analyses. BLI can be used to accelerate the evaluation of experimental therapeutic strategies and whole body imaging offers the opportunity of revealing the effects of novel approaches on key steps in disease processes.

  5. PET-based molecular nuclear neuro-imaging

    International Nuclear Information System (INIS)

    Kim, Jong Ho

    2004-01-01

    Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy

  6. PET-based molecular nuclear neuro-imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Ho [Gil Medical Center, Gachon (Korea, Republic of)

    2004-04-01

    Molecular nuclear neuro-imaging in CNS drug discovery and development can be divided into four categories that are clearly inter-related. (1) Neuroreceptor mapping to examine the involvement of specific neurotransmitter system in CNS diseases, drug occupancy characteristics and perhaps examine mechanisms of action;(2) Structural and spectroscopic imaging to examine morphological changes and their consequences;(3) Metabolic mapping to provide evidence of central activity and CNS fingerprinting the neuroanatomy of drug effects;(4) Functional mapping to examine disease-drug interactions. In addition, targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation('stem cell pharmacology'). Future exploitation of stem cell biology, including enhanced release of therapeutic factors through genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. With continued improvements in instrumentation, identification of better imaging probes by innovative chemistry, molecular nuclear neuro-imaging promise to play increasingly important roles in disease diagnosis and therapy.

  7. The development of nuclear medicine molecular imaging: An era of multiparametric imaging

    International Nuclear Information System (INIS)

    Zhu Yuyuan; Huang Gang

    2010-01-01

    Nuclear medical molecular imaging is developing toward a multimodality and multitracer future. Abundant complementary data generated from different tracers in different modalities are successfully serving the biological research and clinical treatment. Among the others, PER-MRI has the greatest potential and will be a research of interest in the near future. This article focused on the evolution history on nuclear medicine from single modality to multimodality, single tracer to multitracer. It also gave a brief summary to the identifications, differences, pros and consofmultimodality, multitracer, multiparametric molecular imaging. Issues, problems and challenges concerned with her development and recognition are also discussed. (authors)

  8. Radiogenomics: Creating a link between molecular diagnostics and diagnostic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Rutman, Aaron M. [Department of Radiology, University of California San Diego Medical Center, San Diego, CA 92103 (United States); Kuo, Michael D. [Department of Radiology, University of California San Diego Medical Center, San Diego, CA 92103 (United States); Center for Translational Medical Systems, University of California San Diego Medical Center, San Diego, CA 92103 (United States)], E-mail: mkuo@ucsd.edu

    2009-05-15

    Studies employing high-throughput biological techniques have recently contributed to an improved characterization of human cancers, allowing for novel sub-classification, better diagnostic accuracy, and more precise prognostication. However, requirement of surgical procurement of tissue among other things limits the clinical application of such methods in everyday patient care. Radiographic imaging is routine in clinical practice but is currently histopathology based. The use of routine radiographic imaging provides a potential platform for linking specific imaging traits with specific gene expression patterns that inform the underlying cellular pathophysiology; imaging features could then serve as molecular surrogates that contribute to the diagnosis, prognosis, and likely gene-expression-associated treatment response of various forms of human cancer. This review focuses on high-throughput methods such as microarray analysis of gene expression, their role in cancer research, and in particular, on novel methods of associating gene expression patterns with radiographic imaging phenotypes, known as 'radiogenomics.' These findings underline a potential future role of both diagnostic and interventional radiologists in genetic assessment of cancer patients with radiographic imaging studies.

  9. Radiogenomics: Creating a link between molecular diagnostics and diagnostic imaging

    International Nuclear Information System (INIS)

    Rutman, Aaron M.; Kuo, Michael D.

    2009-01-01

    Studies employing high-throughput biological techniques have recently contributed to an improved characterization of human cancers, allowing for novel sub-classification, better diagnostic accuracy, and more precise prognostication. However, requirement of surgical procurement of tissue among other things limits the clinical application of such methods in everyday patient care. Radiographic imaging is routine in clinical practice but is currently histopathology based. The use of routine radiographic imaging provides a potential platform for linking specific imaging traits with specific gene expression patterns that inform the underlying cellular pathophysiology; imaging features could then serve as molecular surrogates that contribute to the diagnosis, prognosis, and likely gene-expression-associated treatment response of various forms of human cancer. This review focuses on high-throughput methods such as microarray analysis of gene expression, their role in cancer research, and in particular, on novel methods of associating gene expression patterns with radiographic imaging phenotypes, known as 'radiogenomics.' These findings underline a potential future role of both diagnostic and interventional radiologists in genetic assessment of cancer patients with radiographic imaging studies.

  10. Molecular image in biomedical research. Molecular imaging unit of the National Cancer Research Center

    International Nuclear Information System (INIS)

    Perez Bruzon, J.; Mulero Anhiorte, F.

    2010-01-01

    This article has two basic objectives. firstly, it will review briefly the most important imaging techniques used in biomedical research indicting the most significant aspects related to their application in the preclinical stage. Secondly, it will present a practical application of these techniques in a pure biomedical research centre (not associated to a clinical facility). Practical aspects such as organisation, equipment, work norms, shielding of the Spanish National Cancer Research Centre (CNIO) Imaging Unit will be shown. This is a pioneering facility in the application of these techniques in research centres without any dependence or any direct relationship with other hospital Nuclear Medicine services. (Author) 7 refs.

  11. Molecular imaging in neurological diseases; Molekulare Bildgebung bei neurologischen Erkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Reimold, M.; Fougere, C. la [Universitaetsklinikum Tuebingen, Abteilung Nuklearmedizin und Klinische Molekulare Bildgebung, Department Radiologie, Tuebingen (Germany)

    2016-07-15

    In neurodegeneration and in neuro-oncology, the standard imaging procedure, magnetic resonance imaging (MRI), shows limited sensitivity and specificity. Molecular imaging with specific positron-emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers allows various molecular targets and metabolic processes to be assessed and is thus a valuable adjunct to MRI. Two important examples are referred to here: amino acid transport for neuro-oncological issues, and the recently approved PET tracers for detecting amyloid depositions during the preclinical stage of Alzheimer's disease. This review discusses the clinical relevance and indications for the following nuclear medicine imaging procedures: amyloid PET, {sup 18}F-fluorodeoxyglucose (FDG)-PET, and dopamine transporter (DaT)-SPECT for the diagnosis of dementia and the differential diagnosis of Parkinson's disease, in addition to amino acid PET for the diagnosis of brain tumors and somatostatin receptor imaging in meningioma. (orig.) [German] Die Magnetresonanztomographie (MRT) weist als Standardverfahren bei neurodegenerativen und neuroonkologischen Fragestellungen eine eingeschraenkte Sensitivitaet und Spezifitaet auf. Die nuklearmedizinische molekulare Bildgebung mit spezifischen Positronenemissionstomographie(PET)- und single-photon-emission-computed-tomography(SPECT)-Tracern ermoeglicht die Darstellung verschiedener molekularer Targets bzw. Stoffwechselprozesse und stellt damit eine wichtige Ergaenzung zur MRT dar. Hier sei exemplarisch auf die Darstellung des Aminosaeuretransports im Rahmen neuroonkologischer Fragestellungen verwiesen, sowie auf die bereits im praeklinischen Stadium der Alzheimer-Demenz nachweisbaren Amyloidablagerungen mit hierfuer seit Kurzem zugelassenen PET-Tracern. Dieser Uebersichtsbeitrag bespricht die klinische Bedeutung bzw. die Indikationen der folgenden nuklearmedizinischen Untersuchungsverfahren: der Amyloid-PET, der {sup 18}F

  12. Cell and Tissue Imaging with Molecularly Imprinted Polymers.

    Science.gov (United States)

    Panagiotopoulou, Maria; Kunath, Stephanie; Haupt, Karsten; Tse Sum Bui, Bernadette

    2017-01-01

    Advanced tools for cell imaging are of particular interest as they can detect, localize and quantify molecular targets like abnormal glycosylation sites that are biomarkers of cancer and infection. Targeting these biomarkers is often challenging due to a lack of receptor materials. Molecularly imprinted polymers (MIPs) are promising artificial receptors; they can be tailored to bind targets specifically, be labeled easily, and are physically and chemically stable. Herein, we demonstrate the application of MIPs as artificial antibodies for selective labeling and imaging of cellular targets, on the example of hyaluronan and sialylation moieties on fixated human skin cells and tissues. Thus, fluorescently labeled MIP nanoparticles templated with glucuronic acid (MIPGlcA) and N-acetylneuraminic acid (MIPNANA) are respectively applied. Two different fluorescent probes are used: (1) MIPGlcA particles, ~400 nm in size are labeled with the dye rhodamine that target the extracellular hyaluronan on cells and tissue specimens and (2) MIP-coated InP/ZnS quantum dots (QDs) of two different colors, ~125 nm in size that target the extracellular and intracellular hyaluronan and sialylation sites. Green and red emitting QDs are functionalized with MIPGlcA and MIPNANA respectively, enabling multiplexed cell imaging. This is a general approach that can also be adapted to other target molecules on and in cells.

  13. In Situ Correlated Molecular Imaging of Chemically Communicating Microbial Communities

    Energy Technology Data Exchange (ETDEWEB)

    Bohn, Paul W. [Univ. of Notre Dame, IN (United States); Shrout, J. D. [Univ. of Notre Dame, IN (United States); Sweedler, J. V. [Univ. of Illinois, Urbana-Champaign, IL (United States); Farrand, S. [Univ. of Illinois, Urbana-Champaign, IL (United States)

    2016-01-25

    This document constitutes the final technical report for DE-SC0006642, In Situ Correlated Molecular Imaging of Chemically Communicating Microbial Communities, a project carried out collaboratively by investigators at Notre Dame and UIUC. The work carried out under DOE support in this project produced advances in two areas: development of new highly sophisticated correlated imaging approaches and the application of these new tools to the growth and differentiation of microbial communities under a variety of environmental conditions. A significant effort involved the creation of technical enhancements and sampling approaches to allow us to advance heterocorrelated mass spectrometry imaging (MSI) and correlated Raman microscopy (CRM) from bacterial cultures and biofilms. We then exploited these measurement advances in heterocorrelated MS/CRM imaging to determine relationship of signaling molecules and excreted signaling molecules produced by P. aeruginosa to conditions relevant to the rhizosphere. In particular, we: (1) developed a laboratory testbed mimic for the rhizosphere to enable microbial growth on slides under controlled conditions; (2) integrated specific measurements of (a) rhamnolipids, (b) quinolone/quinolones, and (c) phenazines specific to P. aeruginosa; and (3) utilized the imaging tools to probe how messenger secretion, quorum sensing and swarming behavior are correlated with behavior.

  14. Biomedical nanotechnology for molecular imaging, diagnostics, and targeted therapy.

    Science.gov (United States)

    Nie, Shuming

    2009-01-01

    Biomedical nanotechnology is a cross-disciplinary area of research in science, engineering and medicine with broad applications for molecular imaging, molecular diagnosis, and targeted therapy. The basic rationale is that nanometer-sized particles such as semiconductor quantum dots and iron oxide nanocrystals have optical, magnetic or structural properties that are not available from either molecules or bulk solids. When linked with biotargeting ligands such as monoclonal antibodies, peptides or small molecules, these nanoparticles can be used to target diseased cells and organs (such as malignant tumors and cardiovascular plaques) with high affinity and specificity. In the "mesoscopic" size range of 5-100 nm diameter, nanoparticles also have large surface areas and functional groups for conjugating to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents.

  15. Contributions on biomedical imaging, with a side-look at molecular imaging

    International Nuclear Information System (INIS)

    Winkler, G.

    2004-05-01

    This report is intended as a brief introduction to the emerging scientific field of biomedical imaging. The breadth of the subject is shown and future fields of research are indicated, which hopefully will serve as a guide to the identification of starting points for the research in 'Biomedical and/or Molecular Imaging' at the GSF-National Research Center for Environment and Health. The report starts with a brief sketch of the history. Then a - necessarily incomplete - list of research topics is presented. It is organized in two parts: the first one addresses medical imaging, and the second one is concerned with biological point aspects of the matter. (orig.) [de

  16. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Science.gov (United States)

    Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

    2015-08-01

    Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  17. Molecular Imaging of Hydrolytic Enzymes Using PET and SPECT.

    Science.gov (United States)

    Rempel, Brian P; Price, Eric W; Phenix, Christopher P

    2017-01-01

    Hydrolytic enzymes are a large class of biological catalysts that play a vital role in a plethora of critical biochemical processes required to maintain human health. However, the expression and/or activity of these important enzymes can change in many different diseases and therefore represent exciting targets for the development of positron emission tomography (PET) and single-photon emission computed tomography (SPECT) radiotracers. This review focuses on recently reported radiolabeled substrates, reversible inhibitors, and irreversible inhibitors investigated as PET and SPECT tracers for imaging hydrolytic enzymes. By learning from the most successful examples of tracer development for hydrolytic enzymes, it appears that an early focus on careful enzyme kinetics and cell-based studies are key factors for identifying potentially useful new molecular imaging agents.

  18. Status and Advances of RGD Molecular Imaging in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ning YUE

    2014-12-01

    Full Text Available Lung cancer has been one of the most common and the highest mortality rates malignant tumors at home and abroad. Sustained angiogenesis was not only the characteristic of malignant tumors, but also the foundation of tumor proliferation, invasion, recurrence and metastasis, it was also one of the hot spots of treatments in lung cancer biology currently. Integrins played an important part in tumor angiogenesis. Arg-Gly-Asp (RGD peptides could combine with integrins specifically, and the application of radionuclide-labeled RGD molecular probes enabled imaging of tumor blood vessels to reflect its changes. The lung cancer imaging of RGD peptides at home and abroad in recent years was reviewed in this article.

  19. Functional histology of tumors as a basis of molecular imaging

    International Nuclear Information System (INIS)

    Ljungkvist, A.S.; Bussink, J.; Rijken, P.F.; Van Der Kogel, A.; Kaanders, J.H.

    2003-01-01

    The aim of this study was to characterize the various elements of the microenvironment and their interrelationships by quantitative image analysis. Tumor cell proliferation, hypoxia, and apoptosis are detected by immunohistochemical methods, and mapped in relation to the vasculature. This allows quantitative relationships to be measured in the context of tissue structure. Guided by e.g., gene expression profiles for hypoxia induced-genes, several molecular markers of tumor hypoxia were identified and are immunohistochemically detectable. We have thus far concentrated on the glucose transporters glut-1 and glut-3, as well as a pH-regulating enzyme, carbonic anhydrase IX. The extent and distribution of hypoxia is assessed by administering nitroimidazole-based markers such as pimonidazole, that can be detected immunohistochemically. Multiple hypoxia markers (CCI-103F, pimonidazole) can be used to study the effects of modifiers of perfusion or oxygenation on the distribution and dynamics of hypoxic cells in the same tumor. Proliferating cells are detected by thymidine analogues. Apoptotic cells are imaged by TUNEL and caspase-3 detection. In xenografted human tumors, examples of the use of quantitative imaging of hypoxia and proliferation are the study of reoxygenation after irradiation, or the investigation of the lifespan and dynamics of hypoxic cell populations over time. Perturbation of the microenvironment after cytotoxic treatments has been investigated by co-registration of the various markers, e.g. after treatment with the hypoxic cytotoxin tirapazamine. The combination of well-timed administration of external markers of hypoxia and proliferation with the detection of intrinsic molecular markers followed by quantitative image-registration yields a comprehensive view of the dynamics of the microenvironment in individual tumors

  20. A gamma-ray tracking detector for molecular imaging

    International Nuclear Information System (INIS)

    Hall, C.J.; Lewis, R.A.; Helsby, W.I.; Nolan, P.; Boston, A.

    2003-01-01

    A design for a gamma-ray detector for molecular imaging is presented. The system is based on solid-state strip detector technology. The advantages of position sensitivity coupled with fine spectral resolution are exploited to produce a tracking detector for use with a variety of isotopes in nuclear medicine. Current design concepts employ both silicon and germanium layers to provide an energy range from 60 keV to >1 MeV. This allows a reference X-ray image to be collected simultaneously with the gamma-ray image providing accurate anatomical registration. The tracking ability of the gamma-ray detector allows ambiguities in the data set to be resolved which would otherwise cause events to be rejected in standard non-tracking system. Efficiency improvements that high solid angle coverage and the use of a higher proportion of events make time resolved imaging and multi-isotope work possible. A modular detector system, designed for viewing small animals has been accepted for funding

  1. Molecular imaging needles: dual-modality optical coherence tomography and fluorescence imaging of labeled antibodies deep in tissue

    Science.gov (United States)

    Scolaro, Loretta; Lorenser, Dirk; Madore, Wendy-Julie; Kirk, Rodney W.; Kramer, Anne S.; Yeoh, George C.; Godbout, Nicolas; Sampson, David D.; Boudoux, Caroline; McLaughlin, Robert A.

    2015-01-01

    Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue. PMID:26137379

  2. Tunable Molecular Logic Gates Designed for Imaging Released Neurotransmitters.

    Science.gov (United States)

    Klockow, Jessica L; Hettie, Kenneth S; Secor, Kristen E; Barman, Dipti N; Glass, Timothy E

    2015-08-03

    Tunable dual-analyte fluorescent molecular logic gates (ExoSensors) were designed for the purpose of imaging select vesicular primary-amine neurotransmitters that are released from secretory vesicles upon exocytosis. ExoSensors are based on the coumarin-3-aldehyde scaffold and rely on both neurotransmitter binding and the change in environmental pH associated with exocytosis to afford a unique turn-on fluorescence output. A pH-functionality was directly integrated into the fluorophore π-system of the scaffold, thereby allowing for an enhanced fluorescence output upon the release of labeled neurotransmitters. By altering the pH-sensitive unit with various electron-donating and -withdrawing sulfonamide substituents, we identified a correlation between the pKa of the pH-sensitive group and the fluorescence output from the activated fluorophore. In doing so, we achieved a twelvefold fluorescence enhancement upon evaluating the ExoSensors under conditions that mimic exocytosis. ExoSensors are aptly suited to serve as molecular imaging tools that allow for the direct visualization of only the neurotransmitters that are released from secretory vesicles upon exocytosis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Raman molecular imaging of brain frozen tissue sections.

    Science.gov (United States)

    Kast, Rachel E; Auner, Gregory W; Rosenblum, Mark L; Mikkelsen, Tom; Yurgelevic, Sally M; Raghunathan, Aditya; Poisson, Laila M; Kalkanis, Steven N

    2014-10-01

    Raman spectroscopy provides a molecular signature of the region being studied. It is ideal for neurosurgical applications because it is non-destructive, label-free, not impacted by water concentration, and can map an entire region of tissue. The objective of this paper is to demonstrate the meaningful spatial molecular information provided by Raman spectroscopy for identification of regions of normal brain, necrosis, diffusely infiltrating glioma and solid glioblastoma (GBM). Five frozen section tissues (1 normal, 1 necrotic, 1 GBM, and 2 infiltrating glioma) were mapped in their entirety using a 300-µm-square step size. Smaller regions of interest were also mapped using a 25-µm step size. The relative concentrations of relevant biomolecules were mapped across all tissues and compared with adjacent hematoxylin and eosin-stained sections, allowing identification of normal, GBM, and necrotic regions. Raman peaks and peak ratios mapped included 1003, 1313, 1431, 1585, and 1659 cm(-1). Tissue maps identified boundaries of grey and white matter, necrosis, GBM, and infiltrating tumor. Complementary information, including relative concentration of lipids, protein, nucleic acid, and hemoglobin, was presented in a manner which can be easily adapted for in vivo tissue mapping. Raman spectroscopy can successfully provide label-free imaging of tissue characteristics with high accuracy. It can be translated to a surgical or laboratory tool for rapid, non-destructive imaging of tumor margins.

  4. Multifunctional nanomaterials for advanced molecular imaging and cancer therapy

    Science.gov (United States)

    Subramaniam, Prasad

    Nanotechnology offers tremendous potential for use in biomedical applications, including cancer and stem cell imaging, disease diagnosis and drug delivery. The development of nanosystems has aided in understanding the molecular mechanisms of many diseases and permitted the controlled nanoscale manipulation of biological phenomena. In recent years, many studies have focused on the use of several kinds of nanomaterials for cancer and stem cell imaging and also for the delivery of anticancer therapeutics to tumor cells. However, the proper diagnosis and treatment of aggressive tumors such as brain and breast cancer requires highly sensitive diagnostic agents, in addition to the ability to deliver multiple therapeutics using a single platform to the target cells. Addressing these challenges, novel multifunctional nanomaterial-based platforms that incorporate multiple therapeutic and diagnostic agents, with superior molecular imaging and targeting capabilities, has been presented in this work. The initial part of this work presents the development of novel nanomaterials with superior optical properties for efficiently delivering soluble cues such as small interfering RNA (siRNA) into brain cancer cells with minimal toxicity. Specifically, this section details the development of non-toxic quantums dots for the imaging and delivery of siRNA into brain cancer and mesenchymal stem cells, with the hope of using these quantum dots as multiplexed imaging and delivery vehicles. The use of these quantum dots could overcome the toxicity issues associated with the use of conventional quantum dots, enabled the imaging of brain cancer and stem cells with high efficiency and allowed for the delivery of siRNA to knockdown the target oncogene in brain cancer cells. The latter part of this thesis details the development of nanomaterial-based drug delivery platforms for the co-delivery of multiple anticancer drugs to brain tumor cells. In particular, this part of the thesis focuses on

  5. Deep Learning in Nuclear Medicine and Molecular Imaging: Current Perspectives and Future Directions.

    Science.gov (United States)

    Choi, Hongyoon

    2018-04-01

    Recent advances in deep learning have impacted various scientific and industrial fields. Due to the rapid application of deep learning in biomedical data, molecular imaging has also started to adopt this technique. In this regard, it is expected that deep learning will potentially affect the roles of molecular imaging experts as well as clinical decision making. This review firstly offers a basic overview of deep learning particularly for image data analysis to give knowledge to nuclear medicine physicians and researchers. Because of the unique characteristics and distinctive aims of various types of molecular imaging, deep learning applications can be different from other fields. In this context, the review deals with current perspectives of deep learning in molecular imaging particularly in terms of development of biomarkers. Finally, future challenges of deep learning application for molecular imaging and future roles of experts in molecular imaging will be discussed.

  6. Photodynamic Inactivation of Mammalian Viruses and Bacteriophages

    Directory of Open Access Journals (Sweden)

    Liliana Costa

    2012-06-01

    Full Text Available Photodynamic inactivation (PDI has been used to inactivate microorganisms through the use of photosensitizers. The inactivation of mammalian viruses and bacteriophages by photosensitization has been applied with success since the first decades of the last century. Due to the fact that mammalian viruses are known to pose a threat to public health and that bacteriophages are frequently used as models of mammalian viruses, it is important to know and understand the mechanisms and photodynamic procedures involved in their photoinactivation. The aim of this review is to (i summarize the main approaches developed until now for the photodynamic inactivation of bacteriophages and mammalian viruses and, (ii discuss and compare the present state of the art of mammalian viruses PDI with phage photoinactivation, with special focus on the most relevant mechanisms, molecular targets and factors affecting the viral inactivation process.

  7. Impact of molecular imaging with PET on healthcare worldwide

    International Nuclear Information System (INIS)

    Alavi, Abbas

    2009-01-01

    Full text: FDG-PET imaging has substantially improved healthcare throughout the world. This technique has been applied to patients with some of the most serious diseases, including cancer, central nervous system disorders, cardiovascular disease and infections including infected prostheses. There is also enormous potential for further improvement in patient management using this technique, for example, in the detection of atherosclerosis and clots, and assessment of muscle function. Studies using FDG-PET methodology have led to the development of many novel radiotracers that have been designed to explore new diagnostic and therapeutic domains. We therefore expect that molecular imaging with PET will play an increasingly central role in research and in the optimal management of patients with many disorders. This will include diagnosing pathological processes at the molecular level and individualizing treatment for these patients. By utilizing PET and the appropriately labeled pharmaceuticals, one will be able to select the most suitable therapeutic drugs for a particular disease, instead of administering drugs to patients without a good idea of the chance of efficacy. Likewise, PET will increasingly play a major role in drug development by demonstrating the degree to which the intended pharmaceutical targets the diseased tissues in animal models and in human beings. PET will also assist in determining the rate of metabolism of the administered drugs by different tissues. PET imaging will also allow accurate staging of cancer and other serious diseases and will be adopted as the most accurate technique for monitoring response to treatment and detecting recurrence. The role of CT and/or MRI as independent modalities in medicine will decrease as the efficacy of PET is realized by scientists and clinicians alike. In particular, the use of contrast agents such as iodinated compounds and gadolinium based agents will be minimized. Similarly, imaging with single gamma

  8. Transferring Biomarker into Molecular Probe: Melanin Nanoparticle as a Naturally Active Platform for Multimodality Imaging

    OpenAIRE

    Fan, Quli; Cheng, Kai; Hu, Xiang; Ma, Xiaowei; Zhang, Ruiping; Yang, Min; Lu, Xiaomei; Xing, Lei; Huang, Wei; Gambhir, Sanjiv Sam; Cheng, Zhen

    2014-01-01

    Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (

  9. Molecular and Ionized Hydrogen in 30 Doradus. I. Imaging Observations

    Science.gov (United States)

    Yeh, Sherry C. C.; Seaquist, Ernest R.; Matzner, Christopher D.; Pellegrini, Eric W.

    2015-07-01

    We present the first fully calibrated H2 1-0 S(1) image of the entire 30 Doradus nebula. The observations were conducted using the NOAO Extremely Wide-field Infrared Imager (NEWFIRM) on the CTIO 4 m Blanco Telescope. Together with a NEWFIRM Brγ image of 30 Doradus, our data reveal the morphologies of the warm molecular gas and ionized gas in 30 Doradus. The brightest H2-emitting area, which extends from the northeast to the southwest of R136, is a photodissociation region (PDR) viewed face-on, while many clumps and pillar features located at the outer shells of 30 Doradus are PDRs viewed edge-on. Based on the morphologies of H2, Brγ, CO, and 8 μm emission, the H2 to Brγ line ratio, and Cloudy models, we find that the H2 emission is formed inside the PDRs of 30 Doradus, 2-3 pc to the ionization front of the H ii region, in a relatively low-density environment <104 cm-3. Comparisons with Brγ, 8 μm, and CO emission indicate that H2 emission is due to fluorescence, and provide no evidence for shock excited emission of this line.

  10. Molecular Imaging Of Metabolic Reprogramming In Mutant IDH Cells

    Directory of Open Access Journals (Sweden)

    Pavithra eViswanath

    2016-03-01

    Full Text Available Mutations in the metabolic enzyme isocitrate dehydrogenase (IDH have recently been identified as drivers in the development of several tumor types. Most notably, cytosolic IDH1 is mutated in 70-90% of low-grade gliomas and upgraded glioblastomas, and mitochondrial IDH2 is mutated in ~20% of acute myeloid leukemia cases. Wild-type IDH catalyzes the interconversion of isocitrate to α-ketoglutarate (α-KG. Mutations in the enzyme lead to loss of wild-type enzymatic activity and a neomorphic activity that converts α-KG to 2-hydroxyglutarate (2-HG. In turn, 2-HG, which has been termed an oncometabolite, inhibits key α-KG- dependent enzymes, resulting in alterations of the cellular epigenetic profile and, subsequently, inhibition of differentiation and initiation of tumorigenesis. In addition, it is now clear that the IDH mutation also induces a broad metabolic reprogramming that extends beyond 2-HG production, and this reprogramming often differs from what has been previously reported in other cancer types. In this review we will discuss in detail what is known to date about the metabolic reprogramming of mutant IDH cells and how this reprogramming has been investigated using molecular metabolic imaging. We will describe how metabolic imaging has helped shed light on the basic biology of mutant IDH cells and how this information can be leveraged to identify new therapeutic targets and to develop new clinically translatable imaging methods to detect and monitor mutant IDH tumors in vivo.

  11. MOLECULAR AND IONIZED HYDROGEN IN 30 DORADUS. I. IMAGING OBSERVATIONS

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Sherry C. C. [Subaru Telescope, National Astronomical Observatory of Japan, 650 North A’ohoku Place, Hilo, HI 96720 (United States); Seaquist, Ernest R.; Matzner, Christopher D. [Department of Astronomy and Astrophysics, University of Toronto, 50 St. George Street, Toronto, ON M5S 3H4 (Canada); Pellegrini, Eric W., E-mail: yeh@naoj.org [Department of Physics and Astronomy, University of Toledo, 2801 West Bancroft Street, Toledo, OH 43606 (United States)

    2015-07-10

    We present the first fully calibrated H{sub 2} 1–0 S(1) image of the entire 30 Doradus nebula. The observations were conducted using the NOAO Extremely Wide-field Infrared Imager (NEWFIRM) on the CTIO 4 m Blanco Telescope. Together with a NEWFIRM Brγ image of 30 Doradus, our data reveal the morphologies of the warm molecular gas and ionized gas in 30 Doradus. The brightest H{sub 2}-emitting area, which extends from the northeast to the southwest of R136, is a photodissociation region (PDR) viewed face-on, while many clumps and pillar features located at the outer shells of 30 Doradus are PDRs viewed edge-on. Based on the morphologies of H{sub 2}, Brγ, CO, and 8 μm emission, the H{sub 2} to Brγ line ratio, and Cloudy models, we find that the H{sub 2} emission is formed inside the PDRs of 30 Doradus, 2–3 pc to the ionization front of the H ii region, in a relatively low-density environment <10{sup 4} cm{sup −3}. Comparisons with Brγ, 8 μm, and CO emission indicate that H{sub 2} emission is due to fluorescence, and provide no evidence for shock excited emission of this line.

  12. Fluorescence imaging with near-infrared light: new technological advances that enable in vivo molecular imaging

    International Nuclear Information System (INIS)

    Ntziachristos, Vasilis; Bremer, Christoph; Weissleder, Ralph

    2003-01-01

    A recent development in biomedical imaging is the non-invasive mapping of molecular events in intact tissues using fluorescence. Underpinning to this development is the discovery of bio-compatible, specific fluorescent probes and proteins and the development of highly sensitive imaging technologies for in vivo fluorescent detection. Of particular interest are fluorochromes that emit in the near infrared (NIR), a spectral window, whereas hemoglobin and water absorb minimally so as to allow photons to penetrate for several centimetres in tissue. In this review article we concentrate on optical imaging technologies used for non-invasive imaging of the distribution of such probes. We illuminate the advantages and limitations of simple photographic methods and turn our attention to fluorescence-mediated molecular tomography (FMT), a technique that can three-dimensionally image gene expression by resolving fluorescence activation in deep tissues. We describe theoretical specifics, and we provide insight into its in vivo capacity and the sensitivity achieved. Finally, we discuss its clinical feasibility. (orig.)

  13. Molecular dynamics of CYP2D6 polymorphisms in the absence and presence of a mechanism-based inactivator reveals changes in local flexibility and dominant substrate access channels.

    Directory of Open Access Journals (Sweden)

    Parker W de Waal

    Full Text Available Cytochrome P450 enzymes (CYPs represent an important enzyme superfamily involved in metabolism of many endogenous and exogenous small molecules. CYP2D6 is responsible for ∼ 15% of CYP-mediated drug metabolism and exhibits large phenotypic diversity within CYPs with over 100 different allelic variants. Many of these variants lead to functional changes in enzyme activity and substrate selectivity. Herein, a molecular dynamics comparative analysis of four different variants of CYP2D6 was performed. The comparative analysis included simulations with and without SCH 66712, a ligand that is also a mechanism-based inactivator, in order to investigate the possible structural basis of CYP2D6 inactivation. Analysis of protein stability highlighted significantly altered flexibility in both proximal and distal residues from the variant residues. In the absence of SCH 66712, *34, *17-2, and *17-3 displayed more flexibility than *1, and *53 displayed more rigidity. SCH 66712 binding reversed flexibility in *17-2 and *17-3, through *53 remained largely rigid. Throughout simulations with docked SCH 66712, ligand orientation within the heme-binding pocket was consistent with previously identified sites of metabolism and measured binding energies. Subsequent tunnel analysis of substrate access, egress, and solvent channels displayed varied bottle-neck radii. Taken together, our results indicate that SCH 66712 should inactivate these allelic variants, although varied flexibility and substrate binding-pocket accessibility may alter its interaction abilities.

  14. Inactivation Data.xlsx

    Data.gov (United States)

    U.S. Environmental Protection Agency — The data set is a spreadsheet that contains results of inactivation experiments that were conducted to to determine the effectiveness of chlorine in inactivating B....

  15. A Partnership Training Program in Breast Cancer Research Using Molecular Imaging Techniques

    National Research Council Canada - National Science Library

    Wang, Paul C

    2006-01-01

    In the first year of this training grant, five faculty members from different departments at the Howard University were trained in molecular imaging with the faculty at the In Vivo Cellular Molecular...

  16. Dosimetry of FDG PET/CT and other molecular imaging applications in pediatric patients

    International Nuclear Information System (INIS)

    Gelfand, Michael J.

    2009-01-01

    Effective doses for PET and SPECT imaging of molecular imaging agents depend on the radiopharmaceutical, administered activity and the weight of the patient. Effective doses for the accompanying CT scan depend on the CT protocol being used. CT protocols can be designed to produce diagnostic quality images, localization images or attenuation correction data without imaging. In each case, the co-registered molecular imaging examination (PET or SPECT) and the CT study must be acquired without patient movement. For PET/CT, attention to the respiratory phase during the CT study is also of critical importance. In addition to the molecular imaging agents 18 F-FDG and 123 I-MIBG that are frequently used in children, additional PET and SPECT imaging agents may have promise for molecular imaging in children. (orig.)

  17. Molecular Imaging and Precision Medicine in Lung Cancer.

    Science.gov (United States)

    Zukotynski, Katherine A; Gerbaudo, Victor H

    2017-01-01

    Precision medicine allows tailoring of preventive or therapeutic interventions to avoid the expense and toxicity of futile treatment given to those who will not respond. Lung cancer is a heterogeneous disease functionally and morphologically. PET is a sensitive molecular imaging technique with a major role in the precision medicine algorithm of patients with lung cancer. It contributes to the precision medicine of lung neoplasia by interrogating tumor heterogeneity throughout the body. It provides anatomofunctional insight during diagnosis, staging, and restaging of the disease. It is a biomarker of tumoral heterogeneity that helps direct selection of the most appropriate treatment, the prediction of early response to cytotoxic and cytostatic therapies, and is a prognostic biomarker in patients with lung cancer. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  18. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    International Nuclear Information System (INIS)

    Vermeulen, Jeroen F; Brussel, Aram SA van; Groep, Petra van der; Morsink, Folkert HM; Bult, Peter; Wall, Elsken van der; Diest, Paul J van

    2012-01-01

    Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. The combination of highly tumor-specific markers glucose transporter 1 (GLUT1), epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF1-R), human epidermal growth factor receptor 2 (HER2), hepatocyte growth factor receptor (MET), and carbonic anhydrase 9 (CAIX) 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6) resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R) that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate

  19. Immunophenotyping invasive breast cancer: paving the road for molecular imaging

    Directory of Open Access Journals (Sweden)

    Vermeulen Jeroen F

    2012-06-01

    Full Text Available Abstract Background Mammographic population screening in The Netherlands has increased the number of breast cancer patients with small and non-palpable breast tumors. Nevertheless, mammography is not ultimately sensitive and specific for distinct subtypes. Molecular imaging with targeted tracers might increase specificity and sensitivity of detection. Because development of new tracers is labor-intensive and costly, we searched for the smallest panel of tumor membrane markers that would allow detection of the wide spectrum of invasive breast cancers. Methods Tissue microarrays containing 483 invasive breast cancers were stained by immunohistochemistry for a selected set of membrane proteins known to be expressed in breast cancer. Results The combination of highly tumor-specific markers glucose transporter 1 (GLUT1, epidermal growth factor receptor (EGFR, insulin-like growth factor-1 receptor (IGF1-R, human epidermal growth factor receptor 2 (HER2, hepatocyte growth factor receptor (MET, and carbonic anhydrase 9 (CAIX 'detected' 45.5% of tumors, especially basal/triple negative and HER2-driven ductal cancers. Addition of markers with a 2-fold tumor-to-normal ratio increased the detection rate to 98%. Including only markers with >3 fold tumor-to-normal ratio (CD44v6 resulted in an 80% detection rate. The detection rate of the panel containing both tumor-specific and less tumor-specific markers was not dependent on age, tumor grade, tumor size, or lymph node status. Conclusions In search of the minimal panel of targeted probes needed for the highest possible detection rate, we showed that 80% of all breast cancers express at least one of a panel of membrane markers (CD44v6, GLUT1, EGFR, HER2, and IGF1-R that may therefore be suitable for molecular imaging strategies. This study thereby serves as a starting point for further development of a set of antibody-based optical tracers with a high breast cancer detection rate.

  20. Optical Molecular Imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity

    Directory of Open Access Journals (Sweden)

    Kun Wang

    2015-09-01

    Full Text Available Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging (CLI, and optical image-guided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.

  1. Radiation-Force Assisted Targeting Facilitates Ultrasonic Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Shukui Zhao

    2004-07-01

    Full Text Available Ultrasonic molecular imaging employs contrast agents, such as microbubbles, nanoparticles, or liposomes, coated with ligands specific for receptors expressed on cells at sites of angiogenesis, inflammation, or thrombus. Concentration of these highly echogenic contrast agents at a target site enhances the ultrasound signal received from that site, promoting ultrasonic detection and analysis of disease states. In this article, we show that acoustic radiation force can be used to displace targeted contrast agents to a vessel wall, greatly increasing the number of agents binding to available surface receptors. We provide a theoretical evaluation of the magnitude of acoustic radiation force and show that it is possible to displace micron-sized agents physiologically relevant distances. Following this, we show in a series of experiments that acoustic radiation force can enhance the binding of targeted agents: The number of biotinylated microbubbles adherent to a synthetic vessel coated with avidin increases as much as 20-fold when acoustic radiation force is applied; the adhesion of contrast agents targeted to αvβ3 expressed on human umbilical vein endothelial cells increases 27-fold within a mimetic vessel when radiation force is applied; and finally, the image signal-to-noise ratio in a phantom vessel increases up to 25 dB using a combination of radiation force and a targeted contrast agent, over use of a targeted contrast agent alone.

  2. Nuclear molecular imaging of paragangliomas; Imagerie moleculaire nucleaire des paragangliomes

    Energy Technology Data Exchange (ETDEWEB)

    Taieb, D.; Tessonnier, L.; Mundler, O. [Service central de biophysique et de medecine nucleaire, CHU de la Timone, 13 - Marseille (France)

    2010-08-15

    Paragangliomas (PGL) are relatively rare neural crest tumors originating in the adrenal medulla (usually called pheochromocytoma), chemoreceptors (i.e., carotid and aortic bodies) or autonomic ganglia. These tumors are highly vascular, usually benign and slow-growing. PGL may occur as sporadic or familial entities, the latter mostly in association with germline mutations of the succinate dehydrogenase (SDH) B, SDHC, SDHD, SDH5, von Hippel-Lindau (VHL), ret proto-oncogene (RET), neurofibromatosis 1 (NF1) (von Recklinghausen's disease), prolyl hydroxylase domain protein 2 (PHD2) genes and TMEM127. Molecular nuclear imaging has a central role in characterization of PGL and include: somatostatin receptor imaging ({sup 111}In, {sup 68}Ga), MIBG scintigraphy ({sup 131}I, {sup 123}I), {sup 18}F-dihydroxy-phenylalanine ({sup 18}F-DOPA) positron emission tomography (PET), and {sup 18}F-deoxyglucose ({sup 18}F-FDG) PET. The choice of the tracer is not yet fully established but the work-up of familial forms often require the combination of multiple approaches. (authors)

  3. Inactivation of Caliciviruses

    Directory of Open Access Journals (Sweden)

    Raymond Nims

    2013-03-01

    Full Text Available The Caliciviridae family of viruses contains clinically important human and animal pathogens, as well as vesivirus 2117, a known contaminant of biopharmaceutical manufacturing processes employing Chinese hamster cells. An extensive literature exists for inactivation of various animal caliciviruses, especially feline calicivirus and murine norovirus. The caliciviruses are susceptible to wet heat inactivation at temperatures in excess of 60 °C with contact times of 30 min or greater, to UV-C inactivation at fluence ≥30 mJ/cm2, to high pressure processing >200 MPa for >5 min at 4 °C, and to certain photodynamic inactivation approaches. The enteric caliciviruses (e.g.; noroviruses display resistance to inactivation by low pH, while the non-enteric species (e.g.; feline calicivirus are much more susceptible. The caliciviruses are inactivated by a variety of chemicals, including alcohols, oxidizing agents, aldehydes, and β-propiolactone. As with inactivation of viruses in general, inactivation of caliciviruses by the various approaches may be matrix-, temperature-, and/or contact time-dependent. The susceptibilities of the caliciviruses to the various physical and chemical inactivation approaches are generally similar to those displayed by other small, non-enveloped viruses, with the exception that the parvoviruses and circoviruses may require higher temperatures for inactivation, while these families appear to be more susceptible to UV-C inactivation than are the caliciviruses.

  4. Molecular Imaging of Tumors Using a Quantitative T1 Mapping Technique via Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2015-07-01

    Full Text Available Magnetic resonance imaging (MRI of glioblastoma multiforme (GBM with molecular imaging agents would allow for the specific localization of brain tumors. Prior studies using T1-weighted MR imaging demonstrated that the SBK2-Tris-(Gd-DOTA3 molecular imaging agent labeled heterotopic xenograft models of brain tumors more intensely than non-specific contrast agents using conventional T1-weighted imaging techniques. In this study, we used a dynamic quantitative T1 mapping strategy to more objectively compare intra-tumoral retention of the SBK2-Tris-(Gd-DOTA3 agent over time in comparison to non-targeted control agents. Our results demonstrate that the targeted SBK2-Tris-(Gd-DOTA3 agent, a scrambled-Tris-(Gd-DOTA3 control agent, and the non-specific clinical contrast agent Optimark™ all enhanced flank tumors of human glioma cells with similar maximal changes on T1 mapping. However, the retention of the agents differs. The non-specific agents show significant recovery within 20 min by an increase in T1 while the specific agent SBK2-Tris-(Gd-DOTA3 is retained in the tumors and shows little recovery over 60 min. The retention effect is demonstrated by percent change in T1 values and slope calculations as well as by calculations of gadolinium concentration in tumor compared to muscle. Quantitative T1 mapping demonstrates the superior binding and retention in tumors of the SBK2-Tris-(Gd-DOTA3 agent over time compared to the non-specific contrast agent currently in clinical use.

  5. Contributions on biomedical imaging, with a side-look at molecular imaging; Beitraege zur biomedizinischen Bildgebung mit einem Seitenblick auf Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, G. (ed.)

    2004-05-01

    This report is intended as a brief introduction to the emerging scientific field of biomedical imaging. The breadth of the subject is shown and future fields of research are indicated, which hopefully will serve as a guide to the identification of starting points for the research in 'Biomedical and/or Molecular Imaging' at the GSF-National Research Center for Environment and Health. The report starts with a brief sketch of the history. Then a - necessarily incomplete - list of research topics is presented. It is organized in two parts: the first one addresses medical imaging, and the second one is concerned with biological point aspects of the matter. (orig.) [German] In diesem Bericht sind einige Beitraege zum Gebiet 'Bildgebende Verfahren in Biologie und Medizin' zusammengestellt. Sie stammen saemtlich aus dem Institut fuer Biomathematik und Biometrie, IBB, am Forschungszentrum fuer Umwelt und Gesundheit, GSF, in Muenchen/Neuherberg, und seinem engeren Umfeld. Ziel war es, zu sichten, was in und um diesen Themenkreis herum an Wissen und sonstiger Kompetenz hier vorhanden ist. Einige am IBB etablierte Gebiete wie Roentgen-Mammographie oder funktionelle Magnetresonanztherapie wurden ausgeblendet. Der Grund ist die Fokussierung auf ein nicht exakt definierbares, neues Gebiet der Bildgebung, das unter dem Namen 'Molecular Imaging' kursiert und derzeit Furore macht macht. (orig.)

  6. Contributions on biomedical imaging, with a side-look at molecular imaging; Beitraege zur biomedizinischen Bildgebung mit einem Seitenblick auf Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, G [ed.

    2004-05-01

    This report is intended as a brief introduction to the emerging scientific field of biomedical imaging. The breadth of the subject is shown and future fields of research are indicated, which hopefully will serve as a guide to the identification of starting points for the research in 'Biomedical and/or Molecular Imaging' at the GSF-National Research Center for Environment and Health. The report starts with a brief sketch of the history. Then a - necessarily incomplete - list of research topics is presented. It is organized in two parts: the first one addresses medical imaging, and the second one is concerned with biological point aspects of the matter. (orig.) [German] In diesem Bericht sind einige Beitraege zum Gebiet 'Bildgebende Verfahren in Biologie und Medizin' zusammengestellt. Sie stammen saemtlich aus dem Institut fuer Biomathematik und Biometrie, IBB, am Forschungszentrum fuer Umwelt und Gesundheit, GSF, in Muenchen/Neuherberg, und seinem engeren Umfeld. Ziel war es, zu sichten, was in und um diesen Themenkreis herum an Wissen und sonstiger Kompetenz hier vorhanden ist. Einige am IBB etablierte Gebiete wie Roentgen-Mammographie oder funktionelle Magnetresonanztherapie wurden ausgeblendet. Der Grund ist die Fokussierung auf ein nicht exakt definierbares, neues Gebiet der Bildgebung, das unter dem Namen 'Molecular Imaging' kursiert und derzeit Furore macht macht. (orig.)

  7. Measurement of the density profile of pure and seeded molecular beams by femtosecond ion imaging

    NARCIS (Netherlands)

    Meng, C.; Janssen, M.H.M.

    2015-01-01

    Here, we report on femtosecond ion imaging experiments to measure the density profile of a pulsed supersonic molecular beam. Ion images are measured for both a molecular beam and bulk gas under identical experimental conditions via femtosecond multiphoton ionization of Xe atoms. We report the

  8. Perspectives in molecular imaging through translational research, human medicine, and veterinary medicine.

    Science.gov (United States)

    Berry, Clifford R; Garg, Predeep

    2014-01-01

    The concept of molecular imaging has taken off over the past 15 years to the point of the renaming of the Society of Nuclear Medicine (Society of Nuclear Medicine and Molecular Imaging) and Journals (European Journal of Nuclear Medicine and Molecular Imaging) and offering of medical fellowships specific to this area of study. Molecular imaging has always been at the core of functional imaging related to nuclear medicine. Even before the phrase molecular imaging came into vogue, radionuclides and radiopharmaceuticals were developed that targeted select physiological processes, proteins, receptor analogs, antibody-antigen interactions, metabolites and specific metabolic pathways. In addition, with the advent of genomic imaging, targeted genomic therapy, and theranostics, a number of novel radiopharmaceuticals for the detection and therapy of specific tumor types based on unique biological and cellular properties of the tumor itself have been realized. However, molecular imaging and therapeutics as well as the concept of theranostics are yet to be fully realized. The purpose of this review article is to present an overview of the translational approaches to targeted molecular imaging with application to some naturally occurring animal models of human disease. © 2013 Published by Elsevier Inc.

  9. Application of Deep Learning in Automated Analysis of Molecular Images in Cancer: A Survey

    Science.gov (United States)

    Xue, Yong; Chen, Shihui; Liu, Yong

    2017-01-01

    Molecular imaging enables the visualization and quantitative analysis of the alterations of biological procedures at molecular and/or cellular level, which is of great significance for early detection of cancer. In recent years, deep leaning has been widely used in medical imaging analysis, as it overcomes the limitations of visual assessment and traditional machine learning techniques by extracting hierarchical features with powerful representation capability. Research on cancer molecular images using deep learning techniques is also increasing dynamically. Hence, in this paper, we review the applications of deep learning in molecular imaging in terms of tumor lesion segmentation, tumor classification, and survival prediction. We also outline some future directions in which researchers may develop more powerful deep learning models for better performance in the applications in cancer molecular imaging. PMID:29114182

  10. Cell inactivation by heavy charged particles

    Energy Technology Data Exchange (ETDEWEB)

    Blakely, E A [Lawrence Berkeley Lab., CA (United States). Cell and Molecular Biology Div.

    1992-06-01

    The inactivation of cells resulting in lethal or aberrant effects by charged particles is of growing interest. Charged particles at extremely high LET are capable of completely eliminating cell-type and cell-line differences in repair capacity. It is still not clear however whether the repair systems are inactivated, or merely that heavy-ion lesions are less repairable. Studies correlating the particle inactivation dose of radioresistant cells with intact DNA analyzed with pulse field gel electrophoresis and other techniques may be useful, but more experiments are also needed to assess the fidelity of repair. For particle irradiations between 40-100 keV/{mu}m there is however evidence for particle-induced activation of specific genes in mammalian cells, and certain repair processes in bacteria. New data are available on the inactivation of developmental processes in several systems including seeds, and cells of the nematode C. elegans. Future experimental and theoretical modeling research emphasis should focus on exploring particle-induced inactivation of endpoints assessing functionality and not just lethality, and on analyzing molecular damage and genetic effects arising in damage but non-inactivated survivors. The discrete nature of selective types of particle damage as a function of radiation quality indicates the value of accelerated ions as probes of normal and aberrant biological processes. Information obtained from molecular analyses of damage and repair must however be integrated into the context of cellular and tissue functions of the organism. (orig.).

  11. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abdollahi, H

    2014-06-01

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging.

  12. SU-E-I-39: Molecular Image Guided Cancer Stem Cells Therapy

    International Nuclear Information System (INIS)

    Abdollahi, H

    2014-01-01

    Purpose: Cancer stem cells resistance to radiation is a problematic issue that has caused a big fail in cancer treatment. Methods: As a primary work, molecular imaging can indicate the main mechanisms of radiation resistance of cancer stem cells. By developing and commissioning new probes and nanomolecules and biomarkers, radiation scientist will able to identify the essential pathways of radiation resistance of cancer stem cells. As the second solution, molecular imaging is a best way to find biological target volume and delineate cancer stem cell tissues. In the other hand, by molecular imaging techniques one can image the treatment response in tumor and also in normal tissue. In this issue, the response of cancer stem cells to radiation during therapy course can be imaged, also the main mechanisms of radiation resistance and finding the best radiation modifiers (sensitizers) can be achieved by molecular imaging modalities. In adaptive radiotherapy the molecular imaging plays a vital role to have higher tumor control probability by delivering high radiation doses to cancer stem cells in any time of treatment. The outcome of a feasible treatment is dependent to high cancer stem cells response to radiation and removing all of which, so a good imaging modality can show this issue and preventing of tumor recurrence and metastasis. Results: Our results are dependent to use of molecular imaging as a new modality in the clinic. We propose molecular imaging as a new radiobiological technique to solve radiation therapy problems due to cancer stem cells. Conclusion: Molecular imaging guided cancer stem cell diagnosis and therapy is a new approach in the field of cancer treatment. This new radiobiological imaging technique should be developed in all clinics as a feasible tool that is more biological than physical imaging

  13. Molecular Imaging and Updated Diagnostic Criteria in Lewy Body Dementias.

    Science.gov (United States)

    Bohnen, Nicolaas I; Müller, Martijn L T M; Frey, Kirk A

    2017-08-14

    The aims of the study were to review recent advances in molecular imaging in the Lewy body dementias (LBD) and determine if these may support the clinical but contested temporal profile distinction between Parkinson disease (PD) with dementia (PDD) versus dementia with Lewy bodies (DLB). There do not appear to be major regional cerebral metabolic or neurotransmitter distinctions between PDD and DLB. However, recent studies highlight the relative discriminating roles of Alzheimer proteinopathies. PDD patients have lower cortical β-amyloid deposition than DLB. Preliminary tau PET studies suggest a gradient of increasing tau binding from cognitively normal PD (absent to lowest) to cognitively impaired PD (low) to DLB (intermediate) to Alzheimer disease (AD; highest). However, tau binding in DLB, including the medial temporal lobe, is substantially lower than in AD. Alzheimer-type proteinopathies appear to be more common in DLB compared to PDD with relative but no absolute differences. Given the spectrum of overlapping pathologies, future α-synuclein ligands are expected to have the best potential to distinguish the LBD from pure AD.

  14. From molecular imaging to systems diagnostics: Time for another paradigm shift?

    International Nuclear Information System (INIS)

    Li, King C.P.

    2009-01-01

    The term 'Molecular Imaging' has hit the consciousness of radiologists only in the past decade although many of the concepts that molecular imaging encompasses has been practiced in biomedical imaging, especially in nuclear medicine, for many decades. Many new imaging techniques have allowed us to interrogate biologic events at the cellular and molecular level in vivo in four dimensions but the challenge now is to translate these techniques into clinical practice in a way that will enable us to revolutionize healthcare delivery. The purpose of this article is to introduce the term 'Systems Diagnostics' and examine how radiologists can become translators of disparate sources of information into medical decisions and therapeutic actions.

  15. Diversity of radioprobes targeted to tumor angiogenesis on molecular functional imaging

    International Nuclear Information System (INIS)

    Lu Xia; Zhang Huabei

    2013-01-01

    Molecular functional imaging could visualize, characterize, and measure the bio- logical processes including tumor angiogenesis at the molecular and cellular levels in humans and other living systems. The molecular probes labeled by a variety of radionuclide used in the field of the nuclear medicine play pivotal roles in molecular imaging of tumor angiogenesis. However, the regulatory role of different probes in tumor angiogenesis has not been systematically illustrated. The current status of tumor angiogenesis imaging with radiolabeled probes of peptide, monoclonal antibody as well as its fragment, especially nanoparticle-based probes to gain insights into the robust tumor angiogenesis development were summarized. It was recognized that only the probes such as nanoparticle-based probes, which truly target the tumor vasculature rather than tumor cells because of poor extravasation, are really tumor angiogenesis imaging agent. The research of molecular probe targeted to angiogenesis would meet its flourish just after the outstanding improvements in the in vivo stability and biocompatibility, tumor-targeting efficacy, and pharmacokinetics of tumor angiogenesis imaging probes are made. Translation to clinical applications will also be critical for the maximize benefits of these novel agents. The future of tumor angiogenesis imaging lies in liable imaging probes and multiple imaging modalities, imaging of protein-protein interactions, and quantitative molecular imaging. (authors)

  16. Molecular Imaging: A Useful Tool for the Development of Natural Killer Cell-Based Immunotherapies

    Directory of Open Access Journals (Sweden)

    Prakash Gangadaran

    2017-09-01

    Full Text Available Molecular imaging is a relatively new discipline that allows visualization, characterization, and measurement of the biological processes in living subjects, including humans, at a cellular and molecular level. The interaction between cancer cells and natural killer (NK cells is complex and incompletely understood. Despite our limited knowledge, progress in the search for immune cell therapies against cancer could be significantly improved by dynamic and non-invasive visualization and tracking of immune cells and by visualization of the response of cancer cells to therapies in preclinical and clinical studies. Molecular imaging is an essential tool for these studies, and a multimodal molecular imaging approach can be applied to monitor immune cells in vivo, for instance, to visualize therapeutic effects. In this review, we discuss the usefulness of NK cells in cancer therapies and the preclinical and clinical usefulness of molecular imaging in NK cell-based therapies. Furthermore, we discuss different molecular imaging modalities for use with NK cell-based therapies, and their preclinical and clinical applications in animal and human subjects. Molecular imaging has contributed to the development of NK cell-based therapies against cancers in animal models and to the refinement of current cell-based cancer immunotherapies. Developing sensitive and reproducible non-invasive molecular imaging technologies for in vivo NK cell monitoring and for real-time assessment of therapeutic effects will accelerate the development of NK cell therapies.

  17. Multiparametric and molecular imaging of breast tumors with MRI and PET/MRI

    International Nuclear Information System (INIS)

    Pinker, K.; Marino, M.A.; Meyer-Baese, A.; Helbich, T.H.

    2016-01-01

    Magnetic resonance imaging (MRI) of the breast is an indispensable tool in breast imaging for many indications. Several functional parameters with MRI and positron emission tomography (PET) have been assessed for imaging of breast tumors and their combined application is defined as multiparametric imaging. Available data suggest that multiparametric imaging using different functional MRI and PET parameters can provide detailed information about the hallmarks of cancer and may provide additional specificity. Multiparametric and molecular imaging of the breast comprises established MRI parameters, such as dynamic contrast-enhanced MRI, diffusion-weighted imaging (DWI), MR proton spectroscopy ( 1 H-MRSI) as well as combinations of radiological and MRI techniques (e.g. PET/CT and PET/MRI) using radiotracers, such as fluorodeoxyglucose (FDG). Multiparametric and molecular imaging of the breast can be performed at different field-strengths (range 1.5-7 T). Emerging parameters comprise novel promising techniques, such as sodium imaging ( 23 Na MRI), phosphorus spectroscopy ( 31 P-MRSI), chemical exchange saturation transfer (CEST) imaging, blood oxygen level-dependent (BOLD) and hyperpolarized MRI as well as various specific radiotracers. Multiparametric and molecular imaging has multiple applications in breast imaging. Multiparametric and molecular imaging of the breast is an evolving field that will enable improved detection, characterization, staging and monitoring for personalized medicine in breast cancer. (orig.) [de

  18. Applications of the Preclinical Molecular Image in Biomedicine; Aplicaciones de la imagen Molecular Preclínica en Biomedicina

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, M.; Bascuñana, P.; Fernández de la Rosa, R.; De Cristobal, J.; García-García, L.; Pozo, M. A.

    2014-07-01

    Molecular imaging is a broad platform, which provides valuable information about physiological and pathophysiological changes in living organisms by non-invasive methods. Depending on the used technique: anatomical, functional metabolic or molecular data could be assessed. Positron Emission Tomography (PET) provides with functional and molecular data, and combined with Computerized Tomography (CT) and Magnetic Resonance (MRI) with the multimodality equipment, it can be exponentially improved. Metabolic pathways and changes on the molecular and cellular level are target in molecular imaging cancer research. Tumour microenvironment, stroma and new vessels can be assessed by PET imaging. Additionally the visualization of functions and monitoring data of provided therapies could be obtained. The aim of the current review is to summarize principles and novel findings in molecular imaging specifically in PET and its application in preclinical cancer research. The theoretical background of techniques and main applications will be highlighted [Spanish] La imagen molecular aporta información muy valiosa, mediante métodos no invasivos, acerca de la fisiología de organismos vivos y sus cambios debidos a patologías. Dependiendo de la técnica utilizada se pueden obtener datos anatómicos, funcionales, metabólicos o moleculares. La Tomografía por Emisión de Positrones (PET) aporta datos metabólicos y moleculares con una alta sensibilidad, y en asociación con la Tomografía Computarizada (TC) o con Resonancia Magnética (RM), con la aparición de los nuevos equipos multimodalidad, las posibilidades de diagnóstico se incrementan exponencialmente. La imagen molecular en investigación oncológica presenta como objetivos principales identificar las diferentes vías metabólicas tumorales y sus cambios a nivel molecular y celular, el comportamiento del microentorno tumoral, aparición de nuevos vasos, estroma, etc. Además, es posible el análisis y cuantificación del

  19. Molecular Imaging of Transporters with Positron Emission Tomography

    Science.gov (United States)

    Antoni, Gunnar; Sörensen, Jens; Hall, Håkan

    Positron emission tomography (PET) visualization of brain components in vivo is a rapidly growing field. Molecular imaging with PET is also increasingly used in drug development, especially for the determination of drug receptor interaction for CNS-active drugs. This gives the opportunity to relate clinical efficacy to per cent receptor occupancy of a drug on a certain targeted receptor and to relate drug pharmacokinetics in plasma to interaction with target protein. In the present review we will focus on the study of transporters, such as the monoamine transporters, the P-glycoprotein (Pgp) transporter, the vesicular monoamine transporter type 2, and the glucose transporter using PET radioligands. Neurotransmitter transporters are presynaptically located and in vivo imaging using PET can therefore be used for the determination of the density of afferent neurons. Several promising PET ligands for the noradrenaline transporter (NET) have been labeled and evaluated in vivo including in man, but a really useful PET ligand for NET still remains to be identified. The most promising tracer to date is (S,S)-[18F]FMeNER-D2. The in vivo visualization of the dopamine transporter (DAT) may give clues in the evaluation of conditions related to dopamine, such as Parkinson's disease and drug abuse. The first PET radioligands based on cocaine were not selective, but more recently several selective tracers such as [11C]PE2I have been characterized and shown to be suitable as PET radioligands. Although there are a large number of serotonin transporter inhibitors used today as SSRIs, it was not until very recently, when [11C]McN5652 was synthesized, that this transporter was studied using PET. New candidates as PET radioligands for the SERT have subsequently been developed and [11C]DASB and [11C]MADAM and their analogues are today the most promising ligands. The existing radioligands for Pgp transporters seem to be suitable tools for the study of both peripheral and central drug

  20. Clinical applications of perfluorocarbon nanoparticles for molecular imaging and targeted therapeutics.

    Science.gov (United States)

    Tran, Trung D; Caruthers, Shelton D; Hughes, Michael; Marsh, John N; Cyrus, Tillmann; Winter, Patrick M; Neubauer, Anne M; Wickline, Samuel A; Lanza, Gregory M

    2007-01-01

    Molecular imaging is a novel tool that has allowed non-invasive diagnostic imaging to transition from gross anatomical description to identification of specific tissue epitopes and observation of biological processes at the cellular level. This technique has been confined to the field of nuclear imaging; however, recent advances in nanotechnology have extended this research to include ultrasound (US) and magnetic resonance (MR) imaging. The exploitation of nanotechnology for MR and US molecular imaging has generated several candidate contrast agents. One multimodality platform, targeted perfluorocarbon (PFC) nanoparticles, is useful for noninvasive detection with US and MR, targeted drug delivery, and quantification.

  1. In vivo quantification of fluorescent molecular markers in real-time by ratio Imaging for diagnostic screening and image-guided surgery

    NARCIS (Netherlands)

    Bogaards, A.; Sterenborg, H. J. C. M.; Trachtenberg, J.; Wilson, B. C.; Lilge, L.

    2007-01-01

    Future applications of "molecular diagnostic screening" and "molecular image-guided surgery" will demand images of molecular markers with high resolution and high throughput (similar to >= 30 frames/second). MRI, SPECT, PET, optical fluorescence tomography, hyper-spectral fluorescence imaging, and

  2. From molecular imaging to personalized radionuclide therapy of cancer

    International Nuclear Information System (INIS)

    Baum, R.P.

    2015-01-01

    Full text of publication follows. 68 Gallium is a positron emitter (t 1/2 68 min) which can be produced from a generator in a convenient, 'in-house' preparation and used for labeling of peptides, e.g. somatostatin analogues (SA) like DOTATOC or DOTATATE for molecular imaging of SSTR expressing tumors. Since 2004, we have performed over 7700 68 Ga PET/CT studies in patients with neuroendocrine tumors (NET) and have established SSTR PET/CT as the new gold standard for imaging G1 and G2 NET (staging, re-staging, therapy response evaluation and detection of unknown primary NET). The same peptides can be labeled with 177 Lutetium or 90 Yttrium for radionuclide therapy, a form of personalized treatment (THERANOSTICS approach). PRRNT is based on the receptor-mediated internalization of SA. Several clinical trials indicate that PRRNT can deliver effective radiation doses to tumors. A German multi-institutional registry study with prospective follow up in 450 patients indicates that PRRT is an effective therapy for patients with G1-2 neuroendocrine tumors, irrespective of previous therapies, with a survival advantage of several years compared to other therapies and only minor side effects. Median overall survival (OS) of all patients from the start of treatment was 59 months. Median progression-free survival (PFS) measured from last cycle of therapy accounted to 41 mo. Median PFS of pancreatic NET was 39 mo. Similar results were obtained for NET of unknown primary (median PFS: 38 mo) whereas NET of small bowel had a median PFS of 51 months. Side effects like 3-4 NEThro- or hemato-toxicity were observed in only 0.2% and 2% of patients respectively. PRRNT is highly effective in the management of NET, even in advanced cases. In patients with progressive neuroendocrine tumors, fractionated, personalized PRRNT with lower doses of radioactivity given over a longer period of time (Bad Berka Concept using sequential (DUO) PRRNT) results in excellent therapeutic responses

  3. A CZT-based blood counter for quantitative molecular imaging.

    Science.gov (United States)

    Espagnet, Romain; Frezza, Andrea; Martin, Jean-Pierre; Hamel, Louis-André; Lechippey, Laëtitia; Beauregard, Jean-Mathieu; Després, Philippe

    2017-12-01

    Robust quantitative analysis in positron emission tomography (PET) and in single-photon emission computed tomography (SPECT) typically requires the time-activity curve as an input function for the pharmacokinetic modeling of tracer uptake. For this purpose, a new automated tool for the determination of blood activity as a function of time is presented. The device, compact enough to be used on the patient bed, relies on a peristaltic pump for continuous blood withdrawal at user-defined rates. Gamma detection is based on a 20 × 20 × 15 mm 3 cadmium zinc telluride (CZT) detector, read by custom-made electronics and a field-programmable gate array-based signal processing unit. A graphical user interface (GUI) allows users to select parameters and easily perform acquisitions. This paper presents the overall design of the device as well as the results related to the detector performance in terms of stability, sensitivity and energy resolution. Results from a patient study are also reported. The device achieved a sensitivity of 7.1 cps/(kBq/mL) and a minimum detectable activity of 2.5 kBq/ml for 18 F. The gamma counter also demonstrated an excellent stability with a deviation in count rates inferior to 0.05% over 6 h. An energy resolution of 8% was achieved at 662 keV. The patient study was conclusive and demonstrated that the compact gamma blood counter developed has the sensitivity and the stability required to conduct quantitative molecular imaging studies in PET and SPECT.

  4. MARS spectral molecular imaging of lamb tissue: data collection and image analysis

    CERN Document Server

    Aamir, R; Bateman, C.J.; Butler, A.P.H.; Butler, P.H.; Anderson, N.G.; Bell, S.T.; Panta, R.K.; Healy, J.L.; Mohr, J.L.; Rajendran, K.; Walsh, M.F.; Ruiter, N.de; Gieseg, S.P.; Woodfield, T.; Renaud, P.F.; Brooke, L.; Abdul-Majid, S.; Clyne, M.; Glendenning, R.; Bones, P.J.; Billinghurst, M.; Bartneck, C.; Mandalika, H.; Grasset, R.; Schleich, N.; Scott, N.; Nik, S.J.; Opie, A.; Janmale, T.; Tang, D.N.; Kim, D.; Doesburg, R.M.; Zainon, R.; Ronaldson, J.P.; Cook, N.J.; Smithies, D.J.; Hodge, K.

    2014-01-01

    Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20 to 140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we ...

  5. Development of Optical Molecular Imaging System for the Acquisition of Bioluminescence Signals from Small Animals

    International Nuclear Information System (INIS)

    Lee, Byeong Il; Kim, Hyeon Sik; Jeong, Hye Jin; Lee, Hyung Jae; Moon, Seung Min; Kwon, Seung Young; Jeong, Shin Young; Bom, Hee Seung; Min, Jung Joon; Choi, Eun Seo

    2009-01-01

    Optical imaging is providing great advance and improvement in genetic and molecular imaging of animals and humans. Optical imaging system consists of optical imaging devices, which carry out major function for monitoring, tracing, and imaging in most of molecular in-vivo researches. In bio-luminescent imaging, small animals containing luciferase gene locally irradiate light, and emitted photons transmitted through skin of the small animals are imaged by using a high sensitive charged coupled device (CCD) camera. In this paper, we introduced optical imaging system for the image acquisition of bio-luminescent signals emitted from small animals. In the system, Nikon lens and four LED light sources were mounted at the inside of a dark box. A cooled CCD camera equipped with a control module was used. We tested the performance of the optical imaging system using effendorf tube and light emitting bacteria which injected intravenously into CT26 tumor bearing nude mouse. The performance of implemented optical imaging system for bio-luminescence imaging was demonstrated and the feasibility of the system in small animal imaging application was proved. We anticipate this system could be a useful tool for the molecular imaging of small animals adaptable for various experimental conditions in future

  6. The development of epidermal growth factor receptor molecular imaging in cancer

    International Nuclear Information System (INIS)

    Zhou Xiaoliang; Wang Hao; Shi Peiji; Liu Jianfeng; Meng Aimin

    2013-01-01

    In vivo epidermal growth factor receptor (EGFR) targeted therapy has great potential for cancer diagnosis and the evaluation of curative effects. Enhancement of EGFR-targeted therapy needs a reliable quantitative molecular imaging method which could enable monitoring of receptor drug binding and receptor occupancy in vivo, and identification of the mutation in EGFR. PET or SPECT is the most advanced molecular imaging technology of non-invasively selecting responders, predicting therapeutic outcome and monitoring EGFR-targeted treatment. This review analyzed the present situation and research progress of molecular imaging agents. (authors)

  7. Molecular MR imaging of cancer gene therapy. Ferritin transgene reporter takes the stage

    International Nuclear Information System (INIS)

    Hasegawa, Sumitaka; Furukawa, Takako; Saga, Tsuneo

    2010-01-01

    Molecular imaging using magnetic resonance (MR) imaging has been actively investigated and made rapid progress in the past decade. Applied to cancer gene therapy, the technique's high spatial resolution allows evaluation of gene delivery into target tissues. Because noninvasive monitoring of the duration, location, and magnitude of transgene expression in tumor tissues or cells provides useful information for assessing therapeutic efficacy and optimizing protocols, molecular imaging is expected to become a critical step in the success of cancer gene therapy in the near future. We present a brief overview of the current status of molecular MR imaging, especially in vivo reporter gene imaging using ferritin and other reporters, discuss its application to cancer gene therapy, and present our research of MR imaging detection of electroporation-mediated cancer gene therapy using the ferritin reporter gene. (author)

  8. Molecular imaging of atherosclerosis in mice with MRI and near-infrared fluorescence imaging

    International Nuclear Information System (INIS)

    Lu Tong; Wen Song; Zhou Guanhui; Ju Shenghong; Teng Gaojun

    2012-01-01

    Objective: To explore the feasibility of detecting atherosclerotic plaques with 7.0 T MRI and near-infrared fluorescence imaging (NIRF) using molecular imaging probes. Methods: Atherosclerotic plaques were established in male atherosclerotic apolipoprotein E knockout (ApoE-/-) mice fed with high-cholesterol diet for 20 weeks. Wild-type C57BL/6 mice were used as negative controls. 7.0 T MRI was performed before and 36 h after intravenously administration of ultrasmall superparamagnetic particle of iron oxide (USPIO). NIR 797 was conjugated with anti-mouse-oxidized modified low density lipoprotein (oxLDL) antibodies to construct an anti-oxLDL-Ab-NIR 797 probe while non-specific IgG-NIR 797 and PBS used as controls. NIRF was performed 24 h after tail vein injection of the probe. Independent sample t-test and one-way analysis of variance were used to analyze the data by SPSS 17.0. Results: In APOE-/-mice, in vivo 36 h post-USPIO T 2 WI images revealed strong focal signal loss in the abdominal aorta than that of pre-USPIO, with relative signal intensity 0.70 ± 0.04 and 1.28 ± 0.06, respectively (t=3.376, P<0.05). The percent of signal reduced was (-56.58 ± 4.25)%. The Prussian blue staining confirmed the depositions of iron particles in the plaque lesions. Significant fluorochrome accumulation in atherosclerotic plaques was demonstrated in aortic root, aortic arch and the starting of descending aorta 24 h after injection of the anti-oxLDL-Ab-NIR 797 probe. Minimal antibody uptake was observed in normal vessels from wild-type mice receiving the anti-oxLDL-Ab-NIR 797 (SNR: 2.29 ± 1.11) and in atherosclerotic vessels from ApoE-/- mice receiving the non-specific IgG-NIR 797 (19.58 ±3.06) or PBS (4.19 ±0.82), which was significantly different from the uptake of anti-oxLDL-Ab-NIR 797 group (42.51 ±5.24, F=25.104, P<0.05). Comparison between oil red O staining and NIRF 24 h after injection of NIR 797 labeled oxLDL-antibody revealed a significant correlation (r=0.738, P

  9. Clinical applications of perfluorocarbon nanoparticles for molecular imaging and targeted therapeutics

    OpenAIRE

    Tran, Trung D; Caruthers, Shelton D; Hughes, Michael; Marsh, John N; Cyrus, Tillmann; Winter, Patrick M; Neubauer, Anne M; Wickline, Samuel A; Lanza, Gregory M

    2007-01-01

    Molecular imaging is a novel tool that has allowed non-invasive diagnostic imaging to transition from gross anatomical description to identification of specific tissue epitopes and observation of biological processes at the cellular level. This technique has been confined to the field of nuclear imaging; however, recent advances in nanotechnology have extended this research to include ultrasound (US) and magnetic resonance (MR) imaging. The exploitation of nanotechnology for MR and US molecul...

  10. Molecular Imaging Probes for Diagnosis and Therapy Evaluation of Breast Cancer

    Directory of Open Access Journals (Sweden)

    Qingqing Meng

    2013-01-01

    Full Text Available Breast cancer is a major cause of cancer death in women where early detection and accurate assessment of therapy response can improve clinical outcomes. Molecular imaging, which includes PET, SPECT, MRI, and optical modalities, provides noninvasive means of detecting biological processes and molecular events in vivo. Molecular imaging has the potential to enhance our understanding of breast cancer biology and effects of drug action during both preclinical and clinical phases of drug development. This has led to the identification of many molecular imaging probes for key processes in breast cancer. Hormone receptors, growth factor receptor, and angiogenic factors, such as ER, PR, HER2, and VEGFR, have been adopted as imaging targets to detect and stage the breast cancer and to monitor the treatment efficacy. Receptor imaging probes are usually composed of targeting moiety attached to a signaling component such as a radionuclide that can be detected using dedicated instruments. Current molecular imaging probes involved in breast cancer diagnosis and therapy evaluation are reviewed, and future of molecular imaging for the preclinical and clinical is explained.

  11. Investigating Atmospheric Oxidation with Molecular Dynamics Imaging and Spectroscopy

    Science.gov (United States)

    Merrill, W. G.; Case, A. S.; Keutsch, F. N.

    2013-06-01

    Volatile organic compounds (VOCs) in the Earth's atmosphere constitute trace gas species emitted primarily from the biosphere, and are the subject of inquiry for a variety of air quality and climate studies. Reactions intiated (primarily) by the hydroxyl radical (OH) lead to a myriad of oxygenated species (OVOCs), which in turn are prone to further oxidation. Investigations of the role that VOC oxidation plays in tropospheric chemistry have brought to light two troubling scenarios: (1) VOCs are responsible in part for the production of two EPA-regulated pollutants---tropospheric ozone and organic aerosol---and (2) the mechanistic details of VOC oxidation remain convoluted and poorly understood. The latter issue hampers the implementation of near-explicit atmospheric simulations, and large discrepancies in OH reactivity exist between measurements and models at present. Such discrepancies underscore the need for a more thorough description of VOC oxidation. Time-of-flight measurements and ion-imaging techniques are viable options for resolving some of the mechanistic and energetic details of VOC oxidation. Molecular beam studies have the advantage of foregoing unwanted bimolecular reactions, allowing for the characterization of specific processes which must typically compete with the complex manifold of VOC oxidation pathways. The focus of this work is on the unimolecular channels of organic peroxy radical intermediates, which are necessarily generated during VOC oxidation. Such intermediates may isomerize and decompose into distinct chemical channels, enabling the unambiguous detection of each pathway. For instance, a (1 + 1') resonance enhanced multiphoton ionization (REMPI) scheme may be employed to detect carbon monoxide generated from a particular unimolecular process. A number of more subtle mechanistic details may be explored as well. By varying the mean free path of the peroxy radicals in a flow tube, the role of collisional quenching in these unimolecular

  12. Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques.

    Directory of Open Access Journals (Sweden)

    Nazanin Hakimzadeh

    Full Text Available Molecular imaging of matrix metalloproteinases (MMPs may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9 with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT imaging that effectively targets atherosclerotic lesions in mice.

  13. Novel molecular imaging ligands targeting matrix metalloproteinases 2 and 9 for imaging of unstable atherosclerotic plaques

    Science.gov (United States)

    Molenaar, Ger; de Waard, Vivian; Lutgens, Esther; van Eck-Smit, Berthe L. F.; de Bruin, Kora; Piek, Jan J.; Eersels, Jos L. H.; Booij, Jan; Verberne, Hein J.; Windhorst, Albert D.

    2017-01-01

    Molecular imaging of matrix metalloproteinases (MMPs) may allow detection of atherosclerotic lesions vulnerable to rupture. In this study, we develop a novel radiolabelled compound that can target gelatinase MMP subtypes (MMP2/9) with high selectivity and inhibitory potency. Inhibitory potencies of several halogenated analogues of MMP subtype-selective inhibitors (N-benzenesulfonyliminodiacetyl monohydroxamates and N-halophenoxy-benzenesulfonyl iminodiacetyl monohydroxamates) were in the nanomolar range for MMP2/9. The analogue with highest inhibitory potency and selectivity was radiolabelled with [123I], resulting in moderate radiochemical yield, and high radiochemical purity. Biodistribution studies in mice, revealed stabilization in blood 1 hour after intravenous bolus injection. Intravenous infusion of the radioligand and subsequent autoradiography of excised aortas showed tracer uptake in atheroprone mice. Distribution of the radioligand showed co-localization with MMP2/9 immunohistochemical staining. In conclusion, we have developed a novel selective radiolabeled MMP2/9 inhibitor, suitable for single photon emission computed tomography (SPECT) imaging that effectively targets atherosclerotic lesions in mice. PMID:29190653

  14. Molecular Imaging : Computer Reconstruction and Practice - Proceedings of the NATO Advanced Study Institute on Molecular Imaging from Physical Principles to Computer Reconstruction and Practice

    CERN Document Server

    Lemoigne, Yves

    2008-01-01

    This volume collects the lectures presented at the ninth ESI School held at Archamps (FR) in November 2006 and is dedicated to nuclear physics applications in molecular imaging. The lectures focus on the multiple facets of image reconstruction processing and management and illustrate the role of digital imaging in clinical practice. Medical computing and image reconstruction are introduced by analysing the underlying physics principles and their implementation, relevant quality aspects, clinical performance and recent advancements in the field. Several stages of the imaging process are specifically addressed, e.g. optimisation of data acquisition and storage, distributed computing, physiology and detector modelling, computer algorithms for image reconstruction and measurement in tomography applications, for both clinical and biomedical research applications. All topics are presented with didactical language and style, making this book an appropriate reference for students and professionals seeking a comprehen...

  15. Multimodality molecular imaging of disease progression in living ...

    Indian Academy of Sciences (India)

    immune cell trafficking, stem cell therapy, transgenic animals and even molecular interactions in living subjects. .... measurement of the effect of absorbed electromagnetic ..... Changes in intracellular pH, electrical impulses by nerve cells and ...

  16. Potential of luminescence based molecular animal imaging in research areas pertaining to cancer biology and therapy

    International Nuclear Information System (INIS)

    Yadav, Hansa D.; Shetake, Neena G.; Balla Murali, M.S.; Kumar, Amit; Pandey, B.N.

    2017-01-01

    Animal imaging is getting tremendous importance in biomedical research areas including drug delivery, radiobiology and cancer research. Even though, imaging techniques like CT, PET, SPECT, MRI are available for experimental animals, luminescence-based molecular imaging is still considered as crucial and common tool for biomedical laboratories due to easy handling/maintenance, cost effectiveness and various strategies available to manipulate the molecules/cells employed for imaging purposes. The Molecular Animal Imaging System available in our laboratory is being utilized for various cancer research activities including measurement of tumor growth kinetics, angiogenesis, therapeutic efficacy evaluation and metastasis studies. Moreover, the imaging system is also been used for radio-luminescence imaging based on Cherenkov radiation of radio-pharmaceuticals. (author)

  17. Dynamic fluorescence imaging with molecular agents for cancer detection

    Science.gov (United States)

    Kwon, Sun Kuk

    Non-invasive dynamic optical imaging of small animals requires the development of a novel fluorescence imaging modality. Herein, fluorescence imaging is demonstrated with sub-second camera integration times using agents specifically targeted to disease markers, enabling rapid detection of cancerous regions. The continuous-wave fluorescence imaging acquires data with an intensified or an electron-multiplying charge-coupled device. The work presented in this dissertation (i) assessed dose-dependent uptake using dynamic fluorescence imaging and pharmacokinetic (PK) models, (ii) evaluated disease marker availability in two different xenograft tumors, (iii) compared the impact of autofluorescence in fluorescence imaging of near-infrared (NIR) vs. red light excitable fluorescent contrast agents, (iv) demonstrated dual-wavelength fluorescence imaging of angiogenic vessels and lymphatics associated with a xenograft tumor model, and (v) examined dynamic multi-wavelength, whole-body fluorescence imaging with two different fluorescent contrast agents. PK analysis showed that the uptake of Cy5.5-c(KRGDf) in xenograft tumor regions linearly increased with doses of Cy5.5-c(KRGDf) up to 1.5 nmol/mouse. Above 1.5 nmol/mouse, the uptake did not increase with doses, suggesting receptor saturation. Target to background ratio (TBR) and PK analysis for two different tumor cell lines showed that while Kaposi's sarcoma (KS1767) exhibited early and rapid uptake of Cy5.5-c(KRGDf), human melanoma tumors (M21) had non-significant TBR differences and early uptake rates similar to the contralateral normal tissue regions. The differences may be due to different compartment location of the target. A comparison of fluorescence imaging with NIR vs. red light excitable fluorescent dyes demonstrates that NIR dyes are associated with less background signal, enabling rapid tumor detection. In contrast, animals injected with red light excitable fluorescent dyes showed high autofluorescence. Dual

  18. Current applications of molecular imaging and luminescence-based techniques in traditional Chinese medicine.

    Science.gov (United States)

    Li, Jinhui; Wan, Haitong; Zhang, Hong; Tian, Mei

    2011-09-01

    Traditional Chinese medicine (TCM), which is fundamentally different from Western medicine, has been widely investigated using various approaches. Cellular- or molecular-based imaging has been used to investigate and illuminate the various challenges identified and progress made using therapeutic methods in TCM. Insight into the processes of TCM at the cellular and molecular changes and the ability to image these processes will enhance our understanding of various diseases of TCM and will provide new tools to diagnose and treat patients. Various TCM therapies including herbs and formulations, acupuncture and moxibustion, massage, Gua Sha, and diet therapy have been analyzed using positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging and ultrasound and optical imaging. These imaging tools have kept pace with developments in molecular biology, nuclear medicine, and computer technology. We provide an overview of recent developments in demystifying ancient knowledge - like the power of energy flow and blood flow meridians, and serial naturopathies - which are essential to visually and vividly recognize the body using modern technology. In TCM, treatment can be individualized in a holistic or systematic view that is consistent with molecular imaging technologies. Future studies might include using molecular imaging in conjunction with TCM to easily diagnose or monitor patients naturally and noninvasively. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  19. Lipid-based nanoparticles for magnetic resonance molecular imaging : design, characterization, and application

    NARCIS (Netherlands)

    Mulder, W.J.M.

    2006-01-01

    In this thesis research is described which was aimed to develop lipidic nanoparticles for the investigation and visualization of atherosclerosis and angiogenesis with both magnetic resonance molecular imaging and optical techniques. The underlying rationale for this is that conventional MR imaging

  20. Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging

    NARCIS (Netherlands)

    Mulder, Willem J. M.; Strijkers, Gustav J.; van Tilborg, Geralda A. F.; Griffioen, Arjan W.; Nicolay, Klaas

    2006-01-01

    In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the

  1. Molecular imaging for theranostics in gastroenterology: one stone to kill two birds.

    Science.gov (United States)

    Ko, Kwang Hyun; Kown, Chang-Il; Park, Jong Min; Lee, Hoo Geun; Han, Na Young; Hahm, Ki Baik

    2014-09-01

    Molecular imaging in gastroenterology has become more feasible with recent advances in imaging technology, molecular genetics, and next-generation biochemistry, in addition to advances in endoscopic imaging techniques including magnified high-resolution endoscopy, narrow band imaging or autofluorescence imaging, flexible spectral imaging color enhancement, and confocal laser endomicroscopy. These developments have the potential to serve as "red flag" techniques enabling the earlier and accurate detection of mucosal abnormalities (such as precancerous lesions) beyond biomarkers, virtual histology of detected lesions, and molecular targeted therapy-the strategy of "one stone to kill two or three birds"; however, more effort should be done to be "blue ocean" benefit. This review deals with the introduction of Raman spectroscopy endoscopy, imaging mass spectroscopy, and nanomolecule development for theranostics. Imaging of molecular pathological changes in cells/tissues/organs might open the "royal road" to either convincing diagnosis of diseases that otherwise would only be detected in the advanced stages or novel therapeutic methods targeted to personalized medicine.

  2. PBCA-based polymeric microbubbles for molecular imaging and drug delivery

    NARCIS (Netherlands)

    Koczera, Patrick; Appold, Lia; Shi, Yang; Liu, Mengjiao; Dasgupta, Anshuman; Pathak, Vertika; Ojha, Tarun; Fokong, Stanley; Wu, Zhuojun; Van Zandvoort, Marc; Iranzo, Olga; Kuehne, Alexander J C; Pich, Andrij; Kiessling, Fabian; Lammers, Twan

    2017-01-01

    Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. We describe different types of targeted and drug-loaded poly(n-butyl cyanoacrylate) (PBCA) MB, and demonstrate their suitability for multiple biomedical applications, including molecular US imaging and US-mediated

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

    NARCIS (Netherlands)

    Vermeulen, J.F.

    2012-01-01

    Breast cancer is the most frequently diagnosed cancer in women. Although breast cancer is mainly diagnosed by mammography, other imaging modalities (e.g. MRI, PET) are increasingly used. The most recent developments in the field of molecular imaging comprise the application of near-infrared

  4. Applications of the Preclinical Molecular Imaging in Biomedicine: Gene Therapy

    International Nuclear Information System (INIS)

    Collantes, M.; Peñuelas, I.

    2014-01-01

    Gene therapy constitutes a promising option for efficient and targeted treatment of several inherited disorders. Imaging techniques using ionizing radiation as PET or SPECT are used for non-invasive monitoring of the distribution and kinetics of vector-mediated gene expression. In this review the main reporter gene/reporter probe strategies are summarized, as well as the contribution of preclinical models to the development of this new imaging modality previously to its application in clinical arena. [es

  5. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    Science.gov (United States)

    2013-09-01

    percent of invasive carcinoma and grows slowly over the course of years. It is very soft and looks like gray-blue gelatin . Two other invasive...Nitin, N., D. J. Javier, et al. (2007). "Widefield and high-resolution reflectance imaging of gold and silver nanospheres." J Biomed Opt 12(5...2010. “Widefield and High-resolution Reflectance Imaging of Gold and Silver Nanospheres.” Journal of Biomedical Optics 12 (5): 051505. doi:10.1117

  6. First PET Center in Mexico: the power of molecular imaging

    International Nuclear Information System (INIS)

    Avila R, M.A.

    2001-01-01

    Positron Emission Tomography (PET) is a non-invasive diagnostic imaging technique modality. It represents the forefront of medical images and was developed as a quantitative technique for imaging biochemical and physiological processes in the human body. PET is unique because it produces images of the body's basic biochemistry or function. Traditional diagnostic techniques such as x-rays, CT scans or MRI, produce images of the body's anatomy or structure. The premise with these techniques is that the change in anatomy or structure that occurs with disease can be seen. However, biochemical processes are also altered with disease and may occur before there is a change gross anatomy. PET is an imaging technique that is used to visualize some of these processes. The development of PET as we know it today began in 1974 with the development of a single ring detector system by Phelps et al. Today, over 350 PET scanners are in use in the world, mainly in the USA (over 140), Europe (particularly in the Anglo-Saxon countries and France) and Japan. Many of these facilities also have their own cyclotron to produce the positron emitters. In the Southern hemisphere, only Australia, Argentina. and recently Mexico, have a very small number of PET facilities. (Author)

  7. First PET Center in Mexico: the power of molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Avila R, M.A. [Unidad PET, Facultad de Medicina, UNAM (Mexico)

    2001-09-01

    Positron Emission Tomography (PET) is a non-invasive diagnostic imaging technique modality. It represents the forefront of medical images and was developed as a quantitative technique for imaging biochemical and physiological processes in the human body. PET is unique because it produces images of the body's basic biochemistry or function. Traditional diagnostic techniques such as x-rays, CT scans or MRI, produce images of the body's anatomy or structure. The premise with these techniques is that the change in anatomy or structure that occurs with disease can be seen. However, biochemical processes are also altered with disease and may occur before there is a change gross anatomy. PET is an imaging technique that is used to visualize some of these processes. The development of PET as we know it today began in 1974 with the development of a single ring detector system by Phelps et al. Today, over 350 PET scanners are in use in the world, mainly in the USA (over 140), Europe (particularly in the Anglo-Saxon countries and France) and Japan. Many of these facilities also have their own cyclotron to produce the positron emitters. In the Southern hemisphere, only Australia, Argentina. and recently Mexico, have a very small number of PET facilities. (Author)

  8. Autonomic innervation of the heart. Role of molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Slart, Riemer H.J.A; Elsinga, Philip H. [Univ. Medical Center Groningen (Netherlands). Nuclear Medicine and Molecular Imaging; Tio, Rene A. [Univ. Medical Center Groningen (Netherlands). Thorax Center Cardiology; Schwaiger, Markus (ed.) [Technische Univ. Muenchen Klinikum Rechts der Isar (Germany). Nuklearmedizinische Klinik

    2015-03-01

    Reviews in detail the value of SPECT-CT and PET-CT in the imaging of cardiac innervation. Details the role of imaging in a range of conditions and diseases. Includes important background on pathophysiology, tracers, radiopharmaceutical production, and kinetic modeling software. This book explains in detail the potential value of the hybrid modalities, SPECT-CT and PET-CT, in the imaging of cardiac innervation in a wide range of conditions and diseases, including ischemic heart disease, diabetes mellitus, heart failure, amyloidosis, heart transplantation, and ventricular arrhythmias. Imaging of the brain-heart axis in neurodegenerative disease and stress and of cardiotoxicity is also discussed. The roles of the various available tracers are fully considered, and individual chapters address radiopharmaceutical development under GMP, imaging physics, and kinetic modeling software. Highly relevant background information is included on the autonomic nervous system of the heart and its pathophysiology, and in addition future perspectives are discussed. Awareness of the importance of autonomic innervation of the heart for the optimal management of cardiac patients is growing, and there is an evident need for objective measurement techniques or imaging modalities. In this context, Autonomic Innervation of the Heart will be of wide interest to clinicians, researchers, and industry.

  9. Autonomic innervation of the heart. Role of molecular imaging

    International Nuclear Information System (INIS)

    Slart, Riemer H.J.A; Elsinga, Philip H.; Tio, Rene A.; Schwaiger, Markus

    2015-01-01

    Reviews in detail the value of SPECT-CT and PET-CT in the imaging of cardiac innervation. Details the role of imaging in a range of conditions and diseases. Includes important background on pathophysiology, tracers, radiopharmaceutical production, and kinetic modeling software. This book explains in detail the potential value of the hybrid modalities, SPECT-CT and PET-CT, in the imaging of cardiac innervation in a wide range of conditions and diseases, including ischemic heart disease, diabetes mellitus, heart failure, amyloidosis, heart transplantation, and ventricular arrhythmias. Imaging of the brain-heart axis in neurodegenerative disease and stress and of cardiotoxicity is also discussed. The roles of the various available tracers are fully considered, and individual chapters address radiopharmaceutical development under GMP, imaging physics, and kinetic modeling software. Highly relevant background information is included on the autonomic nervous system of the heart and its pathophysiology, and in addition future perspectives are discussed. Awareness of the importance of autonomic innervation of the heart for the optimal management of cardiac patients is growing, and there is an evident need for objective measurement techniques or imaging modalities. In this context, Autonomic Innervation of the Heart will be of wide interest to clinicians, researchers, and industry.

  10. Integrated Molecular Imaging and Therapy for Breast Cancer

    National Research Council Canada - National Science Library

    Panchapakesan, Balaji

    2008-01-01

    ...) and NIR dosing of cancer cells using SWCNT. While previous studies have shown the transport of DNA into cells using nanotubes, in this study we show multi-component molecular targeting of both IGF1R and Her2 surface markers in cancer cells...

  11. Development of neuroradiology. From the visualization of bones to molecular imaging

    International Nuclear Information System (INIS)

    Reith, W.

    2005-01-01

    Since the discovery of X-rays, rapid and significant progress has been and continues to be made in imaging techniques, particularly neuroradiology. Milestones along the way included use of contrast agents, digital subtraction angiography, computed tomography, and magnetic resonance imaging. The most recent achievements are visualization of cerebral activation and fiber systems in the brain parenchyma. Application of new contrast agents seems to make imaging at the ''molecular'' level also possible. (orig.) [de

  12. SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

    Science.gov (United States)

    Palumbo, Barbara; Buresta, Tommaso; Nuvoli, Susanna; Spanu, Angela; Schillaci, Orazio; Fravolini, Mario Luca; Palumbo, Isabella

    2014-01-01

    Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET) represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI) is discussed. PMID:24897023

  13. Coronary magnetic resonance imaging: visualization of the vessel lumen and the vessel wall and molecular imaging of arteriothrombosis

    International Nuclear Information System (INIS)

    Spuentrup, Elmar; Botnar, Rene M.

    2006-01-01

    Coronary magnetic resonance (MR) imaging has dramatically emerged over the last decade. Technical improvements have enabled reliable visualization of the proximal and midportion of the coronary artery tree for exclusion of significant coronary artery disease. However, current technical developments focus also on direct visualization of the diseased coronary vessel wall and imaging of coronary plaque because plaques without stenoses are typically more vulnerable with higher risk of plaque rupture. Plaque rupture with subsequent thrombosis and vessel occlusion is the main cause of myocardial infarction. Very recently, the first success of molecular imaging in the coronary arteries has been demonstrated using a fibrin-specific contrast agent for selective visualization of coronary thrombosis. This demonstrates in general the high potential of molecular MR imaging in the field of coronary artery disease. In this review, we will address recent technical advances in coronary MR imaging, including visualization of the lumen and the vessel wall and molecular imaging of coronary arteriothrombosis. First results of these new approaches will be discussed. (orig.)

  14. From molecular imaging to systems diagnostics: Time for another paradigm shift?

    Energy Technology Data Exchange (ETDEWEB)

    Li, King C.P. [Department of Radiology, Methodist Hospital, Weill Cornell Medical College, 6565 Fannin Street, D280 Houston, TX 77030 (United States)], E-mail: kli@tmhs.org

    2009-05-15

    The term 'Molecular Imaging' has hit the consciousness of radiologists only in the past decade although many of the concepts that molecular imaging encompasses has been practiced in biomedical imaging, especially in nuclear medicine, for many decades. Many new imaging techniques have allowed us to interrogate biologic events at the cellular and molecular level in vivo in four dimensions but the challenge now is to translate these techniques into clinical practice in a way that will enable us to revolutionize healthcare delivery. The purpose of this article is to introduce the term 'Systems Diagnostics' and examine how radiologists can become translators of disparate sources of information into medical decisions and therapeutic actions.

  15. Potentials and limits of modern tomographic methods (CT, MR, PET) in molecular imaging

    International Nuclear Information System (INIS)

    Hentschel, M.; Paul, D.; Moser, E.; Brink, I.

    2007-01-01

    The present survey gives an introduction into the basics of computed tomography, magnetic resonance tomography and positron emission tomography. The current potentials of these methods in relation to their temporal, spatial and contrast resolutions as well as their sensitivities within clinical routine and experimental studies (in vitro, ex vivo) will be presented. Computed tomography constitutes the anatomical reference method with well defined contrast, high spatial resolution but low sensitivity (10 -2 mol/l) for functional and molecular imaging. Magnetic resonance tomography represents the anatomical method for research with variable tissue contrast, physiological image information, highest spatial resolution but moderate sensitivity (10 -3 -10 -5 mol/l) for functional and molecular imaging. Positron emission tomography offers good suitability for molecular imaging due to highest sensitivity (10 -11 -10 -12 mol/l). However, the spatial resolution of positron emission tomography is low. (orig.)

  16. Recent Advances in Cardiac Computed Tomography: Dual Energy, Spectral and Molecular CT Imaging

    Science.gov (United States)

    Danad, Ibrahim; Fayad, Zahi A.; Willemink, Martin J.; Min, James K.

    2015-01-01

    Computed tomography (CT) evolved into a powerful diagnostic tool and it is impossible to imagine current clinical practice without CT imaging. Due to its widespread availability, ease of clinical application, superb sensitivity for detection of CAD, and non-invasive nature, CT has become a valuable tool within the armamentarium of the cardiologist. In the last few years, numerous technological advances in CT have occurred—including dual energy CT (DECT), spectral CT and CT-based molecular imaging. By harnessing the advances in technology, cardiac CT has advanced beyond the mere evaluation of coronary stenosis to an imaging modality tool that permits accurate plaque characterization, assessment of myocardial perfusion and even probing of molecular processes that are involved in coronary atherosclerosis. Novel innovations in CT contrast agents and pre-clinical spectral CT devices have paved the way for CT-based molecular imaging. PMID:26068288

  17. Integration of molecular imaging in treatment planning and delivery of modern radiotherapy

    International Nuclear Information System (INIS)

    Jacob, V.; Wilkens, J.J.

    2011-01-01

    Among various imaging modalities currently available, positron emission tomography (PET) has the potential to visualize processes on a molecular level. Molecular imaging, often also referred to as functional or biological imaging, brought a new dimension to diagnostics and therapy of cancer by providing images of metabolism and other processes in the human body and in tumours. PET was first applied for diagnostics and staging of various tumours with high diagnostic precision. Modern radiotherapy asks increasingly for individualized treatment strategies, taking molecular imaging into account. Technical developments over the last years, in particular methods to register various imaging modalities within software packages for treatment planning and target delineation, facilitated the use of PET imaging in radiotherapy. In order to exploit the full potential of modern high-precision radiotherapy, exact imaging procedures are necessary, for example for precise target volume definition. In the long run, concepts employing an inhomogeneous dose prescription based on biological imaging may become routine in clinical applications, leading to individualized, biologically adaptive therapy. (orig.)

  18. In Silico Affinity Profiling of Neuroactive Polyphenols for Post-Traumatic Calpain Inactivation: A Molecular Docking and Atomistic Simulation Sensitivity Analysis

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar

    2014-12-01

    Full Text Available Calcium-activated nonlysosomal neutral proteases, calpains, are believed to be early mediators of neuronal damage associated with neuron death and axonal degeneration after traumatic neural injuries. In this study, a library of biologically active small molecular weight calpain inhibitors was used for model validation and inhibition site recognition. Subsequently, two natural neuroactive polyphenols, curcumin and quercetin, were tested for their sensitivity and activity towards calpain’s proteolytic sequence and compared with the known calpain inhibitors via detailed molecular mechanics (MM, molecular dynamics (MD, and docking simulations. The MM and MD energy profiles (SJA6017 < AK275 < AK295 < PD151746 < quercetin < leupeptin < PD150606 < curcumin < ALLN < ALLM < MDL-28170 < calpeptin and the docking analysis (AK275 < AK295 < PD151746 < ALLN < PD150606 < curcumin < leupeptin < quercetin < calpeptin < SJA6017 < MDL-28170 < ALLM demonstrated that polyphenols conferred comparable calpain inhibition profiling. The modeling paradigm used in this study provides the first detailed account of corroboration of enzyme inhibition efficacy of calpain inhibitors and the respective calpain–calpain inhibitor molecular complexes’ energetic landscape and in addition stimulates the polyphenol bioactive paradigm for post-SCI intervention with implications reaching to experimental in vitro, in cyto, and in vivo studies.

  19. Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatment, and Therapeutic Modalities

    Science.gov (United States)

    2011-02-01

    Therapeutic and Imaging Agents to Lung Cancer (PI and co-PI: Renata Pasqualini , Ph.D., Wadih Arap, M.D., Ph.D.) The studies outlined in this proposal...with Drs. Pasqualini , Arap, and Wistuba. The IHC staining of lung cancer TMAs (390 cases) has been completed. We are working with investigators to...Project 3, R. Pasqualini ). This project was completed and a manuscript is in preparation by Dr. Pasqualini’s lab. b) Molecular abnormalities

  20. The research progress of dual-modality probes for molecular imaging

    International Nuclear Information System (INIS)

    Cao Feng; Chen Yue

    2010-01-01

    Various imaging modalities have been exploited to investigate the anatomic or functional dissemination of tissues in the body. However, no single imaging modality allows overall structural, functional, and molecular information as each imaging modality has its own unique strengths and weaknesses. The combination of two imaging modalities that investigates the strengths of different methods might offer the prospect of improved diagnostic abilities. As more and more dual-modality imaging system have become clinically adopted, significant progress has been made toward the creation of dual-modality imaging probes, which can be used as novel tools for future multimodality systems. These all-in-one probes take full advantage of two different imaging modalities and could provide comprehensive information for clinical diagnostics. This review discusses the advantages and challenges in developing dual-modality imaging probes. (authors)

  1. Molecular imaging in the management of cervical cancer

    Directory of Open Access Journals (Sweden)

    Chyong-Huey Lai

    2012-08-01

    Full Text Available Positron emission tomography (PET, magnetic resonance imaging (MRI, and integrated 18-fluorodeoxyglucose (18F-FDG PET/computed tomography are valuable techniques for assessing prognosis, treatment response after the completion of concurrent chemoradiation, suspicious or documented recurrence, unexplained post therapy elevations in tumor markers, and the response to salvage treatment when managing cervical cancer. However, PET plays a limited role in the primary staging of MRI-defined node-negative patients. Currently, 18F-FDG is still the only tracer approved for routine use, but several novel targeting PET compounds, high-Tesla MRI machines, diffusion-weighted imaging without contrast, and dynamic nuclear polarized-enhanced 13C-MR spectroscopic imaging may hold promising applications.

  2. Nanotechnology-Enabled Optical Molecular Imaging of Breast Cancer

    Science.gov (United States)

    2011-07-01

    quantitatively and dynamically detect molecular markers of breast cancer in vivo without tissue removal or directly after removal in a surgical...hour oshells by c es, the nano ting to a fin ER2- positiv (CHTN) th tinction spect ter of 276 nm sert depicts co microscopy. n was visua rption...conclusively determine the penetration depth of the nanoshells. Additionally, a quantitative difference of the nanoshell signal at the surface of the Her2

  3. Molecular spectral imaging system for quantitative immunohistochemical analysis of early diabetic retinopathy.

    Science.gov (United States)

    Li, Qingli; Zhang, Jingfa; Wang, Yiting; Xu, Guoteng

    2009-12-01

    A molecular spectral imaging system has been developed based on microscopy and spectral imaging technology. The system is capable of acquiring molecular spectral images from 400 nm to 800 nm with 2 nm wavelength increments. The basic principles, instrumental systems, and system calibration method as well as its applications for the calculation of the stain-uptake by tissues are introduced. As a case study, the system is used for determining the pathogenesis of diabetic retinopathy and evaluating the therapeutic effects of erythropoietin. Some molecular spectral images of retinal sections of normal, diabetic, and treated rats were collected and analyzed. The typical transmittance curves of positive spots stained for albumin and advanced glycation end products are retrieved from molecular spectral data with the spectral response calibration algorithm. To explore and evaluate the protective effect of erythropoietin (EPO) on retinal albumin leakage of streptozotocin-induced diabetic rats, an algorithm based on Beer-Lambert's law is presented. The algorithm can assess the uptake by histologic retinal sections of stains used in quantitative pathology to label albumin leakage and advanced glycation end products formation. Experimental results show that the system is helpful for the ophthalmologist to reveal the pathogenesis of diabetic retinopathy and explore the protective effect of erythropoietin on retinal cells of diabetic rats. It also highlights the potential of molecular spectral imaging technology to provide more effective and reliable diagnostic criteria in pathology.

  4. Molecular imaging agents for SPECT (and SPECT/CT)

    International Nuclear Information System (INIS)

    Gnanasegaran, Gopinath; Ballinger, James R.

    2014-01-01

    The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers. (orig.)

  5. Towards imaging of ultrafast molecular dynamics using FELs

    NARCIS (Netherlands)

    Rouzee, A.; Johnsson, P.; Rading, L.; Siu, W.; Huismans, Y.; Duesterer, S.; Redlin, H.; Tavella, F.; Stojanovic, N.; Al-Shemmary, A.; Lepine, F.; Holland, D. M. P.; Schlathölter, Thomas; Hoekstra, R.; Fukuzawa, H.; Ueda, K.; Vrakking, M. J. J.; Hundertmark, A.

    2013-01-01

    The dissociation dynamics induced by a 100 fs, 400 nm laser pulse in a rotationally cold Br-2 sample was characterized by Coulomb explosion imaging (CEI) using a time-delayed extreme ultra-violet (XUV) FEL pulse, obtained from the Free electron LASer in Hamburg (FLASH). The momentum distribution of

  6. Molecular imaging agents for SPECT (and SPECT/CT)

    Energy Technology Data Exchange (ETDEWEB)

    Gnanasegaran, Gopinath [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); Ballinger, James R. [Guy' s and St Thomas' NHS Foundation Trust, Department of Nuclear Medicine, London (United Kingdom); King' s College London, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom)

    2014-05-15

    The development of hybrid single photon emission computed tomography/computed tomography (SPECT/CT) cameras has increased the diagnostic value of many existing single photon radiopharmaceuticals. Precise anatomical localization of lesions greatly increases diagnostic confidence in bone imaging of the extremities, infection imaging, sentinel lymph node localization, and imaging in other areas. Accurate anatomical localization is particularly important prior to surgery, especially involving the parathyroid glands and sentinel lymph node procedures. SPECT/CT plays a role in characterization of lesions, particularly in bone scintigraphy and radioiodine imaging of metastatic thyroid cancer. In the development of novel tracers, SPECT/CT is particularly important in monitoring response to therapies that do not result in an early change in lesion size. Preclinical SPECT/CT devices, which actually have spatial resolution superior to PET/CT devices, have become essential in characterization of the biodistribution and tissue kinetics of novel tracers, allowing coregistration of serial studies within the same animals, which serves both to reduce biological variability and reduce the number of animals required. In conclusion, SPECT/CT increases the utility of existing radiopharmaceuticals and plays a pivotal role in the evaluation of novel tracers. (orig.)

  7. Homing peptide guiding optical molecular imaging for the diagnosis of bladder cancer

    Science.gov (United States)

    Yang, Xiao-feng; Pang, Jian-zhi; Liu, Jie-hao; Zhao, Yang; Jia, Xing-you; Li, Jun; Liu, Reng-xin; Wang, Wei; Fan, Zhen-wei; Zhang, Zi-qiang; Yan, San-hua; Luo, Jun-qian; Zhang, Xiao-lei

    2014-11-01

    Background: The limitations of primary transurethral resection of bladder tumor (TURBt) have led the residual tumors rates as high as 75%. The intraoperative fluorescence imaging offers a great potential for improving TURBt have been confirmed. So we aim to distinguish the residual tumors and normal mucosa using fluorescence molecular imaging formed by conjugated molecule of the CSNRDARRC bladder cancer homing peptide with fluorescent dye. The conjugated molecule was abbreviated FIuo-ACP. In our study, we will research the image features of FIuo-ACP probe targeted bladder cancer for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo. Methods: After the FIuo-ACP probe was synthetized, the binding sites, factors affecting binding rates, the specificity and the targeting of Fluo-ACP labeled with bladder cancer cells were studied respectively by laser scanning confocal microscope (LSCM), immunofluorescence and multispectral fluorescence ex vivo optical molecular imaging system. Results: The binding sites were located in nucleus and the binding rates were correlated linearly with the dose of probe and the grade of pathology. Moreover, the probe has a binding specificity with bladder cancer in vivo and ex vivo. Tumor cells being labeled by the Fluo-ACP, bright green spots were observed under LSCM. The tissue samples and tumor cells can be labeled and identified by fluorescence microscope. Optical molecular imaging of xenograft tumor tissues was exhibited as fluorescent spots under EMCCD. Conclusion: The CSNRDARRC peptides might be a useful bladder cancer targeting vector. The FIuo-ACP molecular probe was suitable for fluorescence molecular imaging diagnosis for bladder cancer in vivo and ex vivo.

  8. Thermal Inactivation Kinetics and Secondary Structure Change of a Low Molecular Weight Halostable Exoglucanase from a Marine Aspergillus niger at High Salinities.

    Science.gov (United States)

    Xue, Dong-Sheng; Liang, Long-Yuan; Lin, Dong-Qiang; Yao, Shan-Jing

    2017-11-01

    Two kinds of exoglucanase were purified from a marine Aspergillus niger. Catalytic ability of halophilic exoglucanase with a lower molecular weight and secondary structure change was analyzed at different salinities. Activity of the low molecular weight exoglucanase in 10% NaCl solution (w/v) was 1.69-fold higher of that in NaCl-free solution. Half-life time in 10% NaCl solution (w/v) was over 1.27-fold longer of that in NaCl-free solution. Free energy change of the low molecular weight exoglucanase denaturation, △G, in 10% NaCl solution (w/v) was 0.54 kJ/mol more than that in NaCl-free solution. Melt point in 10% NaCl solution (w/v), 52.01 °C, was 4.21 °C higher than that in NaCl-free solution, 47.80 °C. K m value, 0.179 mg/ml in 10% NaCl solution (w/v) was less 0.044 mg/ml than that, 0.224 mg/ml, in NaCl-free solution. High salinity made content of α-helix increased. Secondary structure change caused by high salinities improved exoglucanase thermostability and catalysis activity. The halophilic exoglucanase from a marine A. niger was valuable for hydrolyzing cellulose at high salinities.

  9. Advances of Molecular Imaging for Monitoring the Anatomical and Functional Architecture of the Olfactory System.

    Science.gov (United States)

    Zhang, Xintong; Bi, Anyao; Gao, Quansheng; Zhang, Shuai; Huang, Kunzhu; Liu, Zhiguo; Gao, Tang; Zeng, Wenbin

    2016-01-20

    The olfactory system of organisms serves as a genetically and anatomically model for studying how sensory input can be translated into behavior output. Some neurologic diseases are considered to be related to olfactory disturbance, especially Alzheimer's disease, Parkinson's disease, multiple sclerosis, and so forth. However, it is still unclear how the olfactory system affects disease generation processes and olfaction delivery processes. Molecular imaging, a modern multidisciplinary technology, can provide valid tools for the early detection and characterization of diseases, evaluation of treatment, and study of biological processes in living subjects, since molecular imaging applies specific molecular probes as a novel approach to produce special data to study biological processes in cellular and subcellular levels. Recently, molecular imaging plays a key role in studying the activation of olfactory system, thus it could help to prevent or delay some diseases. Herein, we present a comprehensive review on the research progress of the imaging probes for visualizing olfactory system, which is classified on different imaging modalities, including PET, MRI, and optical imaging. Additionally, the probes' design, sensing mechanism, and biological application are discussed. Finally, we provide an outlook for future studies in this field.

  10. Current perspectives in the use of molecular imaging to target surgical treatments for genitourinary cancers.

    Science.gov (United States)

    Greco, Francesco; Cadeddu, Jeffrey A; Gill, Inderbir S; Kaouk, Jihad H; Remzi, Mesut; Thompson, R Houston; van Leeuwen, Fijs W B; van der Poel, Henk G; Fornara, Paolo; Rassweiler, Jens

    2014-05-01

    Molecular imaging (MI) entails the visualisation, characterisation, and measurement of biologic processes at the molecular and cellular levels in humans and other living systems. Translating this technology to interventions in real-time enables interventional MI/image-guided surgery, for example, by providing better detection of tumours and their dimensions. To summarise and critically analyse the available evidence on image-guided surgery for genitourinary (GU) oncologic diseases. A comprehensive literature review was performed using PubMed and the Thomson Reuters Web of Science. In the free-text protocol, the following terms were applied: molecular imaging, genitourinary oncologic surgery, surgical navigation, image-guided surgery, and augmented reality. Review articles, editorials, commentaries, and letters to the editor were included if deemed to contain relevant information. We selected 79 articles according to the search strategy based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis criteria and the IDEAL method. MI techniques included optical imaging and fluorescent techniques, the augmented reality (AR) navigation system, magnetic resonance imaging spectroscopy, positron emission tomography, and single-photon emission computed tomography. Experimental studies on the AR navigation system were restricted to the detection and therapy of adrenal and renal malignancies and in the relatively infrequent cases of prostate cancer, whereas fluorescence techniques and optical imaging presented a wide application of intraoperative GU oncologic surgery. In most cases, image-guided surgery was shown to improve the surgical resectability of tumours. Based on the evidence to date, image-guided surgery has promise in the near future for multiple GU malignancies. Further optimisation of targeted imaging agents, along with the integration of imaging modalities, is necessary to further enhance intraoperative GU oncologic surgery. Copyright © 2013

  11. Dynamical image-charge effect in molecular tunnel junctions

    DEFF Research Database (Denmark)

    Jin, Chengjun; Thygesen, Kristian Sommer

    2014-01-01

    the finite IC formation time affects charge transport through a molecule suspended between two electrodes. For a single-level model, an analytical treatment shows that the conductance is suppressed by a factor Z(2), where Z is the quasiparticle renormalization factor, compared to the static IC approximation...... that the dynamical corrections can reduce the conductance by more than a factor of two when compared to static GW or density functional theory where the molecular energy levels have been shifted to match the exact quasiparticle levels....

  12. Ultraviolet inactivation of papain

    International Nuclear Information System (INIS)

    Baugher, J.F.; Grossweiner, L.I.

    1975-01-01

    Flash photolysis transient spectra (lambda > 250 nm) of aqueous papain showed that the initial products are the neutral tryptophan radical Trp (lambdasub(max) 510 nm), the tryptophan triplet state 3 Trp (lambdasub(max) 460 nm), the disulfide bridge electron adduct -SS - - (lambdasub(max) 420 nm) and the hydrated electron esub(aq) - . The -SS - - yield was not altered by nitrous oxide or air, indicating that the formation of this product does not involve electrons in the external medium. The original papain preparation was activated by irradiating under nitrogen. The action spectrum supports previous work attributing the low initial activity to blocking of cysteinyl site 25 with a mixed disulfide. Flask lamp irradiation in nitrogen led to activation at low starting activities and inactivation at higher starting activities, while only inactivation at the same quantum yield was observed with air saturation. The results are consistent with photoionization of an essential tryptophyl residue as the key inactivating step. (author)

  13. Progress in molecular nuclear medicine imaging of pancreatic beta cells

    International Nuclear Information System (INIS)

    Wu Haifei; Yin Hongyan; Liu Shuai; Zhang Yifan

    2010-01-01

    Diabetes mellitus is a common and frequently occurring disease which seriously threaten the health of human beings. Type 1 and type 2 diabetes respectively results from being destroyed and insufficient beta-cell mass. The associated symptoms appear until 50%-60% decrease of beta-cell mass. Because pancreas is deeply located in the body, with few beta-cell mass, the current methods of clinical diagnosis are invasive and late. So diagnosis of metabolism disease of beta-cell early non-invasively becomes more and more popular, imaging diagnosis of diabetes mellitus becomes the focus of researches, but how to estimate the mass of beta-cell still an important subject in imaging technology. (authors)

  14. Advancing Precision Nuclear Medicine and Molecular Imaging for Lymphoma.

    Science.gov (United States)

    Wright, Chadwick L; Maly, Joseph J; Zhang, Jun; Knopp, Michael V

    2017-01-01

    PET with fluorodeoxyglucose F 18 ( 18 F FDG-PET) is a meaningful biomarker for the detection, targeted biopsy, and treatment of lymphoma. This article reviews the evolution of 18 F FDG-PET as a putative biomarker for lymphoma and addresses the current capabilities, challenges, and opportunities to enable precision medicine practices for lymphoma. Precision nuclear medicine is driven by new imaging technologies and methodologies to more accurately detect malignant disease. Although quantitative assessment of response is limited, such technologies will enable a more precise metabolic mapping with much higher definition image detail and thus may make it a robust and valid quantitative response assessment methodology. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Recombinant carcinoembryonic antigen as a reporter gene for molecular imaging

    International Nuclear Information System (INIS)

    Kenanova, Vania; Barat, Bhaswati; Olafsen, Tove; Chatziioannou, Arion; Herschman, Harvey R.; Wu, Anna M.; Braun, Jonathan

    2009-01-01

    Reporter genes can provide a way of noninvasively assessing gene activity in vivo. However, current reporter gene strategies may be limited by the immunogenicity of foreign reporter proteins, endogenous expression, or unwanted biological activity. We have developed a reporter gene based on carcinoembryonic antigen (CEA), a human protein with limited normal tissue expression. To construct a CEA reporter gene for PET, a CEA minigene (N-A3) was fused to the extracellular and transmembrane domains of the human FcγRIIb receptor. The NA3-FcγRIIb recombinant gene, driven by a CMV promoter, was transfected in Jurkat (human T cell leukemia) cells. Expression was analyzed by flow cytometry, immunohistochemistry (IHC), and microPET imaging. Flow cytometry identified Jurkat clones stably expressing NA3-FcγRIIb at low, medium, and high levels. High and medium NA3-FcγRIIb expression could also be detected by Western blot. Reporter gene positive and negative Jurkat cells were used to establish xenografts in athymic mice. IHC showed staining of the tumor with high reporter gene expression; medium and low N-A3 expression was not detected. MicroPET imaging, using an anti-CEA 124 I-labeled single-chain Fv-Fc antibody fragment, demonstrated that only high N-A3 expression could be detected. Specific accumulation of activity was visualized at the N-A3 positive tumor as early as 4 h. MicroPET image quantitation showed tumor activity of 1.8 ± 0.2, 15.2 ± 1.3, and 4.6 ± 1.2 percent injected dose per gram (%ID/g) at 4, 20, and 48 h, respectively. Biodistribution at 48 h demonstrated tumor uptake of 4.8 ± 0.8%ID/g. The CEA N-A3 minigene has the potential to be used as a reporter gene for imaging cells in vivo. (orig.)

  16. Pheochromocytoma and Paraganglioma: Current Functional and Future Molecular Imaging

    International Nuclear Information System (INIS)

    Blanchet, Elise M.; Martucci, Victoria; Pacak, Karel

    2012-01-01

    Paragangliomas are neural crest-derived tumors, arising either from chromaffin sympathetic tissue (in adrenal, abdominal, intra-pelvic, or thoracic paraganglia) or from parasympathetic tissue (in head and neck paraganglia). They have a specific cellular metabolism, with the ability to synthesize, store, and secrete catecholamines (although most head and neck paragangliomas do not secrete any catecholamines). This disease is rare and also very heterogeneous, with various presentations (e.g., in regards to localization, multifocality, potential to metastasize, biochemical phenotype, and genetic background). With growing knowledge, notably about the pathophysiology and genetic background, guidelines are evolving rapidly. In this context, functional imaging is a challenge for the management of paragangliomas. Nuclear imaging has been used for exploring paragangliomas for the last three decades, with MIBG historically as the first-line exam. Tracers used in paragangliomas can be grouped in three different categories. Agents that specifically target catecholamine synthesis, storage, and secretion pathways include: 123 and 131I-metaiodobenzylguanidine (123/131I-MIBG), 18F-fluorodopamine (18F-FDA), and 18F-fluorodihydroxyphenylalanine (18F-FDOPA). Agents that bind somatostatin receptors include 111In-pentetreotide and 68Ga-labeled somatostatin analog peptides (68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE). The non-specific agent most commonly used in paragangliomas is 18F-fluorodeoxyglucose (18F-FDG). This review will first describe conventional scintigraphic exams that are used for imaging paragangliomas. In the second part we will emphasize the interest in new PET approaches (specific and non-specific), considering the growing knowledge about genetic background and pathophysiology, with the aim of understanding how tumors behave, and optimally adjusting imaging technique for each tumor type.

  17. Insight into the Molecular Imaging of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Abishek Arora

    2016-01-01

    Full Text Available Alzheimer’s disease is a complex neurodegenerative disease affecting millions of individuals worldwide. Earlier it was diagnosed only via clinical assessments and confirmed by postmortem brain histopathology. The development of validated biomarkers for Alzheimer’s disease has given impetus to improve diagnostics and accelerate the development of new therapies. Functional imaging like positron emission tomography (PET, single photon emission computed tomography (SPECT, functional magnetic resonance imaging (fMRI, and proton magnetic resonance spectroscopy provides a means of detecting and characterising the regional changes in brain blood flow, metabolism, and receptor binding sites that are associated with Alzheimer’s disease. Multimodal neuroimaging techniques have indicated changes in brain structure and metabolic activity, and an array of neurochemical variations that are associated with neurodegenerative diseases. Radiotracer-based PET and SPECT potentially provide sensitive, accurate methods for the early detection of disease. This paper presents a review of neuroimaging modalities like PET, SPECT, and selected imaging biomarkers/tracers used for the early diagnosis of AD. Neuroimaging with such biomarkers and tracers could achieve a much higher diagnostic accuracy for AD and related disorders in the future.

  18. Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging.

    Science.gov (United States)

    Fan, Quli; Cheng, Kai; Hu, Xiang; Ma, Xiaowei; Zhang, Ruiping; Yang, Min; Lu, Xiaomei; Xing, Lei; Huang, Wei; Gambhir, Sanjiv Sam; Cheng, Zhen

    2014-10-29

    Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated αvβ3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. The multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation.

  19. Measurement of the density profile of pure and seeded molecular beams by femtosecond ion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Congsen [LaserLaB Amsterdam, VU University Amsterdam, de Boelelaan 1083, 1081 HV Amsterdam (Netherlands); Department of Physics, National University of Defense Technology, Changsha 410073 (China); Janssen, Maurice H. M. [LaserLaB Amsterdam, VU University Amsterdam, de Boelelaan 1083, 1081 HV Amsterdam (Netherlands)

    2015-02-15

    Here, we report on femtosecond ion imaging experiments to measure the density profile of a pulsed supersonic molecular beam. Ion images are measured for both a molecular beam and bulk gas under identical experimental conditions via femtosecond multiphoton ionization of Xe atoms. We report the density profile of the molecular beam, and the measured absolute density is compared with theoretical calculations of the centre line beam density. Subsequently, we discuss reasons accounting for the differences between measurements and calculations and propose that strong skimmer interference is the most probable cause for the differences. Furthermore, we report on experiments measuring the centre line density of seeded supersonic beams. The femtosecond ion images show that seeding the heavy Xe atom at low relative seed fractions (1%-10%) in a light carrier gas like Ne results in strong relative enhancements of up to two orders of magnitude.

  20. New avenue in the treatment of temporal lobe epilepsy by classical anti-epileptics: A hypothetical establishment of executioner Caspase 3 inactivation by molecular modeling

    Directory of Open Access Journals (Sweden)

    M Vijey Aanandhi

    2015-01-01

    Full Text Available Patients with temporal lobe epilepsy (TLE are prescribed first-line antiepileptic drugs and surgery to the management of this disorder. Unfortunately, the surgical treatment has been shown to be beneficial for the selected patients but fails to provide a seizure-free outcome in 20-30% of TLE patients. In our present study, we investigate the possibilities of marketed antiepileptic drugs in a different manner to improve the present situation in TLE. Molecular docking simulation study and various open source computational tools were used to perform the study. AutoDock 4.2 MGL tools, Pymol visualize tools, Patch dock server, and Swarm Dock servers (protein-protein docking were used to perform the molecular modeling. FTsite and computed atlas of surface topography of protein open source server were used to understand the pocket and ligand binding information respectively. Toxtree application was used to determine the toxicity profile of the drug by Cramers rule. The obtained molecular docking models (Caspase 3, Procaspase 8, and Fas-associated death domain [FADD] with selected compounds (Clonazepam, Clobazepam, and Retigabine showed promising trio blocking event of FADD, Caspase 3, and Procaspase 8 (−6.66 kcal, −8.1 kcal, 6.46 kcal by Clonazepam respectively. Protein-protein interaction study (Swarm Dock, Patch Dock server indicated promising results that helped to establish our hypothesis. Toxtree showed a quantitative structure toxicity relationship report that helps to clarify the toxicity of the selected compounds. Clonazepam showed a trio inhibition property that may lead to develop a new era of the new generation benzodiazepine prototype drugs in the future. Filtered compounds will further process for higher in vitro, in vivo models for better understanding of the mechanism.

  1. Molecular imaging techniques in magnetic resonance imaging and nuclear imaging; Molekulare Bildgebung in der Magnetresonanztomographie und der Nuklearmedizin

    Energy Technology Data Exchange (ETDEWEB)

    Hoegemann, D.; Basilion, J.P.; Weissleder, R. [Center for Molecular Imaging Research, Massachusetts General Hospital, Charleston, MA (United States)

    2001-02-01

    The identification of genetic and biochemical changes allows a more conclusive characterization and classification of disease. Up to now this information is mostly obtained through in vitro analysis after resection or biopsy by immunohistopathology and molecular biology. There is a definite need for non-invasive detection and repeated monitoring of such changes in experimental research as well as in clinical trials. Therefore, it is necessary to develop radiological imaging techniques that not only visualize morphologic and physiologic alterations, but track genetic and biochemical processes. This short review reports some of the various ongoing research projects that address this problem and provide some very promising approaches. (orig.) [German] Die Bestimmung genetischer und biochemischer Veraenderungen erlaubt in zunehmendem Masse die eindeutige Charakterisierung und Klassifikation von Erkrankungen. Bisher ist hierzu in der Regel eine gezielte immunohistopathologische oder molekularbiologische In-vitro-Analyse nach Resektion oder Entnahme einer Biopsie erforderlich. In der experimentellen Forschung wie auch in der klinischen Anwendung sind bildgebende Verfahren wuenschenswert, die eine nichtinvasive Detektion und ein wiederholt durchfuehrbares Monitoring gewaehrleisten. Aus diesem Grunde ist die Entwicklung radiologischer Untersuchungsmethoden erforderlich, die ueber die morphologischen und physiologischen Veraenderungen hinaus eine Beurteilung der genetischen und biochemischen Vorgaenge ermoeglichen. In diesem kurzen Uebersichtsartikel werden einige der zahlreichen aktuellen Forschungsprojekte zusammengefasst, die sich mit diesem Problem beschaeftigen und inzwischen aussichtsreiche Techniken zur Verfuegung stellen. (orig.)

  2. Imaging Multi-Particle Atomic and Molecular Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Landers, Allen [Auburn Univ., AL (United States)

    2016-02-12

    Final Report for Grant Number: DE- FG02-10ER16146 This grant supported research in basic atomic, molecular and optical physics related to the interactions of atoms and molecules with photons and electrons. The duration of the grant was the 5 year period from 4/1/2010 – 10/31/2015. All of the support from the grant was used to pay salaries of the PI, graduate students, and undergraduates and travel to conferences and meetings. The results were in the form of publications in peer reviewed journals. There were 20 peer reviewed publications over these 5 years with 2 of the publications in Physical Review Letters and 1 in Nature; all of the other articles were in respected peer reviewed journals (Physical Review A, New Journal of Physics, Journal of Physics B ...).

  3. Molecular targeting of angiogenesis for imaging and therapy

    International Nuclear Information System (INIS)

    Brack, Simon S.; Neri, Dario; Dinkelborg, Ludger M.

    2004-01-01

    Angiogenesis, i.e. the proliferation of new blood vessels from pre-existing ones, is an underlying process in many human diseases, including cancer, blinding ocular disorders and rheumatoid arthritis. The ability to selectively target and interfere with neovascularisation would potentially be useful in the diagnosis and treatment of angiogenesis-related diseases. This review presents the authors' views on some of the most relevant markers of angiogenesis described to date, as well as on specific ligands which have been characterised in pre-clinical animal models and/or clinical studies. Furthermore, we present an overview on technologies which are likely to have an impact on the way molecular targeting of angiogenesis is performed in the future. (orig.)

  4. Radiosynthesis of [{sup 18}F]fluoromethyldeoxyspergualin for molecular imaging of heat shock proteins

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Pradip; Li, King C. [Department of Radiology, Nuclear Medicine Division, Methodist Hospital Research Institute, Weill Cornell Medical College, 6565 Fannin Street, MB1-066, Houston, TX 77030 (United States); Lee, Daniel Y., E-mail: dlee@tmhs.or [Department of Radiology, Nuclear Medicine Division, Methodist Hospital Research Institute, Weill Cornell Medical College, 6565 Fannin Street, MB1-066, Houston, TX 77030 (United States)

    2011-03-15

    To probe the in vivo role of stress response factors in normal physiology and in solid tumors we have designed a stable {sup 18}F-labeled molecular imaging agent based on a ligand for heat shock protein 70 (HSP70). We describe the synthesis of [{sup 18}F] fluorodeoxymethylspergualin ([{sup 18}F]MeDSG) as a new radiopharmaceutical probe using a prosthetic group, [{sup 18}F]SFB, for efficient and rapid radiolabeling. Ongoing molecular imaging studies are under way to detect HSP70 expression in tumors by positron emission tomography.

  5. Effect of Chinese Herbal Medicine on Molecular Imaging of Neurological Disorders.

    Science.gov (United States)

    Yao, Yao; Chen, Ting; Huang, Jing; Zhang, Hong; Tian, Mei

    2017-01-01

    Chinese herbal medicine has been used to treat a wide variety of neurological disorders including stroke, Alzheimer's disease, and Parkinson's disease. However, its mechanism behind the effectiveness remains unclear. Recently, molecular imaging technology has been applied for this purpose, since it can assess the cellular or molecular function in a living subject by using specific imaging probes and/or radioactive tracers, which enable efficient analysis and monitoring the therapeutic response repetitively. This chapter reviews the in vivo functional and metabolic changes after administration of Chinese herbal medicine in various neurological disorders and provides perspectives on the future evaluations of therapeutic response of Chinese herbal medicine. © 2017 Elsevier Inc. All rights reserved.

  6. Targeting the treatment of drug abuse with molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schiffer, Wynne K. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)], E-mail: wynne@bnl.gov; Liebling, Courtney N.B.; Patel, Vinal; Dewey, Stephen L. [Medical Department, Brookhaven National Laboratory, Upton, NY 11973 (United States)

    2007-10-15

    Although imaging studies in and of themselves have significant contributions to the study of human behavior, imaging in drug abuse has a much broader agenda. Drugs of abuse bind to molecules in specific parts of the brain in order to produce their effects. Positron emission tomography (PET) provides a unique opportunity to track this process, capturing the kinetics with which an abused compound is transported to its site of action. The specific examples discussed here were chosen to illustrate how PET can be used to map the regional distribution and kinetics of compounds that may or may not have abuse liability. We also discussed some morphological and functional changes associated with drug abuse and different stages of recovery following abstinence. PET measurements of functional changes in the brain have also led to the development of several treatment strategies, one of which is discussed in detail here. Information such as this becomes more than a matter of academic interest. Such knowledge can provide the bases for anticipating which compounds may be abused and which may not. It can also be used to identify biological markers or changes in brain function that are associated with progression from drug use to drug abuse and also to stage the recovery process. This new knowledge can guide legislative initiatives on the optimal duration of mandatory treatment stays, promoting long-lasting abstinence and greatly reducing the societal burden of drug abuse. Imaging can also give some insights into potential pharmacotherapeutic targets to manage the reinforcing effects of addictive compounds, as well as into protective strategies to minimize their toxic consequences.

  7. Targeting the treatment of drug abuse with molecular imaging

    International Nuclear Information System (INIS)

    Schiffer, Wynne K.; Liebling, Courtney N.B.; Patel, Vinal; Dewey, Stephen L.

    2007-01-01

    Although imaging studies in and of themselves have significant contributions to the study of human behavior, imaging in drug abuse has a much broader agenda. Drugs of abuse bind to molecules in specific parts of the brain in order to produce their effects. Positron emission tomography (PET) provides a unique opportunity to track this process, capturing the kinetics with which an abused compound is transported to its site of action. The specific examples discussed here were chosen to illustrate how PET can be used to map the regional distribution and kinetics of compounds that may or may not have abuse liability. We also discussed some morphological and functional changes associated with drug abuse and different stages of recovery following abstinence. PET measurements of functional changes in the brain have also led to the development of several treatment strategies, one of which is discussed in detail here. Information such as this becomes more than a matter of academic interest. Such knowledge can provide the bases for anticipating which compounds may be abused and which may not. It can also be used to identify biological markers or changes in brain function that are associated with progression from drug use to drug abuse and also to stage the recovery process. This new knowledge can guide legislative initiatives on the optimal duration of mandatory treatment stays, promoting long-lasting abstinence and greatly reducing the societal burden of drug abuse. Imaging can also give some insights into potential pharmacotherapeutic targets to manage the reinforcing effects of addictive compounds, as well as into protective strategies to minimize their toxic consequences

  8. Molecular Beacon-Based MicroRNA Imaging During Neurogenesis.

    Science.gov (United States)

    Lee, Jonghwan; Kim, Soonhag

    2016-01-01

    The fluorescence monitoring system for examining endogenous microRNA (miRNA) activity in cellular level provides crucial information on not only understanding a critical role of miRNA involving a variety of biological processes, but also evaluating miRNA expression patterns in a noninvasive manner. In this protocol, we report the details of a new procedure for a molecular beacon-based miRNA monitoring system, which includes the illustration scheme for miRNA detection strategy, exogenous miRNA detection, and measurement of endogenous miRNA expression level during neurogenesis. The fluorescence signal of miR-124a beacon quenched by BHQ2 was gradually recovered as increasing concentration of the miR-124a in tube. The functional work of miR-124a beacon was examined in intracellular environment, allowing for the internalization of the miR-124a beacon by lipofectamine, which resulted in activated fluorescent signals of the miR-124a beacon in the HeLa cells after the addition of synthetic miR-124a. The endogenous miR-124a expression level was detected by miR-124a beacon system during neurogenesis, showing brighter fluorescence intensity in cytoplasmic area of P19 cells after induction of neuronal differentiation by retinoic acid. The molecular beacon based-miRNA detection technique could be applicable to the simultaneous visualization of a variety of miRNA expression patterns using different fluorescence dyes. For the study of examining endogenous miRNA expression level using miRNA-beacon system, if cellular differentiation step is already prepared, transfection step of miR-124a beacon into P19 cells, and acquisition of activated fluorescence signal measured by confocal microscope can be conducted approximately within 6 h.

  9. Small animal SPECT and its place in the matrix of molecular imaging technologies

    International Nuclear Information System (INIS)

    Meikle, Steven R; Kench, Peter; Kassiou, Michael; Banati, Richard B

    2005-01-01

    Molecular imaging refers to the use of non-invasive imaging techniques to detect signals that originate from molecules, often in the form of an injected tracer, and observe their interaction with a specific cellular target in vivo. Differences in the underlying physical principles of these measurement techniques determine the sensitivity, specificity and length of possible observation of the signal, characteristics that have to be traded off according to the biological question under study. Here, we describe the specific characteristics of single photon emission computed tomography (SPECT) relative to other molecular imaging technologies. SPECT is based on the tracer principle and external radiation detection. It is capable of measuring the biodistribution of minute ( -10 molar) concentrations of radio-labelled biomolecules in vivo with sub-millimetre resolution and quantifying the molecular kinetic processes in which they participate. Like some other imaging techniques, SPECT was originally developed for human use and was subsequently adapted for imaging small laboratory animals at high spatial resolution for basic and translational research. Its unique capabilities include (i) the ability to image endogenous ligands such as peptides and antibodies due to the relative ease of labelling these molecules with technetium or iodine (ii) the ability to measure relatively slow kinetic processes (compared with positron emission tomography, for example) due to the long half-life of the commonly used isotopes and (iii) the ability to probe two or more molecular pathways simultaneously by detecting isotopes with different emission energies. In this paper, we review the technology developments and design tradeoffs that led to the current state-of-the-art in SPECT small animal scanning and describe the position SPECT occupies within the matrix of molecular imaging technologies. (topical review)

  10. Current research in nuclear medicine and molecular imaging in Italy: highlights of the 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging.

    Science.gov (United States)

    Cuocolo, A

    2011-06-01

    The 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging (AIMN) took place in Rimini on March 18-21, 2011 under the chairmanship of Professor Stefano Fanti. The program was of excellent quality and put a further step for the settlement of the standardized AIMN congress structure. A large industrial exhibition demonstrated the latest technological innovations and developments within the field. The congress was a great success with more than 1100 total participants and more than 360 abstracts received. Of these, 40 abstracts were accepted for oral and 285 for poster presentations. The original investigations presented were related to different areas of nuclear medicine and molecular imaging, with particular focus on advances in instrumentation and data processing, progress in radiochemistry and pharmacy, novel diagnostics and therapeutics, and new insights in well established areas of clinical application, such as oncology, cardiology, neurology, psychiatry, endocrinology, paediatrics, and infection and inflammation. Noteworthy, several presentations at this congress, focusing on quantitative interpretation of the imaging data and on pragmatic endpoints, such as adverse outcomes, identified when nuclear medicine procedures achieved clinical effectiveness for patient care and patient management and further demonstrated that nuclear medicine plays a crucial role in the contemporary medical scenario. This highlights lecture is only a brief summary of the large amount of data presented and discussed, which can be found in much greater detail in the congress abstract book, published as volume 55, supplement 1 of the Q J Nucl Med Mol Imaging in April 2011.

  11. A parallel adaptive finite element simplified spherical harmonics approximation solver for frequency domain fluorescence molecular imaging

    International Nuclear Information System (INIS)

    Lu Yujie; Zhu Banghe; Rasmussen, John C; Sevick-Muraca, Eva M; Shen Haiou; Wang Ge

    2010-01-01

    Fluorescence molecular imaging/tomography may play an important future role in preclinical research and clinical diagnostics. Time- and frequency-domain fluorescence imaging can acquire more measurement information than the continuous wave (CW) counterpart, improving the image quality of fluorescence molecular tomography. Although diffusion approximation (DA) theory has been extensively applied in optical molecular imaging, high-order photon migration models need to be further investigated to match quantitation provided by nuclear imaging. In this paper, a frequency-domain parallel adaptive finite element solver is developed with simplified spherical harmonics (SP N ) approximations. To fully evaluate the performance of the SP N approximations, a fast time-resolved tetrahedron-based Monte Carlo fluorescence simulator suitable for complex heterogeneous geometries is developed using a convolution strategy to realize the simulation of the fluorescence excitation and emission. The validation results show that high-order SP N can effectively correct the modeling errors of the diffusion equation, especially when the tissues have high absorption characteristics or when high modulation frequency measurements are used. Furthermore, the parallel adaptive mesh evolution strategy improves the modeling precision and the simulation speed significantly on a realistic digital mouse phantom. This solver is a promising platform for fluorescence molecular tomography using high-order approximations to the radiative transfer equation.

  12. Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

    Science.gov (United States)

    Bhargava, Rohit; Madabhushi, Anant

    2016-07-11

    Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

  13. Recent Advance of Biological Molecular Imaging Based on Lanthanide-Doped Upconversion-Luminescent Nanomaterials

    Directory of Open Access Journals (Sweden)

    Yuanzeng Min

    2014-02-01

    Full Text Available Lanthanide-doped upconversion-luminescent nanoparticles (UCNPs, which can be excited by near-infrared (NIR laser irradiation to emit multiplex light, have been proven to be very useful for in vitro and in vivo molecular imaging studies. In comparison with the conventionally used down-conversion fluorescence imaging strategies, the NIR light excited luminescence of UCNPs displays high photostability, low cytotoxicity, little background auto-fluorescence, which allows for deep tissue penetration, making them attractive as contrast agents for biomedical imaging applications. In this review, we will mainly focus on the latest development of a new type of lanthanide-doped UCNP material and its main applications for in vitro and in vivo molecular imaging and we will also discuss the challenges and future perspectives.

  14. Optical-based molecular imaging: contrast agents and potential medical applications

    International Nuclear Information System (INIS)

    Bremer, Christoph; Ntziachristos, Vasilis; Weissleder, Ralph

    2003-01-01

    Laser- and sensitive charge-coupled device technology together with advanced mathematical modelling of photon propagation in tissue has prompted the development of novel optical imaging technologies. Fast surface-weighted imaging modalities, such as fluorescence reflectance imaging (FRI) and 3D quantitative fluorescence-mediated tomography have now become available [1, 2]. These technical advances are paralleled by a rapid development of a whole range of new optical contrasting strategies, which are designed to generate molecular contrast within a living organism. The combination of both, technical advances of light detection and the refinement of optical contrast media, finally yields a new spectrum of tools for in vivo molecular diagnostics. Whereas the technical aspects of optical imaging are covered in more detail in a previous review article in ''European Radiology'' [3], this article focuses on new developments in optical contrasting strategies and design of optical contrast agents for in vivo diagnostics. (orig.)

  15. Systems Biology-Driven Hypotheses Tested In Vivo: The Need to Advancing Molecular Imaging Tools.

    Science.gov (United States)

    Verma, Garima; Palombo, Alessandro; Grigioni, Mauro; La Monaca, Morena; D'Avenio, Giuseppe

    2018-01-01

    Processing and interpretation of biological images may provide invaluable insights on complex, living systems because images capture the overall dynamics as a "whole." Therefore, "extraction" of key, quantitative morphological parameters could be, at least in principle, helpful in building a reliable systems biology approach in understanding living objects. Molecular imaging tools for system biology models have attained widespread usage in modern experimental laboratories. Here, we provide an overview on advances in the computational technology and different instrumentations focused on molecular image processing and analysis. Quantitative data analysis through various open source software and algorithmic protocols will provide a novel approach for modeling the experimental research program. Besides this, we also highlight the predictable future trends regarding methods for automatically analyzing biological data. Such tools will be very useful to understand the detailed biological and mathematical expressions under in-silico system biology processes with modeling properties.

  16. Molecular Imaging to Identify Tumor Recurrence following Chemoradiation in a Hostile Surgical Environment

    Directory of Open Access Journals (Sweden)

    Olugbenga T. Okusanya

    2015-01-01

    Full Text Available Surgical biopsy of potential tumor recurrence is a common challenge facing oncologists, surgeons, and cancer patients. Imaging modalities have limited ability to accurately detect recurrent cancer in fields affected by previous surgery, chemotherapy, or radiation. However, definitive tissue diagnosis is often needed to initiate treatment and to direct therapy. We sought to determine if a targeted fluorescent intraoperative molecular imaging technique could be applied in a clinical setting to assist a surgical biopsy in a “hostile” field. We describe the use of a folate-fluorescein conjugate to direct the biopsy of a suspected recurrent lung adenocarcinoma invading the mediastinum that had been previously treated with chemoradiation. We found that intraoperative imaging allowed the identification of small viable tumor deposits that were otherwise indistinguishable from scar and necrosis. Our operative observations were confirmed by histology, fluorescence microscopy, and immunohistochemistry. Our results demonstrate one possible application and clinical value of intraoperative molecular imaging.

  17. Final Technical Report for SISGR: Ultrafast Molecular Scale Chemical Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hersam, Mark C. [Northwestern Univ., Evanston, IL (United States). Dept. of Materials Science and Engineering; Guest, Jeffrey R. [Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials; Guisinger, Nathan P. [Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials; Hla, Saw Wai [Argonne National Lab. (ANL), Argonne, IL (United States). Center for Nanoscale Materials; Schatz, George C. [Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry; Seideman, Tamar [Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry; Van Duyne, Richard P. [Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry

    2017-04-10

    The Northwestern-Argonne SISGR program utilized newly developed instrumentation and techniques including integrated ultra-high vacuum tip-enhanced Raman spectroscopy/scanning tunneling microscopy (UHV-TERS/STM) and surface-enhanced femtosecond stimulated Raman scattering (SE-FSRS) to advance the spatial and temporal resolution of chemical imaging for the study of photoinduced dynamics of molecules on plasmonically active surfaces. An accompanying theory program addressed modeling of charge transfer processes using constrained density functional theory (DFT) in addition to modeling of SE-FSRS, thereby providing a detailed description of the excited state dynamics. This interdisciplinary and highly collaborative research resulted in 62 publications with ~ 48% of them being co-authored by multiple SISGR team members. A summary of the scientific accomplishments from this SISGR program is provided in this final technical report.

  18. Radiopharmaceuticals: nanoparticles like multi-functional systems for the obtaining in vivo of molecular images

    International Nuclear Information System (INIS)

    Ferro F, G.; Ramirez de la Cruz, F. M.; Ocampo G, B. E.; Morales A, E.; Santos C, C. L.; Mendoza S, A. N.

    2010-01-01

    The techniques of obtaining direct or indirect molecular images detect and register the space-temporary distribution of molecular or cellular processes for biochemical, biological, diagnostic and therapeutic applications. The advanced techniques of image like the nuclear magnetic resonance, the single photon emission computed tomography, the positron emission tomography and the images of optic fluorescence have been used successfully to detect these processes. On the other hand, the utility of the nanoparticles for any application is dependent of the physicochemical properties that present, being possible to modify their surface when making them react with different biomolecules what allows the formation of conjugates with specific molecular recognition. The joint of various protein molecules, peptides or oligonucleotides to the surface of a nanoparticle produce a multi-functional system able to increase the multivalent joints from the nanoparticles-biomolecules to their receivers for the obtaining of molecular images in vivo. The peptides stimulate, regulate or inhibit numerous functions of the life, acting mainly as information transmitters and activity coordinators of several tissues in the organism. The receivers of regulator peptides are over represented in numerous types of cancer cells and they are protein structures. These receivers have been used as white molecular of marked peptides, to locate primary malignant tumors and their metastasis, using the diagnostic techniques of molecular image mentioned above, which consist basically on the radio peptides use and conjugated peptides to fluoro chromes, to metallic nanoparticles and nano crystals. A summary of the work is presented carried out by the personnel of the Radio-active Materials and Chemistry Departments of the Instituto Nacional de Investigaciones Nucleares in this field. (Author)

  19. Molecular imaging of lipids in cells and tissues

    Science.gov (United States)

    Borner, Katrin; Malmberg, Per; Mansson, Jan-Eric; Nygren, Hakan

    2007-02-01

    The distribution pattern of lipid species in biological tissues was analyzed with imaging mass spectrometry (TOF-SIMS; time-of-flight secondary ion mass spectrometry). The first application shows distribution of a glycosphingolipid, the galactosylceramide-sulfate (sulfatide) with different hydrocarbon chain lengths and the fatty acids palmitate and oleate in rat cerebellum. Sulfatides were seen localized in regions suggested as paranodal areas of rat cerebellar white matter as well as in the granular layer, with highest concentrations at the borders of the white matter. Different distribution patterns could be shown for the fatty acid C16:0 palmitate and C18:1 oleate in rat cerebellum, which seem to origin partly from the hydrocarbon chains of phosphatidylcholine. Results were shown for two different tissue preparation methods, which were plunge-freezing and cryostat sectioning as well as high-pressure freezing, freeze-fracturing and freeze-drying. The second application shows TOF-SIMS analysis on a biological trial of choleratoxin treatment in mouse intestine. The effect of cholera toxin on lipids in the intestinal epithelium was shown by comparing control and cholera toxin treated mouse intestine samples. A significant increase of the cholesterol concentration was seen after treatment. Cholesterol was mainly localized to the brush border of enterocytes of the intestinal villi, which could be explained by the presence of cholesterol-rich lipid rafts present on the microvilli or by relations to cholesterol uptake. After cholera toxin exposure, cholesterol was seen increased in the nuclei of enterocytes and apparently in the interstitium of the villi. We find that imaging TOF-SIMS is a powerful tool for studies of lipid distributions in cells and tissues, enabling the elucidation of their role in cell function and biology.

  20. Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

    Directory of Open Access Journals (Sweden)

    Joel Saltz

    2018-04-01

    Full Text Available Summary: Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumor-infiltrating lymphocytes (TILs based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment. : Tumor-infiltrating lymphocytes (TILs were identified from standard pathology cancer images by a deep-learning-derived “computational stain” developed by Saltz et al. They processed 5,202 digital images from 13 cancer types. Resulting TIL maps were correlated with TCGA molecular data, relating TIL content to survival, tumor subtypes, and immune profiles. Keywords: digital pathology, immuno-oncology, machine learning, lymphocytes, tumor microenvironment, deep learning, tumor-infiltrating lymphocytes, artificial intelligence, bioinformatics, computer vision

  1. Characterization of nanoparticle-based contrast agents for molecular magnetic resonance imaging

    International Nuclear Information System (INIS)

    Shan, Liang; Chopra, Arvind; Leung, Kam; Eckelman, William C.; Menkens, Anne E.

    2012-01-01

    The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, ∼4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.

  2. The characterization of an economic and portable LED-based photoacoustic imaging system to facilitate molecular imaging

    Directory of Open Access Journals (Sweden)

    Ali Hariri

    2018-03-01

    Full Text Available Photoacoustic imaging (PAI is a non-invasive, high-resolution hybrid imaging modality that combines optical excitation and ultrasound detection. PAI can image endogenous chromophores (melanin, hemoglobin, etc. and exogenous contrast agents in different medical applications. However, most current equipment uses sophisticated and complicated OPO lasers with tuning and stability features inconsistent with broad clinical deployment. As the number of applications of PAI in medicine increases, there is an urgent need to make the imaging equipment more compact, portable, and affordable. Here, portable light emitting diode – based photoacoustic imaging (PLED-PAI was introduced and characterized in terms of system specifications, light source characterizations, photoacoustic spatial/temporal resolution, and penetration. The system uses two LED arrays attached to the sides of a conventional ultrasound transducer. The LED pulse repetition rate is tunable between 1 K Hz, 2 K Hz, 3 K Hz, and 4 K Hz. The axial resolution was 0.268 mm, and the lateral resolution was between 0.55 and 0.59 mm. The system could detect optical absorber (pencil lead at a depth of 3.2 cm and the detection limits of indocyanine green (ICG and methylene blue (MB were 9 μM and 0.78 mM. In vivo imaging of labeled human mesenchymal stem cells was achieved to confirm compatibility with small animal imaging. The characterization we report here may have value to other groups evaluating commercially available photoacoustic imaging equipment. Keywords: Portable photoacoustic imaging, LED, Optoacoustic imaging, Molecular imaging

  3. Epigenetic inactivation of CHFR in human tumors

    OpenAIRE

    Toyota, Minoru; Sasaki, Yasushi; Satoh, Ayumi; Ogi, Kazuhiro; Kikuchi, Takefumi; Suzuki, Hiromu; Mita, Hiroaki; Tanaka, Nobuyuki; Itoh, Fumio; Issa, Jean-Pierre J.; Jair, Kam-Wing; Schuebel, Kornel E.; Imai, Kohzoh; Tokino, Takashi

    2003-01-01

    Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin–ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, w...

  4. Molecular imaging of serotonin degeneration in mild cognitive impairment.

    Science.gov (United States)

    Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

    2017-09-01

    Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic

  5. Hybrid gold nanoparticles in molecular imaging and radiotherapy

    International Nuclear Information System (INIS)

    Katti, K.V.; Kannan, R.; Katti, K.; Kattumuri, V.; Pandrapragada, R.; Rahing, V.; Cutler, C.; Boote, E.; Casteel, S.W.; Smith, C.J.; Robertson, J.D.; Jurrison, S.

    2006-01-01

    Metallic nanoparticles, because of their size, chemical and physical properties, are particularly attractive as therapeutic probes in treating cancer. Central to any clinical advances in nanoparticulate based therapy will be to produce hybrid nanoparticles that can be targeted to vascular, extracellular or cell surface receptors. Development of hybrid nanoparticles that specifically target cancer vasculature has received considerable attention. Most cancers have leaky vasculature and the defective vascular architecture, created due to the rapid vascularisation necessary to serve fast growing cancers, in combination with poor lymphatic drainage allows increased permeation and retention effects. The leaky vasculature, because of higher porosity and permeability, serve as natural high affinity targets to metallic nanoparticles. Another attractive approach toward the application of nanotechnology to nanomedicine is the utility of nanoparticles that display inherent therapeutic properties. For example radioactive gold nanoparticles present attractive prospects in therapy of cancer. The radioactive properties of Au-198 (β(max) = 0.96 MeV; t(1/2) = 2.7 d) and Au-199 (β(max) 0.46 MeV; t(1/2) = 3.14 d) make them ideal candidates for use in radiotherapeutic applications. In addition, they both have imageable gamma emissions for dosimetry and pharmacokinetic studies and Au-199 can be made carrier-free by indirect methods. Gold nanoparticles are of interest for treatment of disease as they can deliver agents directly into cells and cellular components with a higher concentration of radioactivity, e.g. higher dose of radioactivity, to cancerous tumor cells

  6. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, J. F.; van der Wall, Elsken; Mali, Willem P Th M; Derksen, Patrick W B; van Diest, Paul J; van Bergen En Henegouwen, Paul M P

    PURPOSE: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. PROCEDURES: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  7. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer

    NARCIS (Netherlands)

    van Brussel, Aram S A; Adams, Arthur; Oliveira, Sabrina; Dorresteijn, Bram; El Khattabi, Mohamed; Vermeulen, Jeroen F.; van der Wall, Elsken; Mali, W.P.T.M.; Derksen, Patrick W B; van Diest, Paul J.; van Bergen En Henegouwen, Paul M P

    Purpose: The aim of this work was to develop a CAIX-specific nanobody conjugated to IRDye800CW for molecular imaging of pre-invasive breast cancer. Procedures: CAIX-specific nanobodies were selected using a modified phage display technology, conjugated site-specifically to IRDye800CW and evaluated

  8. Translation of New Molecular Imaging Approaches to the Clinical Setting : Bridging the Gap to Implementation

    NARCIS (Netherlands)

    van Es, Suzanne C; Venema, Clasina M; Glaudemans, Andor W J M; Lub-de Hooge, Marjolijn N; Elias, Sjoerd G; Boellaard, Ronald; Hospers, Geke A P; Schröder, Carolina P; de Vries, Elisabeth G E

    Molecular imaging with PET is a rapidly emerging technique. In breast cancer patients, more than 45 different PET tracers have been or are presently being tested. With a good rationale, after development of the tracer and proven feasibility, it is of interest to evaluate whether there is a potential

  9. Translation of New Molecular Imaging Approaches to the Clinical Setting : Bridging the Gap to Implementation

    NARCIS (Netherlands)

    van Es, Suzanne C; Venema, Clasina M; Glaudemans, Andor W J M; Lub-de Hooge, Marjolijn N; Elias, Sjoerd G; Boellaard, Ronald; Hospers, Geke A.P.; Schröder, Carolina P; de Vries, Elisabeth G E

    2016-01-01

    Molecular imaging with PET is a rapidly emerging technique. In breast cancer patients, more than 45 different PET tracers have been or are presently being tested. With a good rationale, after development of the tracer and proven feasibility, it is of interest to evaluate whether there is a potential

  10. Identification of a Common Binding Mode for Imaging Agents to Amyloid Fibrils from Molecular Dynamics Simulations

    DEFF Research Database (Denmark)

    Skeby, Katrine Kirkeby; Sørensen, Jesper; Schiøtt, Birgit

    2013-01-01

    experimentally due to the insoluble nature of amyloid fibrils. This study uses molecular dynamics simulations to investigate the interactions between 13 aromatic amyloid imaging agents, entailing 4 different organic scaffolds, and a model of an amyloid fibril. Clustering analysis combined with free energy...

  11. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine. PMID:28078184

  12. Application of molecular imaging combined with genetic screening in diagnosing MELAS, diabetes and recurrent pancreatitis.

    Science.gov (United States)

    Zhiping, W; Quwen, L; Hai, Z; Jian, Z; Peiyi, G

    2016-01-01

    We report molecular imaging combined with gene diagnosis in a family with 7 members who carried an A3243G mutation in mitochondrial tRNA and p.Thr 137 Met in cationic trypsinogen (PRSS1) gene presented with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), diabetes, and recurrent pancreatitis. DNA sequencing was used to detect and validate mitochondrial DNA and PRSS1. We also verified that mitochondrial heterozygous mutations and c.410 C>T mutation causing p.Thr 137 Met could be detected in oral epithelial cells or in urine sediment cells. In addition, molecular imaging was carried out in the affected family members. In this pedigree, MELAS syndrome accompanied by pancreatitis was an important clinical feature, followed by diabetes. Heteroplasmy of the mtDNA A3243G and c.410 C>T mutation of PRSS1 was found in all tissue samples of these patients, but no mutations were found in 520 normal control and normal individuals of the family. However, based on molecular imaging observations, patients with relatively higher lactate/pyruvate levels had more typical and more severe symptoms, particularly those of pancreatic disease (diabetes or pancreatitis). MELAS syndrome may be associated with pancreatitis. For the diagnosis, it is more reasonable to perform molecular imaging combined with gene diagnosis.

  13. Oligometastatic prostate cancer: shaping the definition with molecular imaging and an improved understanding of tumor biology.

    Science.gov (United States)

    Joice, Gregory A; Rowe, Steven P; Pienta, Kenneth J; Gorin, Michael A

    2017-11-01

    The aim of this review is to discuss how novel imaging modalities and molecular markers are shaping the definition of oligometastatic prostate cancer. To effectively classify a patient as having oligometastatic prostate cancer, diagnostic tests must be sensitive enough to detect subtle sites of metastatic disease. Conventional imaging modalities can readily detect widespread polymetastatic disease but do not have the sensitivity necessary to reliably classify patients as oligometastatic. Molecular imaging using both metabolic- and molecularly-targeted radiotracers has demonstrated great promise in aiding in our ability to define the oligometastatic state. Perhaps the most promising data to date have been generated with radiotracers targeting prostate-specific membrane antigen. In addition, early studies are beginning to define biologic markers in the oligometastatic state that may be indicative of disease with minimal metastatic potential. Recent developments in molecular imaging have allowed for improved detection of metastatic prostate cancer allowing for more accurate staging of patients with oligometastatic disease. Future development of biologic markers may assist in defining the oligometastatic state and determining prognosis.

  14. Precision medicine and molecular imaging: new targeted approaches toward cancer therapeutic and diagnosis.

    Science.gov (United States)

    Ghasemi, Mojtaba; Nabipour, Iraj; Omrani, Abdolmajid; Alipour, Zeinab; Assadi, Majid

    2016-01-01

    This paper presents a review of the importance and role of precision medicine and molecular imaging technologies in cancer diagnosis with therapeutics and diagnostics purposes. Precision medicine is progressively becoming a hot topic in all disciplines related to biomedical investigation and has the capacity to become the paradigm for clinical practice. The future of medicine lies in early diagnosis and individually appropriate treatments, a concept that has been named precision medicine, i.e. delivering the right treatment to the right patient at the right time. Molecular imaging is quickly being recognized as a tool with the potential to ameliorate every aspect of cancer treatment. On the other hand, emerging high-throughput technologies such as omics techniques and systems approaches have generated a paradigm shift for biological systems in advanced life science research. In this review, we describe the precision medicine, difference between precision medicine and personalized medicine, precision medicine initiative, systems biology/medicine approaches (such as genomics, radiogenomics, transcriptomics, proteomics, and metabolomics), P4 medicine, relationship between systems biology/medicine approaches and precision medicine, and molecular imaging modalities and their utility in cancer treatment and diagnosis. Accordingly, the precision medicine and molecular imaging will enable us to accelerate and improve cancer management in future medicine.

  15. Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer

    Czech Academy of Sciences Publication Activity Database

    Polášek, Miloslav; Yang, Y.; Schühle, D. T.; Yaseen, M. A.; Kim, Y. R.; Sung, Y. S.; Guimaraes, A. R.; Caravan, P.

    2017-01-01

    Roč. 7, Aug 14 (2017), č. článku 8114. ISSN 2045-2322 Institutional support: RVO:61388963 Keywords : fibrosis * molecular imaging * pancreatic cancer Subject RIV: FD - Oncology ; Hematology OBOR OECD: Oncology Impact factor: 4.259, year: 2016 https://www.nature.com/ articles /s41598-017-08838-6

  16. Magnetically engineered smart thin films: toward lab-on-chip ultra-sensitive molecular imaging.

    Science.gov (United States)

    Hassan, Muhammad A; Saqib, Mudassara; Shaikh, Haseeb; Ahmad, Nasir M; Elaissari, Abdelhamid

    2013-03-01

    Magnetically responsive engineered smart thin films of nanoferrites as contrast agent are employed to develop surface based magnetic resonance imaging to acquire simple yet fast molecular imaging. The work presented here can be of significant potential for future lab-on-chip point-of-care diagnostics from the whole blood pool on almost any substrates to reduce or even prevent clinical studies involve a living organism to enhance the non-invasive imaging to advance the '3Rs' of work in animals-replacement, refinement and reduction.

  17. SPECT and PET Serve as Molecular Imaging Techniques and in Vivo Biomarkers for Brain Metastases

    Directory of Open Access Journals (Sweden)

    Barbara Palumbo

    2014-06-01

    Full Text Available Nuclear medicine techniques (single photon emission computerized tomography, SPECT, and positron emission tomography, PET represent molecular imaging tools, able to provide in vivo biomarkers of different diseases. To investigate brain tumours and metastases many different radiopharmaceuticals imaged by SPECT and PET can be used. In this review the main and most promising radiopharmaceuticals available to detect brain metastases are reported. Furthermore the diagnostic contribution of the combination of SPECT and PET data with radiological findings (magnetic resonance imaging, MRI is discussed.

  18. Molecular images as a tool in research. From radiopharmacy to radiopharmacology

    International Nuclear Information System (INIS)

    Zubillaga, M.

    2008-01-01

    Full text: The rapidly emerging biomedical research discipline of Molecular Imaging (MI) enables the visualization, characterization and quantification of biologic process taking place at the cellular and sub-cellular levels within the intact living organism. The overall goal of MI is to interrogate biologic process in the cell of a living subject to report on and reveal their molecular abnormalities that form the basis of disease. This is in contrast to classical diagnostic imaging where documented findings are the result of the end effects of these molecular alterations, usually in the form of macroscopic and well-established gross pathology. MI includes the field of Nuclear Medicine (SPECT and PET) and other strategies that do not depend on radioactivity to produce imaging signals (optical, bioluminescence and Magnetic Resonance). The emergence of MI strategies has made possible the achievement of several important biomedical research goals that open the door to advancement of study in molecular medicine. These various accomplishments include: (1) development of non invasive 'in vivo' imaging methods to reflect gene expression and more complex events such as protein-protein interactions; (2) ability to monitor multiple molecular events near simultaneously; (3) capacity to follow cell trafficking and cell targeting; (4) optimization of drug and gene therapy; (5) capability of imaging drug effects at a molecular and cellular level; (6) assessment of disease progression at a molecular pathologic level; (7) advancement of the possibility of achieving all the above mentioned goals rapidly, reproducibly and quantitatively, in support of monitoring a time-dependent manner the experimental, developmental, environmental and therapeutic influences on gene products in a single living subject. Although many laboratory based proof-of-principle and validation studies have been conducted using MI approaches, a great deal more experimental research will be necessary to

  19. Facilitating in vivo tumor localization by principal component analysis based on dynamic fluorescence molecular imaging

    Science.gov (United States)

    Gao, Yang; Chen, Maomao; Wu, Junyu; Zhou, Yuan; Cai, Chuangjian; Wang, Daliang; Luo, Jianwen

    2017-09-01

    Fluorescence molecular imaging has been used to target tumors in mice with xenograft tumors. However, tumor imaging is largely distorted by the aggregation of fluorescent probes in the liver. A principal component analysis (PCA)-based strategy was applied on the in vivo dynamic fluorescence imaging results of three mice with xenograft tumors to facilitate tumor imaging, with the help of a tumor-specific fluorescent probe. Tumor-relevant features were extracted from the original images by PCA and represented by the principal component (PC) maps. The second principal component (PC2) map represented the tumor-related features, and the first principal component (PC1) map retained the original pharmacokinetic profiles, especially of the liver. The distribution patterns of the PC2 map of the tumor-bearing mice were in good agreement with the actual tumor location. The tumor-to-liver ratio and contrast-to-noise ratio were significantly higher on the PC2 map than on the original images, thus distinguishing the tumor from its nearby fluorescence noise of liver. The results suggest that the PC2 map could serve as a bioimaging marker to facilitate in vivo tumor localization, and dynamic fluorescence molecular imaging with PCA could be a valuable tool for future studies of in vivo tumor metabolism and progression.

  20. Epigenetic inactivation of CHFR in human tumors.

    Science.gov (United States)

    Toyota, Minoru; Sasaki, Yasushi; Satoh, Ayumi; Ogi, Kazuhiro; Kikuchi, Takefumi; Suzuki, Hiromu; Mita, Hiroaki; Tanaka, Nobuyuki; Itoh, Fumio; Issa, Jean-Pierre J; Jair, Kam-Wing; Schuebel, Kornel E; Imai, Kohzoh; Tokino, Takashi

    2003-06-24

    Cell-cycle checkpoints controlling the orderly progression through mitosis are frequently disrupted in human cancers. One such checkpoint, entry into metaphase, is regulated by the CHFR gene encoding a protein possessing forkhead-associated and RING finger domains as well as ubiquitin-ligase activity. Although defects in this checkpoint have been described, the molecular basis and prevalence of CHFR inactivation in human tumors are still not fully understood. To address this question, we analyzed the pattern of CHFR expression in a number of human cancer cell lines and primary tumors. We found CpG methylation-dependent silencing of CHFR expression in 45% of cancer cell lines, 40% of primary colorectal cancers, 53% of colorectal adenomas, and 30% of primary head and neck cancers. Expression of CHFR was precisely correlated with both CpG methylation and deacetylation of histones H3 and H4 in the CpG-rich regulatory region. Moreover, CpG methylation and thus silencing of CHFR depended on the activities of two DNA methyltransferases, DNMT1 and DNMT3b, as their genetic inactivation restored CHFR expression. Finally, cells with CHFR methylation had an intrinsically high mitotic index when treated with microtubule inhibitor. This means that cells in which CHFR was epigenetically inactivated constitute loss-of-function alleles for mitotic checkpoint control. Taken together, these findings shed light on a pathway by which mitotic checkpoint is bypassed in cancer cells and suggest that inactivation of checkpoint genes is much more widespread than previously suspected.

  1. Companion diagnostics and molecular imaging-enhanced approaches for oncology clinical trials.

    Science.gov (United States)

    Van Heertum, Ronald L; Scarimbolo, Robert; Ford, Robert; Berdougo, Eli; O'Neal, Michael

    2015-01-01

    In the era of personalized medicine, diagnostic approaches are helping pharmaceutical and biotechnology sponsors streamline the clinical trial process. Molecular assays and diagnostic imaging are routinely being used to stratify patients for treatment, monitor disease, and provide reliable early clinical phase assessments. The importance of diagnostic approaches in drug development is highlighted by the rapidly expanding global cancer diagnostics market and the emergent attention of regulatory agencies worldwide, who are beginning to offer more structured platforms and guidance for this area. In this paper, we highlight the key benefits of using companion diagnostics and diagnostic imaging with a focus on oncology clinical trials. Nuclear imaging using widely available radiopharmaceuticals in conjunction with molecular imaging of oncology targets has opened the door to more accurate disease assessment and the modernization of standard criteria for the evaluation, staging, and treatment responses of cancer patients. Furthermore, the introduction and validation of quantitative molecular imaging continues to drive and optimize the field of oncology diagnostics. Given their pivotal role in disease assessment and treatment, the validation and commercialization of diagnostic tools will continue to advance oncology clinical trials, support new oncology drugs, and promote better patient outcomes.

  2. Molecular imaging in drug development: Update and challenges for radiolabeled antibodies and nanotechnology.

    Science.gov (United States)

    Colombo, Ilaria; Overchuk, Marta; Chen, Juan; Reilly, Raymond M; Zheng, Gang; Lheureux, Stephanie

    2017-11-01

    Despite the significant advancement achieved in understanding the molecular mechanisms responsible for cancer transformation and aberrant proliferation, leading to novel targeted cancer therapies, significant effort is still needed to "personalize" cancer treatment. Molecular imaging is an emerging field that has shown the ability to characterize in vivo the molecular pathways present at the cancer cell level, enabling diagnosis and personalized treatment of malignancies. These technologies, particularly SPECT and PET also permit the development of novel radiotheranostic probes, which provide capabilities for diagnosis and treatment with the same agent. The small therapeutic index of most anticancer agents is a limitation in the drug development process. Incorporation of molecular imaging in clinical research may help in overcoming this limitation and favouring selection of patient populations most likely to achieve benefit from targeted therapy. This review will focus on two of the most advanced theranostic approaches with promising potential for application in the clinic: 1) therapeutic monoclonal antibodies which may be linked to a radionuclide for SPECT or PET imaging to guide cancer diagnosis, staging, molecular characterization, and assessment of the response to treatment and 2) multifunctional nanotechnology that allows image guided drug delivery through encapsulation of multiple therapeutic, targeting and imaging agents into a single nanoparticle. Porphysome, a liposome-like nanoparticle, is an example of a novel and promising application of nanotechnology for cancer diagnosis and treatment. These technologies have proven to be effective in preclinical models, warranting further clinical investigation to advance their application for the benefit of cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Targeted gold nanoparticles enable molecular CT imaging of cancer: an in vivo study

    Directory of Open Access Journals (Sweden)

    Reuveni T

    2011-11-01

    Full Text Available Tobi Reuveni1, Menachem Motiei1, Zimam Romman2, Aron Popovtzer3, Rachela Popovtzer11Faculty of Engineering and the Institute of Nanotechnology and Advanced Materials, Bar-ilan University, Ramat Gan, 2GE HealthCare, Tirat Hacarmel, 3Department of Otorhinolaryngology, Head and Neck Surgery and Onology, Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, IsraelAbstract: In recent years, advances in molecular biology and cancer research have led to the identification of sensitive and specific biomarkers that associate with various types of cancer. However, in vivo cancer detection methods with computed tomography, based on tracing and detection of these molecular cancer markers, are unavailable today. This paper demonstrates in vivo the feasibility of cancer diagnosis based on molecular markers rather than on anatomical structures, using clinical computed tomography. Anti-epidermal growth factor receptor conjugated gold nanoparticles (30 nm were intravenously injected into nude mice implanted with human squamous cell carcinoma head and neck cancer. The results clearly demonstrate that a small tumor, which is currently undetectable through anatomical computed tomography, is enhanced and becomes clearly visible by the molecularly-targeted gold nanoparticles. It is further shown that active tumor targeting is more efficient and specific than passive targeting. This noninvasive and nonionizing molecular cancer imaging tool can facilitate early cancer detection and can provide researchers with a new technique to investigate in vivo the expression and activity of cancer-related biomarkers and molecular processes.Keywords: functional computed tomography, molecular imaging, gold nanoparticles, biologically targeted in vivo imaging, contrast agents

  4. Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

    International Nuclear Information System (INIS)

    Bowsher, James; Giles, William; Yin, Fang-Fang; Yan, Susu; Roper, Justin

    2014-01-01

    Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min

  5. Onboard functional and molecular imaging: A design investigation for robotic multipinhole SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Bowsher, James, E-mail: james.bowsher@duke.edu; Giles, William; Yin, Fang-Fang [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 and Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Yan, Susu [Medical Physics Graduate Program, Duke University, Durham, North Carolina 27710 (United States); Roper, Justin [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)

    2014-01-15

    Purpose: Onboard imaging—currently performed primarily by x-ray transmission modalities—is essential in modern radiation therapy. As radiation therapy moves toward personalized medicine, molecular imaging, which views individual gene expression, may also be important onboard. Nuclear medicine methods, such as single photon emission computed tomography (SPECT), are premier modalities for molecular imaging. The purpose of this study is to investigate a robotic multipinhole approach to onboard SPECT. Methods: Computer-aided design (CAD) studies were performed to assess the feasibility of maneuvering a robotic SPECT system about a patient in position for radiation therapy. In order to obtain fast, high-quality SPECT images, a 49-pinhole SPECT camera was designed which provides high sensitivity to photons emitted from an imaging region of interest. This multipinhole system was investigated by computer-simulation studies. Seventeen hot spots 10 and 7 mm in diameter were placed in the breast region of a supine female phantom. Hot spot activity concentration was six times that of background. For the 49-pinhole camera and a reference, more conventional, broad field-of-view (FOV) SPECT system, projection data were computer simulated for 4-min scans and SPECT images were reconstructed. Hot-spot localization was evaluated using a nonprewhitening forced-choice numerical observer. Results: The CAD simulation studies found that robots could maneuver SPECT cameras about patients in position for radiation therapy. In the imaging studies, most hot spots were apparent in the 49-pinhole images. Average localization errors for 10-mm- and 7-mm-diameter hot spots were 0.4 and 1.7 mm, respectively, for the 49-pinhole system, and 3.1 and 5.7 mm, respectively, for the reference broad-FOV system. Conclusions: A robot could maneuver a multipinhole SPECT system about a patient in position for radiation therapy. The system could provide onboard functional and molecular imaging with 4-min

  6. Photodynamic inactivation of bacteria using polyethylenimine-chlorin(e6) conjugates: Effect of polymer molecular weight, substitution ratio of chlorin(e6) and pH.

    Science.gov (United States)

    Huang, Liyi; Zhiyentayev, Timur; Xuan, Yi; Azhibek, Dulat; Kharkwal, Gitika B; Hamblin, Michael R

    2011-04-01

    Antimicrobial photodynamic therapy (APDT) is a novel technique to treat local infections. Previously we reported that the attachment of chlorin(e6) to polyethylenimine (PEI) polymers to form PEI-ce6 conjugates is an effective way to improve ce6 PDT activity against bacteria. The aim of this work was to explore how the polymer molecular weight, substitution ratio (SR) of ce6 and pH value affect the PDT efficacy. We have synthesized PEI-ce6(10) (MW = 60,000, SR = 1) and PEI-ce6(11) (MW = 60,000, SR = 5) and compared these with the previous PEI-ce6(9) (MW = 10,000, SR = 1). We tested the PDT efficacy of these three conjugates against Gram-negative E. coli and Gram-positive bacteria (S. aureus and E. fecalis) at three different pH values (5.0, 7.4, 10.0) that may affect the charge on both the bacterial cells and on the conjugate (that has both basic and acidic groups). PEI-ce6(9) and PEI-ce6(10) were the most effective against these tested bacteria. The PDT effect of all three conjugates depended on pH values. The effective order was pH = 10.0 > pH = 7.4 > pH = 5.0 on E. coli. For S. aureus and E. fecalis the order was pH = 5.0 > pH = 10.0 > pH = 7.4. PEI-ce6(11) PDT activity was worse than PEI-ce6(10) activity which is probably connected to the fact that ce6 molecules are self-quenched within the PEI-ce6(11) molecule. Ce6 quenching within the PEI-ce6 molecules was proved by analyzing fluorescence spectra of PEI-ce6 conjugates at different pH values. There were no differences in bacterial uptake between different pH values in three PEI-ce6 conjugates. We assume high pH (rather than low pH as was hypothesized) disaggregates the conjugates, so the higher pH was more effective than the lower pH against E. coli. But for Gram-positive bacteria, low pH was more effective possibly due to more overall positive charge on the conjugate. Copyright © 2011 Wiley-Liss, Inc.

  7. Molecular imaging and the unification of multilevel mechanisms and data in medical physics

    International Nuclear Information System (INIS)

    Nikiforidis, George C.; Sakellaropoulos, George C.; Kagadis, George C.

    2008-01-01

    Molecular imaging (MI) constitutes a recently developed approach of imaging, where modalities and agents have been reinvented and used in novel combinations in order to expose and measure biologic processes occurring at molecular and cellular levels. It is an approach that bridges the gap between modalities acquiring data from high (e.g., computed tomography, magnetic resonance imaging, and positron-emitting isotopes) and low (e.g., PCR, microarrays) levels of a biological organization. While data integration methodologies will lead to improved diagnostic and prognostic performance, interdisciplinary collaboration, triggered by MI, will result in a better perception of the underlying biological mechanisms. Toward the development of a unifying theory describing these mechanisms, medical physicists can formulate new hypotheses, provide the physical constraints bounding them, and consequently design appropriate experiments. Their new scientific and working environment calls for interventions in their syllabi to educate scientists with enhanced capabilities for holistic views and synthesis.

  8. Direct molecular analysis of whole-body animal tissue sections by MALDI imaging mass spectrometry.

    Science.gov (United States)

    Reyzer, Michelle L; Chaurand, Pierre; Angel, Peggi M; Caprioli, Richard M

    2010-01-01

    The determination of the localization of various compounds in a whole animal is valuable for many applications, including pharmaceutical absorption, distribution, metabolism, and excretion (ADME) studies and biomarker discovery. Imaging mass spectrometry is a powerful tool for localizing compounds of biological interest with molecular specificity and relatively high resolution. Utilizing imaging mass spectrometry for whole-body animal sections offers considerable analytical advantages compared to traditional methods, such as whole-body autoradiography, but the experiment is not straightforward. This chapter addresses the advantages and unique challenges that the application of imaging mass spectrometry to whole-body animal sections entails, including discussions of sample preparation, matrix application, signal normalization, and image generation. Lipid and protein images obtained from whole-body tissue sections of mouse pups are presented along with detailed protocols for the experiments.

  9. Full-direct method for imaging pharmacokinetic parameters in dynamic fluorescence molecular tomography

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Guanglei, E-mail: guangleizhang@bjtu.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); Department of Biomedical Engineering, School of Computer and Information Technology, Beijing Jiaotong University, Beijing 100044 (China); Pu, Huangsheng; Liu, Fei; Bai, Jing [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); He, Wei [China Institute of Sport Science, Beijing 100061 (China); Luo, Jianwen, E-mail: luo-jianwen@tsinghua.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); Center for Biomedical Imaging Research, School of Medicine, Tsinghua University, Beijing 100084 (China)

    2015-02-23

    Images of pharmacokinetic parameters (also known as parametric images) in dynamic fluorescence molecular tomography (FMT) can provide three-dimensional metabolic information for biological studies and drug development. However, the ill-posed nature of FMT and the high temporal variation of fluorophore concentration together make it difficult to obtain accurate parametric images in small animals in vivo. In this letter, we present a method to directly reconstruct the parametric images from the boundary measurements based on hybrid FMT/X-ray computed tomography (XCT) system. This method can not only utilize structural priors obtained from the XCT system to mitigate the ill-posedness of FMT but also make full use of the temporal correlations of boundary measurements to model the high temporal variation of fluorophore concentration. The results of numerical simulation and mouse experiment demonstrate that the proposed method leads to significant improvements in the reconstruction quality of parametric images.

  10. Next Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

    Science.gov (United States)

    2016-07-01

    AWARD NUMBER: W81XWH- 14-1-0192 TITLE: Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer...DATES COVERED 4. TITLE AND SUBTITLE Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue

  11. Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Toumpanakis, Christos; Kim, Michelle K; Rinke, Anja; Bergestuen, Deidi S; Thirlwell, Christina; Khan, Mohid S; Salazar, Ramon; Oberg, Kjell

    2014-01-01

    Molecular imaging modalities exploit aspects of neuroendocrine tumors (NET) pathophysiology for both diagnostic imaging and therapeutic purposes. The characteristic metabolic pathways of NET determine which tracers are useful for their visualization. In this review, we summarize the diagnostic value of all available molecular imaging studies, present data about their use in daily practice in NET centers globally, and finally make recommendations about the appropriate use of those modalities in specific clinical scenarios. Somatostatin receptor scintigraphy (SRS) continues to have a central role in the diagnostic workup of patients with NET, as it is also widely available. However, and despite the lack of prospective randomized studies, many NET experts predict that Gallium-68 ((68)Ga)-DOTA positron emission tomography (PET) techniques may replace SRS in the future, not only because of their technical advantages, but also because they are superior in patients with small-volume disease, in patients with skeletal metastases, and in those with occult primary tumors. Carbon-11 ((11)C)-5-hydroxy-L-tryptophan (5-HTP) PET and (18)F-dihydroxyphenylalanine ((18)F-DOPA) PET are new molecular imaging techniques of limited availability, and based on retrospective data, their sensitivities seem to be inferior to that of (68)Ga-DOTA PET. Glucagon-like-peptide-1 (GLP-1) receptor imaging seems promising for localization of the primary in benign insulinomas, but is currently available only in a few centers. Fluorine-18 ((18)F)-fluorodeoxyglucose ((18)F-FDG) PET was initially thought to be of limited value in NET, due to their usually slow-growing nature. However, according to subsequent data, (18)F-FDG PET is particularly helpful for visualizing the more aggressive NET, such as poorly differentiated neuroendocrine carcinomas, and well-differentiated tumors with Ki67 values >10%. According to limited data, (18)F-FDG-avid tumor lesions, even in slow-growing NET, may indicate a more

  12. Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

    Science.gov (United States)

    Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

    2015-09-01

    The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular

  13. Functional and molecular imaging with MRI: potential applications in paediatric radiology

    International Nuclear Information System (INIS)

    Arthurs, Owen J.; Gallagher, Ferdia A.

    2011-01-01

    MRI is a very versatile tool for noninvasive imaging and it is particularly attractive as an imaging technique in paediatric patients given the absence of ionizing radiation. Recent advances in the field of MRI have enabled tissue function to be probed noninvasively, and increasingly MRI is being used to assess cellular and molecular processes. For example, dynamic contrast-enhanced MRI has been used to assess tissue vascularity, diffusion-weighted imaging can quantify molecular movements of water in tissue compartments and MR spectroscopy provides a quantitative assessment of metabolite levels. A number of targeted contrast agents have been developed that bind specifically to receptors on the vascular endothelium or cell surface and there are several MR methods for labelling cells and tracking cellular movements. Hyperpolarization techniques have the capability of massively increasing the sensitivity of MRI and these have been used to image tissue pH, successful response to drug treatment as well as imaging the microstructure of the lungs. Although there are many challenges to be overcome before these techniques can be translated into routine paediatric imaging, they could potentially be used to aid diagnosis, predict disease outcome, target biopsies and determine treatment response noninvasively. (orig.)

  14. The molecular imaging approach to image infections and inflammation by nuclear medicine techniques

    NARCIS (Netherlands)

    Signore, Alberto; Glaudemans, Andor W. J. M.

    2011-01-01

    Inflammatory and infectious diseases are a heterogeneous class of diseases that may be divided into infections, acute inflammation and chronic inflammation. Radiological imaging techniques have, with the exception of functional MRI, high sensitivity but lack in specificity. Nuclear medicine

  15. Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

    Science.gov (United States)

    Davis, Margaret T.; Holmes, Sophie E.; Pietrzak, Robert H.; Esterlis, Irina

    2018-01-01

    Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders. The present paper provides a comprehensive review and synthesis of all positron emission tomography and single photon emission computed tomography imaging publications focused on the examination of molecular targets in individuals with major depressive disorder, posttraumatic stress disorder, or bipolar disorder to date. Critical discussion of discrepant findings and broad strengths and weaknesses of the current body of literature is provided. Recommended future directions for the field of molecular imaging to further elucidate the neurobiological substrates of chronic stress-related disorders are also discussed. This article is part of the inaugural issue for the journal focused on various aspects of chronic stress. PMID:29862379

  16. PET for molecular imaging of cancer: a tool for tailored therapy

    International Nuclear Information System (INIS)

    Kjaer, Andreas

    2014-01-01

    The concept of personalised medicine has led to a need for improved phenotyping as well as prediction of treatment response early after therapy initiation. Most of the molecular biology methods used today need tissue sampling for in vitro analysis. In contrast, molecular imaging allows for non-invasive studies at the molecular level in living, intact organisms. Accordingly, molecular imaging with PET has been one of the most successful techniques in such phenotyping and response prediction using FDG. In addition, recent development of new PET tracers has further improved the value of PET in tumor characterization. Such new PET tracers allow for visualization of tumor specific receptors and tissue characteristics such as ability to metastasize. Furthermore, PET has a high sensitivity and allows for quantification and is not prone to sampling error as seen with biopsies. We will present examples of development of probes targeting the somatostatin receptor type 2, over-expressed in neuroendocrine tumors, including our first-in-man studies of 64 Cu-DOTATATE. Also development in probes for visualization of the invasive phenotype will be presented. Finally, with the most recent development of true integrated PET/MRI scanners has now become possible to add information from MRI. The value of such hybrid imaging will also be briefly discussed. (author)

  17. PET for molecular imaging of cancer: a tool for tailored therapy

    International Nuclear Information System (INIS)

    Kjaer, Andreas

    2013-01-01

    The concept of personalised medicine has led to a need for improved phenotyping as well as prediction of treatment response early after therapy initiation. Most of the molecular biology methods used today need tissue sampling for in vitro analysis. In contrast, molecular imaging allows for non-invasive studies at the molecular level in living, intact organisms. Accordingly, molecular imaging with PET has been one of the most successful techniques in such phenotyping and response prediction using FDG. In addition, recent development of new PET tracers has further improved the value of PET in tumor characterization. Such new PET tracers allow for visualization of tumor specific receptors and tissue characteristics such as ability to metastasize. Furthermore, PET has a high sensitivity and allows for quantification and is not prone to sampling error as seen with biopsies. We will present examples of development of probes targeting the somatostatin receptor type 2, over-expressed in neuroendocrine tumors, including our first-in-man studies of 64Cu-DOTATATE. Also development in probes for visualization of the invasive phenotype will be presented. Finally, with the most recent development of true integrated PET/MRI scanners it has now become possible to add information from MRI. The value of such hybrid imaging will also be briefly discussed. (author)

  18. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

    Science.gov (United States)

    Ahn, Byeong-Cheol

    2016-01-01

    Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

  19. Technological advances in Preclinical Molecular Imaging; Avances tecnológicos en Imagen Molecular Preclínica

    Energy Technology Data Exchange (ETDEWEB)

    Peña-Zalbidea, S.; Vaquero, J.

    2014-07-01

    Molecular imaging is undergoing an intense activity, mainly due to the availability of new detection and image reconstruction technologies, which in recent years have improved significantly both the resolution and sensitivity of these methods. The greatest potential for innovation comes from multimodality imaging, which combines information from more than one imaging technique and exploits the synergies between them. The main arguments in favour of these devices are the possibility of performing intrinsically registered scans in a minimum time and without moving the animal. Currently, the combination of PET and MRI as a hybrid imaging modality is receiving great attention and although its potential is clear, as it was with the PET/CT, this technology will have to overcome certain limitations and demonstrate its value for different applications. [Spanish] La imagen molecular es un área de investigación muy activa acelerada en los últimos años por la disponibilidad de nuevas tecnologías de detección y reconstrucción de imágenes. Estas innovaciones han permitido mejorar considerablemente tanto la resolución como la sensibilidad de las imágenes obtenidas sobre modelos preclínicos desarrollados en pequeños animales (ratón y rata principalmente). El mayor potencial de esta tecnología proviene de la imagen multimodalidad, que combina información de más de una técnica de imagen y explota las posibles sinergias entre ellas al integrar en una sola imagen “forma y función”. Los principales argumentos a favor de estos dispositivos multimodales son la posibilidad de hacer las exploraciones intrínsecamente registradas en un tiempo reducido, y sin necesidad de mover el animal entre diferentes equipos. De todas las posibles combinaciones la que está reclamando más la atención últimamente es la PET/IRM (tomografía por emisión de positrones e imagen de resonancia magnética), aunque de momento la PET/CT (tomografía por emisión de positrones y tomograf

  20. Development of new Molecular Imaging probes; Desarrollo de nuevas sondas de Imagen Molecular

    Energy Technology Data Exchange (ETDEWEB)

    Gómez-Vallejo, V.; Baz, Z.; Llop, J.

    2014-07-01

    Nuclear Imaging techniques such as positron emission tomography (PET) and single photon emission computerized tomography (SPECT) are essential tools for the early diagnose of certain pathologies, and have been widely applied to the mechanistic investigation of disease, the visualization of biological and physiological phenomena and in the process of drug development. PET and SPECT require the administration of a radiotracer (compound labelled with a radioactive nuclide) to the subject under investigation (patient, healthy volunteer or experimental animal). Due to their high sensitivity and their noninvasive nature, nuclear imaging techniques have a great potential. However, only a few radiotracers are currently routinely used in clinical diagnose. In contrast, new tracers suitable for the visualization of new targets or showing improved specificity, selectivity or pharmacokinetic properties are continuously designed, synthesized and assayed in the preclinical setting. Far from performing an exhaustive revision of the new radiotracers currently under development, this paper aims to collate recent advances related to the preparation of novel nuclear imaging probes, which have a significant scientific impact in terms of literature volume, and which could be translated to the clinical environment in the near future. First, peptides and nanoparticles (NPs) are discussed. Finally, antibody derivatives and the recently developed pretargeting strategy, which enables the visualization of tumours while lowering significantly the effective dose posed on the subject under investigation, will be briefly covered. [Spanish] Las técnicas de imagen nuclear, entre las que se encuentran la tomografía por emisión de positrones (PET) y la tomografía por emisión de fotón único (SPECT) son herramientas fundamentales no sólo en el entorno clínico diagnóstico, sino también para el estudio mecanístico de determinadas patologías, la visualización de procesos biol

  1. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    Science.gov (United States)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-05-05

    Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

  2. Molecular imaging of atherosclerotic plaques with technetium-99m-labelled antisense oligonucleotides

    International Nuclear Information System (INIS)

    Qin Guangming; Zhang Yongxue; Cao Wei; An Rui; Gao Zairong; Xu Wendai; Zhang Kaijun; Li Guiling; Li Shuren

    2005-01-01

    The purpose of this study was to visualise experimental atherosclerotic lesions using radiolabelled antisense oligonucleotides (ASONs). Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 60 days. In vivo and ex vivo imaging was performed in atherosclerotic rabbits and normal control rabbits after i.v. injection of 92.5±18.5 MBq 99m Tc-labelled ASON or 99m Tc-labelled sense oligonucleotides. Immediately after the in vivo imaging, the animals were sacrificed and ex vivo imaging of the aortic specimens was performed. Biodistribution of radiolabelled c-mycASON was evaluated in vivo in atherosclerotic rabbits. Planar imaging revealed accumulation of 99m Tc-labelled c-mycASON in atherosclerotic lesions along the artery wall. Ex vivo imaging further demonstrated that the area of activity accumulation matched the area of atherosclerotic lesions. In contrast, no atherosclerotic lesions were found in the vessel wall and no positive imaging results were obtained in animals of the control group. This molecular imaging approach has potential for non-invasive imaging of atherosclerotic plaques at an early stage. (orig.)

  3. Imaging modes of atomic force microscopy for application in molecular and cell biology.

    Science.gov (United States)

    Dufrêne, Yves F; Ando, Toshio; Garcia, Ricardo; Alsteens, David; Martinez-Martin, David; Engel, Andreas; Gerber, Christoph; Müller, Daniel J

    2017-04-06

    Atomic force microscopy (AFM) is a powerful, multifunctional imaging platform that allows biological samples, from single molecules to living cells, to be visualized and manipulated. Soon after the instrument was invented, it was recognized that in order to maximize the opportunities of AFM imaging in biology, various technological developments would be required to address certain limitations of the method. This has led to the creation of a range of new imaging modes, which continue to push the capabilities of the technique today. Here, we review the basic principles, advantages and limitations of the most common AFM bioimaging modes, including the popular contact and dynamic modes, as well as recently developed modes such as multiparametric, molecular recognition, multifrequency and high-speed imaging. For each of these modes, we discuss recent experiments that highlight their unique capabilities.

  4. Document authentication at molecular levels using desorption atmospheric pressure chemical ionization mass spectrometry imaging.

    Science.gov (United States)

    Li, Ming; Jia, Bin; Ding, Liying; Hong, Feng; Ouyang, Yongzhong; Chen, Rui; Zhou, Shumin; Chen, Huanwen; Fang, Xiang

    2013-09-01

    Molecular images of documents were obtained by sequentially scanning the surface of the document using desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS), which was operated in either a gasless, solvent-free or methanol vapor-assisted mode. The decay process of the ink used for handwriting was monitored by following the signal intensities recorded by DAPCI-MS. Handwritings made using four types of inks on four kinds of paper surfaces were tested. By studying the dynamic decay of the inks, DAPCI-MS imaging differentiated a 10-min old from two 4 h old samples. Non-destructive forensic analysis of forged signatures either handwritten or computer-assisted was achieved according to the difference of the contour in DAPCI images, which was attributed to the strength personalized by different writers. Distinction of the order of writing/stamping on documents and detection of illegal printings were accomplished with a spatial resolution of about 140 µm. A Matlab® written program was developed to facilitate the visualization of the similarity between signature images obtained by DAPCI-MS. The experimental results show that DAPCI-MS imaging provides rich information at the molecular level and thus can be used for the reliable document analysis in forensic applications. © 2013 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons, Ltd.

  5. Optical Molecular Imaging of Epidermal Growth Factor Receptor Expression to Improve Detection of Oral Neoplasia

    Directory of Open Access Journals (Sweden)

    Nitin Nitin

    2009-06-01

    Full Text Available Background: The development of noninvasive molecular imaging approaches has the potential to improve management of cancer. Methods: In this study, we demonstrate the potential of noninvasive topical delivery of an epidermal growth factor-Alexa 647 (EGF-Alexa 647 conjugate to image changes in epidermal growth factor receptor expression associated with oral neoplasia. We report a series of preclinical analyses to evaluate the optical contrast achieved after topical delivery of EGF-Alexa 647 in a variety of model systems, including cells, three-dimensional tissue cultures, and intact human tissue specimens using wide-field and high-resolution fluorescence imaging. Data were collected from 17 different oral cancer patients: eight pairs of normal and abnormal biopsies and nine resected tumors were examined. Results: The EGF-dye conjugate can be uniformly delivered throughout the oral epithelium with a penetration depth exceeding 500 µm and incubation time of less than 30 minutes. After EGF-Alexa 647 incubation, the presence of oral neoplasia is associated with a 1.5- to 6.9-fold increase in fluorescence contrast compared with grossly normal mucosa from the same patient with both wide-field and high-resolution fluorescence imaging. Conclusions: Results illustrate the potential of EGF-targeted fluorescent agents for in vivo molecular imaging, a technique that may aid in the diagnosis and characterization of oral neoplasia and allow real-time detection of tumor margins.

  6. Breaching Biological Barriers: Protein Translocation Domains as Tools for Molecular Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Benjamin L. Franc

    2003-10-01

    Full Text Available The lipid bilayer of a cell presents a significant barrier for the delivery of many molecular imaging reagents into cells at target sites in the body. Protein translocation domains (PTDs are peptides that breach this barrier. Conjugation of PTDs to imaging agents can be utilized to facilitate the delivery of these agents through the cell wall, and in some cases, into the cell nucleus, and have potential for in vitro and in vivo applications. PTD imaging conjugates have included small molecules, peptides, proteins, DNA, metal chelates, and magnetic nanoparticles. The full potential of the use of PTDs in novel in vivo molecular probes is currently under investigation. Cells have been labeled in culture using magnetic nanoparticles derivatized with a PTD and monitored in vivo to assess trafficking patterns relative to cells expressing a target antigen. In vivo imaging of PTD-mediated gene transfer to cells of the skin has been demonstrated in living animals. Here we review several natural and synthetic PTDs that have evolved in the quest for easier translocation across biological barriers and the application of these peptide domains to in vivo delivery of imaging agents.

  7. The use of molecular imaging of gene expression by radiotracers in gene therapy

    International Nuclear Information System (INIS)

    Richard-Fiardo, P.; Franken, P.R.; Harrington, K.J.; Vassaux, G.; Cambien, B.

    2011-01-01

    Introduction: Progress with gene-based therapies has been hampered by difficulties in monitoring the biodistribution and kinetics of vector-mediated gene expression. Recent developments in non-invasive imaging have allowed researchers and clinicians to assess the location, magnitude and persistence of gene expression in animals and humans. Such advances should eventually lead to improvement in the efficacy and safety of current clinical protocols for future treatments. Areas Covered: The molecular imaging techniques for monitoring gene therapy in the living subject, with a specific highlight on the key reporter gene approaches that have been developed and validated in preclinical models using the latest imaging modalities. The applications of molecular imaging to biotherapy, with a particular emphasis on monitoring of gene and vector biodistribution and on image-guided radiotherapy. Expert Opinion: Among the reporter gene/probe combinations that have been described so far, one stands out, in our view, as the most versatile and easy to implement: the Na/I symporter. This strategy, exploiting more than 50 years of experience in the treatment of differentiated thyroid carcinomas, has been validated in different types of experimental cancers and with different types of oncolytic viruses and is likely to become a key tool in the implementation of human gene therapy. (authors)

  8. Justifying molecular images in cell biology textbooks: From constructions to primary data.

    Science.gov (United States)

    Serpente, Norberto

    2016-02-01

    For scientific claims to be reliable and productive they have to be justified. However, on the one hand little is known on what justification precisely means to scientists, and on the other the position held by philosophers of science on what it entails is rather limited; for justifications customarily refer to the written form (textual expressions) of scientific claims, leaving aside images, which, as many cases from the history of science show are relevant to this process. The fact that images can visually express scientific claims independently from text, plus their vast variety and origins, requires an assessment of the way they are currently justified and in turn used as sources to justify scientific claims in the case of particular scientific fields. Similarly, in view of the different nature of images, analysis is required to determine on what side of the philosophical distinction between data and phenomena these different kinds of images fall. This paper historicizes and documents a particular aspect of contemporary life sciences research: the use of the molecular image as vehicle of knowledge production in cell studies, a field that has undergone a significant shift in visual expressions from the early 1980s onwards. Focussing on textbooks as sources that have been overlooked in the historiography of contemporary biomedicine, the aim is to explore (1) whether the shift of cell studies, entailing a superseding of the optical image traditionally conceptualised as primary data, by the molecular image, corresponds with a shift of justificatory practices, and (2) to assess the role of the molecular image as primary data. This paper also explores the dual role of images as teaching resources and as resources for the construction of knowledge in cell studies especially in its relation to discovery and justification. Finally, this paper seeks to stimulate reflection on what kind of archival resources could benefit the work of present and future epistemic

  9. Molecular imaging of hypoxia in non-small-cell lung cancer

    International Nuclear Information System (INIS)

    Yip, Connie; Blower, Philip J.; Goh, Vicky; Landau, David B.; Cook, Gary J.R.

    2015-01-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  10. Molecular imaging of hypoxia in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yip, Connie [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); National Cancer Centre, Department of Radiation Oncology, Singapore (Singapore); St Thomas' Hospital, Imaging 2, London (United Kingdom); Blower, Philip J. [King' s College London, St Thomas' Hospital, Department of Imaging Chemistry and Biology, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Goh, Vicky [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Landau, David B. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Department of Clinical Oncology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom); Cook, Gary J.R. [King' s College London, St Thomas' Hospital, Department of Cancer Imaging, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); St Thomas' Hospital, Clinical PET Imaging Centre, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2015-05-01

    Non-small-cell lung cancer (NSCLC) is the commonest cancer worldwide but survival remains poor with a high risk of relapse, particularly after nonsurgical treatment. Hypoxia is present in a variety of solid tumours, including NSCLC. It is associated with treatment resistance and a poor prognosis, although when recognised may be amenable to different treatment strategies. Thus, noninvasive assessment of intratumoral hypoxia could be used to stratify patients for modification of subsequent treatment to improve tumour control. Molecular imaging approaches targeting hypoxic cells have shown some early success in the clinical setting. This review evaluates the evidence for hypoxia imaging using PET in NSCLC and explores its potential clinical utility. (orig.)

  11. First-in-Human Ultrasound Molecular Imaging With a VEGFR2-Specific Ultrasound Molecular Contrast Agent (BR55) in Prostate Cancer: A Safety and Feasibility Pilot Study.

    Science.gov (United States)

    Smeenge, Martijn; Tranquart, François; Mannaerts, Christophe K; de Reijke, Theo M; van de Vijver, Marc J; Laguna, M Pilar; Pochon, Sibylle; de la Rosette, Jean J M C H; Wijkstra, Hessel

    2017-07-01

    BR55, a vascular endothelial growth factor receptor 2 (VEGFR2)-specific ultrasound molecular contrast agent (MCA), has shown promising results in multiple preclinical models regarding cancer imaging. In this first-in-human, phase 0, exploratory study, we investigated the feasibility and safety of the MCA for the detection of prostate cancer (PCa) in men using clinical standard technology. Imaging with the MCA was performed in 24 patients with biopsy-proven PCa scheduled for radical prostatectomy using a clinical ultrasound scanner at low acoustic power. Safety monitoring was done by physical examination, blood pressure and heart rate measurements, electrocardiogram, and blood sampling. As first-in-human study, MCA dosing and imaging protocol were necessarily fine-tuned along the enrollment to improve visualization. Imaging data were correlated with radical prostatectomy histopathology to analyze the detection rate of ultrasound molecular imaging with the MCA. Imaging with MCA doses of 0.03 and 0.05 mL/kg was adequate to obtain contrast enhancement images up to 30 minutes after administration. No serious adverse events or clinically meaningful changes in safety monitoring data were identified during or after administration. BR55 dosing and imaging were fine-tuned in the first 12 patients leading to 12 subsequent patients with an improved MCA dosing and imaging protocol. Twenty-three patients underwent radical prostatectomy. A total of 52 lesions were determined to be malignant by histopathology with 26 (50%) of them seen during BR55 imaging. In the 11 patients that were scanned with the improved protocol and underwent radical prostatectomy, a total of 28 malignant lesions were determined: 19 (68%) were seen during BR55 ultrasound molecular imaging, whereas 9 (32%) were not identified. Ultrasound molecular imaging with BR55 is feasible with clinical standard technology and demonstrated a good safety profile. Detectable levels of the MCA can be reached in patients

  12. Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

    Science.gov (United States)

    Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

    2017-01-01

    Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

  13. The Changing Face of Vascular Interventional Radiology: The Future Role of Pharmacotherapies and Molecular Imaging

    International Nuclear Information System (INIS)

    Tapping, Charles R.; Bratby, Mark J.

    2013-01-01

    Interventional radiology has had to evolve constantly because there is the ever-present competition and threat from other specialties within medicine, surgery, and research. The development of new technologies, techniques, and therapies is vital to broaden the horizon of interventional radiology and to ensure its continued success in the future. In part, this change will be due to improved chronic disease prevention altering what we treat and in whom. The most important of these strategies are the therapeutic use of statins, Beta-blockers, angiotensin-converting enzyme inhibitors, and substances that interfere with mast cell degeneration. Molecular imaging and therapeutic strategies will move away from conventional techniques and nano and microparticle molecular technology, tissue factor imaging, gene therapy, endothelial progenitor cells, and photodynamic therapy will become an important part of interventional radiology of the future. This review looks at these new and exciting technologies

  14. Detection of high molecular weight proteins by MALDI imaging mass spectrometry.

    Science.gov (United States)

    Mainini, Veronica; Bovo, Giorgio; Chinello, Clizia; Gianazza, Erica; Grasso, Marco; Cattoretti, Giorgio; Magni, Fulvio

    2013-06-01

    MALDI imaging mass spectrometry (IMS) is a unique technology to explore the spatial distribution of biomolecules directly on tissues. It allows the in situ investigation of a large number of small proteins and peptides. Detection of high molecular weight proteins through MALDI IMS still represents an important challenge, as it would allow the direct investigation of the distribution of more proteins involved in biological processes, such as cytokines, enzymes, neuropeptide precursors and receptors. In this work we compare the traditional method performed with sinapinic acid with a comparable protocol using ferulic acid as the matrix. Data show a remarkable increase of signal acquisition in the mass range of 20k to 150k Th. Moreover, we report molecular images of biomolecules above 70k Th, demonstrating the possibility of expanding the application of this technology both in clinical investigations and basic science.

  15. The Changing Face of Vascular Interventional Radiology: The Future Role of Pharmacotherapies and Molecular Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tapping, Charles R., E-mail: crtapping@doctors.org.uk; Bratby, Mark J., E-mail: mark.bratby@ouh.nhs.uk [Oxford University Hospitals, John Radcliffe Hospital, Department of Radiology (United Kingdom)

    2013-08-01

    Interventional radiology has had to evolve constantly because there is the ever-present competition and threat from other specialties within medicine, surgery, and research. The development of new technologies, techniques, and therapies is vital to broaden the horizon of interventional radiology and to ensure its continued success in the future. In part, this change will be due to improved chronic disease prevention altering what we treat and in whom. The most important of these strategies are the therapeutic use of statins, Beta-blockers, angiotensin-converting enzyme inhibitors, and substances that interfere with mast cell degeneration. Molecular imaging and therapeutic strategies will move away from conventional techniques and nano and microparticle molecular technology, tissue factor imaging, gene therapy, endothelial progenitor cells, and photodynamic therapy will become an important part of interventional radiology of the future. This review looks at these new and exciting technologies.

  16. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Feng-Yang, E-mail: fyzheng16@fudan.edu.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Lu, Qing, E-mail: lu.qing@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Huang, Bei-Jian, E-mail: huang.beijian@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Xia, Han-Sheng, E-mail: zs12036@126.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Yan, Li-Xia, E-mail: dndyanlixia@163.com [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Xi, E-mail: wang.xi@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Yuan, Wei, E-mail: yuan.wei@zs-hospital.sh.cn [Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Wang, Wen-Ping, E-mail: wang.wenping@zs-hospital.sh.cn [Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032 (China); Shanghai Institute of Medical Imaging, Shanghai 200032 (China)

    2017-01-15

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  17. Imaging features of automated breast volume scanner: Correlation with molecular subtypes of breast cancer

    International Nuclear Information System (INIS)

    Zheng, Feng-Yang; Lu, Qing; Huang, Bei-Jian; Xia, Han-Sheng; Yan, Li-Xia; Wang, Xi; Yuan, Wei; Wang, Wen-Ping

    2017-01-01

    Highlights: • ABVS imaging features have a strong correlation with breast cancer molecular subtypes. • Retraction phenomenon on the coronal planes was the most important predictor for Luminal A and Triple Negative subtypes. • ABVS expand the scope of ultrasound in identifying breast cancer molecular subtypes. - Abstract: Objectives: To investigate the correlation between the imaging features obtained by an automated breast volume scanner (ABVS) and molecular subtypes of breast cancer. Methods: We examined 303 malignant breast tumours by ABVS for specific imaging features and by immunohistochemical analysis to determine the molecular subtype. ABVS imaging features, including retraction phenomenon, shape, margins, echogenicity, post-acoustic features, echogenic halo, and calcifications were analysed by univariate and multivariate logistic regression analyses to determine the significant predictive factors of the molecular subtypes. Results: By univariate logistic regression analysis, the predictive factors of the Luminal-A subtype (n = 128) were retraction phenomenon (odds ratio [OR] = 10.188), post-acoustic shadowing (OR = 5.112), and echogenic halo (OR = 3.263, P < 0.001). The predictive factors of the Human-epidermal-growth-factor-receptor-2-amplified subtype (n = 39) were calcifications (OR = 6.210), absence of retraction phenomenon (OR = 4.375), non-mass lesions (OR = 4.286, P < 0.001), absence of echogenic halo (OR = 3.851, P = 0.035), and post-acoustic enhancement (OR = 3.641, P = 0.008). The predictors for the Triple-Negative subtype (n = 47) were absence of retraction phenomenon (OR = 5.884), post-acoustic enhancement (OR = 5.255, P < 0.001), absence of echogenic halo (OR = 4.138, P = 0.002), and absence of calcifications (OR = 3.363, P = 0.001). Predictors for the Luminal-B subtype (n = 89) had a relatively lower association (OR ≤ 2.328). By multivariate logistic regression analysis, retraction phenomenon was the strongest independent predictor for

  18. Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Elham Khanicheh

    Full Text Available BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1 with contrast enhanced ultrasound (CEU could assess treatment effects on endothelial phenotype in early atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day. At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM and control microbubbles (MB(Ctr. Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM in non-treated animals (MB(VCAM 2±0.3 vs MB(Ctr 0.7±0.2, p<0.01, but not in statin-treated animals (MB(VCAM 0.8±0.2 vs MB(Ctr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM signal. CONCLUSIONS: Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.

  19. Molecular imaging of myocardial infarction with Gadofluorine P – A combined magnetic resonance and mass spectrometry imaging approach

    Directory of Open Access Journals (Sweden)

    Fabian Lohöfer

    2018-04-01

    Full Text Available Background: Molecular MRI is becoming increasingly important for preclinical research. Validation of targeted gadolinium probes in tissue however has been cumbersome up to now. Novel methodology to assess gadolinium distribution in tissue after in vivo application is therefore needed. Purpose: To establish combined Magnetic Resonance Imaging (MRI and Mass Spectrometry Imaging (MSI for improved detection and quantification of Gadofluorine P deposition in scar formation and myocardial remodeling. Materials and methods: Animal studies were performed according to institutionally approved protocols. Myocardial infarction was induced by permanent ligation of the left ascending artery (LAD in C57BL/6J mice. MRI was performed at 7T at 1 week and 6 weeks after myocardial infarction. Gadofluorine P was used for dynamic T1 mapping of extracellular matrix synthesis during myocardial healing and compared to Gd-DTPA. After in vivo imaging contrast agent concentration as well as distribution in tissue were validated and quantified by spatially resolved Matrix-Assisted Laser Desorption Ionization (MALDI MSI and Laser Ablation – Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS imaging. Results: Both Gadofluorine P enhancement as well as local tissue content in the myocardial scar were highest at 15 minutes post injection. R1 values increased from 1 to 6 weeks after MI (1.62 s−1 vs 2.68 s−1, p = 0.059 paralleled by an increase in Gadofluorine P concentration in the infarct from 0.019 mM at 1 week to 0.028 mM at 6 weeks (p = 0.048, whereas Gd-DTPA enhancement showed no differences (3.95 s−1 vs 3.47 s−1, p = 0.701. MALDI-MSI results were corroborated by elemental LA-ICP-MS of Gadolinium in healthy and infarcted myocardium. Histology confirmed increased extracellular matrix synthesis at 6 weeks compared to 1 week. Conclusion: Adding quantitative MSI to MR imaging enables a quantitative validation of Gadofluorine P distribution in the heart

  20. Nonlinear microrheology and molecular imaging to map microscale deformations of entangled DNA networks

    Science.gov (United States)

    Wu, Tsai-Chin; Anderson, Rae

    We use active microrheology coupled to single-molecule fluorescence imaging to elucidate the microscale dynamics of entangled DNA. DNA naturally exists in a wide range of lengths and topologies, and is often confined in cell nucleui, forming highly concentrated and entangled biopolymer networks. Thus, DNA is the model polymer for understanding entangled polymer dynamics as well as the crowded environment of cells. These networks display complex viscoelastic properties that are not well understood, especially at the molecular-level and in response to nonlinear perturbations. Specifically, how microscopic stresses and strains propagate through entangled networks, and what molecular deformations lead to the network stress responses are unknown. To answer these important questions, we optically drive a microsphere through entangled DNA, perturbing the system far from equilibrium, while measuring the resistive force the DNA exerts on the bead during and after bead motion. We simultaneously image single fluorescent-labeled DNA molecules throughout the network to directly link the microscale stress response to molecular deformations. We characterize the deformation of the network from the molecular-level to the mesoscale, and map the stress propagation throughout the network. We further study the impact of DNA length (11 - 115 kbp) and topology (linear vs ring DNA) on deformation and propagation dynamics, exploring key nonlinear features such as tube dilation and power-law relaxation.

  1. Application of Machine Learning tools to recognition of molecular patterns in STM images

    Science.gov (United States)

    Maksov, Artem; Ziatdinov, Maxim; Fujii, Shintaro; Kiguchi, Manabu; Higashibayashi, Shuhei; Sakurai, Hidehiro; Kalinin, Sergei; Sumpter, Bobby

    The ability to utilize individual molecules and molecular assemblies as data storage elements has motivated scientist for years, concurrent with the continuous effort to shrink a size of data storage devices in microelectronics industry. One of the critical issues in this effort lies in being able to identify individual molecular assembly units (patterns), on a large scale in an automated fashion of complete information extraction. Here we present a novel method of applying machine learning techniques for extraction of positional and rotational information from scanning tunneling microscopy (STM) images of π-bowl sumanene molecules on gold. We use Markov Random Field (MRF) model to decode the polar rotational states for each molecule in a large scale STM image of molecular film. We further develop an algorithm that uses a convolutional Neural Network combined with MRF and input from density functional theory to classify molecules into different azimuthal rotational classes. Our results demonstrate that a molecular film is partitioned into distinctive azimuthal rotational domains consisting typically of 20-30 molecules. In each domain, the ``bowl-down'' molecules are generally surrounded by six nearest neighbor molecules in ``bowl-up'' configuration, and the resultant overall structure form a periodic lattice of rotational and polar states within each domain. Research was supported by the US Department of Energy.

  2. Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer.

    Science.gov (United States)

    Wu, Mingxiang; Ma, Jie

    2017-04-01

    Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  3. Conception and synthesis of the new cryptophane for the applications in xenon NMR molecular imaging

    International Nuclear Information System (INIS)

    Gao, Bo

    2016-01-01

    Among all the imaging techniques, magnetic resonance imaging (MRI) offers several advantages owing to its low invasiveness, its harmlessness and its spatial in-depth resolution but suffers from poor sensitivity. To address this issue, different strategies were proposed, including the utilization of hyper-polarizable species such as "1"2"9Xe. Xenon is an inert gas with a polarizable electronic cloud which leads to an extreme sensitivity to its chemical environment. Its capacity of being hyper-polarized makes it possible to obtain a significant gain of sensitivity. Nevertheless, xenon has no specificity to any biological target therefore it needs to be encapsulated and vectorized. Different molecular cages were proposed and we are particularly interested in cryptophane which is one of the best candidates for xenon encapsulation. In this context, the objective of this thesis is to design new cryptophanes which can be used as molecular platforms to construct novel "1"2"9Xe MRI biosensors usable for in vivo imaging. To meet this demand, these cryptophanes should be mono-functionalizable and enough soluble in water. In this thesis, the polyethylene glycol (PEG) group is used to improve the poor solubility of the hydrophobic molecular cage. And there is a systematic discussion of how to break the symmetry of cryptophanes and different strategies were attempted to synthesize mono-functionalized cryptophanes. As a result, several PEGylated mono-functionalized cryptophanes were obtained and their properties for encapsulating xenon were tested [fr

  4. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma.

    Directory of Open Access Journals (Sweden)

    Mathieu Salaün

    Full Text Available Several matrix metalloproteinases (MMPs are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging.To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma.K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors.In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27, but in none of the non-invasive (0/4 (p=0.001.MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer.

  5. MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

    Science.gov (United States)

    Salaün, Mathieu; Peng, Jing; Hensley, Harvey H.; Roder, Navid; Flieder, Douglas B.; Houlle-Crépin, Solène; Abramovici-Roels, Olivia; Sabourin, Jean-Christophe; Thiberville, Luc; Clapper, Margie L.

    2015-01-01

    Introduction Several matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging. Objective To characterize and monitor the activity of MMPs during the progression of lung adenocarcinoma. Methods K-rasLSL-G12D mice were imaged serially during the development of adenocarcinomas using fluorescence molecular tomography (FMT) and a probe specific for MMP-2, -3, -9 and -13. Lung tumors were identified using FMT and MRI co-registration, and the probe concentration in each tumor was assessed at each time-point. The expression of Mmp2, -3, -9, -13 was quantified by qRT-PCR using RNA isolated from microdissected tumor cells. Immunohistochemical staining of overexpressed MMPs in animals was assessed on human lung tumors. Results In mice, 7 adenomas and 5 adenocarcinomas showed an increase in fluorescent signal on successive FMT scans, starting between weeks 4 and 8. qRT-PCR assays revealed significant overexpression of only Mmp-13 in mice lung tumors. In human tumors, a high MMP-13 immunostaining index was found in tumor cells from invasive lesions (24/27), but in none of the non-invasive (0/4) (p=0.001). Conclusion MMP-13 is detected in early pulmonary invasive adenocarcinomas and may be a potential target for molecular imaging of lung cancer. PMID:26193700

  6. Development of a calibration protocol for quantitative imaging for molecular radiotherapy dosimetry

    International Nuclear Information System (INIS)

    Wevrett, J.; Fenwick, A.; Scuffham, J.; Nisbet, A.

    2017-01-01

    Within the field of molecular radiotherapy, there is a significant need for standardisation in dosimetry, in both quantitative imaging and dosimetry calculations. Currently, there are a wide range of techniques used by different clinical centres and as a result there is no means to compare patient doses between centres. To help address this need, a 3 year project was funded by the European Metrology Research Programme, and a number of clinical centres were involved in the project. One of the required outcomes of the project was to develop a calibration protocol for three dimensional quantitative imaging of volumes of interest. Two radionuclides were selected as being of particular interest: iodine-131 ( 131 I, used to treat thyroid disorders) and lutetium-177 ( 177 Lu, used to treat neuroendocrine tumours). A small volume of activity within a scatter medium (water), representing a lesion within a patient body, was chosen as the calibration method. To ensure ease of use in clinical centres, an “off-the-shelf” solution was proposed – to avoid the need for in-house manufacturing. The BIODEX elliptical Jaszczak phantom and 16 ml fillable sphere were selected. The protocol was developed for use on SPECT/CT gamma cameras only, where the CT dataset would be used to correct the imaging data for attenuation of the emitted photons within the phantom. The protocol corrects for scatter of emitted photons using the triple energy window correction technique utilised by most clinical systems. A number of clinical systems were tested in the development of this protocol, covering the major manufacturers of gamma camera generally used in Europe. Initial imaging was performed with 131 I and 177 Lu at a number of clinical centres, but due to time constraints in the project, some acquisitions were performed with 177 Lu only. The protocol is relatively simplistic, and does not account for the effects of dead-time in high activity patients, the presence of background activity

  7. Low molecular weight dextran provides similar optical coherence tomography coronary imaging compared to radiographic contrast media.

    Science.gov (United States)

    Frick, Kyle; Michael, Tesfaldet T; Alomar, Mohammed; Mohammed, Atif; Rangan, Bavana V; Abdullah, Shuaib; Grodin, Jerrold; Hastings, Jeffrey L; Banerjee, Subhash; Brilakis, Emmanouil S

    2014-11-01

    Optical coherence tomography (OCT) coronary imaging requires displacement of red blood cells from the vessel lumen. This is usually accomplished using radiographic contrast. Low molecular weight dextran has low cost and is safe in low volumes. In the present study, we compared dextran with contrast for coronary OCT imaging. Fifty-one vessels in 26 patients were sequentially imaged using manual injection of radiographic contrast (iodixanol) and dextran. OCT images were analyzed at 1 mm intervals to determine the image clarity (defined as a visible lumen border > 270°) and to measure the lumen area and lumen diameter. To correct for the refractive index of dextran, the dextran area measurements were multiplied by 1.117 and the dextran length measurements were multiplied by 1.057. A total of 3,418 cross-sections (1,709 with contrast and 1,709 with dextran) were analyzed. There were no complications related to OCT imaging or to contrast or dextran administration. Clear image segments were observed in 97.0% vs. 96.7% of the cross-sections obtained with contrast and dextran, respectively (P = 0.45). The mean lumen areas were also similar: 6.69 ± 1.95 mm(2) with iodixanol vs. 7.06 ± 2.06 mm(2) with dextran (correlation coefficient 0.984). The image quality and measurements during OCT image acquisition are similar for dextran and contrast. Dextran could be used instead of contrast for OCT imaging, especially in patients in whom contrast load minimization is desired. © 2013 Wiley Periodicals, Inc.

  8. The pivotal role of multimodality reporter sensors in drug discovery: from cell based assays to real time molecular imaging.

    Science.gov (United States)

    Ray, Pritha

    2011-04-01

    Development and marketing of new drugs require stringent validation that are expensive and time consuming. Non-invasive multimodality molecular imaging using reporter genes holds great potential to expedite these processes at reduced cost. New generations of smarter molecular imaging strategies such as Split reporter, Bioluminescence resonance energy transfer, Multimodality fusion reporter technologies will further assist to streamline and shorten the drug discovery and developmental process. This review illustrates the importance and potential of molecular imaging using multimodality reporter genes in drug development at preclinical phases.

  9. Torsional tapping atomic force microscopy for molecular resolution imaging of soft matter

    Science.gov (United States)

    Hobbs, Jamie; Mullin, Nic

    2012-02-01

    Despite considerable advances in image resolution on challenging, soft systems, a method for obtaining molecular resolution on `real' samples with significant surface roughness has remained elusive. Here we will show that a relatively new technique, torsional tapping AFM (TTAFM), is capable of imaging with resolution down to 3.7 Angrstrom on the surface of `bulk' polymer films [1]. In TTAFM T-shaped cantilevers are driven into torsional oscillation. As the tip is offset from the rotation axis this provides a tapping motion. Due to the high frequency and Q of the oscillation and relatively small increase in spring constant, improved cantilever dynamics and force sensitivity are obtained. As the tip offset from the torsional axis is relatively small (typically 25 microns), the optical lever sensitivity is considerably improved compared to flexural oscillation. Combined these give a reduction in noise floor by a factor of 12 just by changing the cantilever geometry. The ensuing low noise allows the use of ultra-sharp `whisker' tips with minimal blunting. As the cantilevers remain soft in the flexural axis, the force when imaging with error is also reduced, further protecting the tip. We will show that this combination allows routine imaging of the molecular structure of semicrystalline polymer films, including chain folds, loose loops and tie-chains in polyethylene, and the helical conformation of polypropylene within the crystal, using a standard, commercial AFM. [4pt] [1] N Mullin, JK Hobbs, PRL 107, 197801 (2011)

  10. Development of Antibody–Drug Conjugates Using DDS and Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Masahiro Yasunaga

    2017-09-01

    Full Text Available Antibody-drug conjugate (ADC, as a next generation of antibody therapeutics, is a combination of an antibody and a drug connected via a specialized linker. ADC has four action steps: systemic circulation, the enhanced permeability and retention (EPR effect, penetration within the tumor tissue, and action on cells, such as through drug delivery system (DDS drugs. An antibody with a size of about 10 nm has the same capacity for passive targeting as some DDS carriers, depending on the EPR effect. In addition, some antibodies are capable of active targeting. A linker is stable in the bloodstream but should release drugs efficiently in the tumor cells or their microenvironment. Thus, the linker technology is actually a typical controlled release technology in DDS. Here, we focused on molecular imaging. Fluorescent and positron emission tomography (PET imaging is useful for the visualization and evaluation of antibody delivery in terms of passive and active targeting in the systemic circulation and in tumors. To evaluate the controlled release of the ADC in the targeted area, a mass spectrometry imaging (MSI with a mass microscope, to visualize the drug released from ADC, was used. As a result, we succeeded in confirming the significant anti-tumor activity of anti-fibrin, or anti-tissue factor-ADC, in preclinical settings by using DDS and molecular imaging.

  11. Residualization Rates of Near Infrared Dyes for the Rational Design of Molecular Imaging Agents

    Science.gov (United States)

    Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M.

    2016-01-01

    Purpose Near infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. Procedures In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, BODIPY, and oxazine/thiazine/carbopyronin). Results We identify residualizing (half-life > 24 hrs) and non-residualizing dyes (half-life < 24 hrs) in both the far red (~650-680 nm) and near infrared (~740-800 nm) regions. Conclusions This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design. PMID:25869081

  12. Development of a compact scintillator-based high-resolution Compton camera for molecular imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kishimoto, A., E-mail: daphne3h-aya@ruri.waseda.jp [Research Institute for Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku, Tokyo (Japan); Kataoka, J.; Koide, A.; Sueoka, K.; Iwamoto, Y.; Taya, T. [Research Institute for Science and Engineering, Waseda University, 3-4-1 Ohkubo, Shinjuku, Tokyo (Japan); Ohsuka, S. [Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita-ku, Hamamatsu, Shizuoka (Japan)

    2017-02-11

    The Compton camera, which shows gamma-ray distribution utilizing the kinematics of Compton scattering, is a promising detector capable of imaging across a wide range of energy. In this study, we aim to construct a small-animal molecular imaging system in a wide energy range by using the Compton camera. We developed a compact medical Compton camera based on a Ce-doped Gd{sub 3}Al{sub 2}Ga{sub 3}O{sub 12} (Ce:GAGG) scintillator and multi-pixel photon counter (MPPC). A basic performance confirmed that for 662 keV, the typical energy resolution was 7.4 % (FWHM) and the angular resolution was 4.5° (FWHM). We then used the medical Compton camera to conduct imaging experiments based on a 3-D imaging reconstruction algorithm using the multi-angle data acquisition method. The result confirmed that for a {sup 137}Cs point source at a distance of 4 cm, the image had a spatial resolution of 3.1 mm (FWHM). Furthermore, we succeeded in producing 3-D multi-color image of different simultaneous energy sources ({sup 22}Na [511 keV], {sup 137}Cs [662 keV], and {sup 54}Mn [834 keV]).

  13. Drift correction for single-molecule imaging by molecular constraint field, a distance minimum metric

    International Nuclear Information System (INIS)

    Han, Renmin; Wang, Liansan; Xu, Fan; Zhang, Yongdeng; Zhang, Mingshu; Liu, Zhiyong; Ren, Fei; Zhang, Fa

    2015-01-01

    The recent developments of far-field optical microscopy (single molecule imaging techniques) have overcome the diffraction barrier of light and improve image resolution by a factor of ten compared with conventional light microscopy. These techniques utilize the stochastic switching of probe molecules to overcome the diffraction limit and determine the precise localizations of molecules, which often requires a long image acquisition time. However, long acquisition times increase the risk of sample drift. In the case of high resolution microscopy, sample drift would decrease the image resolution. In this paper, we propose a novel metric based on the distance between molecules to solve the drift correction. The proposed metric directly uses the position information of molecules to estimate the frame drift. We also designed an algorithm to implement the metric for the general application of drift correction. There are two advantages of our method: First, because our method does not require space binning of positions of molecules but directly operates on the positions, it is more natural for single molecule imaging techniques. Second, our method can estimate drift with a small number of positions in each temporal bin, which may extend its potential application. The effectiveness of our method has been demonstrated by both simulated data and experiments on single molecular images

  14. Optimizing ultrasound molecular imaging of secreted frizzled related protein 2 expression in angiosarcoma.

    Directory of Open Access Journals (Sweden)

    James K Tsuruta

    Full Text Available Secreted frizzled related protein 2 (SFRP2 is a tumor endothelial marker expressed in angiosarcoma. Previously, we showed ultrasound molecular imaging with SFRP2-targeted contrast increased average video pixel intensity (VI of angiosarcoma vessels by 2.2 ± 0.6 VI versus streptavidin contrast. We hypothesized that redesigning our contrast agents would increase imaging performance. Improved molecular imaging reagents were created by combining NeutrAvidin™-functionalized microbubbles with biotinylated SFRP2 or IgY control antibodies. When angiosarcoma tumors in nude mice reached 8 mm, time-intensity, antibody loading, and microbubble dose experiments optimized molecular imaging. 10 minutes after injection, the control-subtracted time-intensity curve (TIC for SFRP2-targeted contrast reached a maximum, after subtracting the contribution of free-flowing contrast. SFRP2 antibody-targeted VI was greater when contrast was formulated with 10-fold molar excess of maleimide-activated NeutrAvidin™ versus 3-fold (4.5 ± 0.18 vs. 0.32 ± 0.15, VI ± SEM, 5 x 106 dose, p < 0.001. Tumor vasculature returned greater average video pixel intensity using 5 x 107 versus 5 x 106 microbubbles (21.2 ± 2.5 vs. 4.5 ± 0.18, p = 0.0011. Specificity for tumor vasculature was confirmed by low VI for SFRP2-targeted, and control contrast in peri-tumoral vasculature (3.2 ± 0.52 vs. 1.6 ± 0.71, p = 0.92. After optimization, average video pixel intensity of tumor vasculature was 14.2 ± 3.0 VI units higher with SFRP2-targeted contrast versus IgY-targeted control (22.1 ± 2.5 vs. 7.9 ± 1.6, p < 0.001. After log decompression, 14.2 ΔVI was equal to ~70% higher signal, in arbitray acoustic units (AU, for SFRP2 versus IgY. This provided ~18- fold higher acoustic signal enhancement than provided previously by 2.2 ΔVI. Basing our targeted contrast on NeutrAvidin™-functionalized microbubbles, using IgY antibodies for our control contrast, and optimizing our imaging protocol

  15. Iron oxide nanoparticle-micelles (ION-micelles for sensitive (molecular magnetic particle imaging and magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Lucas W E Starmans

    Full Text Available BACKGROUND: Iron oxide nanoparticles (IONs are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. METHODS AND RESULTS: IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles. Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles bound to blood clots. CONCLUSIONS: The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular MPI and warrants further investigation of the Fib

  16. A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism

    International Nuclear Information System (INIS)

    Niccolini, Flavia; Politis, Marios

    2016-01-01

    To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism. MEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded. Seventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABA A receptors in PSP, MSA, and CBS patients were included in this review. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques to distinguish between parkinsonian syndromes. Microglial activation has been found in all forms of atypical parkinsonism and reflects the known distribution of neuropathologic changes in these disorders. Opioid receptors are decreased in the striatum of PSP and MSA patients. Subcortical cholinergic dysfunction was more severe in MSA and PSP than Parkinson's disease patients although no significant changes in cortical cholinergic receptors were seen in PSP with cognitive impairment. GABA A receptors were decreased in metabolically affected cortical and subcortical regions in PSP patients. PET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments. (orig.)

  17. The effects of ecstasy on neurotransmitter systems: a review on the findings of molecular imaging studies.

    Science.gov (United States)

    Vegting, Yosta; Reneman, Liesbeth; Booij, Jan

    2016-10-01

    Ecstasy is a commonly used psychoactive drug with 3,4-methylenedioxymethamphetamine (MDMA) as the main content. Importantly, it has been suggested that use of MDMA may be neurotoxic particularly for serotonergic (5-hydroxytryptamine (5-HT)) neurons. In the past decades, several molecular imaging studies examined directly in vivo the effects of ecstasy/MDMA on neurotransmitter systems. The objective of the present study is to review the effects of ecstasy/MDMA on neurotransmitter systems as assessed by molecular imaging studies in small animals, non-human primates and humans. A search in PubMed was performed. Eighty-eight articles were found on which inclusion and exclusion criteria were applied. Thirty-three studies met the inclusion criteria; all were focused on the 5-HT or dopamine (DA) system. Importantly, 9 out of 11 of the animal studies that examined the effects of MDMA on 5-HT transporter (SERT) availability showed a significant loss of binding potential. In human studies, this was the case for 14 out of 16 studies, particularly in heavy users. In abstinent users, significant recovery of SERT binding was found over time. Most imaging studies in humans that focused on the DA system did not find any significant effect of ecstasy/MDMA use. Preclinical and clinical molecular imaging studies on the effects of ecstasy/MDMA use/administration on neurotransmitter systems show quite consistent alterations of the 5-HT system. Particularly, in human studies, loss of SERT binding was observed in heavy ecstasy users, which might reflect 5-HT neurotoxicity, although alternative explanations (e.g. down-regulation of the SERT) cannot be excluded.

  18. A systematic review of lessons learned from PET molecular imaging research in atypical parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

    Niccolini, Flavia; Politis, Marios [Neurodegeneration Imaging Group, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King' s College London, London (United Kingdom)

    2016-11-15

    To systematically review the previous studies and current status of positron emission tomography (PET) molecular imaging research in atypical parkinsonism. MEDLINE, ISI Web of Science, Cochrane Library, and Scopus electronic databases were searched for articles published until 29th March 2016 and included brain PET studies in progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). Only articles published in English and in peer-reviewed journals were included in this review. Case-reports, reviews, and non-human studies were excluded. Seventy-seven PET studies investigating the dopaminergic system, glucose metabolism, microglial activation, hyperphosphorilated tau, opioid receptors, the cholinergic system, and GABA{sub A} receptors in PSP, MSA, and CBS patients were included in this review. Disease-specific patterns of reduced glucose metabolism have shown higher accuracy than dopaminergic imaging techniques to distinguish between parkinsonian syndromes. Microglial activation has been found in all forms of atypical parkinsonism and reflects the known distribution of neuropathologic changes in these disorders. Opioid receptors are decreased in the striatum of PSP and MSA patients. Subcortical cholinergic dysfunction was more severe in MSA and PSP than Parkinson's disease patients although no significant changes in cortical cholinergic receptors were seen in PSP with cognitive impairment. GABA{sub A} receptors were decreased in metabolically affected cortical and subcortical regions in PSP patients. PET molecular imaging has provided valuable insight for understanding the mechanisms underlying atypical parkinsonism. Changes at a molecular level occur early in the course of these neurodegenerative diseases and PET imaging provides the means to aid differential diagnosis, monitor disease progression, identify of novel targets for pharmacotherapy, and monitor response to new treatments. (orig.)

  19. Radical inactivation of a biological sulphydryl molecule

    International Nuclear Information System (INIS)

    Lin, W.S.; Lal, M.; Gaucher, G.M.; Armstrong, D.A.

    1977-01-01

    Reactive species produced from the free radical-induced chain oxidation of low molecular weight sulphydryl-containing molecules in aerated solutions deactivate the sulphydryl-containing enzyme papain, forming both reparable mixed disulphides and non-reparable products. This inactivation is highly efficient for penicillamine and glutathione, but almost negligible with cysteine, which is a protector of papain for [cysteine] / [papain] >= 5 under all conditions used. In the case of glutathione, superoxide dismutase caused only a small reduction in the inactivation and peroxide yields were small, implying that the deactivating species are not .O 2 - but RSOO. radicals or products from them. For penicillamine, however, dimutase was highly effective and the peroxide yields were relatively large, demonstrating that .O 2 - or a radical with similar capabilities for forming H 2 O 2 and being deactivated by dismutase was involved. Although in the presence of dismutase penicillamine is a better protector of non-reparable papain inactivation than glutathione, it suffers from a deficiency in that the papain-penicillamine mixed disulphide, which is always formed, cannot be repaired by spontaneous reaction with RSH molecules. (author)

  20. Pathogen inactivation techniques.

    Science.gov (United States)

    Pelletier, J P R; Transue, S; Snyder, E L

    2006-01-01

    The desire to rid the blood supply of pathogens of all types has led to the development of many technologies aimed at the same goal--eradication of the pathogen(s) without harming the blood cells or generating toxic chemical agents. This is a very ambitious goal, and one that has yet to be achieved. One approach is to shun the 'one size fits all' concept and to target pathogen-reduction agents at the Individual component types. This permits the development of technologies that might be compatible with, for example, plasma products but that would be cytocidal and thus incompatible with platelet concentrates or red blood cell units. The technologies to be discussed include solvent detergent and methylene blue treatments--designed to inactivate plasma components and derivatives; psoralens (S-59--amotosalen) designed to pathogen-reduce units of platelets; and two products aimed at red blood cells, S-303 (a Frale--frangible anchor-linker effector compound) and Inactine (a binary ethyleneimine). A final pathogen-reduction material that might actually allow one material to inactivate all three blood components--riboflavin (vitamin B2)--is also under development. The sites of action of the amotosalen (S-59), the S-303 Frale, Inactine, and riboflavin are all localized in the nucleic acid part of the pathogen. Solvent detergent materials act by dissolving the plasma envelope, thus compromising the integrity of the pathogen membrane and rendering it non-infectious. By disrupting the pathogen's ability to replicate or survive, its infectivity is removed. The degree to which bacteria and viruses are affected by a particular pathogen-reducing technology relates to its Gram-positive or Gram-negative status, to the sporulation characteristics for bacteria, and the presence of lipid or protein envelopes for viruses. Concerns related to photoproducts and other breakdown products of these technologies remain, and the toxicology of pathogen-reduction treatments is a major ongoing area

  1. Targeting Phosphatidylserine with a 64Cu-Labeled Peptide for Molecular Imaging of Apoptosis.

    Science.gov (United States)

    Perreault, Amanda; Richter, Susan; Bergman, Cody; Wuest, Melinda; Wuest, Frank

    2016-10-03

    Molecular imaging of programmed cell death (apoptosis) in vivo is an innovative strategy for early assessment of treatment response and treatment efficacy in cancer patients. Externalization of phosphatidylserine (PS) to the cell membrane surface of dying cells makes this phospholipid an attractive molecular target for the development of apoptosis imaging probes. In this study, we have radiolabeled PS-binding 14-mer peptide FNFRLKAGAKIRFG (PSBP-6) with positron-emitter copper-64 ( 64 Cu) for PET imaging of apoptosis. Peptide PSBP-6 was conjugated with radiometal chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through an aminovaleric acid (Ava) linker for subsequent radiolabeling with 64 Cu to prepare radiotracer 64 Cu-NOTA-Ava-PSBP-6. PS-binding potencies of PSBP-6, NOTA-Ava-PSBP-6, and nat Cu-NOTA-Ava-PSBP-6 were determined in a competitive radiometric PS-binding assay. Radiotracer 64 Cu-NOTA-Ava-PSBP-6 was studied in camptothecin-induced apoptotic EL4 mouse lymphoma cells and in a murine EL4 tumor model of apoptosis using dynamic PET imaging. Peptide PSBP-6 was also conjugated via an Ava linker with fluorescein isothiocyanate (FITC). FITC-Ava-PSBP-6 was evaluated in flow cytometry and fluorescence confocal microscopy experiments. Radiopeptide 64 Cu-NOTA-Ava-PSBP-6 was synthesized in high radiochemical yields of >95%. The IC 50 values for PS-binding potency of PSBP-6, NOTA-Ava-PSBP-6, and nat Cu-NOTA-PSBP-6 were 600 μM, 30 μM, and 23 μM, respectively. A competitive radiometric cell binding assay confirmed binding of 64 Cu-NOTA-Ava-PSBP-6 to camptothecin-induced apoptotic EL4 cells in a Ca 2+ -independent manner. PET imaging studies demonstrated significantly higher uptake of 64 Cu-NOTA-Ava-PSBP-6 in apoptotic EL4 tumors (SUV 5min 0.95 ± 0.04) compared to control tumors (SUV 5min 0.74 ± 0.03). Flow cytometry studies showed significantly higher binding of FITC-Ava-PSBP-6 to EL4 cells treated with camptothecin compared to untreated cells

  2. Free radical inactivation of trypsin

    International Nuclear Information System (INIS)

    Cudina, Ivana; Jovanovic, S.V.

    1988-01-01

    Reactivities of free radical oxidants, radical OH, Br2-anion radical and Cl 3 COO radical and a reductant, CO2-anion radical, with trypsin and reactive protein components were determined by pulse radiolysis of aqueous solutions at pH 7, 20 0 C. Highly reactive free radicals, radical OH, Br2-anion radical and CO2-anion radical, react with trypsin at diffusion controlled rates. Moderately reactive trichloroperoxy radical, k(Cl 3 COO radical + trypsin) preferentially oxidizes histidine residues. The efficiency of inactivation of trypsin by free radicals is inversely proportional to their reactivity. The yields of inactivation of trypsin by radical OH, Br2-anion radical and CO2-anion radical are low, G(inactivation) = 0.6-0.8, which corresponds to ∼ 10% of the initially produced radicals. In contrast, Cl 3 COO radical inactivates trypsin with ∼ 50% efficiency, i.e. G(inactivation) = 3.2. (author)

  3. Magnetosomes used as biogenic MRI contrast agent for molecular imaging of glioblastoma model

    International Nuclear Information System (INIS)

    Boucher, Marianne

    2016-01-01

    This work takes place in the context of molecular imaging, which aims at tailoring medical treatments and therapies to the individual context by revealing molecular or cellular phenomenon of medical interest in the less invasive manner. In particular, it can be achieved with MRI molecular imaging using engineered iron-oxide contrast agent.This PhD thesis focuses on the study of a new class of iron-oxide contrast agent for high field MRI. Indeed, magnetosomes are natural iron-oxide vesicles produced by magneto-tactic bacteria. These bacteria synthesized such magnetic vesicles and ordered them like a nano-compass in order to facilitate their navigation in sediments. This explains why magnetosomes are awarded with tremendous magnetic properties: around 50 nm, mono-crystalline, single magnetic domain and high saturation magnetization. Furthermore, a wide variety of bacterial strains exist in nature and size and shape of magnetosomes are highly stable within strain and can be very different between strains. Finally, magnetosomes are naturally coated with a bi-lipidic membrane whose content is genetically determined. Lately, researchers have unravelled magnetosomes membrane protein contents, opening the way to create functionalized magnetosomes thanks to fusion of the gene coding for a protein of interest with the gene coding for an abundant protein at magnetosomes membrane.A new alternative path using living organisms to tackle the production of engineered high efficiency molecular imaging probes have been investigated with magneto-tactic bacteria in this PhD. The production and engineering of magnetosomes have been carried out by our partner, the Laboratoire de Bio-energetique Cellulaire (LBC, CEA Cadarache), and will be presented and discussed. We then characterized magnetosomes as contrast agent for high field MRI. We showed they present very promising contrasting properties in vitro, and assessed this observation in vivo by establishing they can be used as efficient

  4. Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations.

    Science.gov (United States)

    Tronel, Claire; Largeau, Bérenger; Santiago Ribeiro, Maria Joao; Guilloteau, Denis; Dupont, Anne-Claire; Arlicot, Nicolas

    2017-04-11

    Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest. We overview alternative molecular targets, for which dedicated radiopharmaceuticals have been proposed, including receptors (purinergic receptors P2X7, cannabinoid receptors, α7 and α4β2 nicotinic acetylcholine receptors, adenosine 2A receptor, folate receptor β) and enzymes (cyclooxygenase, nitric oxide synthase, matrix metalloproteinase, β-glucuronidase, and enzymes of the kynurenine pathway), with a particular focus on their respective contribution for the understanding of microglial involvement in neurodegenerative diseases. We discuss opportunities for these potential molecular targets for PET imaging regarding their selectivity for microglia expression and polarization, in relation to the mechanisms by which microglia actively participate in both toxic and neuroprotective actions in brain diseases, and then take into account current clinicians' expectations.

  5. Molecular imaging of cannabis leaf tissue with MeV-SIMS method

    Science.gov (United States)

    Jenčič, Boštjan; Jeromel, Luka; Ogrinc Potočnik, Nina; Vogel-Mikuš, Katarina; Kovačec, Eva; Regvar, Marjana; Siketić, Zdravko; Vavpetič, Primož; Rupnik, Zdravko; Bučar, Klemen; Kelemen, Mitja; Kovač, Janez; Pelicon, Primož

    2016-03-01

    To broaden our analytical capabilities with molecular imaging in addition to the existing elemental imaging with micro-PIXE, a linear Time-Of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry (MeV-SIMS) was constructed and added to the existing nuclear microprobe at the Jožef Stefan Institute. We measured absolute molecular yields and damage cross-section of reference materials, without significant alteration of the fragile biological samples during the duration of measurements in the mapping mode. We explored the analytical capability of the MeV-SIMS technique for chemical mapping of the plant tissue of medicinal cannabis leaves. A series of hand-cut plant tissue slices were prepared by standard shock-freezing and freeze-drying protocol and deposited on the Si wafer. We show the measured MeV-SIMS spectra showing a series of peaks in the mass area of cannabinoids, as well as their corresponding maps. The indicated molecular distributions at masses of 345.5 u and 359.4 u may be attributed to the protonated THCA and THCA-C4 acids, and show enhancement in the areas with opened trichome morphology.

  6. Molecular imaging of cannabis leaf tissue with MeV-SIMS method

    Energy Technology Data Exchange (ETDEWEB)

    Jenčič, Boštjan, E-mail: bostjan.jencic@ijs.si [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); Jeromel, Luka [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); Ogrinc Potočnik, Nina [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); M4I, Maastricht University, Peter Debijelaan 25A, 6229 HX Maastricht (Netherlands); Vogel-Mikuš, Katarina [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); University of Ljubljana, Biotechnical Faculty, Dept. of Biology, Večna pot 11, SI-1000 Ljubljana (Slovenia); Kovačec, Eva; Regvar, Marjana [University of Ljubljana, Biotechnical Faculty, Dept. of Biology, Večna pot 11, SI-1000 Ljubljana (Slovenia); Siketić, Zdravko [Ruđer Bošković Institute, P.O. Box 180, 10000 Zagreb (Croatia); Vavpetič, Primož; Rupnik, Zdravko; Bučar, Klemen; Kelemen, Mitja; Kovač, Janez; Pelicon, Primož [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia)

    2016-03-15

    To broaden our analytical capabilities with molecular imaging in addition to the existing elemental imaging with micro-PIXE, a linear Time-Of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry (MeV-SIMS) was constructed and added to the existing nuclear microprobe at the Jožef Stefan Institute. We measured absolute molecular yields and damage cross-section of reference materials, without significant alteration of the fragile biological samples during the duration of measurements in the mapping mode. We explored the analytical capability of the MeV-SIMS technique for chemical mapping of the plant tissue of medicinal cannabis leaves. A series of hand-cut plant tissue slices were prepared by standard shock-freezing and freeze-drying protocol and deposited on the Si wafer. We show the measured MeV-SIMS spectra showing a series of peaks in the mass area of cannabinoids, as well as their corresponding maps. The indicated molecular distributions at masses of 345.5 u and 359.4 u may be attributed to the protonated THCA and THCA-C4 acids, and show enhancement in the areas with opened trichome morphology.

  7. Molecular imaging of cannabis leaf tissue with MeV-SIMS method

    International Nuclear Information System (INIS)

    Jenčič, Boštjan; Jeromel, Luka; Ogrinc Potočnik, Nina; Vogel-Mikuš, Katarina; Kovačec, Eva; Regvar, Marjana; Siketić, Zdravko; Vavpetič, Primož; Rupnik, Zdravko; Bučar, Klemen; Kelemen, Mitja; Kovač, Janez; Pelicon, Primož

    2016-01-01

    To broaden our analytical capabilities with molecular imaging in addition to the existing elemental imaging with micro-PIXE, a linear Time-Of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry (MeV-SIMS) was constructed and added to the existing nuclear microprobe at the Jožef Stefan Institute. We measured absolute molecular yields and damage cross-section of reference materials, without significant alteration of the fragile biological samples during the duration of measurements in the mapping mode. We explored the analytical capability of the MeV-SIMS technique for chemical mapping of the plant tissue of medicinal cannabis leaves. A series of hand-cut plant tissue slices were prepared by standard shock-freezing and freeze-drying protocol and deposited on the Si wafer. We show the measured MeV-SIMS spectra showing a series of peaks in the mass area of cannabinoids, as well as their corresponding maps. The indicated molecular distributions at masses of 345.5 u and 359.4 u may be attributed to the protonated THCA and THCA-C4 acids, and show enhancement in the areas with opened trichome morphology.

  8. Light at the end of the tunnel in radiation therapy: molecular imaging in radiation research

    International Nuclear Information System (INIS)

    Rao, V.L. Papineni

    2013-01-01

    Accurate dose delivery to malignant tissue in radiotherapy is quite important for enhancing the treatment efficacy while minimizing morbidity of surrounding normal tissues. Advances in therapeutic strategies and diagnosis technologies along with our understanding of the biology of tumor response to radiation therapy have paved way to allow nearly 60% of current cancer patients to be treated with Radiation Therapy. The confluence of molecular imaging and nanotechnology fields are bridging physics and medicine and are quickly making strides in opening new avenues and therapeutic strategies that complement radiation therapy - with a distinct footprint in immunotherapy, adoptive cell therapy, and targeted chemotherapy. Incorporating optical imaging in radiation therapy in my laboratory, we demonstrated that molecular probes can monitor radiation-induced physiological changes at the target and off-target sites using in vivo molecular imaging approaches. Further we show endogenous bioluminescence resulting from whole body irradiation, which is distinct from the Cherenkov radiation. Mice without anesthesia were held in ventilated mouse pie cage and subjected to 5 Gy X-ray irradiation using commercially available X-RAD320 irradiator (1 Gy/min; F2 beam hardening filter 1.5 mm Al, 0.25 mm Cu, 0.75 mm Sn,). The endogenous bioluminescence from the subjects was captured using cooled CCD camera. Significant increase (up to 100 fold) in the amounts of photons released as bioluminescence was detected during 5 min capture from the mice subjected to irradiation compared to that of the control. To determine the early inflammatory response, the reactive oxygen species (ROS) activity was monitored using L-012 (8-amino-5-chloro-7-phenylpyridol (3,4-d)pyridazine-1,4(2H,3H) dione), a chemiluminescence reporter. L-012 was administered (i.p) after 15 min of irradiation. Chemiluminescence resulting from the irradiation induced ROS activity, possible through the action of the

  9. Inactivation of Microorganisms

    Science.gov (United States)

    Alzamora, Stella Maris; Guerrero, Sandra N.; Schenk, Marcela; Raffellini, Silvia; López-Malo, Aurelio

    Minimal processing techniques for food preservation allow better retention of product flavor, texture, color, and nutrient content than comparable conventional treatments. A wide range of novel alternative physical factors have been intensely investigated in the last two decades. These physical factors can cause inactivation of microorganisms at ambient or sublethal temperatures (e.g., high hydrostatic pressure, pulsed electric fields, ultrasound, pulsed light, and ultraviolet light). These technologies have been reported to reduce microorganism population in foods while avoiding the deleterious effects of severe heating on quality. Among technologies, high-energy ultrasound (i.e., intensities higher than 1 W/cm2, frequencies between 18 and 100 kHz) has attracted considerable interest for food preservation applications (Mason et al., 1996; Povey and Mason, 1998).

  10. Mean inactivation dose (D)

    International Nuclear Information System (INIS)

    Vijayakumar, S.; Ng, T.C.; Raudkivi, U.; Meaney, T.J.

    1990-01-01

    By predicting treatment outcome to radiotherapy from in vitro radiobiological parameters, not only individual patient treatments can be tailored, but also new promising treatment protocols can be tried in patients in whom unfavorable outcome is predicted. In this respect, choosing the right parameter can be very important. Unlike D 0 and N which provide information of the distal part of the survival curve, mean inactivation dose (D) estimates overall radiosensitivity. However, the parameters reflecting the response at the clinically relevant low-dose region are neglected in the literature. In a literature survey of 98 papers in which survival curves or D 0 /N were used, only in 2 D was used. In 21 papers the D 0 /n values were important in drawing conclusions. By calculating D in 3 of these 21 papers, we show that the conclusion drawn may be altered with the use of D. The importance of ''low-dose-region-parameters'' is reviewed. (orig.)

  11. Impairment of retrograde neuronal transport in oxaliplatin-induced neuropathy demonstrated by molecular imaging.

    Directory of Open Access Journals (Sweden)

    Dawid Schellingerhout

    Full Text Available BACKGROUND AND PURPOSE: The purpose of our study was to utilize a molecular imaging technology based on the retrograde axonal transport mechanism (neurography, to determine if oxaliplatin-induced neurotoxicity affects retrograde axonal transport in an animal model. MATERIALS AND METHODS: Mice (n = 8/group were injected with a cumulative dose of 30 mg/kg oxaliplatin (sufficient to induce neurotoxicity or dextrose control injections. Intramuscular injections of Tetanus Toxin C-fragment (TTc labeled with Alexa 790 fluorescent dye were done (15 ug/20 uL in the left calf muscles, and in vivo fluorescent imaging performed (0-60 min at baseline, and then weekly for 5 weeks, followed by 2-weekly imaging out to 9 weeks. Tissues were harvested for immunohistochemical analysis. RESULTS: With sham treatment, TTc transport causes fluorescent signal intensity over the thoracic spine to increase from 0 to 60 minutes after injection. On average, fluorescence signal increased 722%+/-117% (Mean+/-SD from 0 to 60 minutes. Oxaliplatin treated animals had comparable transport at baseline (787%+/-140%, but transport rapidly decreased through the course of the study, falling to 363%+/-88%, 269%+/-96%, 191%+/-58%, 121%+/-39%, 75%+/-21% with each successive week and stabilizing around 57% (+/-15% at 7 weeks. Statistically significant divergence occurred at approximately 3 weeks (p≤0.05, linear mixed-effects regression model. Quantitative immuno-fluorescence histology with a constant cutoff threshold showed reduced TTc in the spinal cord at 7 weeks for treated animals versus controls (5.2 Arbitrary Units +/-0.52 vs 7.1 AU +/-1.38, p0.56, T-test. CONCLUSION: We show-for the first time to our knowledge-that neurographic in vivo molecular imaging can demonstrate imaging changes in a model of oxaliplatin-induced neuropathy. Impaired retrograde neural transport is suggested to be an important part of the pathophysiology of oxaliplatin-induced neuropathy.

  12. Noninvasive imaging of multiple myeloma using near infrared fluorescent molecular probe

    Science.gov (United States)

    Hathi, Deep; Zhou, Haiying; Bollerman-Nowlis, Alex; Shokeen, Monica; Akers, Walter J.

    2016-03-01

    Multiple myeloma is a plasma cell malignancy characterized by monoclonal gammopathy and osteolytic bone lesions. Multiple myeloma is most commonly diagnosed in late disease stages, presenting with pathologic fracture. Early diagnosis and monitoring of disease status may improve quality of life and long-term survival for multiple myeloma patients from what is now a devastating and fatal disease. We have developed a near-infrared targeted fluorescent molecular probe with high affinity to the α4β1 integrin receptor (VLA-4)overexpressed by a majority of multiple myeloma cells as a non-radioactive analog to PET/CT tracer currently being developed for human diagnostics. A near-infrared dye that emits about 700 nm was conjugated to a high affinity peptidomimmetic. Binding affinity and specificity for multiple myeloma cells was investigated in vitro by tissue staining and flow cytometry. After demonstration of sensitivity and specificity, preclinical optical imaging studies were performed to evaluate tumor specificity in murine subcutaneous and metastatic multiple myeloma models. The VLA-4-targeted molecular probe showed high affinity for subcutaneous MM tumor xenografts. Importantly, tumor cells specific accumulation in the bone marrow of metastatic multiple myeloma correlated with GFP signal from transfected cells. Ex vivo flow cytometry of tumor tissue and bone marrow further corroborated in vivo imaging data, demonstrating the specificity of the novel agent and potential for quantitative imaging of multiple myeloma burden in these models.

  13. Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores

    Science.gov (United States)

    Miller, Jessica P.; Habimana-Griffin, LeMoyne; Edwards, Tracy S.; Achilefu, Samuel

    2017-06-01

    Similarity of skin cancer with many benign skin pathologies requires reliable methods to detect and differentiate the different types of these lesions. Previous studies have explored the use of disparate optical techniques to identify and estimate the invasive nature of melanoma and basal cell carcinoma with varying outcomes. Here, we used a concerted approach that provides complementary information for rapid screening and characterization of tumors, focusing on squamous cell carcinoma (SCC) of the skin. Assessment of in vivo autofluorescence lifetime (FLT) imaging of endogenous fluorophores that are excitable at longer wavelengths (480 nm) than conventional NADH and FAD revealed a decrease in the short FLT component for SCC compared to normal skin, with mean values of 0.57±0.026 ns and 0.61±0.021 ns, respectively (p=0.004). Subsequent systemic administration of a near-infrared fluorescent molecular probe in SCC bearing mice, followed by the implementation of image processing methods on data acquired from two-dimensional and three-dimensional fluorescence molecular imaging, allowed us to estimate the tumor volume and depth, as well as quantify the fluorescent probe in the tumor. The result suggests the involvement of lipofuscin-like lipopigments and riboflavin in SCC metabolism and serves as a model for staging SCC.

  14. Molecular image guided radiation therapy-MIGRT in radiobioluminescence and nanoradioguidance

    International Nuclear Information System (INIS)

    Rao, V.L. Papineni

    2014-01-01

    Accurate dose delivery to malignant tissue in radiotherapy is essential for enhancing the treatment efficacy while minimizing morbidity of surrounding normal tissues. Advances in therapeutic strategies and diagnosis technologies along with our understanding of the biology of tumor response to radiation therapy have paved way to allow nearly 60% of current cancer patients to be treated with Radiation Therapy. The confluence of molecular imaging and nanotechnology fields are bridging physics and medicine and are quickly making strides in opening new avenues and therapeutic strategies that complement radiation therapy - with a distinct footprint in immunotherapy, adoptive cell therapy, and targeted chemotherapy. Incorporating optical imaging in radiation therapy in my laboratory, endogenous bioluminescence resulting from whole body irradiation in different organs, and in different animals, which is distinct from the Cherenkov radiation. The endogenous bioluminescence in response to irradiation is coined recently as radiobioluminescence. Thus with the necessity, the design, construction, and validation of Molecular Image Guided Radiation Therapy (MIGRT) instrumentation for preclinical theragnostics is carried out

  15. Molecular PET imaging for biology-guided adaptive radiotherapy of head and neck cancer.

    Science.gov (United States)

    Hoeben, Bianca A W; Bussink, Johan; Troost, Esther G C; Oyen, Wim J G; Kaanders, Johannes H A M

    2013-10-01

    Integration of molecular imaging PET techniques into therapy selection strategies and radiation treatment planning for head and neck squamous cell carcinoma (HNSCC) can serve several purposes. First, pre-treatment assessments can steer decisions about radiotherapy modifications or combinations with other modalities. Second, biology-based objective functions can be introduced to the radiation treatment planning process by co-registration of molecular imaging with planning computed tomography (CT) scans. Thus, customized heterogeneous dose distributions can be generated with escalated doses to tumor areas where radiotherapy resistance mechanisms are most prevalent. Third, monitoring of temporal and spatial variations in these radiotherapy resistance mechanisms early during the course of treatment can discriminate responders from non-responders. With such information available shortly after the start of treatment, modifications can be implemented or the radiation treatment plan can be adapted tailing the biological response pattern. Currently, these strategies are in various phases of clinical testing, mostly in single-center studies. Further validation in multicenter set-up is needed. Ultimately, this should result in availability for routine clinical practice requiring stable production and accessibility of tracers, reproducibility and standardization of imaging and analysis methods, as well as general availability of knowledge and expertise. Small studies employing adaptive radiotherapy based on functional dynamics and early response mechanisms demonstrate promising results. In this context, we focus this review on the widely used PET tracer (18)F-FDG and PET tracers depicting hypoxia and proliferation; two well-known radiation resistance mechanisms.

  16. Correlating TEM images of damage in irradiated materials to molecular dynamics simulations

    International Nuclear Information System (INIS)

    Schaeublin, R.; Caturla, M.-J.; Wall, M.; Felter, T.; Fluss, M.; Wirth, B.D.; Diaz de la Rubia, T.; Victoria, M.

    2002-01-01

    TEM image simulations are used to couple the results from molecular dynamics (MD) simulations to experimental TEM images. In particular we apply this methodology to the study of defects produced during irradiation. MD simulations have shown that irradiation of FCC metals results in a population of vacancies and interstitials forming clusters. The limitation of these simulations is the short time scales available, on the order of 100 s of picoseconds. Extrapolation of the results from these short times to the time scales of the laboratory has been difficult. We address this problem by two methods: we perform TEM image simulations of MD simulations of cascades with an improved technique, to relate defects produced at short time scales with those observed experimentally at much longer time scales. On the other hand we perform in situ TEM experiments of Au irradiated at liquid-nitrogen temperatures, and study the evolution of the produced damage as the temperature is increased to room temperature. We find that some of the defects observed in the MD simulations at short time scales using the TEM image simulation technique have features that resemble those observed in laboratory TEM images of irradiated samples. In situ TEM shows that stacking fault tetrahedra are present at the lowest temperatures and are stable during annealing up to room temperature, while other defect clusters migrate one dimensionally above -100 deg. C. Results are presented here

  17. Molecular Imaging to Predict Response to Targeted Therapies in Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ingrid Leguerney

    2017-01-01

    Full Text Available Molecular magnetic resonance imaging targeted to an endothelial integrin involved in neoangiogenesis was compared to DCE-US and immunochemistry to assess the early response of three different therapeutic agents in renal cell carcinoma. Human A498 renal cells carcinoma was subcutaneously inoculated into 24 nude mice. Mice received either phosphate-buffered saline solution, sunitinib, everolimus, or bevacizumab during 4 days. DCE-US and molecular MRI targeting αvβ3 were performed at baseline and 4 days after treatment initiation. PI, AUC, relaxation rate variations ΔR2⁎, and percentage of vessels area quantified on CD31-stained microvessels were compared. Significant decreases were observed for PI and AUC parameters measured by DCE-US for bevacizumab group as early as 4 days, whereas molecular αvβ3-targeted MRI was able to detect significant changes in both bevacizumab and everolimus groups. Percentage of CD31-stained microvessels was significantly correlated with DCE-US parameters, PI (R=0.87, p=0.0003 and AUC (R=0.81, p=0.0013. The percentage of vessel tissue area was significantly reduced (p<0.01 in both sunitinib and bevacizumab groups. We report an early detection of neoangiogenesis modification after induction of targeted therapies, using DCE-US or αvβ3-targeted MRI. We consider these outcomes should encourage clinical trial developments to further evaluate the potential of this molecular MRI technique.

  18. Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

    Science.gov (United States)

    Daryaei, Iman; Pagel, Mark D

    2015-01-01

    Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

  19. A new crossed molecular beam apparatus using time-sliced ion velocity imaging technique

    International Nuclear Information System (INIS)

    Wu Guorong; Zhang Weiqing; Pan Huilin; Shuai Quan; Jiang Bo; Dai Dongxu; Yang Xueming

    2008-01-01

    A new crossed molecular beam apparatus has been constructed for investigating polyatomic chemical reactions using the time-sliced ion velocity map imaging technique. A unique design is adopted for one of the two beam sources and allows us to set up the molecular beam source either horizontally or vertically. This can be conveniently used to produce versatile atomic or radical beams from photodissociation and as well as electric discharge. Intensive H-atom beam source with high speed ratio was produced by photodissociation of the HI molecule and was reacted with the CD 4 molecule. Vibrational-state resolved HD product distribution was measured by detecting the CD 3 product. Preliminary results were also reported on the F+SiH 4 reaction using the discharged F atom beam. These results demonstrate that this new instrument is a powerful tool for investigating chemical dynamics of polyatomic reactions.

  20. Harnessing Preclinical Molecular Imaging to Inform Advances in Personalized Cancer Medicine.

    Science.gov (United States)

    Clark, Peter M; Ebiana, Victoria A; Gosa, Laura; Cloughesy, Timothy F; Nathanson, David A

    2017-05-01

    Comprehensive molecular analysis of individual tumors provides great potential for personalized cancer therapy. However, the presence of a particular genetic alteration is often insufficient to predict therapeutic efficacy. Drugs with distinct mechanisms of action can affect the biology of tumors in specific and unique ways. Therefore, assays that can measure drug-induced perturbations of defined functional tumor properties can be highly complementary to genomic analysis. PET provides the capacity to noninvasively measure the dynamics of various tumor biologic processes in vivo. Here, we review the underlying biochemical and biologic basis for a variety of PET tracers and how they may be used to better optimize cancer therapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  1. A hardware investigation of robotic SPECT for functional and molecular imaging onboard radiation therapy systems

    International Nuclear Information System (INIS)

    Yan, Susu; Tough, MengHeng; Bowsher, James; Yin, Fang-Fang; Cheng, Lin

    2014-01-01

    Purpose: To construct a robotic SPECT system and to demonstrate its capability to image a thorax phantom on a radiation therapy flat-top couch, as a step toward onboard functional and molecular imaging in radiation therapy. Methods: A robotic SPECT imaging system was constructed utilizing a gamma camera detector (Digirad 2020tc) and a robot (KUKA KR150 L110 robot). An imaging study was performed with a phantom (PET CT Phantom TM ), which includes five spheres of 10, 13, 17, 22, and 28 mm diameters. The phantom was placed on a flat-top couch. SPECT projections were acquired either with a parallel-hole collimator or a single-pinhole collimator, both without background in the phantom and with background at 1/10th the sphere activity concentration. The imaging trajectories of parallel-hole and pinhole collimated detectors spanned 180° and 228°, respectively. The pinhole detector viewed an off-centered spherical common volume which encompassed the 28 and 22 mm spheres. The common volume for parallel-hole system was centered at the phantom which encompassed all five spheres in the phantom. The maneuverability of the robotic system was tested by navigating the detector to trace the phantom and flat-top table while avoiding collision and maintaining the closest possible proximity to the common volume. The robot base and tool coordinates were used for image reconstruction. Results: The robotic SPECT system was able to maneuver parallel-hole and pinhole collimated SPECT detectors in close proximity to the phantom, minimizing impact of the flat-top couch on detector radius of rotation. Without background, all five spheres were visible in the reconstructed parallel-hole image, while four spheres, all except the smallest one, were visible in the reconstructed pinhole image. With background, three spheres of 17, 22, and 28 mm diameters were readily observed with the parallel-hole imaging, and the targeted spheres (22 and 28 mm diameters) were readily observed in the pinhole

  2. Facile Fabrication of Animal-Specific Positioning Molds For Multi-modality Molecular Imaging

    International Nuclear Information System (INIS)

    Park, Jeong Chan; Oh, Ji Eun; Woo, Seung Tae

    2008-01-01

    Recently multi-modal imaging system has become widely adopted in molecular imaging. We tried to fabricate animal-specific positioning molds for PET/MR fusion imaging using easily available molding clay and rapid foam. The animal-specific positioning molds provide immobilization and reproducible positioning of small animal. Herein, we have compared fiber-based molding clay with rapid foam in fabricating the molds of experimental animal. The round bottomed-acrylic frame, which fitted into microPET gantry, was prepared at first. The experimental mice was anesthetized and placed on the mold for positioning. Rapid foam and fiber-based clay were used to fabricate the mold. In case of both rapid foam and the clay, the experimental animal needs to be pushed down smoothly into the mold for positioning. However, after the mouse was removed, the fabricated clay needed to be dried completely at 60 .deg. C in oven overnight for hardening. Four sealed pipe tips containing [ 18 F]FDG solution were used as fiduciary markers. After injection of [ 18 F]FDG via tail vein, microPET scanning was performed. Successively, MRI scanning was followed in the same animal. Animal-specific positioning molds were fabricated using rapid foam and fiber-based molding clay for multimodality imaging. Functional and anatomical images were obtained with microPET and MRI, respectively. The fused PET/MR images were obtained using freely available AMIDE program. Animal-specific molds were successfully prepared using easily available rapid foam, molding clay and disposable pipet tips. Thanks to animal-specific molds, fusion images of PET and MR were co-registered with negligible misalignment

  3. Molecular imaging of in vivo redox dynamics using magnetic resonance system

    International Nuclear Information System (INIS)

    Utsumi, Hideo; Yasukawa, Keiji

    2008-01-01

    Homeostatic failure through redox systems in vivo results in abnormality in mitochondrial function, protein expression and metabolism leading to many diseases like lifestyle related ones and cancer. It is therefore important to see redox dynamics for early prevention of the diseases. This paper describes development of machines for electron spin resonance (ESR) imaging of the redox state, for Overhauser Effect MRI (OMRI), application of nitroxyl-probes and state of redox project by authors. They have developed the ESR equipments hitherto, including the latest 300 MHz one, with which images of a mouse given carbamoyl-PROXYL probe are obtained and fused with MRI images for anatomical positioning: resonator for both ESR and MRI coils has been developed for animal images. Philips OMRI machine has been able to give separate images of reduction and oxidation in animals given appropriate probe compounds, which lead to molecular imaging of redox using such probes as 14 N- and 15 N-nitroxyl radicals with different membrane permeability. Application of nitroxyl-radicals like hydroxyl-TEMPO has made it possible for the animal diseases caused by oxidative stress to be analyzed by ESR/spin probe method, and derivatization of the probe results in detection of its distribution in various cell and body areas even in nanometer-space. Authors' project concerns the development of the processing system of redox dynamics/OMRI-integrated images, of better probe complexes and application of these to actual model animals. The techniques are thought to be important in the fields of medicare and new drug development in future. (R.T.)

  4. Quantum dot-based molecular imaging of cancer cell growth using a clone formation assay.

    Science.gov (United States)

    Geng, Xia-Fei; Fang, Min; Liu, Shao-Ping; Li, Yan

    2016-10-01

    This aim of the present study was to investigate clonal growth behavior and analyze the proliferation characteristics of cancer cells. The MCF‑7 human breast cancer cell line, SW480 human colon cancer cell line and SGC7901 human gastric cancer cell line were selected to investigate the morphology of cell clones. Quantum dot‑based molecular targeted imaging techniques (which stained pan‑cytokeratin in the cytoplasm green and Ki67 in the cell nucleus yellow or red) were used to investigate the clone formation rate, cell morphology, discrete tendency, and Ki67 expression and distribution in clones. From the cell clone formation assay, the MCF‑7, SW480 and SGC7901 cells were observed to form clones on days 6, 8 and 12 of cell culture, respectively. These three types of cells had heterogeneous morphology, large nuclear:cytoplasmic ratios, and conspicuous pathological mitotic features. The cells at the clone periphery formed multiple pseudopodium. In certain clones, cancer cells at the borderline were separated from the central cell clusters or presented a discrete tendency. With quantum dot‑based molecular targeted imaging techniques, cells with strong Ki67 expression were predominantly shown to be distributed at the clone periphery, or concentrated on one side of the clones. In conclusion, cancer cell clones showed asymmetric growth behavior, and Ki67 was widely expressed in clones of these three cell lines, with strong expression around the clones, or aggregated at one side. Cell clone formation assay based on quantum dots molecular imaging offered a novel method to study the proliferative features of cancer cells, thus providing a further insight into tumor biology.

  5. Radiopharmaceuticals: nanoparticles like multi-functional systems for the obtaining in vivo of molecular images; Radiofarmacos: nanoparticulas como sistemas multifuncionales para la obtencion in vivo de imagenes moleculares

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Ramirez de la Cruz, F. M.; Ocampo G, B. E.; Morales A, E.; Santos C, C. L.; Mendoza S, A. N., E-mail: guillermina.ferro@inin.gob.m [ININ, Departamento de Materiales Radiactivos, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2010-07-01

    The techniques of obtaining direct or indirect molecular images detect and register the space-temporary distribution of molecular or cellular processes for biochemical, biological, diagnostic and therapeutic applications. The advanced techniques of image like the nuclear magnetic resonance, the single photon emission computed tomography, the positron emission tomography and the images of optic fluorescence have been used successfully to detect these processes. On the other hand, the utility of the nanoparticles for any application is dependent of the physicochemical properties that present, being possible to modify their surface when making them react with different biomolecules what allows the formation of conjugates with specific molecular recognition. The joint of various protein molecules, peptides or oligonucleotides to the surface of a nanoparticle produce a multi-functional system able to increase the multivalent joints from the nanoparticles-biomolecules to their receivers for the obtaining of molecular images in vivo. The peptides stimulate, regulate or inhibit numerous functions of the life, acting mainly as information transmitters and activity coordinators of several tissues in the organism. The receivers of regulator peptides are over represented in numerous types of cancer cells and they are protein structures. These receivers have been used as white molecular of marked peptides, to locate primary malignant tumors and their metastasis, using the diagnostic techniques of molecular image mentioned above, which consist basically on the radio peptides use and conjugated peptides to fluoro chromes, to metallic nanoparticles and nano crystals. A summary of the work is presented carried out by the personnel of the Radio-active Materials and Chemistry Departments of the Instituto Nacional de Investigaciones Nucleares in this field. (Author)

  6. CMOS Time-Resolved, Contact, and Multispectral Fluorescence Imaging for DNA Molecular Diagnostics

    Directory of Open Access Journals (Sweden)

    Nan Guo

    2014-10-01

    Full Text Available Instrumental limitations such as bulkiness and high cost prevent the fluorescence technique from becoming ubiquitous for point-of-care deoxyribonucleic acid (DNA detection and other in-field molecular diagnostics applications. The complimentary metal-oxide-semiconductor (CMOS technology, as benefited from process scaling, provides several advanced capabilities such as high integration density, high-resolution signal processing, and low power consumption, enabling sensitive, integrated, and low-cost fluorescence analytical platforms. In this paper, CMOS time-resolved, contact, and multispectral imaging are reviewed. Recently reported CMOS fluorescence analysis microsystem prototypes are surveyed to highlight the present state of the art.

  7. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

    OpenAIRE

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-01-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (P

  8. Molecular Hydrogen Images of Star Forming Regions in the Magellanic Clouds

    Science.gov (United States)

    Probst, Ronald G.; Barba, R.; Bolatto, A.; Chu, Y.; Points, S.; Rubio, M.; Smith, C.

    2011-01-01

    The Large and Small Magellanic Clouds exhibit a variety of star formation physics with multiple phase components in low metallicity, gas rich environments. The 10 K, 100 K, and 104 K regimes are well explored. We are imaging LMC and SMC star forming regions in 2.12 micron H2 emission which arises in the 1000 K transition zone of molecular clouds. This is an NOAO Survey program using the widefield IR camera NEWFIRM on the CTIO 4-m Blanco telescope during its limited southern deployment. The data set will have immediate morphological applications and will provide target selection for followup infrared spectroscopy. We will provide a public archive of fully calibrated images with no proprietary period. NOAO is operated by the Association of Universities for Research in Astronomy, under cooperative agreement with the National Science Foundation.

  9. Inflammation Modulates Murine Venous Thrombosis Resolution In Vivo: Assessment by Multimodal Fluorescence Molecular Imaging

    Science.gov (United States)

    Ripplinger, Crystal M.; Kessinger, Chase W.; Li, Chunqiang; Kim, Jin Won; McCarthy, Jason R.; Weissleder, Ralph; Henke, Peter K.; Lin, Charles P.; Jaffer, Farouc A.

    2012-01-01

    Objective Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here we develop and evaluate two integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture, and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo. Methods and Results Murine DVT were created with topical 5% FeCl3 application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase (MMP) activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy (IVM). Day 4 analyses showed robust relationships among in vivo thrombus macrophages, MMP activity, and FITC-dextran deposition (r>0.70, pthrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (pthrombus resolution. PMID:22995524

  10. Super-Resolution Molecular and Functional Imaging of Nanoscale Architectures in Life and Materials Science

    KAUST Repository

    Habuchi, Satoshi

    2014-06-12

    Super-resolution (SR) fluorescence microscopy has been revolutionizing the way in which we investigate the structures, dynamics, and functions of a wide range of nanoscale systems. In this review, I describe the current state of various SR fluorescence microscopy techniques along with the latest developments of fluorophores and labeling for the SR microscopy. I discuss the applications of SR microscopy in the fields of life science and materials science with a special emphasis on quantitative molecular imaging and nanoscale functional imaging. These studies open new opportunities for unraveling the physical, chemical, and optical properties of a wide range of nanoscale architectures together with their nanostructures and will enable the development of new (bio-)nanotechnology.

  11. Exploration of target molecules for molecular imaging of inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    Higashikawa, Kei; Akada, Naoki; Yagi, Katsuharu [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan); Watanabe, Keiko; Kamino, Shinichiro; Kanayama, Yousuke; Hiromura, Makoto [Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan); Enomoto, Shuichi, E-mail: senomoto@pharm.okayama-u.ac.jp [Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama 700-8530 (Japan); Multiple Molecular Imaging Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047 (Japan)

    2011-07-08

    Highlights: {sup {yields}18}F-FDG PET could discriminate each inflamed area of IBD model mice clearly. {sup {yields}18}F-FDG PET could not discriminate the difference of pathogenic mechanism. {yields} Cytokines and cytokine receptors expression was different by pathogenic mechanism. {yields} Cytokines and cytokine receptors would be new target molecules for IBD imaging. -- Abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternative probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD appeared. In

  12. Quantitative study of luminescence optical tomography. Application to sources localisation in molecular imaging

    International Nuclear Information System (INIS)

    Boffety, Matthieu

    2010-01-01

    Molecular imaging is a major modality in the field of preclinical research. Among the existing methods, techniques based on optical detection of visible or near infrared radiation are the most recent and are mainly represented by luminescence optical tomography techniques. These methods allow for 3D characterization of a biological medium by reconstructing maps of concentration or localisation of luminescent beacons sensitive to biological and chemical processes at the molecular or cellular scale. Luminescence optical tomography is based on a model of light propagation in tissues, a protocol for acquiring surface signal and a numerical inversion procedure used to reconstruct the parameters of interest. This thesis is structured around these three axes and provides an answer to each problem. The main objective of this study is to introduce and present the tools to evaluate the theoretical performances of optical tomography methods. One of its major outcomes is the realisation of experimental tomographic reconstructions from images acquired by an optical imager designed for 2D planar imaging and developed by the company Quidd. In a first step we develop the theory of transport in scattering medium to establish the concept on which our work will rely. We present two different propagation models as well as resolution methods and theoretical difficulties associated with them. In a second part we introduce the statistical tools used to characterise tomographic systems. We define and apply a procedure to simple situations in luminescence optical tomography. The last part of this work presents the development of an inversion procedure. After introducing the theoretical framework we validate the procedure from numerical data before successfully applying it to experimental measurements. (author) [fr

  13. The use of anatomical information for molecular image reconstruction algorithms: Attention/Scatter correction, motion compensation, and noise reduction

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Se Young [School of Electrical and Computer Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan (Korea, Republic of)

    2016-03-15

    PET and SPECT are important tools for providing valuable molecular information about patients to clinicians. Advances in nuclear medicine hardware technologies and statistical image reconstruction algorithms enabled significantly improved image quality. Sequentially or simultaneously acquired anatomical images such as CT and MRI from hybrid scanners are also important ingredients for improving the image quality of PET or SPECT further. High-quality anatomical information has been used and investigated for attenuation and scatter corrections, motion compensation, and noise reduction via post-reconstruction filtering and regularization in inverse problems. In this article, we will review works using anatomical information for molecular image reconstruction algorithms for better image quality by describing mathematical models, discussing sources of anatomical information for different cases, and showing some examples.

  14. Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT

    Directory of Open Access Journals (Sweden)

    Iosif A. Mendichovszky

    2016-11-01

    Full Text Available Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal ‘incidentalomas’ detected on modern computed tomography (CT or magnetic resonance imaging (MRI. A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL or metastases (e.g., bronchial, renal. Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing’s syndrome, phaeochromocytoma. Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11C-metomidate PET-CT in primary aldosteronism.

  15. Tracking molecular dynamics without tracking: image correlation of photo-activation microscopy

    International Nuclear Information System (INIS)

    Pandžić, Elvis; Rossy, Jérémie; Gaus, Katharina

    2015-01-01

    Measuring protein dynamics in the plasma membrane can provide insights into the mechanisms of receptor signaling and other cellular functions. To quantify protein dynamics on the single molecule level over the entire cell surface, sophisticated approaches such as single particle tracking (SPT), photo-activation localization microscopy (PALM) and fluctuation-based analysis have been developed. However, analyzing molecular dynamics of fluorescent particles with intermittent excitation and low signal-to-noise ratio present at high densities has remained a challenge. We overcame this problem by applying spatio-temporal image correlation spectroscopy (STICS) analysis to photo-activated (PA) microscopy time series. In order to determine under which imaging conditions this approach is valid, we simulated PA images of diffusing particles in a homogeneous environment and varied photo-activation, reversible blinking and irreversible photo-bleaching rates. Further, we simulated data with high particle densities that populated mobile objects (such as adhesions and vesicles) that often interfere with STICS and fluctuation-based analysis. We demonstrated in experimental measurements that the diffusion coefficient of the epidermal growth factor receptor (EGFR) fused to PAGFP in live COS-7 cells can be determined in the plasma membrane and revealed differences in the time-dependent diffusion maps between wild-type and mutant Lck in activated T cells. In summary, we have developed a new analysis approach for live cell photo-activation microscopy data based on image correlation spectroscopy to quantify the spatio-temporal dynamics of single proteins. (paper)

  16. Tracking molecular dynamics without tracking: image correlation of photo-activation microscopy

    Science.gov (United States)

    Pandžić, Elvis; Rossy, Jérémie; Gaus, Katharina

    2015-03-01

    Measuring protein dynamics in the plasma membrane can provide insights into the mechanisms of receptor signaling and other cellular functions. To quantify protein dynamics on the single molecule level over the entire cell surface, sophisticated approaches such as single particle tracking (SPT), photo-activation localization microscopy (PALM) and fluctuation-based analysis have been developed. However, analyzing molecular dynamics of fluorescent particles with intermittent excitation and low signal-to-noise ratio present at high densities has remained a challenge. We overcame this problem by applying spatio-temporal image correlation spectroscopy (STICS) analysis to photo-activated (PA) microscopy time series. In order to determine under which imaging conditions this approach is valid, we simulated PA images of diffusing particles in a homogeneous environment and varied photo-activation, reversible blinking and irreversible photo-bleaching rates. Further, we simulated data with high particle densities that populated mobile objects (such as adhesions and vesicles) that often interfere with STICS and fluctuation-based analysis. We demonstrated in experimental measurements that the diffusion coefficient of the epidermal growth factor receptor (EGFR) fused to PAGFP in live COS-7 cells can be determined in the plasma membrane and revealed differences in the time-dependent diffusion maps between wild-type and mutant Lck in activated T cells. In summary, we have developed a new analysis approach for live cell photo-activation microscopy data based on image correlation spectroscopy to quantify the spatio-temporal dynamics of single proteins.

  17. The combination design for open and endoscopic surgery using fluorescence molecular imaging technology

    Science.gov (United States)

    Mao, Yamin; Jiang, Shixin; Ye, Jinzuo; An, Yu; Yang, Xin; Chi, Chongwei; Tian, Jie

    2015-03-01

    For clinical surgery, it is still a challenge to objectively determine tumor margins during surgery. With the development of medical imaging technology, fluorescence molecular imaging (FMI) method can provide real-time intraoperative tumor margin information. Furthermore, surgical navigation system based on FMI technology plays an important role for the aid of surgeons' precise tumor margin decision. However, detection depth is the most limitation exists in the FMI technique and the method convenient for either macro superficial detection or micro deep tissue detection is needed. In this study, we combined advantages of both open surgery and endoscopic imaging systems with FMI technology. Indocyanine green (ICG) experiments were performed to confirm the feasibility of fluorescence detection in our system. Then, the ICG signal was photographed in the detection area with our system. When the system connected with endoscope lens, the minimum quantity of ICG detected by our system was 0.195 ug. For aspect of C mount lens, the sensitivity of ICG detection with our system was 0.195ug. Our experiments results proved that it was feasible to detect fluorescence images with this combination method. Our system shows great potential in the clinical applications of precise dissection of various tumors

  18. Anatomical image-guided fluorescence molecular tomography reconstruction using kernel method

    Science.gov (United States)

    Baikejiang, Reheman; Zhao, Yue; Fite, Brett Z.; Ferrara, Katherine W.; Li, Changqing

    2017-01-01

    Abstract. Fluorescence molecular tomography (FMT) is an important in vivo imaging modality to visualize physiological and pathological processes in small animals. However, FMT reconstruction is ill-posed and ill-conditioned due to strong optical scattering in deep tissues, which results in poor spatial resolution. It is well known that FMT image quality can be improved substantially by applying the structural guidance in the FMT reconstruction. An approach to introducing anatomical information into the FMT reconstruction is presented using the kernel method. In contrast to conventional methods that incorporate anatomical information with a Laplacian-type regularization matrix, the proposed method introduces the anatomical guidance into the projection model of FMT. The primary advantage of the proposed method is that it does not require segmentation of targets in the anatomical images. Numerical simulations and phantom experiments have been performed to demonstrate the proposed approach’s feasibility. Numerical simulation results indicate that the proposed kernel method can separate two FMT targets with an edge-to-edge distance of 1 mm and is robust to false-positive guidance and inhomogeneity in the anatomical image. For the phantom experiments with two FMT targets, the kernel method has reconstructed both targets successfully, which further validates the proposed kernel method. PMID:28464120

  19. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis

    Science.gov (United States)

    Sun, Dawei; Nakao, Shintaro; Xie, Fang; Zandi, Souska; Bagheri, Abouzar; Kanavi, Mozhgan Rezaei; Samiei, Shahram; Soheili, Zahra-Soheila; Frimmel, Sonja; Zhang, Zhongyu; Ablonczy, Zsolt; Ahmadieh, Hamid; Hafezi-Moghadam, Ali

    2014-01-01

    Diabetic retinopathy (DR) is a microvascular complication of diabetes and a leading cause of vision loss. Biomarkers and methods for early diagnosis of DR are urgently needed. Using a new molecular imaging approach, we show up to 94% higher accumulation of custom designed imaging probes against vascular endothelial growth factor receptor 2 (VEGFR-2) in retinal and choroidal vessels of diabetic animals (PM. R., Samiei, S., Soheili, Z.-S., Frimmel, S., Zhang, Z., Ablonczy, Z., Ahmadieh, H., Hafezi-Moghadam, A. Molecular imaging reveals elevated VEGFR-2 expression in retinal capillaries in diabetes: a novel biomarker for early diagnosis. PMID:24903276

  20. Molecular Imaging of Gene Expression and Efficacy following Adenoviral-Mediated Brain Tumor Gene Therapy

    Directory of Open Access Journals (Sweden)

    Alnawaz Rehemtulla

    2002-01-01

    Full Text Available Cancer gene therapy is an active area of research relying upon the transfer and subsequent expression of a therapeutic transgene into tumor cells in order to provide for therapeutic selectivity. Noninvasive assessment of therapeutic response and correlation of the location, magnitude, and duration of transgene expression in vivo would be particularly useful in the development of cancer gene therapy protocols by facilitating optimization of gene transfer protocols, vector development, and prodrug dosing schedules. In this study, we developed an adenoviral vector containing both the therapeutic transgene yeast cytosine deaminase (yCD along with an optical reporter gene (luciferase. Following intratumoral injection of the vector into orthotopic 9L gliomas, anatomical and diffusion-weighted MR images were obtained over time in order to provide for quantitative assessment of overall therapeutic efficacy and spatial heterogeneity of cell kill, respectively. In addition, bioluminescence images were acquired to assess the duration and magnitude of gene expression. MR images revealed significant reduction in tumor growth rates associated with yCD/5-fluorocytosine (5FC gene therapy. Significant increases in mean tumor diffusion values were also observed during treatment with 5FC. Moreover, spatial heterogeneity in tumor diffusion changes were also observed revealing that diffusion magnetic resonance imaging could detect regional therapeutic effects due to the nonuniform delivery and/or expression of the therapeutic yCD transgene within the tumor mass. In addition, in vivo bioluminescence imaging detected luciferase gene expression, which was found to decrease over time during administration of the prodrug providing a noninvasive surrogate marker for monitoring gene expression. These results demonstrate the efficacy of the yCD/5FC strategy for the treatment of brain tumors and reveal the feasibility of using multimodality molecular and functional imaging

  1. A tri-modal molecular imaging agent for sentinel lymph node mapping

    International Nuclear Information System (INIS)

    Qin, Zhengtao; Hoh, Carl K.; Hall, David J.; Vera, David R.

    2015-01-01

    Introduction: We report an “instant kit” method to radiolabel fluorescent-tilmanocept with 68 Ga and 99m Tc for tri-modal molecular imaging of sentinel lymph nodes (SLNs). Methods: Solutions of sodium acetate, 68 GaCl 3 and Na 99m TcO 4 were added successively to a “kit vial” containing lyophilized 800CW-tilmanocept, SnCl 2 , trehalose and ascorbic acid. After a 30-min incubation, the pH was neutralized with PBS. No purification was required. Radiochemical and fluorescence purity was measured by HPLC and ITLC techniques. In vitro stability was measured by standing gel chromatography (SGC) and ITLC by a 100-fold dilution 0.25 h after radiolabeling. In vivo stability was measured by SGC and ITLC after an 11 h incubation in human plasma. A dose (0.1 nmol, ~ 1 MBq 68 Ga, ~ 25 MBq 99m Tc) was injected to the footpad of 4 mice. Popliteal SLNs were imaged by PET and fluorescence imaging systems at 0.5, 24, 48, 72 h, then excised and assayed for 99m Tc. Results: Radiochemical and fluorescent purity exceeded 98%. The in vitro stability assay demonstrated high irreversibility of both radiolabels and the fluorescent label, and in vivo stability assay demonstrated high stability of the technetium and fluorescent labels to plasma metabolism. Popliteal SLNs were identified by PET and fluorescence imaging within 0.5 h of injection. SLN fluorescence intensity remained constant for 72 h, when ~ 1% of the injected dose resided in the SLN. Conclusions: Fluorescent-labeled tilmanocept can be radiolabeled with 68 Ga and 99m Tc by the sequential addition of each generator eluate to a lyophilized kit. The resulting tri-modal agent provides: PET images for pre-operative SLN mapping, fluorescence imaging up to 72 hours after injection, and quantitative radiometric measurement of SLN accumulation after excision.

  2. Fast automatic segmentation of anatomical structures in x-ray computed tomography images to improve fluorescence molecular tomography reconstruction.

    Science.gov (United States)

    Freyer, Marcus; Ale, Angelique; Schulz, Ralf B; Zientkowska, Marta; Ntziachristos, Vasilis; Englmeier, Karl-Hans

    2010-01-01

    The recent development of hybrid imaging scanners that integrate fluorescence molecular tomography (FMT) and x-ray computed tomography (XCT) allows the utilization of x-ray information as image priors for improving optical tomography reconstruction. To fully capitalize on this capacity, we consider a framework for the automatic and fast detection of different anatomic structures in murine XCT images. To accurately differentiate between different structures such as bone, lung, and heart, a combination of image processing steps including thresholding, seed growing, and signal detection are found to offer optimal segmentation performance. The algorithm and its utilization in an inverse FMT scheme that uses priors is demonstrated on mouse images.

  3. Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics

    Science.gov (United States)

    Buckle, Tessa; van der Wal, Steffen; van Malderen, Stijn J.M.; Müller, Larissa; Kuil, Joeri; van Unen, Vincent; Peters, Ruud J.B.; van Bemmel, Margaretha E.M.; McDonnell, Liam A.; Velders, Aldrik H.; Koning, Frits; Vanhaeke, Frank; van Leeuwen, Fijs W. B.

    2017-01-01

    Background: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. Methods: A hybrid label that contained both a DTPA chelate (that was coordinated with either 165Ho or 111In) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of (165Ho-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging (165Ho), 3) compare in vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging (165Ho) was linked to fluorescence-based analysis of excised tissue samples (Cy5). Results: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 ± 141 nM and 245 ± 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging (165Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the

  4. Special conference of the American Association for Cancer Research on molecular imaging in cancer: linking biology, function, and clinical applications in vivo.

    Science.gov (United States)

    Luker, Gary D

    2002-04-01

    The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.

  5. Quantitative Impact of Plasma Clearance and Down-regulation on GLP-1 Receptor Molecular Imaging.

    Science.gov (United States)

    Zhang, Liang; Thurber, Greg M

    2016-02-01

    Quantitative molecular imaging of beta cell mass (BCM) would enable early detection and treatment monitoring of type 1 diabetes. The glucagon-like peptide-1 (GLP-1) receptor is an attractive target due to its beta cell specificity and cell surface location. We quantitatively investigated the impact of plasma clearance and receptor internalization on targeting efficiency in healthy B6 mice. Four exenatide-based probes were synthesized that varied in molecular weight, binding affinity, and plasma clearance. The GLP-1 receptor internalization rate and in vivo receptor expression were quantified. Receptor internalization (54,000 receptors/cell in vivo) decreased significantly within minutes, reducing the benefit of a slower-clearing agent. The multimers and albumin binding probes had higher kidney and liver uptake, respectively. Slow plasma clearance is beneficial for GLP-1 receptor peptide therapeutics. However, for exendin-based imaging of islets, down-regulation of the GLP-1 receptor and non-specific background uptake result in a higher target-to-background ratio for fast-clearing agents.

  6. Molecular Imaging of Stem Cells: Tracking Survival, Biodistribution, Tumorigenicity, and Immunogenicity

    Directory of Open Access Journals (Sweden)

    Eugene Gu, Wen-Yi Chen, Jay Gu, Paul Burridge, Joseph C. Wu

    2012-01-01

    Full Text Available Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity.

  7. 124Iodine: A Longer-Life Positron Emitter Isotope—New Opportunities in Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Giuseppe Lucio Cascini

    2014-01-01

    Full Text Available 124Iodine (124I with its 4.2 d half-life is particularly attractive for in vivo detection and quantification of longer-term biological and physiological processes; the long half-life of 124I is especially suited for prolonged time in vivo studies of high molecular weight compounds uptake. Numerous small molecules and larger compounds like proteins and antibodies have been successfully labeled with 124I. Advances in radionuclide production allow the effective availability of sufficient quantities of 124I on small biomedical cyclotrons for molecular imaging purposes. Radioiodination chemistry with 124I relies on well-established radioiodine labeling methods, which consists mainly in nucleophilic and electrophilic substitution reactions. The physical characteristics of 124I permit taking advantages of the higher PET image quality. The availability of new molecules that may be targeted with 124I represents one of the more interesting reasons for the attention in nuclear medicine. We aim to discuss all iodine radioisotopes application focusing on 124I, which seems to be the most promising for its half-life, radiation emissions, and stability, allowing several applications in oncological and nononcological fields.

  8. A novel high resolution, high sensitivity SPECT detector for molecular imaging of cardiovascular diseases

    Science.gov (United States)

    Cusanno, F.; Argentieri, A.; Baiocchi, M.; Colilli, S.; Cisbani, E.; De Vincentis, G.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lucentini, M.; Magliozzi, M. L.; Majewski, S.; Marano, G.; Musico, P.; Musumeci, M.; Santavenere, F.; Torrioli, S.; Tsui, B. M. W.; Vitelli, L.; Wang, Y.

    2010-05-01

    Cardiovascular diseases are the most common cause of death in western countries. Understanding the rupture of vulnerable atherosclerotic plaques and monitoring the effect of innovative therapies of heart failure is of fundamental importance. A flexible, high resolution, high sensitivity detector system for molecular imaging with radionuclides on small animal models has been designed for this aim. A prototype has been built using tungsten pinhole and LaBr3(Ce) scintillator coupled to Hamamatsu Flat Panel PMTs. Compact individual-channel readout has been designed, built and tested. Measurements with phantoms as well as pilot studies on mice have been performed, the results show that the myocardial perfusion in mice can be determined with sufficient precision. The detector will be improved replacing the Hamamatsu Flat Panel with Silicon Photomultipliers (SiPMs) to allow integration of the system with MRI scanners. Application of LaBr3(Ce) scintillator coupled to photosensor with high photon detection efficiency and excellent energy resolution will allow dual-label imaging to monitor simultaneously the cardiac perfusion and the molecular targets under investigation during the heart therapy.

  9. Molecular imaging of the tumor microenvironment for precision medicine and theranostics.

    Science.gov (United States)

    Penet, Marie-France; Krishnamachary, Balaji; Chen, Zhihang; Jin, Jiefu; Bhujwalla, Zaver M

    2014-01-01

    Morbidity and mortality from cancer and their associated conditions and treatments continue to extract a heavy social and economic global burden despite the transformative advances in science and technology in the twenty-first century. In fact, cancer incidence and mortality are expected to reach pandemic proportions by 2025, and costs of managing cancer will escalate to trillions of dollars. The inability to establish effective cancer treatments arises from the complexity of conditions that exist within tumors, the plasticity and adaptability of cancer cells coupled with their ability to escape immune surveillance, and the co-opted stromal cells and microenvironment that assist cancer cells in survival. Stromal cells, although destroyed together with cancer cells, have an ever-replenishing source that can assist in resurrecting tumors from any residual cancer cells that may survive treatment. The tumor microenvironment landscape is a continually changing landscape, with spatial and temporal heterogeneities that impact and influence cancer treatment outcome. Importantly, the changing landscape of the tumor microenvironment can be exploited for precision medicine and theranostics. Molecular and functional imaging can play important roles in shaping and selecting treatments to match this landscape. Our purpose in this review is to examine the roles of molecular and functional imaging, within the context of the tumor microenvironment, and the feasibility of their applications for precision medicine and theranostics in humans. © 2014 Elsevier Inc. All rights reserved.

  10. Molecular mechanism of DNA replication-coupled inactivation of the initiator protein in Escherichia coli: interaction of DnaA with the sliding clamp-loaded DNA and the sliding clamp-Hda complex.

    Science.gov (United States)

    Su'etsugu, Masayuki; Takata, Makoto; Kubota, Toshio; Matsuda, Yusaku; Katayama, Tsutomu

    2004-06-01

    In Escherichia coli, the ATP-DnaA protein initiates chromosomal replication. After the DNA polymerase III holoenzyme is loaded on to DNA, DnaA-bound ATP is hydrolysed in a manner depending on Hda protein and the DNA-loaded form of the DNA polymerase III sliding clamp subunit, which yields ADP-DnaA, an inactivated form for initiation. This regulatory DnaA-inactivation represses extra initiation events. In this study, in vitro replication intermediates and structured DNA mimicking replicational intermediates were first used to identify structural prerequisites in the process of DnaA-ATP hydrolysis. Unlike duplex DNA loaded with sliding clamps, primer RNA-DNA heteroduplexes loaded with clamps were not associated with DnaA-ATP hydrolysis, and duplex DNA provided in trans did not rescue this defect. At least 40-bp duplex DNA is competent for the DnaA-ATP hydrolysis when a single clamp was loaded. The DnaA-ATP hydrolysis was inhibited when ATP-DnaA was tightly bound to a DnaA box-bearing oligonucleotide. These results imply that the DnaA-ATP hydrolysis involves the direct interaction of ATP-DnaA with duplex DNA flanking the sliding clamp. Furthermore, Hda protein formed a stable complex with the sliding clamp. Based on these, we suggest a mechanical basis in the DnaA-inactivation that ATP-DnaA interacts with the Hda-clamp complex with the aid of DNA binding. Copyright Blackwell Publishing Limited

  11. Molecular imaging in patients with mood disorders: a review of PET findings

    International Nuclear Information System (INIS)

    Chen, Qiaozhen; Liu, Weibo; Li, Huichun; Zhang, Hong; Tian, Mei

    2011-01-01

    Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders. (orig.)

  12. Molecular imaging in patients with mood disorders: a review of PET findings

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Qiaozhen [Zhejiang University, Department of Nuclear Medicine, Second Affiliated Hospital, School of Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Department of Psychiatry, Second Affiliated Hospital, School of Medicine, Hangzhou (China); Zhejiang University, Medical PET Center, Hangzhou (China); Zhejiang University, Institute of Nuclear Medicine and Molecular Imaging, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Liu, Weibo; Li, Huichun [Zhejiang University, Department of Psychiatry, Second Affiliated Hospital, School of Medicine, Hangzhou (China); Zhang, Hong [Zhejiang University, Department of Nuclear Medicine, Second Affiliated Hospital, School of Medicine, Hangzhou, Zhejiang (China); Zhejiang University, Medical PET Center, Hangzhou (China); Zhejiang University, Institute of Nuclear Medicine and Molecular Imaging, Hangzhou (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Tian, Mei [The University of Texas MD Anderson Cancer Center, Department of Experimental Diagnostic Imaging, Houston, TX (United States)

    2011-07-15

    Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders. (orig.)

  13. Molecular imaging of the paracrine proangiogenic effects of progenitor cell therapy in limb ischemia.

    Science.gov (United States)

    Ryu, Jae Choon; Davidson, Brian P; Xie, Aris; Qi, Yue; Zha, Daogang; Belcik, J Todd; Caplan, Evan S; Woda, Juliana M; Hedrick, Catherine C; Hanna, Richard N; Lehman, Nicholas; Zhao, Yan; Ting, Anthony; Lindner, Jonathan R

    2013-02-12

    Stem cells are thought to enhance vascular remodeling in ischemic tissue in part through paracrine effects. Using molecular imaging, we tested the hypothesis that treatment of limb ischemia with multipotential adult progenitor cells (MAPCs) promotes recovery of blood flow through the recruitment of proangiogenic monocytes. Hind-limb ischemia was produced in mice by iliac artery ligation, and MAPCs were administered intramuscularly on day 1. Optical imaging of luciferase-transfected MAPCs indicated that cells survived for 1 week. Contrast-enhanced ultrasound on days 3, 7, and 21 showed a more complete recovery of blood flow and greater expansion of microvascular blood volume in MAPC-treated mice than in controls. Fluorescent microangiography demonstrated more complete distribution of flow to microvascular units in MAPC-treated mice. On ultrasound molecular imaging, expression of endothelial P-selectin and intravascular recruitment of CX(3)CR-1-positive monocytes were significantly higher in MAPC-treated mice than in the control groups at days 3 and 7 after arterial ligation. Muscle immunohistology showed a >10-fold-greater infiltration of monocytes in MAPC-treated than control-treated ischemic limbs at all time points. Intravital microscopy of ischemic or tumor necrosis factor-α-treated cremaster muscle demonstrated that MAPCs migrate to perimicrovascular locations and potentiate selectin-dependent leukocyte rolling. In vitro migration of human CD14(+) monocytes was 10-fold greater in response to MAPC-conditioned than basal media. In limb ischemia, MAPCs stimulate the recruitment of proangiogenic monocytes through endothelial activation and enhanced chemotaxis. These responses are sustained beyond the MAPC lifespan, suggesting that paracrine effects promote flow recovery by rebalancing the immune response toward a more regenerative phenotype.

  14. Molecular Ultrasound Imaging of Early Vascular Response in Prostate Tumors Irradiated with Carbon Ions

    Directory of Open Access Journals (Sweden)

    Moritz Palmowski

    2009-09-01

    Full Text Available Individualized treatments with combination of radiotherapy and targeted drugs require knowledge about the behavior of molecular targets after irradiation. Angiogenic marker expression has been studied after conventional radiotherapy, but little is known about marker response to charged particles. For the very first time, we used molecular ultrasound imaging to intraindividually track changes in angiogenic marker expression after carbon ion irradiation in experimental tumors. Expression of intercellular adhesion molecule-1 (ICAM-1 and of αvβ3-integrin in subcutaneous AT-1 prostate cancers in rats treated with carbon ions (16 Gy was studied using molecular ultrasound and immunohistochemistry. For this purpose, cyanoacrylate microbubbles were synthesized and linked to specific ligands. The accumulation of targeted microbubbles in tumors was quantified before and 36 hours after irradiation. In addition, tumor vascularization was analyzed using volumetric Doppler ultrasound. In tumors, the accumulation of targeted microbubbles was significantly higher than in nonspecific ones and could be inhibited competitively. Before irradiation, no difference in binding of αvβ3-integrin-specific or ICAM-1-specific microbubbles was observed in treated and untreated animals. After irradiation, however, treated animals showed a significantly higher binding of αvβ3-integrin-specific microbubbles and an enhanced binding of ICAM-1-specific microbubbles than untreated controls. In both groups, a decrease in vascularization occurred during tumor growth, but no significant difference was observed between irradiated and nonirradiated tumors. In conclusion, carbon ion irradiation upregulates ICAM-1 and αvβ3-integrin expression in tumor neovasculature. Molecular ultrasound can indicate the regulation of these markers and thus may help to identify the optimal drugs and time points in individualized therapy regimens.

  15. Radiation protection in image installations Preclinical Molecular; Protección radiológica en instalaciones de Imagen Molecular Preclínica

    Energy Technology Data Exchange (ETDEWEB)

    Martí-Climent, J. M.; Collantes, M.; Prieto, E.; Morán, V.; Ecay, M.; Peñuelas, I.

    2014-07-01

    The preclinical image includes several molecular imaging techniques using ionizing radiation, particularly the single photon emission computed tomography (SPECT), the positron emission tomography (PET) and the autoradiographic image. Each technique uses different probes which allow imaging of a variety of metabolic processes. Sometimes they are used together with X-ray equipment which can obtain anatomical images. Consequently, research performed in preclinical molecular imaging facilities should be done in a context in which radiation protection is applied. Within radiological risks to the staff operating such facilities, the irradiation produced to hands due to the administration of radiotracers and to animals manipulation should be of major concern; therefore training and shielding are important. The design of the radioactive facility will be determined by the various activities undertaken. In particular, it will depend on the various preclinical molecular imaging techniques that would be developed and on the functional relationship that the facility has with the institution in which it is placed; particularly the animal housing facility and radiopharmacy unit. [Spanish] La imagen preclínica engloba distintas técnicas de imagen molecular que utilizan radiaciones ionizantes, destacando la tomografía por emisión de fotón único (SPECT), la tomografía de emisión de positrones (PET) y la imagen autorradiográfica. Cada una de ellas utiliza distintas sondas que permiten obtener imágenes de una gran variedad de procesos metabólicos. En ocasiones se emplean junto a equipos de rayos X que permiten obtener imágenes anatómicas. En consecuencia, la investigación en las instalaciones de imagen molecular preclínica deberá realizarse en un contexto en el que se aplique la protección radiológica. De entre los riesgos radiológicos del personal que opera este tipo de instalaciones destaca la irradiación de las manos producida tanto por la administración de los

  16. Metal-Based Systems for Molecular Imaging Applications - COST D38 Annual Workshop - Scientific Program and Abstracts

    International Nuclear Information System (INIS)

    Mikolajczak, R.

    2009-01-01

    The main objective of the Action is the development of metal-based imaging probes for cellular and molecular imaging applications, based on MRI, PET, SPECT and optical imaging that will facilitate early diagnosis, assessment of disease progression and treatment evaluation.The goal of this Action is to further the development of innovative imaging probes through the pursuit of innovations in a number of different areas, ranging from the design of imaging units endowed with enhanced sensitivity to the control of the structural and electronic determinants responsible for the molecular recognition of the target molecule.At present, in vivo diagnostic systems basically assess the structure and function of human organs. Therefore, for important diseases such as cancer and cardiovascular pathologies,and also diseases of the central nervous system, only the late symptoms are detected. It is expected that the advances in genomics and proteomics will have a tremendous impact on human health care of the future. However, advances in molecular biology are already redefining diseases in terms of molecular abnormalities. With this knowledge, new generations of diagnostic imaging agents can be defined that aim at the detection of those molecular processes in vivo.The molecular imaging approach offers a great potential for earlier detection and characterisation of disease, and evaluation of treatment. However, more research is necessary to bring these ideas to clinical applications and a key aspect relates to the development of high-specificity, high-sensitivity imaging probes for the different detection modalities. Additionally, the Action includes research activities dealing with the exploitation of peculiar nuclear properties of given isotopes for therapeutic effects, thus integrating the diagnostic and the therapeutic stages.Apart from its use in early diagnosis in clinical practice, the molecular imaging approach will have also a major impact on the development of new

  17. A Silicon SPECT System for Molecular Imaging of the Mouse Brain.

    Science.gov (United States)

    Shokouhi, Sepideh; Fritz, Mark A; McDonald, Benjamin S; Durko, Heather L; Furenlid, Lars R; Wilson, Donald W; Peterson, Todd E

    2007-01-01

    We previously demonstrated the feasibility of using silicon double-sided strip detectors (DSSDs) for SPECT imaging of the activity distribution of iodine-125 using a 300-micrometer thick detector. Based on this experience, we now have developed fully customized silicon DSSDs and associated readout electronics with the intent of developing a multi-pinhole SPECT system. Each DSSD has a 60.4 mm × 60.4 mm active area and is 1 mm thick. The strip pitch is 59 micrometers, and the readout of the 1024 strips on each side gives rise to a detector with over one million pixels. Combining four high-resolution DSSDs into a SPECT system offers an unprecedented space-bandwidth product for the imaging of single-photon emitters. The system consists of two camera heads with two silicon detectors stacked one behind the other in each head. The collimator has a focused pinhole system with cylindrical-shaped pinholes that are laser-drilled in a 250 μm tungsten plate. The unique ability to collect projection data at two magnifications simultaneously allows for multiplexed data at high resolution to be combined with lower magnification data with little or no multiplexing. With the current multi-pinhole collimator design, our SPECT system will be capable of offering high spatial resolution, sensitivity and angular sampling for small field-of-view applications, such as molecular imaging of the mouse brain.

  18. Residualization Rates of Near-Infrared Dyes for the Rational Design of Molecular Imaging Agents.

    Science.gov (United States)

    Cilliers, Cornelius; Liao, Jianshan; Atangcho, Lydia; Thurber, Greg M

    2015-12-01

    Near-infrared (NIR) fluorescence imaging is widely used for tracking antibodies and biomolecules in vivo. Clinical and preclinical applications include intraoperative imaging, tracking therapeutics, and fluorescent labeling as a surrogate for subsequent radiolabeling. Despite their extensive use, one of the fundamental properties of NIR dyes, the residualization rate within cells following internalization, has not been systematically studied. This rate is required for the rational design of probes and proper interpretation of in vivo results. In this brief report, we measure the cellular residualization rate of eight commonly used dyes encompassing three core structures (cyanine, boron-dipyrromethene (BODIPY), and oxazine/thiazine/carbopyronin). We identify residualizing (half-life >24 h) and non-residualizing (half-life <24 h) dyes in both the far-red (~650-680 nm) and near-infrared (~740-800 nm) regions. This data will allow researchers to independently and rationally select the wavelength and residualizing nature of dyes for molecular imaging agent design.

  19. In Situ Molecular Imaging of the Biofilm and Its Matrix

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Yuanzhao; Zhou, Yufan; Yao, Juan; Szymanski, Craig J.; Fredrickson, Jim K.; Shi, Liang; Cao, B.; Zhu, Zihua; Yu, Xiao-Ying

    2016-11-15

    Molecular mapping of live biofilms at submicron resolution presents a grand challenge. Here, we present the first chemical mapping results of biofilm extracellular polymeric sub-stance (EPS) components in biofilms using correlative imaging be-tween super resolution florescence microscopy and liquid time-of-flight secondary ion mass spectrometry (ToF-SIMS). Shewanella oneidensis is used as a model organism. Heavy metal anions chro-mate (Cr2O72-) consisting of chromium Cr (VI) was a model envi-ronmental stressor used to treat the biofilms. Of particular interest, biologically relevant water clusters have been first observed in the biofilms. Characteristic fragments of biofilm matrix components such as proteins, polysaccharides, and lipids can be spatially im-aged. Furthermore, characteristic fatty acids (e.g., palmitic acid), quinolone signal, and riboflavin fragments are found to respond af-ter the biofilm is treated with Cr (VI), leading to biofilm dispersion. Significant changes in water clusters and quorum sensing signals indicative of intercellular communication in the aqueous environ-ment are observed, suggesting that they might result in fatty acid synthesis and inhibit riboflavin production. The Cr (VI) reduction seems to follow the Mtr pathway leading to Cr (III) formation. Our approach potentially opens a new avenue for mechanistic insight of microbial community processes and communications using in situ imaging mass spectrometry and superresolution optical micros-copy.

  20. The use of molecular imaging combined with genomic techniques to understand the heterogeneity in cancer metastasis

    Science.gov (United States)

    Chowdhury, R; Ganeshan, B; Irshad, S; Lawler, K; Eisenblätter, M; Milewicz, H; Rodriguez-Justo, M; Miles, K; Ellis, P; Groves, A; Punwani, S

    2014-01-01

    Tumour heterogeneity has, in recent times, come to play a vital role in how we understand and treat cancers; however, the clinical translation of this has lagged behind advances in research. Although significant advancements in oncological management have been made, personalized care remains an elusive goal. Inter- and intratumour heterogeneity, particularly in the clinical setting, has been difficult to quantify and therefore to treat. The histological quantification of heterogeneity of tumours can be a logistical and clinical challenge. The ability to examine not just the whole tumour but also all the molecular variations of metastatic disease in a patient is obviously difficult with current histological techniques. Advances in imaging techniques and novel applications, alongside our understanding of tumour heterogeneity, have opened up a plethora of non-invasive biomarker potential to examine tumours, their heterogeneity and the clinical translation. This review will focus on how various imaging methods that allow for quantification of metastatic tumour heterogeneity, along with the potential of developing imaging, integrated with other in vitro diagnostic approaches such as genomics and exosome analyses, have the potential role as a non-invasive biomarker for guiding the treatment algorithm. PMID:24597512

  1. Microultrasound Molecular Imaging of Vascular Endothelial Growth Factor Receptor 2 in a Mouse Model of Tumor Angiogenesis

    Directory of Open Access Journals (Sweden)

    Joshua J. Rychak

    2007-09-01

    Full Text Available High-frequency microultrasound imaging of tumor progression in mice enables noninvasive anatomic and functional imaging at excellent spatial and temporal resolution, although microultrasonography alone does not offer molecular scale data. In the current study, we investigated the use of microbubble ultrasound contrast agents bearing targeting ligands specific for molecular markers of tumor angiogenesis using high-frequency microultrasound imaging. A xenograft tumor model in the mouse was used to image vascular endothelial growth factor receptor 2 (VEGFR-2 expression with microbubbles conjugated to an anti-VEGFR-2 monoclonal antibody or an isotype control. Microultrasound imaging was accomplished at a center frequency of 40 MHz, which provided lateral and axial resolutions of 40 and 90 μm, respectively. The B-mode (two-dimensional mode acoustic signal from microbubbles bound to the molecular target was determined by an ultrasound-based destruction-subtraction scheme. Quantification of the adherent microbubble fraction in nine tumor-bearing mice revealed significant retention of VEGFR-2-targeted microbubbles relative to control-targeted microbubbles. These data demonstrate that contrast-enhanced microultrasound imaging is a useful method for assessing molecular expression of tumor angiogenesis in mice at high resolution.

  2. Functional size analysis of bioactive materials by radiation inactivation

    International Nuclear Information System (INIS)

    Kume, Tamikazu

    1994-01-01

    When the research on various proteins including enzymes is carried out, first molecular weight is measured. The physical chemical methods used for measuring molecular weight cannot measure it in the state of actually acting in living bodies. Radiation inactivation method is the unique method which can measure the molecular weight of the active substances in living bodies. Paying attention to this point, recently it is attempted to measure the activity unit of enzymes, receptors and others, and to apply to the elucidation of their functions. In this report, the concept of the method of measuring molecular size based on radiation inactivation, the detailed experimental method and the points to which attention must be paid are described. Also its application to the elucidation of living body functions according to the example of the studies by the author is reported. The concept of the measurement of molecular weight by radiation inactivation is based on target theory. The preparation of samples, the effect of oxygen, radiation sources, dosimetry, irradiation temperature, internal standard process and so on are reported. The trend of the research is shown. (K.I.)

  3. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

    2015-03-15

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

  4. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    International Nuclear Information System (INIS)

    Bradshaw, Tyler J.; Bowen, Stephen R.; Deveau, Michael A.; Kubicek, Lyndsay; White, Pamela; Bentzen, Søren M.; Chappell, Richard J.; Forrest, Lisa J.; Jeraj, Robert

    2015-01-01

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV max ; SUV mean ) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R 2 . Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV mean (P=.018), and midtreatment FLT SUV max (P=.006). Large decreases in FLT SUV mean from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV max (P=.022) in combination with large FLT response from

  5. The Use of Radiation Detectors in Medicine: The Future of Molecular Imaging and Multimodality Imaging: Advantages and Technological Challenges (3/3)

    CERN Multimedia

    CERN. Geneva

    2009-01-01

    The development of radiation detectors in the field of nuclear and particle physics has had a terrific impact in medical imaging since this latter discipline took off in late ’70 with the invention of the CT scanners. The massive use in High Energy Physics of position sensitive gas detectors, of high Z and high density scintillators coupled to Photomultiplier (PMT) and Position Sensitive Photomultipliers (PSPMT), and of solid state detectors has triggered during the last 30 years a series of novel applications in Medical Imaging with ionizing radiation. The accelerated scientific progression in genetics and molecular biology has finally generated what it is now called Molecular Imaging. This field of research presents additional challenges not only in the technology of radiation detector, but more and more in the ASIC electronics, fast digital readout and parallel software. In this series of three lectures I will try to present how high energy physics and medical imaging development have both benefited by t...

  6. Efficiency of superoxide anions in the inactivation of selected dehydrogenases

    International Nuclear Information System (INIS)

    Rodacka, Aleksandra; Serafin, Eligiusz; Puchala, Mieczyslaw

    2010-01-01

    The most ubiquitous of the primary reactive oxygen species, formed in all aerobes, is the superoxide free radical. It is believed that the superoxide anion radical shows low reactivity and in oxidative stress it is regarded mainly as an initiator of more reactive species such as · OH and ONOO - . In this paper, the effectiveness of inactivation of selected enzymes by radiation-generated superoxide radicals in comparison with the effectiveness of the other products of water radiolysis is examined. We investigate three enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH). We show that the direct contribution of the superoxide anion radical to GAPDH and ADH inactivation is significant. The effectiveness of the superoxide anion in the inactivation of GAPDH and ADG was only 2.4 and 2.8 times smaller, respectively, in comparison with hydroxyl radical. LDH was practically not inactivated by the superoxide anion. Despite the fact that the studied dehydrogenases belong to the same class of enzymes (oxidoreductases), all have a similar molecular weight and are tetramers, their susceptibility to free-radical damage varies. The differences in the radiosensitivity of the enzymes are not determined by the basic structural parameters analyzed. A significant role in inactivation susceptibility is played by the type of amino acid residues and their localization within enzyme molecules.

  7. Efficiency of superoxide anions in the inactivation of selected dehydrogenases

    Energy Technology Data Exchange (ETDEWEB)

    Rodacka, Aleksandra, E-mail: olakow@biol.uni.lodz.p [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Serafin, Eligiusz, E-mail: serafin@biol.uni.lodz.p [Laboratory of Computer and Analytical Techniques, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Puchala, Mieczyslaw, E-mail: puchala@biol.uni.lodz.p [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2010-09-15

    The most ubiquitous of the primary reactive oxygen species, formed in all aerobes, is the superoxide free radical. It is believed that the superoxide anion radical shows low reactivity and in oxidative stress it is regarded mainly as an initiator of more reactive species such as {sup {center_dot}}OH and ONOO{sup -}. In this paper, the effectiveness of inactivation of selected enzymes by radiation-generated superoxide radicals in comparison with the effectiveness of the other products of water radiolysis is examined. We investigate three enzymes: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH). We show that the direct contribution of the superoxide anion radical to GAPDH and ADH inactivation is significant. The effectiveness of the superoxide anion in the inactivation of GAPDH and ADG was only 2.4 and 2.8 times smaller, respectively, in comparison with hydroxyl radical. LDH was practically not inactivated by the superoxide anion. Despite the fact that the studied dehydrogenases belong to the same class of enzymes (oxidoreductases), all have a similar molecular weight and are tetramers, their susceptibility to free-radical damage varies. The differences in the radiosensitivity of the enzymes are not determined by the basic structural parameters analyzed. A significant role in inactivation susceptibility is played by the type of amino acid residues and their localization within enzyme molecules.

  8. Photoelectron photoion coincidence imaging of ultrafast control in multichannel molecular dynamics.

    Science.gov (United States)

    Lehmann, C Stefan; Ram, N Bhargava; Irimia, Daniel; Janssen, Maurice H M

    2011-01-01

    The control of multichannel ionic fragmentation dynamics in CF3I is studied by femtosecond pulse shaping and velocity map photoelectron photoion coincidence imaging. When CF3I is photoexcited with femtosecond laser pulses around 540 nm there are two major ions observed in the time-of-flight mass spectrum, the parent CF3I+ ion and the CF3+ fragment ion. In this first study we focussed on the influence of LCD-shaped laser pulses on the molecular dynamics. The three-dimensional recoil distribution of electrons and ions were imaged in coincidence using a single time-of-flight delay line detector. By fast switching of the voltages on the various velocity map ion lenses after detection of the electron, both the electron and the coincident ion are measured with the same imaging detector. These results demonstrate that a significant simplification of a photoelectron-photoion coincidence imaging apparatus is in principle possible using switched lens voltages. It is observed that shaped laser fields like chirped pulses, double pulses, and multiple pulses can enhance the CF3+CF3I+ ratio by up to 100%. The total energetics of the dynamics is revealed by analysis of the coincident photoelectron spectra and the kinetic energy of the CF3+ and I fragments. Both the parent CF3I+ and the CF3+ fragment result from a five-photon excitation process. The fragments are formed with very low kinetic energy. The photoelectron spectra and CF3+/CF3I+ ratio vary with the center wavelength of the shaped laser pulses. An optimal enhancement of the CF3+/CF3I+ ratio by about 60% is observed for the double pulse excitation when the pulses are spaced 60 fs apart. We propose that the control mechanism is determined by dynamics on neutral excited states and we discuss the results in relation to the location of electronically excited (Rydberg) states of CF3I.

  9. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models.

    Directory of Open Access Journals (Sweden)

    Scott B Raymond

    Full Text Available Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP, across a large age range (9-26 months, with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.

  10. Infrared images of reflection nebulae and Orion's bar: Fluorescent molecular hydrogen and the 3.3 micron feature

    International Nuclear Information System (INIS)

    Burton, M.G.; Moorhouse, A.; Brand, P.W.J.L.; Roche, P.F.; Geballe, T.R.

    1989-01-01

    Images were obtained of the (fluorescent) molecular hydrogen 1-0 S(1) line, and of the 3.3 micron emission feature, in Orion's Bar and three reflection nebulae. The emission from these species appears to come from the same spatial locations in all sources observed. This suggests that the 3.3 micron feature is excited by the same energetic UV-photons which cause the molecular hydrogen to fluoresce

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

    International Nuclear Information System (INIS)

    Ferro F, G.; Torres G, E.; Gonzalez V, A.; Murphy, C.A. de

    2006-01-01

    Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. 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 99m Tc-HYNlC-TOC and 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 99m Tc-HYNlC-TOC or 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. 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 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)

  12. Sodium and T1rho MRI for molecular and diagnostic imaging of articular cartilage.

    Science.gov (United States)

    Borthakur, Arijitt; Mellon, Eric; Niyogi, Sampreet; Witschey, Walter; Kneeland, J Bruce; Reddy, Ravinder

    2006-11-01

    In this article, both sodium magnetic resonance (MR) and T1rho relaxation mapping aimed at measuring molecular changes in cartilage for the diagnostic imaging of osteoarthritis are reviewed. First, an introduction to structure of cartilage, its degeneration in osteoarthritis (OA) and an outline of diagnostic imaging methods in quantifying molecular changes and early diagnostic aspects of cartilage degeneration are described. The sodium MRI section begins with a brief overview of the theory of sodium NMR of biological tissues and is followed by a section on multiple quantum filters that can be used to quantify both bi-exponential relaxation and residual quadrupolar interaction. Specifically, (i) the rationale behind the use of sodium MRI in quantifying proteoglycan (PG) changes, (ii) validation studies using biochemical assays, (iii) studies on human OA specimens, (iv) results on animal models and (v) clinical imaging protocols are reviewed. Results demonstrating the feasibility of quantifying PG in OA patients and comparison with that in healthy subjects are also presented. The section concludes with the discussion of advantages and potential issues with sodium MRI and the impact of new technological advancements (e.g. ultra-high field scanners and parallel imaging methods). In the theory section on T1rho, a brief description of (i) principles of measuring T1rho relaxation, (ii) pulse sequences for computing T1rho relaxation maps, (iii) issues regarding radio frequency power deposition, (iv) mechanisms that contribute to T1rho in biological tissues and (v) effects of exchange and dipolar interaction on T1rho dispersion are discussed. Correlation of T1rho relaxation rate with macromolecular content and biomechanical properties in cartilage specimens subjected to trypsin and cytokine-induced glycosaminoglycan depletion and validation against biochemical assay and histopathology are presented. Experimental T1rho data from osteoarthritic specimens, animal models

  13. Optimization and performance evaluation of a conical mirror based fluorescence molecular tomography imaging system

    Science.gov (United States)

    Zhao, Yue; Zhang, Wei; Zhu, Dianwen; Li, Changqing

    2016-03-01

    We performed numerical simulations and phantom experiments with a conical mirror based fluorescence molecular tomography (FMT) imaging system to optimize its performance. With phantom experiments, we have compared three measurement modes in FMT: the whole surface measurement mode, the transmission mode, and the reflection mode. Our results indicated that the whole surface measurement mode performed the best. Then, we applied two different neutral density (ND) filters to improve the measurement's dynamic range. The benefits from ND filters are not as much as predicted. Finally, with numerical simulations, we have compared two laser excitation patterns: line and point. With the same excitation position number, we found that the line laser excitation had slightly better FMT reconstruction results than the point laser excitation. In the future, we will implement Monte Carlo ray tracing simulations to calculate multiple reflection photons, and create a look-up table accordingly for calibration.

  14. A small molecular pH-dependent fluorescent probe for cancer cell imaging in living cell.

    Science.gov (United States)

    Ma, Junbao; Li, Wenqi; Li, Juanjuan; Shi, Rongguang; Yin, Gui; Wang, Ruiyong

    2018-05-15

    A novel pH-dependent two-photon fluorescent molecular probe ABMP has been prepared based on the fluorophore of 2, 4, 6-trisubstituted pyridine. The probe has an absorption wavelength at 354 nm and corresponding emission wavelength at 475 nm with the working pH range from 2.20 to 7.00, especially owning a good liner response from pH = 2.40 to pH = 4.00. ABMP also has excellent reversibility, photostability and selectivity which promotes its ability in analytical application. The probe can be excited with a two-photon fluorescence microscopy and the fluorescence cell imaging indicated that the probe can distinguish Hela cancer cells out of normal cells with a two-photon fluorescence microscopy which suggested its potential application in tumor cell detection. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Inactivation of Candida biofilms by non-thermal plasma and its enhancement for fungistatic effect of antifungal drugs.

    Directory of Open Access Journals (Sweden)

    Yi Sun

    Full Text Available We investigated the antifungal effect of non-thermal plasma, as well as its combination with common antifungal drugs, against Candida biofilms. A direct current atmospheric pressure He/O(2 (2% plasma microjet (PMJ was used to treat Candida biofilms in a 96-well plate. Inactivation efficacies of the biofilms were evaluated by XTT assay and counting colony forming units (CFUs. Morphological properties of the biofilms were evaluated by Scanning Electron Microscope (SEM. The sessile minimal inhibitory concentrations (SMICs of fluconazole, amphotericin B, and caspofungin for the biofilms were also tested. Electron Spin Resonance (ESR spectroscopy was used to detect the reactive oxygen species (ROS generated directly and indirectly by PMJ. The Candida biofilms were completely inactivated after 1 min PMJ treatment, where severely deformed fungal elements were observed in SEM images. The SMICs of the tested antifungal drugs for the plasma-treated biofilms were decreased by 2-6 folds of dilution, compared to those of the untreated controls. ROS such as hydroxyl radical ((•OH, superoxide anion radical ((•O(2 (- and singlet molecular oxygen ((1O(2 were detected by ESR. We hence conclude that He/O(2 (2% plasma alone, as well as in combination with common antifungal drugs, is able to inactivate Candida biofilms rapidly. The generation of ROS is believed to be one of the underlying mechanisms for the fungicidal activity of plasma.

  16. Translation of New Molecular Imaging Approaches to the Clinical Setting: Bridging the Gap to Implementation.

    Science.gov (United States)

    van Es, Suzanne C; Venema, Clasina M; Glaudemans, Andor W J M; Lub-de Hooge, Marjolijn N; Elias, Sjoerd G; Boellaard, Ronald; Hospers, Geke A P; Schröder, Carolina P; de Vries, Elisabeth G E

    2016-02-01

    Molecular imaging with PET is a rapidly emerging technique. In breast cancer patients, more than 45 different PET tracers have been or are presently being tested. With a good rationale, after development of the tracer and proven feasibility, it is of interest to evaluate whether there is a potential meaningful role for the tracer in the clinical setting-such as in staging, in the (early) prediction of a treatment response, or in supporting drug choices. So far, only (18)F-FDG PET has been incorporated into breast cancer guidelines. For proof of the clinical relevance of tracers, especially for analysis in a multicenter setting, standardization of the technology and access to the novel PET tracer are required. However, resources for PET implementation research are limited. Therefore, next to randomized studies, novel approaches are required for proving the clinical value of PET tracers with the smallest possible number of patients. The aim of this review is to describe the process of the development of PET tracers and the level of evidence needed for the use of these tracers in breast cancer. Several breast cancer trials have been performed with the PET tracers (18)F-FDG, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), and (18)F-fluoroestradiol ((18)F-FES). We studied them to learn lessons for the implementation of novel tracers. After defining the gap between a good rationale for a tracer and implementation in the clinical setting, we propose solutions to fill the gap to try to bring more PET tracers to daily clinical practice. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  17. Mapping molecular adhesion sites inside SMIL coated capillaries using atomic force microscopy recognition imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leitner, Michael [Institute of Biophysics, Johannes Kepler University Linz, Gruberstrasse 40, 4020 Linz (Austria); Stock, Lorenz G. [Division of Chemistry and Bioanalytics, Department of Molecular Biology, University Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg (Austria); Christian Doppler Laboratory for Innovative Tools for the Characterization of Biosimilars, University Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg (Austria); Traxler, Lukas [Institute of Biophysics, Johannes Kepler University Linz, Gruberstrasse 40, 4020 Linz (Austria); Leclercq, Laurent [Institut des Biomolécules Max Mousseron (IBMM, UMR 5247, CNRS, Université de Montpellier, Ecole Nationale Supérieure de Chimie de Montpellier), Place Eugène Bataillon, CC 1706, 34095 Montpellier (France); Bonazza, Klaus; Friedbacher, Gernot [Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/164, 1060 Vienna (Austria); Cottet, Hervé [Institut des Biomolécules Max Mousseron (IBMM, UMR 5247, CNRS, Université de Montpellier, Ecole Nationale Supérieure de Chimie de Montpellier), Place Eugène Bataillon, CC 1706, 34095 Montpellier (France); Stutz, Hanno [Division of Chemistry and Bioanalytics, Department of Molecular Biology, University Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg (Austria); Christian Doppler Laboratory for Innovative Tools for the Characterization of Biosimilars, University Salzburg, Hellbrunnerstrasse 34, 5020 Salzburg (Austria); Ebner, Andreas, E-mail: andreas.ebner@jku.at [Institute of Biophysics, Johannes Kepler University Linz, Gruberstrasse 40, 4020 Linz (Austria)

    2016-08-03

    Capillary zone electrophoresis (CZE) is a powerful analytical technique for fast and efficient separation of different analytes ranging from small inorganic ions to large proteins. However electrophoretic resolution significantly depends on the coating of the inner capillary surface. High technical efforts like Successive Multiple Ionic Polymer Layer (SMIL) generation have been taken to develop stable coatings with switchable surface charges fulfilling the requirements needed for optimal separation. Although the performance can be easily proven in normalized test runs, characterization of the coating itself remains challenging. Atomic force microscopy (AFM) allows for topographical investigation of biological and analytical relevant surfaces with nanometer resolution and yields information about the surface roughness and homogeneity. Upgrading the scanning tip to a molecular biosensor by adhesive molecules (like partly inverted charged molecules) allows for performing topography and recognition imaging (TREC). As a result, simultaneously acquired sample topography and adhesion maps can be recorded. We optimized this technique for electrophoresis capillaries and investigated the charge distribution of differently composed and treated SMIL coatings. By using the positively charged protein avidin as a single molecule sensor, we compared these SMIL coatings with respect to negative charges, resulting in adhesion maps with nanometer resolution. The capability of TREC as a functional investigation technique at the nanoscale was successfully demonstrated. - Highlights: • SMIL coating allows generation of homogeneous ultra-flat surfaces. • Molecular electrostatic adhesion forces can be determined in the inner wall of CZE capillary with picoNewton accuracy. • Topographical images and simultaneously acquired adhesion maps yield morphological and chemical information at the nanoscale.

  18. PET molecular imaging of peripheral and central inflammatory processes targeting the TSPO 18 kDa

    International Nuclear Information System (INIS)

    Bernards, Nicholas

    2014-01-01

    The purpose of this study was to determine the in vivo potential of the TSPO 18 kDa as a bio-marker of inflammation, with the use of its radioligand [ 18 F]DPA-714, to non-invasively quantify the inflammatory state within the scope of various pathologies. Multiple animal models of various inflammatory diseases, to include: inflammatory bowel disease, neuro-inflammation, and septic shock, were developed and put in place by adapted measures. The animals well-being and the subsequent inflammation was evaluated. The inflammatory state was measured using quantitative PET imaging with the TSPO radioligand [ 18 F]DPA-714 and correlated to the expression of conventional inflammatory markers using microscopy. Based on the observed data, we were able to distinguish control groups from treated groups when using [ 18 F]DPA-714. This TSPO radioligand permitted us to quantify the inflammatory level and to observe evolutionary changes in the inflammatory state of the disease in multiple models. The PET results, using the [ 18 F]DPA-714 signal was correlated with an increased TSPO expression at cellular level. Results indicate that [ 18 F]DPA-714 is a suitable tracer for studying inflammation of multiple diseases. [ 18 F]DPA-714 could be a good molecular probe to non-invasively evaluate the level and localization of inflammation. Moreover, in vivo imaging using this TSPO ligand is potentially a powerful tool to stage and certainly to follow the evolution and therapeutic efficiency at molecular level in inflammatory diseases. (author) [fr

  19. Label-free molecular imaging of bacterial communities of the opportunistic pathogen Pseudomonas aeruginosa

    Science.gov (United States)

    Baig, Nameera; Polisetti, Sneha; Morales-Soto, Nydia; Dunham, Sage J. B.; Sweedler, Jonathan V.; Shrout, Joshua D.; Bohn, Paul W.

    2016-09-01

    Biofilms, such as those formed by the opportunistic human pathogen Pseudomonas aeruginosa are complex, matrix enclosed, and surface-associated communities of cells. Bacteria that are part of a biofilm community are much more resistant to antibiotics and the host immune response than their free-floating counterparts. P. aeruginosa biofilms are associated with persistent and chronic infections in diseases such as cystic fibrosis and HIV-AIDS. P. aeruginosa synthesizes and secretes signaling molecules such as the Pseudomonas quinolone signal (PQS) which are implicated in quorum sensing (QS), where bacteria regulate gene expression based on population density. Processes such as biofilms formation and virulence are regulated by QS. This manuscript describes the powerful molecular imaging capabilities of confocal Raman microscopy (CRM) and surface enhanced Raman spectroscopy (SERS) in conjunction with multivariate statistical tools such as principal component analysis (PCA) for studying the spatiotemporal distribution of signaling molecules, secondary metabolites and virulence factors in biofilm communities of P. aeruginosa. Our observations reveal that the laboratory strain PAO1C synthesizes and secretes 2-alkyl-4-hydroxyquinoline N-oxides and 2-alkyl-4-hydroxyquinolones in high abundance, while the isogenic acyl homoserine lactone QS-deficient mutant (ΔlasIΔrhlI) strain produces predominantly 2-alkyl-quinolones during biofilm formation. This study underscores the use of CRM, along with traditional biological tools such as genetics, for studying the behavior of microbial communities at the molecular level.

  20. The benefits of paired-agent imaging in molecular-guided surgery: an update on methods and applications (Conference Presentation)

    Science.gov (United States)

    Tichauer, Kenneth M.

    2016-03-01

    One of the major complications with conventional imaging-agent-based molecular imaging, particularly for cancer imaging, is variability in agent delivery and nonspecific retention in biological tissue. Such factors can account to "swamp" the signal arising from specifically bound imaging agent, which is presumably indicative of the concentration of targeted biomolecule. In the 1950s, Pressman et al. proposed a method of accounting for these delivery and retention effects by normalizing targeted antibody retention to the retention of a co-administered "untargeted"/control imaging agent [1]. Our group resurrected the approach within the last 5 years, finding ways to utilize this so-called "paired-agent" imaging approach to directly quantify biomolecule concentration in tissue (in vitro, ex vivo, and in vivo) [2]. These novel paired-agent imaging approaches capable of quantifying biomolecule concentration provide enormous potential for being adapted to and optimizing molecular-guided surgery, which has a principle goal of identifying distinct biological tissues (tumor, nerves, etc…) based on their distinct molecular environment. This presentation will cover the principles and nuances of paired-agent imaging, as well as the current status of the field and future applications. [1] D. Pressman, E. D. Day, and M. Blau, "The use of paired labeling in the determination of tumor-localizing antibodies," Cancer Res, 17(9), 845-50 (1957). [2] K. M. Tichauer, Y. Wang, B. W. Pogue et al., "Quantitative in vivo cell-surface receptor imaging in oncology: kinetic modeling and paired-agent principles from nuclear medicine and optical imaging," Phys Med Biol, 60(14), R239-69 (2015).

  1. Transcription-Based Molecular Imaging and Gene Therapy for Castration-resistant and Metastatic Prostate Cancer in Translational Models

    OpenAIRE

    Jiang, Ziyue

    2013-01-01

    The advanced stage of prostate cancer is the second leading cause of cancer-related death for American men. Novel, effective treatment options and more cancer-specific diagnostic tools are urgently needed to facilitate patient management. Here, we explored the construction and application of an array of gene-based molecular imaging and therapeutic vectors in a variety of clinically relevant settings. These vectors exploit prostate cancer-specific promoters to control the transcription of imag...

  2. Observation of the molecular organization of calcium release sites in fast- and slow-twitch skeletal muscle with nanoscale imaging

    OpenAIRE

    Jayasinghe, Isuru D.; Munro, Michelle; Baddeley, David; Launikonis, Bradley S.; Soeller, Christian

    2014-01-01

    Localization microscopy is a fairly recently introduced super-resolution fluorescence imaging modality capable of achieving nanometre-scale resolution. We have applied the dSTORM variation of this method to image intracellular molecular assemblies in skeletal muscle fibres which are large cells that critically rely on nanoscale signalling domains, the triads. Immunofluorescence staining in fixed adult rat skeletal muscle sections revealed clear differences between fast- and slow-twitch fibres...

  3. Antibody or Antibody Fragments: Implications for Molecular Imaging and Targeted Therapy of Solid Tumors

    Directory of Open Access Journals (Sweden)

    Katerina T. Xenaki

    2017-10-01

    Full Text Available The use of antibody-based therapeutics has proven very promising for clinical applications in cancer patients, with multiple examples of antibodies and antibody–drug conjugates successfully applied for the treatment of solid tumors and lymphomas. Given reported recurrence rates, improvements are clearly still necessary. A major factor limiting the efficacy of antibody-targeted cancer therapies may be the incomplete penetration of the antibody or antibody–drug conjugate into the tumor. Incomplete tumor penetration also affects the outcome of molecular imaging, when using such targeting agents. From the injection site until they arrive inside the tumor, targeting molecules are faced with several barriers that impact intratumoral distribution. The primary means of antibody transport inside tumors is based on diffusion. The diffusive penetration inside the tumor is influenced by both antibody properties, such as size and binding affinity, as well as tumor properties, such as microenvironment, vascularization, and targeted antigen availability. Engineering smaller antibody fragments has shown to improve the rate of tumor uptake and intratumoral distribution. However, it is often accompanied by more rapid clearance from the body and in several cases also by inherent destabilization and reduction of the binding affinity of the antibody. In this perspective, we discuss different cancer targeting approaches based on antibodies or their fragments. We carefully consider how their size and binding properties influence their intratumoral uptake and distribution, and how this may affect cancer imaging and therapy of solid tumors.

  4. Quantification of low molecular weight compounds by MALDI imaging mass spectrometry - A tutorial review.

    Science.gov (United States)

    Rzagalinski, Ignacy; Volmer, Dietrich A

    2017-07-01

    Matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) permits label-free in situ analysis of chemical compounds directly from the surface of two-dimensional biological tissue slices. It links qualitative molecular information of compounds to their spatial coordinates and distribution within the investigated tissue. MALDI-MSI can also provide the quantitative amounts of target compounds in the tissue, if proper calibration techniques are performed. Obviously, as the target molecules are embedded within the biological tissue environment and analysis must be performed at their precise locations, there is no possibility for extensive sample clean-up routines or chromatographic separations as usually performed with homogenized biological materials; ion suppression phenomena therefore become a critical side effect of MALDI-MSI. Absolute quantificati