DOCSLIB.ORG

Imaging Biomarker Development and Optimization of 195Mpt-Cisplatin

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Imaging Biomarker Development and Optimization of 195Mpt-Cisplatin Pt-cisplatin 195m Ga-DOTATATE 68 and Else Aagje Aalbersberg Imaging biomarker development development biomarker Imaging and optimization of and optimization Imaging biomarker development and optimization of 195mPt-cisplatin and 68Ga-DOTATATE Else Aagje Aalbersberg Imaging biomarker development and optimization of 195mPt-cisplatin and 68Ga-DOTATATE Else Aagje Aalbersberg ISBN: 978-94-6323-813-7 © Else Aagje Aalbersberg Cover design and layout: © evelienjagtman.com Printed by: Gildeprint Imaging biomarker development and optimization of 195mPt-cisplatin and 68Ga-DOTATATE Ontwikkeling en optimalisatie van 195mPt-cisplatin en 68Ga-DOTATATE als biomarker (met een samenvatting in het Nederlands) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof.dr. H.R.B.M. Kummeling, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op dinsdag 29 oktober 2019 des middags te 12.45 uur door Else Aagje Aalbersberg geboren op 16 oktober 1987 te Waalre Promotor: Prof. dr. G.D. Valk Copromotoren: Dr. M.P.M. Stokkel Dr. W.V. Vogel This research was performed at the department of Nuclear Medicine at the Antoni van Leeuwenhoek hospital, Amsterdam, the Netherlands. Printing of this thesis was financially supported by: 2Quart Medical BV Advanced Accelerator Applications ChipSoft Ipsen MILabs NKI-AVL NRG Pfizer CONTENTS CHAPTER 1. General introduction 9 CHAPTER 2. Preclinical imaging characteristics and quantification of Platinum- 19 195m SPECT Eur J Nucl Med Mol Imaging. 2017;44:1347-1354. CHAPTER 3. Toxicity, efficacy and tumour imaging of195m Pt-cisplatin in mice 37 Manuscript in preparation. CHAPTER 4. Pre-hydration in cisplatin-based CCRT: effects on tumour 53 concentrations and treatment outcome Radiother Oncol. 2019;134:30-36. CHAPTER 5. A practical guide to production and PET/CT imaging of 68Ga- 71 DOTATATE for neuroendocrine tumors in daily clinical practice J Vis Exp. 2019 Apr 17;(146). CHAPTER 6. Differences in uptake between68 Ga-DOTATATE and 68Ga-HA- 89 DOTATATE: a retrospective study in 342 patients Submitted and under review. CHAPTER 7. Influence of Lanreotide on Uptake of68 Ga-DOTATATE in Patients 107 with Neuroendocrine Tumours: a Prospective Intra-Patient Evaluation Eur J Nucl Med Mol Imaging. 2019;46:696-703. CHAPTER 8. Parameters to predict progression free and overall survival after 125 peptide receptor radionuclide therapy: a multivariate analysis in 782 patients J Nucl Med. 2019 [e-pub ahead of print]. CHAPTER 9. General discussion 145 ADDENDUM Nederlandse samenvatting 163 Dankwoord 171 Affiliations 177 Publications 183 Curriculum Vitae 187 Chapter 1 General introduction General introduction GENERAL INTRODUCTION 1 Cancer affects people worldwide, causing approximately 9.6 million deaths in 2018 globally, making it the second leading cause of death after cardiovascular disease.1 The socio-economic impact of cancer is enormous, and it was estimated that the worldwide cost of cancer was $1.16 trillion in 2010. Although cancer remains a deadly disease, the 10-year survival rate for all cancers has increased in the Netherlands from 32% in 1961-1970 to 54% in 2006-2010.2 This increase in survival is due to both early detection and improved treatment strategies, in which new anti-cancer drugs play a pivotal role. However, with the increasing number of drugs and drug-classes (chemotherapy, targeted therapy, immunotherapy, etc.) either approved or in development, other challenges present itself. The first challenge is selecting the most effective drug for a patient when many alternatives are available. Since ineffective treatment wastes valuable time and allows for disease progression, the most effective drug for an individual patient should be identified prior to the start of treatment based on patient- or tumor characteristics. This not only benefits individual patients, but also society as a whole since many modern therapies come at a high economic cost. The second challenge is choosing the drug with the least side-effects for a patient, without compromising treatment outcome. Side-effects can be severe, impact quality of life, and require dose adjustments, leading to sub-optimal treatment. The third challenge is performing response-assessment at the right time allowing for alterations of the treatment-regimen. Premature response-assessment can unjustly conclude that a drug is ineffective while late response-assessment risks disease progression under ineffective therapy. Nuclear medicine and quantitative imaging biomarkers could play a pivotal role in overcoming these challenges. Nuclear medicine Nuclear medicine employs radiopharmaceuticals for imaging of organ function or pathophysiology of disease. In contrast to anatomical imaging, nuclear molecular imaging provides information at the cellular or molecular level. These changes often present themselves on molecular imaging prior to anatomical changes which occur later in the course of a disease.3 Due to the nano- to picomolar sensitivity of nuclear medicine imaging modalities, tracer amounts of radiopharmaceuticals provide accurate information without interfering with the biological process that is being studied.4 Ideally, the half-life of the radioactive isotope that is used matches the duration of the biologically relevant distribution of the molecule being investigated. This ensures complete imaging of the desired physiological process without causing excess radiation dose.4 Furthermore, data can be acquired over time through dynamic or serial imaging. With the increasing number of molecules, linkers, and isotopes becoming available, and the advances in imaging technology, the field of nuclear medicine is diversifying and gaining importance in healthcare.3 11 Chapter 1 Imaging biomarkers When a nuclear medicine examination is used to diagnose or stage cancer or to predict or monitor treatment efficacy or toxicity, this is known as an imaging biomarker. A biomarker is defined as ‘a characteristic that is measured as an indicator of normal biological processes, or responses to an exposure or intervention, including therapeutic interventions.’5 Biomarkers in nuclear medicine often fall in the category of diagnostic biomarker, but are also used as monitoring biomarker, response biomarker, predictive biomarker, prognostic biomarker, or safety biomarker.5 Imaging biomarkers can provide non-invasive data for tumor detection, monitoring, and response assessment, and examine all pathological- and normal organ tissues in one non-invasive examination, even providing data on heterogeneity within a tissue.6 In order for an imaging biomarker to be applicable in healthcare, it should measure a relevant (biological) feature, be measured quantitatively or categorically, be both repeatable and reliable, and should be validated both technically and clinically.7 This requires standardized acquisition, reconstruction, and analysis protocols. For patient selection in clinical oncological care, predictive and prognostic nuclear imaging biomarkers are gaining importance. A classic example in nuclear medicine is radioactive iodine, in which scintigraphic uptake of iodine is demonstrated with a low-dose of 123I or 131I prior to high-dose therapy with 131I.8 In the past decade imaging of radiolabeled drugs, peptides, and antibodies has increased tremendously for treatment selection, with 68Ga-labeled peptides and 89Zr-labeled antibodies as frontrunners. Uptake of 68Ga-labeled peptides is a prerequisite for treatment with 177Lu-labeled peptides in both neuroendocrine tumors and prostate cancer, while 89Zr-labeled antibodies related to the immune system (immunoPET) are currently being explored for patient selection prior to immunotherapy. Imaging biomarkers not only provide essential information in routine clinical care, but can also be instrumental in clinical trials. In an era where oncological treatment is shifting from traditional chemotherapies to molecular therapies or personalized medicine, patient selection, or patient enrichment, in clinical trials has become increasingly important.9 Introducing (imaging) biomarkers as early as phase I trials could accelerate research and decrease the number of negative phase II and phase III trials and increase the a priori chance of success.4,7,9,10 Up-front selection of patients with (imaging) biomarkers could prevent drugs from being effective only in a sub-group of a larger clinical trial.11,12 When used appropriately, imaging biomarkers could enhance drug discovery, aid in smart clinical trial design to improve the clinical management of oncological patients. The concept of imaging biomarkers is identical for each different type of cancer or different therapy, but each requires its own radiolabeled molecule, imaging protocol, and (pre-)clinical testing and validation. In this thesis, the described aspects of biomarker imaging are explored for two different radiolabeled molecules.Part 1 of this thesis describes the first pre-clinical 12 General introduction steps for the introduction of 195mPt-cisplatin as an imaging biomarker for cisplatin treatment. Additionally, factors that influence the biodistribution of cisplatin are investigated.Part 2 1 focusses on 68Ga-somatostatin receptor imaging for neuroendocrine tumors, factors that influence the uptake of68 Ga-somatostatin receptor imaging, and the subsequent treatment with 177Lu-somatostatin analogues. Part 1: Cisplatin Cisplatin (cis-diamminedichloridoplatinum(II)) is a traditional chemotherapeutic drug that
Load more

Recommended publications
  • Circular of the Bureau of Standards No. 562: Bibliography of Research on Deuterium and Tritium Compounds 1945 and 1952
    NBS CIRCULAR 562 Bibliography of Research on Deuterium and Tritium Compounds 1945 to 1952 UNITED STATES DEPARTMENT OF COMMERCE NATIONAL BUREAU OF STANDARDS PERIODICALS OF THE NATIONAL BUREAU OF STANDARDS (Published monthly) The National Bureau of Standards is engaged in fundamental and applied research in physics, chemistry, mathematics, and engineering. Projects are conducted in fifteen fields: electricity and electronics, optics and metrology, heat and power, atomic and radiation physics, chemistry, mechanics, organic and fibrous materials, metallurgy, mineral products, building technology, applied mathematics, data process¬ ing systems, cryogenic engineering, radio propagation, and radio standards. The Bureau has custody of the national standards of measurement and conducts research leading to the improvement of scientific and engineering standards and of techniques and methods of measurement. Testing methods and in¬ struments are developed; physical constants and properties of materials are determined; and technical processes are investigated. Journal of Research The Journal presents research papers by authorities in the specialized fields of physics, mathematics, chemistry, and engineering. Complete details of the work are presented, including laboratory data, experimental procedures, and theoretical and mathematical analyses. Annual subscription: domestic, $4.00; 25 cents additional for foreign mailing. Technical News Bulletin Summaries of current research at the National Bureau of Standards are published each month in the Technical News Bulletin. The articles are brief, with emphasis on the results of research, chosen on the basis of their scientific or technologic importance. Lists of all Bureau publications during the preceding month are given, including Research Papers, Handbooks, Applied Mathematics Series, Building Mate¬ rials and Structures Reports, Miscellaneous Publications, and Circulars.
    [Show full text]
  • Recent Advances in Multi-Modality Molecular Imaging of Small Animals
    8/3/2016 Recent Advances in Multi-modality Molecular Imaging of Small Animals Benjamin M. W. Tsui, Ph.D. Department of Radiology August 3, 2016 1 Outline Introduction Early developments of molecular imaging (MI) of small animals (SA) Development of multi-modality MI of SA – Instrumentation – Image reconstruction and processing methods Recent advances Comparing Biomedical Imaging Techniques US MRI X-ray CT SPECT PET OPTICAL Anatomical Yes Yes Yes No No No Functional Yes Yes No Yes Yes Yes Resolution Sub- Sub- Sub- <1 mm ~1 mm Sub- millimeter millimeter millimeter (0.6 – 0.3mm) micron Molecular No Good No Excellent Excellent Excellent Target Molecular targeting No Poor No Good Excellent Poor sensitivity Translational Yes Yes Yes Yes Yes No 1 8/3/2016 Traditional Nuclear Medicine Imaging Techniques an important function imaging modality Activity labels tracer or biomarkers w/ radioisotope distribution administers radio-tracer into patient Gamma detects photon emissions using position- photons sensitive detectors Collimator Provides localization & biodistribution information of radiotracers - e.g., perfusion, potassium analog, monoclonal antibody Scintillation Clinical applications crystal Scintillation - e.g., cardiac and kidney functions, cancer Camera Positioning Photomultiplier detection, neurological disorders circuitry tube array EMISSION COMPUTED TOMOGRAPHY (ECT) an important function imaging modality Nuclear imaging combined with computed tomography (Image reconstruction from multiple projections) Categories of ECT - PET
    [Show full text]
  • First Observation of Alpha Decay of 190-Pt to the First Excited Level (E
    First observation of α decay of 190Pt to the first excited 186 level (Eexc = 137.2 keV) of Os P. Bellia, R. Bernabeia,b,1, F. Cappellac,d, R. Cerullie, F.A. Danevichf , A. Incicchittic, M. Laubensteine, S.S. Nagornyf , S. Nisie, O.G. Polischukf , V.I. Tretyakf aINFN, Sezione di Roma “Tor Vergata”, I-00133 Rome, Italy bDipartimento di Fisica, Universita` di Roma “Tor Vergata” I-00133 Rome, Italy cINFN, Sezione di Roma “La Sapienza”, I-00185 Rome, Italy dDipartimento di Fisica, Universita` di Roma La “Sapienza”, I-00185 Rome, Italy eINFN, Laboratori Nazionali del Gran Sasso, 67010 Assergi (AQ), Italy f Institute for Nuclear Research, MSP 03680 Kyiv, Ukraine Abstract The alpha decays of naturally occurring platinum isotopes, which are accompanied by the emission of γ quanta, have been searched for deep underground (3600 m w.e.) in the Gran Sasso National Laboratories of the INFN (Italy). A sample of Pt with mass of 42.5 g and a natural isotopic composition has been measured with a low background HP Ge detector (468 cm3) during 1815 h. The alpha decay of 190Pt to the first excited 186 π + level of Os (J = 2 , Eexc = 137.2 keV) has been observed for the first time, with +0.4 ± × 14 the half-life determined as: T1/2 = 2.6−0.3(stat.) 0.6(syst.) 10 yr. The T1/2 limits for 16 20 the α decays of other Pt isotopes have been determined at level of T1/2 ≃ 10 − 10 yr. These limits have been set for the first time or they are better than those known from earlier experiments.
    [Show full text]
  • 5.696-Mev - I I 31-Mis 4 * 206 (Rihl Scale) - 400 ,— 400 - 5:94:5S\P
    Lawrence Berkeley National Laboratory Recent Work Title ALPHA DECAY PROPERTIES OP NEUTRONS DEFICIENT ISOTOPES OF EMANATION Permalink https://escholarship.org/uc/item/2gr31474 Authors Nunnia, Matti J. Valli, Kalevi Hyde, Earl K. Publication Date 1966-05-01 eScholarship.org Powered by the California Digital Library University of California UCRL-16735 Rev. University of California Ernest 0. Lawrence Radiation Laboratory ALPHA DECAY PROPERTIES OF NEUTRON DEFICIENT ISOTOPES OF EMANATION TWO-WEEK LØAN COPY This is a library Circulating Copy which may be borróibed for two weeks. For a personal retention copy, call Tech. Info. DivIsIon, Ext. 5545 rk, California DISCLAIMER This document was prepared as an account of work sponsored by the United States Government. While this document is believed to contain correct information, neither the United States Government nor any agency thereof, nor the Regents of the University of California, nor any of their employees, makes any warranty, express or implied, or assumes any legal responsibility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by its trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof, or the Regents of the University of California. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof or the Regents of the University of California. II3 Supitte to Pc1 Revie; I9 UL16755 Rev.
    [Show full text]
  • Preclinical SPECT Imaging Based on Compact Collimators and High Resolution Scintillation Detectors
    Preklinische SPECT-beeldvorming gebaseerd op compacte collimatoren en hogeresolutiescintillatiedetectoren Preclinical SPECT Imaging Based on Compact Collimators and High Resolution Scintillation Detectors Karel Deprez Promotoren: prof. dr. S. Vandenberghe, prof. dr. R. Van Holen Proefschrift ingediend tot het behalen van de graad van Doctor in de Ingenieurswetenschappen Vakgroep Elektronica en Informatiesystemen Voorzitter: prof. dr. ir. J. Van Campenhout Faculteit Ingenieurswetenschappen en Architectuur Academiejaar 2013 - 2014 ISBN 978-90-8578-672-6 NUR 954, 959 Wettelijk depot: D/2014/10.500/18 Department of Electronics and Information Systems Medical Image and Signal Processing (MEDISIP) Faculty of Engineering and Architecture Ghent University MEDISIP IBiTech Campus Heymans, Blok B De Pintelaan 185 9000 Ghent Belgium Promotors Prof. dr. Stefaan Vandenberghe Prof. dr. Roel Van Holen Board of examiners Prof. dr. ir. Patrick De Baets, Ghent University, chairman Dr. Michael Tytgat, Ghent University / CERN, secretary Prof. dr. Luc Van Hoorebeke, Ghent University Prof. dr. Dennis Schaart, Delft University of Technology, The Netherlands Prof. dr. Carlo Fiorini, Politecnico di Milano, Italy Dr. Samuel Espana˜ Palomares, Advanced Imaging Unit, Centro Nacional de Inves- tigaciones Cardiovasculares (CNIC), Spain Dr. Peter Bruyndonckx, Bruker MicroCT, Belgium This work was supported by the 7th Framework Programme (FP7) of the European Union through the SUBLIMA project (Grant Agreement No 241711) Acknowledgements The work presented in this dissertation started in 2008, shortly after the birth of my daughter, and was finished in early 2014. Before I started at the university I had been working for several years as a electronics design engineer at Barco and Gemidis. The first thing that struck me when I started at the university was the content of my work.
    [Show full text]
  • High Specific Radioactivites of Cobalt, Platinum, and Iridium From
    Ames Laboratory ISC Technical Reports Ames Laboratory 12-1951 High specific ar dioactivites of cobalt, platinum, and iridium from photonuclear reactions Darleane Christian Iowa State College Don S. Martin Jr. Iowa State College Follow this and additional works at: http://lib.dr.iastate.edu/ameslab_iscreports Part of the Atomic, Molecular and Optical Physics Commons, Nuclear Commons, and the Quantum Physics Commons Recommended Citation Christian, Darleane and Martin, Don S. Jr., "High specific ar dioactivites of cobalt, platinum, and iridium from photonuclear reactions" (1951). Ames Laboratory ISC Technical Reports. 37. http://lib.dr.iastate.edu/ameslab_iscreports/37 This Report is brought to you for free and open access by the Ames Laboratory at Iowa State University Digital Repository. It has been accepted for inclusion in Ames Laboratory ISC Technical Reports by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. High specific ar dioactivites of cobalt, platinum, and iridium from photonuclear reactions Abstract The tta ainment of high specific cta ivities is an important requirement for the detect i on and utilization of radioactivities produced by photonuclear reactions. If an element different from the target element is produced suitable chemical procedures for the separation of the radioactive atoms from the target atoms can usually be found. However, finding rapid and efficient methods for separating isotopes of the target element formed by the (y,n) reaction presents a more difficult problem. To facilitate the study of the properties of cobalt and platinum actiities produced in the synchrotron by (y,n) reactions, an attempt was made to find complexes of these elements which would undergo Szilard-Chalmers type reactions.
    [Show full text]
  • Arxiv:1006.4033V2 [Nucl-Ex] 8 Sep 2010
    Discovery of Calcium, Indium, Tin, and Platinum Isotopes S. Amos, J. L. Gross, M. Thoennessen∗ National Superconducting Cyclotron Laboratory and Department of Physics and Astronomy, Michigan State University, East Lansing, MI 48824, USA Abstract Currently, twenty-four calcium, thirty-eight indium, thirty-eight tin and thirty-nine platinum isotopes have been observed and the discovery of these isotopes is discussed here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented. arXiv:1006.4033v2 [nucl-ex] 8 Sep 2010 ∗Corresponding author. Email address: [email protected] (M. Thoennessen) Preprint submitted to Atomic Data and Nuclear Data Tables November 1, 2018 Contents 1. Introduction . 4 2. Discovery of 35−58Ca ................................................................................... 5 2.1. 36Ca ............................................................................................ 5 2.2. 37Ca ............................................................................................ 7 2.3. 38Ca ............................................................................................ 7 2.4. 39Ca ............................................................................................ 7 2.5. 40Ca ............................................................................................ 7 2.6. 41Ca ............................................................................................ 8 2.7. 42;43Ca .........................................................................................
    [Show full text]
  • The Nuclear Properties of Gold
    The Nuclear Properties of Gold THE APPLICATIONS OF ITS ISOTOPES IN MEDICINE AND IN INDUSTRY Leslie Myerscough The Radiochemical Centre, Amersham, England Gold has in all twenty-four radioisotopes, although only two of them have half-lives which make them suitable, in combination with the normal chemical inertness of gold, for use in clinical work or in. industrial research and control. Their production methods and some of their most important applications in these fields are described. Radioisotopes are isotopes in which the nuclei of the atoms contain either more or fewer neutrons than The Isotopes of Gold are present in the naturally occurring stable iostopes of the elements. Such nuclei are unstable, and they Mode of Decay tend in time to change into stable configurations by Mass Half E radioactive decay. The primary radioactive decay Number Life e. d 'o ' process is always either the emission of a charged ^a r4W ww caw cja particle (an alpha particle, a positron or a beta 177 1.35 sec x particle), or the capture by the nucleus of an orbital 178 2.65 sec x electron. These processes change the charge on the 179 7.25 sec x nucleus, yielding a nucleus which is chemically a 181 11.55 sec x x different element. The product nucleus has a lower 183 45.5 sec x energy content than the parent radioactive nucleus; the difference in energy appears as the energy of 185 4.3 min x x various kinds of radiations which are emitted. 186 12 min x x 187 8 min x x These radiations consist of charged particles 188 8 min x x accompanied in many cases by electro-magnetic 189 29.7 min x x radiation in the form of gamma-rays.
    [Show full text]
  • Imaging Technologies for Preclinical Models of Bone and Joint Disorders
    Tremoleda et al. EJNMMI Research 2011, 1:11 http://www.ejnmmires.com/content/1/1/11 REVIEW Open Access Imaging technologies for preclinical models of bone and joint disorders Jordi L Tremoleda1*, Magdy Khalil1, Luke L Gompels2, Marzena Wylezinska-Arridge1, Tonia Vincent2 and Willy Gsell1 Abstract Preclinical models for musculoskeletal disorders are critical for understanding the pathogenesis of bone and joint disorders in humans and the development of effective therapies. The assessment of these models primarily relies on morphological analysis which remains time consuming and costly, requiring large numbers of animals to be tested through different stages of the disease. The implementation of preclinical imaging represents a keystone in the refinement of animal models allowing longitudinal studies and enabling a powerful, non-invasive and clinically translatable way for monitoring disease progression in real time. Our aim is to highlight examples that demonstrate the advantages and limitations of different imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging. All of which are in current use in preclinical skeletal research. MRI can provide high resolution of soft tissue structures, but imaging requires comparatively long acquisition times; hence, animals require long-term anaesthesia. CT is extensively used in bone and joint disorders providing excellent spatial resolution and good contrast for bone imaging. Despite its excellent structural assessment of mineralized structures, CT does not provide in vivo functional information of ongoing biological processes. Nuclear medicine is a very promising tool for investigating functional and molecular processes in vivo with new tracers becoming available as biomarkers.
    [Show full text]
  • Hybrid Gamma Camera Imaging: Translation from Bench to Bedside
    Hybrid Gamma Camera Imaging: Translation from Bench to Bedside A thesis submitted to the University of Nottingham for the degree of Doctor of Philosophy by Aik Hao Ng MMed.Phys. Radiological Sciences, Division of Clinical Neuroscience, School of Medicine September 2017 Declaration I, Aik Hao Ng declare that the work presented in this thesis is my own original work based on the research undertaken during my PhD study period unless otherwise referenced or acknowledged. ii “Life is like riding a bicycle. To keep your balance, you must keep moving.” - Albert Einstein Abstract There is increasing interest in the use of small field of view (SFOV) portable gamma cameras in medical imaging. A novel hybrid optical-gamma camera (HGC) has been developed through a collaboration between the Universities of Leicester and Nottingham. This system offers high resolution gamma and optical imaging and shows potential for use at the patient bedside, or in the operating theatre. The aim of this thesis was to translate the HGC technology from in vitro laboratory studies to clinical use in human subjects. Pilot studies were undertaken with the HGC as part of this thesis. Furthermore, efforts have been made to transform the HGC technologies into a new medical device, known as Nebuleye. Initial physical evaluation of the pre-production prototype camera was carried out as part of the device developmental process, highlighting some aspects of the design that require further modification. A complete and rigorous testing scheme to assess the pre-production prototype camera has been developed and successfully implemented. The newly introduced tests enabled the system uniformity, system sensitivity, detector head shielding leakage, optical-gamma image alignment and optical image quality of the hybrid camera to be assessed objectively.
    [Show full text]
  • ORNL's Neutron Sources and Nuclear Astrophysics
    2 Vol. 34, No. 2, 2001 1 Editorial: Basic Research 16 Modeling a Fusion Plasma at ORNL Heating Process and Stellarator 2 ORNL’s Search for Rare 22 Isotopes 17 Neutron Sources and Nanoscale Science 2 ORNL Theorists and the Nuclear Shell Model 18 Quantum-Dot Arrays for Computation 5 Beam Technologies Enable HRIBF Experiments 20 Carbon Nanotubes and Nanofibers: The 7 Neutrons, “Stripes,” and Self-Assembly Challenge Superconductivity 22 Incredible Shrinking Labs: 12 Weighing a Move to the ORNL’s Neutron Sources 8 Nanoscale and Nuclear Astrophysics 24 Basic Geochemical 10 Modeling Magnetic Mate- Research Supports Energy rials for Electronic Devices Industries 12 In Quest of a Quark: 26 Fermi Award Winner ORNL’s Role in the Opened New Fields in PHENIX Particle Detector 20 Atomic Physics 14 New Hope for the Blind 28 Improving the Internet’s from a Spinach Protein Quality of Service 15 Human Susceptibility and 29 QOS for Wireless Mouse Biology Communication This issue provides highlights of basic research at ORNL, including research on producing, characterizing, and finding applications for carbon nanotubes produced at ORNL by several techniques. The cover shows single-wall carbon nanotubes created by laser vaporization (note pink laser plume), which were then chemically purified and spray-deposited onto a substrate. The image above the cover image shows a carbon nanotube on electrodes, a possible nanoscale replacement for today’s microscale silicon transistors. See pp. 20-21 for a description of this and other nanoscale research. Images by Jason Fowlkes, Derek Austin, and Henrik Schittenhelm. Basic Research at ORNL Basic Research at ORNL: A Distinguished Past, An Exciting Future RNL has a time-honored tradition of basic research accomplish- ments in physics, chemistry, biology, and the materials sciences.
    [Show full text]
  • Oqnf-9203164—1 De92 016800 Exotic Nuclear Shapes And
    OQNF-9203164—1 DE92 016800 EXOTIC NUCLEAR SHAPES AND CONFIGURATIONS THAT CAN BE STUDIED AT HIGH SPIN USING RADIOACTIVE ION BEAMS J. D. Garrett Physics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831-6371, USA ABSTRACT The variety of new research possibilities afforded by the culmination of the two frontier areas of nuclear structure: high spin and studies far from nuclear stability (utilizing intense radioactive ion beams) are discussed. Topics presented include: new regions of exotic nuclear shape (e.g. superdeformation, hyperdeformation, and reflection-asymmetric shapes); the population of and consequences of populating exotic nuclear configurations; and complete spectroscopy (i.e. the overlap of state of the art low- and high-spin studies in the same nucleus). Likewise, the various beams needed for proton- and neutron-rich high spin studies also are discussed. DISCLAIMER This report was prepared as an account of work sponsored by an agency of the United Slates Government. Neither the United States Government nor any agency thereof, nor any of their employees, makes any warranty, express or implied, or assumes any legal liability or responsi- bility for the accuracy, completeness, or usefulness of any information, apparatus, product, or process disclosed, or represents that its use would not infringe privately owned rights. Refer- ence herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, rccom- mendaiiun, or favoring by the United Stales Government or any agency thereof. The views and opinions of authors expressed herein do not necessarily slate or reflect those of the United Stiles Government or any agency thereof.
    [Show full text]