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Xerox University Microfilms INFORMATION TO USERS This material was produced from a microfilm copy of the original document. While the most advanced technological means to photograph and reproduce this document have been used, the quality is heavily dependent upon the quality of the original submitted. The following explanation of techniques is provided to help you understand markings or patterns which may appear on this reproduction. 1.The sign or "target" for pages apparently lacking from the document photographed is "Missing Page(s)". If it was possible to obtain the missing page(s) or section, they are spliced into the film along with adjacent pages. This may have necessitated cutting thru an image and duplicating adjacent pages to insure you complete continuity. 2. When an image on the film is obliterated with a large round black mark, it is an indication that the photographer suspected that the copy may have moved during exposure and thus cause a blurred image. You will find a good image of the page in the adjacent frame. 3. When a map, drawing or chart, etc., was part of the material being photographed the photographer followed a definite method in "sectioning" the material. It is customary to begin photoing at the upper left hand corner of a large sheet and to continue photoing from left to right in equal sections with a small overlap. If necessary, sectioning is continued again — beginning below the first row and continuing on until complete. 4. The majority of users indicate that the textual content is of greatest value, however, a somewhat higher quality reproduction could be made from "photographs" if essential to the understanding of the dissertation. Silver prints of "photographs" may be ordered at additional charge by writing the Order Department, giving the catalog number, title, author and specific pages you wish reproduced. 5. PLEASE NOTE: Some pages may have indistinct print. Filmed as received. Xerox University Microfilms 300 North Zeeb Road Ann Arbor, Michigan 48106 P':* tevi 1 74-11,071 WIELAND, Bruce Wendell, 1937- DEVELOPMENT AND EVALUATION OF FACILITIES FOR THE EFFICIENT PRODUCTION OF COMPOUNDS LABELED WITH CARBON-11 AND OXYGEN-15 AT THE WASHINGTON UNIVERSITY MEDICAL CYCLOTRON. The Ohio State University, Ph.D., 1973 Engineering, nuclear i. University Microfilms, A XEROX Company, Ann Arbor, Michigan 1 THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED. DEVELOPMENT AND EVALUATION OF FACILITIES FOR THE EFFICIENT PRODUCTION OF COMPOUNDS LABELED WITH CARBON-11 AND OXYGEN-15 AT THE WASHINGTON UNIVERSITY MEDICAL CYCLOTRON DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Bruce W. Wieland, B.S. The Ohio State University 1973 Reading Committee: Professor Donald D. Glower, Chairman Professor Robert F. Redmond Professor Walter E. Carey Approved by Advisor, Department of Nuclear Engineering TO THE MEMORY OF MY FATHER IN RECOGNITION OF HIS CONTRIBUTIONS AS AN EDUCATOR ii ACKNOWLEDGMENTS My parents, Stephen and Mathilda Wieland, have provided me with a continuing respect and personal motivation for the education process through the example of their two lifetimes of productive service in the Iowa public school system. My pretty wife, Edna, while pursuing her own career in counseling and teaching, has helped me through several troubled times during the course of my dqctoral program. She has also applied her expertise in English to the careful reading and revision of this dissertation. Dr. Michel Ter-Pogossian of Washington University supplied much appreciated guidance, patience, and financial support while directing the dissertation research project in his Division of Radiation Sciences at the Edward Mallinckrodt Institute of Radiology. Dr. Donald Glower of The Ohio State University has been unwavering in his encouragement and support as advisor and as sponsor of my NIH Special Research Fellowship throughout the entire program. Dr. Robert Redmond of The Ohio State University has provided thoughtful assistance during the coursework portion of the program, and has coordinated the dissertation phase. Dr. William Hunter of The Ohio State University supplied recommen­ dations and assistance with regard to physiology, nuclear medicine, and medical cyclotron applications during the coursework phase. He was also helpful in applying for and maintaining NIH support. Dr. Michael Welch of Washington University and Dr. Walter Carey of The Ohio State University made valuable suggestions after a careful reading of the dissertation. John Hood at the Washington University Physics Cyclotron was a source of frequent and friendly technical advice on medical cyclotron problems. Lee Troutt and William Margenau, operators of the Washington Uni­ versity Medical Cyclotron, were a source of congenial and capable assis­ tance in performing experiments, and made numerous helpful suggestions during the research project. Julius Hecht of the Division of Radiation Sciences deserves thanks for technical assistance and careful preparation of the dissertation figures. Susan Hartner of the Division of Radiation Sciences accomplished the typing and proofreading of the draft and final copies of the dissertation in an extremely capable, pleasant, and much appreciated manner. ill I am grateful to Dr. John Eichling, Dr. Michael Phelps, Dr. Michael Welch, Dr. Marcus Raichle, Dr. Robert Grubb, Dr. Michael Loberg, Dr. Kenneth Larson, Dr. Edward Hoffman, Dr. Judith Metzger, Maria Straatmann, Katherine Anderson, Nizar Mullani, Carol Coble, and Ruby Hicks, for their friendship, advice, and technical assistance during my stay in the Division of Radiation Sciences. The National Institutes of Health provided financial support for this program with Special Research Fellowship GM-41730 from September 18, 1968, through October 24, 1971, and from December 6 , 1971, through March 28, 1973. Partial support was also provided by NIH Grant No. 5 P01 HL13851 from May 1, 1971 through August 31, 1973. iv VITA 15 April 1937 Birthplace - Carroll, Iowa 1955 - 1959 Engineering Trainee, John Deere Waterloo Tractor Works, Waterloo, Iowa 1960 B.S., Mechanical Engineering, Iowa State University, Ames, Iowa 1960 - 1966 Engineer and Nuclear Analyst, Oak Ridge National Laboratory, Oak Ridge, Tennessee 1961 Instructor (2nd Lt.)* U.S. Army Nuclear Power Field Office, Fort Belvoir, Virginia 1965 Postgraduate Certificate, Oak Ridge School of Reactor Technology, Oak Ridge, Tennessee 1967 - 1968 Research Engineer, Battelle Memorial Institute, Columbus, Ohio 1968 - 1973 NIH Special Research Fellow, Department of Nuclear Engineering, The Ohio State University, Columbus, Ohio 1971 - 1973 Research Associate, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri v PUBLICATIONS Production of short-lived isotopes by charged particle accelerators, M.E. Phelps and B.W. Wieland, Physics in Medicine and Biology, Vol. 18, No. 2, 284-286, March, 1973. Techniques for irradiating high temperature materials in a steep flux gradient, G.W. Keilholtz, R.E. Moore, M.F. Osborne, B.W. Wieland, and A.F. Zulliger. Proceedings of the May 1966 International Symposium on Capsule Irradiation Experiments, Pleasanton, California. Analysis of the High Flux Isotope Reactor fuel element shipping cask (Shielding analysis, Provisions for criticality control, Provisions for ruptured fuel elements), B.W. Wieland. ORNL-TM-959, January 1965. Temperature distributions in fuel samples irradiated in Engineering Test Reactor lattice position J-12, 6 .H. Llewellyn and B.W. Wieland. ORNL-CF-64-5-60, May 1964. Review of stress calculations for Tower Shielding Reactor II (Shield and supports, Vertical scanning components), B.W. Wieland. ORNL-CF- 63-5-30, May 1963. vi FIELDS OF STUDY Major Field: Nuclear Engineering Studies in Nuclear Physics: Professor H.J. Hausman Studies in Nuclear Detection Instrumentation: Professor R.A. Krakowski Studies in Pulse and Digital Electronics: Professor D.W. Miller Studies in Mathematical Statistics and Biomedical Computer Applications: Professor T.A. Willke Studies in Physiology and Nuclear Medicine: Dr. W.W. Hunter, Jr. vii TABLE OF CONTENTS Page DEDICATION ii ACKNOWLEDGMENTS iii VITA v PUBLICATIONS vi FIELDS OF STUDY vii LIST OF TABLES x LIST OF FIGURES xli Chapter 1. INTRODUCTION 1 1.1 Scope of Research Objectives 1 1.2 Utilization of the Washington University 3 Medical Cyclotron 1.3 In Vivo Studies of Cerebral Circulation n and Metabolism 1.4 Assessment of the Requirements for Labeled 16 Compounds 2. CYCLOTRON PERFORMANCE AND RELIABILITY 21 2.1 Characterization of the Cyclotron Beam 21 2.2 Development of a Gas-Cooled Beam Window 26 Assembly 2.3 Modifications to Cyclotron Components 32 2.4 Future Work 37 3. TARGET AND LABELING SYSTEMS 42 3.1 Development of a New Target for the 42 Production of H e viii Page 3.2 Investigation of a Photosynthetic 58 Process for Labeling Glucose with C 3.3 Design of a Hc/15o Tandem Target Assembly 70 and Associated Labeling Systems 3.4 Future Work 88 4. CONCLUSIONS 97 4.1 Evaluation of Equipment and Procedures 97 Implemented to Achieve Efficient Production 4.2 Applications to Other Cyclotrons 100 4.3 Future Work 104 APPENDICES A. Procedures for In Vivo Studies Utilizing Compounds 107 Labeled with and ^ C B. Beam Energy Measurements 111 C. Beam Mapping Measurements 114 D. Prototype Beam Window Development 130 E. Parameter Study of Uptake of ^ C 02 by Swiss Chard 141 Leaves F. Design of Gas Chamber for the Production of *^0 161 G. Range and
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