Radiopharmaceuticals: Chemistry and Pharmacology PDF
Preview Radiopharmaceuticals: Chemistry and Pharmacology
DRUGS AND THE PHARMACEUTICAL SCIENCES A Series of Textbooks and Monographs edited by James Swarbrick School of Pharmacy University of North Carolina Chape! Hill, North Carolina 1. Pharmacokinetics, MHo Gibaldi and Donald Perrier 2. Good Manufacturing Practices for Pharmaceuticais: A Plan for Totai Quaiity Control, Sidney H. Wi/iig, Murray M. Tuckerman, and William S. Hitchings IV 3. Microencapsulation, edited by J. R. Nixon 4. Drug Metabolism: Chemical and Biochemical Aspects, Bernard Testa and Peter Jenner 5. New Drugs: Discovery and Development, edited by Alan A. Rubin 6. Sustained and Controiied Release Drug Delivery Systems, edited by Joseph R. Robinson 7. Modern Pharmaceutics, edited by Gilbert S. Banker and Christopher T. Rhodes 8. Prescription Drugs in Short Supply: Case Histories, Michael A. Schwartz 9. Activated Charcoai: Antidotal and Other Medical Uses, David O. Cooney 10. Concepts in Drug Metabolism (in two parts), edited by Peter Jenner and Bernard Testa 11. Pharmaceutical Analysis: Modern Methods (in two parts), edited by James W. Munson 12. Techniques of Solubilization of Drugs, edited by Samuel H. Yalkowsky 13. Orphan Drugs, edited by Fred E. Kerch 14. Novel Drug Delivery Systems: Fundamentals, Developmental Concepts, Biomedical Assessments, Yie W. Chien 15. Pharmacokinetics: Second Edition, Revised and Expanded, MHo Gibaldi and Donald Perrier 16. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control, Second Edition, Revised and Expanded, Sidney H. \MHig, Murray M. Tuckerman, and William S. Hitchings IV 17. Formuiation of Veterinary Dosage Forms, edited by Jack Biodinger 18. Dermatological Formulations: Percutaneous Absorption, Brian W. Barry 19. The Clinical Research Process in the Pharmaceutical Industry, edited by Gary M. Matoren 20. Microencapsulation and Related Drug Processes, Patrick B. Deasy 21. Drugs and Nutrients: The Interactive Effects, edited by Daphne A. Roe and T. Colin Campbell 22. Biotechnology of Industrial Antibiotics, Erick J. Vandamme 23. Pharmaceutical Process Validation, edited by Bernard T. Loftus and Robert A. Nash 24. Anticancer and Interferon Agents: Synthesis and Properties, edited by Raphael M. Ottenbrite and George B. Butler 25. Pharmaceutical Statistics: Practical and Clinical Applications, Sanford Bolton 26. Drug Dynamics for Analytical, Clinical, and Biological Chemists, Benja min J. Gudzinowicz, Burrows T. Younkin, Jr., and Michael J. Gudzino- wicz 27. Modern Analysis of Antibiotics, edited by Adjoran Aszalos 28. Solubility and Related Properties, Kenneth C. James 29. Controlled Drug Delivery: Fundamentals and Applications, Second Edi tion, Revised and Expanded, edited by Joseph R. Robinson and Vincent H. Lee 30. New Drug Approval Process: Clinical and Regulatory Management, edited by Richard A. Guarino 31. Transdermal Controlled Systemic Medications, edited by Yie W. Chien 32. Drug Delivery Devices: Fundamentals and Applications, edited by Praveen Tyle 33. Pharmacokinetics: Regulatory • Industrial • Academic Perspectives, edited by Peter G. Welling and Francis L. S. Tse 34. Clinical Drug Trials and Tribulations, edited by Alien E. Cato 35. Transdermal Drug Delivery: Developmental Issues and Research Ini tiatives, edited by Jonathan Hadgraft and Richard H. Guy 36. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms, edited by James W. McGinity 37. Pharmaceutical Pelletization Technology, edited by Isaac Ghebre- Sellassie 38. Good Laboratory Practice Regulations, edited by Alien F. Hirsch 39. Nasal Systemic Drug Delivery, Yie W. Chien, Kenneth S. E. Su, and Shyi-Feu Chang 40. Modern Pharmaceutics: Second Edition, Revised and Expanded, edited by Gilbert S. Banker and Christopher T. Rhodes 41. Specialized Drug Delivery Systems: Manufacturing and Production Tech nology, edited by Praveen Tyle 42. Topical Drug Delivery Formulations, edited by David W. Osborne and Anton H. Amann 43. Drug Stability: Principles and Practices, Jens T. Carstensen 44. Pharmaceutical Statistics: Practical and Clinical Applications, Second Edition, Revised and Expanded, Sanford Bolton 45. Biodegradable Polymers as Drug Delivery Systems, edited by Mark Chasin and Robert Langer 46. Preclinical Drug Disposition; A Laboratory Handbook, Francis L. S. Tse and James J. Jaffe 47. HPLC in the Pharmaceutical Industry, edited by Godwin W. Fong and Stanley K. Lam 48. Pharmaceutical Bioequivalence, edited by Peter G. Welling, Francis L. S. Tse, and Shrikant V. Dinghe 49. Pharmaceutical Dissolution Testing, Umesh V. Banakar 50. Novel Drug Delivery Systems: Second Edition, Revised and Expanded, Yie W. Chien 51. Managing the Clinical Drug Development Process, David M. Cocchetto and Ronald V. Nardi 52. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control, Third Edition, edited by Sidney H. WiiUg and James R. Stoker 53. Prodrugs: Topical and Ocular Drug Delivery, edited by Kenneth B. Sloan 54. Pharmaceutical Inhalation Aerosol Technology, edited by Anthony J. Hickey 55. Radiopharmaceuticals: Chemistry and Pharmacology, edited by Adrian D. Nunn Additional Volumes in Preparation Pharmaceutical Process Validation: Second Edition, Revised and Ex panded, edited by ira R. Berry and Robert A. Nash Chemistry and Pharmacology edited by Adrian D. Nunn Bristoi-Myers Squibb Pharmaceutical Research Institute New Brunswick, New Jersey Marcel Dekker, Inc. New York • Basel • Hong Kong ISBN: 0-8247-8624-6 This book is printed on acid-free paper. Copyright © 1992 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Marcel Dekker, Inc. 270 Madison Avenue, New York, New York 10016 Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA PREFACE Nuclear medicine exists in two forms which use slightly different technology to produce images of the in vivo distribution of injected radioactive compounds. For routine clinical use single photon emission tomography (SPECT) predominates and uses mainly Technetium-99m. On the other hand, there is an extensive research effort using positron emission tomography (PET), and here Carbon-11, Fluorine-18 and Oxygen-15 are most used. As yet PET has not been widely used in a clinical setting because the radionuclides it uses are short lived and cyclotron produced. Clinically, nuclear medicine has been viewed as the Cinderella of medical imaging because it is seen as being ’low tech* (having been around for much longer), is relatively inexpensive to perform, and because the resolution of nuclear imaging devices is inferior to that of the newer CT or MRJ machines. This means that morphological images obtained by the latter devices are in almost all cases superior. Radiopharmaceuticals have held a similar position relative to therapeutic drugs because of the dominant position of metal complexes which has isolated the practitioners from the main pharmaceutical chemistry population. Coupled with the scarcity of knowledge of the element most frequently used in radiopharmaceutical chemistry, technetium (a result of current stocks of the element being totally man-made), this has generated a view of radiopharmaceutical chemistry as being something of a 'Black Art’ and an imprecise one at that. iii Iv Preface In recent years the pressure on nuclear medicine to relinquish morphological imaging to better techniques has fueled attempts to develop functional imaging. Here nuclear medicine has an advantage over the other techniques as the quantities of tracer injected are many orders of magnitude less than those used for CT or MRI and so do not disturb the very processes that are being measured. In addition, the availability of radionuclides of carbon, fluorine and oxygen allows the study of compounds that are well known in conventional pharmaceutical circles. As a result, nuclear medicine has started to exploit its true niche, that of measuring regional function. Along with this has come an evolution, some would say a revolution, in radiopharmaceutical chemistry. Some ten years ago the routine clinical field, dominated by technetium, concentrated on increasing the delivery of drug to specific tissues. For example, about 50% of the injected dose of phosphonate complexes are taken up by the skeleton within about half an hour after injection and used to depict blood flow which is indicative of new bone deposition around métastasés. About 90% of the injected dose of iminodiacetic acid complexes can be excreted by the liver within about the same time to measure the excretory functions of this organ and its associated systems. In recent years attention has concentrated on designing compounds that measure perfusion and here the common targets of the myocardium and the brain have presented much more formidable problems. Needless to say, there are now a variety of technetium compounds that are efficacious for the measurement of perfusion in these tissues and a large body of structure distribution (as opposed to activity) relationships has been constructed. This knowledge includes not only information on the stereo specific interaction of metal complexes with enzyme systems and transport mechanisms, information which is adaptable to compounds other than metal complexes. Preface In the PET field the blossoming of knowledge of receptor systems has proven irresistible, and much work has been expended in radiolabelling receptor binders and using them to gain quantitative information on receptors in vivo as a function of disease or therapy. To a limited extent this has also occurred in the SPECT field. In many cases this has led to significant interaction between pharmaceutical companies and PET centers in attempts to better understand the pharmacology of new (and old!) therapeutic drugs. In addition, as measurement techniques have improved, the routine analysis of metabolism using PET techniques has occurred. The use of PET techniques is not just an extension of classical drug metabolism and pharmacological techniques; it provides a quantum leap in information. Already the use of such techniques to examine, for instance, receptor occupancy in psychoactive drug therapy is being discussed as are means of diagnosing or staging disease and therapy by measuring receptor density or occupancy. This book is arranged somewhat along the traditional competitive lines of SPECT vs PET. In the past there has been a great gulf between the clinical usefulness of SPECT agents vs PET and the scientific elegance of PET vs SPECT. This gulf is rapidly closing. The clinical use of PET agents is becoming routine and technetium-based SPECT agents are now as scientifically elegant as their PET counterparts. The authors were asked to write their chapters in such a way as to provide a review for the practitioners of the disciplines embodied in them yet still provide easily obtainable information to non-practitioners. It is not the intent of this book to list every radioactive compound made and used in vivo and how to make it; rather it is to describe the philosophy behind why one approach is better than another. In addition, an attempt has been made to present the current state of knowledge such that others may glean as yet unseen information from it. The chapters on technetium agents should displace any misconceptions that abound
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