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INTERNATIONAL ATOMIC ENERGY AGENCY VIENNA @ ISBN 978–92–0–107008–1 09-01471_P1344_covI-IV.indd 1 2009-03-17 10:11:58 STRATEGIES FOR CLINICAL IMPLEMENTATION AND QUALITY MANAGEMENT OF PET TRACERS The following States are Members of the International Atomic Energy Agency: AFGHANISTAN GUATEMALA OMAN ALBANIA HAITI PAKISTAN ALGERIA HOLY SEE PALAU ANGOLA HONDURAS PANAMA ARGENTINA HUNGARY PARAGUAY ARMENIA ICELAND PERU AUSTRALIA INDIA PHILIPPINES AUSTRIA INDONESIA POLAND AZERBAIJAN IRAN, ISLAMIC REPUBLIC OF PORTUGAL BANGLADESH IRAQ QATAR BELARUS IRELAND REPUBLIC OF MOLDOVA BELGIUM ISRAEL ROMANIA BELIZE ITALY RUSSIAN FEDERATION BENIN JAMAICA SAUDI ARABIA BOLIVIA JAPAN SENEGAL BOSNIA AND HERZEGOVINA JORDAN SERBIA BOTSWANA KAZAKHSTAN SEYCHELLES BRAZIL KENYA SIERRA LEONE BULGARIA KOREA, REPUBLIC OF SINGAPORE BURKINA FASO KUWAIT SLOVAKIA CAMEROON KYRGYZSTAN SLOVENIA CANADA LATVIA SOUTH AFRICA CENTRAL AFRICAN LEBANON SPAIN REPUBLIC LIBERIA SRI LANKA CHAD LIBYAN ARAB JAMAHIRIYA SUDAN CHILE LIECHTENSTEIN SWEDEN CHINA LITHUANIA SWITZERLAND COLOMBIA LUXEMBOURG SYRIAN ARAB REPUBLIC COSTA RICA MADAGASCAR CÔTE D’IVOIRE MALAWI TAJIKISTAN CROATIA MALAYSIA THAILAND CUBA MALI THE FORMER YUGOSLAV CYPRUS MALTA REPUBLIC OF MACEDONIA CZECH REPUBLIC MARSHALL ISLANDS TUNISIA DEMOCRATIC REPUBLIC MAURITANIA TURKEY OF THE CONGO MAURITIUS UGANDA DENMARK MEXICO UKRAINE DOMINICAN REPUBLIC MONACO UNITED ARAB EMIRATES ECUADOR MONGOLIA UNITED KINGDOM OF EGYPT MONTENEGRO GREAT BRITAIN AND EL SALVADOR MOROCCO NORTHERN IRELAND ERITREA MOZAMBIQUE UNITED REPUBLIC ESTONIA MYANMAR OF TANZANIA ETHIOPIA NAMIBIA UNITED STATES OF AMERICA FINLAND NEPAL URUGUAY FRANCE NETHERLANDS UZBEKISTAN GABON NEW ZEALAND VENEZUELA GEORGIA NICARAGUA VIETNAM GERMANY NIGER YEMEN GHANA NIGERIA ZAMBIA GREECE NORWAY ZIMBABWE The Agency’s Statute was approved on 23 October 1956 by the Conference on the Statute of the IAEA held at United Nations Headquarters, New York; it entered into force on 29 July 1957. The Headquarters of the Agency are situated in Vienna. Its principal objective is “to accelerate and enlarge the contribution of atomic energy to peace, health and prosperity throughout the world’’. STRATEGIES FOR CLINICAL IMPLEMENTATION AND QUALITY MANAGEMENT OF PET TRACERS INTERNATIONAL ATOMIC ENERGY AGENCY VIENNA, 2009 COPYRIGHT NOTICE All IAEA scientific and technical publications are protected by the terms of the Universal Copyright Convention as adopted in 1952 (Berne) and as revised in 1972 (Paris). The copyright has since been extended by the World Intellectual Property Organization (Geneva) to include electronic and virtual intellectual property. Permission to use whole or parts of texts contained in IAEA publications in printed or electronic form must be obtained and is usually subject to royalty agreements. Proposals for non-commercial reproductions and translations are welcomed and considered on a case-by-case basis. Enquiries should be addressed to the IAEA Publishing Section at: Sales and Promotion, Publishing Section International Atomic Energy Agency Wagramer Strasse 5 P.O. Box 100 1400 Vienna, Austria fax: +43 1 2600 29302 tel.: +43 1 2600 22417 email: [email protected] http://www.iaea.org/books © IAEA, 2009 Printed by the IAEA in Austria March 2009 STI/PUB/1344 IAEA Library Cataloguing in Publication Data Strategies for clinical implementation and quality management of PET tracers. — Vienna : International Atomic Energy Agency, 2009. p. ; 24 cm. STI/PUB/1344 ISBN 978–92–0–107008–1 Includes bibliographical references. 1. Radiopharmaceuticals — Quality control. 2. Tomography, Emission — Quality control. I. International Atomic Energy Agency. IAEAL 09–00567 FOREWORD Positron emission tomography (PET) methodologies, which visualize in vivo biochemical, physiological and pharmacological processes, together with the availability of hybrid imaging modalities (PET with computer tomography (PET/CT) imaging), have revolutionized patient diagnosis, disease staging, disease management and therapy follow-up. These technologies have opened up fascinating possibilities for new non-invasive medical care and individualized patient management unlike those seen before in a clinical setting. There is immense global interest in PET, with accelerated investment in the clinical setting. The radiotracers used for PET are very different from conventional nuclear medicine radiopharmaceuticals. They have extremely short half-lives, which means that they have to be produced close to the clinical user. The time available for the labelling of PET molecules (including purification and quality control) is very limited, which presents new challenges and a need for more proficient systems to be established before clinical use. The busy and demanding nature of clinical settings adds to the complexities and creates a need for more robust quality management programmes. This publication focuses on clinical settings and was compiled following several IAEA Consultants Meetings and with the benefit of the contributions of individual experts. It aims to raise awareness of the issues involved and suggests ways of reducing risk. The purpose of these guidelines is to encourage a proactive approach to each aspect of parametric release and to propose practical test methods for each criterion for parametric acceptance, thereby helping end users to ensure the quality of PET products. It is hoped that these criteria will stimulate further cooperation among various countries worldwide in the development of a set of harmonized acceptance test criteria for PET systems and sensible quality assurance (QA) standards for all PET tracers. Many countries and IAEA Member States are in the process of creating rules governing the production of clinically safe and effective PET radiopharmaceuticals for human use. Where such rules are available, it is encouraged that they be used. The guidelines presented in this book will be useful for those Member States who have yet to develop such rules or who simply wish to adopt them for national usage. They are not meant to replace existing regulatory or local oversight. This publication should be a useful resource for both researchers and practitioners. Continuous reliable development and quality supply of radiopharmaceuticals for patients worldwide is vital for sustained development of nuclear medicine. The IAEA is grateful to all the contributors and reviewers of these guidelines. The IAEA officer responsible for this publication was K.K. Solanki of the Division of Human Health. EDITORIAL NOTE Although great care has been taken to maintain the accuracy of information contained in this publication, neither the IAEA nor its Member States assume any responsibility for consequences which may arise from its use. The use of particular designations of countries or territories does not imply any judgement by the publisher, the IAEA, as to the legal status of such countries or territories, of their authorities and institutions or of the delimitation of their boundaries. The mention of names of specific companies or products (whether or not indicated as registered) does not imply any intention to infringe proprietary rights, nor should it be construed as an endorsement or recommendation on the part of the IAEA. CONTENTS 1. INTRODUCTION . 1 1.1. Scope . 1 1.2. Background . 1 1.3. PET radiopharmaceuticals . 2 1.4. Differences between 99mTc and PET radiopharmacy . 5 1.5. IAEA operational guidance on hospital radiopharmacy . 8 1.6. Overview of quality programme . 11 1.7. Criteria for synthesis of a new PET radiopharmaceutical . 13 1.8. Summary of a new class of PET tracers . 15 1.9. IAEA consultants meeting . 19 1.10. The role of this publication . 20 2. EFFECTIVE TRANSLATION OF PET RESEARCH INTO CLINICAL PRACTICE . 21 2.1. Scope . 21 2.2. Chemical aspects . 22 2.3. Biological aspects . 24 2.4. First studies on humans . 26 2.5. Conclusions . 27 3. OVERSIGHT COMMITTEES . 27 3.1. Scope . 27 3.2. Introduction . 28 3.3. Role of oversight committees . 29 3.4. Overview of existing regulations . 29 3.5. Alternative to existing oversight committees . 38 3.6. EANM guidelines for PET radiopharmacy . 43 4. TERMINOLOGY . 44 4.1. Radiopharmaceuticals . 44 4.2. Charged particle bombardment of target materials . 45 4.3. Radioactive decay . 46