RADIOPHARMACY: AN UPDATE A TECHNOLOGIST’S GUIDE Produced with the kind support of TABLE OF CONTENTS Foreword 4 Andrea Santos Introduction 6 MarieClaire Attard Chapter 1 The History of Radiopharmacy 8 Marius Mada Chapter 2 Theoretical Basics of Radiopharmacy 18 Zéna Wimana Chapter 3 Radiopharmacy Design and Radiation Protection 32 Lei Li Corrigan Chapter 4 Generators used in Nuclear Medicine 42 David Gilmore and Daniel Tempesta Chapter 5 Cyclotron- and Nuclear Reactor-Produced Radioisotopes 52 Sergio do Carmo and Francisco Alves Chapter 6 Conventional Nuclear Medicine Radiopharmaceuticals 72 Lurdes Gano and Antonio Paulo Chapter 7 PET Radiopharmaceuticals 96 Lei Li Corrigan Chapter 8 Radiopharmaceuticals used in Therapy 104 Christelle Terwinghe and Christophe M Deroose Chapter 9 Blood Labelling for Nuclear Imaging 114 Naseer Khan and Giorgio Testanera Chapter 10 Good Manufacturing Practice for Radiopharmaceuticals within 124 the Hospital Environment Kishor Solanki Chapter 11 Translational Approach to Radiopharmaceutical Development 138 Latifa Rbah-Vidal and Pedro Fragoso Costa EANM TECHNOLGIST’S GUIDE 3 RADIOPHARMACY: AN UPDATE FOREWORD FOREWORD Foreword Nuclear medicine, which encompasses the medical field of molecular imaging and radionuclide therapy, brings together many disciplines, and radiopharmacy requires that pharmacy, physics and medicine work together within a synergetic environment. It is undeniable that within nuclear medicine the baseline of any good procedure is the design and preparation of the radioactive pharmaceutical, referred to as the radiopharmaceutical. After the introduction of a radio- (EANM-TC) made a joint effort to produce radiopharmacy to the current generator- to our colleagues from the Society of pharmaceutical into clinical practice, a book entitled The Radiopharmacy. and cyclotron-produced radioisotopes, Nuclear Medicine and Molecular Imaging– it is essential that the production and This publication was intended to help conventional nuclear medicine, PET Technologist Section (SNMMI-TS) for their preparation of the radiopharmaceutical professionals from different locations and and therapeutic radiopharmaceuticals. contribution to the book. are done by highly qualified professionals, professions to optimise their practice Additionally, good manufacturing practice In addition, I am very grateful for the with a good theoretical background and in radiopharmacy. Due to the rapid (GMP), the translational approach to work of the EANM-TC editorial group and highly developed practical skills. Within a evolution of nuclear medicine and its radiopharmaceutical production and to Rick Mills for his editing, reviewing and multidisciplinary team, nuclear medicine associated procedures and practices in radiation protection concerns in the support throughout the entire process. technologists are professionals who radiopharmacy, the EANM-TC reached the design and workflow of a radiopharmacy Lastly, the EANM Board and the Executive are recognized for their competence in decision that it is time to revisit the topic of are explored. Office deserve my words of appreciation preparing radiopharmaceuticals and are radiopharmacy and to produce an update I would like to thank each of the authors for their support in ensuring the continuity also responsible for performing the control to the previous edition of this guide. of this book for lending their time to this of this project. Radiopharmacy: an Update tests to determine the quality of the Radiopharmacy: an Update is the project and for helping us to produce would not have been possible without the preparations. outcome of the work of the EANM- a guide that reflects their expertise. contribution of all the above mentioned. The European Association of Nuclear TC in drawing together the expertise A special word of appreciation is due to Thank you very much! Medicine (EANM) is a reference scientific of many authors in order to produce the Translational Molecular Imaging and body for the global nuclear medicine a guide that addresses a variety of Therapy Committee for their contribution community. Taking this into account, in radiopharmacy-related topics, from to this publication. Andrea Santos 2008 the EANM Technologist Committee the history and basic principles of I would also like to express my gratitude Chair of the Technologist Committee 4 EANM TECHNOLGIST’S GUIDE EANM TECHNOLGIST’S GUIDE 5 RADIOPHARMACY: AN UPDATE RADIOPHARMACY: AN UPDATE INTRODUCTION INTRODUCTION Introduction In 2008, the EANM Technologist Committee published a Technologist’s Guide entitled The Radiopharmacy. It is available online through the EANM website and covers topics relevant to daily radiopharmacy practice, such as design, preparation, dispensing and documentation. Since then, many radiopharmaceutical practices have changed, especially with the introduction of new radiotracers. This year’s Technologist’s Guide includes collection of information that will prove the basics, starting from history of an essential aid in the clinical setting and radiopharmaceuticals, and proceeds to will keep the technologist up to date with the high-end radiopharmaceuticals used the latest radiopharmacy principles and in translational medicine. Illustrations practices. and tables have been included to facilitate the understanding of certain MarieClaire Attard principles. The most widely used Main-Editor on behalf of the editors radiopharmaceuticals in SPECT and PET have been dealt with separately because of the breadth of development since the previous publication in 2008. This year’s Technologist’s Guide also covers radiopharmaceuticals used in therapy. Authors from different backgrounds have contributed to the Guide, ensuring that it will be an important addition to the knowledge base required to perform radiopharmacy. It is an unmissable 6 EANM TECHNOLGIST’S GUIDE EANM TECHNOLGIST’S GUIDE 7 RADIOPHARMACY: AN UPDATE RADIOPHARMACY: AN UPDATE THE HISTORY OF RADIOPHARMACY by Marius Mada 1 CHAPTER 1 CHAPTER 1 EARLY PIONEERS THE HISTORY OF RADIOPHARMACY OF HISTORY THE Two scientists paved the way for radiology radium and thorium compounds being efficient, while others saw advantages were being developed, attention was RADIOPHARMACY OF HISTORY THE and radiopharmacy at the end of the tried in almost all areas of medicine. A in using an interval therapy, i.e. multiple, being drawn to the dangerous effects nineteenth century. Wilhelm Conrad “radium frenzy” ensued, and radioactivity regular but weaker radiation doses of radioactive substances on patients. It Roentgen (1845–1923) discovered X-rays was used for the treatment of pulmonary (fractionated radiation). For more than a was observed that following prolonged in 1895, which for the first time provided tuberculosis, elephantiasis and epilepsy, decade, supporters in both camps tried to exposure to radium plasters, inflammation an insight into the living body. Only a year to name just a few conditions. strengthen their position with numerous or redness of the skin occurred, culminating later, Henri Becquerel (1852–1908) found Furthermore, tumours were treated with publications before the scientific dispute in malignant inflammation. «[One] knows that certain naturally occurring substances radioactive substances with promising was settled in favour of fractionated today that radium rays are able to cause emit radiation that is visible over distances results. In addition to external application, radiation [1, 2]. carcinoma cells to fade and thus contribute and can penetrate black paper and by 1905 internal application of radioactive to the healing of cancerous ulcers. blacken photographic plates. Marie and materials (radium bromide or sulphate) However, it must be remembered that Pierre Curie discovered that uranium and was being performed using various DANGERS OF RADIOACTIVITY other tissues besides the carcinoma are polonium have this property and named methods of placing the substance. Metal With the increasing use of radionuclides, strongly attacked by the rays.» In addition, this phenomenon radioactivity (Fig. 1). It capsules, needles, glass tubes and other the need to protect healthcare it was observed that small mammals, soon became clear that these rays should suitable containers were used so that the professionals was soon recognised. Even such as mice, died within a few hours find application in many different scientific radiation source could be removed from today, Geiger counters and film dosimeters when exposed to intense radiation [3]. fields, especially in medicine. the body once the treatment had been are standard equipment in radiology and Following the initial application of completed. The radiation treatment of nuclear medicine departments and are RADIATION THERAPY CULTURE X-rays in the treatment of skin diseases, tumours continued following the First not dissimilar to the devices from the past In the early twentieth century, the scientific radioactive substances were also used in World War and progress was recorded (Fig. 2). world was fascinated by the therapeutic this area. Scientific journals at the time particularly in measuring more precisely At the same time as the early devices to potential of radioactive compounds but reported successes in therapeutic hair the dose applied. Already at this stage aid protection of healthcare professionals was also aware of the dangers they can removal and treatment for acne or copper there were two approaches to treatment: rash associated with syphilis. Soon, the one group of physicians considered a use