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Therapeutic Radionuclide Generators: 90Sr/90Y and 188W/188Re Generators 90 Sr/ 90 Y and 188 W/ 188 Re Generators

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Therapeutic Radionuclide Generators: 90Sr/90Y and 188W/188Re Generators 90 Sr/ 90 Y and 188 W/ 188 Re Generators 252 pages; 13.8 mm technical reportS series no. Radionuclide generators are efficient means to enhance the availability of short lived radioisotopes used in medicine and industry. Technologies for the preparation of 90Sr/90Y and 188W/188Re generator systems developed through an IAEA coordinated research project are presented in this publication. Analytical methods 470 that are essential for evaluating the safety of radionuclides used in therapy are also described. Technical Reports SeriEs No. 470 By adapting the technologies described in this publication, these generators can be fabricated to cost effectively provide 90Y and 188Re for basic research and radiopharmaceutical preparation. Therapeutic Radionuclide Generators: Therapeutic Radionuclide Generators: 90Sr/90Y and 188W/188Re Generators 90 Sr/ 90 Y and 188 W/ 188 Re Generators INTERNATIONAL ATOMIC ENERGY AGENCY VIENNA ISBN 978–92–0–111408–2 ISSN 0074–1914 D470_covI-IV.indd 1 2009-07-17 09:06:44 THERAPEUTIC RADIONUCLIDE GENERATORS: 90Sr/90Y AND 188W/188Re GENERATORS The following States are Members of the International Atomic Energy Agency: AFGHANISTAN GREECE OMAN ALBANIA GUATEMALA PAKISTAN ALGERIA HAITI PALAU ANGOLA HOLY SEE PANAMA ARGENTINA HONDURAS PARAGUAY ARMENIA HUNGARY PERU AUSTRALIA ICELAND PHILIPPINES AUSTRIA INDIA POLAND AZERBAIJAN INDONESIA PORTUGAL BAHRAIN IRAN, ISLAMIC REPUBLIC OF QATAR BANGLADESH IRAQ REPUBLIC OF MOLDOVA BELARUS IRELAND ROMANIA BELGIUM ISRAEL RUSSIAN FEDERATION BELIZE ITALY SAUDI ARABIA BENIN JAMAICA BOLIVIA JAPAN SENEGAL BOSNIA AND HERZEGOVINA JORDAN SERBIA BOTSWANA KAZAKHSTAN SEYCHELLES BRAZIL KENYA SIERRA LEONE BULGARIA KOREA, REPUBLIC OF SINGAPORE BURKINA FASO KUWAIT SLOVAKIA BURUNDI KYRGYZSTAN SLOVENIA CAMEROON LATVIA SOUTH AFRICA CANADA LEBANON SPAIN CENTRAL AFRICAN LIBERIA SRI LANKA REPUBLIC LIBYAN ARAB JAMAHIRIYA SUDAN CHAD LIECHTENSTEIN SWEDEN CHILE LITHUANIA SWITZERLAND CHINA LUXEMBOURG SYRIAN ARAB REPUBLIC COLOMBIA MADAGASCAR TAJIKISTAN COSTA RICA MALAWI THAILAND CÔTE D’IVOIRE MALAYSIA THE FORMER YUGOSLAV CROATIA MALI REPUBLIC OF MACEDONIA CUBA MALTA TUNISIA CYPRUS MARSHALL ISLANDS TURKEY CZECH REPUBLIC MAURITANIA UGANDA DEMOCRATIC REPUBLIC MAURITIUS UKRAINE OF THE CONGO MEXICO UNITED ARAB EMIRATES DENMARK MONACO UNITED KINGDOM OF DOMINICAN REPUBLIC MONGOLIA GREAT BRITAIN AND ECUADOR MONTENEGRO NORTHERN IRELAND EGYPT MOROCCO EL SALVADOR MOZAMBIQUE UNITED REPUBLIC ERITREA MYANMAR OF TANZANIA ESTONIA NAMIBIA UNITED STATES OF AMERICA ETHIOPIA NEPAL URUGUAY FINLAND NETHERLANDS UZBEKISTAN FRANCE NEW ZEALAND VENEZUELA GABON NICARAGUA VIETNAM GEORGIA NIGER YEMEN GERMANY NIGERIA ZAMBIA GHANA 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’’. TECHNICAL REPORTS SERIES No. 470 THERAPEUTIC RADIONUCLIDE GENERATORS: 90Sr/90Y AND 188W/188Re GENERATORS 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 July 2009 STI/DOC/010/470 IAEA Library Cataloguing in Publication Data Therapeutic radionuclide generators : 90Sr/90Y and 188W/188Re generators. — Vienna : International Atomic Energy Agency, 2009. p. ; 24 cm. - (Technical reports series, ISSN 0074-1914 ; no. 470) STI/DOC/010/470 ISBN 978–92–0–111408–2 Includes bibliographical references. 1. Radioisotopes — Therapeutic use. 2. Radiopharmaceuticals. 3. Radionuclide generators. I. International Atomic Energy Agency. II. Series: Technical reports series (International Atomic Energy Agency) ; 470. IAEAL 09–00587 FOREWORD Rapid progress in preclinical and clinical research realized over the past two decades has stimulated broad interest in the use of radionuclides for targeted therapy of cancer and for other therapeutic applications using unsealed sources. The use of radiopharmaceuticals labelled with short lived radioisotopes for these applications has advantages such as higher rates of dose delivery and shorter hospital stays. Wider use of targeted therapy using radiopharmaceuticals requires the reliable availability of cost effective products of short lived radionuclides from dependable sources and suppliers. The use of short lived radionuclides is thus often restricted to places with local production of these radionuclides or places that are well connected to production facilities. An important additional strategy is the use of radionuclide generator systems that utilize parent radionuclides with long physical half-lives of months or years. The daughter can be extracted from these radionuclide generators at periodic intervals to obtain short lived radionuclides for formulation of therapeutic radiopharmaceuticals. Hence, there is great interest in developing technologies for therapeutic radionuclide generators. To address this need, the IAEA implemented a coordinated research project (CRP) on the development of generator technologies for therapeutic radionuclides. This publication is based on the work carried out at participating institutions in several Member States aimed at developing generator prototypes using various separation techniques. The two radionuclide generators described in this publication are based on 90Sr/90Y and 188W/188Re generator systems. Strontium-90 has a physical half-life of over 28 years, and 188W has a physical half-life of 69 days. Radionuclide generators prepared from these long lived parents can serve as convenient production systems to provide the therapeutic radioisotopes 90Y and 188Re on a routine basis. By adapting the technologies described in this publication, 90Sr/90Y and 188W/188Re generators can be fabricated for cost effective production of 90Y and 188Re for radiopharmaceutical preparation. The IAEA thanks all the participants in the CRP for their contributions to this publication and F.F. Knapp, Jr., for his valuable help in editing this report. The IAEA officer responsible for this publication was M.R.A Pillai of the Division of Physical and Chemical Sciences. 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. The authors are responsible for having obtained the necessary permission for the IAEA to reproduce, translate or use material from sources already protected by copyrights. Material prepared by authors who are in contractual relation with governments is copyrighted by the IAEA, as publisher, only to the extent permitted by the appropriate national regulations. CONTENTS CHAPTER 1. INTRODUCTION . 1 1.1. Background . 1 1.2. Objective . 1 1.3. Scope . 2 1.4. Structure . 2 CHAPTER 2. OVERVIEW OF THE CRP . 3 2.1. Introduction . 3 2.2. Objectives of the CRP . 6 2.3. Key issues addressed during the CRP . 6 2.4. Work plan of the CRP . 8 2.5. Summary of the work reported from different participating groups . 9 2.6. Scientific achievements of the CRP . 15 2.7. Cooperation among participants . 24 2.8. Conclusion . 24 CHAPTER 3. PROTOCOLS DEVELOPED UNDER THE CRP . 27 3.1. Supported liquid membrane based 90Sr/90Y generator . 27 3.2. Electrochemical 90Sr/90Y generator . 30 3.3. BARC method for estimating the radionuclidic purity of 90Y by extraction paper chromatography . 33 3.4. 188W/188Re alumina based generator . 35 3.5. In-house preparation of silver cation column for trapping chloride anion from saline eluant for concentration of 188Re solution. 39 CHAPTER 4. PRELIMINARY STUDIES OF THE DEVELOPMENT OF 90Sr/90Y GENERATORS AT IPEN, BRAZIL. 45 J.A. Osso, Jr., G. Barrio, A. Oliveira, B.S. Marczewski, V. Moraes, F. Camargo, R.C. Nieto, K.N. Suzuki, C.R.B.R. Dias, P.R.C. Lopes, N.C. Silva, A.L.C.P. Lima, B.L. Faintuch, J. Mengatti, E. Bortoleti, N.P. Sosa, C.P.G. Da Silva 4.1. Introduction . 45 4.2. Materials . 46 4.3. Experimental procedures . 46 4.4. Results and discussion . 47 4.5. Conclusion
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