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Optimization of Synthesis and Quality Control Procedures for the Preparation of 18F and 123I Labelled Peptides for Nuclear Medicine

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Optimization of Synthesis and Quality Control Procedures for the Preparation of 18F and 123I Labelled Peptides for Nuclear Medicine IAEA-TECDOC-1310 Optimization of synthesis and quality control procedures for the preparation of 18F and 123I labelled peptides for nuclear medicine September 2002 The originating Section of this publication in the IAEA was: Industrial Applications and Chemistry Section International Atomic Energy Agency Wagramer Strasse 5 P.O. Box 100 A-1400 Vienna, Austria OPTIMIZATION OF SYNTHESIS AND QUALITY CONTROL PROCEDURES FOR THE PREPARATION OF 18F AND 123I LABELLED PEPTIDES FOR NUCLEAR MEDICINE IAEA, VIENNA, 2002 IAEA-TECDOC-1310 ISBN 92–0–116802–0 ISSN 1011–4289 © IAEA, 2002 Printed by the IAEA in Austria September 2002 FOREWORD The development of radiopharmaceuticals based on biochemical concepts, which have potential for use in in vivo diagnostics in nuclear medicine, is an active and fertile area of research. Of particular relevance is the use of biomolecules such as monoclonal antibodies and peptides labelled either with positron or gamma emitting radionuclides. Fluorine-18 (18F) and Iodine-123 (123I) are excellent cyclotron-produced radionuclides that are being used to make radiopharmaceuticals for positron emission tomography (PET) and single photon emission tomography (SPECT) studies. The Internatinal Atomic Energy Agency (IAEA) realized the potential of 18F and 123I labelled peptides for in vivo diagnosis and took into account the interest and research potential of many scientists from developing Member States for acquiring or expanding expertise in this field. Although considerable progress in 18F and 123I chemistry for radiolabelling of biomolecules has been reported in the recent past, there was still a need to do more research to optimize selective labelling procedures of peptides. Such research work would involve use of prosthetic chemical groups, which would facilitate coupling of these halogens to peptides. Also important are the quality control aspect and in vitro and in vivo evaluation in experimental animals. In 1997, upon the recommendation of a group of experts, the IAEA organized a Co-ordinated Research Project (CRP) on Optimization of Synthesis and Quality Control Procedures for the Preparation of 18F and 123I Labelled Peptides. Eight scientists from Asia, Latin America and Europe participated in the CRP. The project was concluded in 2000. The participating laboratories reached a proficiency level that allowed them to use the technology and skills of radiohalogenation of peptides and proteins via the prosthetic group approach to label compounds of clinical interest. Laboratory procedures for the synthesis and labelling of three prosthetic groups, including procedures for their isolation and formulation prior to peptide coupling are included in this report. The results of intercomparison exercises on the performance of several chromatography techniques for quality control as well as the protocols for biological evaluation are also reported. This report is valuable for research groups working in the field of protein based radiopharmaceutical development. It would advance research in the promising field of radiolabelled peptides for peptide receptor based diagnosis and therapy. Developing Member States having programmes in cyclotron based nuclear medicine would benefit from research in this area. The IAEA wishes to thank all the participants in the CRP for their valuable contributions. The IAEA officer responsible for this CRP was H. Vera Ruiz of the Division of Physical and Chemical Sciences. EDITORIAL NOTE This publication has been prepared from the original material as submitted by the authors. The views expressed do not necessarily reflect those of the IAEA, the governments of the nominating Member States or the nominating organizations. 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. CONTENTS 1. INTRODUCTION ...........................................................................................................................1 2. SCOPE OF THE CO-ORDINATED RESEARCH PROJECT........................................................2 2.1. Selection of the peptide.............................................................................................................2 2.2. Labelling methods.....................................................................................................................2 2.2.1. Labelling using the SIB method .....................................................................................3 2.2.2. Labelling with 18F...........................................................................................................3 2.3. In vitro and in vivo evaluation studies......................................................................................3 3. LABORATORY PROTOCOLS ......................................................................................................3 3.1. Synthesis of the reference compound for chemotactic peptide.................................................3 3.2. Precursor synthesis....................................................................................................................4 3.3. Radiosynthesis of SIB and SFB................................................................................................6 3.4. Conjugation of the prosthetic group to peptide or protein ........................................................7 3.5. Quality control ..........................................................................................................................7 3.6. Biological evaluation ................................................................................................................8 3.6.1. Somatostatin receptor binding peptides..........................................................................8 3.6.2. Pretreatment, competition and displacement studies......................................................9 3.6.3. Growth inhibition of HTB-121 and AR42J cells by SSTR binding agonists.................9 3.6.4. Chemotactic peptides......................................................................................................9 3.6.5. Cell preparation ..............................................................................................................9 3.6.6. Competitive inhibition of [3H]fMLF binding ...............................................................10 3.6.7. Superoxide production assay ........................................................................................10 3.6.8. Įvȕ3 integrin antagonists..............................................................................................10 4. COLLABORATIVE ACTIVITIES ...............................................................................................11 5. CONCLUSIONS OF THE CRP ....................................................................................................11 6. PUBLICATIONS AND PRESENTATIONS ORIGINATING FROM THE CRP .......................13 6.1. International publications........................................................................................................13 6.2. Presentations in national and international conferences .........................................................13 6.3. National publication................................................................................................................14 BIBLIOGRAPHY ..................................................................................................................................15 REPORTS BY PARTICIPANTS IN THE CO-ORDINATED RESEARCH PROJECT 123I labelled vasoactive intestinal peptide: Optimization of the radioiodination method, in vivo and in vitro assays ..........................................................................23 O.R. Pozzi, E.O. Sajaroff, M. Edreira, S.I. Gomez, A. Manzini Optimization of syntheses, quality control procedures and in vitro/in vivo evaluation of 18F and 123I radiopharmaceuticals based on peptides.........................................................................59 E. Bortoleti de Araújo, C. Pagano, G. da Silva, N.P.S. de Pereira, E. Muramoto, M.T. Colturato Radioiodination of vasoactive intestinal peptide (VIP)..........................................................................73 Y. Wang, L. Wang, D. Yin Development and preclinical evaluation of radiolabelled somatostatin receptor agonists and DvE3-integrin antagonists ...........................................................................................93 G. Stöcklin, H.J. Wester, R. Haubner, M. Schottelius Optimization of synthesis and quality control procedures for the preparations of 18F and 123I labelled peptides...................................................................................105 S.C. Archimandritis, S. Potamianos, A.D. Varvarigou Preparation of 125I labelled compound..................................................................................................117 H. Rafii, D. Beiki, M. Matlubi, A.R. Jalilian, F. Motamedi, A.R.,
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