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IAEA-TECDOC-1228 Therapeutic applications of radiopharmaceuticals Proceedings of an international seminar held in Hyderabad, India, 18–22 January 1999 June 2001 The originating Sections of this publication in the IAEA were: Nuclear Medicine Section Industrial Applications and Chemistry Section International Atomic Energy Agency Wagramer Strasse 5 P.O. Box 100 A-1400 Vienna, Austria THERAPEUTIC APPLICATIONS OF RADIOPHARMACEUTICALS IAEA, VIENNA, 2001 IAEA-TECDOC-1228 ISSN 1011–4289 © IAEA, 2001 Printed by the IAEA in Austria June 2001 FOREWORD The potential of radionuclides in therapy has been recognised for many decades. A number of radionuclides such as iodine-131, phosphorous-32, yttrium-90 and I-131 MIBG have been in use for the treatment of many benign and malignant disorders. Recently, however, there has been a significant growth of this branch of nuclear medicine with the introduction of a number of new radionuclides and radiopharmaceuticals for the treatment of metastatic bone pain, neuroendocrine and other tumours. The prospect of localising or treating neoplastic diseases using specific antibodies labelled with radioactive isotopes capable of delivering large amounts of internally administered radiation may have the potential to fulfil the promise of Ehrlich’s “magic bullet”, which has tantalised investigators worldwide for the past sixty years. Recent success in this area has been largely due to genetic and molecular techniques that now permit production of a large number of suitable peptides and monoclonal antibodies directed against specific epitopes individually characteristic of specific tumours. The input of the radiochemist and the development of labelling techniques that do not destroy the immunological integrity of the monoclonal antibodies have also been essential ingredients of the success story. Recent significant advances in monoclonal antibody techniques for pretargeting make it very likely that radiopharmaceuticals will become an important part of therapy for various cancers. It may also be possible that in addition to the use of beta particles, alpha particles may soon become a mainstay of therapeutic nuclear medicine. Cancer researchers, looking for an extremely potent and highly specific way to target cancer cells, are investigating the use of monoclonal antibodies and peptides attached to alpha emitting radionuclides in early clinical trials. Today the field of radionuclide therapy is going through an extremely interesting and exciting phase and is poised for greater growth and development in the coming years. The IAEA organised an international seminar at Hyderabad, India, with the objective of bringing together in one place medical professionals and biomedical researchers from all over the world who are engaged in clinical research & development aspects of radionuclide therapy. The seminar addressed some of the current trends in therapeutic nuclear medicine, evaluated the established procedures and assessed the re- emergence of certain old procedures. Ninety-nine official participants and 11 observers from 36 countries participated in the seminar. A total of 48 scientific papers and 13 invited lectures on a wide spectrum of basic and clinical aspects of radionuclide therapy were presented. The topics included research and development in the field of therapeutic radiopharmaceuticals, treatment of thyroid disorders with I-131 and metastatic bone pain with Sr-153, radionuclide therapy with monoclonal antibodies and peptides, radiation synovectomy, intravascular radionuclide therapy and treatment of neuroendocrine tumours. One of the novel applications of radionuclide therapy presented during the seminar was the use of I-131-CD-20 monoclonal antibodies for the treatment of non-Hodgkin’s lymphoma. The seminar also highlighted the importance of dosimetry in radionuclide therapy. This publication contains papers and invited lectures presented at the seminar. The IAEA officers responsible for the publication were A.K. Padhy of the Division of Human Health and 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 Summary.................................................................................................................................................. 1 1. INVITED PAPERS Dosimetry in radionuclide therapy.......................................................................................................... 9 G. Riccabona New aspects of radionuclide therapy of bone and joint diseases.......................................................... 18 M. Fischer Radiolabelled peptides: New radiopharmaceuticals for targeted therapy............................................. 23 M. Chinol Monoclonal antibodies to the pretargeting approach: Developments in the radiopharmaceuticals for radioimmunotherapy ............................................................................. 31 M. Chinol Management of hyperthyroidism .......................................................................................................... 39 M. Poshyachinda Current trends in radionuclide therapy.................................................................................................. 47 K.E. Britton Experience with radioimmunotherapy and radio-peptide therapy ........................................................ 49 K.E. Britton, M. Granowska The role of mathematical models in the optimization of radiopharmaceutical therapy........................ 51 C. Divgi Radioimmunotherapy: Opportunities, obstacles and challenges, with special reference to developing countries .................................................................................................. 55 C. Divgi Rhenium radioisotopes for therapeutic radiopharmaceutical development.......................................... 59 F.F. Knapp, A.L. Beets, J. Pinkert, J. Kropp, W.Y. Lin, S.Y. Wang 2. RADIOPHARMACEUTICALS 90Y-preparation and some preliminary results on labelling of radiopharmaceuticals........................... 69 S. Malja, K. Schomacher, G. Damani, T. Cuci, E. Malja, A. Salaku 90Y of high purity for medical applications........................................................................................... 79 A.X. Castillo, K.I. Olive, E.O. Alvarez 90Y and 105Rh labelled preparations: Potential therapeutic agents ........................................................ 84 M. Venkatesh, C. Usha, M.R.A. Pillai Radiochemical processing of radionuclides (105Rh, 166Ho, 153Sm, 186Re and 188Re) for targeted radiotherapy................................................................................................................ 90 P.R. Unni, K. Kothari, M.R.A. Pillai Study on the preparation and stability of 188Re biomolecules via EHDP ............................................. 99 G. Ferro-Flores, L. Garcia-Salinas, L. Paredes-Gutierrez, K. Hashimoto, L. Melendez-Alafort, C.A. Murphy Re-186-bleomycine: Radiopharmaceutic for diagnosis and therapy .................................................. 104 S. Szostak, S. Tustanowski, B. Birkenfeld, R. Almakiewicz Rhenium-186 direct labelled HigG ..................................................................................................... 107 V. Lungu, G. Mihailescu, G. Dumitrescu Trials to optimize dosimetry for 153Sm-EDTMP therapy to improve therapeutic effects................... 112 G. Riccabona, R. Moncayo-Naveda; M. Oberlandstätter, E. Donnemiller, D.Kendler Radiopharmaceuticals of DTPA, DMSA and EDTA labelled with holmium-166 ............................. 118 M. Rahman, H. Matsouka, S. Takami, K. Terunuma Studies on the preparation and evaluation of colloidal chromic phosphate — 32P for possible therapeutic use.................................................................................................... 125 G. Prabhakar, K.S. Mehra, N. Ramamoorthy 153Sm complexes of phosphonic acid ligands...................................................................................... 133 M.A. Majali, A.R. Mathakar, S. Banerjec, G. Samuel, M.R.A. Pillai, H.H. Shimpi, O.P.D. Noronha, A.M. Samuel 99m 188 MAG2GABA-biocytin synthesized with new intermediates for radiolabelling Tc and Re........ 140 S.H. Ahn, T.H. Choi, C.W. Choi, S.D. Yang, K.S. Woo, W.S. Chung, S.M. Lim 3. THYROID CANCER Radioiodine therapy in management of thyroid carcinoma — A review of 138 patients................... 149 A.S. Hossain, S. Hossain, N. Hafiz, D.A. Taslima, H. Rashid Role of high dose I-131 in treatment of differentiated thyroid carcinoma: An experience of 354 patients at INMOL.................................................................................... 155
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  • Particle Accelerators and Detectors for Medical Diagnostics and Therapy Arxiv:1601.06820V1 [Physics.Med-Ph] 25 Jan 2016

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    Particle Accelerators and Detectors for medical Diagnostics and Therapy Habilitationsschrift zur Erlangung der Venia docendi an der Philosophisch-naturwissenschaftlichen Fakult¨at der Universit¨atBern arXiv:1601.06820v1 [physics.med-ph] 25 Jan 2016 vorgelegt von Dr. Saverio Braccini Laboratorium f¨urHochenenergiephysik L'aspetto pi`uentusiasmante della scienza `eche essa incoraggia l'uomo a insistere nei suoi sogni. Guglielmo Marconi Preface This Habilitation is based on selected publications, which represent my major sci- entific contributions as an experimental physicist to the field of particle accelerators and detectors applied to medical diagnostics and therapy. They are reprinted in Part II of this work to be considered for the Habilitation and they cover original achievements and relevant aspects for the present and future of medical applications of particle physics. The text reported in Part I is aimed at putting my scientific work into its con- text and perspective, to comment on recent developments and, in particular, on my contributions to the advances in accelerators and detectors for cancer hadrontherapy and for the production of radioisotopes. Dr. Saverio Braccini Bern, 25.4.2013 i ii Contents Introduction 1 I 5 1 Particle Accelerators and Detectors applied to Medicine 7 2 Particle Accelerators for medical Diagnostics and Therapy 23 2.1 Linacs and Cyclinacs for Hadrontherapy . 23 2.2 The new Bern Cyclotron Laboratory and its Research Beam Line . 39 3 Particle Detectors for medical Applications of Ion Beams 49 3.1 Segmented Ionization Chambers for Beam Monitoring in Hadrontherapy 49 3.2 Proton Radiography with nuclear Emulsion Films . 62 3.3 A Beam Monitor Detector based on doped Silica Fibres .