Somatostatin Analogues E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Wissenschaft und neue Technologien
• Sprache: Englisch

Seitenzahl: 672

Veröffentlichungsjahr: 2015

Beschreibung

Featuring chapters from specialists in endocrinology, physiology, pathology, and nuclear medicine, this book provides a multidisciplinary approach to a wide variety of issues concerning somatostatin and its analogues. The book:

• Provides the most up-to-date coverage of somatostatin analog use in diagnostic and therapy
• Integrating the specialties of endocrinology, physiology, pathology, and nuclear medicine, providing the multidisciplinary approach to the topic
• Focuses on future applications, novel compounds, and areas for further research
• Covers topics by authors who are renowned experts and researchers in the field

Leseprobe

SOMATOSTATIN ANALOGUES

From Research to Clinical Practice

Edited by

ALICJA HUBALEWSKA-DYDEJCZYK

ALBERTO SIGNORE

MARION DE JONG

RUDI A. DIERCKX

JOHN BUSCOMBE

CHRISTOPHE VAN DE WIELE

Copyright © 2015 by John Wiley & Sons, Inc. All rights reserved

Published by John Wiley & Sons, Inc., Hoboken, New JerseyPublished simultaneously in Canada

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Library of Congress Cataloging-in-Publication Data

Somatostatin analogues : from research to clinical practice / edited by Alicja Hubalewska-Dydejczyk, Alberto Signore, Marion de Jong, Rudi A. Dierckx, John Buscombe, Christophe Van de Wiele.    p. ; cm.  Includes bibliographical references and index.

  ISBN 978-1-118-52153-3 (cloth)I. Hubalewska-Dydejczyk, Alicja, editor. [DNLM:  1. Somatostatin–analogs & derivatives.  2. Receptors, Somatostatin–therapeutic use. 3. Somatostatin–therapeutic use. WK 515]  QP572.S59  612.405–dc23

          2014043035

CONTRIBUTORS

Manuela Albertelli, Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy

Richard P. Baum, THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Zentralklinik Bad Berka, Germany

Lisa Bodei, Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy

Adrienne H. Brouwers, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

John Buscombe, Addenbrookes Hospital, Cambridge, UK

Adele Cassenti, Department of Oncology, University of Turin, Orbassano, Turin, Italy

Marco Chianelli, Endocrinology Unit, “Regina Apostolorum” Hospital, Albano (Rome), Italy

Rudi A. Dierckx, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, and University Medical Center of Groningen, Groningen, The Netherlands

Philip H. Elsinga, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, and University Medical Center of Groningen, Groningen, The Netherlands

Melpomeni Fani, Clinic of Radiology and Nuclear Medicine, University of Basel Hospital, Basel, Switzerland

Diego Ferone, Endocrinology Unit, Department of Internal Medicine and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy

Helle-Brit Fiebrich, Department of Medical Oncology, University of Groningen, and University Medical Center of Groningen, Groningen, The Netherlands

Luz Kelly Anzola Fuentes, Nuclear Medicine, ClinicaColsanitas, Bogotà, Colombia

Aleksandra Gilis-Januszewska, Department of Endocrinology with Nuclear Medicine Unit, Medical College, Jagiellonian University, Krakow, Poland

Wouter W. de Herder, Department of Internal Medicine, Erasmus MC, Sector of Endocrinology, Rotterdam, The Netherlands

Anouk N.A. van der Horst-Schrivers, Departments of Medical Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

Alicja Hubalewska-Dydejczyk, Department of Endocrinology with Nuclear Medicine Unit, Medical College, Jagiellonian University, Krakow, Poland

Agata Jabrocka-Hybel, Department of Endocrinology, University Hospital in Krakow; Department of Endocrinology, Medical College, Jagiellonian University, Krakow, Poland

Werner Jaschke, Department of Radiology, Innsbruck Medical University, Innsbruck, Austria

Marion de Jong, Department of Nuclear Medicine and Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

Boen L.R. Kam, Department of Nuclear Medicine and Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

Ido P. Kema, Department of Laboratory Center, University of Groningen, and University Medical Center of Groningen, Groningen, The Netherlands

Mark Konijnenberg, Erasmus MC, Rotterdam, The Netherlands

Klaas Pieter Koopmans, Department of Radiology and Nuclear Medicine, Martini Hospital Groningen, Groningen, The Netherlands

Eric P. Krenning, Department of Nuclear Medicine and Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

Harshad R. Kulkarni, THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Zentralklinik Bad Berka, Germany

Dik J. Kwekkeboom, Department of Nuclear Medicine and Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

Thera P. Links, Department of Endocrinology, University of Groningen, and University Medical Center Groningen, Groningen, The Netherlands

Helmut R. Maecke, Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany

Theodosia Maina, Molecular Radiopharmacy, INRASTES, NCSR “Demokritos,” Athens, Greece

Frédérique Maire, Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, Clichy and Université Paris Denis-Diderot, Paris, France

Renata Mikołajczak, Radioisotope Centre Polatom, National Centre for Nuclear Research, Otwock, Poland

Berthold A. Nock, Molecular Radiopharmacy, INRASTES, NCSR “Demokritos,” Athens, Greece

Dorota Pach, Department of Endocrinology, University Hospital in Krakow; Department of Endocrinology with Nuclear Medicine Unit, Medical College, Jagiellonian University, Krakow, Poland

Giovanni Paganelli, Division of Nuclear Medicine, European Institute of Oncology, Milan, Italy

Mauro Papotti, Department of Oncology, University of Turin, Orbassano, Turin, Italy

Daniel Putzer, Department of Radiology, Innsbruck Medical University, Innsbruck, Austria

Ida Rapa, Department of Oncology, University of Turin, Orbassano, Turin, Italy

Luisella Righi, Department of Oncology, University of Turin, Orbassano, Turin, Italy

Philippe Ruszniewski, Service de Gastroentérologie-Pancréatologie, Hôpital Beaujon, Clichy and Université Paris Denis-Diderot, Paris, France

Alberto Signore, Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, Faculty of Medicine and Psychology, “Sapienza” University of Rome, Rome, Italy

Anna Sowa-Staszczak, Department of Endocrinology, University Hospital in Krakow, Krakow, Poland

Agnieszka Stefańska, Department of Endocrinology, University Hospital in Krakow, Krakow, Poland

Aikaterini Tatsi, Molecular Radiopharmacy, INRASTES, NCSR “Demokritos,” Athens, Greece

Jaap J.M. Teunissen, Department of Nuclear Medicine and Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

Marily Theodoropoulou, Department of Endocrinology, Max Planck Institute of Psychiatry, München, Germany

Henri J.L.M. Timmers, Department of Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Malgorzata Trofimiuk-Müldner, Department of Endocrinology with Nuclear Medicine Unit, Medical College, Jagiellonian University, Krakow, Poland

Christophe Van de Wiele, Department of Nuclear Medicine, Ghent University Hospital, Belgium

Irene J. Virgolini, Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria

Esther I. van Vliet, Department of Nuclear Medicine and Radiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands

Marco Volante, Department of Oncology, University of Turin, Orbassano, Turin, Italy

Elisabeth G.E. de Vries, Department of Medical Oncology, University of Groningen, and University Medical Center of Groningen, Groningen, The Netherlands

Dietmar Waitz, Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria

Annemiek M.E. Walekamp, Department of Medical Oncology, University of Groningen, and University Medical Center of Groningen, Groningen, The Netherlands

Gerlig Widmann, Department of Radiology, Innsbruck Medical University, Innsbruck, Austria

PREFACE

Motto of the book:

You cannot hope to build a better world without improving the individuals. To that end each of us must work for his own improvement and at the same time share a general responsibility for all humanity, our particular duty being to aid those to whom we think we can be most useful.

—Maria Sklodowska-Curie

Huge progress has been made in recent years in modern medicine owing to, inter alia, the development of molecular biology. Better understanding of the nature of the disease is a continuous challenge to look for more effective forms of diagnostics and therapy resulting in the improvement of the quality of life of our patients.

The model example of such progress is “somatostatin story”. Somatostatin isolation over 40 years ago not only resulted in the Nobel Prize for its discoverers but has also greatly impacted the current clinical practice. The hormone, which at beginning was known only as regulating factor, has now become a potent drug and imaging medium. It has changed the fate of many acromegalic patients and has been applied in other oncological and non-oncological diseases.

Somatostatin was the first peptide to be obtained by bacterial recombination. Although its first therapeutic administration took place before the exact mechanisms of its action were elucidated, it was the discovery of somatostatin receptors and their subtypes, which gave rise to interdisciplinary research leading to the use of somatostatin analogues in routine clinical practice.

The development of radiolabeled somatostatins has to some degree defined the development of nuclear medicine over the past 20 years. During this journey, much has been learned about the nature of cancer with particular reference to those tumors originating from neuroendocrine tissue. What has been unique about this process is the key role played by nuclear medicine scientists both clinical and preclinical. Initial work was supported by industry with imaging agents such as In-111 pentetreotide and Tc-99m depreotide becoming licensed products. However, for the past 10 years, every new advance has been led by academia, and not industry. Nuclear medicine has been able to care for the patient is a holistic way, imaging for diagnosis, staging and re-staging, and treatment to palliate symptoms and extend life. To aid in this nuclear medicine, physicians have interacted with a wide range of clinicians and built multidisciplinary clinics, a pattern followed in other cancer types.

The nuclear medicine community continues to innovate using radiolabeled somatostatin analogues: developing Lu-177 as a therapeutic isotope offering efficacy with reduced toxicity, using Ga-68 DOTATATE in imaging which differentiated thyroid cancer, and the administrating Y-90 DOTATOC intra-arterially for treating gliomas. All these innovations depended on the imagination, careful science, and dedication of a range of scientists and clinicians around the world.

The best examples of somatostatin research importance in clinical practice are neuroendocrine tumors, particularly originating from the gastroenteropancreatic system. Whilst it is true that neuroendocrine tumors are rare. The slow progression of many tumors has resulted in a prevalence that is much higher than the incidence and at any time 10% of patients visiting gastroenterological oncology clinics may have neuroendocrine tumors. Firstly, somatostatin and its analogues were applied to control the clinical symptoms in syndromic patients, particularly carcinoid ones. Then somatostatin receptor scintigraphy in its various forms became the imaging of choice in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients. Development of radioguided surgery improved the surgical outcomes. The diagnostic application of the radiolabeled somatostatin analogues led to the therapeutic approach with In-111, replaced by 90-Y and 177-Lu labeled compounds. Those centers worldwide that offer radio-peptide therapy for neuroendocrine tumors have together treated more patients than the centers that use licensed radiolabeled products to treat much more common lymphomas. But the last word has not been said yet. Locoregional therapies for liver metastases with alpha-particles emitting isotopes are being tested. Although the direct cytostatic effect of “old” non-labeled somatostatin analogues in neuroendocrine tumors has been confirmed, the new ones seem to be even more promising. Currently there are attempts to organize and unify the GEP-NET classification to establish important prognostic factors, which would allow the prediction of the disease outcome with a great probability, and to choose optimal diagnostic and therapeutic options for each individual patient. Those methods have still not been optimized and remain a huge challenge in this field of oncology.

The book presented to you is a compendium of current knowledge on the use of somatostatin analogues in diagnostics and therapy, and it also shows the directions of further research in this field. The authors of the book chapters are experts of various scientific disciplines involved in work on somatostatin analogues as well as well-known authorities interested in management of patients with different neoplasms, especially neuroendocrine tumors. The book has been greatly supported by, among others, people actively working in the European Neuroendocrine Tumor Society (ENETs) and those who managed COST Actions (European Cooperation in the field of Scientific and Technical Research) devoted to the development of targeted therapy based on radiolabeled somatostatin compounds. Last but not least involved has been the International Research group in Immuno-Scintigraphy and Therapy (IRIST) and the editors of this book have all been or are Presidents of IRIST. This group has been intimately involved in the development of radiolabeled somatostatins for diagnosis and therapy and as such, is ideally placed to share this knowledge with a wider medical audience.

We should believe the words said by Orioson Swett Marden: There is no medicine like hope, no incentive so great and no tonic so powerful as expectations of something better than tomorrow, and that every day of our work helps our patients. Hence, there still is a field for development of research to find out the new compounds with superior efficacy to current treatments, or labeled molecules to be used in imaging diagnostics.

We hope that this book will become a guide for all those who deal with the issue presented herein.

ALICJA HUBALEWSKA-DYDEJCZYK, ALBERTO SIGNORE,

MARION DE JONG, RUDI A. DIERCKX,

JOHN BUSCOMBE, AND CHRISTOPHE VAN DE WIELE

ACKNOWLEDGMENTS

We would like to acknowledge all people managing and actively participating in COST BM0607 Action for providing the idea of this book and constant encouragement. We would like to thank all the contributors for their work and for enabling us to complete the book in timely fashion. The input of the coworkers from our departments should be stressed for helping us with obtaining good quality artwork for the book. And last but not least, a special note of appreciation is to be given to our families for constant support and endless patience.

ALICJA HUBALEWSKA-DYDEJCZYK, ALBERTO SIGNORE,

MARION DE JONG, RUDI A. DIERCKX,

JOHN BUSCOMBE, AND CHRISTOPHE VAN DE WIELE

1SOMATOSTATIN: THE HISTORY OF DISCOVERY

MALGORZATA TROFIMIUK-MÜLDNER AND ALICJA HUBALEWSKA-DYDEJCZYK

Department of Endocrinology with Nuclear Medicine Unit, Medical College, Jagiellonian University, Krakow, Poland

ABBREVIATIONS

FDA

the Food and Drug Administration

GIF

growth hormone-inhibiting factor

PET

positron emission tomography

SPECT

single photon emission computed tomography

SRIF

somatotropin release-inhibiting factor

Now, here, you can see, it takes all the running you can do, to keep in the same place. If you want to get somewhere else, you must run at least twice as fast as that!Lewis Carroll, Through the Looking Glass

The beginning of the second half of the twentieth century, the great era of discovery of factors regulating anterior pituitary hormones synthesis and release, resulted also in isolation and characterization of somatostatin. The history started with search for growth hormone-releasing factor. In 1968, Krulich and colleagues noted that extracts from different parts of rat hypothalamus either stimulated or inhibited release of pituitary growth hormone [1] . The inhibiting substance was named growth hormone-inhibiting factor (GIF). The group of Roger Guillemin developed highly sensitive assay for rat growth hormone, which enabled the confirmation of negative linear relationship between the production of the growth hormone by anterior pituitary cell culture and amount of hypothalamic extract added [2] . About 500,000 sheep hypothalami later Brazeau and Guillemin isolated the substance responsible for inhibiting effect—somatotropin release-inhibiting factor—SRIF. The structure of 14-aminoacid peptide was then sequenced, the sequence of the residues confirmed, and the molecule was resynthesized. The synthetic molecule inhibiting properties were confirmed in both in vivo and in vitro experiments. The result of the discovery was paper published in Science in 1973 [3] . Roger Guillemin renamed the hormone—since 1973 it has been known as the somatostatin [4] . The new hormone was extracted also from hypothalami of other species.

Those times were also regarded the gut hormones era. In 1969, Hellman and Lernmark announced the inhibiting effect of extract from alfa-1 cells of pigeon pancreas on insulin secretion from pancreatic islets derived from obese, hyperglycemic mice [5] . In 1974, group of C. Gale from Seattle noticed the lowering of fasting insulin and glucagon levels in baboons as well as tampering of arginine-stimulated insulin release by somatostatin—directly and in dose-dependent manner [6] . This finding was confirmed also in other animal models and humans shortly after. As the hypothalamic somatostatin seemed to act locally, the search for local, pancreatic source of the hormone started. The antibodies against somatostatin proved to be useful tool. The presence of somatostatin in delta (D) cells of the pancreas (formerly alfa-1 cells) was proved by immunofluorescence [7, 8] . In 1979, somatostatin was isolated from the pigeon pancreas, and next from other species [9] . The somatostatin-reactive cells were also found in gastrointestinal mucosa, and then in other tissues, including tumors. Concurrently, the multiple groups worked on the somatostatin action and its pan-inhibiting properties were gradually characterized. In 1977, Roger Guillemin and Andrew Schally were awarded the Nobel Prize in medicine and physiology for their work on somatostatin and other regulating hormones. Of interest, somatostatin-like peptides were also discovered in plants [10] .

Other somatostatin forms, somatostatin-28 particularly, and somatostatin precursor—preprosomatostatin—were characterized in late 1970s/early 1980s. Human cDNA coding preprosomatostatin was isolated and cloned in 1982 [11, 12] .

The possible pathological implications and potential therapeutic use of somatostatin were postulated early in the somatostatin discovery era. The clinical description of somatostatin-producing pancreatic tumor in human came from Larsson and colleagues in 1977 [13] . Somatostatin administration to block the growth hormone secretion in acromegalic patients was reported as early as in 1974 [14] . The potency of the hormone to block carcinoid flush was also observed in late 1970s and early 1980s [15, 16] . Somatostatin was the first human peptide to be produced by bacterial recombination. In 1977 Itakura, Riggs and Boyer group synthesized gene for somatostatin-14, fused it with Escherichia coli beta-galactosidase gene on the plasmid and transformed the E. coli bacteria with chimeric plasmid DNA. As the result, they obtained the functional human polypeptide [17] . The synthesis of recombinant human somatostatin led to the commercial human recombinant insulin production.

Although it was possible to produce somatostatin in large quantities, the short half-life of the hormone was one of the reasons why the native hormone was not feasible for routine clinical practice. The search for more stable yet functional hormone analogue started in 1974. The search was focused on the peptide analogues. The somatostatin receptor agonists were first to be used in clinical practice. In 1980–1982, octapeptide SMS 201–995 was synthetized and proved to be more resistant to degradation and more potent than native hormone in inhibiting growth hormone synthesis [18] . The drug, currently known as octreotide, was the first Food and Drug Administration (FDA)-approved somatostatin analogue. It was followed by other analogues, such as lanreotide (BIM 23014), and by the long-acting formulas. High selective affinity of octreotide and lanreotide for somatostatin receptor type 2 (lesser to the receptor types 3 and 5) was one of the triggers for further research. In 2005 vapreotide (RC160), somatostatin analogue with additional affinity to receptor type 4, was initially accepted for treatment of acute oesophageal variceal bleeding and granted the orphan drug status in 2008 in the United States (although final FDA approval has not been granted). Lately, promising results of large phase III studies on “universal” multitargeted somatostatin analogue, cyclohexapeptide SOM-230 pasireotide, in acromegaly and Cushing’s disease, have been published [19, 20] . The drug has been granted the European Medicines Agency and the FDA approval for pituitary adrenocorticotropic hormone (ACTH)-producing adenomas treatment. The research on first nonpeptide receptor subtype selective agonists was published in 1998; however, none of tested compounds have been introduced to clinical practice [21] . The studies on somatostatin receptors antagonists have been conducted since 1990s.

The other areas for research were somatostatin receptors. The high affinity-binding sites for somatostatin were found on pancreatic cells and in brain surface by group of J.C. Reubi in 1981–1982. The different pharmacological properties of the receptors were noted early. At the beginning two types of somatostatin receptors, with high and low affinity for octreotide, were characterized [22, 23] . In 1990s, all five subtypes of somatostatin receptors were cloned and their function was discovered. The other important step was the discovery of the somatostatin receptors overexpression in tumor cells, particularly of neuroendocrine origin [24] . This led to the first successful trials on diagnostic use of radioisotope-labeled hormones. The iodinated octreotide was used in localization of the neuroendocrine tumors in 1989–1990 [25, 26] . The Iodine-123 was replaced by the Indium-111, and later on by the Technetium 99 m [27–29] . The first Gallium-68 labeled somatostatin analogues for positron emission tomography (PET) studies were proposed in 1993 [30] . Feasibility of labeled somatostatin receptor antagonist for single photon emission computed tomography (SPECT) or PET tumor imaging has been reported in 2011 [31] . Together with diagnostics, the concept of therapeutic use radioisotope labeled somatostatin analogues has evolved. The first peptides for therapy were those labeled with Indium-111 [32] . In 1997, the Yttrium-90 labeled analogues, followed by Lutetium-177 labeled ones, were introduced in palliative treatment of neuroendocrine disseminated tumors [33, 34] .

The co-expression of somatostatin and dopamine receptors, as well as discovery of receptor heterodimerization, led to the search for chimeric somatostatin-dopamine molecules, dopastatins [35] . Other area of recent research is cortistatin, a member of somatostatin peptides family, with somatostatin receptors affinity but also with distinct properties [36] .

Summing up the multicenter research on somatostatin led to the discovery of the hormone probably second only to the insulin in its clinical use.

REFERENCES

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[23] Reubi, J. C.; Rivier, J.; Perrin, M.; et al. Endocrinology 1982, 110, 1049–1051.

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