Ernst Schering Research Foundation Workshop 62 PET Chemistry
Ernst Schering Research Foundation Workshop 62
PET Chemistry
The Driving Force in Molecular Imaging
P.A. Schubiger, L. Lehmann, M. Friebe Editors
With 140 Figures and 20 Tables
123
Series Editors: G. Stock and M. Lessl
Library of Congress Control Number: 2006927239 ISSN 0947-6075
ISBN-10 3-540-32623-5 Springer Berlin Heidelberg New York ISBN-13 978-3-540-32623-6 Springer Berlin Heidelberg New York
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Preface
Personalized medicine employing patient-based tailor-made therapeutic drugs is taking over treatment paradigms in a variety of fields in oncology and the central nervous system. The success of such therapies is mainly dependent on efficacious therapeutic drugs and a selective imaging probe for identification of potential responders as well as therapy monitoring for an early benefit assessment. Molecular imaging (MI) is based on the selective and specific interaction of a molecular probe with a biological target which is visualized through nuclear, magnetic resonance, near infrared or other methods. Therefore it is the method of choice for patient selection and therapy monitoring as well as for specific end- point monitoring in modern drug development. PET (positron emitting tomography), a nuclear medical imaging modality, is ideally suited to produce three-dimensional images of various targets or processes. The rapidly increasing demand for highly selective probes for MI strongly pushes the development of new PET tracers and PET chemistry.
‘PET chemistry’ can be defined as the study of positron-emitting compounds regarding their synthesis, structure, composition, reactivity, nuclear properties and processes and their properties in natural and un- natural environments. In practice PET chemistry is strongly influenced by the unique properties of the radioisotopes used (e.g., half-life, chemi- cal reactivity, etc.) and integrates scientific aspects of nuclear-, organic-, inorganic- and biochemistry.
VI Preface The 62nd Ernst Schering Foundation Workshop ‘PET Chemistry – The Driving Force in Molecular Imaging’ is the first in the history of the Foundation devoted to special aspects of the synthesis and characteriza- tion of PET tracers. The purpose of the workshop was to gain a deeper insight into the complex applications and emerging technologies in the area of PET chemistry. New inventions in this field have a strong impact on MI, preclinical and clinical research, new therapeutic drug develop- ment, clinical routine applications and new chemical concepts.
The contributions from the invited experts that are compiled in this book demonstrate the focus and the large investment of effort over the last decade towards the advancement of PET chemistry as the cornerstone of MI today. New ideas in this exciting field translate into practical benefit very quickly. Scientific aspects covered by the workshop included re- flections on a variety of PET isotopes such as11C,68Ga,64Cu,86Y,76Br,
77Br,124I and their impact on the MI field. The main focus was put on
18F, the ‘workhorse’ of PET. The contributions embraced a broad spec- trum of new technical features such as the application of microwaves, microreactors and modules in the synthesis and development of new PET tracers.
The open atmosphere that prevailed during interdisciplinary discus- sions, and the dedication towards the goal of advancing the shared field of expertise, led to a profound contribution to PET chemistry.
We wish to express our sincere gratitude to all participants for their contributions to both the workshop and to this book. We are also grateful to the Schering Research Foundation for the generous support in making the workshop a great success.
Berlin, May 2006, August Schubiger Lutz Lehman Matthias Friebe
Contents
1 Molecular Imaging with PET – Open Questions?
P.A. Schubiger . . . . 1 2 Fluorine-18 Labeling Methods: Features and Possibilities
of Basic Reactions
H.H. Coenen . . . . 15 3 Fluorine-18 Labeling of Small Molecules:
The Use of18F-Labeled Aryl Fluorides Derived
from No-Carrier-Added [18F]Fluoride as Labeling Precursors F. Wuest . . . . 51 4 Fluorine-18 Labeling of Peptides and Proteins
H.J. Wester, M. Schottelius . . . . 79 5 [18F]Fluoropyridines: From Conventional Radiotracers
to the Labeling of Macromolecules Such as Proteins and Oligonucleotides
F. Dollé . . . . 113 6 Production of Non-standard PET Radionuclides
and the Application of Radiopharmaceuticals Labeled with these Nuclides
M.J. Welch, R. Laforest, J.S. Lewis . . . . 159
VIII Contents 7 Carbon-11 Labeling Chemistry
Based upon [11C]Methyl Iodide
F. Wuest, M. Berndt, T. Kniess . . . . 183 8 68Ga-PET Radiopharmacy: A Generator-Based Alternative
to18F-Radiopharmacy
H.R. Maecke, J.P. André . . . . 215 9 Microwaving in F-18 Chemistry:
Quirks and Tweaks
S. Stone-Elander, N. Elander, J.-O. Thorell,
A. Fredriksson . . . . 243 10 Micro-reactors for PET Tracer Labeling
S.Y. Lu, V.W. Pike . . . . 271 11 Synthesis Modules and Automation in F-18 Labeling
R. Krasikova . . . . 289 12 Pharmacological Prerequisites for PET Ligands
and Practical Issues in Preclinical PET Research
S.M. Ametamey, M. Honer . . . . 317 13 Positron Emission Tomography Imaging
as a Key Enabling Technology in Drug Development
T.J. McCarthy . . . . 329 Previous Volumes Published in This Series . . . . 341
List of Editors and Contributors
Editors
Schubiger, P.A.
Animal Imaging Center – PET, Center for Radiopharmaceutical Science of ETH, PSI and USZ, ETH Hönggerberg D-CHAB, Wolfgang-Pauli Str. 10, 8093 Zürich, Switzerland
(e-mail: august.schubiger@pharma.ethz.ch)
Friebe, M.
Corporate Research, Schering AG, Müller Str. 178, 13342 Berlin, Germany (e-mail: matthias.friebe@schering.de)
Lehmann, L.
Corporate Research, Schering AG, Müller Str. 178, 13342 Berlin, Germany (e-mail: lutz.lehmann@schering.de)
Contributors
Ametamey, S.M.
Animal Imaging Center-PET, Center for Radiopharmaceutical Science of ETH, PSI and USZ, ETH-Hönggerberg, D-CHAB, Wolfgang-Pauli-Str. 10, 8093 Zürich, Switzerland
(e-mail: simon.ametamey@pharma.ethz.ch)
André, J. P.
Centro de Química, Campus de Gultar, Universidade do Minho, 4710-057 Braga, Portugal
X List of Editors and Contributors
Berndt, M.
PET Tracer Department, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Centre Rossendorf, P.O. Box 510119, 01328 Dresden, Germany
Coenen, H.H.
Institut für Nuklearchemie (INC), Forschungszentrum Jülich GmbH, Wilhelm-Johnen-Str., 52425 Jülich, Germany
(e-mail: h.h.coenen@fz-juelich.de)
Dollé, F.
Service Hospitalier Frédéric Joliot, Département de Recherche Médicale – CEA, 4 Place du Général Leclerc, 91406 Orsay, France
(e-mail: frederic.dolle@cea.fr)
Elander, N.
Department of Physics, Albanova Center for Physics, Astronomy and Biotechnology, Stockholm University, 10691 Stockholm, Sweden
Fredriksson, A.
Karolinska Pharmacy Research Department, Karolinska University Hospital, 17176 Stockholm, Sweden
Honer, M.
Center for Radiopharmaceutical Science of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences, ETH-Hönggerberg D-CHAB, Wolfgang-Pauli-Str. 10, 8093 Zürich, Switzerland
Kniess, T.
PET Tracer Department, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Centre Rossendorf, P.O. Box 510119, 01328 Dresden, Germany
Krasikova, R.
Institute of the Human Brain, Russian Academy of Science, 9 Pavlov Str., 197376 St. Petersburg, Russia
(e-mail: raisa@ihb.spb.ru)
List of Editors and Contributors XI
Laforest, R.
Division of Radiological Sciences, Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110, USA
Lewis, J.S.
Division of Radiological Sciences, Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110, USA
Lu, S.Y.
PET Radiopharmaceutical Sciences, Molecular Imaging Branch, National Institute of Mental Health, NIH, Building 10, Room B3C346, 10 Center Drive, MSC1003, Bethesda, MA 20892-1003, USA (e-mail: ShuiyuLu@mail.nih.gov)
McCarthy, T.J.
Pfizer Global Research and Development, 49 Hancock Dr., Mystic, CT 06355, USA (e-mail: timothy.j.mccarthy@pfizer.com)
Maecke, H.R.
Division of Radiological Chemistry, University Hospital Basel, 4031 Basel, Switzerland
(e-mail hmaecke@uhbs.ch)
Pike, V.W.
PET Radiopharmaceutical Sciences, Molecular Imaging Branch, National Institute of Mental Health, NIH, Building 10, Room B3C346, 10 Center Drive, MSC1003, Bethesda, MA 20892-1003, USA
Schottelius, M.
Nuklearmedizinische Klinik und Poliklinik und Institut für Radiochemie, Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany
Stone-Elander, S.
Department of Clinical Neuroscience, Positron Emission Tomography, Karolin- ska Pharmacy, Karolinska University Hospital, 17176 Stockholm, Sweden (e-mail: sharon.stone-elander@karolinska.se)
XII List of Editors and Contributors
Thorell, J.-O.
Karolinska Pharmacy Research Department, Karolinska University Hospital, 17176 Stockholm, Sweden
Welch, M.J.
Division of Radiological Sciences, Department of Radiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Blvd., St. Louis, MO 63110, USA (e-mail: WelchM@mir.wustl.edu)
Wester, H. J.
Nuklearmedizinische Klinik und Poliklinik und Institut für Radiochemie, Technische Universität München, Ismaninger Str. 22, 81675 Munich, Germany (e-mail: H.J.Wester@lrz.tum.de)
Wuest, F.
PET Tracer Department, Institute of Bioinorganic and Radiopharmaceutical Chemistry, Research Centre Rossendorf,
P.O. Box 510119, 01328 Dresden, Germany (e-mail: f.wuest@fz-rossendorf.de)
