Ernst Schering Research Foundation Workshop 49 Molecular Imaging

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Ernst Schering Research Foundation Workshop 49

Molecular Imaging

An Essential Tool in Preclinical Research, Diagnostic Imaging, and Therapy

A.A. Bogdanov Jr., K. Licha Editors

With 79 Figures

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Series Editors: G. Stock and M. Lessl

Library of Congress Control Number: 2004103454 ISSN 0947-6075

ISBN 3-540-21021-0 Springer Berlin Heidelberg New York

This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law.

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Preface

ªMolecular imagingº has been previously defined as ªthe in vivo characterization and measurement of biologic processes at the cellu- lar and molecular level.º This broad definition emerged during the last few years as a consequence of the convergence of molecular and cell biology with imaging science, including medical physics and technology. One of the major goals of molecular imaging has be- come the development of noninvasive strategies of ªmolecular profil- ingº in living subjects, i.e., the acquisition and analysis of maps re- flecting the spatial and temporal distribution of a given molecular target at a precise anatomical location without biopsies. The map- ping of disease-relevant gene expression profiles in vivo would be especially important for individualizing established therapy regimens in clinical practice and selecting patients for novel experimental therapies.

The 49th Ernst Schering Foundation Workshop, ªMolecular Imag- ing; An Essential Tool in Preclinical Research, Diagnostic Imaging, and Therapy,º is the second in the history of the foundation devoted to this topic. The purpose of the workshop was to discuss and over- view multiple applications and emerging technologies in the area of diagnostic imaging including its fundamental capabilities in preclinical research, the opportunities for medical care, and the options in- volving therapeutic concepts. The contributions from leading clinical and basic researchers included in this book clearly demonstrate the large strides that are being taken in recent years toward attaining the scientific goals of molecular imaging, and toward translating new ideas in this exciting and rapidly evolving field into practical bene-

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fit. Scientific disciplines covered in the workshop were molecular and cell biology, synthetic chemistry and radiochemistry, spectro- scopic and magnetic analytics, and imaging techniques. From the perspective of application, the workshop included topics in the area of magnetic resonance imaging, radiodiagnostics (PET and SPECT), radiotherapy, ultrasound imaging, optical imaging, and photodynamic therapy.

Feedback from the participants led to the conclusion that the in- terdisciplinary nature and scientific diversity of this area of science was well reflected during the workshop, attracted great interest, and led to a better understanding of each other's expertise and knowledge.

We wish to express our sincere gratitude to all participants for their contributions to the workshop and to this book. We also thank the Ernst Schering Research Foundation for the generous support in making the workshop a great success.

VI Preface

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Contents

1 Oligonucleotides as Radiopharmaceuticals

B. Tavitian . . . . 1 2 Imaging Protein-Protein Interactions in Whole Cells

and Living Animals

D. Piwnica-Worms, K. E. Luker . . . . 35 3Radiolabeled Peptides in Nuclear Oncology:

Influence of Peptide Structure and Labeling Strategy on Pharmacology

H. R. Maecke . . . . 43 4 Pretargeted Radioimmunotherapy

G. Paganelli . . . . 73 5 PET/CT: Combining Function and Morphology

T.F. Hany, G.K. von Schulthess . . . . 85 6 High Relaxivity Contrast Agents for MRI

and Molecular Imaging

S. Aime, A. Barge, E. Gianolio, R. Pagliarin, L. Silengo, L. Tei . . . . 99 7 Luminescent Lanthanide Complexes as Sensors

and Imaging Probes

D. Parker, Y. Bretonni re . . . . 123

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8 Magnetic Resonance Signal Amplification Probes A.A. Bogdanov Jr., J.W. Chen, H.W. Kang,

R. Weissleder . . . . 147 9 Imaging of Proteases for Tumor Detection

and Differentiation

C. Bremer . . . . 153 10 Molecular Imaging with Targeted Ultrasound Contrast

Microbubbles

A.L. Klibanov . . . . 171 11 Noninvasive Real-Time In Vivo Bioluminescent Imaging

of Gene Expression and of Tumor Progression and Metastasis

C.W.G.M. Lowik, M.G. Cecchini, A. Maggi,

G. van der Pluijm . . . . 193 12 Targeted Optical Imaging and Photodynamic Therapy

N. Solban, B. Ortel, B. Pogue, T. Hasan . . . . 229 Previous Volumes Published in This Series . . . . 259

VIII Contents

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List of Editors and Contributors

Editors

Bogdanov, A.A. Jr.

Center for Molecular Imaging Research, Building 149, Massachusetts General Hospital, 13th Street, Charleston, MA 02129, USA

e-mail: [email protected] Licha, K.

Medicinal Chemistry 6, Schering AG, Mçllerstr. 170±178, 13342 Berlin, Germany

e-mail: [email protected]

Contributors Aime, S.

Dipartimento di Chimica I.F.M. e Centro per il Molecular Imaging, Universit di Torino, Via P. Giuria 7, 10125 Turin, Italy

e-mail: [email protected] Barge, A.

e-mail: [email protected] Bremer, C.

Westfålische Wilhelms-Universitåt, Mçnster Institut fçr Klinische Radiologie, Albert-Schweitzer-Straûe 33, 48129 Mçnster, Germany e-mail: [email protected]

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Bretonni re, Y.

University of Durham Department of Chemistry, South Road, Durham DH1 3LE, UK

e-mail: [email protected] Cecchini, M.G.

Urology Research Laboratory, Department of Urology and Department of Clinical Research, University of Bern, MEM C813, Murtenstr. 35, 3010 Bern, Switzerland

e-mail: [email protected] Chen, J.W.

Massachusetts General Hospital, Center for Molecular Imaging Research, Building 149, 13th Street, Charleston, MA 02129, USA Gianolio, E.

e-mail: [email protected] Hany, T.F.

University Hospital Zurich Dept. of Medical Radiology/Division of Nuclear Medicine, Råmistraûe 100, 8091 Zurich, Switzerland e-mail: [email protected]

Hasan, T.

Wellmann Laboratories of Photomedicine, Harvard Medical School Massachusetts General Hospital, 540 Blossom Street, Bartlett 314, Boston, MA 02114, USA

e-mail: [email protected] Kang, H.W.

Massachusetts General Hospital, Center for Molecular Imaging Research, Building 149, 13th Street, Charleston, MA 02129, USA Klibanov, A.L.

University of Virginia Medical Center, Cardiovascular Division, Box 100158, Charlottesville, VA 22908, USA

X List of Editors and Contributors

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Lowik, C.

Department of Endocrinology, Building 1, C4-R86 Leiden University Medical Center, Albinusdreet 2, 2333 ZA Leiden, The Netherlands e-mail: [email protected]

Luker, K.E.

Molecular Imaging Center, Mallinckrodt Institute of Radiology, and Department of Molecular Biology and Pharmacology, Washington University Medical School, Box 8225, 510 S. Kingshighway Blvd, St. Louis, MO 63110, USA

Maecke, H.R.

Institute of Nuclear Medicine, Division of Radiological Chemistry, University Hospital Basel, 4031 Basel, Switzerland

e-mail: [email protected] Maggi, A.

Department of Pharmacological Sciences and Center of Excellence on Neurogenerative Disease, University of Milan, Italy

Ortel, B.

Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

e-mail: [email protected] Paganelli, G.

European Institute of Oncology, Division of Nuclear Medicine, 20141 Milan, Italy

e-mail: [email protected] Pagliarin, R.

Dipartimento di Chimica Organica e Industriale,

Universit di Milano, Viale Venezian 21, 20133 Milan, Italy Parker, D.

University of Durham Department of Chemistry, South Road, Durham DH1 3LE, UK

List of Editors and Contributors XI

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Piwnica-Worms, D.

Washington University School of Medicine Molecular Imaging Center, 510 S. Kingshighway Blvd, Box 8225 St. Louis, MO 63110, USA e-mail: [email protected]

van der Pluijm, G.

Department of Endocrinology, Building 1, C4-R86 Leiden University Medical Center, Albinusdreet 2, 2333 ZA Leiden, The Netherlands Pogue, B.

Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA

Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA

von Schulthess, G.K.

Clinic and Policlinic of Nuclear Medicine, University Hospital Zçrich, Råmistrasse 100, 8091 Zurich, Switzerland

Silengo, L.

Dipartimento di Genetica, Biologia e Biochimica, Universit di Torino, Via Santona 5-bis, 10126 Turin, Italy

Solban, N.

Wellman Laboratories of Photomedicine, Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA

Tavitian, B.

INSERM ERM 103Service Hospitalier, Frdric Joliot CEA Direction des Sciences du Vivant Direction de la Recherche Medicale, 4 place du General Leclerc, 91401 Orsay Cedex, France

e-mail: [email protected] Tei, L.

Dipartimento di Medicina Interna, Universit di Torino, C. so Dogliotti 14, 10125 Turin, Italy

Weissleder, R.

Massachusetts General Hospital, Center for Molecular Imaging Research, Building 149, 13th Street, Charleston, MA 02129, USA e-mail: [email protected]

XII List of Editors and Contributors