PET Studies on Amino Acid Metabolism and Protein Synthesis: Proceedings of a Workshop held in Lyon, France within the framework of the European Community Medical and Public Health Research

269 Pages·1993·6.99 MB·English

by  A. Lajtha

PET STUDIES ON AMINO ACID METABOLISM AND PROTEIN SYNTHESIS
Developments in Nuclear Medicine
VOLUME 23
Series Editor. Peter H. Cox
The titles published in this series are listed at the end of this volume.
PET Studies on
Amino Acid Metabolism
and Protein Synthesis
Proceedings of a Workshop held in Lyon, France
within the framework of the European Community
Medical and Public Health Research
edited by
B. M. MAZOYER
Groupe d'lmagerie Neuro-fonctionelle,
Service Hospitalier Frederic Joliot,
CEA-DRIPP Orsay,
et Höpital R. Debre,
Paris, France
W. D. HEISS
Max-Planck-Institute for Neurological Research,
Cologne, Germany
and
D. COMAR
E. E.C. Concerted Action on PET Investigations
of Cellular Regeneration and Degeneration,
Service Hospitalier Frederic Joliot,
Höpital d'Orsay,
Orsay, France
Springer Science+Business Media, B.V.
Library of Congress Cataloging-in-Publication Data
PET studie s o f amino aci d metabolis m an d protei n synthesi s :
proceedings o f workshop hel d i n Lyon, franc e withi n th e framework of
the European Community medica l an d publi c healt h researc h / edite d
by B.M. Mazoyer, W.-D. Heiss , and D. Comar.
p. cm . — (Developments i n nuclear medicin e ; 23)
Includes bibliographica l reference s an d index .
ISBN 978-94-010-4706-7 ISBN 978-94-011-1620-6 (eBook)
DOI 10.1007/978-94-011-1620-6
1. Amino acids—Metabolism—Congresses . 2 . Tomography, Emission-
-Congresses. 3 . Proteins—Synthesis—Congresses . 4 . Brain—Tumors -
-Diagnosis—Congresses . I . Mazoyer, B. M. II . Heiss, W.-D. (Wol f
-Dieter) , 1939- III . Coma,r D. IV . European Economic Community.
V. Series .
[DNLM: 1 . Amino Acids—metabolism—congresses . 2 . Proteins -
-biosynthesis—congresses . 3 . Tomography, Emission-Computed-
-congresses. W 1 DE998KF v.23 ]
QP561.P84 199 3
612.3'98--dc2 0
DNLM/DCL
for Librar y o f Congress 92-4895 1
ISBN 978-94-010-4706-7
Printed on acid-free paper
All Rights Reserved
© 1993 Springer Science+Business Media Dordrecht
Originally published by Kluwer Academci Publishers in 1993
No part of the material protected by this copyright notice may be reproduced or
utilized in any form or by any means, electronic or mechanical,
including photocopying, recording or by any information storage and
retrieval system, without written permission from the copyright owner.
MEDICAL AND HEALTH RESEARCH PROGRAMME OF THE EC
BIOMEDICAL ENGINEERING IN THE EUROPEAN COMMUNITY
The involvement of the European Community (EC) in the field of Medical and Health Research
started in 1978 with the first Programme which contained three projects. Since then, it has
steadily expanded and it will include around 120 projects by the end of the fourth Programme
(1987-1991).
The general goal of the programme is clearly to contribute to a better quality of life by improving
health, and its distinctive feature is to strengthen European collaboration in order to achieve this
goal.
The main objectives of this collaboration are:
increase the scientific efficiency of the relevant research and development efforts in the
Member States through their gradual coordination at Community level following the mobiliza
tion of the available research potential of national programmes, and also their economic
efficiency through sharing of tasks and strengthening the joint use of available health research
resources,
improve scientific and technological knowledge in the research and development areas selected
for their importance to all Member States, and promote its efficient transfer into practical
applications, taking particular account of potential industrial and economic developments in
the areas concerned,
optimize the capacity and economic efficiency of health care efforts throughout the countries
and regions of the Community.
The current programme consists of six research targets. Four are related to major health
problems: CANCER, AIDS, AGE-RELATED PROBLEMS, and PERSONAL ENVIRONMENT
AND LIFE-STYLE RELATED PROBLEMS; two are related to health resources: MEDICAL
TECHNOLOGY DEVELOPMENT and HEALTH SERVICES RESEARCH.
Funds are provided by the Community for relevant "concerted action" activities which consist of
research COLLABORATION and COORDINATION in EC Member States and/or in other
European participant countries. NElWORKS of research institutes can be set up and supported by
means of meetings, workshops, short-term staff exchanges/visits to other countries, information
dissemination and so on; centralized facilities such as data banks, computing, and preparation and
distribution of reference materials can also be funded. The funds are not direct research grants;
the institutes concerned must fund the research activities carried out within their own countries -
it is the international coordination activitie~ ,\'hich are eligible for Community support. Each such
research network is placed under the responsibility of a PROJECT LEADER chosen from among
the leading scientists in the network, with the assistance of a PROJECT MANAGEMENT GROUP
representing the teams participating in the network.
The Commission of the European Communities is assisted in the execution of this programme by
a Management and Coordination Advisory Committee (CGC - Medical and Health Research),
and by Concerted Action Committees (COMACs) and Working Parties, composed of repre
sentatives and of scientific experts respectively, designated by the competent authorities of the
Member States.
Other European countries, not belonging to the EC but participating in COST (Cooperation on
Science and Technology) may take part in the Programme.
The present work was conducted according to the advice of COMAC-BME which supervises the
coordination of research in biomedical engineering (BME) within the Medical Technology
Development target.
More information may be obtained from: Commission of the European Communities
Directorate General XII-F-6
200 Rue de la Loi
B - 1049 Brussels
CONTENTS
Preface xi
List of Contributors Xlll
PART ONE: Biochemistry and animal studies
1. Cerebral protein turnover: aspects and problems 1
A. Lajtha, D. Dunlop, and M. Banay-Schwartz
2. Determination of regional rates of cerebral protein synthesis in vivo with
L-[ 1-14C]leucine as the tracer amino acid 19
C. Beebe Smith
3. Methionine metabolism in rat brain 41
P. Bobillier, E. Grange, A. Gharib, M. Leclerc, N. Sarda and P. Lepetit
4. Protein synthesis studies in rats with methionine 53
A.M. Planas, C. Prenant, B.M. Mazoyer, S. Chadan, D. Comar and
L. DiGiamberardino
Discussion 69
PART TWO: PET Radiochemistry
5. Carbon-l1 amino acids, labeling and metabolites 75
W. Vaalburg, P.H. Elsinga and A.M.J. Paans
6. Quality control aspects in the preparation of [llC]-methionine 81
K. Nagren
7. Production of L-[18P]fluoro amino acids for protein synthesis: overview
and recent developments in nucleophilic syntheses 89
C. Lemaire
8. Biochemistry and evaluation of fluoroamino acids 109
H.H. Coenen
Discussion 131
viii
PART THREE: Amino acid uptake modeling
9. Kinetic modeling of fluorotyrosine uptake 133
K. Wienhard, K. Herholz, H.H. Coenen, J. Rudolf, P. Kling, G. Stocklin
and W.-D. Heiss
10. Kinetic modeling of carbon-ll labeled amino acids 149
G. Blomqvist
11. Carbon-ll labeled tyrosine as a probe for modeling the protein
synthesis rate 161
A.M.J. Paans, P.H. Elsinga and W. Vaalburg
12. Kinetic modeling of carbon-ll labeled methionine 175
H. Lundqvist
13. Approaches to quantitative analysis of amino acid transport and
metabolism 183
G.-J. Meyer, J. van den Hoff, W. Burchert and H. Hundeshagen
14. HC-methionine and rubidium uptake in human brain tumors:
82
comparison of carrier dependent blood-brain barrier transport 197
U. Roelcke, E.W. Radii and K.L. Leenders
Discussion 201
PART FOUR: Clinical applications
15. Tracers for clinical evaluation of gliomas: a neurologist's view 203
K. Herholz
16. PET studies of amino acid metabolism: integration in clinical routine
and current research on intracranial tumours 215
K. Ericson
17. Uptake of [llC]methionine in non-brain tumors 223
S. Leskinen-Kallio
18. Utilization of amino acid transport rates for the differential diagnosis
of brain tumors 227
G.-J. Meyer, W. Burchert, K.-F. Gratz and H. Hundeshagen
ix
19. Use of amino acid uptake and protein synthesis rates for tumour
diagnosis 237
H. Lundqvist
20. HC-methionine uptake in brain tumors measured by PET: early clinical
results 243
B. Sadzot, B. Kaschten, G. Delfiore, J.M. Peters, A. Stevenaert,
G. Franck and D. Comar
21. HC-labeled methionine uptake in gliomas: modification after
therapy and metabolic correlations 255
M.-C. Petit-Taboue, F. Dauphin and J.-M. Derlon
22. In vivo incorporation of labeled methionine into proteins in brain
tumors 265
A.M. Planas, B. Kaschten, B. Sadzot, A. Stevenaert, L. DiGiamberardino
and D. Comar
Discussion 267
PREFACE
Parameters such as membrane transport, metabolism and protein incorporation govern the
fate of amino acids in living tissue. Is it possible to use positron tomography to measure
some of them, and what is their meaning in normal and pathological situations?
These questions have been addressed for a long time and no satisfactory answer has yet
been given.
This book, which derives from an EEC workshop organized in the frame of the Concerted
Action on 'PET Investigation of Cellular Regeneration and Degeneration', held in Lyon
in February 1992, gives the present state of knowledge in this field based on the most
recent studies. Contributions from 24 leading European and American scientists are
presented and discussed in the following four parts:
biochemistry and animal studies;
amino acids labelling with positron emittors, quality control and metabolites
measurement;
kinetic modelling of amino acids transport, metabolism, and protein incorporation;
clinical use of amino acids.
The book will aid and interest biochemists, radiochemists, pharmacologists, neurologists,
oncologists and medical imaging scientists.
The editors wish to express their gratitude to Y. Guillet (Hopital R. Debre, Paris) and D.
Wietrich (E.C. Concerted Action, Orsay) for their invaluable assistance in preparing this
book.
The Editors
LIST OF CONTRIBUTORS
G. Blomqvist, Department of Clinical Neurophysiology, Karolinska Hospital, S-104 01
STOCKHOLM, Sweden
P. Bobillier, Laboratory of Pathological Anatomy, CNRS URA 1195, Rue G. Paradin,
F-69372 LYON Cedex 08, France
Co-authors: E. Grange, A. Gharib, M. Leclerc, N. Sarda and P. Lepetit
H.H. Coenen, Clinic for Nuclear Medicine, University of Essen, Hufelandstrasse 55,
DW-4300 ESSEN, Germany
D. Comar, EEC Concerted Action on PET, Service Hospitalier Frederic Joliot, Hopital
D'Orsay, F-91406 ORSA Y, France
J.-M. Derlon, Cyceron, Boulevard Henri Becquerel, P.O. Box 5027, F-14021 CAEN
Cedex, France
K. Ericson, Department of Neuroradiology, Karolinska Hospital, S-104 01 STOCKHOLM,
Sweden,
W.-D. Heiss, Max-Planck-Institute for Neucological Research, Gleueler Str 50, DW-5000
COLOGNE, Germany
K. Herholz, Max-Planck-Institute, for Neurological Research, University Clinic, Gleueler
Str 50, DW-5000 COLOGNE, Germany
A. Lajtha, N.S. Kline Institute for Psychiatric Research, Center for Neurochemistry,
ORANGEBURG, NY 10962, U.S.A.
Co-authors: D. Dunlop and M. Banay-Schwartz
C. Lemaire, Liege University, B-30, Cyclotron Research Center, B-4000 LIEGE, Belgium
S. Leskinen-Kallio, Department of Oncology and Radiotherapy, Turku University Central
Hospital, SF-20520 TURKU, Finland
H. Lundqvist, Department of Radiation Sciences, P.O. Box 535, S-751 21 UPPSALA,
Sweden
B.M. Mazoyer, Groupe d'Imagerie Neuro-fonctionelle, Service Hopitalier Frederic Joliot,
CEA-DRIPP , Hopital R. Debre, 45, Boulevard Serrurier, F-75019 PARIS, France
G.J. Meyer, Department of Nuclear Medicine and Special Biophysics, DW-3000
HANNOVER 61, Germany
Co-authors Chapter 13: J. van den Hoff, W. Burchert and H. Hundeshagen
Co-authors Chapter 18: W. Burchert, K.-F. Gratz and H. Hundeshagen
K. NAgren, Turku Medical Cyclotron-PET Center, Radiochemistry Laboratory, Turku
University, Porthaninkatu 3, SF-20500 TURKU, Finland
A.M.J. Paans, PET Center, University Hospital Groningen, P.O. Box 30.001, 9700 RB
GRONINGEN, The Netherlands
Co-authors: P.H. Elsinga and W. Vaalburg
M.-C. Petit-Taboue, Cyceron, Boulevard Henri Becquerel, P.O. Box 5027, F-14021
CAEN Cedex, France
Co-authors: F. Dauphin and J.-M. Derlon