xxx
W. Mohnike · G. Hör · H. R. Schelbert (Eds.)
Oncologic and Cardiologic PET/CT-Diagnosis
An Interdisciplinary Atlas and Manual
I
xxx
Wolfgang Mohnike · Gustav Hör
Heinrich R. Schelbert (Eds.)
Oncologic and
Cardiologic
PET/CT-Diagnosis
An Interdisciplinary Atlas and Manual
With DVD-ROM
With contributions by
Thomas Beyer · Konrad Mohnike · Stefan Käpplinger
With 909 Figures, 803 in Color and 24 Tables
123
III
IV
xxxxx
Wolfgang Mohnike, MD
Professor
Diagnostisch Therapeutisches Zentrum
am Frankfurter Tor
Kadiner Strasse 23
10243 Berlin
Germany
Gustav Hör, MD
Professor
Klinik für Nuklearmedizin und Zentrum der Radiologie
Klinikum der J. W. Goethe-Universität
Theodor-Stern-Kai 7
60950 Frankfurt/Main
Germany
Heinrich R. Schelbert, MD, PhD
Gerorge V. Taplin Professor
Department of Molecular and Medical Pharmacology
David Greffen School of Medicine at UCLA
University of California at Los Angeles
650 Charles E. Young Drive South
Los Angeles, CA 90095
USA
ISBN 978-3-540-74090-2
e-ISBN 978-3-540-74091-9
DOI 10.1007 / 978-3-540-74091-9
Library of Congress Control Number: 2008923539
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, speciﬁ cally
the rights of translation, reprinting, reuse of illustrations, recitations, broadcasting, reproduction on microﬁ lm 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.
The use of general descriptive names, trademarks, etc. in this publication does not imply, even in the absence of a speciﬁc
statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general
use.
Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained
in this book. In every individual case the user must check such information by consulting the relevant literature.
Cover design: Frido Steinen-Broo, eStudio Calamar, Spain
Layout: PublishingServices Teichmann, 69256 Mauer, Germany
Printed on acid-free paper
9876543210
springer.com
xxx
Foreword
Panels of experts in the USA und Europe agree that positron emission
tomography (PET) is the imaging method that has been most rapidly
accepted in the last decade.
In a review by Beyer and Townsend it was observed that in ﬁve years
PET/CT has taken the place of coregistration. In institutions equipped with
a combined PET/CT tomograph the advantages are increasingly recognised
– particularly in pulmonology and thorax surgery.
The NNT (number needed to treat) is the standard according to which
the number of patients to be successfully treated is measured. Careful
diagnosis involving PET/CT with effective treatment can and must reduce
the NNT.
The simultaneous preparation of fusion images in PET/CT shortens
the examination time, spares the patient the time needed for two visits
to the doctor and provides nuclear medical specialists and radiologists
with anatometabolic images: Anatomy, (surrounding) structure, localisation and molecular biology expand the diagnostic framework. The current trend points towards PET/CT as a standard diagnostic method in
oncology.
The dynamism of the development process is reﬂected already in the
case studies shown here whose pictorial documentation is based on three
generations of apparatus. The case studies document how PET/CT opens up
new diagnostic options for the patient when the conventionally established
examination methods fail. Decades of experience have taught us that such
situations are by no means the exception, even today.
This book is intended to help answer the following questions: What
are the strengths of PET/CT? What are its current limits, and what is its
development potential?
On the enclosed DVD you will ﬁnd a comprehensive overview of additional literature, the entire text in electronic form and several case studies
which – when examined with the viewer – give an impression of the three
dimensional nature of the studies.
Professor Dr. Gustav Hör
Specialist in Roentgenology and Radiology
Specialist in Nuclear Medicine
V
xxx
Acknowledgements
The part of this PET/CT Manual that deals with oncology is based on the
German PET/CT Atlas by Mohnike and Hör, published in 2006, which has
now been updated and expanded. At the same time, the important indication for PET(/CT) in cardiology receives the attention it urgently requires in
the form of the important contribution by Prof. H. Schelbert. We thank him
for his profound commitment and for taking on this task at short notice,
as well as Prof. G. Hör for his European view of cardiological PET(/CT)
examination options presented in his customary, esteemed manner.
The compilation and publication of an English-language manual was a
real challenge for non-native speakers and could not have been achieved
without the thorough and highly committed supervision of the journalist
Ms S. Thürk M.A.
I am also grateful to my son, Konrad Mohnike, and to Dipl.-Phys. S.
Käpplinger for their thorough checking of the manuscripts, as well as to
Privatdozent Dr. T. Beyer for his careful revision of his contribution. Dr. U.
Heilmann, Ms A. Hinze and Ms W. McHugh of Springer-Verlag were also
of great assistance to us.
Thanks also go to Dr. T. Eberhard, diagnostic radiology specialist, C.
Voelkel, radiologist, Prof. J. Schmidt and I. Volkova, nuclear medicine of
the Diagnostic Therapeutic Centre (DTZ) in Berlin, my brother, Privatdozent Dr. Klaus Mohnike (Magdeburg University), and Dr. O. Blankenstein (paediatrician at Charité Berlin) for the working up of ﬁndings.
Special thanks go to Ms K. Stein of Siemens Medical Solutions and Dipl.Math. Mr W. Lauermann for producing the DVD.
We would also like to thank Ms B. Engfer and Ms Y. Fobbe, medical
radiological technicians, as well as all other staff, at the DTZ. Our thanks
also go to Dipl.-Chem. Mr B. Zimontkowski and Mr J. Reinke, who were
always ready to assist me with their help and advice.
We especially thank Messrs M. Reitermann, Dr. R. Radmanesh, N.
Franke, R. Krämer and Dr. F. Anton of Siemens Medical Solutions for
their fair and unbureaucratic assistance.
Finally, I would like to thank my wife, Bettina, for her constructive
advice and patience throughout the project.
Professor Wolfgang Mohnike
VII
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Contents
1
Introduction –
3
Positron Emission Tomography: Past and Present
1
1.1 Survey . . . . . . . . . . . . . . . . . . . . . . . . . .
Physical and Biochemical Fundamentals . . . .
PET in National and International
Medical Care Systems. . . . . . . . . . . . . . . . .
1
2
1.2 Technological Variants and Developments .
Coincidence PET vs. Dedicated PET . . . . .
Differentiated PET Evaluation . . . . . . . . .
Radiotherapeutic Tools . . . . . . . . . . . . .
PET/CT – a New Key Technology . . . . . . .
Influence of PET/CT on PET . . . . . . . . . .
Studies Dealing with the Cost Efficiency of
PET Alone . . . . . . . . . . . . . . . . . . . . .
PET/CT or Comparison of
Co-Registered Findings? . . . . . . . . . . . .
“Standard” (CARE)-CT and PET/CT . . . . .
PET/MRI? . . . . . . . . . . . . . . . . . . . . .
American Joint Committee on Cancer . . . .
PET Screening in Japan and Taiwan . . . . .
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1.3 Increased FDG Uptake Due to Physiological
and Technical Factors . . . . . . . . . . . . . . . .
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1.4 References . . . . . . . . . . . . . . . . . . . . . . .
8
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Fundamentals
Thomas Beyer . . . . . . . . . . . . . . . . . . . . .
11
2.1 Preface . . . . . . . . . . . . . . . . . . . . . . . . . .
Positron Emission Tomography (PET) . . . . . .
Radioisotopes and PET Tracers . . . . . . . . . .
Coincidence Measurement and Quantification .
PET Measurement Results and Reconstruction .
PET Scanners and Scintillation Detectors . . . .
11
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2.2 Combined PET/CT . . . . . . . . . . . . . . . . .
Retrospective Image Fusion . . . . . . . . . . .
The PET/CT Prototype . . . . . . . . . . . . . .
CT-Based Attenuation Correction . . . . . . .
Commercialization of PET/CT . . . . . . . . . .
New Technical Developments in PET/CT . . .
PET/CT Acquisition Protocols . . . . . . . . . .
Sources of Errors and Optimization Options .
Radiation Protection Aspects . . . . . . . . . .
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2.3 Conclusion . . . . . . . . . . . . . . . . . . . . . . .
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2.4 References . . . . . . . . . . . . . . . . . . . . . . .
40
Pneumology
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43
3.1 Bronchial Carcinoma (BC) . . . . . . . . . . . . .
43
3.2 Significance of FDG-PET in Diagnostic and
Therapeutic Management . . . . . . . . . . . . . 44
Critical Evaluation of Diagnosis Management . 45
3.3 Guidelines for 18F-FDG-PET Indications . . . .
45
3.4 Technical and Biochemical Factors . . . . . . .
Is Coincidence PET Equivalent to
Full-Ring PET? . . . . . . . . . . . . . . . . . . .
PET as Metabolism and Proliferation Marker .
Innovative Radiopharmacy . . . . . . . . . . .
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3.5 Special PET Indications . . . . . .
False-Negative PET . . . . . . . . .
False-Positive PET . . . . . . . . . .
How Useful Is Integrated PET/CT?
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3.6 SCLC (Small-Cell Lung Cancer) . . . . . . . . . .
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3.7 Pleural Processes . . . . . . . . . . . . . . . . . .
Malignant Pleural Tumours (Mesothelioma) . .
Imaging Methods . . . . . . . . . . . . . . . . . .
48
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49
3.8 Case Studies . . . . . . . . . . . . . . . . . . . . .
Patient 1 Scar Carcinoma of the Lung . . . . .
Patient 2 Pneumonia . . . . . . . . . . . . . . .
Patient 3 Lymph Node Metastases of a
Squamous Cell Carcinoma . . . . . .
Patient 4 Metastasized Bronchial Carcinoma .
Patient 5 Round Focus in the Lung . . . . . . .
Patient 6 Metastasized Bronchial Carcinoma .
Patient 7 Metastasized Adenocarcinoma in the
Left Lower Lobe of the Lung . . . . .
Patient 8 Downstaging of a Squamous Cell
Carcinoma of the Lung . . . . . . . .
Patient 9 Preoperative Staging of a
Bronchial Carcinoma . . . . . . . . .
Patient 10 Pleural Carcinosis after
Pneumectomy . . . . . . . . . . . . . .
Patient 11 Recurrence of a Brain Metastasis . .
Patient 12 Pleural Mesothelioma . . . . . . . . .
Patient 13 Prevention of Non-Curative
Thoracic Surgery . . . . . . . . . . . .
Patient 14 Upstaging of a
Bronchial Carcinoma . . . . . . . . .
Patient 15 Bilateral Metastases of an NSCLC
in the Suprarenal Glands . . . . . . .
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3.9 References . . . . . . . . . . . . . . . . . . . . . . .
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4
Gastroenterology .
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4.1 Introduction . . . . . . . . . . . . . .
Molecular Strategy . . . . . . . . . . .
Metabolic Influencing Factors . . . .
PET Screening? . . . . . . . . . . . . .
Incidentally Detected Lesions (IDL)
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4.2 Oesophageal Carcinoma . . . . . . . . . . . . . .
PET in Diagnosis Management of
Oesophageal Carcinoma . . . . . . . . . . . . . .
88
4.3 Gastric Carcinoma . . . . . . . . . . . . . . . . . .
MALT Lymphomas . . . . . . . . . . . . . . . . .
90
90
4.4 Colorectal Carcinomas . . . . . . .
Treatment . . . . . . . . . . . . . . .
Status of PET . . . . . . . . . . . . .
PET/CT as the Optimum . . . . . .
PET Indications . . . . . . . . . . .
Limitations of PET . . . . . . . . . .
Artefacts . . . . . . . . . . . . . . . .
FDG-PET . . . . . . . . . . . . . . .
Alternative and Adjuvant Markers
Synopsis . . . . . . . . . . . . . . . .
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4.5 Liver and Biliary Tract Carcinomas . . . . . . .
95
4.6 Gastrointestina Stromal Tumours . . . . . . . .
95
4.7 Pancreas Carcinomas . . . . . . . . . . . . . .
Imaging . . . . . . . . . . . . . . . . . . . . . .
Curative Treatment . . . . . . . . . . . . . . .
New Gene-Based Treatment Strategies . . . .
Indications . . . . . . . . . . . . . . . . . . . .
DGN Classes, Consequences . . . . . . . . . .
Impact of SUVs on Survival Time . . . . . . .
False-Negative/-Positive PET Findings . . . .
Pancreas NETs (Neuroendocrine Tumours) .
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4.8 Neuroendocrine Tumours (NETs) of the
Gastrointestinal Tract . . . . . . . . . . . .
Carcinoids . . . . . . . . . . . . . . . . . . .
Conventional Diagnostics . . . . . . . . .
NET Spectrum . . . . . . . . . . . . . . . .
Biochemistry . . . . . . . . . . . . . . . . .
High Secretors . . . . . . . . . . . . . . . .
Low (Non-)Secretors . . . . . . . . . . . . .
Limitations of PET . . . . . . . . . . . . . .
4.9
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Case Studies . . . . . . . . . . . . . . . . . . . . . .
Patient 1 Oesophageal Carcinoma . . . . . . .
Patient 2 Lymph Node Metastasis of an
Oesophageal Carcinoma . . . . . . .
Patient 3 Downstaging of an
Oesophageal Carcinoma. . . . . . . .
Patient 4 Carcinoma of the Head
of the Pancreas . . . . . . . . . . . . .
Patient 5 Metastasized Carcinoma
of the Head of the Pancreas . . . . .
Patient 6 Carcinoma of the Body
of the Pancreas . . . . . . . . . . . . .
100
100
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107
110
112
Patient 7 Hepatocellular Carcinoma with
Multiple Metastases . . . . . . . . . .
Patient 8 Gastric Carcinoma . . . . . . . . . . .
Patient 9 Leiomyoma of the Stomach . . . . . .
Patient 10 Follow-Up of an Adenocarcinoma
of the Stomach . . . . . . . . . . . . .
Patient 11 Staging of an Adenocarcinoma
of the Stomach . . . . . . . . . . . . .
Patient 12 Staging of a Carcinoma of the
Corpus of the Stomach . . . . . . . .
Patient 13 Lymph Node Metastasis
from Gastric Carcinoma . . . . . . .
Patient 14 Extended Metastatic Spread
to the Liver from Adenocarcinoma
of the Stomach . . . . . . . . . . . . .
Patient 15 Caecum Carcinoma . . . . . . . . . .
Patient 16 Carcinoma of the Colon Ascendens .
Patient 17 T1 Carcinoma of the Colon . . . . . .
Patient 18 Adenocarcinoma of the
Sigmoid Colon. . . . . . . . . . . . . .
Patient 19 Liver Metastasis of a
Colon Carcinoma . . . . . . . . . . . .
Patient 20 Lymphoma Conglomerate
Following Colon Carcinoma . . . . .
Patient 21 Lung Metastasis
Following Colon Carcinoma . . . . .
Patient 22 Pulmonary, Hepatic and
Lymphogenic Metastatic Spread
Following Sigmoid Carcinoma . . . .
Patient 23 Metastasized Sigmoid Carcinoma . .
Patient 24 Peritoneal Carcinosis and Ascites
Following Sigmoid Carcinoma . . . .
Patient 25 Lung Metastasis Following
Sigmoid Carcinoma . . . . . . . . . .
Patient 26 Liver Metastasis Following
Sigmoid Carcinoma . . . . . . . . . .
Patient 27 Lymph Node Metastasis
Following Sigmoid Carcinoma . . . .
Patient 28 Metastatic Spread to the Liver
Following Rectal Carcinoma . . . . .
Patient 29 Liver and Lung Metastases
Following Rectal Carcinoma . . . . .
Patient 30 Rectal Carcinoma
with Lymph Node Metastases . . . .
Patient 31 Suprarenal and Lung Metastases
Following Rectal Carcinoma . . . . .
Patient 32 Lung and Bone Metastases
Following Rectal Carcinoma . . . . .
Patient 33 Suprarenal Metastasis
of a Rectal Carcinoma . . . . . . . . .
Patient 34 Restaging of a Rectal Carcinoma . .
Patient 35 Suprarenal and Lung Metastases
Associated with Rectal Carcinoma .
Patient 36 Restaging of a Rectal Carcinoma . .
Patient 37 Local Recurrence and Liver
Metastases of a Rectal Carcinoma . .
Patient 38 Extended Metastatic Spread of a
Mesenterial Conglomerate Tumour .
Patient 39 GIST Tumour with
Liver Involvement . . . . . . . . . . .
Patient 40 Malignoma in the Left
Epigastric Region . . . . . . . . . . . .
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Patient 41 GIST, Metastasis at the
Greater Curvature of the Stomach .
Patient 42 Tumour Recurrence with
Status Post GIST of the Stomach . .
Patient 43 Therapy Response Follow-Up
Examination Post GIST Resection .
Patient 44 Therapy Follow-Up in the
Case of GIST . . . . . . . . . . . . .
. 186
. 187
. 189
. 193
4.10 References . . . . . . . . . . . . . . . . . . . . . . . 200
5
Gynaecology .
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5.1 Introduction . . . . . . . . . . . . . . . . . . . . . 206
The Importance of
Nuclear Medical Methods . . . . . . . . . . . . . 206
5.2 Breast Cancers . . . . . . . . . . . . . . . . . . .
Mammography . . . . . . . . . . . . . . . . . . .
Tumour Markers . . . . . . . . . . . . . . . . . .
CT and MRI . . . . . . . . . . . . . . . . . . . . .
18F-Fluoride . . . . . . . . . . . . . . . . . . . . .
SPECT . . . . . . . . . . . . . . . . . . . . . . . .
Sentinel Node Scintigraphy (SNS) . . . . . . . .
Positron Emission Tomography . . . . . . . . .
Preoperative Axillary Staging . . . . . . . . . .
Extra-Axillary Metastases . . . . . . . . . . . .
Treatment Monitoring . . . . . . . . . . . . . .
Potentials and Limitations of PET . . . . . . .
Special Neuro-Oncological Problems/Pitfalls .
PET Screening? . . . . . . . . . . . . . . . . . . .
Risk Stratification . . . . . . . . . . . . . . . . .
PET/CT . . . . . . . . . . . . . . . . . . . . . . . .
Assessment of the Bone Status . . . . . . . . .
18F-Fluoride PET . . . . . . . . . . . . . . . . . .
Diagnostic Imaging of the Breast: Indications
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5.3 Ovarian Cancer . . . . . . .
Tumour Types . . . . . . .
Conventional Diagnostics
PET . . . . . . . . . . . . . .
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5.4 Peritoneal Cancer (PC) . . . . . . . . . . . . . . . 215
5.5 Cervical Cancer . . . . . . . . . . . . . . . . . . . . 215
PET Diagnostics . . . . . . . . . . . . . . . . . . . 215
5.6 Case Studies . . . . . . . . . . . . . . . . . . . . . .
Patient 1 Lymph Node Metastasis with Status
Post Carcinoma of the Right Breast
and Ovarian Carcinoma
on Both Sides . . . . . . . . . . . . . .
Patient 2 Inflammatory Breast Cancer . . . . .
Patient 3 Breast Cancer with
Osseous Metastases . . . . . . . . . .
Patient 4 Preoperative Staging of a
Breast Cancer . . . . . . . . . . . . . .
216
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218
220
222
Patient 5 Restaging of a Breast Cancer . . . . . 224
Patient 6 Restaging of a Breast Cancer . . . . . 226
Patient 7 Confirmation of the
Diagnosis “Breast Cancer” . . . . . . 228
Patient 8 Psammoma . . . . . . . . . . . . . . . 230
Patient 9 Ovarian Cancer . . . . . . . . . . . . . 232
Patient 10 Restaging of an Ovarian Cancer . . . 234
Patient 11 Therapy Response of a
Metastasized Ovarian Cancer . . . . 236
Patient 12 Metastasized Cervical Cancer . . . . 238
Patient 13 Bone Metastasis of a
Corpus Uteri Cancer . . . . . . . . . . 240
Patient 14 Trophoblastic Tumour . . . . . . . . . 242
Patient 15 Malignant Ovarian Cyst . . . . . . . 244
Patient 16 Peritoneal Carcinosis Due to
Ovarian Cancer . . . . . . . . . . . . . 245
Patient 17 Metastasized Endometrial
Carcinoma . . . . . . . . . . . . . . . . 248
Patient 18 Exclusion of Metastatic Spread of an
Endometrial Carcinoma . . . . . . . . 250
Patient 19 Therapy Control in Case of
Ovarian Carcinoma . . . . . . . . . . 252
Patient 20 Lymph Node and Bone Metastases in
Case of Ovarian Carcinoma . . . . . 254
Patient 21 Local Recurrence of Breast Cancer . 256
Patient 22 Restaging of a Breast Cancer after
Chemotherapy . . . . . . . . . . . . . 259
Patient 23 Restaging of a Breast Cancer after
Rise in Tumour Marker Level . . . . 261
Patient 24 Primary Staging of a Breast Cancer . 262
Patient 25 Restaging of a Breast Cancer after
Reduction in Tumour Marker Level . 264
Patient 26 Pre-Therapeutic Staging of a
Breast Cance . . . . . . . . . . . . . . . 267
Patient 27 Restaging of a
Metastasized Breast Cancer. . . . . . 269
Patient 28 Detection of Metastases by PET/CT
with Negative Conventional Imaging 271
Patient 29 Therapy Control of a
Metastasized Breast Cancer . . . . . 275
Patient 30 Therapy Control of a
Metastasized Breast Cancer . . . . . 276
Patient 31 Evaluation of Radiotherapy Response
in Case of Metastasized
Breast Cancer . . . . . . . . . . . . . . 279
Patient 32 Restaging of a Breast Cancer . . . . . 283
Patient 33 Restaging of a Breast Cancer
Revealing a Fracture Risk in the
C6 Vertebral Body . . . . . . . . . . . 285
Patient 34 Restaging of a Breast Cancer with
PET/CT Providing Much More
Detailed Information . . . . . . . . . 287
Patient 35 Pleural Carcinosis in a Patient
with Breast Cancer . . . . . . . . . . . 290
Patient 36 Lung Metastases of a Breast Cancer . 292
Patient 37 Bone Metastases of a Breast Cancer . 294
Patient 38 Male Patient with
Metastasized Breast Cancer . . . . . 296
5.7 References . . . . . . . . . . . . . . . . . . . . . . . . 298
XI
XII
xxxxx
6
Urology .
Patient 26 First Diagnosis
of a Prostate Carcinoma . . . . . . . . 361
Patient 27 Response Evaluation
of a Prostate Carcinoma . . . . . . . . 362
. . . . . . . . . . . . . . . . . . . . . . 303
6.1 Introduction . . . . . . . . . . . . . . . . . . . . . 303
6.2 Renal Malignancies . . . . . . . . . . . . . . . . . 304
Introduction . . . . . . . . . . . . . . . . . . . . . 304
Diagnostics . . . . . . . . . . . . . . . . . . . . . . 304
6.9 References . . . . . . . . . . . . . . . . . . . . . . . 363
6.3 Adrenal Tumours . . . . . . . . . . . . . . . . . . 305
Imaging Diagnostics . . . . . . . . . . . . . . . . 305
7
Head and Neck Region
. . . . . . . . . 369
7.1
Head and Neck Tumours
18F-FDG-PET . . . . . . .
FDG-PET Pitfalls . . . . .
PET Indications . . . . .
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6.4 Bladder Carcinoma . . . . . . . . . . . . . . . . . 305
Status of PET . . . . . . . . . . . . . . . . . . . . . 306
6.5 Prostate Carcinoma . . . . . . . . . . . .
Introduction . . . . . . . . . . . . . . . .
Diagnostics . . . . . . . . . . . . . . . . .
Treatment . . . . . . . . . . . . . . . . . .
Status of Individual Imaging Methods .
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306
306
306
309
309
6.6 Germ Cell Tumours . . . . . . . . . . . . . . . . . 313
Introduction . . . . . . . . . . . . . . . . . . . . . 313
PET Study Situation . . . . . . . . . . . . . . . . . 314
6.7 Penis Carcinoma . . . . . . . . . . . . . . . . . . . 315
6.8 Case Studies . . . . . . . . . . . . . . . . . . . . . .
Patient 1 Malignoma of the Base of the Bladder .
Patient 2 Malignoma of the Posterior Wall
of the Bladder . . . . . . . . . . . . . .
Patient 3 Metastasis in the Suprarenal Gland
on the Left Side . . . . . . . . . . . . .
Patient 4 Metastasis in the Suprarenal Gland
on the Right Side . . . . . . . . . . . .
Patient 5 Metastasized Renal Cell Carcinoma .
Patient 6 Restaging after Chemotherapy . . . .
Patient 7 Restaging after
Tumour Nephrectomy . . . . . . . . .
Patient 8 Recurrence after
Tumour Nephrectomy . . . . . . . . .
Patient 9 Metastasized Prostate Carcinoma . .
Patient 10 Metastasized Prostate Carcinoma . .
Patient 11 Restaging of a Prostate Carcinoma .
Patient 12 Lymph Node Metastasis
of a Prostate Carcinoma . . . . . . . .
Patient 13 First Diagnosis
of a Prostate Carcinoma . . . . . . . .
Patient 14 Restaging of a Prostate Carcinoma .
Patient 15 Restaging of a Prostate Carcinoma .
Patient 16 Therapy Control for Metastatized
Prostate Carcinoma . . . . . . . . . .
Patient 17 Staging of a Prostate Carcinoma . . .
Patient 18 Local Recurrence
of a Prostate Carcinoma . . . . . . . .
Patient 19 Lymph Node Metastasis
of a Prostate Carcinoma . . . . . . . .
Patient 20 Lymph Node Metastases
of a Prostate Carcinoma . . . . . . . .
Patient 21 First Diagnosis
of a Prostate Carcinoma . . . . . . . .
Patient 22 Prostatitis . . . . . . . . . . . . . . . .
Patient 23 Prostatitis . . . . . . . . . . . . . . . .
Patient 24 Prostatitis . . . . . . . . . . . . . . . .
Patient 25 Restaging of a Prostate Carcinoma .
316
316
318
320
322
325
327
330
332
334
336
338
340
342
343
345
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369
371
373
373
7.2 Thyroid Carcinomas . . . . . . . . . . . . . . . . . 374
18
F-FDG-PET . . . . . . . . . . . . . . . . . . . . . 375
7.3 Case Studies . . . . . . . . . . . . . . . . . . . . . . 378
Patient 1 CUP Tumour . . . . . . . . . . . . . . 378
Patient 2 Tumour Recurrence of
an Atypical Laryngeal Carcinoid . . 380
Patient 3 Restaging of
an Oropharyngeal Carcinoma . . . . 381
Patient 4 Hypopharyngeal Carcinoma . . . . . 384
Patient 5 Restaging after Multiple Carcinoma 386
Patient 6 Auricle Carcinoma . . . . . . . . . . . 388
Patient 7 Tonsillar and Laryngeal Carcinoma
and Carcinoma of the Base
of the Tongue . . . . . . . . . . . . . . 390
Patient 8 Recurrence of a Squamous
Cell Carcinoma of the Tongue . . . . 392
Patient 9 Tonsillar Carcinoma . . . . . . . . . . 394
Patient 10 Restaging of a Small-Cell Carcinoma
of the Left Principal Nasal Cavity . . 396
Patient 11 Recurrence of a
Vocal Cord Carcinoma. . . . . . . . . 400
Patient 12 Cerebral Metastatic Spread of a
Bronchial Carcinoma . . . . . . . . . 402
Patient 13 Cystadenocarcinoma of the
Lacrimal Sac . . . . . . . . . . . . . . 405
Patient 14 Alzheimer’s Disease . . . . . . . . . . 406
Patient 15 Oligodendroglioma
on the Left Side . . . . . . . . . . . . . 408
Patient 16 Low-Malignancy Brain Tumour
on the Left Side . . . . . . . . . . . . . 410
Patient 17 Hypophyseal Metastasis . . . . . . . . 413
7.4
References . . . . . . . . . . . . . . . . . . . . . . . 415
8
Dermatology .
347
349
351
352
353
354
355
356
357
359
. . . . . . . . . . . . . . . . . 419
8.1 Malignant Melanoma (MM)
Introduction . . . . . . . . .
Significance of PET . . . . .
Pitfalls
PET Indications . . . . . . .
. . . . . . . . . . . . 419
. . . . . . . . . . . . 419
. . . . . . . . . . . . 421
421
. . . . . . . . . . . . 421
8.2 Case Studies . . . . . . . . . . . . . . . . . . . . . . 422
Patient 1 Malignant Melanoma
of the Right Thigh . . . . . . . . . . . 422
Patient 2 Recurrent Melanoma . . . . . . . . . 424
xxx
Patient 3 Metastasized Melanoma . . . . . . . 426
Patient 4 Choroidal Melanoma . . . . . . . . . 427
Patient 5 Metastasized Amelanotic
Melanoma . . . . . . . . . . . . . . . . 428
11 Paediatric Oncology .
. . . . . . . . . . . 487
11.1 Introduction . . . . . . . . . . . . . . . . . . . . . 487
Changes in the Range of Clinical Indications . . 488
8.3 References . . . . . . . . . . . . . . . . . . . . . . . 433
11.2 Lymphomas in Childhood . . . . . . . . . . . . . 488
Staging, Restaging, Prognosis and
Therapy Control . . . . . . . . . . . . . . . . . . . 488
9
11.3 Oncological Orthopaedics in Childhood . . . . . 488
Lymphomas .
. . . . . . . . . . . . . . . . . . 435
11.4 Neuroblastomas . . . . . . . . . . . . . . . . . . . 488
9.1 Introduction . . . . . . . . . . . . . . . . . . . . . 435
9.2 Diagnosis . . . . . . . . . . . . . . . . . .
Imaging Methods . . . . . . . . . . . . .
FDG-PET . . . . . . . . . . . . . . . . . .
Response Evaluation . . . . . . . . . . .
Comparison of FDG-PET, 67Ga and CT .
Autologous Stem Cell Therapy . . . . . .
PET/CT Restaging . . . . . . . . . . . . .
Artefacts . . . . . . . . . . . . . . . . . . .
Other Problems . . . . . . . . . . . . . .
PET Indications . . . . . . . . . . . . . .
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9.3 Case Studies . . . . . . . . . . . . . . . . . . . .
Patient 1 Follicular
Non-Hodgkin’s Lymphoma . . . . .
Patient 2 Metastasized
Non-Hodgkin’s Lymphoma . . . . .
Patient 3 B-Cell Lymphoma in the
Hypopharynx . . . . . . . . . . . . .
Patient 4 B-Cell Lymphoma . . . . . . . . . .
Patient 5 Lymphogranulomatosis,
Nodular Sclerosis . . . . . . . . . . .
Patient 6 T-Cell Lymphoma of the
Cervical Lymph Tract . . . . . . . .
Patient 7 B-Cell Lymphoma . . . . . . . . . .
Patient 8 Restaging of Hodgkin’s Disease . .
Patient 9 Recurrent Hodgkin’s Lymphomas .
Patient 10 Chronic Lymphatic Leukaemia . .
Patient 11 Restaging of the Multiple Myeloma
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436
436
437
437
438
438
438
439
439
439
. 440
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. 442
. 444
. 446
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449
451
454
459
461
461
. . . . . . 465
10.1 Introduction . . . . . . . . . . . . . . . . . . . . . 465
10.2 Significance of PET . . . . . . . . . . . . . . . . . 465
PET Tracers . . . . . . . . . . . . . . . . . . . . . . 466
PET Indications . . . . . . . . . . . . . . . . . . . 466
10.3 Case Studies . . . . . . . . . . . . . . . . . . . .
Patient 1 Sweat Gland Carcinoma . . . . . .
Patient 2 Haemangioendothelioma . . . . .
Patient 3 Chondrosarcoma . . . . . . . . . .
Patient 4 Medullary Osteosarcoma . . . . .
Patient 5 Clear Cell Sarcoma . . . . . . . . .
Patient 6 Rhabdomyosarcoma . . . . . . . .
Patient 7 Rhabdomyosarcoma
of the Left Thigh . . . . . . . . . .
Patient 8 Embryonal Rhabdomyosarcoma .
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11.6 Nesidioblastosis
(Congenital Hyperinsulinism) . . . . . . . . . . . 489
11.7 Case Studies . . . . . . . . . . . . . . . . . . . . .
Patient 1 Status Post Osteogenous Sarcoma .
Patient 2 Status Post Mastitis . . . . . . . . .
Patient 3 Embryonal Rhabdomyosarcoma . .
Patient 4 Focal Congenital Hyperinsulinism
Patient 5 Focal Congenital Hyperinsulinism
Patient 6 Focal Congenital Hyperinsulinism
Patient 7 Diffuse Congenital
Hyperinsulinism . . . . . . . . . . .
Patient 8 Focal Congenital Hyperinsulinism
Patient 9 Focal Congenital Hyperinsulinism
Patient 10 Focal Congenital Hyperinsulinism
Patient 11 Langerhans Cell Histiocytosis . . .
Patient 12 Langerhans Cell Histiocytosis,
Staging and Restaging . . . . . . . .
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490
490
491
492
494
496
498
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500
502
504
506
508
. 510
11.8 References . . . . . . . . . . . . . . . . . . . . . . . . 514
. 448
9.4 References . . . . . . . . . . . . . . . . . . . . . . . 463
10 Oncological Orthopaedics.
11.5 Malignant Melanomas . . . . . . . . . . . . . . . 488
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467
467
470
473
476
478
480
. . 482
. . 484
10.4 References . . . . . . . . . . . . . . . . . . . . . . . 486
12 CUP Tumours .
. . . . . . . . . . . . . . . . . 515
(Cancer of Unknown Primary)
12.1 Introduction . . . . . . . . . . . . . . . . . . . . . 515
12.2 Significance of PET . . . . . . . . . . . . . . . . .
Cancer of Unknown Primary:
Indication for PET/CT? . . . . . . . . . . . . . . .
Studies Available . . . . . . . . . . . . . . . . . . .
Artefacts, Pitfalls and Metabolic Heterogeneity .
12.3 Case Studies . . . . . . . . . . . . . . . .
Patient 1 Carcinoma of the Base
of the Tongue . . . . . . . .
Patient 2 Carcinoma of the Base
of the Tongue . . . . . . . .
Patient 3 Oropharyngeal Carcinoma
Patient 4 Cholangiocarcinoma . . . .
Patient 5 Pancreatic Carcinoma . . .
Patient 6 Carcinoma of the
Head of the Pancreas . . .
Patient 7 Mamma Carcinoma . . . .
Patient 8 CUP Tumour . . . . . . . .
Patient 9 Mamma Carcinoma . . . .
Patient 10 Carcinoma of the Base
of the Tongue . . . . . . . .
Patient 11 Bronchial Carcinoma . . .
Patient 12 Bronchial Carcinoma . . .
516
516
516
516
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518
520
523
526
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528
530
533
536
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. . . . . . 540
. . . . . . 542
12.4 References . . . . . . . . . . . . . . . . . . . . . . . 544
XIII
XIV
xxxxx
13 Pitfalls
. . . . . . . . . . . . . . . . . . . . . . . 545
14 Radiotherapeutic Aspects .
. . . . . . 625
13.1 Testicular Carcinoma and
Other Primary Tumours . . . . . . . . . . . . . . 546
Universal Organ Spectrum of SPT . . . . . . . . 546
14.1 Introduction . . . . . . . . . . . . . . . . . . . . . 625
13.2 Physiological Accumulation of FDG . . . . . . . 547
14.4 Fundamentals Governing the Use of PET/CT Data
for Radiotherapy – Bits and Bytes and DICOM . . .626
13.3 False Positive FDG Accumulations in the
Oncological Sense . . . . . . . . . . . . . . . . . . 547
13.4 Artefacts Due to Technical Factors . . . . . . . . 547
13.5 False Negative PET Findings . . . . . . . . . . . . 547
13.6 Case Studies Secondary Tumours . . . . . . . .
Patient 1 Inflammatory Carcinoma of the
Breast and Papillary Carcinoma
of the Inner Genital Tract . . . . . .
Patient 2 Carcinoma in Situ with Osteoplastic
Metastases 10 years later . . . . . . .
Patient 3 Recurrence of a Sigmoid Carcinoma,
Compression of the Left Ureter . . .
Patient 4 Cervical Carcinoma and
Rectal Carcinoma . . . . . . . . . . .
Patient 5 Mamma Carcinoma and
Colon Carcinoma . . . . . . . . . . . .
Patient 6 Mamma Carcinoma and
Sigmoid Carcinoma . . . . . . . . . .
Patient 7 Thymoma . . . . . . . . . . . . . . . .
Patient 8 Prostate Carcinoma and
Colon Carcinoma . . . . . . . . . . . .
Patient 9 Renal Cell and Prostate Carcinoma .
Patient 10 Prostate Carcinoma and
Colon Carcinoma . . . . . . . . . . . .
Patient 11 Carcinoma in Situ of the Rectum
and Bronchial Carcinoma . . . . . . .
Patient 12 Non-Hodgkin’s Lymphoma and
Bronchial Carcinoma . . . . . . . . .
Patient 13 Mamma Carcinoma and
Bronchial Carcinoma . . . . . . . . .
Patient 14 Coecum, Bronchial and
Renal Carcinoma . . . . . . . . . . . .
Patient 15 Mamma, Cervical and
Rectal Carcinoma . . . . . . . . . . .
Patient 16 Parotid and Colon Carcinoma . . . .
548
548
551
14.2 PET-Assisted Radiotherapy Planning . . . . . . 625
14.3 Advantages of PET/CT Integration . . . . . . . . 626
14.5 Case Studies . . . . . . . . . . . . . . . . . . . .
Patient 1 Prostate Cancer . . . . . . . . . . .
Patient 2 Oropharyngeal Cancer . . . . . .
Patient 3 Breast Cancer . . . . . . . . . . . .
Patient 4 Prostate Cancer . . . . . . . . . . .
Patient 5 Squamous Cell Carcinoma of the
Oral Cavity . . . . . . . . . . . . .
Patient 6 Bronchial Cancer . . . . . . . . . .
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630
630
632
634
636
. . 638
. . 640
14.6 References . . . . . . . . . . . . . . . . . . . . . . . 643
554
556
558
560
561
564
566
568
570
574
577
579
583
586
13.7 Case Studies
Physiologically Increased Uptake . . . . . . . . . 589
Patient 17–21 . . . . . . . . . . . . . . . . . . . . . 589
13.8 Case Studies
Non-Oncological Increased Uptake of
Inflammatory Genesis . . . . . . . . . . . . . . . 593
Patient 22–31 . . . . . . . . . . . . . . . . . . . . . 593
15 Nuclear Cardiology .
. . . . . . . . . . . . 645
– the Situation in Europe
15.1 Introduction . . . . . . . . . . . . . .
Development of Nuclear Cardiology
and the Present State . . . . . . . . .
Molecular Cardiac Imaging . . . . .
Fusion Imaging . . . . . . . . . . . . .
SPECT and SPECT/CT . . . . . . . . .
MRI and PET/MRI . . . . . . . . . . .
. . . . . . . 645
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645
647
649
650
652
15.2 Cardiac PET/CT . . . . . . . . . . . . . . . . .
Coronary Sclerosis . . . . . . . . . . . . . . .
Diabetes Mellitus and Coronary Sclerosis .
Plaque Imaging . . . . . . . . . . . . . . . . .
Perfusion . . . . . . . . . . . . . . . . . . . .
Vitality . . . . . . . . . . . . . . . . . . . . . .
Radiation Exposure and
Contrast Medium Safety . . . . . . . . . . .
Artefacts . . . . . . . . . . . . . . . . . . . . .
Invasive Diagnostics, Treatment and
Treatment Monitoring . . . . . . . . . . . . .
Prevention . . . . . . . . . . . . . . . . . . . .
Remarks on the Catalogue for
Further Training for the Specialization in
Nuclear Medicine . . . . . . . . . . . . . . .
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652
652
654
655
656
657
. . . 657
. . . 658
. . . 658
. . . 661
. . . 661
13.9 Case Studies
Artefacts . . . . . . . . . . . . . . . . . . . . . . . 611
Patient 32–39 . . . . . . . . . . . . . . . . . . . . . 611
15.3 Case Studies . . . . . . . . . . . . . . . . . . .
Patient 1 Mild CHD . . . . . . . . . . . . .
Patient 2 Status Post Revascularization .
Patient 3 Status Post Anterior Infarction
and Sextuple Bypass . . . . . . .
Patient 4 Surprise Finding
of Stem Stenosis. . . . . . . . . .
13.10 References . . . . . . . . . . . . . . . . . . . . . . . 622
15.4 Reference . . . . . . . . . . . . . . . . . . . . . . . 676
. . . 663
. . . 663
. . . 666
. . . 668
. . . 672
xxx
16 Cardiac PET and PET/CT .
. . . . . . . . 687
– the Situation in the USA
16.1 Introduction . . . . . . . . . . . . . . . . . . . . . 687
16.2 Coronary Artery Disease . . . . . . . . . . . . . . 687
Imaging with PET . . . . . . . . . . . . . . . . . . 688
Accuracy of PET and PET/CT Stress-Rest
Myocardial Perfusion Imaging . . . . . . . . . . 693
Advantages of Myocardial Perfusion Imaging
with PET . . . . . . . . . . . . . . . . . . . . . . . . 696
Hybrid PET/CT Myocardial Perfusion Imaging
in Coronary Artery Disease . . . . . . . . . . . . 697
16.3 Myocardial Viability . . . . . . . . . . . . . . . . 698
Concepts and Pathophysiology . . . . . . . . . . 699
Assessment of Myocardial Viability . . . . . . . 699
Imaging of Myocardial Perfusion
and Metabolism . . . . . . . . . . . . . . . . . . . 701
Clinical Implications of
Perfusion Metabolism Imaging . . . . . . . . . . 705
PET/CT vs. Stand-Alone PET . . . . . . . . . . . . 707
Clinical Indications of
Perfusion Metabolism Imaging . . . . . . . . . . 708
16.4 Vascular Inflammation and Atherosclerosis . . 709
16.4.1
Large Vessel Vasculitis . . . . . . . . 709
16.4.2
Atherosclerosis and Plaque Imaging 711
16.5 Future Developments . . . . . . . . . . . . . . . . 714
16.6 References . . . . . . . . . . . . . . . . . . . . . . . . 714
17 Future Trends: Molecular PET .
. . . 721
17.1 Technical Potential and
Software Optimization . . . . . . . . . . . . . . . 721
17.2 Molecular PET . . . . . . . . . . . . . . . . . . . . 722
Tumour Vitality and
Glucose Transporters (GLUT) . . . . . . . . . . . 722
Therapeutic and Diagnostic Potential . . . . . . 722
17.3 Final Remark . . . . . . . . . . . . . . . . . . . . . 723
17.4 References . . . . . . . . . . . . . . . . . . . . . . . 724
Subject Index . . . . . . . . . . . . . . . . . .
727
XV
1.1
1
Survey
Introduction
Positron Emission Tomography: Past and Present
CONTENTS
1.1 Survey 1
Physical and Biochemical Fundamentals 2
PET in National and
International Medical Care Systems 2
1.2 Technological Variants and Developments 4
Coincidence PET vs. Dedicated PET 4
Differentiated PET Evaluation 4
Radiotherapeutic Tools 5
PET/CT – a New Key Technology 5
Influence of PET/CT on PET 5
Studies Dealing with the Cost Efficiency of
PET Alone 6
PET/CT or Comparison of
Co-Registered Findings? 6
“Standard” (CARE)-CT and PET/CT 6
PET/MRI? 6
American Joint Committee on Cancer 7
PET Screening in Japan and Taiwan 7
1.3 Increased FDG Uptake Due to Physiological and
Technical Factors 7
1.4 References
8
1.1 Survey
Interdisciplinary cooperation, in which nuclear medicine has been involved for more than 50 years, is
indispensable to optimize oncological diagnosis and
therapy. The processes have developed from tumourafﬁne radionuclides (with measuring probes), such as
67Ga citrate [35], rectilinear scanners and gamma cameras via marked monoclonal antibodies (immunoscintigraphy [5]) up to high-tech SPECT [14], coincidence imaging (hybrid PET), PET, PET centres (see the
references on the DVD [Ö 1.1]) or PET/CT centres.
The status report of the “Intersociety Dialogue”
in the USA [18] should be mandatory reading for
everyone operating PET/CT scanners or arranging
PET/CT examinations for clinically proven lesion
ﬁndings, but particularly for medically trained
medical economists. Recommendations issued by
interdisciplinary expert committees have a higher
competency rating than protocol variants (e.g. options, technical speciﬁcations, methodological preferences, clinical application and information on the
radiation exposure for the patient and staff as well
as the population): For example, the technical staff
is exposed to radiation doses amounting to 5.5 mSv
[19, 31]. Since the early 1950s, Brownell has reported
on positron emitters used to detect brain tumours
and till the end of the 1990s on PET cameras and the
PET evolution [11, 12, 13]. Among the PET pioneers,
Ter-Pogossian also played a major role. Few know
that “bone blood ﬂow” with 18F and the positron
camera were already described in 1965 [69]. Today,
numerous multi-author publications dealing with
PET and PET/CT are available. The transfer of new
know-how from the scientiﬁc level to health policy
is usually considerably delayed. Furthermore, the
missing adaptation to European standards regarding remuneration by the statutory health insurance
companies still remains a restraint for modern di-
1
2
1
Introduction
agnostic standards and a nuisance for well-informed
patients and physicians in Germany.
The cost efﬁciency of PET has been discussed
since the early 1980s [26], and the question who is
to establish the PET/CT ﬁndings also has not yet
been deﬁnitely answered. This dispute is absurd:
The maximization of information gained for the
patient with PET/CT is not seriously criticized [74],
and this information is of course fused (as described
above) in the interdisciplinary efforts of nuclear
medicine physicians and radiologists. Occasionally,
the discussion is whether hybrid systems (so-called
coincidence PET) and “dedicated PET” can be assessed identically. Finally, the difference concerning
the dimension of the detectable lesion size tips the
balance in favour of the precision of the full-ring
systems (4–6 mm). The same applies to so-called
breast dedicated gamma cameras [63].
SPECT methods, multi-detector systems and pinhole SPECT (P-SPECT) have improved the detection
of smaller lesions (lymph nodes). P-SPECT has proven
useful for navigated SLN biopsy. Offering SPECT/CT
as an alternative to PET/CT [62] overshoots the mark.
Of course, it can be readily understood that the borders of organs can be better deﬁned with an increased
tracer uptake and that the functional relevance of CT
lesions can be better characterized, but the precision
of PET/CT with regard to functional considerations
cannot be achieved. The following restriction applies
to PET and PET/CT: Even high-resolution equipment
is unable to detect micrometastases. Under the most
favourable conditions, the detection limits of SPECT
range from 8–10 mm and for PET from 4–6 mm. Micro-PET systems are only suitable for small animal
experiments. Detection, localization and molecular
vitality diagnosis of tumours and recurrences are
postulates with intended differentiation between limited disease and extensive disease. PET has opened
the way to this extended framework, and PET/CT has
more exactly deﬁned the diagnostic potential.
Physical and Biochemical Fundamentals
The discovery of the positron in 1932 by Anderson
[1] opened the way for the evolution of PET, which
ﬁnally led to exclusive PET/CT [48]. Increased glucose consumption as an energy source for the growing tumour cell is the unrivalled metabolic leitmotif
of PET. The Nobel Prize winner Otto Warburg had
already published his ﬁndings in 1924/25 as a member of the former German Kaiser Wilhelm Institute
[78, 77, 79]. Biological experiments with radioactively
labeled ﬂuorides were already carried out in 1940 [72],
but we had to wait until 18F-FDG could be synthesized
in 1977/78 to implement PET in clinical applications
[34, 36, 37]. Studies dealing with the biochemical
hexokinase composition have been published since
1978 [49]. Differentiated information concerning the
factors inﬂuencing the uptake of 18F-FDG, a chemical glucose analogue that ﬁnally initiated worldwide
tumour studies with PET, is available today. PET was
ﬁrst initiated several decades ago [2, 28, 60]. The ﬁrst
information for general practitioners was published
in the ofﬁcial journal of the German Medical Association (Deutsches Ärzteblatt) in 1993 [34].
PET in National and
International Medical Care Systems
PET in the US Medical Care System. The number
of PET systems used in North America, particularly in the highly populated regions, is impressive.
Statistical investigations reveal that a PET scanner
is available to 97% of the US population within a
radius of 75 miles [55]. The quick and comparatively unbureaucratic PET allocation in the USA
developed in a concerted action of PET physicians
(nuclear medicine, radiology, cardiology, oncology,
neurology, and psychiatry) and ultimately also in
agreement with leading institutions (the NIH, NCI,
Academy of Molecular Medicine, Institute of Clinical PET and SNIDD 1), contrary to other countries
which, with considerable variations, still maintain a
wait-and-see attitude regarding the use of PET.
According to a Europe-wide study, Belgium is the
leading European country in the ﬁeld of PET [7]. For
all PET indications, the European demand for PET
examinations amounts to 2,026 per 1 million inhabitants. More than 1,000 positron emission tomographs are already available in the USA (> 500 PET/
CT). Recurrent tumours and therapy control have
long since been accepted indications for at least six
tumours in the USA [17], and applications have been
made for seven further entities (see below).
1
Society of Nuclear Imaging and Drug Development
1.1
Accepted: diagnosis, staging and restaging of
NSCLC (non-small-cell lung cancer), colorectal
and oesophageal cancer, head and neck cancer,
lymphoma and melanoma.
Applied for: pancreas, brain, small-cell lung cancer, cervix, ovary, multiple myeloma, testicles
(petition submitted to the Secretary of Health,
signed by 37 US senators).
Present situation: Since the beginning of 2005,
the US health insurance programme Medicare
has borne all costs associated with PET examinations: PET(-CT) is nowadays used to diagnose
all types of cancer, and a PET database has been
established [cooperation of the National Cancer
Institute (NCI), the Society of Oncology and patient representatives. More detailed information
is available from these institutions].
In Germany, PET(-CT) is still a subject of political
discussion. Three symposiums about PET/CT took
place in Berlin on 5 May 2004, 9 December 2004 and
1 June 2005 [44]. These meetings gave further impetus to encourage compensation for doctors for PET
examinations and for technical upkeep [6, 8].
The precarious situation of the social security
systems resulting from high unemployment rates
and demographic changes as well as medical progress with the corresponding increase in ﬁnancial
turnover in the health care sector has led to the
predominance of economics. The administrations of
the legal health insurances treat this like a doctrine,
emphasizing primarily ﬁnancial beneﬁts, especially
when considering the introduction of new medical
procedures. This approach is often short-sighted,
and the costs that actually have to be paid per patient, including the therapy resulting from the diagnosis, are neglected. Using the example of NSCLC,
Oberender [50] discussed attainable objectives of
economical nuclear medicine, taking into account
the relevant literature (see also Chap. Pneumology).
Representative documents were also established
in Cologne. The supplementary volume edited by
Czernin (2004) is a compilation of state-of-the-art
essays [20]. Paediatric oncology has only been using
PET and PET/CT moderately to date [32].
Tidal Wave of Costs for Cancer Patients. The National Cancer Institute (NCI) in the USA registers an
escalation in health care costs (amounting to several
billion [109] dollars), the sum of which covers more
Survey
than 10% of the total medical costs, whereby more
than 50% have to be paid for the treatment of carcinomas of the breast, the bronchial system and the
prostate, as well as other tumours.
Tabular data are available for PET regarding the
sensitivity, speciﬁcity, accuracy, impact on management and therapy of more than 18,000 patients [30]
and of more than 7,000 patients according to the
selection rules established by evidence-based medicine [59]. In cost-beneﬁt analyses, the so-called net
beneﬁt can be calculated by deducting the investment costs from the savings [50]. The clinical classiﬁcation of the PET evaluation is continually updated by expert commissions. Many PET priorities
are classiﬁed into class 1a and 1b. These can nowadays be categorized as PET core competencies. Due
to the lack of legal provisions regulating doctors’
remunerations for PET examinations, Germany lags
behind in Europe [48] – regardless of the innovative
potential of German scientists and clinical physicians who have taken an active part in the worldwide
progress of modern PET diagnosis.
Paradoxically, Germany is in fact the leading European country with 80–100 positron emission tomographs (in hospitals and practices), with one PET
scanner per 1 million inhabitants. However, this
equipment is only available to those who can afford
the high costs of PET examinations, mainly because
their private health insurance covers these costs. The
allowance procedure established for PET compensation in cases of lung cancer is a ﬁrst step towards
achieving world standards. Beyond this, agreements
with individual health insurance companies in the
ﬁelds of bronchial carcinoma, breast carcinoma
and malignant lymphoma have, in addition to their
practical contribution towards patient care, the responsibility to improve the analysis of data. This
development shows that views have changed, also
in Germany. Arguments blocking discussion are no
longer acceptable, particularly with regard to a decision taken by the German Federal Constitutional
Court on 6 December 2005, according to which every
patient is entitled to be treated with state-of-the-art
equipment and methods. However, the PET problem
is just another example of the actually existing deﬁciencies in the medical care system. Nonetheless,
the ﬁrst positive steps have been taken.
In the ﬁeld of basic research, especially in the
development of medicines, even big centres (and
also industry/university associations) are not able
3
4
1
Introduction
to make use of molecular PET and micro-PET studies. We cite a modiﬁed quotation from Immanuel
Kant that perfectly captures the situation, asking:
How long will it still take until the “immanent logic
of truth” has made its way?
PET Centres in the Federal Republic of Germany.
Pilot institutions were installed in the early 1980s,
with the ﬁrst PET centres established in Hannover,
Heidelberg and Jülich. Frankfurt was one of the late
entrants, ﬁrst installing a PET system in 1994. From
1994 to 1999, PET scanners were increasingly used
and helped to diagnose more than 3,000 patients; in
2005, the number rose to more than 6,000 patients.
However, the PET/CT scanners used have not yet
been fully developed with regard to technological
and clinical aspects. Since then, it has become obvious that “PET alone” is in fact able to meet the expected general requirements, but PET/CT nevertheless provides an even more differentiated standard
with regard to the required indications.
Among others, a PET/CT scanner was installed in
the Diagnostic Therapeutic Centre (DTZ) in Berlin
in October 2003. Non-invasive heart examinations
can also be carried out using the new generation
of PET/CT equipment (PET/CT high resolution or
Biograph 64, respectively). In the meantime, the expansion of PET/CT equipment with high-deﬁnition
measurement technology has taken place. Currently,
over 5,000 patients have been examined in the Diagnostic Therapeutic Centre (DTZ) (December 2007).
1.2 Technological Variants and
Developments
A detailed survey of PET and PET/CT technology
is given in Chapter 2, “Fundamentals”. We will at
this point only present selected notes from a PET
physician’s view.
Coincidence PET vs. Dedicated PET
Even the stages of the lowest technological development of PET have unquestionably proven useful in
practice. Using the example of breast cancer, it can
be clearly shown that a resolution of about 2 cm is
inferior to classical full-ring PET. Even more, coincidence PET cannot compete with the high-tech
variant PET/CT. New approaches were proposed to
improve the SUV, such as attenuation correction,
patient positioning aids and fusion images in case
of PET/CT.
Differentiated PET Evaluation
Since 1980, pioneer studies have dealt with regional
tissue perfusions and myocardial, brain and tumour metabolism (with 15O, 11C and 18F) as well as
with graphical analyses and ﬂux constants, linear
regression analyses and neuronal networks associated with dementias. Cerebral studies marked the
beginning of multimodal (comparative) diagnosis
with PET, CT and MR [47, 56, 57]. Aids are quantitative parameters (in the simplest case SUV) and – in
the ﬁeld of research – more expensive measurements
(PATLAK analysis). Reconstruction and attenuation correction tools have been improved, and socalled navigation tools have been developed. In this
context, we have to distinguish between expensive
methods that are unaffordable in clinical routine
use and simpler score-based and index-based semiquantitative evaluation concepts.
SUV (Standardized Uptake Value). The SUV has
been criticized for being an impermissible simplification and defined as having “silly useless
value” [42]. Too many factors influencing the result are taken into account in this calculation so
that a great inter-institutional and also a great
inter-patient variance are observed. The “lean
body mass” was described as a correct reference
parameter. In summary, the following SUV modifications should be mentioned: dual-phase early/
late PET, SUV time quotient, and so-called total
lesion indices that are score-based.
In the meantime, several teams have postulated a SUV bonus for follow-up and therapy control
[9, 42, 67]. The most acceptable approach (which is
nevertheless not unproblematic) is the intra-individual comparison of the FDG uptake values prior to
and after therapy. Compartment analyses determining the inﬂux and transﬂux constants yield more
precise results, but are not practicable. Meanwhile,
1.2
controversially positive data are available, too. More
expansive kinetic analyses (PATLAK) are only eligible for studies [53, 54]. The beneﬁt that can be
achieved with the dual-time technique (PET scans
after 90 min and 1–4 h later) is being discussed
[24].
Prognostic Evaluation with SUV. Follow-up observation of the SUV must be evaluated cautiously. For
example, what does it mean to the patient if a longer
survival time is postulated in case of lower SUVs
than for higher values if a difference of just a few
weeks is not statistically signiﬁcant?
Radiotherapeutic Tools
In addition to the above-mentioned software and
navigation techniques, the following approaches are
being further investigated for PET applications in
radiotherapy (see also Chap. “Radiotherapy”):
fully integrated PET/CT simulators,
image segmentation and
delimitation of the biological target volume.
Neuronuclear medical and neuroradiologic procedures used to image brain tumours will not be
taken into account in this survey [57].
PET/CT – a New Key Technology
Speciﬁc impulses are due to PET/CT technology,
which has now reached the milestone of the 3D version. Stage classiﬁcation (“overall TNM stage”) has
become more precise: 77% vs. 54% (MR), T-stage
80% (PET/CT) vs. 52% (MRI), N-stage 93% vs. 79%
with MRI, while PET und MRI yield similar results
according to the Essener Study (published by the
University Hospital of Essen, Germany).
Townsend [15, 68] notes (“PET/CT today/tomorrow”) that this already plays an evident role based
on the improved acceptance and preliminary results
of studies. Five years after PET/CT was developed
[15, 39, 46], clinical integration of this new imaging method made unexpectedly quick progress, although only a minority sees the necessity of fused
images in approximately 7% of all cases (see below).
Technological Variants and Developments
Schulthess [73] has published documentation of
the experience gained in Zurich, Switzerland, which
meets its match only in a few German institutions
(e.g. Essen, Ulm). Recently, a rather comprehensive
report dealing with the latest progress in the ﬁeld
of PET and PET/CT was published in a book edited
by Baum [6].
PET/CT should be available to all insured patients, but this is not the case in Germany yet [17].
Nevertheless, the number of installations in Germany since the ﬁrst edition of this book has virtually trebled. We are expecting a continuation of this
dynamic development in the next few years. More
than 5,000 patients (as of December 2007) have been
examined solely in Berlin. In other expert centres
in Germany, the number of examinations probably
exceeds 10,000.
Influence of PET/CT on PET
In Johns Hopkins Medical Institutions in Baltimore,
the frequency of PET examinations has increased
by 900% (!) in the 3 years since PET/CT was introduced [75, 76]. This does not mean that PET alone
is absolutely outdated. But optimized protocols and
new navigation tools eliminate problems and help to
give answers to open questions regarding the necessity of a “standard care CT” with or without oral/IV
contrast agents and to prevent PET artefacts.
A study published by the University Hospital of
Ulm, Germany, in 2004 conﬁrms that PET/CT detects at least 13% of those tumour recurrences that
would not have been detected with PET or CT alone
[43]. The discussion on the necessity of RCT (“randomized clinical trials”) has given rise to certain
doubts (“about errors with probabilities” [80]).
Shortfalls of CT alone are:
the tumour vitality cannot be evaluated;
the lymph node malignancy around/below 1 cm
cannot be interpreted;
the solitary foci of the lung depend on a waitand-see strategy;
the response classiﬁcation after therapy is inadequate;
the change of the morphological tumour load
(mass) after therapy is not decisive;
there is no information about the metabolic activity and proliferation of DNA synthesis;
5
6
1
Introduction
hypoxia potential of the tumour environment?
tumour-speciﬁc receptors?
little experience with “functional genomics/proteomics (reporter gene, reporter probe)”.
Shortfalls of PET alone are:
morphology, the invasion into neighbouring organs cannot be displayed;
the exact level of the lymph nodes (e.g. in the ENT
area) cannot be localized by the surgeon;
tumours/metastases in the chest wall/pleura cannot be separated;
mislocations of liver metastases in the lung (respiratory artefacts);
mislocations of infraclavicular foci and apical foci;
bone/soft tissue and brain metastases can be better diagnosed by CT.
PET/CT or Comparison of
Co-Registered Findings?
Studies Dealing with the Cost Efficiency
of PET Alone
“Standard” (CARE)-CT and PET/CT
Pertinent studies must be completed by economic
follow-up studies dealing with PET/CT to determine
precisely the reduction factor due to management
cost minimization. Fused PET/CT images compensate the shortfalls: This imaging method
perfects the anatomo-metabolic/molecular (nano)
diagnosis,
favours an improved therapy strategy and response control,
reduces incorrect staging,
optimizes molecular radiotherapy,
localizes metabolic, molecular genetic (gene
transfer) mechanisms and receptor-controlled
signal transduction,
implements stem cell research,
provides, for example, repair control after acute
myocardial infarction, migration kinetics of progenetor cells [65, 23].
PET/CT avoids the problems arising from separate co-registrations with subsequent image fusion:
Errors during mathematical adjustment of the algorithms, mislocation of lesions and interval events
(differences in hydration, intestinal ﬁ lling, defecation artefacts). Lesions were incidentally detected by
PET in the gastrointestinal tract only in 3% of the
cases, however with an essential risk of precancerous lesions [41].
Reports published by the University of Aachen,
Germany, were irritating [58]: According to these
reports, essential supplementary information was
only made available in 6.7% of all cases. Experts
from Zürich contradicted this minority opinion [74].
From a critical point of view, some kind of combined acquisition of PET and CT data is necessary
in almost 50–67% of all cases to localize lesions
precisely. In Berlin, a majority tactic is based on
the triad: image fusion, separate evaluation of CT
(radiologist) and PET (nuclear medicine physician),
with concerted expertise of the PET/CT team for
deﬁnite medical co-evaluation.
At present, this decision is made by the radiologist
[3]. If a standard, contrast-enhanced CT is already
available before the PET/CT examination is carried
out, it must be clariﬁed whether – for example, in
case of an ametabolic or hypometabolic FDG constellation – active metastases are present or not (metastatic conversion in case of an FDG-positive primary
tumour). An exclusion of false-positive PET might
increase the need for contrast-enhanced CT (CE-CT).
The intestinal wall and abdominal lymph nodes may
be a problem in native CT. Oral contrast agents are
usually applied in case of gastrointestinal tumours;
in case of bolus passages, an FDG uptake that is not
due to a tumour must under all circumstances be
excluded, e.g. with a two-phase PET (see above, [24]).
A diagnostic CT is considered obligatory within the
scope of radiotherapy planning and to prepare for
surgical procedures, but not for PET- and PET/CTbased chemotherapy and radiotherapy control.
PET/MRI?
Tumour detection with magnetic resonance imaging (MRI alone) was ﬁrst reported by Damadian
[21]. A continuing competitive argument about the
authorship was provoked by the award of the Nobel
Prize to Mansﬁeld in 2003. In any case, MRI has a
1.3
Increased FDG Uptake Due to Physiological and Technical Factors
competent morphologically based status today [71].
Initial steps towards the development of PET/MRI
(“fusion image”) and a back-up following the rules
of the current medical state are taking place [61].
American Joint Committee on Cancer
The basic categories of the tumour classiﬁcations
were developed in 1997 [29]. In principle, these categories can also be used for PET and PET/CT:
T (tumour size, extent),
N (regional lymph nodes, the number of inﬁ ltrated lymph nodes determines the expected survival time),
M (distant metastases).
A current revision of the lymph node imaging
concept developed by Massachusetts General Hospital, Boston (2004), deals with new approaches regarding multimodal imaging, for example, in the
ﬁeld of risk stratiﬁcation of prostate patients [16] and
breast cancer patients [81], also taking into account
problems related to false-negative intraoperative explorations [22].
tic strategies (surgery, radiochemotherapy as primary option) [66, 27, 38].
PET Experiments in Japan. Within 10 years, 40,000
asymptomatic test persons were examined (“most
cancers” – 3/5 in males, 4/5 in females – were PETpositive); ﬁve persons obtained unnecessary surgical interventions. In 1.14% of all cases PET could
detect a tumour (3,165 persons).
PET Experiments in Taiwan. A total of 3,631 patients underwent a PET examination, and a tumour
was found in 1.05% of all cases (in 24 cases falsepositive ﬁndings were detected). Both PET teams
defended their PET motives with incomprehensible
arguments. They will have to answer the following
critical questions:
How many carcinomas were not detected?
Were quality-of-life indicators taken into account?
Which inclusion/exclusion criteria were used?
Which methods were used as the gold standard,
and which results did they yield?
Were the studies prospectively randomized?
How was the radiation exposure justiﬁed vis-àvis the (above all the young) test persons? Were
they informed of the exposure?
How was carcinoma prevalence distributed?
What about the costs and cost efﬁciency?
PET Screening in Japan and Taiwan
A majority of all PET experts worldwide agree that
a (clinically not indicated) search in oncology is untenable, and even less acceptable in healthy persons.
Mass screenings are only conducted in two countries, Japan and Taiwan. After this approach had
been controversially discussed in Germany, Silverman (UCLA/USA) extensively criticised this concept
[64]. Impetus was given by articles from Japan and
Taiwan. In the meantime, the rejection is accounted
for by the majority vote being negative. However, no
objection could be raised against the observance
of (unexpected) chance ﬁndings. Nuclear medicine
and radiology have already been working on this
problem for decades [52, 70, 40]. This is detailed in
the chapters on organs.
(Pre-)malignant lesions can be discovered incidentally. The possible early detection of recurrent
carcinomas is also worth mentioning as the course
setter towards altering the diagnostic and therapeu-
It is in fact interesting that computed tomography
is concerned by this screening problem in spite of
the experience gained over a long period of time.
1.3 Increased FDG Uptake Due
to Physiological and
Technical Factors
The physicians evaluating the PET images must be
properly informed of artefacts and pitfalls (due to
physiological and technical factors), and also of
the reasons for potentially positive PET ﬁndings
in case of benign processes, such as autoimmune
lymphoproliferative syndrome (ALPS), WAT (white
adipose tissue) and BAT (“brown adipose tissue”)
[33, 51, 82], for which radio-iodine-labeled MIBG
seems to be useful.
7
8
1
Introduction
Atherosclerotic plaques with high macrophage
potential accumulate FDG and other radiolabeled
components (e.g. MCP-1, matrix metal proteinases)
and are being tested at present. In the area of larger
vessels (aorta, carotids, experimentally also in the
area of the coronary vessels), an increased macrophage capacity indicates plaque instability.
Increased glucose levels impair the PET result
[44]. The multitude of causes ranges from inﬂammation/infection with consecutive false-positive PET
ﬁndings up to septic bone surgery/orthopaedics. It
is important to know more than 100 (!) causes of
benign processes in 37 organs [4] with focal or diffuse hypometabolic FDG uptake.
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2.1
2
Preface
Fundamentals
Thomas Beyer
CONTENTS
2.1 Preface 11
Positron Emission Tomography (PET) 11
Radioisotopes and PET Tracers 12
Coincidence Measurement and Quantification 13
PET Measurement Results and Reconstruction 14
PET Scanners and Scintillation Detectors 16
2.2 Combined PET/CT 18
Retrospective Image Fusion 18
The PET/CT Prototype 18
CT-Based Attenuation Correction 20
Commercialization of PET/CT 21
New Technical Developments in PET/CT 23
PET/CT Acquisition Protocols 29
Sources of Errors and Optimization Options 30
Radiation Protection Aspects 37
2.3 Conclusion 40
2.1 Preface
The focus in the ﬁeld of diagnostic imaging in oncology is shifting more and more from CT-controlled
anatomical imaging to molecular/functional imaging with positron emission tomography (PET). Both
imaging methods developed in parallel for the past
25 years before they were combined for the ﬁrst time
in one unit at the end of the 1990s. As a diagnostic
method PET/CT has numerous advantages over PET
and CT alone, which will be discussed below with
regard to the equipment used and described from a
medical point of view by taking into account exemplary cases in the main part of this book.
2.4 References 40
Positron Emission Tomography (PET)
T. Beyer, PhD
Timaq medical imaging Inc., Technopark Luzern,
D4 Platz 4, 6039-Root, Switzerland
Tracer Principle. Contrary to radiological or morphological examination methods, nuclear-medical
imaging methods show the functionality of the
organism with in-vivo studies by means of emission measurements. With this method, a tracer is
brought into the body, and the radiation emitted
by this tracer, consisting of a carrier molecule (e.g.
glucose) coupled with a radioactive isotope (e.g. 18F),
is detected from outside the body (Fig. 2.1).
The tracer principle was introduced by George
de Hevesy in the 1920s [39]. This idea is based on
the fact that the system (i.e. the patient) is not to be
disturbed during the examination. The biological
function (metabolism) can then be examined with
minute quantities of a substance (tracer) that cannot be distinguished from conventional substances
available in the body and involved in selected metabolism processes. This can be achieved by radioactive labeling of the tracer. This is done by replacing
special ion groups of the original molecule in the
11
12
2
Fundamentals
Tracer
X-ray tube
Detector ring
Detector
a
c
b
Fig. 2.1a–c. Oncological imaging. a CT transmission measurement.
b Emission measurement with PET. c PET/CT as equipment combination consisting of both PET and CT with the possibility to perform
both examinations quasi-simultaneously
tracer molecule by radioactive isotopes or groups; in
this way, the chemical properties of the molecule are
not modiﬁed, or at least not in such a way that they
are not involved in the ﬁrst metabolism steps in the
body. The radiation emitted by the tracer then allows the localization of the distribution of the tracer
and the tracking of its metabolism in vivo.
The choice and production of a radioactively labeled tracer used for diagnostic imaging depends
on the physiological and biochemical metabolic processes (e.g. blood ﬂow, metabolism, receptor binding) that are to be observed and on the properties
of the radioisotopes (half-life, radiation protection)
as well. The tracer development process starts with
the selection of the radioisotope (for PET or SPECT).
Isotopes that are not available on the market must
be produced “onsite”.
Radioisotopes and PET Tracers
If we consider the multitude of artiﬁcially produced
radioisotopes, we see that positron emitters (E+) have
several advantages over photon emitters [66]. The
distribution of the E+ emitters may be tracked from
the outside by a coincidence measurement, which is
a better measurement method than the acquisition
of single gamma rays (“single photon emitter”). During the coincidence measurement, pairs of 511 keV
annihilation photons created after the emission of a
positron and its crossing with an electron are measured and used to localize the radiotracer and then
also for attenuation correction (Fig. 2.2). Although a
rather expensive infrastructure with both a cyclotron
and a radiochemical laboratory must be available in
the vicinity of the PET scanner to produce short-lived
2.1
PET
detector
ring
I(x)
511 keV
Patient
CH2
HO
D2
β+
e–
H
p→n + β+ + ne
Preface
I0
O
OH
H
OH
HO
Annihilation
H
H
511 keV
H
D1
18
TX
F
Fig. 2.2. Electronic coincidence measurement with PET. A tracer (for example FDG [18F]-ﬂuorodesoxyglucose) is injected.
A positron is emitted through radioactive decay of 18F (E+-emitter), which attracts an electron and then decays into two
511 keV annihilation photons emitted 180 degrees apart. The straight line on which the decay took place can be clearly
identiﬁed by the detection of the two annihilation photons in opposite detectors D1 and D2. The emission activity is underestimated due to self-absorption [I(x) < I0]. The absorption coefﬁcients (μ) for each possible detector combination Di–Dj can
be ascertained with a transmission source (TX) rotating around the patient
isotopes such as 15O (2-min half-life), these short-lived
isotopes are very useful in studies dealing with metabolic processes, which only last a few seconds or minutes and thus require repetitive short measurements.
However, authentic labeling of the biomolecule
is impossible in many cases. This is the reason why
analogue biogenic isotopes must be used to ensure
that the biological activity and thus the metabolic
process to be observed are maintained after the
tracer molecule has been labeled. Table 2.1 lists the
most frequently used PET isotopes. As the half-life of
the four most important PET isotopes (11C, 13N, 15O
and 18F) is rather short (20.4 min, 10 min, 2 min and
109 min), high doses must be produced with short
labeling processes. An external production and delivery to PET installations without a cyclotron are
presently only established for 18F-labeled tracers.
Generally the labeling position of the biomolecule with the positron emitter is chosen according to the metabolic process to be observed as well
as the stabilization of the biological activity. Steric
and electronic effects may considerably modify the
physiological properties of the labeled molecules. It
is therefore often difﬁcult to prognosticate the behaviour of newly developed tracers, so the scientists
developing such new tracers need to have comprehensive experience (with regard to both chemical
and biological features). But in many cases the molecule and its metabolic properties are in fact known
and may therefore be more reliably used to visualize
selected physiological processes.
Table 2.1. Most commonly used PET isotopes, radioactive
half-life T½, maximum emission energy Emax and average
free path length in water (soft tissue)
Isotope
T1/2 (min)
Emax (MeV)
Rp (mm)
15O
2.05
1.72
0.7
13N
9.9
1.19
0.5
11C
20.4
0.97
0.3
18F
109.7
0.64
0.2
62Cu
9.74
2.93
14.3
68Ga
68.0
1.9
9
82Rb
1.25
3.36
16.5
124 I
6019.2
2.13
10.2
Coincidence Measurement and
Quantification
The measuring principle of PET is based on two assumptions (Fig. 2.2):
the positron was located on the straight line deﬁned by the two detected annihilation photons
and
the annihilation photons are emitted 180 degrees
apart.
In practice, the two assumptions are just approximations. Strictly speaking, the positron is emitted
13
14
2
Fundamentals
with an energy whose amount depends on the isotope concerned (see Table 2.1); thus, that the location
of the emission process cannot be ﬁ xed on a straight
line. Furthermore, the annihilation photons are not
emitted exactly 180 degrees apart. Both processes
must be taken into account for an exact description
of the spatial resolution of a PET scanner.
The advantage of coincidence measurement of
PET is that the localization and quantiﬁcation of
the tracer distribution do not depend on the spatial distribution of the tracer. Contrary to SPECT
(single photon emission tomography) based on
the detection of single photons, the PET signal
does not depend on the depth of the tracer in
the tissue, and it may always be unequivocally
assigned to a connection line (or connection volume) according to the coincidence measurement.
The measured coincidence rate only depends on
the total attenuation along the line connecting
the detectors (Fig. 2.3). The true intensity of the
tracer distribution may then be determined if the
attenuation along these connection lines is known,
regardless of the position along this line (or the
depth in the tissue).
PET Measurement Results and
Reconstruction
A detected PET event is valid if the following requirements are met:
the two annihilation photons were detected within a certain time window (coincidence window,
e.g. 12 ns),
the line connecting the two detectors that have
registered the event is within a pre-deﬁned acceptance angle and
both annihilation photons are detected within a predeﬁned energy window (typically 350–650 keV).
Figure 2.4 shows schematically possible events
detected during a PET scan. Individual photons are
called singles, and two singles meeting the above requirements form a coincidence event, also called a
prompt event. Prompts summarize true coincidences
(trues), random coincidences (randoms) and scattered events (scatters). All events, except the trues,
contribute to a falsiﬁcation of the true tracer distribution and have to be corrected to guarantee an
absolutely reliable quantiﬁcation. All PET (and PET/
Emission scan
Transmission scan
L
= exp { – ∫ μ (x, 511keV) dx}
I
0
L
I = I0 exp { – ∫ μ (x, 511keV) dx}
0
Transmission
Emission
I0
AC-PET
Fig. 2.3. The measured emission signal I is smaller than the true signal I0, because some annihilation photons (511 keV) cannot
reach the detector due to self-absorption. Due to the coincidence principle of PET, the attenuation along all lines connecting the
detector elements can be measured by performing an external transmission measurement and using a transmission source of
known intensity, and the attenuation correction factor can then be calculated by dividing the known by the measured transmission
intensity. The lower row shows the attenuation information (transmission), the uncorrected emission distribution (emission) and
the PET image after attenuation correction (AC-PET) by using the example of a patient with a 3-cm large hamartoma. The tumour
would not have been detected on an uncorrected emission image (material made available by Paul E. Kinahan, PhD, Seattle, WA)
2.1
Preface
700
Tr
[kcps]
S
A
S
Ra
NEC
Trues
Randoms
Scatter
0
20
[kBq/ml]
Fig. 2.4. Measurement events in PET are called prompts. Such a coincidence consists of two singles (S) and has to meet
the requirements stipulated in the text. Pairs of unscattered singles produced by a single annihilation event are called true
coincidences (trues). If these pairs were produced during different annihilation events, they are called random coincidences
(randoms). Among other factors, the share of randoms directly depends on the coincidence time window width. Coincidences with one or more scatter event(s) (green) are called scattered coincidences (scatters). The number of scatters depends
on the object and not of the count rate. The straight line on which the positron was detected is mispositioned due to both the
randoms and scatters so that the tracer distribution is ﬁnally not correctly displayed. The graph on the right shows count
rates (Tr trues, Ra randoms, NEC noise equivalent counts) for a full-ring PET with the 3D imaging mode
CT) scanners available on the market are able to correct randoms and scatters. The randoms are usually
estimated by means of a staggered electronic time
window and subtracted from the prompts [21]. With
the use of new detector materials enabling shorter
coincidence windows [48], the random rate may be
minimized prospectively. The rate of scattered events
is usually determined by taking into account simulated scatter distribution patterns and estimations
regarding the tracer distribution, and the result is
also subtracted from the prompts. In this context, the
possibilities related to an improved energy resolution
of the detectors are also taken into consideration to
distinguish prospectively between the true and scattered coincidences by taking into account the energy
to which the detector has been exposed.
All PET events are documented in so-called
sinograms, i.e. in a kind of polar coordinate system
in which the distance and the rotation angle of a
certain coincidence line (connecting two activated
detectors) is registered with reference to the centre
of the detector ring (Fig. 2.5). A line in a sinogram
represents, for example, a parallel projection of a
certain projection angle where the individual projection points include the sum of all prompts along
a parallel detector combination.
After completion of the scan, the sinograms are
used to reconstruct PET images reﬂecting the distribution of the tracer in the area examined. The sinograms must previously be multiplied with the attenuation correction factors to obtain quantitative PET
images. PET image reconstruction was originally
governed by the ﬁ ltered backprojection based on the
approaches proposed by the Austrian Johann Radon
who was the ﬁrst to show how one can determine an
object function from its line integrals in 1917. In the
context of PET, one can draw conclusions regarding
the original tracer distribution (object function) by
taking into account the projections of the emission
signals (sinograms) and projecting them back from
the directions I. In this context, supplementary efforts by CORMAC and others in the 1950s and 1960s
led to mathematical concepts of image reconstruction from projections, which are known today as
ﬁ ltered backprojection [19]. In 1975 Ter-Pogossian,
Phelps and Hoffman were the ﬁrst to describe a
PET scanner with implemented FBP reconstruction
[54, 60]. During the FBP reconstruction, the line
integrals are convoluted with a ﬁ lter (ramp ﬁ lter)
prior to backprojection in order to eliminate blurring during the backprojection. A ramp ﬁ lter has
negative sidebands suppressing marginal blurring
of the projections outside the object function during
the backprojection.
Due to the inadequacies of FBP in case of poor
count rates (because of short scan times or low activity applied), alternative image reconstruction algorithms have been greatly elaborated for PET scanners during the past years. Iterative reconstruction
approaches have meanwhile been established that,
contrary to FBP, are also able to take into account
tracer distribution models (i.e. ﬁrst estimations) and
15
16
2
Fundamentals
may thus improve the reconstruction of the true
tracer distribution [26]. Figure 2.5 shows such an
example of an iterative, attenuation-weighted image
reconstruction for a FDG whole-body scan.
PET Scanners and Scintillation Detectors
PET scans are based on the concept of scintillation
detectors coupled to a photomultiplier (PMT). By
arranging the detectors around the patient (Fig. 2.3)
or by rotating partial detector rings around the main
axis of the patient and connecting opposite detector
pairs in a coincidence detection circuit, it is possible to register the tracer distribution in vivo and
then to quantify and reconstruct this distribution
as discussed above.
Since the ﬁrst coincidence measurements, PET
measurements have been mainly based on the use of
inorganic scintillators. In addition to NaI (Tl), which
was originally used as the standard material, in the
1980s BGO (Bi4Ge3O12) was considered because of its
higher density and atomic mass number and BaF2
because of its short decay time; in fact, BGO soon
became the standard detector material in commercial PET scanners. Other scintillators, such as CsF,
CsI and GSO (Gd 2SiO5), have comparable decay
times and light yields, but only GSO is still used in
whole-body PET scanners today. Table 2.2 provides
a survey of the current PET scintillators with their
most important physical properties.
x
z
f
z
p(s,f)
s
Sinogram
PET scanner
3DRP
1994
FORE + AWOSEM
Reconstructed image
2001
Fig. 2.5. Single measurement events are sorted in sinograms in the PET. A straight line in a sinogram [p (s, f)] corresponds
to a parallel projection with a deﬁ ned projection angle in the scanner. The sinograms are used to reconstruct the emission
images (right side). The reconstruction techniques have become increasingly sophisticated over the past years. A comparison
with the same data set is shown below: the image on the left side was reconstructed with algorithms used in 1994 and on the
one on the right side was reconstructed with algorithms used in 2001 with iterative and attenuation-weighted approaches.
(Materials made available by David W. Townsend, PhD, UT Knoxville, TN, and Paul E. Kinahan, PhD, Seattle, WA)
2.1
Table 2.2. Physical properties of the PET detector materials
Property
NaI(Tl)
BGO
LSO
GSO
Density [g/ml]
3.67
7.13
7.4
6.7
Effective Z
51
74
66
61
Decay time [ns]
230
300
35–45
30–60
Photons/MeV
38.000
8.200
28.000
10.000
Light yield [% NaI]
100
15
75
25
Hygroscopic
Yes
No
No
No
A PET detector must be able to detect the single
events (singles) with
a high efﬁciency,
a high spatial resolution,
short dead times and
a high time and energy resolution.
Furthermore, the material must not be too expensive because otherwise the voluminous detectors
would no longer be affordable [49]. The selection of a
PET detector depends on a multitude of physical and
other parameters that are differently weighted by
the different suppliers. At present, three crystal materials are being used in PET (and PET/CT) scanners:
BGO, GSO and LSO (for more detailed information,
refer to [52] and [41]). In general, PET detector materials coupled to a photomultiplier (PMT) should
Preface
have a short attenuation length (< 1.5 cm),
induce a high photoelectric effect (> 0.3),
have a short decay time (< 100 ns),
be available at low cost (< $ 20 per ml) and
have a high light yield (> 8,000 photons per
MeV).
All of these requirements inﬂuence the count rate
behaviour of a PET scanner. However, Table 2.2 also
shows that actually none of these current PET detector materials meets all these requirements perfectly,
so the selection of the detector is always a compromise between cost and beneﬁts.
PET scanners typically consist of a row of several
detector rings arranged side-by-side and covering an
axial examination length of at least 15 cm altogether.
Longer areas (torso, whole body) are thus examined
by scanning these areas with several staggered PET
positions, i.e. by moving the patient discontinuously through the PET scanner. Figure 2.6 shows
currently used detector modules and arrangements
in modern PET scanners that may be divided into
partial-ring and full-ring scanners for whole-body
examinations.
In addition, some PET systems are equipped with
so-called septa, i.e. partial discs that may be placed
between the detector rings and thus, for example,
minimize the scattered events among the different
detector rings, but also limit the absolute sensitivity.
Detector
a
b
c
PMT
d
Block detector
e
Segment detector
f
Detector block
Fig 2.6a–e. Diagrams of currently used PET scanners: a rotating partial ring, b full ring and c full ring consisting of
segments. The designs a and b are based on so-called block detectors (d,f), whereas (e) is the basic component for design
(c). In all cases several single crystals are coupled to a photomultiplier. The activated detector element can be unequivocally
localized by means of special matching processes
17
18
2
Fundamentals
If the septa are placed in the PET ﬁeld of view, we
are talking about a 2D PET scan; if they are parked
outside the ﬁeld of view and the detectors are ready
to detect cross-ring coincidences, then we are talking about 3D PET scans. The advantages and disadvantages of the 2D and 3D acquisition modes are
discussed in detail by Cox [24].
2.2 Combined PET/CT
As a technological extension of PET, combined PET/
CT is a non-invasive imaging method used to display
anatomical and molecular correlations by a quasisimultaneous examination. Since the ﬁrst PET/CT
prototypes were introduced in 1998, this imaging
technology has developed at a rapid pace. Due to
the use of fast PET detector materials in PET/CT
scanners and the use of CT for attenuation correction, oncological whole-body scans can today be
completed in less than 20 min. PET/CT also has a
logistical advantage for the patient and the clinician since both examinations – as far as justiﬁed by
clinical ﬁndings – may be acquired quasi-simultaneously and only a single, integrated diagnosis must
be elaborated.
Nevertheless, there are numerous methodical
sources of error, mainly due to the use of CT-based
attenuation correction, which can be compensated
for or minimized by using optimized acquisition
protocols. With these improvements, PET/CT may
be successfully used as a component of modern
diagnostic imaging.
Retrospective Image Fusion
The ﬁrst serious tests trying to register and fuse image data of different complementary – mostly neurological – studies (CT and PET, MRI and PET) were
run in the 1990s [55, 56, 64, 65]. These approaches
were based on linear registration approaches that
put the image volumes in spatial congruence. For
the brain, which may be interpreted as a rigid organ,
a linear registration approach is a realistic assumption. However, this does not apply to extra-cranial
regions to be examined where a spatial image reg-
istration may also be useful from a clinical point of
view, because on the one hand the individual organs
may not be considered as being rigid, and on the
other hand the movement between the individual
examinations may be considered as being linear. An
image fusion of different and complementary image
volumes of the thorax or abdomen must therefore
be based on non-linear registration approaches that
may often just be partly automated or not automated
at all, the registration accuracy of which may not be
reviewed by standardized methods yet and that are
not used in clinical routine yet due to their complexity.
Although software-controlled retrospective image
fusion has considerably contributed to the acceptance
of multimodal imaging, particularly due to the successful application in the ﬁeld of neurological research,
the corresponding approaches could not really make
their way in clinical practice for applications outside
the brain. As PET and CT scanners were generally
accepted and largely available in the 1990s, the development engineers then tried to fuse the PET/CT hardware to provide a diagnostic instrument that might be
used for non-invasive anatomic-metabolic imaging in
the clinical routine and is efﬁcient for both therapy
planning and follow-up. Prospective image registration with fused hardware will become indispensable
in future, all the more since PET examinations with
highly speciﬁc tracers, whose PET images will no longer contain anatomical background information, will
presumably become increasingly important.
The PET/CT Prototype
The ﬁ rst PET/CT scanner was installed in May
1998 at the University of Pittsburgh Medical Center (USA) and was in operation until July 2001
(Fig. 2.7a). The PET/CT prototype still represents
the best possible integration of the hardware components today. The CT and PET components were
installed on the front and back side of a common
aluminium rack rotating with 30 rpm. The exterior
gantry was 168 cm high and 170 cm wide with a
tunnel length of 110 cm. The transversal opening of
the gantry had the same size as the opening of the
PET, i.e. 60 cm. The CT and PET components were
arranged at a distance of 60 cm from each other
along the axial scan direction [5].