Nuclear Medicine

V m

William D. Leslie

I. David Greenberg

a d e m e c u

LANDES

BIOSCIENCE

Nuclear

Medicine

William D. Leslie, MD, FRCPC, ABNM, MSc

University of Manitoba

Winnipeg, Manitoba, Canada

I. David Greenberg, MDCM, FRCPC, ABR, ABNM

University of Manitoba

Winnipeg, Manitoba, Canada

Nuclear Medicine

GEORGETOWN, TEXAS

U.S.A.

vademecum

L A N D E S

B I O S C I E N C E

VADEMECUM

Nuclear Medicine

LANDES BIOSCIENCE

Georgetown, Texas U.S.A.

Copyright ©2003 Landes Bioscience

All rights reserved.

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Landes Bioscience, 810 S. Church Street, Georgetown, Texas, U.S.A. 78626

Phone: 512/ 863 7762; FAX: 512/ 863 0081

ISBN: 1-57059-644-1

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ongoing research, equipment development, changes in governmental regulations and the

rapid accumulation of information relating to the biomedical sciences, the reader is urged to

carefully review and evaluate the information provided herein.

Contents

1. An Introduction to Nuclear Medicine ............................... 1

Brian Lentle and Anna Celler

Introduction ............................................................................................... 1

History ....................................................................................................... 1

Comparative Imaging and the Role of Nuclear Medicine ............................ 4

Radionuclide Production ............................................................................ 5

Radionuclide Decay .................................................................................... 8

Detection Systems .................................................................................... 10

Clinical Practice ........................................................................................ 13

A Perspective on the Future ...................................................................... 14

2. Radiation Effects and Safety ........................................... 16

Michael J. Chamberlain

Introduction ............................................................................................. 16

Radiation Dosimetry ................................................................................ 16

Radiation Effects and Carcinogenesis ........................................................ 19

Principles of Radiation Protection ............................................................. 24

Practical Aspects of Radiation Protection .................................................. 25

Frequently Asked Questions (FAQs) ......................................................... 28

3. Myocardial Perfusion Imaging ........................................ 31

Robert Corne and I. David Greenberg

Introduction ............................................................................................. 31

Physiologic and Technical Considerations ................................................. 31

Clinical Role in the Diagnosis of Coronary Artery Disease........................ 41

Clinical Role in Prognosis and Risk Stratification ..................................... 50

Clinical Role in Defining Myocardial Viability ......................................... 54

Frequently Asked Questions (FAQs) ......................................................... 55

4. Equilibrium Radionuclide Angiocardiography ............... 60

I. David Greenberg and Robert Corne

Introduction ............................................................................................. 60

Technical Considerations .......................................................................... 60

Clinical Applications ................................................................................. 64

Frequently Asked Questions (FAQ)s ......................................................... 72

5. Thromboembolic Disease ............................................... 75

Daniel F. Worsley and Philip S. Wells

Introduction ............................................................................................. 75

Technical Considerations in Lung Scanning ............................................. 75

Diagnosis of Acute Pulmonary Embolism ................................................. 83

Evaluation of Pulmonary Hypertension .................................................... 88

Frequently Asked Questions (FAQs) ......................................................... 88

6. Bone Densitometry ......................................................... 93

William D. Leslie and Bruce E. Roe

Pathophysiology of Bone Loss and Osteoporotic Fractures ........................ 93

Technical Aspects of Bone Densitometry .................................................. 97

Clinical Role of Bone Densitometry ....................................................... 104

Clinical Management of Osteoporosis .................................................... 110

Frequently Asked Questions (FAQs) ....................................................... 117

7. Skeletal Disorders ......................................................... 121

Leonard Rosenthall and Peter MacDonald

Introduction ........................................................................................... 121

Skeletal Anatomy and Physiology ........................................................... 121

Technical Considerations ........................................................................ 121

Trauma ................................................................................................... 122

Osteomyelitis .......................................................................................... 129

Vascular Disorders .................................................................................. 131

Joint Prostheses ....................................................................................... 134

Radionuclide Synovectomy ..................................................................... 137

Frequently Asked Questions (FAQs) ....................................................... 138

8. Skeletal Oncology ......................................................... 141

Leonard Rosenthall and Ralph Wong

Introduction ........................................................................................... 141

Primary Benign Bone Tumors ................................................................. 141

Primary Malignant Bone Tumors ............................................................ 149

Diagnosis and Follow-Up of Skeletal Metastases ..................................... 152

Frequently Asked Questions (FAQs) ....................................................... 159

9. Kidney .......................................................................... 163

Michael Hoskinson and Keevin Bernstein

Introduction ........................................................................................... 163

Renal Physiology..................................................................................... 163

Technical Considerations ........................................................................ 165

Clinical Role in Acute Renal Failure........................................................ 172

Clinical Role in Hydronephrosis ............................................................. 174

Clinical Role in Renovascular Hypertension ........................................... 179

Clinical Role in the Renal Transplant Patient .......................................... 188

Frequently Asked Questions (FAQs) ....................................................... 195

10. Gastrointestinal............................................................. 196

Peter Hollett and Ford Bursey

Introduction ........................................................................................... 196

Clinical Role in Esophageal Motility Disorders ....................................... 196

Clinical Role in Gastric Motility Disorders ............................................. 199

Clinical Role in the Localization of Gastrointestinal Bleeding................. 203

Clinical Role of Urea Breath Testing....................................................... 206

Frequently Asked Questions (FAQs) ....................................................... 208

11. Hepatobiliary Imaging .................................................. 211

Reinhard Kloiber and Gary R. May

Introduction ........................................................................................... 211

Radiopharmaceuticals ............................................................................. 211

Clinical Role in the Evaluation of the Biliary Tree ................................... 214

Clinical Role in the Characterization of Liver Masses .............................. 225

Frequently Asked Questions (FAQs) ....................................................... 231

12. Inflammatory Disorders ................................................ 233

William D. Leslie and Pierre Plourde

Pathophysiology of Inflammation ........................................................... 233

Technical Considerations ........................................................................ 234

Clinical Role: General Principles ............................................................. 244

Clinical Role in Fever of Unknown Origin (FUO).................................. 249

Clinical Role in Vascular Graft Infection ................................................. 252

Frequently Asked Questions (FAQ’s) ...................................................... 255

13. Thyroid Disorders......................................................... 260

Albert A. Driedger and Thomas J. McDonald

Thyroid Anatomy and Physiology........................................................... 260

Technical Aspects of Thyroid Scintigraphy .............................................. 262

Thyrotoxicosis ........................................................................................ 265

Hypothyroidism ..................................................................................... 269

Thyroid Nodules .................................................................................... 270

Thyroid Cancer ...................................................................................... 270

Frequently Asked Questions (FAQs) ....................................................... 275

14. Radionuclide Therapy of Thyroid Disorders ................ 276

Albert A. Driedger and Thomas J. McDonald

Introduction ........................................................................................... 276

Benign Thyroid Disorders ....................................................................... 276

Follicular Cell-Derived Thyroid Cancers ................................................. 282

Frequently Asked Questions (FAQs) ....................................................... 294

15. Tumor Imaging ............................................................. 297

A.J.B. McEwan

Introduction ........................................................................................... 297

Mechanisms of Radiopharmaceutocal Uptake ......................................... 297

Radiopharmaceuticals Used in Cancer Management ............................... 299

Contributions of Nuclear Medicine to Cancer Imaging .......................... 305

Radioisotope Therapy ............................................................................. 333

Frequently Asked Questions ................................................................... 336

16. Neuropsychiatric Disorders........................................... 340

Jean-Paul Soucy, Denis Lacroix and Catherine Kissel

Introduction ........................................................................................... 340

Regional Cerebral Perfusion .................................................................... 340

Energy Metabolism and Neurotransmission Studies ................................ 350

Cerebrospinal Fluid Assessment .............................................................. 353

Intracranial Mass Lesions ........................................................................ 358

Conclusions ............................................................................................ 360

Frequently Asked Questions (FAQs) ....................................................... 361

17. Pediatric Nuclear Medicine ........................................... 365

David Gilday

Introduction ........................................................................................... 365

Technical Considerations ........................................................................ 365

Clinical Role in the Assessment of Childhood

Musculoskeletal Disorders ....................................................................... 367

Clinical Role in Childhood Malignancies................................................ 370

Clinical Role in Neonatal Jaundice ......................................................... 373

Clinical Role in Rectal Bleeding.............................................................. 376

Clinical Role in Genitourinary Disorders ................................................ 378

Frequently Asked Questions (FAQ’s) ...................................................... 382

Appendix ....................................................................... 384

Half-lives and prinicipal emissions from common radionuclides ............. 384

Effective dose from common radiologic and nuclear

medicine procedures ............................................................................... 385

Index ............................................................................. 386

Editors

Contributors

William D. Leslie, MD, FRCPC, ABNM, MSc

Associate Professor of Medicine and Radiology

University of Manitoba

Winnipeg, Manitoba, Canada

Chapters 6 and 12

Keevin Bernstein

Associate Professor of Medicine

University of Manitoba

Winnipeg, Manitoba, Canada

Chapter 9

Ford Bursey

Associate Professor of Medicine

Memorial University of Newfoundland

St. John’s, Newfoundland, Canada

Chapter 10

Anna Celler

Medical Imaging Research Group

Nuclear Medicine

University of British Columbia

Vancouver, British Columbia, Canada

Chapter 1

Michael J. Chamberlain

Professor of Radiology

University of Ottowa

Ottawa, Ontario, Canada

Chapter 2

Robert Corne

Associate Professor of Medicine

and Radiology

University of Manitoba

Winnipeg, Manitoba, Canada

Chapters 3 and 4

Albert A. Driedger

Professor of Nuclear Medicine

and Oncology

University of Western Ontario

London, Ontario, Canada

Chapters 13 and 14

David Gilday

Professor of Radiology

University of Toronto

Chapter 17

Peter Hollett

Professor of Radiology

Memorial University of Newfoundland

St. John’s, Newfoundland, Canada

Chapter 10

Michael Hoskinson

Nuclear Medicine

University of Alberta

Edmonton, Alberta, Canada

Chapter 9

Catherine Kissel

Associate Professor of Medicine

Université de Montreal

Montreal, Quebec, Canada

Chapter 16

I. David Greenberg, MDCM, FRCPC, ABR, ABNM

Associate Professor of Radiology

University of Manitoba

Winnipeg, Manitoba, Canada

Chapters 3 and 4

Reinhard Kloiber

Clinical Professor of Radiology

University of Calgary

Calgary, Alberta, Canada

Chapter 11

Denis Lacroix

Assistant Professor of Psychiatry

Université de Montreal

Montreal, Quebec, Canada

Chapter 16

Brian Lentle

Emeritus Professor

Radiology

University of British Columbia

Vancouver, British Columbia, Canada

Chapter 1

Peter MacDonald

Associate Professor of Orthopedic Surgery

University of Manitoba

Winnipeg, Manitoba, Canada

Chapter 7

Gary R. May

Clinical Associate Professor of Medicine

University of Calgary

Calgary, Alberta, Canada

Chapter 11

Thomas J. McDonald

Professor of Medicine

University of Western Ontario

London, Ontario, Canada

Chapters 13 and 14

A. J. B. McEwan

Professor, Department of Oncology

University of Alberta

Edmonton, Alberta, Canada

Chapter 15

Pierre Plourde

Associate Professor of Medical

Microbiology

University of Manitoba

Winnipeg, Manitoba, Canada

Chapter 12

Bruce E. Roe

Associate Professor of Medicine

University of Manitoba

Winnipeg, Manitoba, Canada

Chapter 6

Leonard Rosenthall

Professor of Radiology

McGill University

Montreal, Quebec, Canada

Chapter 7, 8

Jean-Paul Soucy

Professor of Nuclear Medicine

University of Ottowa

Ottawa, Ontario, Canada

Chapter 16

Philip S. Wells

Medicine

University of Ottowa

Ottawa, Ontario, Canada

Chapter 5

Ralph Wong

Assistant Professor of Hematology

and Oncology

University of Manitoba

Winnipeg, Manitoba, Canada

Chapter 8

Daniel F. Worsley

Assistant Professor of Radiology

University of British Columbia

Vancouver, BC, Canada

Chapter 5

“The expert at anything was once a beginner.”

-Hayes

In an era of spectacular medical advances, it is easy to become immune to

the announcement of new “breakthroughs”. This in no way lessens the

remarkable achievements of diagnostic imaging over the last few years in

which the field of Nuclear Medicine has shared. To the outsider the spe￾cialty of Nuclear Medicine can appear confusing and esoteric since it oper￾ates in a world of invisible radioactive emissions, nuclear decay charts and

obscure elements. In reality, the distance from the cyclotron to the bedside

is a short one and this young specialty has matured and been integrated into

many aspects of patient care. In fact, the array of agents and techniques that

can be used for diagnosis and therapy is so broad that only the most com￾monly used and widely available can be covered in this handbook. The

material covers traditional aspects of Nuclear Medicine as well as the newest

advances in the field. In this handbook, the role of Nuclear Medicine tech￾niques in diagnosis and treatment is presented in conjunction with the

essential elements of radiopharmacology, instrumentation and radiation pro￾tection. This handbook is not intended to be as comprehensive as a nuclear

medicine textbook but will provide a more thorough presentation of the

specialty than is afforded when it shares the stage with other diagnostic im￾aging modalities. It was designed to be a practical and accessible handbook

for trainees in both imaging and clinical sciences.

Junior physicians and trainees will learn how to take this imaging science

and apply it to the real-life problems encountered in clinical medicine. Most

clinical chapters are jointly authored by a Nuclear Medicine specialist and

an experienced clinician, an approach that is unique among Nuclear Medicine

texts. The individuals selected are clinical practitioners, not ivory tower

researchers, which gives them a firsthand appreciation of the challenges of

clinical medicine. For readers that find that they have a thirst to learn more

about Nuclear Medicine, this handbook will serve as a guide to the specialty

and to more comprehensive textbooks listed below. Perhaps others will be

stimulated to consider Nuclear Medicine as an exciting career opportunity.

Certainly the future is bright for a specialty that has come so far in so short

a time.

William D. Leslie

I. David Greenberg

Preface

Comprehensive References

1. Harbert JC, Eckelman WC, Neumann RD, eds. Nuclear Medicine Diagnosis and Therapy.

New York: Thieme Medical Publishers, Inc., 1996.

2. Wagner HN, Szabo Z, Buchanan JW, eds. Principles of Nuclear Medicine. Second Ed.

Philadelphia: W.B. Saunders Company, 1995.

3. Murray ICP, Ell PJ, Strauss HW, eds. Nuclear Medicine in Clinical Diagnosis and

Treatment. Second Ed. Edinburgh: Churchill Livingstone, 1994.

4. Sandler MP, Patton JA, Coleman RE, Gottschalk A, Wachers FJT, Hoffer P. Diagnostic

Nuclear Medicine. Third Ed. Baltimore: Williams & Wilkins, 1996.

5. Henkin RE, Boles MA, Dillehay GL, Halama JR, Karesh SM, Wagner RH et al, eds.

Nuclear Medicine. St. Louis: Mosby, 1996.

CHAPTER 1

CHAPTER 1

An Introduction to Nuclear Medicine

Brian Lentle and Anna Celler

Introduction

Nuclear medicine is defined as that medical specialty concerned with the use of

unsealed sources of radiation in the diagnosis and treatment of disease.

Disease usually begins as disordered function. While an exception to this might

be trauma, many accidents also may be due to altered behavior. Thus altered function

often anticipates structural or morphological change by months or even years. Other

techniques used in diagnostic imaging (e.g., radiography, computed tomography

[CT] and magnetic resonance imaging [MRI]) largely focus on the identification of

disordered structure although with the emergence of advanced MRI methods this is

beginning to change. The power of nuclear medicine in clinical diagnosis rests with

its ability to detect altered function with great sensitivity. For this reason nuclear

medicine has contributed not only to clinical diagnosis but, to a degree unmatched

by other imaging methods, to an understanding of disease mechanisms.

History

Modern clinical radiology began with one seminal event, namely Wilhelm

Röntgen’s discovery of X-rays in November 1895. Nuclear medicine had not one

but many parents. Bequerel discovered radioactivity in early 1896. Both of these

discoveries were serendipitous. Röntgen, a German physicist, was experimenting in

his laboratory in Würzburg. While working with cathode-ray tubes in a darkened

room he noticed, by chance, fluorescence at a distance. He went on to discover that

this fluorescence was caused by penetrating, but hitherto undiscovered, radiations

from the cathode-ray tubes. He called these X-rays, using the algebraic symbol “x”

for an unknown. Before the end of that year Röntgen had used the new rays to

image the internal structure of the body—the bones of his wife’s hand.

Subsequently Henri Becquerel (Fig. 1) discovered natural radioactivity in February

1896. The story has it that he placed lumps of pitchblende on sealed photographic

film in sunlight, intent on finding out if the rays of the sun induced any penetrating

fluorescence in the mineral. By chance, on developing the film after a cloudy day he

was surprised to find as much blackening of the photographic emulsion as had

occurred in bright sunlight. He realized that the pitchblende itself was a source of

the energetic rays.

Later Mme. (Dr.) Marie and Dr. Pierre Curie working in Paris described natural

radioactivity and discovered radium. Subsequently Mme. (Dr.) Irène Curie was to

observe the artificial induction of radioactivity. Rutherford, a British-educated, New

Zealand physicist working at McGill University in Montreal went on to discover the

structure of the atom. All won Nobel prizes—Becquerel and Curie jointly.

Nuclear Medicine, edited by William D. Leslie and I. David Greenberg.

©2003 Landes Bioscience.

2 Nuclear Medicine

1

Another important insight came when a Hungarian scientist—George de Hevesy

(a former student of Rutherford)—first used the tracer principle (Fig. 2). He

experimented with a plant having its roots in a water bath containing a radioactive

isotope of lead. Hevesy was able to follow the rate of passage of the tracer through

Figure 1. A stamp commemorating Becquerel’s discovery of radioactivity for which

he received a Nobel Prize.

An Introduction to Nuclear Medicine

3

1

the stem of the plant with an instrument capable of detecting and measuring radio￾activity. This use of radioactive atoms, present in minute amounts but acting as a

marker of other, non-radioactive atoms came to be called the tracer principle. It

only required that Hevesy’s insight be translated to people instead of plants, and for

the tracer to be administered by injection instead of through a plant’s root system,

for the power of nuclear medicine to become clear.

Figure 2. A stamp celebrating the anniversary of the Nobel Prize awarded to de

Hevesy for the discovery of the tracer principle.

4 Nuclear Medicine

1

Without a capacity to image the distribution of radiotracers in the body, how￾ever, there might be little to remark upon concerning the importance of nuclear

medicine. Dr. Benedict Cassen developed the first rectilinear scanner to image trac￾ers by virtue of the gamma rays they emit. This was followed by the development of

the gamma camera, able to image both static and changing distributions of radioac￾tive tracers in the body, by Dr. Hal Anger. He, Dr. David Kuhl and others went on

to develop the concept of tomographic sectional imaging in nuclear medicine.

Nuclear medicine, while beginning in the late nineteenth century, gained mo￾mentum through the twentieth. Medicine in the twenty-first century will continue

to be fundamentally changed by the insights it provides.

Comparative imaging and the Role of Nuclear Medicine

Classical radiology had been rooted in studies of structure. That is changing as

physiological images and sometimes measurements are being made with CT and,

especially, functional MRI and spectroscopy. Nevertheless, from first principles it

will be difficult to match the power of nuclear medicine in, for example, detecting

receptor binding.

Another decisive advantage of nuclear medicine is its capacity to be used in whole

body imaging. The idea of whole body MRI “screening” has been mooted but its

value is speculative and it would be expensive. In contrast, nuclear medicine body

imaging is unsurpassed in the search for disease not causing local symptoms, such as

metastatic tumor spread or occult infections.

As we have seen, the first technique which allowed us to “see” the inside of the

human body was X-ray imaging. Very soon, however, it was followed by other

techniques such as nuclear medicine, ultrasound (US), CT and, more recently, MRI.

In order to realize the possibilities and limitations of each technique and to better

understand their place in the diagnostic process it is important to consider the physical

process that each modality employs. In differing degrees most methods are capable

of anatomical and functional imaging and almost all techniques can examine both

when special contrast agents or other modifications are used.

Attenuation of electromagnetic radiation (which depends on the electron density

of the material) is the physical principle used in X-ray imaging or CT. The resulting

images represent differences in transmission of the X-rays (a form of electromagnetic

radiation) or, indirectly, differences in their attenuation by tissues and, thereby, the

anatomy of the subject. If a special contrast agent is introduced any images made

will reflect the distribution of this agent and such images may depict a particular

organ’s function. Similarly, from the physical point of view, US measures sound

wave transmission and reflection in the body and MRI is sensitive to body water

contents because hydrogen atoms in water molecules are responsible for the majority

of the magnetic signal detected by MRI. Again, in both situations, the images display

more particularly the anatomy, not function. Recently developed functional MRI

(fMRI), however, is sensitive to the flow of the blood in the body while doppler US

can additionally measure the movement, for example of blood, within an imaged

organ.

Nuclear medicine, by contrast, is a technique that is intrinsically functional because

it measures radiation emitted by a tracer which has been introduced into a patient’s

body, usually by injection, and for which the location and concentration are directly