Bone Scanning in Clinical Practice

Edited by Ignac Fogelman

With 217 Figures

Springer-Verlag London Berlin Heidelberg New York Paris Tokyo

Ignac Fogelman BSc, MD, MRCP Consultant Physician, Department of Nuclear Medicine, Guy's Hospital, St. Thomas Street, London SEI 9RT.

ISBN-13: 978-1-4471-1409-3 e-ISBN-13: 978-1-4471-1407-9 DOl: 10.1007/978-1-4471-1407-9

Library of Congress Cataloging-in-Publication Data Bone scanning in clinical practice. Includes bibliographies and index. 1. Bones-Diseases-Diagnosis. 2. Radioisotope scanning. I. Fogelman. Ignac. 1948- . [DNLM: 1. Bone and Bones-radionuclide imaging. 2. Tomography. Emission Computed. WE 225 B7128] RC930.5.B65 1986 616.7'107575 86-13824

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© Springer-Verlag Berlin Heidelberg 1987

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This book is dedicated to Coral. Gayle and Richard

Preface

The most frequently requested investigation in any nuclear medicine department remains the technetium-99m (99mTc)-labelled diphosphonate bone scan. Despite rapid advances in all imaging modalities. there has been no serious challenge to the role of bone scanning in the evaluation of the skeleton. The main reason for this is the exquisite sensitivity of the bone scan for lesion detection. combined with clear visualisation of the whole skeleton. In recent years several new diphosphonate agents have become available with claims for superior imaging of the skeleton. Essentially. they all have higher affinity for bone. thus allowing the normal skeleton to be visualised all the more clearly. However. as will be dis­cussed. this may occur at some cost to the principal role of bone scanning. lesion detection.

The major strength of nuclear medicine is its ability to provide functional and physiological information. With bone scanning this leads to high sensitivity for focal disease if there has been any disturbance of skeletal metabolism. However. in many other clinical situations. and particularly in metabolic bone disease. more generalised alteration in skeletal turnover may occur. and quantitation of diphosphonate uptake by the skeleton can provide valuable clinical information.

The use of single photon emission tomography (SPECT) for imaging the skeleton is increas­ingly being shown to be of value in problematic cases where results from planar images may be equivocal. Measurement of bone mineral content by single and dual photon absorp­tiometry is currently of considerable interest as physicians and the public alike become more aware of the major health issues relating to osteoporosis. These are some of the newer aspects of the use of radioisotopes in the investigation of bone disease which have been included in the present text.

In Bone Scanning in Clinical Practice a group of experts from the UK and North America have joined forces to bring together their experience with "bone scanning". Topics covered. in addition to the aforementioned. include the history of bone scanning. mechanisms of uptake of diphosphonate in bone. the normal bone scan. and the role of bone scanning in clinical practice. The aim of this book is to provide a source of reference relating to bone scan imaging for all those who are interested in the skeleton. While I believe the information presented will be of value to those in nuclear medicine. I hope that others in fields such as endocrinology. rheumatology. orthopaedics and oncology will find much of relevance to their clinical practice.

London. 1986 Ignac Fogelman

Contents

Introduction I. Fogelman . ............................................................. xvii

1 The Bone Scan-Historical Aspects 1. Fogelman. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Introduction ............................................................ 1 Bone Scanning with Strontium-8 5 and Fluorine-I 8 ............................ 2 Introduction of 99mTc Phosphate ............................................ 3 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2 99mTc Diphosphonate Uptake Mechanisms on Bone M. D. Francis and I. Fogelman ............................................... 7

Introduction ........................................................... . Reduction of 99mTc04 - ................................................... . Calcium Content of Tissues ................................................ .

7 7 9

Diphosphonate Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 10 Diphosphonate Chain Length. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 11 Mechanism of 99mTc Diphosphonate Adsorption on Bone. . . . . . . . . . . . . . . . . . . . . . . .. 14 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 16

3 The Normal Bone Scan M. V. Merrick. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 19

Introduction ............................................................ 19 Technical Considerations .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 19

Radiopharmaceutical .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 19 Radiopharmaceutical Quality ............................................ 19 Timing of Images. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20 Equipment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20 Count Density. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20 Radiographic Technique. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 22 Patient Factors ........................................................ 23 Digital Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 23

Normal Appearances ..................................................... 24 Head ................................................................ 24

x Contents

Neck ................................................................. 25 Thorax ............................................................... 25 Spine................................................................ 27 Pelvis... . . . . . . . .. . .. . .. . . . .. . . .. . .. . . . . ... . . . . .. . . . .. ..... . . . .. . . . ... 27 Limbs.. . . . . . . . . .. . .. .. . . . .. . .. . . . . . . .. .. . . . .. . . . . .. . . .. . . . . .... . .. . .. 27

Conclusion ............................................................. 29 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 29

4 99mTc Diphosponate Bone-scanning Agents 1. Fogelman. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 31

Introduction ............................................................ 31 Properties Required of a Bone-scanning Agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 31 99mTc Diphosphonate Bone-scanning Agents .................................. 32

99mTc Hydroxyethylidene Diphosphonate (HEDP) . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 32 99mTc Methylene Diphosphonate (MDP) .................................... 34 99mTc Hydroxymethylene Diphosphonate (HMDP) . . . . . . . . . . . . . . . . . . . . . . . . . . .. 34 99mTc Dicarboxypropane Diphosphonate (DPD) .............................. 35

Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 35 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 39

5 Bone Scanning in Metastatic Disease J. H. McKillop . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 41 Introduction ............................................................ 41 Appearances of Metastases on the Bone Scan ..... . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 41 Significance of Bone Scan Abnormalities in the Cancer Patient. . . . . . . . . . . . . . . . . . .. 43

Effects of Surgical Procedures on the Bone Scan .............................. 45 Indications for Bone Scanning in Extraosseous Malignancy. . . . . . . . . . . . . . . . . . . . . .. 45

Pretreatment Staging and Routine Follow-up After Primary Therapy. . . . . . . . . . . .. 45 Investigation of the Patient with a Clinical Suspicion of Bone Metastases .... . . . . .. 46 Assessment of Response to Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 46

Bone Scanning in Individual Tumours ....................................... 48 Breast Cancer ......................................................... 48 Lung Cancer. . .. . . . . . . . . .. . . . .. . . . .. . . . . . . . . . . . .. . . . . . . . . .. . . . . . . .. . .. 52 Prostatic Cancer ....................................................... 53 Urinary Tract Cancer ................................................... 54 Gynaecological Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 54 Alimentary Cancer ......... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 55 Melanoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 55 Thyroid Cancer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 56 Nervous System Tumours ............................................... 56 Head and Neck Tumours ................................................ 56

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 57

6 The Bone Scan in Primary Bone Tumours and Marrow Disorders J. H. McKillop . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 61

Introduction ............................................................ 61 Primary Bone Tumours ................................................... 61

Isotope Bone Scanning in the Differential Diagnosis of a Primary Bone Tumour. . . .. 61

Contents xi

Osteogenic Sarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 63 Paget's Sarcoma .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 65 Ewing's Sarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 65 Chondrosarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 66 Osteoid Osteoma ................ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 66 Osteoclastoma and Bone Cysts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 67 Miscellaneous Bone Lesions .............................................. 68

Marrow Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 69 Multiple Myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 69 Histiocytosis .......................................................... 69 Mastocytosis .......................................................... 69 Lymphomas and Leukaemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 69

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 70

7 The Bone Scan in Metabolic Bone Disease 1. Fogelman. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 73

Introduction ............................................................ 73 Why is the Bone Scan Abnormal? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 73 Bone Scan Appearances .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 74

Renal Osteodystrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 77 Primary Hyperparathyroidism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 78 Osteomalacia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 79 Osteoporosis .......................................................... 81 Reflex Sympathetic Dystrophy Syndrome and Migratory Osteolysis .............. 83 Miscellaneous Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 83

References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 86

8 The Bone Scan in Paget's Disease I. Fogelman. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 89

Introduction ............................................................ 89 Bone Scan Appearances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 90 Differential Diagnosis ..................................................... 90 Comparison ofBone Scanning and Radiography ............................... 93 Anatomical Distribution of Lesions .......................................... 99 Correlation of Symptoms with Sites of Activity on Bone Scan ..................... 99 Evaluation of Treatment ................................................... 100 Clinical Use ofBone Scanning .............................................. 102 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

9 The Role of Bone Scanning, Gallium and Indium Imaging in Infection K. Mldo, D. A. Navarro. G. M. Segall and 1. R. McDougall . .......................... 105

Introduction ............................................................ 105 Radiopharmaceuticals and Methods ......................................... 10 5 Acute Osteomyelitis ...................................................... 107

Pathology ............................................................ 107 Animal Studies ........................................................ 107 Patient Studies ........................................................ 107

xii Contents

Osteomyelitis in Diabetic Patients ......................................... 109 Summary of Evidence for Application of Bone Scanning ....................... 109 Role of Radiolabelled Leucocytes in Diagnosis of Acute Osteomyelitis ........ . . . .. 110 Role of 67Ga in Diagnosis of Acute Osteomyelitis .............................. 111

Diagnosis of Septic Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . III Summary ............................................................. 114

Diagnosis ofInfected Prosthetic Joint ......................................... 114 Summary ............................................................. 116

Chronic Osteomyelitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116 Role of Single Photon Emission Computed Tomography of Skeleton ................ 118 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118

10 The Bone Scan in Traumatic and Sports Injuries P. Matin ................................................................ 121

Introduction ............................................................ 121 Stress Fractures and Periosteal Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 Shin Splints and Enthesopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 5 Covert Fractures ........................................... . . . . . . . . . . . . . . 126 Traumatic Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 127 Delayed Union and Non-union .............................................. 128 Radionuclide Arthroscopy ................................................. 130 Detection of Skeletal Muscle Injury .......................................... 130 References .............................................................. 132

11 The Bone Scan in Arthritis L. Rosenthall . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

Introduction ............................................................ 133 Synovitis ............................................................... 134

Juvenile Rheumatoid Arthritis ............................................ 13 7 Response to Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 Quantitative Joint Imaging ............................................... 138 Value of a Negative Joint Scan Result ...................................... 139

Sacroiliitis .............................................................. 140 Ankylosing Spondylitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142

Osteoarthritis ........................................................... 142 Transient (Toxic) Synovitis of the Hip ........................................ 144 Reflex Sympathetic Dystrophy Syndrome ..................................... 145 Regional Migratory Osteoporosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 146 Trochanteric Bursitis ..................................................... 147 Plantar Fasciitis (Calcaneal Periostitis) ....................................... 148 References .............................................................. 149

12 The Bone Scan in Avascular Necrosis , 1. Rosenthall . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 151

Introduction ............................................................ 151 Steroid-induced Osteonecrosis ............... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 Drug-induced Osteonecrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 Idiopathic Osteonecrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 155

Contents xiii

Osteonecrosis Following Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157 Caisson Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 161 Legg-Perthes Disease ..................................................... 162 Slipped Capital Femoral Epiphysis ........................................... 163 Sickle Cell Disease .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 163 Gaucher's Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Radiation Osteonecrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165 Frostbite . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Electrical Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 167 Juvenile Kyphosis ........................................................ 170 Bone Graft Revascularisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 172

13 Orthopaedic Applications of Single Photon Emission Computed Tomographic Bone Scanning B. D. Collier ............................................................. 175

Introduction ............................................................ 175 Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 Techniques ............................................................. 176 Clinical Applications ...................................................... 177

Lumbar Spine ......................................................... 177 Hips ................................................................. 179 Knees ................................................................ 181 Temporomandibular Joints. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185

Summary and Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186

14 The Bone Scan in Paediatrics 1. Gordon and A. M. Peters . ................................................. 189

Introduction ............................................................ 189 Radioisotopes ........................................................... 189

99mTc_MDP ............................................................ 189 99mTc Colloid ....... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193 lllIn WBC ............................................................ 193 67GaCitrate ........................................................... 193

Clinical Indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 Hip .................................................................. 198 Symptoms in Other Joints ................................................ 199 Localised Bone Pain .................................................... 201 Generalised Bone Pain in Infancy .......................................... 204 Generalised Bone Pain in Childhood. Including Malignancy .................... 205 The Neonate/Infant .................................................... 207

References .............................................................. 209

15 Soft Tissue Uptake of Bone Agents H. W. Gray .............................................................. 211

Introduction ............................................................ 211 Pathophysiology ......................................................... 211

xiv Contents

Bone Scan Appearances ................................................... 212 Incidental Findings ..................................................... 212 Diagnostic Applications ................................................. 226 Artefacts ............................................................. 228

References .............................................................. 231

16 Quantitative 99mTc Diphosphonate Uptake Measurements M. L. Smith ............................................................. 237

Introduction ............................................................ 237 Factors Influencing 99mTc Diphosphonate Uptake Measurements .................. 237

Radiopharmaceutical ................................................... 237 Timing of Studies ...................................................... 238 Renal Function ........................................................ 239 Age and Sex ........................................................... 239 Control Population ..................................................... 239 Data Processing .................................... -.................... 239

Methods of Quantitation ................................................... 240 Local Measurements .................................................... 240 Whole-body Measurements .............................................. 243

Summary ............................................................... 246 References .............................................................. 247

17 Measurements of Bone Mineral by Photon Absorptiometry H. W. Wahner ........................................................... 249

Introduction ............................................................ 249 Clinical Relevance ofBone Mass ............................................. 249 Review of Different Techniques for Measuring Bone Mass ........................ 250 Single Photon Absorptiometry for the Evaluation of Cortical Bone in the

Appendicular Skeleton .................................................. 250 Dual Photon Absorptiometry for the Evaluation of Mineral in the Spinal Bone ........ 251 Quantitative Computed Tomography ........................................ 253 Clinical Applications of Photon Absorptiometry Methods ........................ 254 References .............................................................. 256

Subject Index ............................................................ 257

Contributors

B. D. Collier MD Director. Nuclear Medicine. Medical College of Wisconsin. Milwaukee. Wisconsin. USA.

1. Fogelman BSc. MD. MRCP Consultant Physician. Department of Nuclear Medicine. Guy's Hospital. London. England.

M. D. Francis BA. MA. PhD Senior Scientist. Norwich Eaton Pharmaceuticals. A Procter and Gamble Company. Norwich. New York. USA.

1. Gordon FRCR Senior Lecturer in Diagnostic Radiology. Institute of Child Health. and Consultant Radiologist. Department of Paediatric Radiology. Hospital for Sick Children. London. England.

H. W. Gray MD. FRCP Consultant Physician. University Department of Medicine. Royal Infirmary. Glasgow. Scotland.

P. Matin MD. FACNP Associate Clinical Professor. University of California. Davis. and Chairman. Department of Nuclear Medicine. Roseville Community Hospital. Roseville. California. USA.

1. R. McDougall MB. ChB. PhD. FRCP. FACP Professor of Radiology and Medicine. Division of Nuclear Medicine. Stanford University School of Medicine. Stanford. California. USA.

J. H. McKillop MB ChB. PhD. MRCP Senior Lecturer and Consultant Physician. University Department of Medicine. Royal Infirmary. Glasgow. Scotland.

xvi Contributors

M. V. Merrick MSc. MRCP. FRCR Consultant in Nuclear Medicine and Senior Lecturer in Medicine and Radiology. Western General Hospital. Edinburgh. Scotland.

K.MidoMD Resident in Nuclear Medicine. Division of Nuclear Medicine. Stanford University School of Medicine. Stanford. California. USA.

D. A. Navarro MD Resident in Nuclear Medicine. Division of Nuclear Medicine. Stanford University School of Medicine. Stanford. California. USA.

A. M. Peters BSc. MD. MRCPath Honorary Consultant Radiologist. Department of Paediatric Radiology. Hospital for Sick Children. and Department of Diagnostic Radiology. Royal Postgraduate Medical School. London. England.

L. Rosenthall MD Professor of Radiology. McGill University. and Director. Division of Nuclear Medicine. The Montreal General Hospital. Montreal. Quebec. Canada.

G. M. Segall MD Resident in Nuclear Medicine. Division of Nuclear Medicine. Stanford University School of Medicine. Stanford. California. USA.

M. L. Smith BSc. MB ChB. MRCP Senior Registrar in Nuclear Medicine. Department of Nuclear Medicine. Addenbrooke's Hospital. Cambridge. England.

H. W. Wahner MD. MS Professor of Laboratory Medicine. Mayo Medical School. and Consultant in Nuclear Medicine. Mayo Clinic. Rochester. Minnesota. USA.

Introduction

1. Fogelman

It is generally accepted that the bone scan is more sensitive than radiography in detecting skeletal disease; however. it is important to be aware that each of these investigations asses­ses different parameters in relation to bone. X-ray absorption reflects bone mineral content and shows the net result of bone destruction and repair. The bone scan. however. is a study of function depending upon osteoblastic activity and. to a lesser extent. skeletal vascularity for uptake of tracer (Davis and Jones 1976). In the context of disease the scan indicates the dynamic response of bone to whatever insult is present. be it traumatic. inflammatory or neoplastic.

If involvement of the skeleton by malignancy is chosen as a specific example of disease. then when tumour cells invade bone they produce two basic effects: bone destruction. usu­ally mediated via osteoclasts. and an osteoblastic reaction. which represents attempts by the surrounding bone to repair the destructive effects (Milch and Changus 1956). Radio­graphs demonstrate both processes; bone destruction is seen as radiolucencies (osteolytic areas) and bone repair as radiodensities (osteosclerotic areas). Bone destruction. however. must be advanced before an abnormality is seen on the radiograph. and it has been suggested that a lesion in trabecular bone must be greater than 1-1.5 cm in diameter. with loss of approximately 50% of bone mineral before radiolucencies will be apparent on a conventional radiograph (Edelstyn et al. 1967). Early in bone repair. insufficient mineral has been laid down to be visualised radiographically as radiodensities. For these reasons the radiograph is normal during the early phase of tumour involvement. and several studies have confirmed that histologically proven metastases may not be detected by radiography (Borak 1942; Shackman and Harrison 1948). The bone scan is based on an entirely different principle. Tracer uptake is not directly dependent on bone destruction. but reflects the functional reac­tion of the bone to tumour invasion. There is an increase in new bone formation with increased skeletal blood flow following tumour invasion and this is demonstrated by high uptake of a bone-seeking radiopharmaceutical. It is important to note that the increased concentration of tracer is not due to or directly dependent on the metabolism of the tumour cells themselves. but is directly related to the local changes in bone metabolism consequent upon tumour invasion.

Thus. early in bone invasion by tumour. a positive bone scan may be associated with normal radiography. As the tumour progresses. the bone destruction it causes will become visible on the radiograph as an osteolytic lesion. In these circumstances bone reaction is considerable. and the bone scan result is also strongly positive. If the tumour does not prog­ress. calcium will be laid down during the healing process in such quantities that sclerotic areas will be visible on the radiograph. At this stage the results of both investigations are positive. Eventually. if the lesion heals completely. there will be extensive calcification pro­ducing a dense appearance on the radiograph. At this stage the bone scan may appear normal.

As the bone scan depends on the metabolic reaction of the bone. it is clear that if there is little or no bone reaction to tumour invasion. the scan may be normal or near normal

xviii Introduction

despite radiographic evidence of bone destruction. This occurs infrequently but may be found in some cases of myeloma (Leonard et al. 1981) and, rarely, with rapidly growing anaplastic carcinoma or, conversely, in cases of indolent tumours such as thyroid cancer (Charkes 1970). If bone destruction is extensive (Goergen et al. 1974), or if bone metabolism is modi­fied by radiotherapy (Cox 1974), a "cold" area may be seen, corresponding to the area of diminished bone activity.

Similarly, in the metabolic bone disorders considerable alteration in bone calcium may occur without detectable change on the radiograph. If there is net balance between bone formation and bone resorption, albeit if both are increased, then these changes may theoreti­cally never be revealed by radiography (De Nardo 1966). Radioactive tracer techniques may circumvent these difficulties since they depend only upon increased bone turnover regardless of the net calcium balance. It is clear, however, that the techniques of skeletal radiography and scintigraphy are in many instances complementary, and maximum diagnostic informa­tion can often be obtained by performing both studies.

References

Borak J (1942) Relationship between the clinical and roentgenological findings in bone metastases. Surg Gynecol Obstet 75: 599-604

Charkes NO (1970) Bone scanning: principles. technique and interpretation. Radiol Clin North Am 8: 259-270 Cox PH (1974) Abnonnalities in skeletal uptake of 99mTc polyphosphate complexes in areas of bone associated

with tissues which have been subjected to radiation therapy. Br J Radiol47: 851-856 Davis AG. Jones AG (1976) Comparison of 99mTc-Iabeled phosphate and phosphonate agents for skeletal imaging.

Semin Nucl Med 6: 19-31 De Nardo GL. Volpe JA. Captain MC (1966) Detection of bone lesions with the strontium-85 scintiscan. J Nucl

Med 7: 219-236 Edelstyn GA. Gillespie PJ. Grebell FS (1967) The radiological demonstration of osseous metastases: experimental

observations. Clin Radiol 18: 158-162 Georgen T. Halpern S. Alazraki N. Heath V. Taketa R. Ashburn W (1974) The "photon defficient" area: a new

concept in bone scanning. J Nucl Med 15: 495 (abstract) Leonard RCF. Owen JP. Proctor SJ. Hamilton PJ (1981) Multiple myeloma: radiology or bone scanning? Clin Radiol

32:291-295 Milch RA. Changus GW (1956) Response of bone to tumour invasion. Cancer 9: 340-351 Shackman R. Harrison CV (1948) Occult bone metastases. Br J Surg 35: 385-389