Keywords: Bone scintigraphy Tumour imaging Pro- [630533]

Keywords: Bone scintigraphy – Tumour imaging – Pro-
cedure guidelines – Indications
Eur J Nucl Med Mol Imaging (2003) 30:BP99–BP106
DOI 10.1007/s00259-003-1347-2Aim
The purpose of this document is to provide general infor-
mation about bone scintigraphy in oncology. Theseguidelines describe procedures currently in routine clini-cal use but should not be interpreted as excluding alterna-tive procedures also employed to obtain equivalent data.It must be remembered that the resources and facilitiesavailable to care for patients may vary from one countryto another and from one medical institution to another.This document has been prepared primarily for nuclearmedicine physicians and is intended to offer assistance inoptimising the diagnostic information that can currentlybe obtained from bone scintigraphy. The correspondingguidelines from the Society of Nuclear Medicine (SNM)have been taken into consideration, reviewed and partial-ly integrated into this text. In addition, the literature onthis topic has been reviewed and discussed by an interna-tional group of distinguished experts.
Background
The radionuclide bone scan is the cornerstone of skeletal
nuclear medicine imaging. Bone scintigraphy is a highlysensitive method for demonstrating disease in bone, of-ten permitting earlier diagnosis or demonstrating morelesions than are found by conventional radiologicalmethods. Primary tumours of bone are relatively rare inadults whereas metastases to bone are very frequent(breast, prostate, lung, head and neck cancer, etc.). Phos-phate analogues can be labelled with
99mTc and are usedUnder the auspices of the Oncology Committee of the European
Association of Nuclear Medicine.
Referees: Bardies M. (INSERM U463, Nantes Cedex, France),Bares R. (Department of Nuclear Medicine, Eberhard-Karls Uni-versity, Tübingen, Germany), Bauer R. (Klinik fur Nucklear-medizin, University of Giessen, Germany), Biersack H.J. (Klinikund Poliklinik fur Nuklearmedizin, University of Bonn, Germa-ny), Coakley A.J. (Department of Nuclear Medicine, Kent andCanterbury Hospital, Canterbury Kent, UK), Flux G. (Departmentof Physics, Royal Marsden Hospital, London, UK), Fogelman I.(Department of Nuclear Medicine, Guys Hospital, London, UK),Lassmann M. (Klinik für Nuklearmedizin, University of Würz-burg, Germany), Mather S.J. (Department of Nuclear Medicine,St. Bartholomew’s Hospital, London, UK), Merrick M.V . (Depart-ment of Nuclear Medicine, Western General Hospital, Edinburgh,UK), Savelli G. (Division of Nuclear Medicine, Istituto Nazionaleper lo Studio e la Cura dei Turmo, Milano, Italy), Tarolo G.L. (Di-vision of Nuclear Medicine, Ospedale San Paolo, Milano, Italy),van Rick P.P. (Department of Nuclear Medicine, AcademischZiekenhuis, Utrecht, The Netherlands).
Emilio Bombardieri ( ✉)
Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italye-mail: [anonimizat] scintigraphy: procedure guidelines for tumour imaging
Emilio Bombardieri1, Cumali Aktolun2, Richard P. Baum3, Angelika Bishof-Delaloye4, John Buscombe5,
Jean François Chatal6, Lorenzo Maffioli7, Roy Moncayo8, Luc Mortelmans9, Sven N. Reske10
1 Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy
2 University of Kocaeli, Turkey
3 PET Center, Bad Berka, Germany
4 CHUV, Lausanne, Switzerland
5 Royal Free Hospital, London, UK
6 CHR, Nantes Cedex, France
7 Ospedale “A. Manzoni”, Lecco, Italy
8 University of Innsbruck, Austria
9 University UZ Gasthuisberg, Louvain, Belgium
10 University of Ulm, Germany
Published online: 1 November 2003
© EANM 2003

for bone imaging because of their good localisation in
the skeleton and rapid clearance from soft tissues.
Bone scintigraphy images the distribution of a radioac-
tive tracer in the skeletal system. It can be performed as:
a) Limited bone scintigraphy or spot views (planar im-
ages of a selected portion of the skeleton)
b) Whole-body bone scintigraphy (planar images of the
entire skeleton in anterior and posterior views)
c) SPET (tomographic image of a portion of the skeleton)d) Multiphase bone scintigraphy (immediate and delayed
images to study blood flow)
In oncology the standard technique of bone scintigraphy
is considered to be the whole-body scan. Limited bonescintigraphy or spot views are indicated only where aspecific clinical problem detected on whole-body imag-ing needs to be clarified. SPET has a higher diagnosticspecificity than planar imaging and may be preferablewhen there is diagnostic uncertainty. Multiphase bonescintigraphy is more useful when trauma or musculo-skeletal inflammation/infection is suspected and is notusually indicated in oncology.
Over recent decades, bone scintigraphy has been used
extensively in the evaluation of oncological patients. Itprovides essential information about the sites of bone le-sions (primary and metastatic tumours), their prognosisand the effectiveness of therapy by showing the sequentialchanges in tracer uptake. Bone scintigraphy offers the ad-vantages of whole-body examination and has the capabili-ty to discover some lesions earlier than other techniques.MRI is potentially more sensitive for some regions but isimpractical as a whole-body screening technique.
Clinical indications
Oncological indications– Primary tumours (e.g. Ewing’s sarcoma, osteosarcoma)
– Staging, evaluation of response to therapy and follow-
up of primary bone tumors
– Secondary tumours (metastases)
Staging and follow-up of neoplastic diseasesDistribution of osteoblastic activity prior to radiomet-abolic therapy (
89Sr, 153Sm-EDTMP, 186Re-HEDP)
Indications for non-neoplastic diseases:
Bone scan changes occur whenever there is an increase
in blood flow to a lesion or there is an alteration in os-teoblastic activity. For this reason, bone scan images alsoreveal abnormalities in non-neoplastic diseases such as:
– Osteomyelitis
– Perthes’ disease, avascular necrosis– Metabolic disorders (Paget’s disease, osteoporosis)
– Arthropathies– Fibrous dysplasia and other rare congenital conditions– Stress fractures, shin splints– Loose or infected joint prosthesis– Low back pain, sacro-iliitis– Reflex sympathetic syndrome– Any other bone injuries
Precautions
– Pregnancy (suspected or confirmed). In the case of a
diagnostic procedure in a patient who is known orsuspected to be pregnant, a clinical decision is neces-sary to weigh the benefits against the possible harmof carrying out any procedure.
– Breast-feeding should be discontinued and milk ex-
pressed and discarded when possible for 24 h (and atleast for 4 h) post radiopharmaceutical administra-tion).
Pre-examination procedures
Patient preparationA thorough explanation of the test should be provided to
the patient in advance by the technologist or physician(including hydration, time taken for scan and details ofthe procedure itself).
Pre-injection
The nuclear medicine physician should take account of
all information that is available for optimal interpretationof bone scintigraphy, especially:
– Relevant history, including type of suspected or
known primary tumour(s) and/or metastases
– Relevant history of fractures, trauma, osteomyelitis,
cellulitis, oedema, arthritis, neoplasms, metabolicbone disease or limitation of function
– Current symptoms, physical findings– Results of previous bone scintigraphy or other recent
nuclear medicine studies (
131I, 67Ga, 111In) (it is strongly
recommended that every effort be made to obtain hardcopies or computer files of previous examinations)
– Results of other imaging studies such as conventional
radiography, CT, MRI (as with previous scintigraphicexaminations, it is recommended that every effort bemade to obtain hard copies or computer files of previ-ous examinations)
– History of therapy that could affect bone scintigraphy
(e.g. antibiotics, steroids, chemotherapy, radiationtherapy, diphosphonates, iron therapy)BP100
European Journal of Nuclear Medicine and Molecular Imaging V ol. 30, No. 1, January 2003

– Orthopaedic and non-orthopaedic surgery affecting
the results of bone scintigraphy
– Relevant laboratory results (e.g. PSA for patients with
prostate cancer)
– Presence of urinary tract abnormalities– Possible contraindications to hydration
Radiopharmaceutical injection,
dosage and administration
The radiopharmaceutical (MDP, HMDP, HDP, etc.)
should be administered by the intravenous route, usingan indwelling catheter or butterfly needle.
The radiopharmaceutical activity to be administered
should be determined after taking account of the Euro-pean Atomic Energy Community Treaty, and in particu-lar article 31, which has been adopted by the Council ofthe European Union (Directive 97/43/EURATOM).This Directive supplements Directive 96/29/EURAT-OM and guarantees health protection of individualswith respect to the dangers of ionising radiation in thecontext of medical exposures. According to this Direc-tive, Member States are required to bring into forcesuch regulations as may be necessary to comply withthe Directive. One of the criteria is the designation ofDiagnostic Reference Levels (DRLs) for radiopharma-ceuticals; these are defined as levels of activity for
groups of standard-sized patients and for broadly de-fined types of equipment. It is expected that these levels
will not be exceeded for standard procedures whengood and normal practice regarding diagnostic andtechnical performance is applied. For the above-men-tioned reasons, the following proposed activity for
99mTc-diphosphonate should be considered only as a
general indication, based on the data in the literatureand current experience. It should be noted that in eachcountry, nuclear medicine physicians should respect theDRLs and the rules set out by local law.
The average activity administered for bone scintigra-
phy by a single i.v. injection should be 500 MBq(300–740 MBq) (8–20 mCi). The organ which receivesthe largest radiation dose is bone (see table of adsorbeddoses, ICRP no. 80, 1998). The activity to be adminis-tered to children should be a fraction of the adult activitycalculated from body weight according to the factorsgiven by the EANM Paediatric Task Group. In children aminimum activity of 40 MBq is necessary in order to ob-tain images of sufficient quality. Practitioners could berequired to justify administration of activities greaterthan local national DRLs.
Post-injection
Unless contraindicated, patients should be well hydrated
and instructed to drink one or more litre of water (four toeight glasses) between the time of injection and the time
of imaging. All patients should be asked to void fre-quently during the interval between injection and de-layed imaging as well as immediately prior to the scan.
Patients should drink a large amount of fluids during
the 24 h after radiopharmaceutical administration.
Physiological distribution
of
99mTc-phosphonates
Phosphonates concentrate in the mineral phase of bone:
nearly two-thirds in hydroxyapatite crystals and one-third in calcium phosphate. Two major factors controlaccumulation of phosphonates in bone, namely bloodflow and extraction efficiency, which in turn depend oncapillary permeability, acid-base balance, parathyroidhormone levels, etc. About 50% of the activity injectedaccumulates in the skeleton. Maximum bone accumula-tion is reached 1 h after injection and the level remainspractically constant up to 72 h. The blood clearance ofthese radiopharmaceuticals is high. Three hours after in-jection only 3% of the administered activity remains inthe bloodstream. The peak of activity through the kid-neys is reached after approximately 20 min. Within 1 h,with normal renal function, more than 30% of the un-bound complex has undergone glomerular filtration andwithin 6 h, 60%. The quantity of phosphonates eliminat-ed via the intestines is insignificant. The biological half-life of phosphonates is 26 h.
In a normal bone scan all but the smallest bones are
recognisable. On the anterior view it is possible to distin-guish the sternum. On the posterior view the bodies ofindividual vertebrae are seen, as well as pedicles andtransverse and spinous processes in the lower dorsal andlumbar regions. In this projection the sacro-iliac jointsusually have the highest uptake. In children the appear-ance of the bone scan is characterised by areas of uptakedue to active growth in the epiphyseal regions. After fu-sion of the epiphyses these areas are no longer visible.
Radiation dosimetry
The estimated adsorbed radiation dose to various organs
in healthy subjects following administration of
99mTc-la-
belled phosphates and phosphonates is given inTable 1.The data are quoted from ICRP no. 80.
Radiopharmaceutical:
technetium [
99mTc] diphosphonates.
DefinitionThe most commonly used diphosphonates are methylene
diphosphonate (MDP), hydroxymethylene diphospho-BP101
European Journal of Nuclear Medicine and Molecular Imaging V ol. 30, No. 1, January 2003

nate (HMDP) and hydroxyethylene diphosphonate
(HDP/HMDP). All are commercially available and sup-plied as a vial containing the relevant diphosphonate, astannous reducing agent and other excipients in a lyo-philised form.
Preparation
99mTc-labelled diphosphonates are prepared by addition
of the required amount of sodium [99mTc]pertechnetate,
diluted in sterile physiological saline, to the vial accord-ing to the manufacturer’s instructions.
Quality control
The radioactive concentration should be determined by
measuring the activity of the vial in a calibrated ionisat-ion chamber. Radiochemical purity may be confirmedusing a TLC method. (Solid-phase ITLC, mobile-phase Imethylethylketone; Rf
99mTc-MDP 0.0, reduced hydro-
lysed 99mTc 0.0, 99mTc-pertechnetate 1.0; mobile phase II
0.9% sodium chloride solution; Rf 99mTc-MDP 1.0, re-duced hydrolysed 99mTc 0.0, 99mTc-pertechnetate 1.0.)
Labelling efficiency should be >95%.
Special precautions
The preparation may be diluted with sterile physiological
saline if required. These radiopharmaceuticals are sub-ject to oxidation, and care should be taken to avoid intro-ducing air into the multidose vial during preparation orremoval of doses. The radiopharmaceutical should beused within 6 h of preparation.
Gamma camera quality control
A strict quality control programme should be routinely
performed, according to the rules of each country, asstated in the Council Directive 97/43/EURATOM.
Image acquisition
Instrumentation– Single- or double-headed gamma camera equipped
with a low-energy, high-resolution collimator
– Energy window: 10% energy window (±5%) centred
over the 140-keV photopeak of
99mTc
Acquisition modality
Routine images are usually obtained between 2 and 5 h
after injection. Later (6–24 h) delayed images result in ahigher target-to-background ratio and may permit betterevaluation of the pelvis if this was obscured by bladderactivity on the routine (2–5 h) images. Six- to 24-h de-layed imaging may be particularly helpful in patientswith renal insufficiency or peripheral circulatory disor-ders and those with urinary retention.
Whole-body bone scintigraphy can be accomplished
with multiple overlapping (spot) images or with continu-ous imaging (i.e. whole-body scan) obtained in both an-terior and posterior projections. In adults, whole-bodystudies are currently preferred. In children, spot viewsare commonly used.
When spot views are used as the primary method of
acquisition, the regions of the skeleton covered by eachspot view must overlap, to avoid missing any area. Thefirst spot view of the axial skeleton, usually the posteriorprojection of the chest, is acquired for approximately500,000 to 1 million counts depending on the field ofview (FOV) of the gamma camera. The larger the FOV ,the larger the number of total counts required to givesimilar count densities over equivalent regions of theskeleton. Moreover, the presence of physiologically highBP102
European Journal of Nuclear Medicine and Molecular Imaging V ol. 30, No. 1, January 2003Table 1. Absorbed radiation dose per unit activity administered
(mGy/MBq), for various organs in healthy subjects following theadministration of
99mTc-labelled phosphates and phosphonates
Organ Adult 15 year olds 5 year olds
Adrenals 0.0021 0.0027 0.0058Bladder 0.048 0.060 0.073Bone surfaces 0.063 0.082 0.22Brain 0.0017 0.0021 0.0043Breast 0.00071 0.00089 0.0022Colon 0.0027 0.0034 0.0061Gallbladder 0.0014 0.0019 0.0042Heart 0.0012 0.0016 0.0034Kidneys 0.0073 0.0088 0.018Liver 0.0012 0.0016 0.0036Lungs 0.0013 0.0016 0.0036Muscles 0.0019 0.0023 0.0044Oesophagus 0.0010 0.0013 0.0030Ovaries 0.0036 0.0046 0.0070Pancreas 0.0016 0.0020 0.0045Red marrow 0.0092 0.010 0.033Skin 0.0010 0.0013 0.0029Small intestine 0.0023 0.0029 0.0053Spleen 0.0014 0.0018 0.0045Stomach 0.0012 0.0015 0.0035Testes 0.0024 0.0033 0.0058Thymus 0.0010 0.0013 0.0030Thyroid 0.0013 0.0016 0.0035Uterus 0.0063 0.0076 0.011Remaining organ 0.0019 0.0023 0.0045Effective dose (mSv/MBq) 0.0057 0.0070 0.014

count density organs (typically the kidneys) may hamper
visualisation of contiguous structures (typically thespine). Each of the remaining spot views is then acquiredfor the same time as the first view. Spot images may beobtained using a 128 ×128 or a 256 ×256 matrix
(>200,000 counts). Whole-body views are usually ob-tained in a matrix of 256 ×1,024.
Computer acquisition, processing and display of im-
ages may be particularly helpful in paediatric popula-tions because of the extreme range of normal uptake.Films of scintigrams photographed with different intensi-ties may also be helpful if digital processing and revieware not available.
When whole-body scanning is used, the count rate
(usually the posterior thorax) should be determined be-fore starting the definitive acquisition. The scanningspeed should be adjusted so that routine anterior andposterior whole-body images obtained 2–5 h after injec-tion each contain >1.5 million counts.
Optional images
In some patients, SPET imaging is helpful to better char-
acterise the presence, location and extent of disease.SPET imaging should be performed as recommended bythe gamma camera manufacturer. Typical acquisition andprocessing parameters with a single-headed gamma cam-era are 360° circular orbit, 60–120 steps, 64 ×64 or great-
er matrix, and 10–40 s/stop. An equivalent total numberof counts should be acquired if continuous acquisition isused.
A pinhole collimator may be used if very high-resolu-
tion images of a specific area are necessary. Approxi-mately 75,000–100,000 counts should be obtained forpinhole collimator views. Zoom magnification or a con-verging collimator may also be used to improve resolu-tion, particularly when small structures or paediatric pa-tients are being imaged. The physician interpreting theimage should be notified when collimators such as a pin-hole, which introduce distortions, are used.
Additional projections, such as lateral, oblique, tan-
gential and special views may be obtained if necessary.
The pelvis can be difficult to evaluate when there is
overlying bladder activity. In patients with pelvic symp-toms, one or more of the following may better visualisethe bony pelvis:
– Repeat images immediately after voiding.
– Sitting-on detector (caudal) or oblique views.– Lateral views.– 24-h delayed images.– SPET acquisition. Single or multiple rapid (5–10 min
per acquisition) SPET acquisition(s) are preferred toavoid artefacts caused by changing activity in thebladder. Bladder artefacts are exaggerated in the planewhere the SPET acquisition begins and ends.– Image immediately following catheterisation of the
bladder. (Note: Bladder catheterisation should be re-served as a last resort for patients in whom visualisa-tion of the pelvis is essential.)
Image processing
No particular processing procedure is needed for planar
images.
In the case of SPET, one should take into account the
different types of gamma camera and software available:careful choice of imaging processing parameters shouldbe adopted in order to optimise the imaging quality.
Interpretation criteria
When evaluating bone scan images, the following points
should be taken into consideration:
– The bone scan is very sensitive for localisation of
skeletal metastases or tumours, but the specificity islow. It must be interpreted in the light of all availableinformation, especially patient history, physical ex-amination, other test results and previous studies.
– Symmetry in the representation of right and left sides
of the skeleton and homogeneity of tracer uptakewithin bone structures are important normal features.Particular attention should be paid to left–right asym-metries and/or heterogeneity of tracer uptake.
Bone abnormalities
– Both increases and decreases in tracer uptake have to be
assessed; abnormalities can be either focal or diffuse.
– Increased (decreased) tracer activity in the bone, com-
pared with that in normal bone, indicates increased(decreased) osteoblastic activity.
– Differential diagnosis can sometimes be based on the
configuration of the abnormality or abnormalities andthe location and number of abnormalities. Most pat-terns are non-specific.
– Focal decrease without adjacent increase in tracer up-
take is less common than focally increased activityand is often caused by benign conditions (attenuation,artefact or absence of bone, e.g. due to surgical resec-tion).
– Decreases in the intensity of tracer uptake and in the
number of abnormalities compared with a previousstudy often indicate improvement or may occur sec-ondary to focal therapy (e.g. radiation therapy).
– Increases in the intensity of tracer uptake and in the
number of abnormalities compared with a previousstudy often indicate progression of disease but mayreflect a flare response to therapy.BP103
European Journal of Nuclear Medicine and Molecular Imaging V ol. 30, No. 1, January 2003

Soft tissue findings
– Normal structures should be noted: kidneys and blad-
der. Tracer uptake in the kidney can be focal or diffuse.
– Generalised increased soft tissue uptake compared
with normal bone can be due to renal failure, dehy-dration or a shortened interval between injection andimaging.
– A generalised decreased soft tissue uptake compared
with normal bone can be due to “superscan” or a pro-longed interval between injection and imaging.
Reporting
The nuclear medicine physician should record appropri-
ate information regarding the patient, especially type ofexamination, date, radiopharmaceutical (administeredactivity and route), a summary of patient history, all cor-related data from previous diagnostic studies and theclinical problem.
The report to the referring physician has to describe:
1. The procedure (whole body, SPET if applicable, ra-
diopharmaceutical, injected activity, delayed images,blood pool images etc.).
2. Findings. Abnormal tracer uptake (increased, de-
creased, pattern of abnormal uptake, bone findings,soft tissue findings).
3. Comparative data (correlation with other diagnostic
results and comparison with previous studies).
4. Interpretation. A clear diagnosis should be given if
possible, accompanied when appropriate by a descrip-tion of the study limitations. Further, more definitivestudies and evaluations should be recommended if thedifferential diagnosis is broad.
Sources of error
– Patient movement
– Greater than necessary collimator-to-patient distance– Imaging too soon after injection, before the radiophar-
maceutical has been optimally cleared from soft tissues
– Injection artefacts– Radiopharmaceutical degradation– Urine contamination or a urinary diversion reservoir– Prosthetic implants, radiographic contrast materials or
other attenuating artefacts which may obscure normalstructures
– Homogeneously increased bony activity (e.g. “super-
scan”)
– Restraint artefacts caused by soft-tissue compression– Prior administration of a higher energy radionuclide
(
131I, 67Ga, 111In) or of a 99mTc radiopharmaceutical
which accumulates in an organ that could obscure orconfound skeletal activity– Significant findings outside the area of interest may
be missed if a limited study is performed
– Changing bladder activity during SPET of the pelvic
region
– Purely lytic lesions– Pubic lesions obscured by underlying bladder activity– Renal failure
Issues requiring further clarification
The role of
99Tc-phosphonate bone scintigraphy in the
follow-up of treated cancer patients is still a matter ofdiscussion. There is general agreement that bone scintig-raphy is indicated in symptomatic patients. However, itis unproven whether bone scintigraphy is cost-effectivein all asymptomatic patients at risk of metastases (thosewith worse prognostic factors). Discussions are ongoingin order to establish which subgroups of patients at highrisk of metastases can benefit from periodic bone scanexaminations.
Although the clinical role of PET (
18F-fluoride and
18F-fluorodeoxyglucose) in the diagnosis and manage-
ment of bone tumours has not yet been fully defined, theavailable reports suggest that it has great potential toprovide further clinically relevant information in thesepatients. The position of
99Tc-phosphonate bone scintig-
raphy in comparison with PET should be better investi-gated (according to tumour type and clinical indications)in order to clarify whether bone scintigraphy can retainits current role in spite of the emerging high diagnosticaccuracy of PET.
Disclaimer
The European Association has written and approved
guidelines to promote the use of nuclear medicine proce-dures with high quality. These general recommendationscannot be applied to all patients in all practice settings.The guidelines should not be deemed inclusive of allproper procedures and exclusive of other procedures rea-sonably directed to obtaining the same results. The spec-trum of patients seen in a specialised practice settingmay be different than the spectrum usually seen in amore general setting. The appropriateness of a procedurewill depend in part on the prevalence of disease in thepatient population. In addition, resources available forpatient care may vary greatly from one European countryor one medical facility to another. For these reasons,guidelines cannot be rigidly applied.
Acknowledgements . The authors thank Ms. Annaluisa De Simone
Sorrentino and Ms. Marije de Jager for their valuable editorial as-sistance.BP104
European Journal of Nuclear Medicine and Molecular Imaging V ol. 30, No. 1, January 2003

Essential references
1. Bares R. Skeletal scintigraphy in breast cancer management.
Q J Nucl Med 1998; 42:43–48.
2. Beauchamp CP. Errors and pitfalls in the diagnosis and treat-
ment of metastatic bone disease. Orthop Clin North Am 2000;
31:675–685.
3. Brown ML, Collier BD, Fogelman I. Bone scintigraphy: part I.
Oncology and infection. J Nucl Med 1993; 34:2236–2240.
4. Brown ML, O’Connor MK, Hung JC, et al. Technical aspects
of bone scintigraphy. Radiol Clin North Am 1993; 31:721–
730.
5. Cameron PJ, Klemp PF, Martindale AA, Turner JH. Prospec-
tive 153Sm-EDTMP-therapy dosimetry by whole-body scin-
tigraphy. Nucl Med Commun 1999; 20:609–615.
6. Collier BD, Fogelman I, Brown ML. Bone scintigraphy: part
2. Orthopedic bone scanning. J Nucl Med 1993; 34:2241–
2246.
7. Collier BD, Fogelman I, Rosenthall L, eds. Skeletal nuclear
medicine. New York: Mosby, 1996.
8. Cook GJ, Fogelman I. Skeletal metastases from breast cancer:
imaging with nuclear medicine. Semin Nucl Med 1999; 29:
69–79.
9. Cook GJ, Fogelman I. The role of nuclear medicine in moni-
toring treatment in skeletal malignancy. Semin Nucl Med
2001; 31:206–211.
10. Cook GJ, Houston S, Rubens R, et al. Detection of bone me-
tastases in breast cancer by 18-FDG-PET: differing metabolicactivity in osteoytic lesions. J Clin Oncol 1998; 16:3375–
3379.
11. Di Leo C, Tarolo GL, Aliberti G, Ardemagni A, Conte A,
Bestetti A, Tagliabue L, Gallazzi M. Stress fracture and coex-istent periosteal reaction (“shin splints”) in a young athlete re-vealed by bone scintigraphy. Nuklearmedizin 2000; 39:N50–
N51.
12. Dose J, Bleckmann C, Bachmann S, et al. Comparison of
FDG-PET and conventional diagnostic procedures for the de-tection of distant metastases in breast cancer patients. Nucl
Med Commun 2002; 23:857–864.
13. Evans AJ, Robertson JF. Magnetic resonance imaging versus
radionuclide scintigraphy for screening in bone metastases.Clin Radiol 2000; 55:653–654.
14. Fogelman I, Collier BD, Brown ML. Bone scintigraphy: part
3. Bone scanning in metabolic bone disease. J Nucl Med 1993;
34:2247–2252.
15. Franzius C, Sciuk J, Daldrup-Link HE, et al. FDG-PET for de-
tection of osseous metastases from malignant primary bone tu-mours: comparison with bone scintigraphy. Eur J Nucl Med
2000; 27:1305–1311.
16. Gallowitsch HJ, Kresnik E, Gasser J, Kumnig G, Igerc I,
Mikosch P, Lind P. F-18 fluorodeoxyglucose positron-emis-sion tomography in the diagnosis of tumor recurrences andmetastases in the follow-up patients with breast carcinoma: acomparison to conventional imaging. Invest Radiol 2003; 38:
250–256.
17. Hain SF, Fogelman I. Nuclear medicine studies in metabolic
bone disease. Semin Musculoskelet Radiol 2002; 6:323–329.
18. Han LJ, Au-Yong TK, Tong WC, et al. Comparison of bone
single-photon emission tomography and planar imaging in de-tection of vertebral metastases in patients with back pain. Eur
J Nucl Med 1998; 25:635–638.
19. Holder LE. Bone scintigraphy in skeletal trauma. Radiol Clin
North Am 1993; 31:739–781.20. ICRP Publication 80 Radiation dose to patients from radio-
pharmaceuticals. Ann ICRP 1998; 28:3.
21. Kane CJ, Amling CL, Johnstone PA, Pak N, Lance RS.
Thrasher JB, Foley JP, Riffenburgh RH, Moul JW. Limitedvalue of bone scintigraphy and computed tomography in as-sessing biochemical failure after radical prostatectomy. Urolo-
gy2003; 61:607–611.
22. Kato K, Aoki J, Endo K. Utility of FDG-PET in differential
diagnosis of benign and malignant fractures in acute to sub-acute phase. Ann Nucl Med 2003; 17:41–46.
23. Kaye J, Hayward M. Soft tissue uptake on
99mTc methylene di-
phosphonate bone imaging: pictorial review. Australas Radiol
2002; 46:13–21.
24. Kodusa S, Yoshimura I, Aizawa T, et al. Can initial prostate
specific antigen determinations eliminate need for bone scansin patients with newly diagnosed prostate carcinoma? A multi-center retrospective study in Japan. Cancer 2002; 94:964–
972.
25. Maffioli L, Zambetti M, Castellani MR, et al. Role of bone
scan in breast cancer follow-up. Tumori 1997; 83:547–549.
26. Mari C, Catafau A, Carrio I. Bone scintigraphy and metabolic
disorders. Q J Nucl Med 1999; 43:259–267.
27. Merrick MV , Beales JS, Garvie N, Leonard RC. Evaluation
and skeletal metastases. Br J Radiol 1992; 65:803–806.
28. Myers RE, Johnston M, Pritchard K, et al. Baseline staging
tests in primary breast cancer: a practice guideline. CMAJ
2001; 164:1439–1444.
29. Nakamoto Y , Osman M, Wahl RL. Prevalence and patterns of
bone metastases detected with positron emission tomographyusing F-18 FDG. Clin Nucl Med 2003; 28:302–307.
30. O’Sullivan JM, Cook GJ. A review of the efficacy of bone
scanning in prostate and breast cancer. Q J Nucl Med 2002;
46:152–159.
31. Ohta M, Tokuda Y , Suzuki Y , et al. Whole body PET for the
evaluation of bony metastases in patients with breast cancer:comparison with
99mTc-MDP bone scintigraphy. Nucl Med
Commun 2001; 22:875–879.
32. Orzel JA, Sawaf NW, Richardson ML. Lymphoma of the skel-
eton: scintigraphic evaluation. AJR 1988; 150:1095–1099.
33. Paediatric Task Group European Association of Nuclear Medi-
cine. A radiopharmaceutical schedule for imaging in paediat-rics. Eur J Nucl Med 1990; 17:127–129.
34. Palmedo H, Guhlke S, Bender H, Sartor J, Schoeneich G,
Risse J, Grunwald F, Knapp FF Jr, Biersack HJ. Dose escala-tion study with rhenium-188 hydroxyethylidene diphospho-nate in prostate cancer patients with osseous metastases. Eur J
Nucl Med 2000; 27:123–130.
35. Pauwels EK, Stokkel MP. Radiopharmaceuticals for bone le-
sions. Imaging and therapy in clinical practice. Q J Nucl Med
2001; 45:18–26.
36. Pomeranz SJ, Pretorius HT, Ramsingh PS. Bone scintigraphy
and multimodality imaging in bone neoplasia: strategies forimaging in the new health climate. Semin Nucl Med 1994;
24:188–207.
37. Ravaioli A, Pasini G, Polselli A, Papi M, Tassinari D,
Arcangeli V , Milandri C, Amadori D, Bravi M, Rossi D, Fattori PP, Pasquini E, Panzini I. Staging of breast cancer: newrecommended standard procedure. Breast Cancer Res Treat
2002; 72:53–60.
38. Rigaud J, Tiguert R, Le Normand L, et al. Prognostic value of
bone scan in patients with metastatic prostate cancer treatedinitially with androgen deprivation therapy. J Urol 2002; 168:
1423–1426.BP105
European Journal of Nuclear Medicine and Molecular Imaging V ol. 30, No. 1, January 2003

39. Rosselli del Turco M, Palli D, Cariddi A, et al. Intensive diag-
nostic follow-up after treatment of primary breast cancer. Arandomised trial. National Research Council Project on BreastCancer Follow Up. JAMA 1994; 271:1953–1957.
40. Rubens RD. Bone metastases. The clinical problem. Eur J
Cancer 1998; 34:210–213.
41. Savelli G, Maffioli L, Maccauro M, et al. Bone scintigraphy
and the added value of SPECT (single photon emission to-mography) in detecting skeletal lesions. Q J Nucl Med 2001;
45:27–37.
42. Sinha P, Freeman LM. Scintigraphy of bone metastases. In:
Khalkhali I, Maublant JC, Goldsmith SJ, eds. Nuclear oncol-ogy. Philadelphia: Lippincott Williams & Wilkins; 2001:526–
544.
43. Wu HC, Yen RF, Shen YY , Kao CH, Lin CC, Lee CC. Com-
paring whole body
18F-2-deoxyglucose positron emission
tomography and technetium-99m methylene diphosphonatebone scan to detect bone metastases in patients with renal cellcarcinomas—a preliminary report. J Cancer Res Clin Oncol
2002; 128:503–506.
44. Yang DC, Rafani RS, Mittal PK, et al. Radionuclide three-
phase whole-body imaging. Clin Nucl Med 2002; 27:419–
426.BP106
European Journal of Nuclear Medicine and Molecular Imaging V ol. 30, No. 1, January 2003