Bone Scintigraphy

Department of Nuclear Medicine

Dr. Pei-Shan Wu

Radiopharmaceuticals

Sr-85: high radiation absorbed dose, poor imaging characteristics, and delayed imaging time (5~7 days)

Sr-87m: Low target-to-background ratios Fluorine 18: positron emission Tc-99m MDP: 140 KeV, 6-hour half-life

distributed rapidly throughout the extracellular fluid space

rapid uptake in bone clearance from the body via the kidneys the skeleton-to-background tissue ratio improves

with time

Technique

1. Patient preparation and follow-up be well hydrated void immediately before study remove metal objects

2. Dosage and route of administration 20 mCi (740MBq) Tc-99m MDP intravenous injection adjust dosage for pediatric patients, minimum 2 mCi

3. Time of imaging 2~4 hr after tracer administration

4. Images: three-phase, whole body, SPECT

Normal bone scan

1. Areas with normally increased activity include: acromioclavicular joints, sternoclavicular joints, scapular tips, costochondral junctions, sacroiliac joints, lower neck, sternum, renal pelves and bladder

2. Pediatric patients: growth centers and cranial sutures3. Pitfalls

- Patient rotation- Urine retained in calyx may overlie lower rib- Urine contamination- Belt buckles, earrings, necklaces, and the like frequently create

cold defects- Recent dental procedures- Radiopharmaceutical problems: breakdown of tag leading to fr

ee pertechnetate causes activity in thyroid and GI tract

Abnormal bone scans

A. Metastatic disease Tumors most likely to metastasize to bone include: bre

ast, lung, prostate, lymphoma, thyroid, renal and neuroblastoma

Tumors in which falsely normal bone scan can be expected include: multiple myeloma, some anaplastic tumors, and pure lytic lesions

Location of metastases: axial skeleton – 80%, skull – 10%, long bones – 10%

Super scan: diffuse symmetrical increased uptake_ tumors frequently causing super scan: prostate, breast, lung bl

adder and lymphoma_ nontumor causes of super scan: hyperparathyroidism, osteom

alacia, Paget’s disease, and fibrous dysplasia

Abnormal bone scans

B. Primary malignant bone tumors Osteogenic sarcoma, chondrosarcoma,

Ewing’s sarcoma

C. Benign primary tumors Osteoid osteoma, bone islands, bone cy

sts, fibrous cortical defects, and others

D. Osteomyelitis and septic arthritis

Abnormal bone scans

E. Fracture

1. Traumatic fracture positive within 24 hours 2/3 return to normal by 1 year child abuse :

_will not detect old, healed fx

_difficult to evaluate around metaphyseal/epiphyseal region

_may miss some skull fractures

Abnormal bone scans

2. Stress fractures Fatigue fracture: caused by repeated abnormal stress

on normal bone_fusiform, longitudinal shape, most often involving posterior tibial

cortex_focal, less than 1/5 length of tibia_common located in junction of middle and distal third of tibia

Insufficiency fracture: resulting from normal stress on abnormal bone_seen in such diseases as: osteoporosis, osteomalacia, paget’s

disease, fibrous dysplasia, and status postirradiation

Abnormal bone scans

F. Metabolic bone disease1. Osteoporosis: normal or decreased uptake2. Osteomalacia:

_vitamin D deficiency _results in failure of bone matrix to calcify_generalized increased skeletal uptake

3. Paget’s disease_increased uptake in bone scan_distribution of lesions: pelvis (70~80%), lumbar-thora

cic vertebrae, femur, skull, scapula, tibia, and humerus

Abnormal bone scans

4. Hyperparathyroidism a. Primary: caused by hyperplasia or tumor of parathyroi

ds 50~80% normal bone scan abnormal uptake at: calvarium, mandible, acromioclavic

ular joint, sternum, lateral humeral epicondyles and hands

soft-tissue calcification in: lungs, stomach, kidneys, heart and periarticular

b. Secondary: associated with chronic renal failure usually have abnormal bone scan super scan focal abnormalities

Abnormal bone scans

G. Avascular necrosis result of: fracture, metabolic disorder, fat embolizati

on, steroids, hemolytic anemia, and vasculitis plain film is normal in early stage (6 months) bone scan: normal for first 48 hr decreased activi

ty increased activity develop degenerative joint disease (increased uptake in the acetabulum)

Legg-Calve-Perthes disease: afftects boys aged 4~8 years

Abnormal bone scans

H. Heterotopic ossification

_associated with paraplegia and quadriplegia

_increased activity in soft tissue

I. Arthritides

1. Degenerative joint disease - most common locations: hands, feet, hips, knees, SI joints and shoulders

2. Rheumatoid arthritis - symmetrical increased uptake: hands feet, knees and cervical spine

Radionuclide inflammation scan and tumor scan

Department of Nuclear Medicine

Dr. Pei-Shan Wu

Application of Radionuclide Imaging in Infection

Radionuclide imaging for detection of infection –Ga-67 scan

–Tc-99m (V) DMSA scan

–Tc-99m HMPAO labeled WBC scan

–Tc-99m labeled IgG scan

Utility in specific diseases –Osteomyelitis

–Painful prosthesis

–AIDS

Gallium-67

Cyclotron produced Half-life: 78 hrsBiological behavior: similar to ferric ion Binding to iron-binding molecules, includi

ng transferrin, lactoferrin, ferritin, siderophores

Gallium-67 scan: Mechanism

Not thoroughly understood Ga-67 citrate binds to transferrin in the blood

 => transported to site of inflammation/infection Localization depends on a number of factors

–Adequate blood supply –Increased vascular permeability –Leaking into areas inflammation/infection

Ga-67 can be used in leukopenic, immunocompromised patients

Within 12-24 hours: Ga-67 firmly bound within lesion

Ga-67 scan: Technique

Dose: –Inflammation: 3-5 mCi –Tumor: 5-10 mCi

Imaging time: –48-72 hr to 1 week –Inflammation: 24 hr; Earlier images: high background: false-ne

gative Imaging parameters:

–Energy: 93, 185, 296 keV peaks –Total body scan, focal view, SEPCT –Medium energy collimator –Bowel activity: bowel preparation

Ga-67 scan: Normal distribution

Liver: greatest Ga-67 uptake Other: Spleen, nasopharynx, lacrimal and saliv

ary glands, bone marrow, scrotum, testes First 24 hours: kidneys, bladder

 - 48-72 hours: kidneys: only faintly visualized After 24 hours, biological clearance through bo

wel Breast uptake: variable, woman’s hormonal cy

cle Thymus: children

Ga-67 scan: image interpretation

Abnormal uptake:≥ liver or spleen abscess= liver clinical important inflammation< bone marrow low-level inflammation

No difference in sensitivity fro acute or chronic infection

Less sensitivity in tuberculosis, fungal infection

Ga-67 scan: Advantages

Whole body survey Sensitive for detection of all inflammatory

process whether or not they are discretely defined anatomically

For detecting source of sepsis Leukopenic, immunocompromised patien

tsTumor detection

Ga-67 scan: Disadvantages

Time delay between injection and imaging Poor spatial definition of anatomically discr

ete lesionsPotential misinterpretation as a result of gall

ium uptake in adjacent organ (e.g. liver) Bowel activity Infection vs tumor

Tc-99m (V) DMSA scan

A tumor scan: e.g. medullary carcinoma of thyroid, soft tissue tumor

Mechanism: –unknown

–hypothesis: resemble phosphate ion distribution

Biodistribution: Cardiovascular system, kidneys Technique

–20 mCi Tc-99m (V) DMSA iv injection

–Imaging: 4 hr post-injection

Tc-99m (V) DMSA scan: Advantages

Good availability High resolution Low price Low radiation dose Preparation technique: Easy Imaging: 4 hr post-injection

Tc-99m (V) DMSA scan: Disadvantages

GU tract infection Infection vs tumor Chronic infection Further study

Scintigraphic diagnosis of osteomyelitis

ESR: Sensitive, but nonspecific Blood culture: 40% negative X-ray

–First imaging study –Not detectable until 10-21 days after onset of symptoms

Scintigraphic methods –Three-phase bone scan –Ga-67 scan –Tc-99m (V) DMSA scan –WBC scan –IgG scan

Three-phase bone scan: Osteomyelitis

Blood flow study: Imaging at 3-5 sec intervals throughout the 1st-2nd minutes after radiotracer administration  

Blood pooling study: Obtain 5-20 min after injection   Delayed scan: 2-4 hr post-injection DD osteomyelitis and cellulitis Cellulitis: diffuse hyperemia, delayed: negative Osteomyelitis: focal hyperemia, delayed: positive Positive:

–24-48 hr after onset of symptoms –Remain positive for months after resolution

Sensitivity: 90-100%, specificity: 75-90%

Ga-67 scan: Osteomyelitis

Positive: within 24-48 hr of symptomatic onset Return to baseline quickly following successful

treatment Sensitivity: 80-90%, specificity: 70% Sequential bone and gallium scans

Positive: Ga-67 uptake is incongruent with the bone scan

Negative: low-trade uptake Equivocal: intense congruent uptake

Neonatal osteomyelitis

Diffuse nature, propensity for complications, paucity of associated signs => whole body image

Three-phase bone scan: –22-68% falsely normal or cold defects –Resolution –Cold lesion: subperiosteal abscess

Bone scan: negative, clinically suspected  => Ga-67 scan

Scintigraphic diagnosis of painful prosthesis

Three-phase bone scan –Focally increased uptake: loosening –Diffuse, uniformly distribution: infection –Not very specific

Ga-67 scan –Differential between pure mechanical loosening and i

nfection Sequential bone-gallium imaging

–Incongruent image: Ga uptake exceed Tc-99m MDP bone radiotracer uptake (spatial, intensity of uptake)

–sensitivity: 70%, specificity: 90%, Accuracy: 80%

Infection in immunosuppressed patients

Diffuse pulmonary uptakePCP

CXR: bilateral diffuse infiltrate from hilum to peripheral

Ga-67: diffuse bilateral pulmonary uptake without nodal or parotid uptake (often before CXR)

Severe in CXR but decreased uptake in Ga-67 deficient immune response poor prognosis

Infection in immunosuppressed patients

CMVLow-grade diffuse lung uptake, perihilarMaybe with ocular(retinitis), adrenal, renal uptak

e, persistent colon uptake(diarrhea)Lymphoid interstitial pneumonia

Low-grade diffuse lung uptake, without nodal uptake, and symmetrically increased parotid uptake

Infection in immunosuppressed patients

Focal pulmonary uptake Bacterial pneumonia: a lobar like, without nodal and

parotid uptake Actinomyces, Nocardia and Aspergillus: multiple sit

es of focal accumulation, frequently with local bone invasion

Nodal uptake Mycobacterium avium-intracellulare (MAI), tubercul

osis, cryptococcal, HSV infection and lymphadenitis, lymphoma

MAI: 25~50% of AIDS, patchy lung uptake with hilar and nonhilar nodal uptake

AIDS: Radionuclide Studies

Ga-67 scan: –Infection, Tumor (lymphoma)

Thallium-201 scan: –tumor (Kaposi’s sarcoma, lymphoma)

Tc-99m HMPAO brain SPECT: –Dementia

AIDS: Ga-67 scan and Tl-201 scan

Kaposi’s sarcoma: –Ga-67: (-), Tl-201: (+)

Infection: –Ga-67: (+), Tl-201: (-)

Lymphoma: –Ga-67: (+), Tl-201: (+)

Overview of Tumor Scintigraphy

Organ-specific tumor imaging radionuclides –Cold spot: Thyroid scan,

Liver scan –Hot spot: Bone scan, con

ventional brain scan

Non-specific tumor imaging radionuclides –Ga-67 –Tl-201 –Tc-99m sestamibi –Tc-99m (V) DMSA –PET (F-18 FDG)

Tumor-type specific radionuclides –Thyroid cancer: I-131

–Adrenal tumors: I-131 MIBG or NP-59

–Hepatocyte origin tumors: Tc-99m DISIDA

–Hemangioma: Tc-99m RBC

Ga-67 scan

Mechanism of tumor localizationAdequate blood supplyVascular premeabilitySpecific tumor-associated transferrin recept

orTumor metabolism

Ga-67 scan – image interpretation

Salivary gland uptake is noted after C/T or R/T Faint symmetrical hilar uptake may be seen no

rmally and is common after C/T Faint or absent liver uptake:

Extensive tumor metastases Hepatic failure C/T (vincristine) given within 24 hrs of Ga-67 injecte

d Iron overload

Ga-67 scan – tumor detectability

Histology: high gradeLesion sizeLocation: superficial > deepTumor detection: lymphoma, HCC, soft

tissue sarcoma, melanoma, lung cancer, head and neck tumors

Tl-201 Chloride tumor scan

Thallium-201: a potassium analogFactors determining tumor cell uptake:

Blood flowTumor viabilityTumor typeSodium-potassium ATPase systemCotransport systemCalcium ion channel system

Clearance by kidney, half-life: 73 hrs

Tl-201 Chloride tumor scan - Clinical application

Brain tumor Correlated with gliomas grade Post-op or post-R/T recurrent Therapeutic effectiveness In AIDS p’t: D.D. lymphoma and toxoplasmosis

Bone and soft tissue tumor Correlation between Tl-201 uptake and response to

C/T Lack of Tl-201 uptake tumor necrosis

Tl-201 Chloride tumor scan - Clinical application

Thyroid cancerAdvantage

Continue thyroid hormoneLocalized thyroid ca (when I-131 negative, but T

G elevated)Disadvantage

Not specificNot predict the potential therapeutic effectivenes

s

Kaposi’s sarcoma: Ga(-), Tl(+)

Tc-99m sestamibi

A lipophilic cationic complexFactors determining tumor cell uptake:

Blood flow Tumor viabilityTumor typeLipophilic cationLarge negative transmembrane potential

Tc-99m sestamibi

Localized in liver, kidney, heart and skeletal muscle

Difficult imaging:Sub-diaphragmatic tumor liver uptake an

d urinary clearanceBrain tumor choroid plexus uptake

Tc-99m sestamibi - Clinical application

Breast cancer Sensitivity 85%, specificity 81% Higher in palpable, lower for lesion < 1cm Fibroadenoma is commonest false positive Diffuse uptake is nonspecific and usually not malign

ancy Useful in

Non-diagnostic mammogram Dense breast or anatomical changed Fibrocystic disease

F-18 FDG tumor imaging

F-18 FDG: F-18 FDG enters the metabolic cycle like glucose, b

ut it is trapped in the tissue in the form of F-18 FDG-6-phosphate without further metabolism

Increased glycolysis associated with malignancy Excreted by kidney

Clinical: lung cancer, colorectal cancer, lymphoma, breast cancer etc.

Lymphoscintigraphy

Clinical applications of lymphoscintigraphy Distinguish lymphatic from venous edema, myxede

ma, lipedema, or other etiology Assess pathways of lymphatic drainage Identify sentinel nodes in patients with melanoma, b

reast, or genitourinary cancer Identify patients at high risk for development of lym

phedema after axillary lymph node dissection Quantify lymphatic flow

Lymphoscintigraphy

MethodologyRadiotracers : colloidal gold(198Au), Tc-99

m labeled tracers (antimony sulfide colloid, sulfur colloid, albumin colloid, HSA)

Tracer: injected into the tumor or surrounding tissue to identify the nodes receiving the lymphatic drainage of that tumor: subcutaneous, Intradermal, and Subfascial Injection

Sentinel lymph node detection and imaging

Lymphatic effluent of a tumor drains initially to one or two lymph nodes before other nodes receive the tumoral drainage

Sentinel node develops lymphatic metastases before other nodes

Careful examination of the sentinel node can be a more accurate predictor of regional nodal metastases than examination of adjacent nodes even if they are located in the same drainage basin as the sentinel node

Sentinel lymph node detection and imaging

If the sentinel node is negative for tumor, then other nodes are not likely to contain metastases, and the patient can be spared the unnecessary morbidity and expense of a more extensive node dissection

To localize the proximal or initial portion of the lymphatic chain, efferent from the tumor, for subsequent surgical excision and histologic diagnosis