Bone Scintigraphy Department of Nuclear Medicine Dr

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Bone Scintigraphy

• Department of Nuclear Medicine
• Dr. Pei-Shan Wu

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Radiopharmaceuticals

• Sr-85 high radiation absorbed dose, poor imaging
  characteristics, and delayed imaging time (57
  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

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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
• 24 hr after tracer administration
• 4. Images three-phase, whole body, SPECT

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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
  sutures
• 3. 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 free pertechnetate causes activity in
  thyroid and GI tract

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Abnormal bone scans

• A. Metastatic disease
• Tumors most likely to metastasize to bone
  include breast, 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 bladder and lymphoma
• _ nontumor causes of super scan
  hyperparathyroidism, osteomalacia, Pagets
  disease, and fibrous dysplasia

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Abnormal bone scans

• B. Primary malignant bone tumors
• Osteogenic sarcoma, chondrosarcoma, Ewings
  sarcoma
• C. Benign primary tumors
• Osteoid osteoma, bone islands, bone cysts,
  fibrous cortical defects, and others
• D. Osteomyelitis and septic arthritis

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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/epiphyse
  al region
• _may miss some skull fractures

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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, pagets disease, fibrous dysplasia,
  and status postirradiation

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Abnormal bone scans

• F. Metabolic bone disease
• 1. Osteoporosis normal or decreased uptake
• 2. Osteomalacia
• _vitamin D deficiency
• _results in failure of bone matrix to calcify
• _generalized increased skeletal uptake
• 3. Pagets disease
• _increased uptake in bone scan
• _distribution of lesions pelvis (7080),
  lumbar-thoracic vertebrae, femur, skull, scapula,
  tibia, and humerus

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Abnormal bone scans

• 4. Hyperparathyroidism
• a. Primary caused by hyperplasia or tumor of
  parathyroids
• 5080 normal bone scan
• abnormal uptake at calvarium, mandible,
  acromioclavicular 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

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Abnormal bone scans

• G. Avascular necrosis
• result of fracture, metabolic disorder, fat
  embolization, steroids, hemolytic anemia, and
  vasculitis
• plain film is normal in early stage (6 months)
• bone scan normal for first 48 hr ? decreased
  activity ? increased activity ? develop
  degenerative joint disease (increased uptake in
  the acetabulum)
• Legg-Calve-Perthes disease afftects boys aged
  48 years

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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

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Radionuclide inflammation scan and tumor scan

• Department of Nuclear Medicine
• Dr. Pei-Shan Wu

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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

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Gallium-67

• Cyclotron produced
• Half-life 78 hrs
• Biological behavior similar to ferric ion
• Binding to iron-binding molecules, including
  transferrin, lactoferrin, ferritin, siderophores

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Gallium-67 scan Mechanism

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

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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-negative
• Imaging parameters
• Energy 93, 185, 296 keV peaks
• Total body scan, focal view, SEPCT
• Medium energy collimator
• Bowel activity bowel preparation

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Ga-67 scan Normal distribution

• Liver greatest Ga-67 uptake
• Other Spleen, nasopharynx, lacrimal and salivary
  glands, bone marrow, scrotum, testes
• First 24 hours kidneys, bladder
•  - 48-72 hours kidneys only faintly visualized
• After 24 hours, biological clearance through
  bowel
• Breast uptake variable, womans hormonal cycle
• Thymus children

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Ga-67 scan image interpretation

• Abnormal uptake
• liver or spleen ? abscess
• liver ? clinical important inflammation
• lt bone marrow ? low-level inflammation
• No difference in sensitivity fro acute or chronic
  infection
• Less sensitivity in tuberculosis, fungal infection

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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 patients
• Tumor detection

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Ga-67 scan Disadvantages

• Time delay between injection and imaging
• Poor spatial definition of anatomically discrete
  lesions
• Potential misinterpretation as a result of
  gallium uptake in adjacent organ (e.g. liver)
• Bowel activity
• Infection vs tumor

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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

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Tc-99m (V) DMSA scan Advantages

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

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Tc-99m (V) DMSA scan Disadvantages

• GU tract infection
• Infection vs tumor
• Chronic infection
• Further study

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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

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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

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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

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Neonatal osteomyelitis

• Diffuse nature, propensity for complications,
  paucity of associated signs gt whole body image
• Three-phase bone scan
• 22-68 falsely normal or cold defects
• Resolution
• Cold lesion subperiosteal abscess
• Bone scan negative, clinically suspected  gt
  Ga-67 scan

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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 infection
• 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

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Infection in immunosuppressed patients

• Diffuse pulmonary uptake
• PCP
• 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

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Infection in immunosuppressed patients

• CMV
• Low-grade diffuse lung uptake, perihilar
• Maybe with ocular(retinitis), adrenal, renal
  uptake, persistent colon uptake(diarrhea)
• Lymphoid interstitial pneumonia
• Low-grade diffuse lung uptake, without nodal
  uptake, and symmetrically increased parotid uptake

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Infection in immunosuppressed patients

• Focal pulmonary uptake
• Bacterial pneumonia a lobar like, without nodal
  and parotid uptake
• Actinomyces, Nocardia and Aspergillus multiple
  sites of focal accumulation, frequently with
  local bone invasion
• Nodal uptake
• Mycobacterium avium-intracellulare (MAI),
  tuberculosis, cryptococcal, HSV infection and
  lymphadenitis, lymphoma
• MAI 2550 of AIDS, patchy lung uptake with
  hilar and nonhilar nodal uptake

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AIDS Radionuclide Studies

• Ga-67 scan
• Infection, Tumor (lymphoma)
• Thallium-201 scan
• tumor (Kaposis sarcoma, lymphoma)
• Tc-99m HMPAO brain SPECT
• Dementia

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AIDS Ga-67 scan and Tl-201 scan

• Kaposis sarcoma
• Ga-67 (-), Tl-201 ()
• Infection
• Ga-67 (), Tl-201 (-)
• Lymphoma
• Ga-67 (), Tl-201 ()

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Overview of Tumor Scintigraphy

• Organ-specific tumor imaging radionuclides
• Cold spot Thyroid scan, Liver scan
• Hot spot Bone scan, conventional 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

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Ga-67 scan

• Mechanism of tumor localization
• Adequate blood supply
• Vascular premeability
• Specific tumor-associated transferrin receptor
• Tumor metabolism

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Ga-67 scan image interpretation

• Salivary gland uptake is noted after C/T or R/T
• Faint symmetrical hilar uptake may be seen
  normally 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
  injected
• Iron overload

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Ga-67 scan tumor detectability

• Histology high grade
• Lesion size
• Location superficial gt deep
• Tumor detection lymphoma, HCC, soft tissue
  sarcoma, melanoma, lung cancer, head and neck
  tumors

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Tl-201 Chloride tumor scan

• Thallium-201 a potassium analog
• Factors determining tumor cell uptake
• Blood flow
• Tumor viability
• Tumor type
• Sodium-potassium ATPase system
• Cotransport system
• Calcium ion channel system
• Clearance by kidney, half-life 73 hrs

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Tl-201 Chloride tumor scan
- Clinical application

• Brain tumor
• Correlated with gliomas grade
• Post-op or post-R/T recurrent
• Therapeutic effectiveness
• In AIDS pt 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

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Tl-201 Chloride tumor scan
- Clinical application

• Thyroid cancer
• Advantage
• Continue thyroid hormone
• Localized thyroid ca (when I-131 negative, but TG
  elevated)
• Disadvantage
• Not specific
• Not predict the potential therapeutic
  effectiveness
• Kaposis sarcoma Ga(-), Tl()

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Tc-99m sestamibi

• A lipophilic cationic complex
• Factors determining tumor cell uptake
• Blood flow
• Tumor viability
• Tumor type
• Lipophilic cation
• Large negative transmembrane potential

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Tc-99m sestamibi

• Localized in liver, kidney, heart and skeletal
  muscle
• Difficult imaging
• Sub-diaphragmatic tumor ? liver uptake and
  urinary clearance
• Brain tumor ? choroid plexus uptake

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Tc-99m sestamibi -
Clinical application

• Breast cancer
• Sensitivity 85, specificity 81
• Higher in palpable, lower for lesion lt 1cm
• Fibroadenoma is commonest false positive
• Diffuse uptake is nonspecific and usually not
  malignancy
• Useful in
• Non-diagnostic mammogram
• Dense breast or anatomical changed
• Fibrocystic disease

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F-18 FDG tumor imaging

• F-18 FDG
• F-18 FDG enters the metabolic cycle like glucose,
  but 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.

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Lymphoscintigraphy

• Clinical applications of lymphoscintigraphy
• Distinguish lymphatic from venous edema,
  myxedema, lipedema, or other etiology
• Assess pathways of lymphatic drainage
• Identify sentinel nodes in patients with
  melanoma, breast, or genitourinary cancer
• Identify patients at high risk for development of
  lymphedema after axillary lymph node dissection
• Quantify lymphatic flow

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Lymphoscintigraphy

• Methodology
• Radiotracers colloidal gold(198Au), Tc-99m
  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

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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

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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