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Radionuclide imaging in bone, inflammation and oncology 吳佩珊醫師
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Radionuclide imaging in bone, inflammation and oncology 吳佩珊醫師


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  • 1. Bone Scintigraphy Department of Nuclear Medicine Dr. Pei-Shan Wu
  • 2. 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
  • 3. 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
  • 4. 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
  • 5. 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, Paget’s disease, and fibrous dysplasia
  • 6. Abnormal bone scans B. Primary malignant bone tumors  Osteogenic sarcoma, chondrosarcoma, Ewing’s sarcoma C. Benign primary tumors  Osteoid osteoma, bone islands, bone cysts, fibrous cortical defects, and others D. Osteomyelitis and septic arthritis
  • 7. 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
  • 8. 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
  • 9. 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. Paget’s disease _increased uptake in bone scan _distribution of lesions: pelvis (70~80%), lumbar- thoracic vertebrae, femur, skull, scapula, tibia, and humerus
  • 10. Abnormal bone scans 4. Hyperparathyroidism a. Primary: caused by hyperplasia or tumor of parathyroids  50~80% 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
  • 11. 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 4~8 years
  • 12. 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
  • 13. Radionuclide inflammation scan and tumor scan Department of Nuclear Medicine Dr. Pei-Shan Wu
  • 14. 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
  • 15. Gallium-67 Cyclotron produced Half-life: 78 hrs Biological behavior: similar to ferric ion Binding to iron-binding molecules, including transferrin, lactoferrin, ferritin, siderophores
  • 16. 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
  • 17. 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
  • 18. 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, woman’s hormonal cycle  Thymus: children
  • 19. 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
  • 20. 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
  • 21. 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
  • 22. 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
  • 23. Tc-99m (V) DMSA scan: Advantages Good availability High resolution Low price Low radiation dose Preparation technique: Easy Imaging: 4 hr post-injection
  • 24. Tc-99m (V) DMSA scan: Disadvantages GU tract infection Infection vs tumor Chronic infection Further study
  • 25. 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
  • 26. 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%
  • 27. 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
  • 28. 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
  • 29. 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%
  • 30. 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
  • 31. 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
  • 32. 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: 25~50% of AIDS, patchy lung uptake with hilar and nonhilar nodal uptake
  • 33. AIDS: Radionuclide Studies Ga-67 scan: –Infection, Tumor (lymphoma) Thallium-201 scan: –tumor (Kaposi’s sarcoma, lymphoma) Tc-99m HMPAO brain SPECT: –Dementia
  • 34. 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: (+)
  • 35. 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
  • 36. Ga-67 scan Mechanism of tumor localization Adequate blood supply Vascular premeability Specific tumor-associated transferrin receptor Tumor metabolism
  • 37. 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
  • 38. Ga-67 scan – tumor detectability Histology: high grade Lesion size Location: superficial > deep Tumor detection: lymphoma, HCC, soft tissue sarcoma, melanoma, lung cancer, head and neck tumors
  • 39. 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
  • 40. 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
  • 41. 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 Kaposi’s sarcoma: Ga(-), Tl(+)
  • 42. Tc-99m sestamibi A lipophilic cationic complex Factors determining tumor cell uptake: Blood flow Tumor viability Tumor type Lipophilic cation Large negative transmembrane potential
  • 43. 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
  • 44. 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 malignancy  Useful in  Non-diagnostic mammogram  Dense breast or anatomical changed  Fibrocystic disease
  • 45. 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.
  • 46. 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
  • 47. 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
  • 48. 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
  • 49. 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