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HOT STUFF

HOT STUFF. Ionizing Radiation in Medicine. Objectives. History of nuclear medicine Benefits of Nuclear Medicine Radiation Biology: interactions and effects Diagnostic and Therapeutic Applications Common Nuclear Medicine procedures. Overview. Over 20 million procedures annually in US

PamelaLan
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HOT STUFF

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  1. HOT STUFF Ionizing Radiation in Medicine

  2. Objectives • History of nuclear medicine • Benefits of Nuclear Medicine • Radiation Biology: interactions and effects • Diagnostic and Therapeutic Applications • Common Nuclear Medicine procedures

  3. Overview • Over 20 million procedures annually in US • Provides information unobtainable by other means • Useful for diagnosis and therapy • Sensitive, can detect many diseases at early stages • Less expensive than exploratory surgery • Based on ionizing radiation • Allows evaluation of physiologic function • Non-invasive, painless

  4. Historical Perspectives • 1896 X radiation discovered by Roentgen • 1896 Ionizing radiation discovered by Becquerel • 1900 Quantum Hypothesis - Planck • 1905 Special Theory of Relativity - Einstein • Continuing interest led to development of the field of Radiation Physics • Advances allowed for the creation of isotopes • varying physical characteristics • 1951 FDA approves I131 as radiopharmaceutical

  5. How it Works Physical and Biological Considerations

  6. Basic Concept • Radiation is used to image or treat disease • external or internal source • Radiopharmaceutical is selected • physical characteristics of radiation source • biological characteristics of target cells • Radiation dose is administered to patient • inhalation, ingestion, injection, or external beam • Imaging is possible due to radiation energy • Therapy is possible due to radiotoxicity

  7. Radiation Physical Characteristics • Nucleus • protons, neutrons • neutrons “stabilize” nucleus • Nuclear instability • increasing nuclear mass => decreasing nuclear stability • Decay to stable state through loss of mass • as energy (E=mc2) in the form of photons • as particles: alpha, beta, positron, neutron • Radiological half-life • time to decay to one-half original activity

  8. RadiationDecay Products • Alpha particle • high mass (2 neutron, 2 protons) • low velocity • Beta • low mass (electron) • intermediate energy • Gamma • very low mass (photon, wave-particle duality) • energetic • Neutron • wide range of energies • activation

  9. Biological EffectsTissue Interaction • Ionizing Radiation Toxicity • disrupts cellular DNA • creates free radicals (peroxides) • Linear Energy Transfer (LET) • Tissue radiosensitivity • relative biological effect • uptake and elimination

  10. ToxicityCellular Effects • Function of ionization density • DNA bonds • repair mechanism overwhelmed • increased mutations • loss of ability to replicate • Free radicals • destruction of cellular contents

  11. Biological InteractionsLinear Energy Transfer (LET) • Measure of ionization density • ionizations/unit volume • Energy (eV) deposited per micrometer of travel • Low LET: gamma, beta, x-radiation • High LET: alpha, neutron radiation

  12. Linear Energy Transfer FIGURE 4.3 Penetrating power of alpha and beta particles. SOURCE: Courtesy of Joseph Jurcic, Memorial Sloan-Kettering Cancer Center.

  13. Biological Interactions Relative Biological Effect • Relative Biological Effect • relative effectiveness of different emissions in producing a biological effect • Quality factor (Q) • tissue effects of different types of radiation • photon, beta = 1 • neutron = 10 • alpha = 20

  14. Biological Interactions Tissue Radiosensitivity • Metabolic Rate • correlates with nutrient uptake rate • Tissue-specific nutrients, configuration • Replication rate • correlates with nutrient uptake rate • Elimination rate • biological half-life

  15. Biological Interactions Uptake and elimination • Nutrient/substrate uptake • attach nucliide to ligand • preferential uptake by target cells • Glucose in brain • Elimination • biological half-life • matabolism • physical half-life

  16. RadiopharmacySelection of Agent: Considerations • High LET • high energy deposition in target cells • ionizations produced in target cells • Low LET • little energy absorbed per unit weight • few ionizations produced in tissue • Target cell specificity • uptake • Exposure to surrounding tissue • ALARA

  17. Commonly used Isotopes

  18. Applications in Medicine Diagnostics

  19. Diagnostic Modalities • Positron Emission Tomography (PET) • Single Photon Emission Computed Tomography (SPECT) • Radioimmunoassay (RIA) • Scintigraphy • Co-Registration • PET with MRI or CT

  20. Diagnostic Studies • Renal function • Coronary artery perfusion and cardiac function • Lung scans for respiratory and blood flow problems • Inflammation and infection • Ortho - fractures, infection, arthritis and tumors • Cancer detection and localization • lymph node evaluation, metastases • GI bleed • Thyroid function • Cerebral perfusion and abnormalities (seizures, memory loss, TBI)

  21. Diagnostic StudiesExposure Risk • Low energy gamma and positron radiations • Low exposure (dose) • comparable to diagnostic x-ray studies • natural background radiation • Low risk • dose received is not harmful to the patient

  22. Positron Emission Tomography • F18 FDG (fluorodeoxyglucose) typically used • weak positron emitter (low radiation dose) • Glucose analog • high uptake by brain, kidney, tumor, cardiac, and lung tissue • physiologic function • Excellent 3-D imaging • precise localization of tissue • monitoring therapeutic efficacy

  23. PET Brain

  24. Monitoring Therapy Esophageal tumor • PET more sensitive than CT for monitoring therapy • Expanding role for PET • Society of Nuclear Medicine, Wieder et.al. 2005

  25. Metastatic Breast Carcinoma • 27 year-old woman initially diagnosed with invasive ductal carcinoma by ultrasound guided biopsy. She underwent bilateral mastectomy, chemotherapy, and right-sided radiation

  26. Scintigraphy compared with PET • 27 year-old woman with history of breast cancer

  27. Case Study • 49 year old man presents for staging after grossly complete excision of a high grade fibrosarcoma from the right groin 1.5 weeks earlier • Uneventful surgery • Progressively increasing pain at the surgical site following removal of a drain 4 days earlier

  28. Post-surgical Abscess • 18F PET study

  29. PET Scan Availability • Increasing availabilty • over 1600 centers nationwide • http://petnetsolutions.com/zportal/portals/pat/find_a_pet_center/imagingcenter • Cost • $3 000 to $6 000 • 3 hours for study • Advantages • metabolic scanning • Provider information • http://www.petscaninfo.com/zportal/portals/phys

  30. SPECT • Less expensive than PET • $1000 v $3000 • Widely available • Commonly used for brain scans, perfusion studies • Sensitivity • cerebral ischemia 90% (v 20% CT) @ 8 hours • fracture 80% @ 24 hours, 95% @ 72 hours • seizure (ictal state) 81-93% • myocardial ischemia 90%

  31. Cerebral IschemiaSensitivity = 90% Clin Nucl Med. 2006 Jul;31(7):376-8

  32. SPECT MUGA Cardiac Function and EF • Tc99m labeled rbc’s • Left ventricular hypertrophy with global hypokinesis • 47 years old with history of CAD

  33. SPECT MUGA Cardiac Function and EF • Tc99m labeled rbc’s • Left ventricular hypertrophy with global hypokinesis • 47 years old with history of CAD

  34. T-cell lymphoma Emission from lateral thighs, right triceps, and inguinal lymph nodes

  35. Scintigraphy • Molecular imaging • indicator of metabolic activity • “hot spots” where uptake is high • Low radiation exposure • Short half-life, low energy gamma radiation • Extensive application in many specialties • Orthopedics, Cardiology, Endocrinology, etc

  36. Case Study X-ray of an 18-month-old boy unable to bear weight on his R leg s/p twisting injury x 2d

  37. Bone Scan at 7 days post-injury

  38. Case Study 18 yo. male with darkening urine, worsening muscle pain, and decreasing urine output over the past 3 days after one day of intense physical exercise

  39. Rhabdomyolisis • Elevated kidney uptake w/o bladder activity • Decreased activity in vastus medialis suggests necrosis

  40. PET/CT Co-registration • Provides anatomical and physiological information

  41. Applications in Medicine Therapeutics

  42. Therapeutic Modalities • Brachytherapy • Ablation • Targeted Alpha Therapy • Gamma knife • External Beam • Boron Neutron Capture Therapy

  43. Therapeutic ApplicationsExamples • Cancer Treatment • Tumor destruction • Palliation of pain • Marrow Transplants

  44. Brachytherapy • Radioactive “seeds” emplaced in surgically implanted tubes • Dose calculation by medical physicist • Tumour geometry determined through imaging modalities

  45. Prostate Cancer Treatment • Tube placement geometry allows creation of interlocking radiation field around target • Field maximizes dose to target while minimizing collateral damage

  46. Iodine Ablation • Ingestion of radioactive cocktail I131 • Dose delivered after surgical thyroidectomy • Patient becomes radioactive • Hospitalized until safe for general public

  47. Targeted Alpha Therapy • Carrier molecule “tagged” with alpha emitter • monoclonal antibodies • Delivery of alpha-emitting isotopes to target • High LET • capable of killing in a range of 1 to 3 cells • Leukemia cells and small solid tumors • Myeloid leukemias, prostate cancer, and lymphoma treatments are under study

  48. Monoclonal AntibodyRadioactive Source Chelated to Agent

  49. BNCT • Boron Neutron Capture Therapy • Boron delivered to target cells • Neutron irradiation => activiation of boron • 11Boron decay yields alpha particles • High LET of alpha deposits energy within 3 cell diameters • kills target while minimizing effect to surrounding tissue

  50. Gamma Knife • Precise location and tumor geometry essential • Cobalt-60 source • high level of penetrating gamma rays • Two hundred one beams focused on target • Delivery controlled by shield • Frame emplaced to hold shield • Procedure lasts about 4 hours

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