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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

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hot stuff

HOT STUFF

Ionizing Radiation in Medicine

objectives
Objectives
  • History of nuclear medicine
  • Benefits of Nuclear Medicine
  • Radiation Biology: interactions and effects
  • Diagnostic and Therapeutic Applications
  • Common Nuclear Medicine procedures
overview
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
slide4
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
how it works

How it Works

Physical and Biological Considerations

basic concept
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
radiation physical characteristics
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
radiation decay products
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
biological effects tissue interaction
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
toxicity cellular effects
ToxicityCellular Effects
  • Function of ionization density
  • DNA bonds
    • repair mechanism overwhelmed
    • increased mutations
    • loss of ability to replicate
  • Free radicals
    • destruction of cellular contents
biological interactions linear energy transfer let
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
linear energy transfer
Linear Energy Transfer

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

biological interactions relative biological effect
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
biological interactions tissue radiosensitivity
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
biological interactions uptake and elimination
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
radiopharmacy selection of agent considerations
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
diagnostic modalities
Diagnostic Modalities
  • Positron Emission Tomography (PET)
  • Single Photon Emission Computed Tomography (SPECT)
  • Radioimmunoassay (RIA)
  • Scintigraphy
  • Co-Registration
    • PET with MRI or CT
diagnostic studies
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)
diagnostic studies exposure risk
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
positron emission tomography
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
monitoring therapy esophageal tumor
Monitoring Therapy Esophageal tumor
  • PET more sensitive than CT for monitoring therapy
  • Expanding role for PET
  • Society of Nuclear Medicine, Wieder et.al. 2005
metastatic breast carcinoma
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
scintigraphy compared with pet
Scintigraphy compared with PET
  • 27 year-old woman with history of breast cancer
case study
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
pet scan availability
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
spect
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%
cerebral ischemia sensitivity 90
Cerebral IschemiaSensitivity = 90%

Clin Nucl Med. 2006 Jul;31(7):376-8

spect muga cardiac function and ef
SPECT MUGA Cardiac Function and EF
  • Tc99m labeled rbc’s
  • Left ventricular hypertrophy with global hypokinesis
  • 47 years old with history of CAD
spect muga cardiac function and ef33
SPECT MUGA Cardiac Function and EF
  • Tc99m labeled rbc’s
  • Left ventricular hypertrophy with global hypokinesis
  • 47 years old with history of CAD
slide34

T-cell lymphoma

Emission from lateral thighs,

right triceps, and inguinal lymph nodes

scintigraphy
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
case study36
Case Study

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

case study38
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

slide39

Rhabdomyolisis

  • Elevated kidney uptake w/o bladder activity
  • Decreased activity in vastus medialis suggests necrosis
pet ct co registration
PET/CT Co-registration
  • Provides anatomical and physiological information
therapeutic modalities
Therapeutic Modalities
  • Brachytherapy
  • Ablation
  • Targeted Alpha Therapy
  • Gamma knife
  • External Beam
  • Boron Neutron Capture Therapy
therapeutic applications examples
Therapeutic ApplicationsExamples
  • Cancer Treatment
  • Tumor destruction
  • Palliation of pain
  • Marrow Transplants
brachytherapy
Brachytherapy
  • Radioactive “seeds” emplaced in surgically implanted tubes
  • Dose calculation by medical physicist
  • Tumour geometry determined through imaging modalities
prostate cancer treatment
Prostate Cancer Treatment
  • Tube placement geometry allows creation of interlocking radiation field around target
  • Field maximizes dose to target while minimizing collateral damage
iodine ablation
Iodine Ablation
  • Ingestion of radioactive cocktail I131
  • Dose delivered after surgical thyroidectomy
  • Patient becomes radioactive
  • Hospitalized until safe for general public
targeted alpha therapy
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
slide49
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
gamma knife
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
therapeutic benefits
Therapeutic Benefits
  • Brain tumors
    • (benign and malignant) brain tumors
    • metastatic lesions
    • allows treatment in hard-to-access (inoperable) areas of the brain.
  • Arteriovenous malformations (AVMs)
    • in brain can cause severe bleeding, headaches or seizures
  • Trigeminal neuralgia
    • create a lesion on the nerve blocking its pain signals
  • Acoustic neuromas
    • lower risk of deafness or loss of facial movement than with conventional surgery.
  • Pituitary tumors
gamma knife52
Gamma Knife
  • Concept: to create an interlocking field of gamma radiation emissions centered on the target
  • Tumour geometry is determined via imaging modality