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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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Ionizing Radiation in Medicine

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  • History of nuclear medicine

  • Benefits of Nuclear Medicine

  • Radiation Biology: interactions and effects

  • Diagnostic and Therapeutic Applications

  • Common Nuclear Medicine procedures

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  • 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

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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

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How it Works

Physical and Biological Considerations

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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

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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

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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

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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

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ToxicityCellular Effects

  • Function of ionization density

  • DNA bonds

    • repair mechanism overwhelmed

    • increased mutations

    • loss of ability to replicate

  • Free radicals

    • destruction of cellular contents

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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

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Linear Energy Transfer

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

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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

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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

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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

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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

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Diagnostic Modalities

  • Positron Emission Tomography (PET)

  • Single Photon Emission Computed Tomography (SPECT)

  • Radioimmunoassay (RIA)

  • Scintigraphy

  • Co-Registration

    • PET with MRI or CT

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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)

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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

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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

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Monitoring Therapy Esophageal tumor

  • PET more sensitive than CT for monitoring therapy

  • Expanding role for PET

  • Society of Nuclear Medicine, Wieder 2005

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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

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Scintigraphy compared with PET

  • 27 year-old woman with history of breast cancer

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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

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Post-surgical Abscess

  • 18F PET study

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PET Scan Availability

  • Increasing availabilty

    • over 1600 centers nationwide


  • Cost

    • $3 000 to $6 000

    • 3 hours for study

  • Advantages

    • metabolic scanning

  • Provider information


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  • 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%

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Cerebral IschemiaSensitivity = 90%

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

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SPECT MUGA Cardiac Function and EF

  • Tc99m labeled rbc’s

  • Left ventricular hypertrophy with global hypokinesis

  • 47 years old with history of CAD

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SPECT MUGA Cardiac Function and EF

  • Tc99m labeled rbc’s

  • Left ventricular hypertrophy with global hypokinesis

  • 47 years old with history of CAD

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T-cell lymphoma

Emission from lateral thighs,

right triceps, and inguinal lymph nodes

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  • 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

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Case Study

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

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Bone Scan at 7 days post-injury

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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

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  • Elevated kidney uptake w/o bladder activity

  • Decreased activity in vastus medialis suggests necrosis

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PET/CT Co-registration

  • Provides anatomical and physiological information

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Therapeutic Modalities

  • Brachytherapy

  • Ablation

  • Targeted Alpha Therapy

  • Gamma knife

  • External Beam

  • Boron Neutron Capture Therapy

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Therapeutic ApplicationsExamples

  • Cancer Treatment

  • Tumor destruction

  • Palliation of pain

  • Marrow Transplants

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  • Radioactive “seeds” emplaced in surgically implanted tubes

  • Dose calculation by medical physicist

  • Tumour geometry determined through imaging modalities

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Prostate Cancer Treatment

  • Tube placement geometry allows creation of interlocking radiation field around target

  • Field maximizes dose to target while minimizing collateral damage

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Iodine Ablation

  • Ingestion of radioactive cocktail I131

  • Dose delivered after surgical thyroidectomy

  • Patient becomes radioactive

  • Hospitalized until safe for general public

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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

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Monoclonal AntibodyRadioactive Source Chelated to Agent

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  • 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

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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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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

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Gamma Knife

  • Concept: to create an interlocking field of gamma radiation emissions centered on the target

  • Tumour geometry is determined via imaging modality