HOT STUFFHOT STUFF

Ionizing Radiation in Ionizing Radiation in MedicineMedicine

ObjectivesObjectives

• History of nuclear medicineHistory of nuclear medicine• Benefits of Nuclear MedicineBenefits of Nuclear Medicine• Radiation Biology: interactions and Radiation Biology: interactions and

effectseffects• Diagnostic and Therapeutic Diagnostic and Therapeutic

ApplicationsApplications• Common Nuclear Medicine Common Nuclear Medicine

proceduresprocedures

OverviewOverview• Over 20 million procedures annually in US Over 20 million procedures annually in US • Provides information unobtainable by Provides information unobtainable by

other meansother means• Useful for diagnosis and therapy Useful for diagnosis and therapy • Sensitive, can detect many diseases at Sensitive, can detect many diseases at

early stages early stages • Less expensive than exploratory surgeryLess expensive than exploratory surgery• Based on ionizing radiationBased on ionizing radiation• Allows evaluation of physiologic functionAllows evaluation of physiologic function• Non-invasive, painlessNon-invasive, painless

Historical PerspectivesHistorical Perspectives• 1896 X radiation discovered by Roentgen 1896 X radiation discovered by Roentgen • 1896 Ionizing radiation discovered by 1896 Ionizing radiation discovered by

Becquerel Becquerel • 1900 Quantum Hypothesis - Planck1900 Quantum Hypothesis - Planck• 1905 Special Theory of Relativity - Einstein1905 Special Theory of Relativity - Einstein• Continuing interest led to development of Continuing interest led to development of

the field of Radiation Physics the field of Radiation Physics • Advances allowed for the creation of Advances allowed for the creation of

isotopesisotopes– varying physical characteristicsvarying physical characteristics

• 1951 FDA approves I1951 FDA approves I131131 as as radiopharmaceuticalradiopharmaceutical

How it WorksHow it Works

Physical and Biological Physical and Biological ConsiderationsConsiderations

Basic ConceptBasic Concept• Radiation is used to image or treat diseaseRadiation is used to image or treat disease

– external or internal sourceexternal or internal source

• Radiopharmaceutical is selectedRadiopharmaceutical is selected– physical characteristics of radiation sourcephysical characteristics of radiation source– biological characteristics of target cellsbiological characteristics of target cells

• Radiation dose is administered to patientRadiation dose is administered to patient– inhalation, ingestion, injection, or external beaminhalation, ingestion, injection, or external beam

• Imaging is possible due to radiation energyImaging is possible due to radiation energy• Therapy is possible due to radiotoxicityTherapy is possible due to radiotoxicity

Radiation Radiation Physical CharacteristicsPhysical Characteristics

• Nucleus Nucleus – protons, neutronsprotons, neutrons– neutrons “stabilize” nucleusneutrons “stabilize” nucleus

• Nuclear instabilityNuclear instability– increasing nuclear mass => decreasing increasing nuclear mass => decreasing

nuclear stabilitynuclear stability• Decay to stable state through loss of Decay to stable state through loss of

massmass– as energy (E=mcas energy (E=mc22) in the form of photons) in the form of photons– as particles: alpha, beta, positron, neutronas particles: alpha, beta, positron, neutron

• Radiological half-life Radiological half-life – time to decay to one-half original activitytime to decay to one-half original activity

RadiationRadiationDecay ProductsDecay Products

• Alpha particle Alpha particle – high mass (2 neutron, 2 protons)high mass (2 neutron, 2 protons)– low velocitylow velocity

• BetaBeta– low mass (electron)low mass (electron)– intermediate energyintermediate energy

• Gamma Gamma – very low mass (photon, wave-particle duality)very low mass (photon, wave-particle duality)– energeticenergetic

• NeutronNeutron– wide range of energieswide range of energies– activationactivation

Biological EffectsBiological EffectsTissue InteractionTissue Interaction

• Ionizing Radiation ToxicityIonizing Radiation Toxicity– disrupts cellular DNAdisrupts cellular DNA– creates free radicals (peroxides)creates free radicals (peroxides)

• Linear Energy Transfer (LET) Linear Energy Transfer (LET) • Tissue radiosensitivityTissue radiosensitivity

– relative biological effectrelative biological effect– uptake and eliminationuptake and elimination

ToxicityToxicityCellular EffectsCellular Effects

• Function of ionization densityFunction of ionization density• DNA bondsDNA bonds

– repair mechanism overwhelmedrepair mechanism overwhelmed– increased mutationsincreased mutations– loss of ability to replicateloss of ability to replicate

• Free radicalsFree radicals– destruction of cellular contentsdestruction of cellular contents

Biological InteractionsBiological InteractionsLinear Energy Transfer (LETLinear Energy Transfer (LET))

• Measure of ionization densityMeasure of ionization density– ionizations/unit volumeionizations/unit volume

• Energy (eV) deposited per Energy (eV) deposited per micrometer of travelmicrometer of travel– Low LET: gamma, beta, x-radiationLow LET: gamma, beta, x-radiation– High LET: alpha, neutron radiationHigh LET: alpha, neutron radiation

Linear Energy TransferLinear Energy Transfer

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

Biological Interactions Biological Interactions Relative Biological EffectRelative Biological Effect

• Relative Biological Effect Relative Biological Effect – relative effectiveness of different relative effectiveness of different

emissions in producing a biological emissions in producing a biological effecteffect

• Quality factor (Q) Quality factor (Q) – tissue effects of different types of tissue effects of different types of

radiationradiation• photon, beta = 1photon, beta = 1• neutron = 10neutron = 10• alpha = 20 alpha = 20

Biological Interactions Biological Interactions Tissue RadiosensitivityTissue Radiosensitivity

• Metabolic RateMetabolic Rate– correlates with nutrient uptake ratecorrelates with nutrient uptake rate

• Tissue-specific nutrients, Tissue-specific nutrients, configurationconfiguration

• Replication rateReplication rate– correlates with nutrient uptake ratecorrelates with nutrient uptake rate

• Elimination rateElimination rate– biological half-lifebiological half-life

Biological Interactions Biological Interactions Uptake and eliminationUptake and elimination

• Nutrient/substrate uptakeNutrient/substrate uptake– attach nucliide to ligandattach nucliide to ligand– preferential uptake by target cellspreferential uptake by target cells

• Glucose in brainGlucose in brain

• EliminationElimination– biological half-lifebiological half-life– matabolismmatabolism– physical half-lifephysical half-life

RadiopharmacyRadiopharmacySelection of Agent: Selection of Agent:

ConsiderationsConsiderations• High LETHigh LET

– high energy deposition in target cellshigh energy deposition in target cells– ionizations produced in target cellsionizations produced in target cells

• Low LETLow LET– little energy absorbed per unit weightlittle energy absorbed per unit weight– few ionizations produced in tissuefew ionizations produced in tissue

• Target cell specificityTarget cell specificity– uptakeuptake

• Exposure to surrounding tissueExposure to surrounding tissue– ALARAALARA

Commonly used IsotopesCommonly used IsotopesIsotope half-life Emission Energy

keVYield% Use

Tc99m 6.02h Gamma 140 89 multiple

I131 8.04d Gammabeta

364606

8189

thyroid

Xe133 5.24d Gammabeta

81346

3699

lung scans

In111 2.83d GammaGamma

245171

9490

leukocytes

Applications in Applications in MedicineMedicineDiagnosticsDiagnostics

Diagnostic ModalitiesDiagnostic Modalities

• Positron Emission Tomography Positron Emission Tomography (PET)(PET)

• Single Photon Emission Computed Single Photon Emission Computed Tomography Tomography (SPECT)(SPECT)

• RadioimmunoassayRadioimmunoassay (RIA) (RIA)

• ScintigraphyScintigraphy• Co-RegistrationCo-Registration

– PET with MRI or CT

Diagnostic StudiesDiagnostic Studies

• Renal function Renal function • Coronary artery perfusion and cardiac functionCoronary artery perfusion and cardiac function• Lung scans for respiratory and blood flow Lung scans for respiratory and blood flow

problems problems • Inflammation and infectionInflammation and infection• Ortho - fractures, infection, arthritis and Ortho - fractures, infection, arthritis and

tumors tumors • Cancer detection and localization Cancer detection and localization

– lymph node evaluation, metastaseslymph node evaluation, metastases• GI bleedGI bleed• Thyroid function Thyroid function • Cerebral perfusion and abnormalities Cerebral perfusion and abnormalities

(seizures, memory loss, TBI)(seizures, memory loss, TBI)

Diagnostic StudiesDiagnostic StudiesExposure RiskExposure Risk

• Low energy gamma and positron Low energy gamma and positron radiationsradiations

• Low exposure (dose)Low exposure (dose)– comparable to diagnostic x-ray studiescomparable to diagnostic x-ray studies– natural background radiationnatural background radiation

• Low riskLow risk– dose received is not harmful to the dose received is not harmful to the

patient patient

Positron Emission Positron Emission TomographyTomography

• FF1818 FDG (fluorodeoxyglucose) typically FDG (fluorodeoxyglucose) typically used used – weak positron emitter (low radiation dose)weak positron emitter (low radiation dose)

• Glucose analogGlucose analog– high uptake by brain, kidney, tumor, high uptake by brain, kidney, tumor,

cardiac, and lung tissuecardiac, and lung tissue– physiologic functionphysiologic function

• Excellent 3-D imagingExcellent 3-D imaging– precise localization of tissue precise localization of tissue – monitoring therapeutic efficacymonitoring therapeutic efficacy

PET BrainPET Brain

Monitoring Therapy Monitoring Therapy Esophageal tumorEsophageal tumor

• PET more sensitive than CT for monitoring therapyPET more sensitive than CT for monitoring therapy• Expanding role for PETExpanding role for PET• Society of Nuclear Medicine, Wieder et.al. 2005Society of Nuclear Medicine, Wieder et.al. 2005

Metastatic Breast Metastatic Breast CarcinomaCarcinoma

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

Scintigraphy compared with Scintigraphy compared with PETPET

• 27 year-old woman with history of breast cancer27 year-old woman with history of breast cancer

Case StudyCase Study

• 49 year old man presents for staging 49 year old man presents for staging after grossly complete excision of a after grossly complete excision of a high grade fibrosarcoma from the high grade fibrosarcoma from the right groin 1.5 weeks earlierright groin 1.5 weeks earlier

• Uneventful surgeryUneventful surgery• Progressively increasing pain at the Progressively increasing pain at the

surgical site following removal of a surgical site following removal of a drain 4 days earlier drain 4 days earlier

Post-surgical AbscessPost-surgical Abscess

• 1818F PET studyF PET study

PET Scan AvailabilityPET Scan Availability• Increasing availabiltyIncreasing availabilty

– over 1600 centers nationwideover 1600 centers nationwide– http://petnetsolutions.com/zportal/portals/http://petnetsolutions.com/zportal/portals/

pat/find_a_pet_center/imagingcenterpat/find_a_pet_center/imagingcenter• CostCost

– $3 000 to $6 000 $3 000 to $6 000 – 3 hours for study3 hours for study

• AdvantagesAdvantages– metabolic scanning metabolic scanning

• Provider informationProvider information– http://http://

www.petscaninfo.com/zportal/portals/physwww.petscaninfo.com/zportal/portals/phys

SPECTSPECT• Less expensive than PETLess expensive than PET

– $1000 v $3000$1000 v $3000

• Widely availableWidely available• Commonly used for brain scans, Commonly used for brain scans,

perfusion studiesperfusion studies• SensitivitySensitivity

– cerebral ischemia 90% (v 20% CT) @ 8 hourscerebral ischemia 90% (v 20% CT) @ 8 hours– fracturefracture 80% @ 24 hours, 95% @ 72 hours 80% @ 24 hours, 95% @ 72 hours– seizure (ictal state) 81-93%seizure (ictal state) 81-93%– myocardial ischemia 90%myocardial ischemia 90%

Cerebral IschemiaCerebral IschemiaSensitivity = 90%Sensitivity = 90%

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

SPECTSPECT MUGA MUGA Cardiac Function and Cardiac Function and

EF EF

• Tc99m labeled rbc’s Tc99m labeled rbc’s • Left ventricular hypertrophy with global Left ventricular hypertrophy with global

hypokinesishypokinesis• 47 years old with history of CAD47 years old with history of CAD

SPECTSPECT MUGA MUGA Cardiac Function and Cardiac Function and

EF EF

• Tc99m labeled rbc’s Tc99m labeled rbc’s • Left ventricular hypertrophy with global Left ventricular hypertrophy with global

hypokinesishypokinesis• 47 years old with history of CAD47 years old with history of CAD

Emission from lateral Emission from lateral thighs, thighs,

right triceps, and right triceps, and inguinal lymph nodesinguinal lymph nodes

T-cell T-cell lymphomalymphoma

ScintigraphyScintigraphy

• Molecular imagingMolecular imaging– indicator of metabolic activityindicator of metabolic activity– ““hot spots” where uptake is highhot spots” where uptake is high

• Low radiation exposureLow radiation exposure– Short half-life, low energy gamma radiation Short half-life, low energy gamma radiation

• Extensive application in many Extensive application in many specialtiesspecialties– Orthopedics, Cardiology, Endocrinology, Orthopedics, Cardiology, Endocrinology,

etcetc

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

Bone Bone ScanScan at 7 days post- at 7 days post-injuryinjury

Case StudyCase Study

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

• Elevated kidney uptake w/o bladder activityElevated kidney uptake w/o bladder activity• Decreased activity in vastus medialis suggests necrosisDecreased activity in vastus medialis suggests necrosis

RhabdomyolRhabdomyolisisisis

PET/CT Co-registrationPET/CT Co-registration

• Provides anatomical and physiological Provides anatomical and physiological information information

Applications in Applications in MedicineMedicine

TherapeuticsTherapeutics

Therapeutic ModalitiesTherapeutic Modalities

• BrachytherapyBrachytherapy• AblationAblation• Targeted Alpha TherapyTargeted Alpha Therapy• Gamma knifeGamma knife• External BeamExternal Beam• Boron Neutron Capture TherapyBoron Neutron Capture Therapy

Therapeutic ApplicationsTherapeutic ApplicationsExamplesExamples

• Cancer TreatmentCancer Treatment• Tumor destructionTumor destruction• Palliation of pain Palliation of pain • Marrow TransplantsMarrow Transplants

BrachytherapyBrachytherapy

• Radioactive “seeds” emplaced in surgically implanted tubesRadioactive “seeds” emplaced in surgically implanted tubes• Dose calculation by medical physicistDose calculation by medical physicist• Tumour geometry determined through imaging modalitiesTumour geometry determined through imaging modalities

Prostate Cancer Prostate Cancer TreatmentTreatment

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

• Field maximizes dose to target while Field maximizes dose to target while minimizing collateral damageminimizing collateral damage

Iodine AblationIodine Ablation

• Ingestion of radioactive cocktail IIngestion of radioactive cocktail I131131

• Dose delivered after surgical Dose delivered after surgical thyroidectomythyroidectomy

• Patient becomes radioactivePatient becomes radioactive• Hospitalized until safe for general Hospitalized until safe for general

publicpublic

Targeted Alpha TherapyTargeted Alpha Therapy

• Carrier molecule “tagged” with alpha Carrier molecule “tagged” with alpha emitter emitter – monoclonal antibodiesmonoclonal antibodies

• Delivery of alpha-emitting isotopes to Delivery of alpha-emitting isotopes to target target – High LET High LET – capable of killing in a range of 1 to 3 cells capable of killing in a range of 1 to 3 cells

• Leukemia cells and small solid tumorsLeukemia cells and small solid tumors• Myeloid leukemias, prostate cancer, and Myeloid leukemias, prostate cancer, and

lymphoma treatments are under studylymphoma treatments are under study

Monoclonal AntibodyMonoclonal AntibodyRadioactive Source Chelated to Radioactive Source Chelated to

AgentAgent

BNCTBNCT

• Boron Neutron Capture TherapyBoron Neutron Capture Therapy• Boron delivered to target cellsBoron delivered to target cells• Neutron irradiation => activiation of Neutron irradiation => activiation of

boronboron• 1111Boron decay yields alpha particlesBoron decay yields alpha particles

– High LET of alpha deposits energy within High LET of alpha deposits energy within 3 cell diameters3 cell diameters

– kills target while minimizing effect to kills target while minimizing effect to surrounding tissuesurrounding tissue

Gamma KnifeGamma Knife

• Precise location and tumor geometry Precise location and tumor geometry essentialessential

• Cobalt-60 sourceCobalt-60 source– high level of penetrating gamma rayshigh level of penetrating gamma rays

• Two hundred one beams focused on Two hundred one beams focused on targettarget

• Delivery controlled by shieldDelivery controlled by shield• Frame emplaced to hold shieldFrame emplaced to hold shield• Procedure lasts about 4 hoursProcedure lasts about 4 hours

Therapeutic BenefitsTherapeutic Benefits• Brain tumors Brain tumors

– (benign and malignant) brain tumors(benign and malignant) brain tumors– metastatic lesionsmetastatic lesions– allows treatment in hard-to-access (inoperable) allows treatment in hard-to-access (inoperable)

areas of the brain. areas of the brain. • Arteriovenous malformations (AVMs)Arteriovenous malformations (AVMs)

– in brain can cause severe bleeding, headaches or in brain can cause severe bleeding, headaches or seizuresseizures

• Trigeminal neuralgiaTrigeminal neuralgia– create a lesion on the nerve blocking its pain create a lesion on the nerve blocking its pain

signalssignals• Acoustic neuromasAcoustic neuromas

– lower risk of deafness or loss of facial movement lower risk of deafness or loss of facial movement than with conventional surgery. than with conventional surgery.

• Pituitary tumors Pituitary tumors

Gamma KnifeGamma Knife

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

• Tumour geometry Tumour geometry is determined via is determined via imaging modalityimaging modality

Questions?Questions?