I-131 Patient Release I-131 Patient Release Criteria based on Criteria based on Measured DataMeasured Data

Presentation by:Presentation by:Christopher B. Martel, CHPChristopher B. Martel, CHPDirector and Radiation Safety Director and Radiation Safety

OfficerOfficerAssistant Professor of RadiologyAssistant Professor of RadiologyBoston University Medical CenterBoston University Medical Center

Study ObjectiveStudy Objective

►Develop a method to demonstrate Develop a method to demonstrate compliance with regulatory release compliance with regulatory release limits for outpatient radioiodine limits for outpatient radioiodine therapy that is:therapy that is: More accurate than current methodsMore accurate than current methods Easier to performEasier to perform Less expensiveLess expensive

OutlineOutline

►Primer on Radioiodine TherapyPrimer on Radioiodine Therapy►Approach using Regulatory Guide 8.39Approach using Regulatory Guide 8.39►Approach using NCRP Report No. 155Approach using NCRP Report No. 155►Approach using Patient-Specific Approach using Patient-Specific

Measured DataMeasured Data

Thyroid DiseasesThyroid Diseases

► Thyroid CancerThyroid Cancer Papillary and/or mixed papillary/follicular ~ 78% Follicular and/or Hurthle cell ~ 17% Medullary ~

4% Anaplastic ~ 1% (Most aggressive) (Most aggressive)

► HyperthyroidismHyperthyroidism Diffuse Toxic GoiterDiffuse Toxic Goiter Toxic Nodular GoiterToxic Nodular Goiter Subacute ThyroiditisSubacute Thyroiditis

► HypothyroidismHypothyroidism

Thyroid Function

► Radioiodine is used Radioiodine is used to determine thyroid to determine thyroid uptake.uptake. Isotopes used include Isotopes used include

I-123 and I-131.I-123 and I-131. Normal uptake Normal uptake

15-25%15-25% Hypo – <10%Hypo – <10% Hyper - >30%Hyper - >30%

Thyroid Uptake ValueThyroid Uptake Value

►Thyroid uptake of Thyroid uptake of radioiodine can be used radioiodine can be used to:to: Determine the therapeutic Determine the therapeutic

dose.dose. Determine if the patient is Determine if the patient is

“releasable” according to “releasable” according to regulatory limits.regulatory limits.

Thyroid Uptake Thyroid Uptake MeasurementsMeasurements

Uptake measurements for Uptake measurements for thyroid thyroid cancercancer patients are performed by: patients are performed by: Counting pills (up to 2 millicuries of I-123) Counting pills (up to 2 millicuries of I-123)

under gamma camera,under gamma camera, Administering pills to patient,Administering pills to patient, imaging the patient’s neck region using a imaging the patient’s neck region using a

gamma camera at 24 hours post gamma camera at 24 hours post administration, andadministration, and

quantifying uptake byquantifying uptake by drawing a region of interest around the drawing a region of interest around the

thyroid region, thyroid region, subtracting background, subtracting background, decay correcting to time of administration, decay correcting to time of administration,

and and dividing by the measured pill counts dividing by the measured pill counts

obtained prior to administration. obtained prior to administration.

Thyroid Uptake Thyroid Uptake MeasurementsMeasurements

Iodine-131 TherapyIodine-131 Therapy

►Used to ablate thyroid cancer Used to ablate thyroid cancer remnants including metastatic disease remnants including metastatic disease after surgical removal of the thyroid.after surgical removal of the thyroid.

►Used to reduce thyroid function for Used to reduce thyroid function for hyperthyroid patientshyperthyroid patients

►Typical administered doses are:Typical administered doses are: Thyroid cancer – 30 to 400 millicuriesThyroid cancer – 30 to 400 millicuries Hyperthyroidism – 5 to 20 millicuriesHyperthyroidism – 5 to 20 millicuries

Patient Release CriteriaPatient Release Criteria

►Regulatory Guide 8.39Regulatory Guide 8.39►NUREG 1556 Vol. 9, Appendix UNUREG 1556 Vol. 9, Appendix U

Patient release can be determined by one Patient release can be determined by one of four methods:of four methods:

1.1.Administered activityAdministered activity2.2.Retained activityRetained activity3.3.Measured dose rateMeasured dose rate4.4.Patient-specific dose calculationPatient-specific dose calculation

Patient Release CriteriaPatient Release Criteria

Release based on:Release based on: Administered activity (< 33 millicuries)Administered activity (< 33 millicuries) Retained activity (< 33 millicuries)Retained activity (< 33 millicuries) Measured dose rate (< 7 millirem/hr at 1 Measured dose rate (< 7 millirem/hr at 1

meter)meter) Patient specific release criteria usingPatient specific release criteria using

►Effective half-lifeEffective half-life►Patient uptakePatient uptake►Public occupancy valuesPublic occupancy values

►Member of public must be < 500 Member of public must be < 500 milliremmillirem

NCRP Report No. 155NCRP Report No. 155

► Appendix A, Equation A.11Appendix A, Equation A.11

( )( )( )

∑∑=

−

−•

=

⋅=n

i

T

t

ieaja

m

jr

ie

release

ijeFTKErTE K

1

693.0

1

1lim

lim

0,6.34

Doses calculated for:Doses calculated for:

0.10.331General Public

0.50.5

0.5

0.250.25

0.33

11

0.3

Family memberNonsleeping partnerAll activities except sleeping with patientSleeping with patient

Dose LimitcSv

Occ. Facto

r

Distance (m)

Group

This goes on forThis goes on for

►Dose to pregnant woman as sleeping Dose to pregnant woman as sleeping partner and nonsleeping partnerpartner and nonsleeping partner

►Dose to pregnant coworkerDose to pregnant coworker►Dose to Children, holding or not Dose to Children, holding or not

holdingholding

►Each has its own distance, occupancy Each has its own distance, occupancy factor and dose limit.factor and dose limit.

Equations allow forEquations allow for

►Equations allow from one to three Equations allow from one to three exponential components.exponential components.

►HOWEVER, recommends the value for HOWEVER, recommends the value for residence time be “taken from residence time be “taken from literature.”literature.”

►Also, makes use of “Zero-time Also, makes use of “Zero-time Exposure Rates” at:Exposure Rates” at: one meter from an upright patient and one meter from an upright patient and one foot from a supine patientone foot from a supine patient

New ApproachNew Approach

►Use the Siemens MK2 Electronic Use the Siemens MK2 Electronic Personal Dosimeter Personal Dosimeter

MK2 SpecificationsMK2 Specifications

►Dose rate linearity Hp(10) 137Cs

►±10% <0.5Sv/h (<50 rem/h)►±20% 0.5Sv/h to 1Sv/h(50 to 100 rem/h)

►Photon, Hp(10) ±50% 15keV to 17keV (ref. 137Cs) ±20% 17keV to 1.5MeV (ref. 137Cs) ±30% 1.5MeV to 6MeV (ref. 137Cs) ±50% 6MeV to 10MeV (ref. 137Cs)

Critical FeatureCritical Feature

Dose profile history: settable interval from 2 seconds to 35 hours, stores transitions of Hp(10) and Hp(0.07) at a resolution of 1μSv (0.1mrem); will store up to 579 records for transitions up to 127μSv or less

Using Mk2Using Mk2

►Determine Determine patient-specificpatient-specific effective effective half-lifehalf-life

►Measure dose rate for calculating dose Measure dose rate for calculating dose at other distances.at other distances.

►Use these values for precise Use these values for precise calculations of dose to individuals of calculations of dose to individuals of concern as specified in NCRP Report concern as specified in NCRP Report No. 155No. 155

Dose MeasurementDose Measurement

► I need to figure out:I need to figure out: Can I accurately determine the effective Can I accurately determine the effective

half-life by measuring exposure rate using half-life by measuring exposure rate using the Mk2?the Mk2?

Can I extrapolate the dose measured on Can I extrapolate the dose measured on contact with the patient using the Mk2 to contact with the patient using the Mk2 to distances of 1 foot and 1 meter?distances of 1 foot and 1 meter?

Measurement OneMeasurement One

►Measurement One: Determine the Measurement One: Determine the half-life of a radionuclide using the half-life of a radionuclide using the Mk2.Mk2. Obtained pills of Iodine-123Obtained pills of Iodine-123 Placed in a neck phantomPlaced in a neck phantom Placed the Mk2 on contact with the Placed the Mk2 on contact with the

phantomphantom Collect total dose measurements for 24 Collect total dose measurements for 24

hourshours Use the dose measurements to calculate Use the dose measurements to calculate

the half-life of the radionuclidethe half-life of the radionuclide Compare to published value of I-123 half-Compare to published value of I-123 half-

lifelife

Half-Life Determination Half-Life Determination ResultsResults

Cumulative Dose versus Time Using the Mk2

0

100

200

300

400

500

600

0 50 100 150 200 250 300 350

Time in 20 minute intervals

Cum

ulat

ive

Dos

e (m

illire

m)

Half-Life Determination Half-Life Determination ResultsResults

►Half-life of I-123 from PlotHalf-life of I-123 from Plot

13.30 hours13.30 hours►Published Half-life (BNL)Published Half-life (BNL)

13.22 hours13.22 hours►Difference 0.6%Difference 0.6%

Measurement TwoMeasurement Two

►Measurement Two: Extrapolating dose Measurement Two: Extrapolating dose measured on contact of patient with measured on contact of patient with Mk2 to one foot and 1 meterMk2 to one foot and 1 meter Used ion chamber to measure exposure Used ion chamber to measure exposure

rate at 0.75 ft, 1.75 ft, and 4 ft from rate at 0.75 ft, 1.75 ft, and 4 ft from patient administered I-131patient administered I-131

Measured dose rate on contact with Measured dose rate on contact with patient using the Mk2patient using the Mk2

Extrapolate data from Mk2 to 1.75 ft and Extrapolate data from Mk2 to 1.75 ft and 4 ft4 ft

Important Factor!Important Factor!

► If thyroid cancer localized, dose to If thyroid cancer localized, dose to distance relationship followed inverse distance relationship followed inverse square rule.square rule.

► If thryoid cancer metastatic, dose to If thryoid cancer metastatic, dose to distance relationship followed inverse distance relationship followed inverse to 1.6 power, which shows body as a to 1.6 power, which shows body as a cylindrical source rather than point cylindrical source rather than point source.source.

Sample Dose to Distance Sample Dose to Distance Relationship for a patientRelationship for a patient

Relationship between Time post administration and Distance/Exposure Rate

0

0.5

1

1.5

2

2.5

0 10 20 30 40 50 60

Time post administration (hrs)

Dis

tan

ce/E

xpo

sure

Rat

e

On Contact Dose Rate Multiplier On Contact Dose Rate Multiplier for Different Disease Typesfor Different Disease Types

0.0570.028One meter

0.3300.250One foot

11On contact

Metastatic DiseaseThyroid OnlyDistance

Dose Rate Extrapolation Dose Rate Extrapolation Measurement ResultsMeasurement Results

Whole Body % of Inital Activity at Time Post Administration

y = 0.9658e-0.0007x

R2 = 0.9941

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 1000 2000 3000 4000 5000 6000

Time Post Administration (min)

Per

cen

t R

emai

nin

g (

%)

Patient data based on gamma camera counts using I-131 diagnostic scan

Effective Half-Life = 16.5 hours

Patient Effective Half Life using Mk2

y = 708.81e-0.0403x

R2 = 0.883

0

50

100

150

200

250

20 30 40 50 60 70 80

Hours post administration

Cum

ulat

ive

dose

per

Hou

rDose Rate Extrapolation Dose Rate Extrapolation

Measurement ResultsMeasurement Results

Effective half-life = 17.20 hours

►Effective Half-Life using Whole Body Effective Half-Life using Whole Body scan by dual head gamma camerascan by dual head gamma camera

16.5 hours16.5 hours►Effective Half-Life using Mk2Effective Half-Life using Mk2

17.20 hours17.20 hours►Difference 4%Difference 4%

Dose Rate Extrapolation Dose Rate Extrapolation Measurement Measurement Sample ResultSample Result

►Dose rate measurements on contact Dose rate measurements on contact with patient using Ion Chamber and with patient using Ion Chamber and compared to Mk2 results were within compared to Mk2 results were within 10%.10%.

►Sample Result: Dose rate measured on Sample Result: Dose rate measured on contact with patient using Ion contact with patient using Ion Chamber was 90 millirem/hr, and Chamber was 90 millirem/hr, and distance corrected Mk2 measured 92 distance corrected Mk2 measured 92 millirem/hr.millirem/hr.

Dose Rate Extrapolation Dose Rate Extrapolation Measurement ResultsMeasurement Results

Summary of ResultsSummary of Results

►Using the Mk2 we can accurately Using the Mk2 we can accurately measure:measure: Patient-specific effective half-life for Patient-specific effective half-life for

radioiodineradioiodine Patient-specific biological removal rate Patient-specific biological removal rate

constant for radioiodineconstant for radioiodine Dose rate (and cumulative dose) on Dose rate (and cumulative dose) on

contact and at distances from the patientcontact and at distances from the patient

Direct Measurement MethodDirect Measurement Method

1.1. Administer diagnostic activity to Administer diagnostic activity to patient patient If I-123, make correction to I-131If I-123, make correction to I-131 If I-131, measured values are normalized If I-131, measured values are normalized

to one millicurieto one millicurie► Obtain cumulative dose data over 24 Obtain cumulative dose data over 24

hourshours► DetermineDetermine λ λ ee and extrapolate and extrapolate

cumulative dose data using cumulative dose data using prescribed therapeutic dose of I-131 prescribed therapeutic dose of I-131 to distances of one foot and one to distances of one foot and one meter applying different tmeter applying different t11

Cumulative DoseCumulative Dose

► DD00 is the expected dose cumulated in the is the expected dose cumulated in the first hour post administrationfirst hour post administration

► Where tWhere t11 and t and t22 are the beginning and are the beginning and ending time point post administration of ending time point post administration of the therapeutic dose. If infinity, first exp = the therapeutic dose. If infinity, first exp = 1, and second = 0.1, and second = 0.

( )210 tt

e

ee eeD

CumDose λλ

λ−− −=

Results from one patientResults from one patient

01019

29177

4252196

11656495

30171151304

78450383413

20411831008972

538311326423581

One MeterOne FootOne MeterOne footTime Post Administration t1 (days)

Dose from t1 to day 9 for Metastatic Disease (millirem)Dose from t1 to day 9 for Thyroid Only (millirem)

Occuapncy Factor of 1

LimitationsLimitations

► Regulatory Guide 8.39 Regulatory Guide 8.39 Uses one size fits all approach with respect to Uses one size fits all approach with respect to

biokineticsbiokinetics Requires nuclear medicine equipmentRequires nuclear medicine equipment

► NCRP Report No. 155NCRP Report No. 155 Cumbersome equationsCumbersome equations Disease type not consideredDisease type not considered Requires nuclear medicine equipmentRequires nuclear medicine equipment

► Proposed MethodProposed Method Requires purchase of dosimeterRequires purchase of dosimeter

StrengthsStrengths

► Regulatory Guide 8.39Regulatory Guide 8.39 Simple approach – easy to calculateSimple approach – easy to calculate

► NCRP Report No. 155NCRP Report No. 155 Allows patient specific data to be usedAllows patient specific data to be used Promotes use of dose to multiple populationsPromotes use of dose to multiple populations

► Proposed MethodProposed Method Uses patient-specific measured dataUses patient-specific measured data Allows use of dose to multiple populationsAllows use of dose to multiple populations Easy to do with EPDEasy to do with EPD Does not require expensive gamma camera timeDoes not require expensive gamma camera time

Future ResearchFuture Research

►Mk2 Method will be used and Mk2 Method will be used and compared against “gold standard” for compared against “gold standard” for effective half-life determinations, and effective half-life determinations, and

►Mk2 Method release/dose to public Mk2 Method release/dose to public results will be compared to Regulatory results will be compared to Regulatory Guide 8.39 and NCRP 155 release/dose Guide 8.39 and NCRP 155 release/dose to public estimatesto public estimates