1. Internal Radiation DosimetryBiokinetic model and Internal Radiation Dose Calculation in Nuclear Medicine By Noor Naslinda Noor Rizan firstname.lastname@example.org
2. Brief Overview Definition MIRD Internal Dosimetry Method Biokinetic Model for Radiopharmaceutical uptake and elimination S-factor Dose to Target Sample Calculation Biokinetic Model for Embryo and Foetus Dose to infant via breast milk Example Summary References
3. Internal Radiation Dosimetry Radiation that happen inside the body due to uptake of radiopharmaceuticals cannot be measured directly. Therefore biokinetic and dosimetric model are needed in order to calculate radiation doses received by a person. Relevant Organization MIRD – Medical Internal Radiation Dose Committee of the Society of Nuclear Medicine Standard methods to estimates internal doses ICRP –International Committee on Radiological Protection Calculate doses for many radiopharmaceuticals based on best available data Local Organization e.g. AELB (Malaysia), ARSAC (UK), NUREG (US) etc Guidelines on radiopharmaceuticals limit, dose to children, etc
4. DefinitionAbsorbed Dose Absorbed Dose (Gray) Energy deposited per unit mass Dm = dε dmJoules/kg = Gray (Gy)*Medium should always be specifiedOld unit - rad, 100rad = 1 Gy
5. Dose Equivalent = Sievert (Sv) To reflect biological effect Absorbed Dose x Radiation Weighting Factor (WR) *was known as effective dose equivalent Effective Dose = Sievert (Sv) • Uniform dose to the whole body that would have the same risk - Dose X Tissue Weighting Factors • Unit sieverts, Sv
6. MIRD Method – 5 steps Consider uptake organ as source organ Part that absorb the radiation as target organ (source and target can be the same organ)Step 1 : Cumulated Activity Target (e.g. lung)Step 2 : S – Factor Radiation raysStep 3 : Dose to Target OrganStep 3 : Effective Dose to Whole body Source (e.g. heart)Step 5 : Total dose for administered activity
7. Activity Activity – rate of disintegration (1 Bq = 1 disintegration per second) = physical decay constantThis represent exponential decay with physical half life
8. Activity Fraction of Pharmaceutical (Fs) = rate of biological uptake and elimination in source organ ‘S’. Activity time curve = how activity in source organ change with time. activity is different to fraction of pharmaceutical because it takes into consideration radioactive decay Activity in source organ = Administered activity x Fraction of pharmaceutical x Decay factor
9. Cumulated Activity Cumulated activity in source organ is defined as area under activity time curve (Bq.sec or MBq.hr) Residence time is defined as accumulated activity divided by administered activity or using effective half-life
10. Residence time is more practical than cumulated activity because it is independent from administered activity. Use of residence time (in hr) instead of cumulated activity (MBq.hr) allows for calculation radiation dose per administered activity.
11. Effective Half -Life λeffective = λ physical + λbiological Biological can be either uptake or eliminationIn terms of half-life,
12. Biokinetic Models of RadiopharmaceuticalUptake for Dosimetry CalculationStep 1: Calculation of Residence Time 5 Basic Biokinetic Model
13. Model 1 – Instantaneous Uptake with No elimination Fs Pharmaceutical e.g. I-131 λp ActivityFraction Time
14. With no pharmaceutical eliminationSince =0Then, residence time:
15. Model 2 – Instantaneous Uptake with Single exponential elimination Fs Pharmaceutical λe + λpFraction Activity Time
16. Instantaneous Uptake with Single exponentialeliminationThen, residence time:
17. Model 3 – Instant Uptake with bi-exponentialelimination e.g. Tc-99m DTPA FsFs a1 λ2 λ1Fs a2 Pharmaceutical Fraction Activity Time
18. Instant Uptake with bi-exponential eliminationandThen, residence time
19. Model 4 – Exponential uptake with no elimination Fs λu Pharmaceutical Activity Fraction Time
20. Exponential uptake and no eliminationResidence time:
21. Model 5 – Exponential uptake and exponentialelimination Fs λu Pharmaceutical λe Activity Fraction Time
22. Exponential uptake and exponential eliminationResidence time:Where,
23. Step 2: The ‘S-Factor’ S-factor is considered to be a calculation of energy emitted by radiation of certain type of isotope and fraction of that energy absorbed by organ. So, S-factor can be define as absorbed dose per unit cumulated activity (Gy/Bq.sec or μGy/MBq.hr) MIRD pamphlet 11 tabulated ‘S’ factor to target organ for large selection of radiopharmaceuticals based on Monte Carlo simulation with ‘70kg mean man’phantom (given in rad/μCi.hr)
24. ‘S’ Factor (MIRD Report 11)
25. Step 3: Dose to Target Organ Absorbed Dose to target organ ‘t’ from all source organs ‘s’ Unit μGy/MBq Equivalent Dose = Absorbed Dose * Radiation Weighting Factor (or Quality factor) Unit (μ Sv/MBq) Its a measure of biological effectiveness of different type of radiation energy. In nuclear medicine the quality factor is 1. In nuclear medicine, absorbed dose = equivalent dose
26. Radiation Radiation Weighting Factor (Quality Factor ) X-rays, gamma rays, beta rays 1 Alpha rays, heavy nuclei 20 Proton 2 * Source ICRP Report 103 Step 4: Effective Dose Effective Dose is the weighted sum of all target organ doses (μSv/MBq)
27. Tissue Weighting Factor (as published by ICRP)
28. Step 5: Total dose for Administered Activity Result * Administered Dose - Absorbed Dose (mGy) - Equivalent Dose (mSv) - Effective Dose (mSv)Dose to Children
29. Final Result MIRD published methods on how to calculated absorbed dose, equivalent dose and effective dose based on several model of radiopharmaceuticals uptake. However, absorbed dose value for a lot of radiopharmaceutical used in nuclear medicine can also be found in ICRP report 53 and 80. This report calculated the data based on best available data on radiopharmaceutical with ‘70 kg mean man’ phantom.
30. So what’s the use of MIRD? MIRD method is useful when we want to do specific calculation or custom calculation for patient based on patient’s individual uptake of radiopharmaceuticals. Example, we want to know dose to uterus for a patient who has a tumour near kidney or adrenal gland which has a high radiopharmaceutical uptake. Usually we take dose to uterus as an estimation for dose to foetus from the ICRP publication. But ICRP result only take into account contribution from standard source organs to uterus. In this case, we can assume that there is an addition source organ, the tumour which will contribute a significant dose to the uterus.
31. Solution Combine dose value from tumour and absorbed dose to uterus from ICRP Report.Example: A patient was given 200MBq of Tc-99m DTPA and a tumour was found near adrenal gland with high radiopharmaceutical uptake. What is the absorbed dose to uterus?From ICRP Report 53 (Tc-DTPA, bi-exponential elimination, normal renal function)Residence time = 1.97hr, Fs = 1.0From MIRD 11, ‘S’ factor for adrenal gland to uterus = 1.1E-6 rad/μCi.hr = 2.97E-01 μGy/MBq.hr*We assume ‘S’ factor for tumor is similar to adrenal gland because of the anatomical position.
32. *From ICRP Publication 53
33. Calculation Additional absorbed dose to uterus from tumour= From ICRP 53 Absorbed Dose to Uterus = 7.9E-03 mGy/MBq. Total absorbed dose to fetus from administered activity=
34. Biokinetic Model for Embryo and Foetus ICRP Publication 88 published biokinetic and dosimetric model also dose coefficient for embryo and foetus due to radiopharmaceutical uptake by mother First 8 weeks of pregnancy (mass < 10g) Dose rate = dose rate to uterus More than 8 weeks Dose rate = maternal activity + activity which has cross the placenta and has accumulated into the foetus tissue. Some radioisotope like iodine can cross the placenta. At birth There might be some activity left in infant. This is use to calculate committed effective dose equivalent until the age of 70 years old
35. Dose to infant via breast milk ICRP 95 gives dose coefficient for ingestion of breast milk by infant after activity uptake by mother. A different biokinetic model for radiation pathway was used in the calculation of the coefficient. An Annex of ICRP Publication 95 also examines the external dose to infants by contact with its mother who has radioactivity uptake. In some case e.g. mother’s uptake of insoluble gamma-emitters. External dose to infant might be higher than internal dose.
36. Example A female patient fell pregnant after 58 days of receiving 15mCi of I-131 for treatment for Thyrotoxicosis. Calculate dose to foetus due to activity administered.Solution:There are 3 ways to solve this.1. Start from scratch using MIRD method.2. Using value from ICRP 533. Using dose coefficient of biokinetic modelling from ICRP 88.
37. Using value from ICRP 53 We calculate from from 58 days onwards. At 58 days, activity remaining = 0.1010 mCi = 3.7370MBq Dose to fetus = dose to uterus. Days/ Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Thyroid Uptake Uptake Uptake Uptake Uptake Uptake Uptake Activity (MBq) 0% 5% 15% 25% 35% 45% 55% (mGy) (mGy) (mGy) (mGy) (mGy) (mGy) (mGy)Absorbed dose at organ 5.40E-02 5.50E-02 5.40E-02 5.20E-02 5.00E-02 4.80E-02 4.60E-02(uterus)/ Adult per unitactivity administered (mGy/MBq)Day one (Administered)(8 May 2012) 562.4 30.37 30.93 30.37 29.24 28.12 27.00 25.87Day five (Discharge) (13 May 2012) 342.06 18.47 18.81 18.47 17.79 17.10 16.42 15.73 Day 40 (18 June2012) 16.73 0.90 0.92 0.90 0.87 0.84 0.80 0.77Day 58 (Might be pregnant) (01/07/12) 3.73 0.20 0.20 0.20 0.19 0.19 0.18 0.17
38. Using ICRP 88 *ICRP publication 88 page 213
39. Result Dose to fetus is around 0.19 – 0.16 mGy. Using biokinetic modeling of ICRP 88, < 8 weeks = dose to uterus From 8 weeks until birth at 38 weeks, the dose is estimated using element specific tissue activities and retention times.
40. Solution At conception effective dose coefficient = 7. 8E-11 Sv/BqActivity, 3.73MBqSo, 7.8E-11*3.54MBq = 0.27 mSVUsing ICRP 53, the value was 0.17 - 0.20 mGy, depending on iodine uptake( = equivalent dose of 0.17 - 0.20mSv)From ICRP 84 (later adapted by IAEA) recommendation, there is no justification for termination of pregnancy as the dose received by foetus <100mGy. There is no evidence of detrimental effects to foetus.
41. Foetus RiskMentrual / Conception age <0.01 Gy 0.05 – 0.1 Gy > 0.1 Gygestational age (weeks)(weeks)0-2 Prior to conception None None None3–4 1–2 None Probably None Possible spontaneous abortion5 – 10 3–8 None Potential effect uncertain Possible malformation, increase with dose11 – 17 9 – 15 None Potential effect uncertain Increased risk mental retardation of deficit in IQ18 – 27 16 – 25 None None IQ deficits not detectable at diagnosis dose> 27 > 25 None None None application to diagnostic medicine * Taken from ICRP 84 and 90
42. Pregnancy and breastfeeding followingtreatment ICRP / IAEA recommends women do not become pregnant until estimated foetal dose falls below 1mGy (100mrem) (diagnostic application) For therapeutic treatment – 6 months after treatment. Not because of radiation dose risk, more to make sure that treatment was effective and follow-up treatment can be carried out without obstruction. Some organization (e.g. ARSAC) published elapsed time between treatment and breastfeeding after taking into account the activity that might transfer to infant for selected radiopharmaceuticals
43. Why we need to know all this?
44. Why we need to know all this?How Bad is Bad? Dosimetry calculation allows us to quantify the doses received by patient and used that as a measurement of radiation risk Sievert was design to represent stochastic biological effects of ionizing radiation. 1 Sv = 5.5% probability of developing cancer (ICRP103) Organization which actively involve in radiation protection use specific dose value as guideline. AELB 2010 guideline : Public <1mSv/yr Radiation worker <20 mSv/ yr Foetus < 1mSv for the duration of pregnancy
45. Dose value can be use as a reference across all radiation related exposure. Effective dose from CT, X-Ray, radiotherapy, dental radiograph, airport security screening can all be sum up together Result from dose calculation can be use as benchmark on whether a certain procedure is worth it or not.
46. References  Dr Richard Lawson, Notes Radiation Dosimetry [Lecture Notes], Manchester Royal Infirmary, (March 2011)  MIRD Pamphlet no 5, Estimates of Absorbed Fractions for Monoenergetic Photon Sources Uniformly Distributed in Various Organs of a Heterogeneous Phantom; L.T. Dillman and F.C.Van der Lage Littman, Society of Nuclear Medicine, New York (1969).  MIRD Pamphlet no 10, Radionuclide Decay and nuclear parameters for use in in radiation dose estimation, L.T. Dillman and F.C.Van der Lage Littman, Society of Nuclear Medicine, New York (1975).  MIRD Pamphlet no 11, ‘S’ Absorbed Dose per unit Cumulated Activity for Selected Radionuclides and Organs , W.S Synder, M.R. Ford, G.G. Warner and S.B. Watson, Society of Nuclear Medicine, New York (1975). [5 ICRP Publication 53 Radiation Dose to Patient from Radiopharmaceuticals, Annals of the ICRP, vol 18,no 1-4 (1987)  ICRP Publication 80 Radiation Dose to Patient from Radiopharmaceuticals, Addendum to ICRP 53, Annals of the ICRP, vol 28,no 3 (1998)  ICRP Publication 84 Pregnancy and Medical Radiation, Annals of the ICRP, vol 30,no 1 (2000) Notes of Guidance on the Clinical Administration of Radiopharmaceuticals and of sealed Radionuclide Sources, Administration of Radioactive Substances Advisory Committee, 2006.
47. References  ICRP Publication 88 Doses to the Embryo and Fetus from Intakes of Radionsuclides by the Mother, Annals of the ICRP, vol 31,no 1-4 (1987)  ICRP Publication 90 Biological Effects after Prenatal Irradiation (Embryo and Fetus), Annals of the ICRP, vol 33,no 1-2 (2000)  ICRP Publication 95 Radiation Dose to Patient from Radiopharmaceuticals, Annals of the ICRP, vol 34,no 1-4 (1987)  ICRP Publication 103, The 2007 Recommendations of the International Commission on Radiological Protection. Annals of the ICRP Vol 37, no 2-4 (2007)  Peraturan-peraturan Perlesenan Tenaga Atom (Perlindung Sinaran Keselamatan Asas) 2010. Lembaga Perlesenan Tenaga Atom, Malaysia (2010)