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Dosimetry of Radiopharmaceuticals

Dosimetry of Radiopharmaceuticals. Radiology Physics Review Course Dawn Banghart, CHP Sr. Health Physicist July, 2010. Course objectives. Complete discussion on Radiation Safety Introduce Dosimetry theory Specific examples including considerations of dose the a fetus.

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Dosimetry of Radiopharmaceuticals

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  1. Dosimetry of Radiopharmaceuticals Radiology Physics Review Course Dawn Banghart, CHP Sr. Health Physicist July, 2010

  2. Course objectives • Complete discussion on Radiation Safety • Introduce Dosimetry theory • Specific examples including considerations of dose the a fetus

  3. Receipt of Radionuclides -DOT • Department of Transportation (DOT) sets standards for packaging, labeling and radioactive materials transport. • Each licensee shall-- • Monitor/swipe package external surfaces for contamination (not later than 3 hours after receipt) • Monitor package external surface radiation levels • Monitor all packages if crushed, wet, or damaged • Immediately notify final delivery carrier and NRC when-- • Removable surface contamination exceeds the limits • Beta/gamma limits = 220 dpm/cm2 • External radiation levels exceed surface limits

  4. 0.4 DOT continued … • Transport Index (TI) is on Yellow II and Yellow III labels only: • Dimensionless number (rounded up to the next tenth) designates the degree of control to be exercised by the carrier during transportation • Denotes maximum radiation level in millirems measured one meter from surface of the package

  5. Label Category Based on TI and Surface Radiation Level Limits

  6. Nuclear Med DOT procedures • After shipment is received, surveys (swipes/instrument measurements) are conducted and entered in to NMIS • All pigs are then removed and placed next to the L-Block • The empty “Ammo” container will still have the shipping placard attached until surveyed for return to manufacturer • Once surveyed, placards are removed and placed inside the container, and container is closed

  7. From recalls … • A Nuclear Medicine Technician is monitoring a Yellow II package by taking a swipe and using a survey meter. They were not wearing a finger ring. Is this ok? • Yellow II package surface dose rate ≤ 50 mrem/hour. Assume survey took 1 minute. Maximum hand dose = 0.8 mrem (50 mrem/(hr*60 min/hr)). • 0.8 mrem x 5 packages/day X 5 days/week x 50 weeks/year = 1042 mrem/yr (1.04 rem/yr) = NO Ring just for package surveys • Nuc Med Techs also work with patients and radiopharmaceutical vials and so for the full scope of their work they DO need a ring

  8. Internal Dosimetry …The calculation of absorbed dose based on internally deposited radioisotopes

  9. Internal Dosimetry Considerations • Quantity of radioactivity in the body • Type (recall LET such as betas vs. alphas), abundance, energies of the radiation emissions • Size and weight of organs and whole body • Rates of organ uptake • Whole body and organ retention times • Fractional energy absorbed within organs and the whole body • Note: Refer to handout for definitions

  10. Definitions (see handout) • Absorbed dose means the energy imparted by ionizing radiation per unit mass of irradiated material. The units of absorbed dose are the rad and the gray (Gy). • Activity is the rate of disintegration (transformation) or decay of radioactive material. The units of activity are the curie (Ci) and the becquerel (Bq). • 1 Ci = 3.7 E10 depletions per second • 1 Bq = 1 depletion per second • Committed dose equivalent means the dose equivalent to organs or tissues of reference that will be received from an intake of radioactive material by an individual during the 50-year period following the intake. • Committed effective dose equivalent is the sum of the products of the tissue weighting factors applicable to each of the body organs or tissues that are irradiated and the committed dose equivalent to these organs or tissues

  11. Definitions (2) … • Dose equivalent means the productof the absorbed dose in tissue and the radiation weighting factor. The units of dose equivalent are the rem and sievert (Sv). • External dose means that portion of the dose equivalent received from radiation sources outside the body. • Radiation Weighting Factor (or Quality Factor) means the factor used to derive dose equivalent from absorbed dose. Takes into account the biological effectiveness (LET) of different types of radiation • Shallow-dose equivalent, which applies to the external exposure of the skin of the whole body or the skin of an extremity, is taken as the dose equivalent at a tissue depth of 0.007 centimeter (7 mg/cm2). • Total Effective Dose Equivalent (TEDE) means the sum of the deep-dose equivalent (for external exposures) and the committed effective dose equivalent (for internal exposures).

  12. Definitions (3) … • Tissue Weighting factor, for an organ or tissue is the proportion of the risk of stochastic effects (i.e., cancer risk) resulting from irradiation of that organ or tissue to the total risk of stochastic effects when the whole body is irradiated uniformly. • Gray (Gy) = SI unit of absorbed dose. One gray = absorbed dose of 1 Joule/kilogram (100 rads). • Rad = US unit of absorbed dose. One rad = absorbed dose of 100 ergs/gram or 0.01 joule/kilogram (0.01 gray). • Rem = dose equivalent = the absorbed dose in rads multiplied by the quality factor (1 rem=0.01 sievert). • Sievert = SI unit of dose equivalent = the absorbed dose in grays multiplied by the Radiation Weighting Factor (or Quality Factor) (1 Sv = 100 rems)

  13. From recalls … • How many transformations per second in 1 MBq? Answer: 1 Bq = 1 transformation per second So there are 1 million transformations in 1 MBq

  14. Radiation Weighting (Quality) Factors • Radiation Weighting Factors in ICRP 30 Note: Weighting Factors are directly related to Linear Energy Transfer  (LET) of the ionizing radiation • Alpha particles 20 • Beta particles (+/-) 1 • Gamma rays/x-rays 1 • Protons 5 • Neutrons (depending on energy) 5 – 20 • For 5 MeV 8 • For unknown energy 10

  15. Tissue Weighting Factors • To compare radiation detriment to a limited portion of the body with detriment to the whole body ICRP derived the concept of effective dose equivalent which utilizes weighting factors for relative risks associated with irradiation of various tissues • Risk factors lead to …Tissue Weighting Factors lead to …Total Effective Dose Equivalent Calculations Note: These factors are intended to apply to stochastic (i.e., cancer) effects only

  16. Risk Coefficients for Stochastic Radiation Effects (10-4/rem) for radiation exposures at low dose rates Note: The below coefficients are based linear-no threshold extrapolations with the inclusion of not just probability of risk but severity of the effect From ICRP-60 and NCRP Report No. 115 Example: 1 rem increases the risk of fatal cancer to a 33 year old Stanford radiologist by 0.04%

  17. From recalls … • What portion of the bowel is most affected by radiation? • Small bowel • Stomach • Colon • Esophagus The small bowel. Projective from the lining of the small bowel are villi. Because the cells of the villi are continually being cast off, new cells continually arise from the crypts of the Lieberkühn. Highly mitotic undifferentiated stem cells are very radiosensitive.

  18. The Dosimetry Systems • International Commission on Radiological Protection (ICRP) • A mathematical approach mainly used for radiological protection (occupational worker) purposes • Incorporates quality factors/weighting factors (estimates of relative biological effectiveness RBE) to estimate risk • Medical Internal Radiation Dosimetry (MIRD) Committee of the Society of Nuclear Medicine formed by SNM in 1968 • A mathematical approach to assess dose and risk to patients from radiopharmaceuticals • Other Dose Assessment systems • RADAR (Radiation Dose Assessment Resource) - integrates various resources that exist in the areas of internal and external dose assessment • IMPACT – CT dose assessment only

  19. Basic Internal Dosimetry Concepts • What information is required to calculate absorbed dose in an organ of interest? Must know: • How many decays in organ • How much activity in organ • How long activity is in organ • Energy from each decay • Fraction of decay energy deposited in organ • Mass of organ • Energy deposited from activity in other organs

  20. ICRP Method Assumptions • Most organs are like spheres • Organ uptakes are instantaneous • Radioactivity is uniformly distributed • Whole body resembles “standard man” • Innovated the idea of summing up organ weighting factors (The more sensitive the organ the greater the factor) to create a whole body “effective dose equivalent”

  21. The MIRD Method Assumptions • Internal organs are not spheres (e.g., ellipsoidal) • Organ uptake not instantaneous • Organ retention times vary • Radioactive material removal from the organ can be represented by exponential function of time Activity Hours

  22. Basic Organ Models • Single Organ • Multiple Organ

  23. Main MIRD Equation D = absorbed dose (rad or Gy) Ã = cumulated activity (mCi-hr or MBq-sec) ni = number of radiations with energy E emitted per nuclear transition Ei = energy per radiation (MeV) øi = fraction of energy absorbed in the target m = mass of target region (g or kg) k = proportionality constant (rad‑g/mCi‑hr‑MeV or Gy‑kg/MBq‑sec‑MeV)

  24. MIRD Equation Simplified Total dose = the sum of doses from each source organ to each target organ: Total dose = Dhk = Ã S = Ãh x S (rk rh) where: • ÃRepresents disintegrations that occur in source organ • Depends on: • Fraction of administered activity in organ • Rate of elimination from source organ • Ãh is the cumulated activity (mCi-hr) for each source organ rh • S is the absorbed dose (rad/mCi-hr) in target rk

  25. Cumulated Activity ÃT = A0 • fh • 1.44 Te • Where • A0 (in mCi or MBq) = initial activity taken into body • Te in hours – “effective” half-life • fh fraction of A0 deposited into organ of concern

  26. From recalls … • Regarding internal radiation dosimetry, the unit for cumulated activity is: • a. mCi • b. mCi*h • c. μCi*h/g • d. μCi/g • e. μCi/cm3 Answer: b

  27. Teff = Tp x Tb • Tp + Tb Effective Half-Life • The effective half-life (Te) is determined by: • Tp = “physical” radioactive decay • Tb = biological elimination

  28. Teff = 20 x 7 20 + 7 Effective Half-life Example: • If Tb = 20 days, and, Tp = 7 days • = 5.2 days • If Half-life of one is long relative to the half-life of the other Teff approaches the shorter of the two: • Tp = 100, and, Tb = 7 • Teff = [(100x7)/(100+7)] = 6.5 • Tp = 100E+9, and, Tb = 7 • Teff = [(100E+9x7)/(100E9+7)] = 7

  29. MIRD • The “S” Factor • Absorbed dose to the target organ per unit of cumulated activity in a specified source organ (rad/mCi). S (rk rh) Note: S-values are tabulated in MIRD pamphlets

  30. MIRD Resources • MIRD Pamphlet No. 11 (Snyder et al. 1975) - S-values are tabulated for the 117 radionuclides and 20 source and target regions defined in the phantom • For Cumulative Activity, biological half-lives are estimated for many of the chemical forms of the radiopharmaceuticals from human and animal studies • In practice NUREG-CR/6345 is used for most nuclear medicine radiopharmaceuticals

  31. MIRD Dosimetry examples:

  32. From recalls … • If a pregnant patient in the second trimester is treated with I-131 for Graves disease, what is the most likely result to the fetus (Note: dose around 3-12 mCi)? a. abnormal organogenesis b. increased incidence of benign and malignant thyroid tumors c. cretinism d. chromosomal abnormality Answer: b

  33. MIRD Assumptions/Limitations • Uniform distribution • Phantom idealized shapes/masses • Organs homogeneous density/composition • Energy disposition over macro versus micro level • Dose due to bremsstrahlung and minor contributors ignored • Most particulate radiation and low energy photons assumed to deposit energy only locally • Residence times for Teff calculations based mainly on animal studies

  34. Example Calculations

  35. Example 1 - Cumulated Activity à Given the activity-time curve at the left – what is the cumulated activity? Ã1=10x1 MBq - day Ã2= 7x1 MBq - day Ã3= 2x1 MBq - day Ã4= 1x1 MBq - day ÃT= 20 MBq - day

  36. Example 2 - Organ Dose • Calculate the absorbed dose to the liver from a 3 mCi injection of 99mTc- sulfur colloid • Assume • 60% activity trapped in liver • 30% by the spleen • 10% by the Red Marrow • With instantaneous uptake and no biological excretion • (Recall: as Tb approches infinity Teff = Tp)

  37. Example 2 cont’d - Organ Dose Key equations: • Ãh = A0 • fh • 1.44 Teff • D = Ã S • Where • A0 is in mCi – initial activity taken into the body • Teff in hours – “effective” half-life • fh fraction of initial activity deposited in organ of concern • S = S-Factor provided in MIRD Pamphlet 11

  38. Example 2 cont’d - Organ Dose Calculate Ãh = A0 • fh • 1.44 Te • ÃLI = 3.0 mCi x 0.60 x 1.44 x 6.0 h = 15,600 mCi • h • ÃSP = 3.0 mCi x 0.30 x 1.44 x 6.0 h = 7780 mCi • h • ÃRM = 3.0 mCi x 0.10 x 1.44 x 6.0 h = 2590 mCi • h Provided S-values: • S (LI LI) = 4.6 x 10-5 rad/uCi • h • S (Li SP) = 9.2 x 10-7 rad/uCi • h • S (LI RM) = 1.6 x 10-6 rad/uCi • h

  39. Example 2 cont’d - Organ Dose Using D = Ã S = (A0 • fh • 1.44 Teff) x S • D (LI LI) = 15,600 mCi•h x 4.6 x 10-5 rad/uCi•h = 0.718 • D (Li SP) = 7780 mCi•h x 9.2 x 10-7 rad/uCi•h = 0.0072 • D (LI RM) = 2590 mCi•h x 1.6 x 10-6 rad/uCi•h = 0.0041 Total Dose to the Liver: • Dtot = 0.729 rad

  40. A Dosimetric Problem simplified • A patient with thyroid carcinoma was administered a tracer dose of 185 MBq (5 mCi) I-131 for a whole-body scan. Uptakes measured at 2 h and 24 h are 5% and 24% respectively. • Three days later a therapy dose of 2.035 GBq (55 mCi) was administered. Percentage activities retained by the whole body at 1 d and 2 d are respectively 25% and 15%. A 2-week pregnancy was detected after administration of radioiodine. • What is the dose to embryo? • Do you advise termination of pregnancy or continuation to full term?

  41. Solution - Cumulated activity Ã: Note: This assumes biological half-life biological half-life of iodine 80 days. The physical half life is 8 days. From the two assume Teff for I131 is 7.3 days

  42. Solution Continued - D = Ã S • Using estimated S Values presented in Approaches To Assessing Doses To The Embryo: • S(U T) at 12th week (fetus ~ 100 mg) = 3.70E-17 Gy/(Bq-sec) • S(U T) at 22 weeks (fetus ~ 2g) = 2.07E-16 Gy/(Bq-sec) • Dose • Total accumulated dose to the embryo up to 12th week is estimated to be • In such a situation, most authorities do not advise abortion D = Ã S = 1.96E+15bq·sec X 3.70E-17 Gy/(Bq-sec) = 0.0723 Gy or 7.23 rad Reference: Reddy, A. R. and Jain, S. C.Approaches To Assessing Doses To The Embryo And Fetus Radiat. Prot. Dosim. 79(1– 4), 289–298 (1998)

  43. Comments on Fetus/Embryo Radiation Exposure • < 10 days “all or nothing” – a lethal effect or no effect • 3-5 weeks after conception high radiation exposure may lead to implantation failure • Fetal doses > 100 mGy (10 Rad) can result in some IQ reduction • Fetal doses around 1000 mGy (100 Rad) can result in severe mental retardation particularly during 8-15 weeks and to a lesser extent at 16-25 weeks • Fetal doses of 100 mGy (10 Rad) are not reached with 3 pelvic CT scans or 20 conventional diagnostic x-rays • 100 mGy (10 Rad) can be reached with fluoroscopically guided pelvis interventional procedures or radiotherapy Reference: IAEA

  44. Effects on embryo and fetusFrom acute exposures Reference: IAEA

  45. Questions?

  46. References • Huda, W. and Slone, R., Review of Radiological Physics 2nd Ed. (2003) • Early, P. and Sodee, D. B, Principles and Practices of Nuclear Medicine 2nd Ed. (1995) • Stabin, M.G. and Sparks, R., Radio-Pharmaceutical Internal Dose Assessment (2001) • The Essential Physics of Medical Imaging, Bushberg, J. et. al. • Lombardi, Max, Radiation Safety in Nuclear Medicine, 2nd Ed. (2007) • NUREG-CR/634 • Reddy, A. R. and Jain, S. C.Approaches To Assessing Doses To The Embryo And Fetus Radiat. Prot. Dosim. 79(1– 4), 289–298 (1998) • RUSSEL, J.G.B., Diagnostic radiation, pregnancy and termination, Br. J. Radiol. 62 733 (1989) 92-3 • http://www.xrayrisk.com/calculator/

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