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Improved estimates of the radiation absorbed dose to the urinary bladder wall
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2014 Phys. Med. Biol. 59 2173 (http://iopscience.iop.org/0031-9155/59/9/2173) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 130.102.42.98 This content was downloaded on 28/05/2014 at 09:04
Please note that terms and conditions apply.
Institute of Physics and Engineering in Medicine Phys. Med. Biol. 59 (2014) 2173–2182
Physics in Medicine and Biology
doi:10.1088/0031-9155/59/9/2173
Improved estimates of the radiation absorbed dose to the urinary bladder wall Martin Andersson 1 , David Minarik 1 , Lennart Johansson 2 , ¨ Soren Mattsson 1 and Sigrid Leide-Svegborn 1 1
Medical Radiation Physics, Department of Clinical Sciences Malm¨o, Lund University, Sk˚ane University Hospital, SE-205 02 Malm¨o, Sweden 2 Department of Radiation Sciences, Ume˚a University, Sweden E-mail: [email protected] Received 2 October 2013 Accepted for publication 23 January 2014 Published 8 April 2014 Abstract
Specific absorbed fractions (SAFs) have been calculated as a function of the content in the urinary bladder in order to allow more realistic calculations of the absorbed dose to the bladder wall. The SAFs were calculated using the urinary bladder anatomy from the ICRP male and female adult reference computational phantoms. The urinary bladder and its content were approximated by a sphere with a wall of constant mass, where the thickness of the wall depended on the amount of urine in the bladder. SAFs were calculated for males and females with 17 different urinary bladder volumes from 10 to 800 mL, using the Monte Carlo computer program MCNP5, at 25 energies of mono-energetic photons and electrons ranging from 10 KeV to 10 MeV. The decay was assumed to be homogeneously distributed in the urinary bladder content and the urinary bladder wall, and the mean absorbed dose to the urinary bladder wall was calculated. The Monte Carlo simulations were validated against measurements made with thermoluminescent dosimeters. The SAFs obtained for a urine volume of 200 mL were compared to the values calculated for the urinary bladder wall using the adult reference computational phantoms. The mean absorbed dose to the urinary wall from 18F-FDG was found to be 77 μGy/MBq formales and 86 μGy/MBq for females, while for 99mTc-DTPA the mean absorbed doses were 80 μGy/MBq for males and 86 μGy/MBq for females. Compared to calculations using a constant value of the SAF from the adult reference computational phantoms, the mean absorbed doses to the bladder wall were 60% higher for 18F-FDG and 30% higher for 99mTc-DTPA using the new SAFs. Keywords: dosimetry, urinary bladder, radiation, absorbed dose, dynamic SAF value S Online supplementary data available from stacks.iop.org/PMB/59/2173/mmedia 0031-9155/14/092173+10$33.00
© 2014 Institute of Physics and Engineering in Medicine Printed in the UK & the USA 2173
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Phys. Med. Biol. 59 (2014) 2173
1. Introduction Radiopharmaceuticals administered for diagnosis are largely excreted from the body through the kidneys and the urinary bladder. As activity is stored in the urine in the bladder, it constitutes an important source of radiation of the bladder wall, as well as a number of neighboring organs, especially when substantial quantities of radionuclides are administered, and when the radionuclides are rapidly excreted. The urinary bladder wall is also considered to be a radiosensitive organ, with a risk of the induction of cancer (ICRP 2007). Over the years, different models have been used to calculate the absorbed dose to the urinary bladder wall. Two static models, based on the Fisher–Snyder (Snyder et al 1978) and Cristy–Eckerman (Cristy and Eckerman 1987) phantoms, assume a constant bladder volume of 202.6 mL and a wall volume of 45.73 cm3. However, the volume of the urinary bladder and the thickness of the bladder wall vary as a function of the rate of filling and emptying, and it is therefore necessary to include the dynamic behavior of the bladder in dosimetric calculations. In 1973, Cloutier et al (1973) calculated absorbed doses from photons to the uterus and the fetus using a dynamic urinary female bladder. To simulate the female bladder, the male urinary bladder of the Fisher–Snyder phantom was scaled by the cubed-root of the ratio of the whole-body masses of women and men. It was assumed that the bladder was ellipsoidal, and was filled at a constant rate until the volume reached 300 mL, when it was emptied. Dose calculations were performed for one bladder filling cycle using Monte Carlo simulations of the average dose per photon emitted by mono-energetic photons with nine different energies for various ages of the fetus. The contribution of electrons to the dose was neglected, and no calculations of the dose to the bladder wall were performed. A few years later, Snyder and Ford (1976) developed a dynamic bladder model to calculate the absorbed dose to the bladder wall based on the ellipsoidal bladder in the Fisher–Snyder phantom with a constant bladder wall mass of 45 g. The absorbed dose to the bladder wall per photon was calculated using Monte Carlo simulations for mono-energetic photons with twelve different energies and seven different bladder volumes ranging from 0 to 500 mL. The absorbed dose to the bladder wall, per photon, was approximated by a bi-exponential function of volume up to 500 mL, for each photon energy. The contribution to the absorbed dose to the bladder wall from electrons was derived using Berger’s point kernels (Berger 1971). Both the average absorbed dose to the bladder wall and the absorbed dose to the inner surface of the wall were calculated. The surface dose rate due to the electrons was calculated using a conservative approach, assuming that half of the dose rate in the bladder content goes to the bladder wall. Diffey and Hilson (1976) simplified the shape of the bladder, assuming it was a sphere, and applied an analytical method to calculate the absorbed dose to the bladder wall from 99m Tc-DTPA for an arbitrary bladder volume until the first voiding. The absorbed dose to the inner surface of the bladder wall was calculated using an exposure rate constant for 99mTc and a conversion factor from roentgen to rad for photons and electrons. The absorbed dose was calculated in the same way as Snyder and Ford (1976). Chen et al (1985) further developed the dynamic model of Diffey and Hilson to include a residual volume different from zero and the possibility of more than one exponential input function. The absorbed dose to the inner surface of the bladder wall was calculated using radionuclide-specific gamma rate constants for photons, and the same conservative approach for electrons as mentioned above. Thomas et al (1992) modified this model to include a nighttime period with a reduction of urinary flow and no voiding. Their model also included a voiding fraction in relation to a fixed residual volume, instead of a residual fraction of 0.07 of the content before voiding. Thomas et al (1992), (1999) used a different gamma rate constant from Chen et al (1985), and calculated the absorbed dose to the inner bladder surface using 2174
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Berger’s point kernels. They also calculated the absorbed dose at two different depths in the bladder wall: one at which 50% of the kinetic energy was absorbed, and another at which 90% of the kinetic energy was absorbed. The absorbed doses from electrons at the two depths were calculated using Berger’s geometrical reduction function from a point kernel to a spherical volume (Berger 1970). Karaiskos et al (2000) performed Monte Carlo simulations of the dynamic model presented by Thomas et al (1992) for 99mTc. By enclosing the urinary bladder in water, they found that the backscatter from surrounding organs and tissue could lead to a 25% underestimation of the photon absorbed dose. Corresponding simulations have also been performed for 131I, and the absorbed dose to the inner surface of the bladder wall was found to differ by up to 12% due to backscattering (Likoka et al 2001). Two different geometries have been used to describe the urinary bladder, since the anterior– posterior and lateral projections give circular and elliptical shapes, respectively (Lotz et al 1987). An ellipsoid was used to simulate the bladder in earlier dynamic urinary models, while in newer models, a spherical shape is assumed to simplify the calculations. Chen et al (1985) stated that both are valid approximations for a full bladder, but an empty bladder has an irregular shape, and neither of the above mentioned shapes is representative. However, the major contribution to the absorbed dose to the bladder wall arises from non-penetrating radiation, and this is relatively independent of the bladder shape (Chen et al 1985). Estimates of the mean absorbed dose to the bladder wall in the present study were based on the specific absorbed fraction (SAF) (Snyder et al 1978), which is the fraction of radiation energy emitted within a source region and absorbed in a target region divided by the mass of the target region. The aim of this study was to improve calculations of the absorbed dose to the urinary bladder wall. This was done by improving the dynamic model of the bladder presented by Thomas et al (1999) by including Monte Carlo-simulated SAF values for different energies and urinary contents. The mean absorbed dose to the urinary bladder wall was subsequently calculated using these values. Simulations were carried out for mono-energetic photons and electrons, and various amounts of urine in the bladder. The urinary bladder was modeled using the spherical bladder approximation together with data from the male and female ICRP/ICRU computational reference voxel phantoms (ICRP 2009), leading to gender-specific results. This work also takes into account biokinetic models that include the bladder wall as a source organ (Stabin 2010), and SAF values were also obtained with the bladder wall as the source and as the target, in contrast to previous work. The volume-specific SAF values for mono-energetic electrons and photons for the two source regions, are given for males and females separately as online supplementary data (available from stacks.iop.org/PMB/59/2173/mmedia). 2. Materials and methods 2.1. Anatomy of the urinary bladder
The geometries for the simulations of the urinary bladder content and the urinary bladder wall were taken from the anatomy of the Adult Reference Computational Phantoms published in the ICRP publication 110 (ICRP 2009). Simulations were performed for both the male and female phantom. The bladder content and the bladder wall were simulated as two spheres, where the bladder content was a sphere inside the bladder wall. The simulations were carried out assuming a homogeneous activity distribution in the source region. To simulate the surrounding tissues and organs, the bladder wall was placed in a water phantom to account for backscatter. 2175
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Simulations were carried out for 17 different bladder content volumes ranging from 10 to 800 mL. The chemical composition and density of the urine in the bladder were taken from the ICRP Adult Reference Computational Phantoms (ICRP 2009). The bladder wall was simulated using a constant mass of 50.01 g for the male and 40.00 g for the female (ICRP 2009). 2.2. Monte Carlo simulations
The SAF values for mono-energetic photons and electrons were calculated in the energy interval of 10 keV to 10 MeV, which is the range of the electrons for the ICRP/ICRU computational voxel phantom (Zankl et al 2012). The Monte Carlo simulations were performed using the computer program MCNP5 version (X-5 2003), with a cutoff energy of 1 keV for both electrons and photons. Each Monte Carlo simulation was performed with 500 000 homogeneously distributed particles, with an overall relative error of 0.0058 (95% CI = 0.0055 to 0.0062) for all simulations. The energy deposited in the bladder wall was obtained from a predefined MCNP detector, F8∗ tally. This detector scores the contribution from each particle and normalizes the total energy deposited per starting particle. The radii of the inner and outer spheres of the bladder wall were calculated according to: rin = 3 3Vi /4π (1) and rout =
3
3(Vi + MB /ρB )/4π
(2)
where rin is the inner radius, rout is the outer radius, MB and ρB are the mass and density of the urinary bladder tissue, respectively, and Vi is the urinary volume (10, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, or 800 mL). 2.3. Thermoluminescent dosimeter measurements
To validate the Monte Carlo simulations, a sphere of polymetylmethacrylate (PMMA) with an outer radius of 39.8 mm and a 1.0 mm thick wall was filled with 70.9 MBq 99mTcpertechnetate, homogeneously distributed in water. Four lithium-fluoride thermoluminescent dosimeters (TLDs), (LiF:Mg,Cu,P, Harshaw TLD-100H, Radcard, Krakow, Poland) were attached to the outside of the sphere for 21 h. The TLDs were evaluated within 24 h using a TLD reader (Harshaw 5500, Gammadata Bicron NE, Wermelskirchen, Germany). Energy correction factors were applied to account for the difference in TLD response between the 60 Co calibration beam and the measurement beam. The same geometry was created in the MCNP program and the composition of the PMMA was taken from the National Institute of Standards and Technology (NIST 2013). 2.4. Absorbed dose calculations
The absorbed dose to the bladder wall was calculated using the dynamic model of Thomas et al (1999), in which the time-dependent bladder content volume, V (t ), was determined by: (3) V (t ) = V0 + U (t ) dt; 0 t < T1 and
V (t ) = Vr +
U (t ) dt;
Tn−1 t < Tn
(4)
where V0 is the initial bladder volume, U (t ) is the rate of flow of urine into the bladder at time t, Vr is the residual volume after voiding, and Tn is the time at which voiding occurs. 2176
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Table 1. The values used to calculate the absorbed dose to the urinary bladder wall resulting from 18F-FDG and 99mTc-DTPA. 18
Rate of flow of urine into the bladder (min−1) with corresponding fractions
F-FDG 3.85E-02 (0.19) 1.24E-03 (0.06)
99m
Tc-DTPA 1.15E-02 (0.579) 1.25E-03 (0.421)
1.0 mL min−1 0.5 mL min−1 09:00 40 min 3.5 h 00:00 6h
Urine inflow: day Urine inflow: night Time of administered activity Time to first voiding Voiding interval Night-time starts Length of night
Two terms were used to calculate the time-dependent activity of the bladder content (A(t )). The first term represents the excretion of the activity from the body to the urinary bladder and the decay of the activity in the bladder, and the second term corrects for the activity that is secreted by each voiding of the bladder: n m Vr 1− A(Ti ) e−λ(t−Ti ) α j (1 − e−λ j t ) − (5) A(t ) = A0 e−λt V (T ) i i j=1 where A0 is the initial activity, λ is the physical decay constant, λ j is the biological elimination constant for the jth component and Vr /V (Ti ) is the voiding fraction of voiding i at time t. The mean absorbed dose to the bladder wall was described using the joint ICRP MIRD formalism (Bolch et al 2009): EiYi (rr ← rs , Ei , V (t )) dt[Gy] (6) A(rs , t ) D(rT , TD ) = rs
i
where A(rs , t ) is the number of disintegrations in the source region rs at time t, Ei and Yi are the mean, or individual, energy and yield, respectively, of decay component i, and (rr ← rs , Ei , V (t )) is the SAF value for energy i for volume V at time t. The mean absorbed dose to the bladder wall from the activity in the bladder content was calculated for 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) and 99mTcdiethylenetriaminepentaacetic acid (99mTc-DTPA). A urine inflow of 1.0 mL min−1 was assumed during the day and an inflow of 0.5 mL min−1 during the night, starting at midnight and lasting 6 h. The activity was administered (at 9 am, with an initial urinary bladder content of 10 mL. The voiding interval was set to 3.5 h, according to the ICRP kidneybladder model (ICRP 198), with an extra voiding just before midnight. The excretion from different compartments to the urinary bladder was taken from Thomas et al (1984), (1999). The parameters used in the calculations are given in table 1. 3. Results and discussion 3.1. Validation of Monte Carlo simulations
All the Monte Carlo-simulated SAF values were slightly higher for females than males, for the same bladder volume, due to the thinner female bladder wall. The electron SAF values for a 200 mL bladder obtained in this study were in agreement with the electron SAF values obtained for a static bladder with the same bladder content, using the same phantom as described by Zankl et al (2012), as can be seen in figures 1 and 2. This indicates that modeling the urinary 2177
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Figure 1. Electron SAF values calculated in this work assuming the bladder content a source region and the bladder wall is the target region for a bladder content of 200 mL together with the corresponding SAF values published by Zankl et al (2012).
Figure 2. Electron SAF values calculated in this work assuming the bladder wall is
the source and the target regions for a bladder content of 200 mL together with the corresponding SAF values published by Zankl et al (2012).
bladder as a sphere is a valid assumption for the calculation of the absorbed dose to the reference man and women given in ICRP Publication 89 (ICRP 2002). The measurement using the PMMA sphere filled with 99mTc and TLDs to validate the Monte Carlo simulations gave an absorbed dose of 6.3 ± 0.6 mGy. The simulated dose was 6.7 ± 0.1 mGy, and the results were consistent within their uncertainties.
3.2. SAF values
A constant, radiopharmaceutical-specific photon exposure rate and the mean electron particle energy were used to calculate the absorbed dose to the inner surface of the bladder wall in the dynamic model by Thomas et al (1999). They also performed calculations at two depths in the 2178
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Figure 3. Male SAF values obtained with the bladder content as the source and the
bladder wall as the target organ, for a fixed bladder content volume of 400 mL, for photons and electrons of different energies.
bladder wall, therefore, it is not possible to compare the results obtained in the present study with those given by Thomas et al (1999). Figure 3 shows the male SAF values obtained using the bladder content as the source region and the bladder wall as target region for both electrons and photons for a fixed volume of 400 mL. At a fixed volume, the SAF values for electrons increase with increasing energy up to 5 MeV. Above 5 MeV the SAF values start to decrease, since the range of the electrons exceeds the thickness of the bladder wall. The SAF value for electron increases with decreasing volume of the bladder content using the equal activity distributed throughout the volume. This increase is a result of a change in wall thickness and more electrons hitting the bladder wall, which is due to a decrease in self-attenuation through the bladder volume. A distinct peak in the SAF values for photons was observed at 20 keV for all bladder volumes. The position of the peak depends on the wall thickness and self-attenuation in the bladder content, although this effect is relatively small. Similar results were found for females. The SAF value decreases with increasing bladder volume at a fixed electron or photon energy. The fraction of energy absorbed outside the source region will decrease with increasing bladder volume and with homogeneously distributed activity. A reduction in the thickness of the bladder wall with increasing volume, assuming constant mass, will also result in a reduction of the SAF value, as can be seen for females in figure 4. Similar results were found for males. When the source and target regions are the same, the SAF decreases with increasing energy because at the higher energies more energy is transported outside the local volume, as can be seen for females in figure 5. Similar results were found for males. For a fixed energy, the SAF values decrease with a larger bladder volume, as shown for males in figure 6. Similar results were found for females. The effect will be greater for higher energies, and greater for photons than for electrons. 3.3. Absorbed dose calculations
The mean absorbed dose per unit administered activity of 99mTc-DTPA calculated using the new SAF values was 77 μGy/MBq for males and 86 μGy/MBq for females. These values are 2179
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Phys. Med. Biol. 59 (2014) 2173
Figure 4. Female SAF values obtained with the bladder content as the source and the
bladder wall as the target organ, for 150 keV photons and electrons, for different bladder volumes.
Figure 5. Female SAF values obtained with the bladder wall as the source and the target, for a fixed bladder content volume of 400 mL, for photons and electrons of different energies.
30% higher than those obtained using the SAF values given by Zankl et al (2012), assuming a constant bladder volume and the same activity parameters. The mean absorbed dose to the bladder wall per unit administered activity from a 18F-FDG injection was found to be 80 μGy/MBq for males and 86 μGy/MBq for females using the SAF values generated in this work, which are 60% higher than the values obtained using the SAF values given by Zankl et al (2012). The reason for this is that the volume of the urinary bladder is predominantly smaller than 200 mL, i.e., the volume used in the ICRP/ICRU adult reference voxel phantom. Calculations with the dynamic SAF values in the present study showed that voiding of the bladder 70 min after the administration of 18F-FDG reduced the mean absorbed dose by 35%. The corresponding values for 99mTc-DTPA are voiding after 80 min, resulting in a reduction of the absorbed dose of 50%. 2180
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Figure 6. Male SAF values obtained with the bladder wall as the source and the target, for 150 keV photons and electrons, for different bladder volumes.
Conclusions New SAF values were calculated to obtain a more realistic estimate of the absorbed dose to the urinary bladder wall. In addition to the more accurate calculation of the mean absorbed dose to the urinary bladder, the accuracy of the calculated effective dose was improved, providing a better estimate of the potential radiation-induced cancer risk. The advantage of using SAF values from mono-energetic electrons and photons is that they can be used for all photon- and electron-emitting radionuclides. It should be noted that this model only addresses the changes in the radiosensitive urinary bladder wall, and does not include the effects of geometrical changes on neighboring organs. Acknowledgment This research was financially supported by the Swedish Radiation Safety Authority (grant no. SSM2013-1420). References Berger M J 1970 Beta-ray dosimetry calculations with the use of point kernels in medical radionuclides, radiation dose and effects AEC Symposium Series No. 20 (USAEC Division of Technical Information) Berger M J 1971 Distribution of absorbed dose around point sources of electrons and beta particles in water and other media MIRD Pamphlet No. 7 (New York: Society of Nuclear medicine) Bolch W, Eckerman K, Sgouros G and Thomas S 2009 MIRD Pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry—standardization of nomenclature J. Nucl. Med. 50 477–84 Chen C-I, Harper P V and Lathrop K A 1985 A simple dynamic model for calculating radiation absorbed dose to the bladder wall 4th Int. Radiopharmaceutical Dosimetry Symp. (Oak Ridge, TN, USA) ed A l Schlafke-Stelson and E E Watson pp 587–612 Cloutier R J, Smith S A, Watson E E, Snyder W S and Warner G G 1973 Dose to the fetus from radionuclides in the bladder Health Phys. 25 147–61 Cristy M and Eckerman K 1987 Specific absorbed fractions of energy at various ages from internal photons sources ORNL/TM-8381 V1-V7 (Oak Ridge, TN, USA: Oak Ridge National Laboratory) Diffey B and Hilson A 1976 Absorbed dose to the bladder from 99mTc-DIPA Br. J. Radiol. 49 196–8 2181
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ICRP 1988 Radiation dose to patients from radiopharmaceuticals Ann. ICRP 18 1–4 (ICRP Publication 53) ICRP 2002 Basic anatomical and physiological data for use in radiological protection: reference values Ann. ICRP 32 3–4 (ICRP Publication 89) ICRP 2007 The 2007 recommendations of the international commission on radiological protection Ann. ICRP 37 2–4 (ICRP Publication 103) ICRP 2009 Adult reference computational phantoms Ann. ICRP 39 2 (ICRP Publication 110) Karaiskos P, Angelopoulos A, Baras P, Dimitriou P, Frantzis A and Sakelliou L 2000 Radiation dose to bladder wall from technetium-99m accumulated in the bladder contents Radiat. Prot. Dosim. 87 281–6 Likoka E, Angelopoulos A, Baras P, Karaiskos P, Pantelis E, Sakelliou L and Dimitriou P 2001 Bladder wall dosimetry for 131I administrated activities Radiat. Prot. Dosim. 95 109–16 Lotz H, Hietala S O and Bergman B 1987 Assessment of residual urine volume during routine cystography and urography Int. Urol. Nephrol. 19 71–4 NIST 2013 (National Institute of Standards and Technology USA) Composition of polymethyl methacralate (Lucite, Perspex, Plexiglass) http://physics.nist.gov/cgi-bin/Star/compos.pl?refer= ap&matno=223 Snyder W S and Ford M R 1976 Estimation of dose to the urinary bladder and to the gonads Radiopharmaceutical Dosimetry Symp. (Oak Ridge, TN, USA, 26–29 April) ed Ri Cloutier, I L Coffey, W 5 Snyder and E E Watson pp 313–50 (HEW Publication (FDA)) Snyder W S, Ford M R and Warner G O 1978 MIRD Pamphlet No. 5 revised: estimates of specific absorbed fractions for photon sources uniformly distributed in various organs of heterogeneous phantom (New York: The Society of Nuclear Medicine) Stabin M G 2010 Proposed revision to the radiation dosimetry of 82Rb Health Phys. 99 811–3 Thomas S R, Atkins H L, McAfee J G, Blaufox M D, Fernandez M, Kirchner P T and Reba R C 1984 Radiation absorbed dose from Tc-99m diethylenetriaminepentaacetic acid (DTPA) J. Nucl. Med. 25 503–5 Thomas S R, Stabin M G, Chen C T and Samaratunga R C 1992 MIRD Pamphlet No. 14: a dynamic urinary bladder model for radiation dose calculations J. Nucl. Med. 33 783–802 Thomas S R, Stabin M G, Chen C T and Samaratunga R C 1999 MIRD Pamphlet No. 14 revised: a dynamic urinary bladder model for radiation dose calculations J. Nucl. Med. 40 102S–23S X-5 Monte Carlo Team 2003 MCNP—a general Monte Carlo N-particle transport code version 5: volume: I. Overview and theory (Los Alamos: National Laboratory) LA-UR-03-1987 Zankl M, Schlattl H, Petoussi-Henss N and Hoeschen C 2012 Electron specific absorbed fractions for the adult male and female ICRP/ICRU reference computational phantoms Phys. Med. Biol. 57 4501–26
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Improved estimates of the radiation absorbed dose to the urinary bladder wall
This content has been downloaded from IOPscience. Please scroll down to see the full text. 2014 Phys. Med. Biol. 59 2173 (http://iopscience.iop.org/0031-9155/59/9/2173) View the table of contents for this issue, or go to the journal homepage for more
Download details: IP Address: 130.102.42.98 This content was downloaded on 28/05/2014 at 09:04
Please note that terms and conditions apply.
Institute of Physics and Engineering in Medicine Phys. Med. Biol. 59 (2014) 2173–2182
Physics in Medicine and Biology
doi:10.1088/0031-9155/59/9/2173
Improved estimates of the radiation absorbed dose to the urinary bladder wall Martin Andersson 1 , David Minarik 1 , Lennart Johansson 2 , ¨ Soren Mattsson 1 and Sigrid Leide-Svegborn 1 1
Medical Radiation Physics, Department of Clinical Sciences Malm¨o, Lund University, Sk˚ane University Hospital, SE-205 02 Malm¨o, Sweden 2 Department of Radiation Sciences, Ume˚a University, Sweden E-mail: [email protected] Received 2 October 2013 Accepted for publication 23 January 2014 Published 8 April 2014 Abstract
Specific absorbed fractions (SAFs) have been calculated as a function of the content in the urinary bladder in order to allow more realistic calculations of the absorbed dose to the bladder wall. The SAFs were calculated using the urinary bladder anatomy from the ICRP male and female adult reference computational phantoms. The urinary bladder and its content were approximated by a sphere with a wall of constant mass, where the thickness of the wall depended on the amount of urine in the bladder. SAFs were calculated for males and females with 17 different urinary bladder volumes from 10 to 800 mL, using the Monte Carlo computer program MCNP5, at 25 energies of mono-energetic photons and electrons ranging from 10 KeV to 10 MeV. The decay was assumed to be homogeneously distributed in the urinary bladder content and the urinary bladder wall, and the mean absorbed dose to the urinary bladder wall was calculated. The Monte Carlo simulations were validated against measurements made with thermoluminescent dosimeters. The SAFs obtained for a urine volume of 200 mL were compared to the values calculated for the urinary bladder wall using the adult reference computational phantoms. The mean absorbed dose to the urinary wall from 18F-FDG was found to be 77 μGy/MBq formales and 86 μGy/MBq for females, while for 99mTc-DTPA the mean absorbed doses were 80 μGy/MBq for males and 86 μGy/MBq for females. Compared to calculations using a constant value of the SAF from the adult reference computational phantoms, the mean absorbed doses to the bladder wall were 60% higher for 18F-FDG and 30% higher for 99mTc-DTPA using the new SAFs. Keywords: dosimetry, urinary bladder, radiation, absorbed dose, dynamic SAF value S Online supplementary data available from stacks.iop.org/PMB/59/2173/mmedia 0031-9155/14/092173+10$33.00
© 2014 Institute of Physics and Engineering in Medicine Printed in the UK & the USA 2173
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Phys. Med. Biol. 59 (2014) 2173
1. Introduction Radiopharmaceuticals administered for diagnosis are largely excreted from the body through the kidneys and the urinary bladder. As activity is stored in the urine in the bladder, it constitutes an important source of radiation of the bladder wall, as well as a number of neighboring organs, especially when substantial quantities of radionuclides are administered, and when the radionuclides are rapidly excreted. The urinary bladder wall is also considered to be a radiosensitive organ, with a risk of the induction of cancer (ICRP 2007). Over the years, different models have been used to calculate the absorbed dose to the urinary bladder wall. Two static models, based on the Fisher–Snyder (Snyder et al 1978) and Cristy–Eckerman (Cristy and Eckerman 1987) phantoms, assume a constant bladder volume of 202.6 mL and a wall volume of 45.73 cm3. However, the volume of the urinary bladder and the thickness of the bladder wall vary as a function of the rate of filling and emptying, and it is therefore necessary to include the dynamic behavior of the bladder in dosimetric calculations. In 1973, Cloutier et al (1973) calculated absorbed doses from photons to the uterus and the fetus using a dynamic urinary female bladder. To simulate the female bladder, the male urinary bladder of the Fisher–Snyder phantom was scaled by the cubed-root of the ratio of the whole-body masses of women and men. It was assumed that the bladder was ellipsoidal, and was filled at a constant rate until the volume reached 300 mL, when it was emptied. Dose calculations were performed for one bladder filling cycle using Monte Carlo simulations of the average dose per photon emitted by mono-energetic photons with nine different energies for various ages of the fetus. The contribution of electrons to the dose was neglected, and no calculations of the dose to the bladder wall were performed. A few years later, Snyder and Ford (1976) developed a dynamic bladder model to calculate the absorbed dose to the bladder wall based on the ellipsoidal bladder in the Fisher–Snyder phantom with a constant bladder wall mass of 45 g. The absorbed dose to the bladder wall per photon was calculated using Monte Carlo simulations for mono-energetic photons with twelve different energies and seven different bladder volumes ranging from 0 to 500 mL. The absorbed dose to the bladder wall, per photon, was approximated by a bi-exponential function of volume up to 500 mL, for each photon energy. The contribution to the absorbed dose to the bladder wall from electrons was derived using Berger’s point kernels (Berger 1971). Both the average absorbed dose to the bladder wall and the absorbed dose to the inner surface of the wall were calculated. The surface dose rate due to the electrons was calculated using a conservative approach, assuming that half of the dose rate in the bladder content goes to the bladder wall. Diffey and Hilson (1976) simplified the shape of the bladder, assuming it was a sphere, and applied an analytical method to calculate the absorbed dose to the bladder wall from 99m Tc-DTPA for an arbitrary bladder volume until the first voiding. The absorbed dose to the inner surface of the bladder wall was calculated using an exposure rate constant for 99mTc and a conversion factor from roentgen to rad for photons and electrons. The absorbed dose was calculated in the same way as Snyder and Ford (1976). Chen et al (1985) further developed the dynamic model of Diffey and Hilson to include a residual volume different from zero and the possibility of more than one exponential input function. The absorbed dose to the inner surface of the bladder wall was calculated using radionuclide-specific gamma rate constants for photons, and the same conservative approach for electrons as mentioned above. Thomas et al (1992) modified this model to include a nighttime period with a reduction of urinary flow and no voiding. Their model also included a voiding fraction in relation to a fixed residual volume, instead of a residual fraction of 0.07 of the content before voiding. Thomas et al (1992), (1999) used a different gamma rate constant from Chen et al (1985), and calculated the absorbed dose to the inner bladder surface using 2174
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Berger’s point kernels. They also calculated the absorbed dose at two different depths in the bladder wall: one at which 50% of the kinetic energy was absorbed, and another at which 90% of the kinetic energy was absorbed. The absorbed doses from electrons at the two depths were calculated using Berger’s geometrical reduction function from a point kernel to a spherical volume (Berger 1970). Karaiskos et al (2000) performed Monte Carlo simulations of the dynamic model presented by Thomas et al (1992) for 99mTc. By enclosing the urinary bladder in water, they found that the backscatter from surrounding organs and tissue could lead to a 25% underestimation of the photon absorbed dose. Corresponding simulations have also been performed for 131I, and the absorbed dose to the inner surface of the bladder wall was found to differ by up to 12% due to backscattering (Likoka et al 2001). Two different geometries have been used to describe the urinary bladder, since the anterior– posterior and lateral projections give circular and elliptical shapes, respectively (Lotz et al 1987). An ellipsoid was used to simulate the bladder in earlier dynamic urinary models, while in newer models, a spherical shape is assumed to simplify the calculations. Chen et al (1985) stated that both are valid approximations for a full bladder, but an empty bladder has an irregular shape, and neither of the above mentioned shapes is representative. However, the major contribution to the absorbed dose to the bladder wall arises from non-penetrating radiation, and this is relatively independent of the bladder shape (Chen et al 1985). Estimates of the mean absorbed dose to the bladder wall in the present study were based on the specific absorbed fraction (SAF) (Snyder et al 1978), which is the fraction of radiation energy emitted within a source region and absorbed in a target region divided by the mass of the target region. The aim of this study was to improve calculations of the absorbed dose to the urinary bladder wall. This was done by improving the dynamic model of the bladder presented by Thomas et al (1999) by including Monte Carlo-simulated SAF values for different energies and urinary contents. The mean absorbed dose to the urinary bladder wall was subsequently calculated using these values. Simulations were carried out for mono-energetic photons and electrons, and various amounts of urine in the bladder. The urinary bladder was modeled using the spherical bladder approximation together with data from the male and female ICRP/ICRU computational reference voxel phantoms (ICRP 2009), leading to gender-specific results. This work also takes into account biokinetic models that include the bladder wall as a source organ (Stabin 2010), and SAF values were also obtained with the bladder wall as the source and as the target, in contrast to previous work. The volume-specific SAF values for mono-energetic electrons and photons for the two source regions, are given for males and females separately as online supplementary data (available from stacks.iop.org/PMB/59/2173/mmedia). 2. Materials and methods 2.1. Anatomy of the urinary bladder
The geometries for the simulations of the urinary bladder content and the urinary bladder wall were taken from the anatomy of the Adult Reference Computational Phantoms published in the ICRP publication 110 (ICRP 2009). Simulations were performed for both the male and female phantom. The bladder content and the bladder wall were simulated as two spheres, where the bladder content was a sphere inside the bladder wall. The simulations were carried out assuming a homogeneous activity distribution in the source region. To simulate the surrounding tissues and organs, the bladder wall was placed in a water phantom to account for backscatter. 2175
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Simulations were carried out for 17 different bladder content volumes ranging from 10 to 800 mL. The chemical composition and density of the urine in the bladder were taken from the ICRP Adult Reference Computational Phantoms (ICRP 2009). The bladder wall was simulated using a constant mass of 50.01 g for the male and 40.00 g for the female (ICRP 2009). 2.2. Monte Carlo simulations
The SAF values for mono-energetic photons and electrons were calculated in the energy interval of 10 keV to 10 MeV, which is the range of the electrons for the ICRP/ICRU computational voxel phantom (Zankl et al 2012). The Monte Carlo simulations were performed using the computer program MCNP5 version (X-5 2003), with a cutoff energy of 1 keV for both electrons and photons. Each Monte Carlo simulation was performed with 500 000 homogeneously distributed particles, with an overall relative error of 0.0058 (95% CI = 0.0055 to 0.0062) for all simulations. The energy deposited in the bladder wall was obtained from a predefined MCNP detector, F8∗ tally. This detector scores the contribution from each particle and normalizes the total energy deposited per starting particle. The radii of the inner and outer spheres of the bladder wall were calculated according to: rin = 3 3Vi /4π (1) and rout =
3
3(Vi + MB /ρB )/4π
(2)
where rin is the inner radius, rout is the outer radius, MB and ρB are the mass and density of the urinary bladder tissue, respectively, and Vi is the urinary volume (10, 50, 100, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, or 800 mL). 2.3. Thermoluminescent dosimeter measurements
To validate the Monte Carlo simulations, a sphere of polymetylmethacrylate (PMMA) with an outer radius of 39.8 mm and a 1.0 mm thick wall was filled with 70.9 MBq 99mTcpertechnetate, homogeneously distributed in water. Four lithium-fluoride thermoluminescent dosimeters (TLDs), (LiF:Mg,Cu,P, Harshaw TLD-100H, Radcard, Krakow, Poland) were attached to the outside of the sphere for 21 h. The TLDs were evaluated within 24 h using a TLD reader (Harshaw 5500, Gammadata Bicron NE, Wermelskirchen, Germany). Energy correction factors were applied to account for the difference in TLD response between the 60 Co calibration beam and the measurement beam. The same geometry was created in the MCNP program and the composition of the PMMA was taken from the National Institute of Standards and Technology (NIST 2013). 2.4. Absorbed dose calculations
The absorbed dose to the bladder wall was calculated using the dynamic model of Thomas et al (1999), in which the time-dependent bladder content volume, V (t ), was determined by: (3) V (t ) = V0 + U (t ) dt; 0 t < T1 and
V (t ) = Vr +
U (t ) dt;
Tn−1 t < Tn
(4)
where V0 is the initial bladder volume, U (t ) is the rate of flow of urine into the bladder at time t, Vr is the residual volume after voiding, and Tn is the time at which voiding occurs. 2176
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Table 1. The values used to calculate the absorbed dose to the urinary bladder wall resulting from 18F-FDG and 99mTc-DTPA. 18
Rate of flow of urine into the bladder (min−1) with corresponding fractions
F-FDG 3.85E-02 (0.19) 1.24E-03 (0.06)
99m
Tc-DTPA 1.15E-02 (0.579) 1.25E-03 (0.421)
1.0 mL min−1 0.5 mL min−1 09:00 40 min 3.5 h 00:00 6h
Urine inflow: day Urine inflow: night Time of administered activity Time to first voiding Voiding interval Night-time starts Length of night
Two terms were used to calculate the time-dependent activity of the bladder content (A(t )). The first term represents the excretion of the activity from the body to the urinary bladder and the decay of the activity in the bladder, and the second term corrects for the activity that is secreted by each voiding of the bladder: n m Vr 1− A(Ti ) e−λ(t−Ti ) α j (1 − e−λ j t ) − (5) A(t ) = A0 e−λt V (T ) i i j=1 where A0 is the initial activity, λ is the physical decay constant, λ j is the biological elimination constant for the jth component and Vr /V (Ti ) is the voiding fraction of voiding i at time t. The mean absorbed dose to the bladder wall was described using the joint ICRP MIRD formalism (Bolch et al 2009): EiYi (rr ← rs , Ei , V (t )) dt[Gy] (6) A(rs , t ) D(rT , TD ) = rs
i
where A(rs , t ) is the number of disintegrations in the source region rs at time t, Ei and Yi are the mean, or individual, energy and yield, respectively, of decay component i, and (rr ← rs , Ei , V (t )) is the SAF value for energy i for volume V at time t. The mean absorbed dose to the bladder wall from the activity in the bladder content was calculated for 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) and 99mTcdiethylenetriaminepentaacetic acid (99mTc-DTPA). A urine inflow of 1.0 mL min−1 was assumed during the day and an inflow of 0.5 mL min−1 during the night, starting at midnight and lasting 6 h. The activity was administered (at 9 am, with an initial urinary bladder content of 10 mL. The voiding interval was set to 3.5 h, according to the ICRP kidneybladder model (ICRP 198), with an extra voiding just before midnight. The excretion from different compartments to the urinary bladder was taken from Thomas et al (1984), (1999). The parameters used in the calculations are given in table 1. 3. Results and discussion 3.1. Validation of Monte Carlo simulations
All the Monte Carlo-simulated SAF values were slightly higher for females than males, for the same bladder volume, due to the thinner female bladder wall. The electron SAF values for a 200 mL bladder obtained in this study were in agreement with the electron SAF values obtained for a static bladder with the same bladder content, using the same phantom as described by Zankl et al (2012), as can be seen in figures 1 and 2. This indicates that modeling the urinary 2177
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Figure 1. Electron SAF values calculated in this work assuming the bladder content a source region and the bladder wall is the target region for a bladder content of 200 mL together with the corresponding SAF values published by Zankl et al (2012).
Figure 2. Electron SAF values calculated in this work assuming the bladder wall is
the source and the target regions for a bladder content of 200 mL together with the corresponding SAF values published by Zankl et al (2012).
bladder as a sphere is a valid assumption for the calculation of the absorbed dose to the reference man and women given in ICRP Publication 89 (ICRP 2002). The measurement using the PMMA sphere filled with 99mTc and TLDs to validate the Monte Carlo simulations gave an absorbed dose of 6.3 ± 0.6 mGy. The simulated dose was 6.7 ± 0.1 mGy, and the results were consistent within their uncertainties.
3.2. SAF values
A constant, radiopharmaceutical-specific photon exposure rate and the mean electron particle energy were used to calculate the absorbed dose to the inner surface of the bladder wall in the dynamic model by Thomas et al (1999). They also performed calculations at two depths in the 2178
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Figure 3. Male SAF values obtained with the bladder content as the source and the
bladder wall as the target organ, for a fixed bladder content volume of 400 mL, for photons and electrons of different energies.
bladder wall, therefore, it is not possible to compare the results obtained in the present study with those given by Thomas et al (1999). Figure 3 shows the male SAF values obtained using the bladder content as the source region and the bladder wall as target region for both electrons and photons for a fixed volume of 400 mL. At a fixed volume, the SAF values for electrons increase with increasing energy up to 5 MeV. Above 5 MeV the SAF values start to decrease, since the range of the electrons exceeds the thickness of the bladder wall. The SAF value for electron increases with decreasing volume of the bladder content using the equal activity distributed throughout the volume. This increase is a result of a change in wall thickness and more electrons hitting the bladder wall, which is due to a decrease in self-attenuation through the bladder volume. A distinct peak in the SAF values for photons was observed at 20 keV for all bladder volumes. The position of the peak depends on the wall thickness and self-attenuation in the bladder content, although this effect is relatively small. Similar results were found for females. The SAF value decreases with increasing bladder volume at a fixed electron or photon energy. The fraction of energy absorbed outside the source region will decrease with increasing bladder volume and with homogeneously distributed activity. A reduction in the thickness of the bladder wall with increasing volume, assuming constant mass, will also result in a reduction of the SAF value, as can be seen for females in figure 4. Similar results were found for males. When the source and target regions are the same, the SAF decreases with increasing energy because at the higher energies more energy is transported outside the local volume, as can be seen for females in figure 5. Similar results were found for males. For a fixed energy, the SAF values decrease with a larger bladder volume, as shown for males in figure 6. Similar results were found for females. The effect will be greater for higher energies, and greater for photons than for electrons. 3.3. Absorbed dose calculations
The mean absorbed dose per unit administered activity of 99mTc-DTPA calculated using the new SAF values was 77 μGy/MBq for males and 86 μGy/MBq for females. These values are 2179
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Figure 4. Female SAF values obtained with the bladder content as the source and the
bladder wall as the target organ, for 150 keV photons and electrons, for different bladder volumes.
Figure 5. Female SAF values obtained with the bladder wall as the source and the target, for a fixed bladder content volume of 400 mL, for photons and electrons of different energies.
30% higher than those obtained using the SAF values given by Zankl et al (2012), assuming a constant bladder volume and the same activity parameters. The mean absorbed dose to the bladder wall per unit administered activity from a 18F-FDG injection was found to be 80 μGy/MBq for males and 86 μGy/MBq for females using the SAF values generated in this work, which are 60% higher than the values obtained using the SAF values given by Zankl et al (2012). The reason for this is that the volume of the urinary bladder is predominantly smaller than 200 mL, i.e., the volume used in the ICRP/ICRU adult reference voxel phantom. Calculations with the dynamic SAF values in the present study showed that voiding of the bladder 70 min after the administration of 18F-FDG reduced the mean absorbed dose by 35%. The corresponding values for 99mTc-DTPA are voiding after 80 min, resulting in a reduction of the absorbed dose of 50%. 2180
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Figure 6. Male SAF values obtained with the bladder wall as the source and the target, for 150 keV photons and electrons, for different bladder volumes.
Conclusions New SAF values were calculated to obtain a more realistic estimate of the absorbed dose to the urinary bladder wall. In addition to the more accurate calculation of the mean absorbed dose to the urinary bladder, the accuracy of the calculated effective dose was improved, providing a better estimate of the potential radiation-induced cancer risk. The advantage of using SAF values from mono-energetic electrons and photons is that they can be used for all photon- and electron-emitting radionuclides. It should be noted that this model only addresses the changes in the radiosensitive urinary bladder wall, and does not include the effects of geometrical changes on neighboring organs. Acknowledgment This research was financially supported by the Swedish Radiation Safety Authority (grant no. SSM2013-1420). References Berger M J 1970 Beta-ray dosimetry calculations with the use of point kernels in medical radionuclides, radiation dose and effects AEC Symposium Series No. 20 (USAEC Division of Technical Information) Berger M J 1971 Distribution of absorbed dose around point sources of electrons and beta particles in water and other media MIRD Pamphlet No. 7 (New York: Society of Nuclear medicine) Bolch W, Eckerman K, Sgouros G and Thomas S 2009 MIRD Pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry—standardization of nomenclature J. Nucl. Med. 50 477–84 Chen C-I, Harper P V and Lathrop K A 1985 A simple dynamic model for calculating radiation absorbed dose to the bladder wall 4th Int. Radiopharmaceutical Dosimetry Symp. (Oak Ridge, TN, USA) ed A l Schlafke-Stelson and E E Watson pp 587–612 Cloutier R J, Smith S A, Watson E E, Snyder W S and Warner G G 1973 Dose to the fetus from radionuclides in the bladder Health Phys. 25 147–61 Cristy M and Eckerman K 1987 Specific absorbed fractions of energy at various ages from internal photons sources ORNL/TM-8381 V1-V7 (Oak Ridge, TN, USA: Oak Ridge National Laboratory) Diffey B and Hilson A 1976 Absorbed dose to the bladder from 99mTc-DIPA Br. J. Radiol. 49 196–8 2181
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ICRP 1988 Radiation dose to patients from radiopharmaceuticals Ann. ICRP 18 1–4 (ICRP Publication 53) ICRP 2002 Basic anatomical and physiological data for use in radiological protection: reference values Ann. ICRP 32 3–4 (ICRP Publication 89) ICRP 2007 The 2007 recommendations of the international commission on radiological protection Ann. ICRP 37 2–4 (ICRP Publication 103) ICRP 2009 Adult reference computational phantoms Ann. ICRP 39 2 (ICRP Publication 110) Karaiskos P, Angelopoulos A, Baras P, Dimitriou P, Frantzis A and Sakelliou L 2000 Radiation dose to bladder wall from technetium-99m accumulated in the bladder contents Radiat. Prot. Dosim. 87 281–6 Likoka E, Angelopoulos A, Baras P, Karaiskos P, Pantelis E, Sakelliou L and Dimitriou P 2001 Bladder wall dosimetry for 131I administrated activities Radiat. Prot. Dosim. 95 109–16 Lotz H, Hietala S O and Bergman B 1987 Assessment of residual urine volume during routine cystography and urography Int. Urol. Nephrol. 19 71–4 NIST 2013 (National Institute of Standards and Technology USA) Composition of polymethyl methacralate (Lucite, Perspex, Plexiglass) http://physics.nist.gov/cgi-bin/Star/compos.pl?refer= ap&matno=223 Snyder W S and Ford M R 1976 Estimation of dose to the urinary bladder and to the gonads Radiopharmaceutical Dosimetry Symp. (Oak Ridge, TN, USA, 26–29 April) ed Ri Cloutier, I L Coffey, W 5 Snyder and E E Watson pp 313–50 (HEW Publication (FDA)) Snyder W S, Ford M R and Warner G O 1978 MIRD Pamphlet No. 5 revised: estimates of specific absorbed fractions for photon sources uniformly distributed in various organs of heterogeneous phantom (New York: The Society of Nuclear Medicine) Stabin M G 2010 Proposed revision to the radiation dosimetry of 82Rb Health Phys. 99 811–3 Thomas S R, Atkins H L, McAfee J G, Blaufox M D, Fernandez M, Kirchner P T and Reba R C 1984 Radiation absorbed dose from Tc-99m diethylenetriaminepentaacetic acid (DTPA) J. Nucl. Med. 25 503–5 Thomas S R, Stabin M G, Chen C T and Samaratunga R C 1992 MIRD Pamphlet No. 14: a dynamic urinary bladder model for radiation dose calculations J. Nucl. Med. 33 783–802 Thomas S R, Stabin M G, Chen C T and Samaratunga R C 1999 MIRD Pamphlet No. 14 revised: a dynamic urinary bladder model for radiation dose calculations J. Nucl. Med. 40 102S–23S X-5 Monte Carlo Team 2003 MCNP—a general Monte Carlo N-particle transport code version 5: volume: I. Overview and theory (Los Alamos: National Laboratory) LA-UR-03-1987 Zankl M, Schlattl H, Petoussi-Henss N and Hoeschen C 2012 Electron specific absorbed fractions for the adult male and female ICRP/ICRU reference computational phantoms Phys. Med. Biol. 57 4501–26
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