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Transitional Epithelium of Urinary Bladder: Dosimetric Data for Cells at Risk in Nuclear Medicine
K. F. Eckerman1 and K. G. Veinot1,2

1
Easterly Scientific, 6412 Westminster Rd., Knoxville, TN 377919
2
Y-12 National Security Complex, P.O. Box 2009, Oak Ridge, TN 37831

Abstract – Most human tumors arise in epithelial protection recommendations, the International
tissues that serve in a secretory and protective manner. Commission on Radiological Protection (ICRP)
This role has been recognized in cancers of the
respiratory and alimentary tracts, and the skin with assigned the urinary bladder tissue weighting
cells at radiogenic risk identified and addressed in the factors of 0.05 and 0.04, respectively, without
dosimetry. Nine out of ten urinary bladder cancers arise addressing the cells at risk [3, 4].
within the transitional epithelium of the bladder. The The dose to the urinary bladder following
transitional epithelium is a stratified epithelium in
which the shape of the surface cells depends on the inhalation and ingestion intakes of radionuclides
degree of stretching as the bladder fills. The epithelium was evaluated in ICRP Publications 30 and 68
is supported by basal cells that lie above a basement [5, 6]. In these assessments non-penetrating
membrane separating the epithelium from the stroma of
radiations (electrons and alphas) emitted within
the bladder wall. The depth of the basal cell depends on
the urine content of the bladder. Data derived in this the urine content of the bladder were considered
work suggest that the absorbed dose to the basal cells to only irradiate the bladder wall. Their
at risk is poorly represented by the absorbed dose to the contribution to the absorbed dose in the wall was
bladder wall. Furthermore, the cells at risk may not
even be irradiated by alpha emissions within the
approximated as one half the absorbed doses to
bladder urine content. These overestimates of the the urine content of the bladder. An ad hoc factor,
bladder dose can impact acceptance of new therapeutic one for electrons, zero for alpha recoil atoms, and
radiopharmaceuticals. 0.01 for alpha and fission fragments, was applied
to the estimated absorbed dose. This factor was
I. Introduction based, in part, on the work of Sullivan et al. [7].
The majority of human tumors arise in
ICRP Publication 133 [8] no longer uses the ad
epithelial tissues that serve in a secretory and
hoc factor but rather averages the absorbed energy
protective manner. At least nine out of ten urinary
derived by Monte Carlo calculations over the
bladder cancers arise within the transitional
mass of the entire bladder wall.
epithelium of the bladder [1]. This epithelium is
The volume of the bladder and thickness of its
unique to the urinary system in its ability to
wall varies over the bladder filling and voiding
change shape as urine accumulates within the
cycle. In occupational radiation protection, ICRP
bladder. Urinary excretion is a major route of
Committee 2 assumes a static urinary bladder
elimination of radionuclides that have entered
model with a urine content of 200 cc [5, 6]. ICRP
systemic circulation. The dosimetric consideration
Committee 3 uses a dynamic bladder model when
of this irradiation source initially arose within the
evaluating administered radiopharmaceuticals [9].
nuclear medicine community [2]. As radio-
However only the time-dependence of the activity
nuclides accumulate within the expanding bladder
in the bladder is considered; the dependence of the
their penetrating emissions (photons) irradiate the
energy deposition in the wall on the urine volume
various tissues of the body. The dose to the
is ignored. For additional information see Thomas
bladder wall was also considered, however no
et al. [10] and Anderson et al. [11].
considerations were given to the distribution of
absorbed dose with depth into the wall and to the
cells at risk. In its 1990 and 2007 radiation

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II. Materials and Methods absorbed dose to the basal cell target. Tally
A. Anatomy of the Urinary Bladder uncertainties were maintained below 5%. The
The main function of the urinary bladder is the MCNP-reported values were expressed in terms of
short-term storage of urine. Structurally the the specific absorbed fraction, SAF, used in the
urinary bladder must store a variable volume of dosimetry of internal emitters [14]; i.e.,
urine while maintaining a minimum ratio of 𝐷𝑇
𝑆𝐴𝐹(𝑇 ← 𝑆) = (1)
epithelial surface area to urine volume to limit 𝐸𝑆
movement of substances between the urine and where 𝐷𝑇 is the MCNP-reported absorbed dose in
body fluids [12]. The epithelium of the bladder is the basal cell target tissue T and 𝐸𝑆 is the energy
unique in its ability to change shape and flatten as of the radiation emitted within source region S.
the bladder fills. The bladder cells adjacent to the The two source regions considered were the urine
urine are referred to as umbrella cells which vary content and the entire bladder wall.
in shape depending on the bladder filling. Beneath
this cell layer are the intermediate cells and the III. Results and Discussion
basal cells that form their replacement (Fig. 1). The specific absorbed fractions for electron,
The anatomical parameters of a spherical urinary photon, and alpha emissions within the urine
bladder model in an adult, as a function of urine content of the bladder and within the bladder wall
content, are given in Table 1. In an adult male, the as a function of the urine content and emitted
mass of the bladder wall is 50 g (40 g in the energy are shown in Figs. 2–4. The electron SAF
female) [8], and the masses of the transitional data of Fig. 2.a for emissions within the urine
epithelium and the basal cell layer are 3.2 and exhibits three regions. Below about 80 keV the
1.2 g, respectively. The depth of the basal cells energy deposited in the basal cells is largely due
ranges from about 300 to 65 µm as the urine to bremsstrahlung. Between 80 and 200 keV the
volume ranges from 50 to 500 ml. SAF reflects the variation in the basal cells’ depth
B. Monte Carlo Simulations with urine content while at higher energies it
Monte Carlo simulations of the energy becomes a function of the volume of urine. The
deposition within the basal cells were performed SAF for electrons emitted within the bladder wall,
for mono-energetic alpha, electron, and photon Fig. 2.b, is independent of the urine content of the
emissions within the urine and bladder wall bladder for energies below 100 keV. Above
(transitional epithelium-lined mucosa, submucosa, 100 keV the SAF is inversely proportional to the
and muscularis layers) assuming the parameters of urine volume.
Table 1. These calculations were performed at the The photon SAF data of Fig. 3 exhibits an
discrete energies addressed in ICRP inverse relationship to the urine content with no
Publication 133; i.e., electrons and photons from marked change in pattern with energy and urine
10 keV to 10 MeV and alpha particles from 2 to content. These data are as expected, i.e., similar to
12 MeV. All calculations were performed using the ICRP Publication 133 values.
MCNP 6.1.1 [13]. In the calculations the bladder Alpha particles of energy less than 8 MeV
model was centered in a water-filled 30 cm emitted within the urine are unable to deposit
diameter sphere (density 1 g cm-3). The elemental energy in the basal cell layer over the range in
composition of urine, transitional epithelium, and urine content (Fig 4.a). Furthermore, no alpha
the rest of the bladder wall were taken from ICRP particles are able to irradiate the basal cells when
Publication 110 [14] with a density of 1 g cm-3. the volume of urine in the bladder was less than
Secondary charged particles were tracked in all 250 cc. Alphas emitted within the bladder wall,
simulations so the reported values represent the

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Transactions on Radiation and Plasma Medical Sciences
Fig. 4.b, irradiate the basal cells regardless of their
energy and urine volume.
ICRP Publication 133 [8] provides SAF values
for alpha, electron, photon, and neutron radiations
to be used in the computation of equivalent dose
coefficients for occupational intakes of
radionuclides. The urinary bladder dose
coefficient is derived assuming a static bladder
model with a urine volume of 200 ml. Figure 5
compares the electron, photon, and alpha SAFs of
ICRP Publication 133 for the bladder wall with
the SAFs for basal cell of this work. For electrons
of energy less than 100 keV the SAF of
Publication 133 overestimates the energy
deposition in the basal cell layer. Above 100 keV
the energy deposition is underestimated. For
photons, the bladder wall as the target provides a
reasonable estimate of the energy deposition in
the basal cell layer, although below 30 keV it
underestimates the energy deposition. For alpha
particles the SAFs of ICRP Publication 133
overestimates the energy deposition in the basal
cells seen in Fig. 5.c. This overestimation stems
from Publication 133 not considering a “dead
layer” within which the deposited energy is of no
biological concern.
For many radiopharmaceuticals the bladder
wall is a highly irradiated tissue and, despite
bladder cancer being assigned a tissue weighting
factor of 0.04, can be a significant contributor to
the effective dose. Past efforts to improve the
estimated dose for radiopharmaceuticals have
focused on a dynamic bladder model with variable
urine entry rates, voiding times, urine volume,
etc., [10, 11] while continuing to average the
absorbed dose over the bladder wall without
regard to its spatial distribution. In light of
growing interest in therapeutic radio-
pharmaceuticals, including the possible role of
alpha emitters, the dosimetric methodology needs
to address the bladder cells at radiogenic risks.
For example, Lassmann and Nosske [16]
evaluated the dosimetry of Ra-223 chloride as a
therapeutic agent using the dosimetric data of
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ICRP Publication 30. Their estimate of the
bladder dose coefficient, 6.6E-08 Sv Bq-1,
embodies the ad hoc factor of 0.01 discussed
above. This work would yield a dose coefficient
of 4.1E-10 Sv Bq-1 for the basal cells. Thus, the
dose of radiogenic significance is overestimated
by about two orders of magnitude—four orders of
magnitude if based on the SAFs of ICRP
Publication 133. The overestimate of the bladder
dose for alpha particles and, to a lesser extent, low
energy electrons is critical in light of interests in
therapeutic Auger [17] and alpha emitters [18].
Furthermore, the means to address such thin target
regions in Monte Carlo calculations has been
demonstrated by Kim et al. [19].
IV. Conclusion
Transitional cell carcinoma is the dominant
urinary bladder cancer, and the basal cells of the
transitional epithelium should be the target tissue
in computational dosimetry. The depth of this
target in the bladder wall is a function of the
volume of urine in the bladder. For occupational
and environmental exposures, averaging the basal
cell dose over the bladder filling-voiding cycles
confirms that a static model with a urine content
of 200 ml is appropriate. Dose estimates for
nuclear medicine administration of
radiopharmaceuticals labeled with short-lived
radionuclides need to consider the effect of
bladder filling and voiding on absorbed energy.
The overestimate of the bladder dose for alpha
emitters and, to a lesser extent, electrons in
current dosimetric calculations can have a
negative impact on possible therapeutic role of
Auger and alpha emitters.
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Table 1. Urinary Bladder Geometry Model

Radii (cm)* Basal Cell Layer (µm)§
Urine
Volume (cc) R1 R2 R3 Depth Thickness
50 2.2854 2.3150 2.8794 295.7 183.4
100 2.8794 2.8982 3.2961 187.5 117.5
150 3.2961 3.3104 3.6278 143.4 90.1
200 3.6278 3.6397 3.9080 118.5 74.6
250 3.9080 3.9182 4.1528 102.2 64.4
300 4.1528 4.1619 4.3718 90.5 57.1
350 4.3718 4.3800 4.5708 81.7 51.6
400 4.5708 4.5783 4.7538 74.8 47.2
450 4.7538 4.7607 4.9237 69.1 43.7
500 4.9237 4.9302 5.0827 64.4 40.7
*R1 is radius of urine volume, R2 radius of basal cell layer, and R3 radius of the
urinary bladder wall. Masses of spherical shells representing the bladder wall
(R1 to R3) is 50 g, transitional epithelium (R1 to R2 + depth of basal layer) is
3.2 g, and the basal cell layer (R2 to R2 + thickness of basal cell layer) is 1.2 g.
§
Basal cells located at tabulated depth in tissue beyond the urine which extends
to the indicated thickness. For example, if the urine volume is 200 cc the radii
of the basal layer spherical shell are 3.6397 and 3.6471 cm.

Fig.1. Sketch of the transitional epithelium of the urinary bladder; adapted from Ref 11.

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Fig. 2. Electron SAFs in the basal cell layer as a function of urine content and electron energy.

Fig. 3. Photon SAFs in the basal cell layer as a function of urine content and photon energy.

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Fig. 4. Alpha SAFs in the basal cell layer as a function of urine content and photon energy.

Fig. 5. Comparison of SAFs of this work with those of ICRP Publication 133.

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