Master of Science Thesis
Accurate activity determination of the alpha emitters
Astatine [211At] and Bismuth [213Bi]
Hana Hameed Bakr
Supervisors:
Stig Palm
Tom Bäck
Department of Radiation Physics
University of Gothenburg
Gothenburg, Sweden
June 2014
1
Abstract
Alpha-radioimmunotherapy (α-RIT) involves α-particle emitting radionuclides for internal
radiotherapy of cancer. The alpha-particle emitting radionuclides undergoes transformation of the
atomic nucleus when they decay. Part of the excess energy is used for kinetic energy of the emitted
alpha particles. The energy range is typically 5–9 MeV with a range in soft tissue of 50–100 µm and a
mean linear energy transfer, LET, of ~100 keV/m.
Astatine-211 is one of the most promising alpha-particle emitters for α-RIT. It has a half-life of 7.216
(±0.007) h. This, together with its chemical characteristics makes it attractive for primarily locoregional therapies.
Another alpha-emitting radionuclide used for α-RIT is bismuth-213 with a half-life of 45.59 (±0.06)
min. It decays by beta emission to 213Po with a branching ratio of 97.91± 0.03. Because of the short
half-life of the daughter nuclide 213 Po, 213Bi can be considered an alpha emitter.
The aim of this work was to accurately determine the activity of 211At and 213Bi. To achieve this aim,
different detector systems were used for this work, including two CRC-15R dose calibrators, two
HPGe detectors, two gamma-well counters and also diodes.
Measurement of 211At with the dose calibrators shows activity readings of 211At that agree with its
physical decay. The gamma-well counter measurements at later time-points show an influence on
the measurements of the daughter nuclide 207Bi. Correction for this influence must be made for
proper cross-calibration.
The measurement of a solid target, where 211At is embedded in a thin Bi layer on a 5 mm aluminum
backing, proved challenging. There was a difference between the measured activity with the dose
calibrator and that measured with a HPGe detector system of ~14 % for measurement of the front
side and ~16 % for the backside of the target. This indicates that a correction must be made for the
dose calibrator reading.
Measurement of 213Bi with the dose calibrator shows directly after elution of the 225Ac/213Bi
generator an amount less than what is expected while after a few hours, the reading instead shows
a higher than expected amount. Further measurements with gamma-well counters and a HPGe
detector shows an influence of the daughter nuclide 209Pb that has a half-life of 3.277 h. These crosscalibrations provide a tool for correcting for daughter element activity and thus provide a more
accurate estimate of the activity.
2
Table of Contents
Abbreviations…………………………………………………………………………………………………………………………...
Introduction………………………………………………………………………………………………………………………………
Materials……………………………………………………………………………………………………………………………….….
1. Decay Data……………………………………………………………………………………………………….................
2. Astatine-211……………………………………………………………………………………………………………………..
2.1 Decay………………………………………………………………………………………………………………..
2.2 Production……………………………………………………………………………………………………....
2.3 Distillation………………………………………………………………………………………………………..
3. Bismuth-213……………………………………………………………………………………………………………………..
3.1 Decay……………………………………………………………….…………………………………….….......
3.2 Production……………………….…………………………………………………………………………......
1. Radioisotope dose calibrators…………….……………………………………………………………………….……
2. Automatic gamma-well counter………………………………….………………………………….………………..
3. High purity germanium (HPGe) detector………………………………………………………………………….
4. Diodes………………………………………………………………………………………………………………………………
Methods……………………………………………………………………………………………………………………………….…..
Radionuclide absorption to vials and tubes………………………………………….……………………..……..
Multiple sampling ……………………………………………………………………………………….……………….……
Volume effect……………………………………………………………………………………………….……………………
Measurement of Astatine-211……….……………………………………………………………………….…….…..
1. Radioisotope dose calibrators…………………………………………………………..………………..
2. Automatic gamma-well counter……………………………………………………………….………..
3. High purity germanium (HPGe) detector…………………………………………..………………
The target……………………………………………………….…………………………………………………………………..
Measurement of Bismuth-213………………….………………………………………….…………….…………….…
1. Radioisotope dose calibrators…………………………………………………………..……………..…
2. Automatic gamma-well counter………………………………………………………………………….
3. High purity germanium (HPGe) detector…………………………………………………..………..
Diodes…………………………………………………………………………………………………………………….…………..
1. Technetium‐99m (99mTc) ………………………………………………….………………………………
2. Astatine-211(211At)……………………………………………………………………………….………….
Results……………………………………………………………………….………………………………………………………..……
Discussion…………………………….…………………………………………….…………………………………………………….
Conclusion …………………………….…………………………………………….……………………………………………………
Acknowledgements……………………………………………………………………….………………………………………....
References………………………………………………………………………………………………………………………………..
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3
Abbreviations
TAT
α-RIT
min
s
h
Bq
g
cm
keV
ml
LET
PBS/BSA
MCA
ROI
HPGe
Targeted alpha therapy
Alpha-radioimmunotherapy
Minutes
Seconds
Hours
Becquerel
Gram
Centimetre
Kiloelectronvolt
Milliliter
Linear energy transfer
Phosphate buffered saline /Bovine Serum Albumin
Multi Channel Analyzer
Region of Interest
High purity germanium detector
4
Introduction
Alpha-radioimmunotherapy (α-RIT) involves α-particle emitting radionuclides for internal
radiotherapy of cancer. The alpha-particle emitting radionuclide undergoes transformation of the
atomic nucleus when they decay. Part of the excess energy is used for kinetic energy of the emitted
alpha particles. The energy range is typically 5–9 MeV with a range in soft tissue of 50–100 µm and a
mean linear energy transfer, LET, of ~100 keV/m (1).
The principle of targeted α therapy (TAT) of cancer is based on the coupling of α-particle-emitting
radionuclides to tumor-selective carrier molecules, for example antibodies or peptides (2).
The alpha-particle emitting radionuclides 211At and 213Bi are used in Gothenburg. 211At is available
every two weeks. The half-life is 7.216 (±0.007) h. The production of 211At is done by bombardment
of 28 MeV α-particles on stable bismuth through the nuclear reaction 209Bi(α,2n)211At at the cyclotron
Unit, Rigshospitalet, Denmark (1). The distillation process is then done locally at the Sahlgrenska
university hospital.
The 213Bi elution is also done at the Sahlgrenska university hospital. The half-life is 45.59 (±0.06) min.
The ITU 225Ac/213Bi generator can produce 213Bi, in transient equilibrium with 225Ac, every few hours
(3).
The aim of this thesis was to accurately determine the activity of 211At and 213Bi. To achieve this aim,
different detector systems were used. Two CRC-15R radioisotope dose calibrators were used for
measurements of activity higher than 1 MBq. The accuracy of these dose calibrators is deteriorating
for lower amounts of activity. Automatic gamma-well counters with NaI(TI) crystals were used for
measurement of activities much less than 1 MBq. High-purity germanium, HPGe, detectors were
used for more accurate determination of the activity in the examined samples. The vials, tubes and
jars were different for the dose calibrator, gamma-well counter and HPGe detector because the
different detector systems were previously calibrated for different geometries.
5
Materials
1. Decay data
All decay data were obtained from the Laboratoire National Henri Becquerel data (4). This set of data
was chosen because it contains a systematic compilation and scientific evaluation of the bestavailable data together with an uncertainty estimate for each data. It is the set of data recommended
by several primary standards laboratories.
2. Astatine-211
2.1 Decay
The half-life of astatine-211 is 7.216 (±0.007) h. One route of 211At decay is to form the daughter
nuclide Bismuth-207. This branch has 41.78 (± 0.08) % probability and involves the emission of an αparticle with 5982.4 (±1.3) keV energy. The half-life of 207Bi is 32.9 (±1.4) years. 211At can also undergo
electron capture (58.22(±0.08) % probability) to form Polonium-211 with a half-life of 0.516 (±0.003)
s. 211Po is an α-emitter with energy of 7594.48 (±0.51) keV. Both207Bi and 211Po decays to form stable
lead-207 (207Pb) (4).
A simplified decay scheme for211At is presented by reactions 1 and 2 and is illustrated in figure1.
(1)
(2)
207
Bi
41.78%
ec
32.9 y
α
100%
211
At
207
S
Pb
Stable
7.216 h
ec
211
58.22%
Po
100%
α
0.516 s
Figure 1: Simplified decay scheme for the radionuclide 211At
The decay of 211At to 211Po involves the emission of characteristic X-Rays with energies between
76.864 keV and 92.983 keV (43.26 (±0.198) % probability for all characteristic X-Rays) as well as the
main gamma-ray of 687.445 keV energy (0.245 (±0.012) % probability).
6
Table 1: Characteristic X-ray emissions of 211At
Energy (keV)
76.864
79.293
89.256
89.807
90.363
92.263
92.618
92.983
Photons per 100 disint.
12.66 ± 0.09
21.08 ± 0.12
7.26 ± 0.12
2.26 ± 0.05
2.2 Production
Astatine-211 was produced by the PET and cyclotron Unit, Rigshospitalet, Denmark, every two
weeks. The production of 211At is done by bombardment of 28 MeV α-particles on stable bismuth
through the nuclear reaction 209Bi(α,2n)211At (1, 5). A Scanditronix MC-32 cyclotron was used to
accelerate the alpha particles.
2.3 Distillation
Astatine-211 was isolated from the dry target by a dry distillation procedure. The bismuth layer was
first mechanically removed from the target (figure 2) and then placed in a small glass cylinder before
being transferred to a furnace.
Figure 2: Apparatus to mechanically remove astatine/bismuth layer from the aluminum backing
A larger glass cylinder was preheated in a furnace to 700 °C. The smaller glass cylinder, holding the
astatine, was placed inside the larger one. Since the boiling point for astatine is 337°C, the 211At is
evaporated and evacuated from the cylinders into a capillary tube. This process was assisted by
keeping reduced pressure on the outlet side. The outlet side of the capillary tube was precooled by
liquid nitrogen to -77 °C so that the evaporated 211At was condensed and trapped to the capillary
tube. The captured 211At was then transferred to a glass vial by rinsing the capillary tube with
chloroform. Finally, the chloroform was evaporated and the remaining 211At resolved in the vial (1).
7
Figure 3: Set-up for dry distillation of astatine-211
3. Bismuth-213
3.1 Decay
The half-life of bismuth-213 is 45.59 (±0.06) min. 213Bi undergoes beta minus emission to form 213Po
(97.91(±0.03) % probability).The half-life of 213Po is 3.7 (±0.05) µs. The generator system which
consists of the parent actinium-225 has been developed; the decay scheme for 225Ac is illustrated in
figure 4. 213Bi undergoes alpha decay to form the 209Tl (2.09 (±0.03) %). The half-life of 209Tl is
2.161(±0.007) min. The daughter nuclide is 209Pb (4). The decay of 213Bi is described by reactions 3
and 4:
(3)
(4)
225
10.0 days
Ac
2221
Fr
4.79 min
217
α
α
32.3 msec
213
At
Bi (45.59 (min)
β
7.216 h
7.216 h
Po
α
α
7.216 h
213
α
7.216 h
7.216 h
209
TI
7.216 h
2.161 min
45.59 min
min
β
225
h
Figure 4: Simplified decay scheme of the7.216
radionuclide
Ac
7.216 h
3.7 µsec
3.277 h
β209
Pb
µsec
7.2167.216
h h
7.216 h 7.216 h
209
Bi
7.216 h
7.216 h
8
3.2 Production
The ITU 225Ac/213Bi generator was used to produce 213Bi. Due to its short half-life, 213Bi rapidly came in
transient equilibrium with 225Ac, and new elutions could be made every 3–4 hours. 213Bi is eluted
using a mixture of 0.3 ml of 0.2 M HCI and 0.3 ml of 0.2 M NaI. The generator is washed with 3 ml
0.01 M HCI before each elution. Elution is performed at a flow rate of 0.15 ml/min directly into a vial
filled with 0.12 ml of 4 M sodium acetate buffer and 0.05 ml of freshly prepared 20% ascorbic acid
solution. The time t=0 was set for when the last fraction of the eluate is leaving the generator column
(3, 6).
(A)
(B)
Figure 5: (A and B) Installation of 225Ac/213Bi generator
4. Radioisotope dose calibrators
Two CRC-15R dose calibrators (Capintec Inc, USA) were used. These are gas-filled ionization
chambers. The Capintec CRC-15R dose calibrator has a well depth of 25.4 cm and an inner diameter
of 6.1 cm. This geometry simulates the ideal 4π geometry of a point source in the center of a
spherical detector. Corrections are made for the deviation from the ideal situation. This type of
ionization chamber is rather insensitive for low levels of activity. At levels lower than approximately 1
MBq, their accuracy is deteriorating although it is possible to measure also lower activities.
Figure 6: Capintec CRC-15R dose calibrator
9
These dose calibrators are typically filled with highly pressurized Argon [18Ar] gas, compressed to
~20 atmospheres (7–9).
5. Automatic gamma-well counter
Two gamma-well counters Wallac 1480 (Wizard) were used. This gamma counter is equipped with a
single 3-inches (3" x 3") crystal of thallium-activated sodium iodine (NaI(TI)). Due to the high counting
efficiency, and to avoid dead-time corrections of >10 %, this detector was used only for low activity,
<10 kBq, measurements.
The sodium iodide detector consists of sodium iodide and a small amount of Tl. The high atomic
number of iodine provides good efficiency for gamma ray detection. The energy resolution of a NaI
detector is, however, relatively low (10–12).
(A)
(B)
Figure 7: Gamma-well counter Wallac 1480 (Wizard)
6. High purity germanium (HPGe) detector
A p-type coaxial HPGe (high-purity germanium detector (Ortec Gem 50P4, USA)) with efficiency 52.3
% and bias +4000 V was used (13). The detector was connected to an MCA device (Ortec, DSPEC jr.
2.0). The MCA was connected to a computer with Gamma vision software (Ortec, USA). Gamma
vision was used for analysis of the spectra (14). The detector was calibrated against a standard
sample of 200 ml and density 1 g/ml (QSA Global GmbH, Source No. RL505). In order to conform to
the standard geometry, similar 200 ml sample jars were used for measurement of 211At and 213Bi and
their daughter radionuclides. The efficiency and the energy calibration were done in this geometry
using the Gamma Vision 6.0 software. The energy calibration of the detector was done by acquiring
spectra from calibration sources emitting photons with energies ranging from 60 to 1836 keV (15).
This was then saved as a calibration file.
A mobile HPGe detector system with efficiency 111.6 % (16) was used for measuring the 211At
targets. This separate system was used because the stationary system was calibrated for close
geometries where the high activity (>300 MBq) of the 211At target would saturate the detector
response. The mobile system allowed for a calibration at greater distances, where the dead-time
10
could be kept reasonably low, i.e. <10 %. This mobile detector was also connected to an MCA device
(Ortec, digiDART, USA) (17, 18). The MCA was connected to a computer with Gamma vision software.
Gamma vision was used for analysis of the spectra. A calibration sample of 152Eu with initial activity of
3.85 MBq (1991-06-01) was used for energy and efficiency calibration of the mobile HPGe. The HPGe
detector was calibrated using 152Eu at 4 m distance and with 2 mm sheet of copper to filter out lowenergy photons that would otherwise increase the dead-time (19).
(A)
(B)
Figure 8: (A) The high-purity germanium detector (Ortec) and (B) 200 ml sample jars
7. Diodes
The Silicon PIN (p-type semiconductor and an n-type semiconductor region with intrinsic
semiconductor region between them) diode is the active element of the detector probe. The size of
the probe is 3x30 mm. It is enclosed in Cu foil and coated with an opaque plastic resin to protect it
from light and stray electromagnetic fields. The system consists of a compact detector probe in
conjunction with a bench amplifier unit (Vario Detect). Each probe is connected to its amplifier unit
through a small-diameter coaxial cable. The system is characterized for being used in the
temperature range 0 to 55°C. The rate of photons incident on the detector is proportional to the
voltage and the registered voltage in mV corresponds to the count-rate (20).
Figure 9: The diodes (PPL) detector
11
Methods
Radionuclide absorption to vials and tubes
Any possible absorption of the radionuclides to the walls of the vials and tubes was tested. Normally,
all tubes were pre-coated with BSA. BSA (Bovine Serum Albumin) is a chemical material that typically
prevents absorption of radionuclides to the walls of the used tubes. To test this, the absorbed
amount following three washings was measured for tubes with and without BSA pre-coating.
Multiple sampling
Multiple samples were used throughout this work. This allowed an estimate of the uncertainties in
individual samples and reduced the uncertainty when comparing activity measurements using
different detector systems.
Volume effect
The volume effect for the radioisotope dose calibrators were examined by increasing the volume by
3 ml additions of liquid and re-measuring the activity.
Measurement of Astatine-211
1. Radioisotope dose calibrators
Measurements of higher amounts, i.e. >1 MBq, of 211At activity were conducted on two dose
calibrators (both CRC-15R dose calibrator, Capintec) using the dial setting 044. The half-life of the
sample was examined by measuring the activity at different times. The decay is expected to follow;
(1)
Where
is reference activity,
is the corrected activity, is the decay constant and t is the time.
The theoretically calculated activity was compared with the activity measured with the dose
calibrator. The first activity measurement with the dose calibrator was used as reference for a
calculated, theoretical, activity. Plotted curves allowed a comparison between the activities
measured with the dose calibrators and the theoretically expected activity with time.
The 211At activity measurements of the dose calibrators were used to study the number of daughter
(207Bi) atoms. The numbers of the 211At atoms were calculated according to equation (2):
(2)
Where A is the activity; N is the number of the nuclide and
is the decay constant.
12
Then the number of the 207Bi atoms was calculated by multiplying the number of decayed 211At atoms
with the 41.78 % probability. Then the corresponding activity of the 207Bi was calculated according to
equation 2, with N now representing the number of 207Bi atoms and λ that for 207Bi.
2. Automatic gamma-well counter
The gamma counter (Wizard 1480; Wallac) was used for measurements with activity less than 10
kBq. The measuring time was 60 sec for 211At. Corrections were made for physical decay during the
measurements with the gamma counter. A calibration factor was calculated from at least three
measurements with the gamma-well counter. All measurements were compared to a activity reading
with dose calibrator.
To study the activity of the daughter radionuclide
several days.
207
Bi, the sample was measured repeatedly for
3. High purity germanium (HPGe) detector
A gamma spectrum was acquired from each sample. The measurements were made after one and
two days to study 211At activity. Following complete decay of 211At, measurements of the longer-lived
daughter radionuclide began. To study the daughter radionuclide (207 Bi), the same sample was used
and the measurement for studying this radionuclide was very long, i.e. more than one day.
The detector was calibrated for measurement geometry with 200 ml samples with a density of 1
g/cm3. The sampling jars for HPGe detector were different from those used in the dose calibrator
because of the differing calibration measurement geometry. In the identified energy spectra the
peaks were correlated to specific radionuclides and their activity.
Peaks in the spectrum were assumed to have a Gaussian distribution. The total number of counts for
each energy peak was determined. To estimate the background level, B, two areas on either side of
the peak were marked. The width of each of these areas corresponded to the peak width. The pulses
in these areas were summed to N1 and N2, and used to obtain the background level by:
(3)
13
N1
CB
N2
Figure 10: Illustration of the ROIs used for estimating the net number of counts in a
defined peak. , N1 and N2 are the total number of counts within each energy interval.
.
Sometimes adjacent areas to the relevant peak could not serve as background according to the
above equation (eq. 3) because this area also contained pulses from a nearby peak. N1 and N2 then
had the half peak width instead of having the same width as the top. The background level was then
the sum of N1 and N2 rather than the average of N1 and N2.
The net pulses, CN, were then calculated as:
(4)
Where CN is the net number of pulses;
number of the backgrounds pulses.
is the gross number of pulses for the peak; and B is the
The activity was calculated by:
(5)
Where ε is the efficiency and was obtained from the calibration data; t is the measurement time; and
f is the branching ratio and is the activity. The calculated activity was corrected to the collection
date. Correction for decay during measurements was made according to:
( )
(
)
(6)
Where CPM is the number of the counts per minutes at reference time ; CPM is the number of the
counts per minutes at the start time
is the decay constant and
is the measurement time (21,
22).
14
Figure 11: Obtained spectrum for
211
At using Gammavision software
The target
The target measurement with HPGe was used to investigate the activity of 211At and 207Bi before
distillation. The target includes an aluminum backing of approximately 5 mm thickness. The mobile
HPGe detector was used for these measurements.
A gamma spectrum was acquired for the target at 4 m distance. The HPGe detector was calibrated
using a calibration sample of 152Eu. The calibration sample used was 3.850 MBq (calibration date 1
June, 1991). The HPGe detector was calibrated using 152Eu at 4 m distance and behind 2 mm sheet of
copper. This material was applied to allow for assaying a high quantity (>200 MBq) of 211At while
maintaining a reasonable (<10 %) dead-time by attenuating the high abundance of 75–95 keV X-ray
photons from 211At (19).
The distance between the target and the detector was the same as with the calibration source, i.e. 4
m. A gamma spectrum obtained from the gamma vision was used for the analyses.
The efficiency was calculated from the calibration spectrum according to equation (7)
(7)
Where ε is the efficiency; t is the measurement time; and f is the branching ratio. The activity was
corrected to the collection date and
is the counts obtained from the calibration spectrum and
calculated according to equation 4.
The efficiency for the 688.67 (0.841 %) and 778.9 (12.97 %) keV photons were calculated from the
calibration spectrum. The energy was selected according to the energy of the peaks from the 211At
15
and 207Bi. The 778.9 keV peak was finally used for the calculation because the branching ratio makes
the number of counts in this peak higher than that for the 688.67 keV photons. A previous
calibration, involving more counts, was then used to find the difference in efficiency between these
two energies. The correction for this absolute calibration was 7.6 %, representing the difference in
detector efficiency for 778.9 keV photons with that for 688.67 keV photons.
The number of the counts from the 687 keV photons from 211At was calculated. The activity of the
target was calculated with equation 5 for both sides (front and back). The results were different. To
compare the results, the absorption of the aluminum (5 mm) was calculated according to:
(8)
Where
is the number of photons before absorption; N is the number of photons after
absorption; is the mass attenuation coefficient and X is the density-thickness of the aluminum (21).
The mass absorption coefficient and aluminum density was obtained from the National Institute of
Standards and Technology in the United States (NIST). The used aluminum density was 2.699 g/cm3
mass attenuation coefficient was 0.07383 cm2/g (23, 24). As an independent reference, the target
had been previously measured, using an HPGe detector, by the production group in Copenhagen. The
measurement obtained from the HPGe detector in Gothenburg, the dose calibrator, and the HPGe
detector measurements in Copenhagen were compared with each other. All of the measurements
with different detectors were corrected to 2014-04-09 08:00 to compare the result easily.
The target material was then removed by scraping the Bi‐Al layer. This results in small flakes. The
activity of the scrapings was then measured with the HPGe detector.
Measurement of Bismuth-213
1. Radioisotope dose calibrators
Measurements of 213Bi activity were made on a dose calibrator (CRC-15R dose calibrator, Capintec)
using the dial setting 775 multiplied by 10.
A theoretical amount of 213Bi activity was calculated according to its physical decay. The reading on
the dose calibrator does not agree with this amount. Initially, directly following elution of the
225
Ac/213Bi generator, it shows an amount less than what is expected. This lower-than-expected
reading lasted for the first 5–10 minutes following elution. After a few hours, the reading instead
shows a higher than expected amount. The readings were drawn as curves in Excel (Microsoft Excel
2010). Then, an exponential trend line was selected to fit these curves. The equation for the fit was
according to
with parameters C and k chosen for the best fit. The half–life was given from fit
equation according to;
( )
( )
( )
(9)
16
Where N is the number of nuclei remaining after time t; N0 is the number of nuclei initially (at time 0)
and λ is the decay constant. The half-life calculated according to:
( )
( )
(10)
When the half-life was calculated from our measurements, it was longer than the correct half-life for
213
Bi (45.59(± 0.06) min).Then the amount of the 209Pb was calculated also for the earlier time-points
and subtracted from the reading of the 213Bi measurement of the dose calibrator. Then a new curve
was generated for the corrected activity, i.e. without 209Pb. When the half-life was calculated from
this new curve, it shows that it is near that of 213Bi.
2. Automatic gamma-well counter
The gamma-well counter measurements used with activity less than 10 kBq and were used to find
results more accurate than that given by the dose calibrator. The measured time was 300 sec. The
measured counts were corrected for background. The generated data were drawn as curves in Excel.
An exponential function was fitted to the data and according to equation 10 the half–life was
calculated.
3. High purity germanium (HPGe) detector
A gamma spectrum was acquired from each sample. The measurements were made a few times to
study 213Bi activity decay.
The detector was calibrated for measurement geometry with 200 ml samples with a density of 1
g/cm3. The sampling jars for HPGe detector were different from those used in the dose calibrator
because of the differing calibration measurement geometry. In the identified energy spectra the
peaks were correlated to specific radionuclides.
Peaks in the spectrum were assumed to have a Gaussian distribution. The total number of counts for
each energy peak was determined. To estimate the background level, B, two areas on either side of
the peak were marked and calculated according to equation 3. The width of these areas
corresponded to the peak width. The numbers of background counts were subtracted from the
counts calculated for the energy peak according to equation 4. The activity was then measured
according to equation 5. The calculated activity was corrected to the collection date according to
equation 6.
17
Diodes
1. Technetium‐99m (99mTc)
The diodes system was tested with 99mTc. The use of 99mTc instead of 211At was due to the fact that
211
At is only delivered every other Wednesday. A molybdenum generator which produces 99mTc is
always present at the radiopharmacy (25). The same type of vial which is used also for the
production of 211At was used here as well, which reduced the attenuation correction that would
otherwise be made for the original 99mTc vial. The activity used was higher than 90 MBq.
2. Astatine-211(211At)
The diodes system was also tested with 211At. The activity used was higher than 40 MBq because the
efficiency of the diodes was low and made it difficult to assess lower amounts of activity. The same
type of vial used also for the production of 211At was used here. This way, the results could be directly
translated to the diode readings during the distillation of 211At.
18
Results
Radionuclide absorption to the vial material
The absorption of the radionuclide 213 Bi to the walls of the vials was tested. The sample was ~1 MBq.
The absorbed amount following three washings was estimated by measuring the emptied vials and
the result shows it is ~ 15 Bq.
Table 2: Number of counts of
213
Bi from the washed vials. The measuring time was 20 sec.
Counts
302
344
Time limit (sec)
20
20
Volume effect
Figure 12 shows the volume dependence of the dose calibrator investigated for a 50 ml tube. The
measurement shows that there is only a small (< 2%) volume dependence up to a volume of 15 ml.
Volume effect
16
Activity (MBq)
15
14
13
12
11
10
0
5
10
Volume (ml)
15
20
Figure 12: The dose calibrator’s volume dependence
19
Astatine-211 activity measurement
Figures 13 and 14 show the measurement of 211At activity at different times for dose calibrators one
and two. The plot shows the decay of 211At with time. The theoretical activity and the measured
activity agree.
Dose calibrator 1
1,E+08
Start
Dose calibrator 1
Calculated activity
Activity (Bq)
1,E+07
1,E+06
1,E+05
1,E+04
0
10
20
Figure 13: The relation between
30
Time (h)
40
50
60
211
At activities at different times for dose calibrator number one
Dose calibrator 2
1,E+08
Start
Dose calibrator 2
Calculated activity
Activity (Bq)
1,E+07
1,E+06
1,E+05
1,E+04
1,E+03
0
10
Figure 14: The relation between
20
30
Time (h)
40
50
60
211
At activities at different times for dose calibrator number two
20
The 211At activity measurements of the dose calibrator number one were used to study the number
of daughter (207Bi) atoms. 211At sample measured with the dose calibrator to 223 MBq. The total
number of atoms for 211At was calculated to 8.4*1012.Then the number of the 207Bi atom calculated to
3.49*1012 by multiplying the number of decayed 211At atoms with the 41.78 % probability. The
activity of 207Bi calculated to 2332 Bq which correspond 1547.74 cps, 92864 counts for 60 seconds for
207
Bi. The same sample measured with the gamma-well counter to ~63000 counts after a few days.
Figure 15 shows the measurement of 211At with gamma-well counters after decay of 211At to an
activity less than 10 kBq, with time. It shows that the number of counts decreases with time but after
two days there is an influence of the decay of the daughter nuclide 207Bi which has a half-life of 32.9
years. A calibration factor, linking the number of counts in the gamma-well counter to the activity
measurement using the dose calibrator, was calculated from at least three measurements in the
gamma-well counter and only after correction for the number of counts originating from 207Bi decay.
The calibration factor was calculated to 0.374 between the dose calibrator and the gamma-well
counter, i.e. the number of counts per second from the gamma-well counter should be divided by
this number to achieve the activity reading of the dose calibrator.
Automatic gamma-well counter
1,E+06
1,E+05
Counts
1,E+04
1,E+03
1,E+02
1,E+01
1,E+00
0
50
100 Time (h) 150
Figure 15: The relation between the numbers of counts from the
200
250
211
At registered at different times
The 211At activities measured with dose calibrators 1 and 2 at different times are shown in tables 3
and 4. All the measured activity of 211At with dose calibrators 1 and 2 were corrected to the date and
time 2014-04-09 08:00 to show the stability of the measurement at different times. Table 5 shows
the measurement of the same sample used with the dose calibrator, but measured again with the
HPGe detector, again corrected to the same date (2014-04-09 08:00). The difference between the
activities measured with dose calibrator number one is ~0.5 % while for the dose calibrator number
two is ~2.7 %. The activity of the 207Bi was measured to ~ 89 Bq using the HPGe detector after a few
days.
21
Table 3: Activity of
211
At measured with dose calibrator 1 and corrected for physical decay
Date and time
ADose calibrator (MBq)
2014-04-09 09:32
6.97
8.07
2014-04-09 13:11
4.90
8.06
2014-04-09 13:37
4.71
8.07
2014-04-09 14:01
4.53
8.07
Table 4: Activity of
Activity(MBq)2014-04-09 08:00
211
Date and time
At measured with dose calibrator 2 and corrected for physical decay
ADose calibrator(MBq)
Activity (MBq) 2014-04-09 08:00
2014-04-09 09:32
6.81
7.89
2014-04-09 13:12
4.86
8.01
2014-04-09 13:38
4.57
7.85
2014-04-09 14:01
4.46
7.95
Table 5: Activity of
211
At measured with an HPGe detector and corrected for physical decay
Date and time
AHPGe-detector-(MBq)
Activity (MBq) 2014-04-09 08:00
2014-04-11 15:36
0.038
8.11
The Target
The results from measuring the target activity with the dose calibrator as well as with HPGe
detectors in Copenhagen and Gothenburg are presented in table 6. All measured activity of the
target were corrected to the date and time 2014-04-16 08:00 to show the stability of the
measurements at different times. The difference between the measured activity with the dose
calibrator and for the HPGe detector in Gothenburg was~ 14 % for measurement of the front side
and ~16 % for the backside. The difference between the measured activity with the dose calibrator
and the HPGe detector measurement in Copenhagen was ~15 %. The difference between the activity
measured with the HPGe detector in Gothenburg and the activity measured with the HPGe detector
in Copenhagen was ~1.2 % for the front side and ~1 % for backside. The difference between the
front- and back-side activity measurements was assumed to be due to the passing of photons
through the 5 mm aluminum. Therefore, the number of counts for the back-side measurement, i.e.
after passing through the 5 mm aluminum, was corrected for the aluminum absorption. The number
of the counts registered from the backside before correction was 9856.91 and 10759 counts after
correction, compared with 11030.5 for front side. The activity of the scraping was measured to
492.29 MBq representing 70.54 % of the original amount. The remaining activity must thus be lost in
the scraping process.
22
Table 6: Activity of the target measured with dose calibrator 2, HPGe detector in the Gothenburg and the HPGe
detector in the Copenhagen
Frontside
Datum och tid
Backside
2014-04-16 08:00
2014-04-16 08:00
ADose calibrator (MBq)
597.84
597.84
AHPGe-detector-Gothenburg (MBq)
697.89
714.05
AHPGe-detector-Copenhagen(MBq)
707.46
707.46
Bismuth-213 activity measurement
The results from the measurement of 213Bi activity at different times with the dose calibrator number
two are shown in figure 16. It shows the influence of the daughter nuclide 209Pb with a half-life of
3.277 h. An exponential fit to the data provided the equation,
which would
213
correlate to a half-life of 52 min while the half-life of Bi is 45.59 min.
Dose calibrator number two
1,E+08
A = 2∙1011∙e-19,19t
Activity(Bq)
1,E+07
1,E+06
1,E+05
1,E+04
09:36
12:00
14:24
16:48
19:12
21:36
Time
Figure 16:
213
Bi activity at different times for dose calibrator number two
23
Figure 17 shows the 213Bi measurement after 4 hours. From an exponential fit the half-life was
calculated to 3.3 h. This is near the half- life of the daughter nuclide 209Pb which is 3.277 hours.
Dose calibrator number two
1,E+06
Activity(Bq)
A = 3∙106∙e-5,042t
1,E+05
1,E+04
1,E+03
14:24
15:36
16:48
18:00
19:12
20:24
Time
Figure17:
213
Bi activity measured with dose calibrator number two at different time
Figure 18 shows the corrected 213Bi activity. The measured 209Pb activity, with a fit equation A =
3∙106∙e-5,042t from figure 17, was subtracted from the measurement with dose calibrator. The
resulting data fit the equation A = 9∙1011∙e-21,7t which correlate to an half-life of 46 min. This is near
the half- life of 213Bi which is 45.59 min.
Dose calibrator number two
1,E+08
A = 9∙1011∙e-21,7t
Activity(Bq)
1,E+07
1,E+06
1,E+05
1,E+04
1,E+03
09:36
12:00
14:24
16:48
19:12
21:36
Time
Figure18:
213
Bi corrected for daughter
209
Pb activity at different time for dose calibrator number two
24
The measurement of 213Bi with gamma-well counters shows more accurately the influence of the
daughter nuclide 209Pb. From an exponential fit the half-life was calculated to 3.266 h. This is near the
half- life of the daughter nuclide 209Pb which is 3.277 hours.
Gamma-well counter/ 213Bi
1,E+06
A = 2∙106∙e-5,093t
Counts
1,E+05
1,E+04
1,E+03
14:24:00
15:36:00
16:48:00
18:00:00
19:12:00
20:24:00
Time
Figure 19: The relation between the numbers of counts from the
213
Bi registered at different times
The measurement of 213Bi with HPGe detector after decay to 1 MBq are shown in table 7. All the
measured activity of 213Bi with dose calibrator two and HPGe detector were corrected to the date
and time 2014-04-09 13:32 to show the stability of the measurement at different times. The
difference between the measurement of the dose calibrator and the HPGe detector is ~20 %.
Table 7: Activity of the
213
Bi measured with dose calibrator 2, HPGe detector with different time and different
measuring time.
2014-04-23 16:49
2014-04-23 17:47
2014-04-23 18:42
2014-04-23 19:45
3236.14
3174.32
601.32
51077.92
ActivityHPGe(MBq)
0,41
0,17
0,07
0,06
Activity(MBq)HPGe (2014-04-23 13:32)
8,25
8,35
8,29
18,13
Activity (MBq)Dose calibrator (2014-04-23 13:32)
10,63
10,63
10,63
10,63
Measuring time(sec)
25
Diodes
Count rate
Measurement with 99mTc was performed to test the diodes system, and the results are shown in
figure 20. The measurement showed a difference in the count rate from the two sides of the
detector.
180
160
140
120
100
80
60
40
20
0
10:19
99mTc
side 1
side2
10:33
10:48
11:02
11:16
11:31
11:45
Time
Figure 20: The relation between the counts rate from the
99m
Tc registered at different times
Measurement with 211At was also made to test the diodes system, and the results are shown in figure
21. Again, the count rate registered for the two sides differ.
211At
45,00
side 1
side 2
40,00
Countrate
35,00
30,00
25,00
20,00
15,00
10,00
5,00
0,00
12:00
12:28
12:57
13:26
Time
13:55
Figure 21: The relation between the counts rate from the
14:24
14:52
211
At registered at different times
26
Discussion
Normally, all vials were pre-coated with BSA in order to prevent absorption of the radionuclide to the
vial walls. A test was done to examine the effect of such pre-coating. One vial, without the standard
BSA pre-coating, was used for measuring the 213Bi elution. After three washings the remaining 213Bi
amount was below any detectable amount using the dose calibrator. When measurements were
performed on the gamma-well counter, the result shows that the absorbed amount is negligible. The
recommendation to pre-coat all vials must, however, remain since even a small amount of
absorption will affect the accuracy of activity measurements following the transfer to another vial or
jar.
Radioisotope dose calibrators are most often referred to as dose calibrators. They are calibrated for a
certain type of vial, typically a 20 ml vial of specific geometry and glass-like material. The dial setting
is valid for a certain amount, often 5 ml, of homogeneously dispersed activity. In this thesis, the
volume effect of the dose calibrator was investigated. The result for 211At measurement showed the
change of the measured activity is less than 2 % up to a volume of 15 ml. This means that there is no
practical need to correct for any volume effect when using the dose calibrator for a quick estimate of
the radioactive amount in a vial, at least up to a volume of 15 ml. The volume effect is then smaller
than the 5 % uncertainty one must expect from a dose calibrator reading.
A very useful method to test if there is any influence of another radionuclide on the measurement is
to follow the physical decay during repeated measurements. This method was used throughout this
thesis. For example, repeated measurements of 211At on the dose calibrators showed a response that
followed the expected physical decay. The influence of daughter 207Bi does not affect these
measurements because the amount produced by 211At decay is much less than what is detectable
with a dose calibrator. On the much more sensitive gamma-well counter, on the other hand, the
small amount of 207Bi can easily be detected and will influence the measurement of 211At after around
two days. The result shows a stable count-rate which is the result of the long half-life of 207Bi. Once
"all", i.e. after >10 t½ 211At has decayed, the amount of 207Bi can be quantified and its influence can be
deduced from the earlier 211At measurements. Likewise, the influence of daughter (to 213Bi) element
209
Pb (through 213Po) can be estimated by measuring the 213Bi sample after >10 t½, i.e. after at least 8
hours. This is more difficult since 209Pb is a pure beta-emitter. Therefore, the measurements were
made with an "open" energy window on the gamma-well counter, allowing for the bremsstrahlung
photons to be measured. Repeated measurements then revealed a calculated half-life very close to
the physical half-life of 209Pb.
When the dose calibrator was cross-calibrated with the gamma-well counter, at first (before the
subtraction of the daughter nuclide) a factor of 1.13 was calculated for late time-points. At that time,
much 211At had decayed to daughter 207Bi, which influenced the measurements. After the correction
for the daughter nuclide the result was 0.374. Therefore, it is very important in any future
measurement with 211At to consider also the daughter nuclide.
Activity of 211At samples were measured with both dose calibrators and HPGe detector systems. The
results were corrected for physical decay to the same time and date. The results show good
agreement between the measurement with the dose calibrator and the HPGe detector. This indicates
that a correct calibration file for the HPGe detector was used. The HPGe detector system also had a
27
more recent calibration file, but the geometry for that calibration did not match the ones used in this
study. Therefore, an older calibration was used, that better matched the geometry of the current
study.
Measurement of the target was done with 4m distance and 2 mm copper sheet to decrease the
detector dead-time. A source of 152Eu was used to calibrate the system at the same distance with the
same 2 mm sheet of copper. The result shows that the measurement of the target with the HPGe
system made in this study was near the results for the target made by a separate HPGe detector
system in Copenhagen. Contrary, the dose calibrator readings deviated, probably because of photon
interactions within the aluminum backing material, from these results (HPGe detectors in
Gothenburg and Copenhagen) and could not be trusted.
The measurement of the target shows a difference in the activity between the front side and
backside. The difference was assumed to be due to scatter of photons in the 5 mm aluminum. When
correction for this was applied, the results from measuring both sides of the target agreed.
The scraping is placed in a furnace of about 700°C for the distillation process. The boiling point of
astatine is 337°C and for bismuth it is 1560°C (26). It is therefore unlikely that any daughter element
207
Bi is extracted in this process, and one can assume that only 211At is vaporized. It is only at this time
that "new" 207Bi starts to be produced by decay of 211At. Measuring the number of 207Bi atoms, at
some late time-point, can therefore provide an estimate of the number of 211At atoms at the time for
distillation.
Repeated measurement of 213Bi with a dose calibrator shows that the measured activity does not
agree with that expected from the physical decay. The calculation of the half-life from the
exponential fit in figure 17 reveal the influence of the daughter nuclide209Pb. The calculation of the
half-life from repeated measurement in a gamma-well counter, set with an open energy window,
after a few hours provide results very close to that expected for 209Pb. This illustrates how important
it is to account for daughter elements when determining the amount of activity of 213Bi. An often
neglected aspect of activity determination is the choice of basic radionuclide decay data.
In this work, the data of Laboratoire National Henri Becquerel data were chosen. This is the database recommended by primary standards laboratories, and has the advantage that all data come
with an evaluated uncertainty. Of interest is the uncertainty in the main gamma from 211At, i.e. the
687.2 (±0.7) keV photon. The abundance is 0.245 (±0.012) per 100 disintegrations. This means that
there is almost 5% uncertainty arising from the decay data, which would not be noted if data without
an evaluated uncertainty estimate were used. If instead the 77–93 keV characteristic X-Ray photons
are used for activity determination, the combined uncertainty of their abundance is less than 0.5%.
However, another problem arises when using the X-Ray photons. This is that the daughter element
207
Bi also emits X-Rays in the same energy range, i.e. 73–88 keV. The influence of this can be reduced
by measuring the sample at times when the remaining amount of 211At is negligible and then
estimate the amount of 207Bi activity. This amount can then is subtracted from the previous 211At
measurements and ideally improve the accuracy of its measurement.
The Silicon PIN diodes are currently used to aid in the distillation process of 211At. It was therefore
difficult to use them for separate activity experiments with 211At. They were instead tested with 99mTc
because of the availability of this radionuclide at the radiopharmacy. The measurement of the diodes
28
shows different sensitivity for the two sides of the detector. It was difficult to provide an activity
calibration for the diodes, particularly for activities less than ~40 MBq.
29
Conclusions
It is important to choose correct decay data. The Laboratoire National Henri Becquerel provides such
data.
Activity of 211At in liquid form could be determined with good accuracy with the dose calibrators.
Activity of 211At in solid form in the aluminum target could be determined with a mobile HPGe
detector system. Corrections needed to be made for scatter in the aluminum. The reading of target
activity in the dose calibrator was not reliable.
Activity of 213Bi determined with dose calibrators deviate from that determined with a HPGe detector
system.
Daughter elements for both
accounted for.
211
At and
213
Bi complicate the activity measurements, and need to be
30
Acknowledgements
I would like to express my gratitude to my supervisor Stig Palm for the encouragement, kindness and
guidance during all my work.
I would like to thank my second supervisor Tom Bäck for your support.
Many thanks to Sture Lindegren, Emma, and Anna for your help with preparing the samples.
Thanks to Rimon Thomas for your help with HPGe detector. Thanks to Afrah Mamour for your
friendship and good idea.
All my friends and colleagues at the Department of Radiation Physics, University of Gothenburg,
Sweden.
And my husband Hawar, for your love, supports, keeping me motivate and who have been there
during my ups and downs.
My grateful thanks to my children: Yara for having a great part in making me happy and Tara for your
love and joy you bring to my life.
My final thanks to my father, my brother and my sisters for all your love and support during the
years.
Thank you!!!!
31
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