Radium-223 Calibration
Sue Hooper
Principal Physicist
Nuclear Medicine
Velindre NHS Trust
31/1/07
NPL Calibrator Workshop
What is Ra-223?
Ra-223 (Alpharadin) –is an alpha
emitting radionuclide
-supplied by Algeta ASA in
Norway
227 Ac
31/1/07
⇒
227Th
⇒
223Ra
NPL Calibrator Workshop
Why use Ra-223?
It is being used in a phase II,
multicentre study for the palliation
of painful bone metastases in
hormone refractory prostate
cancer patients
cf Sr-89 (Metastron) and Sm-153
(Quadramet) - both β emitters
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NPL Calibrator Workshop
Range in tissue
Tissue range for 223 Ra < 100 µm (α)
Cf
Tissue range for 89Sr < 8mm (β)
Quality F actor: α particles = 20
γ rays & β particles =1
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NPL Calibrator Workshop
Activities of Ra-223 involved
Patients are entered into one of
four randomisation arms:
5, 25, 50 or 100 kBq/kg
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NPL Calibrator Workshop
Physical Properties of
Ra-223
T½ = 11.43 days
α energy (average) = 5.78 MeV (accounts for 93.5% of
emitted energy); <4% as β particles; <2% as γ
radiation
β energy/decay: 1MeV (ave)
γ energy/decay: 0.4 MeV
γ energy:
269 keV (13.6%)
154 keV (6.04%)
324 keV (3.9%)
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NPL Calibrator Workshop
Decay Scheme of Ra-223
223
Ra
11.43 d
α, 5.78 ΜeV
219
Rn
3.96 s
Combined energy
for the complete
decay of Ra-223 &
daughters
α, 6.88 MeV
215
= 28MeV
Po
1.78 ms
α, 7.53 MeV
211
Pb
36.1 m
Some γ (0.9 MeV
total) is also emitted
β-, 0.45 MeV
211
Bi
2.17 m
α (99.727 %), 6.68 MeV
207
β- (0.273 %), 0.01 MeV
211
Tl
4.77 m
Po
516 ms
β , 0.49 MeV
α, 7.59 MeV
-
207
Pb
stable
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NPL Calibrator Workshop
Courtesy of Algeta
Container for Ra-223
•
•
•
•
20 ml glass vial
Conc 500 or 1000 kBq/ml
Maximum activity in vial =23 MBq
Dose rate from unshielded vial
outer wall:
100µSv/h/MBq
10cm from vial : 6µSv/h/MBq
100 cm from vial: 0.06 µSv/h/MBq
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NPL Calibrator Workshop
Calibration Procedure (SOP)
The company send out a SOP
“Dial setting of Radioisotope
Dose Calibrators for
measurement of the
radioisotope Radium-223 at
clinical centres prior to clinical
trials with Alpharadin.”
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NPL Calibrator Workshop
Calibration Procedure (SOP)
1. Purpose - to find the dial
setting for the Dose
Calibrator!
2. Responsibility and Authority tells you to follow SOP and
return the results
3. Definitions –None
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NPL Calibrator Workshop
Calibration Procedure (SOP)
4. Procedure : Scheme 1 is used
to decay correct the activity
in the Ra-223 solution
Scheme 2 is used to document
the affirmative measurements
for the dial setting
(more detail to follow)
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NPL Calibrator Workshop
Calibration Procedure (SOP)
• Perform standard QA & bkgd
checks for calibrator
• Read stated activity of Ra-223 on
label of vial. Use supplied Volume
Correction chart to correct the
stated activity for decay to the
measuring time. Corr act = Ac
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NPL Calibrator Workshop
Vol corr chart
Days from ref date
Vol. x factor (Vmf)
-5
-4
-3
-2
-1
0
1
2
3
4
0.74
0.78
0.83
0.88
0.94
1
1.06
1.13
1.20
1.27
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NPL Calibrator Workshop
Calibration Procedure (SOP)
•
•
•
•
Place the Ra-223 in the calibrator making
sure it is centred in the measuring chamber
Adjust the calibrator until it displays the
decay corr activity Ac
Note the calibrator factor/setting for
further measurements of unknown activity
Perform 3 measurements with the Ra-223
standard source. Allow calibrator to return
to bkgd between the measurements. All
three measurements should be ± 5% of Ac
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NPL Calibrator Workshop
Calibration Procedure (SOP)
5. References –None
6. Revision –First
7. Appendices –Scheme 1 and
Scheme 2
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NPL Calibrator Workshop
Calibrator at Velindre
• Capintec CRC15 Beta
- consists of a chamber (for γ
emitters) and a beta counter (for
pure β emitters)
- measurements of Ra-223
performed in the ionisation
chamber
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NPL Calibrator Workshop
In practice!
•
Receive vial of Ra-223
Activity (MBq) on date @ 1200 CET
(no hours on decay chart – so can only
do approximate activity if
measurements not made at this time)
Our factor appeared to be between
Cal #240 and Cal #250 (1 dec place)
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NPL Calibrator Workshop
In practice!
•
Measurement repeated the following
day at 12:00 (should have been 11:00!)
Activity in vial calculated to 2 dec
places using Vol Corr Chart.
SPC button pressed to display 2 dec
places on calibrator -factor then
appeared to CAL #251 using the vial
jig supplied with the calibrator.
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NPL Calibrator Workshop
Results
Scheme 1-Decay correction of Ra-223 standard soln
Stated
Act
(A)
6MBq
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Decay corr
Calib date Date of
act in std
(std soln) Calib of
dose calib soln
Ac= A x cf
from vol
corr table
21.7.05 13.7.05
@12:00 @12:00
9.67MBq
NPL Calibrator Workshop
Ra-223
calib
no/factor
CAL
#251
Results
Scheme 2 Affirmative measurements
Activity
Activity
Decay
Activity
Affirmative
Affirmative
corrected Affirmative
Activity measurement 1 measurement 2 measurement 3
Ac
(MBq)
(MBq)
(MBq)
(MBq)
9.67
31/1/07
9.62
9.60
NPL Calibrator Workshop
9.76
In practice!
•
Results faxed off to company – no
information ever received back if we were
right or wrong despite me asking.
•
As for syringe measurements…….
Every centre involved in the trial is using
the same factor as derived for the vial. Our
syringe jig drops activity down into
calibrated part of the chamber. Purely go on
volume dispensed. Vial activity means Ra223 solution in equilibrium, not necessarily
the case for the syringe.
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NPL Calibrator Workshop
New Calibration SOP
•
Purpose and Responsibility not changed much
•
Definitions – now defines a dose calibrator, sample calib date
(prior to calib date the activity is higher than stated, after
the activity is less), isotope calibration factor or number
•
Procedure –corr the std activity for decay according to the
formula
(
Ac = A0 . e
- ln2 * d )
11.43
where
A0 is stated activity of the vial
d = no of days (this number is below zero in the case where the dose
calibrator dial setting is performed before the sample calibration date)
Recording the measurements appears to be the same
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NPL Calibrator Workshop
New Calibration SOP
•
References None
•
Revision – Second -changes from the first edition:
The procedure for decay correction of the stated activity is
converted from a correction based on a decay table to a
direct decay correction by means of a standard decay formula
for radioactive substance.
Minor linguistic updates are performed.
A user friendlier version of Scheme 1 and 2 is presented.
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NPL Calibrator Workshop