31/1/07 NPL Calibrator Workshop

Radium-223 Calibration

Sue Hooper

Principal PhysicistNuclear 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 ⇒227Th ⇒

223Ra

31/1/07 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

31/1/07 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 = 20γ rays & β particles =1

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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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Physical Properties of Ra-223

T½ = 11.43 daysα energy (average) = 5.78 MeV (accounts for 93.5% of

emitted energy); <4% as β particles; <2% as γradiation

β energy/decay: 1MeV (ave)γ energy/decay: 0.4 MeVγ energy: 269 keV (13.6%)

154 keV (6.04%)324 keV (3.9%)

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Decay Scheme of Ra-223223Ra11.43 d

219Rn3.96 s

α, 5.78 ΜeV

211Bi2.17 m

211Pb36.1 m

215Po1.78 ms

207Tl4.77 m

207Pbstable

211Po516 ms

α, 6.88 MeV

α, 7.53 MeV

α, 7.59 MeV

β-, 0.45 MeV

β- (0.273 %), 0.01 MeV

β-, 0.49 MeV

α (99.727 %), 6.68 MeV

Combined energyfor the complete decay of Ra-223 & daughters

= 28MeV

Some γ (0.9 MeVtotal) is also emitted

Courtesy of Algeta

31/1/07 NPL Calibrator Workshop

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/MBq10cm from vial : 6µSv/h/MBq100 cm from vial: 0.06 µSv/h/MBq

31/1/07 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.”

31/1/07 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

31/1/07 NPL Calibrator Workshop

Calibration Procedure (SOP)4. Procedure : Scheme 1 is used

to decay correct the activity in the Ra-223 solutionScheme 2 is used to document the affirmative measurements for the dial setting

(more detail to follow)

31/1/07 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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Vol corr chartDays from ref date Vol. x factor (Vmf)

-5 0.74-4 0.78-3 0.83-2 0.88-1 0.940 11 1.062 1.133 1.204 1.27

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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

31/1/07 NPL Calibrator Workshop

Calibration Procedure (SOP)5. References –None6. Revision –First7. Appendices –Scheme 1 and

Scheme 2

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Calibrator at Velindre• Capintec CRC15 Beta- consists of a chamber (for γemitters) and a beta counter (for pure β emitters)

- measurements of Ra-223 performed in the ionisation chamber

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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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In practice!• Measurement repeated the following

day at 12:00 (should have been 11:00!)Activity in vial calculated to 2 decplaces using Vol Corr Chart.

SPC button pressed to display 2 decplaces on calibrator -factor then appeared to CAL #251 using the vial jig supplied with the calibrator.

31/1/07 NPL Calibrator Workshop

ResultsScheme 1-Decay correction of Ra-223 standard soln

Stated Act(A)

Calib date(std soln)

Date of Calib of dose calib

Decay corract in std solnAc= A x cffrom volcorr table

Ra-223 calibno/factor

6MBq 21.7.05@12:00

13.7.05 @12:00

9.67MBq CAL #251

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ResultsScheme 2 Affirmative measurements

Decay corrected Activity

Ac

(MBq)

Activity Affirmative

measurement 1

(MBq)

Activity Affirmative

measurement 2

(MBq)

Activity Affirmative

measurement 3

(MBq)

9.67 9.62 9.60 9.76

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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 Ra-223 solution in equilibrium, not necessarily the case for the syringe.

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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

where

A0 is stated activity of the viald = 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

( - ln2 * d )11.43

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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.