CALIBRATIONS FOR Ra-223 CHLORIDE SPECT

1st European Congress of Medical Physics , September 1-4,2016

CALIBRATIONS FOR Ra-223 DICHLORIDE SPECT QUANTITATIVE IMAGING

Aretaieion Hospital Synefia Stella1, Vamvakas Ioannis2,3, Avgousti Rafaela1, Souvatzoglou Michael2, Limouris George2, Lyra Maria1, 2 1

Radiation Physics Unit, 2Nuclear Medicine Department 1st Department of Radiology, National & Kapodistrian University of Athens 3

Iaso General Hospital, Medical Physics Dep., Athens, Greece

CALIBRATIONS for Ra-223 Dichloride SPECT imaging are

useful in dosimetry calculations • Radium-223 Dichloride has been approved by European Medical Agency (EMA), for therapy of bone metastasis of advanced prostate cancer, by the name Xofigo • Its chemical similarity to calcium, its short-range & high-LET α-particles provide means to destroy bone micro metastases.

XOFIGO (Ra-223-dichloride) pharmaceutical information Bayer Xofigo

• XOFIGO (Ra 223 dichloride) is provided as a clear, colourless and sterile isotonic solution for injection with pH 6.0 -8.0. • Each mL of solution contains 1100 kBq Ra-223 dichloride corresponding to 0.58 ng Ra-223, at the reference date. • Each vial contains 6 mL of solution • 6.6 MBq Ra-223 dichloride at the reference date. • Ra -223 is present in the solution as a free ion.

Mol formula: 223RaCl2

Mol weight:293.9 g/mol

Objective: Ra-223 SPECT quantitative imaging to be used for bio-distribution and dosimetry calculations.

• In Ra-223-chloride bone therapy response estimation the absorbed doses achieved should be verified. so

• Calibration and correction factors of the instruments used (Dose Calibrator – SPECT-γcamera) should be determined

Actinium-227 Decay Chain-/ Ra-223 Production

Ac-227 Generators are used in the Production of Ra-223 for Radionuclide bone therapies

Preparation and use of an Ac-227 generator for Ra-223 production

Physical properties of Ra-223 • Atomic Z= • Half Life = • Mean particle energy =

88 11.43 days 5.64 MeV

(weighted average of emissions)

• Maximum energy = • Average Range =

7.59 MeV 45 μm

• High Linear Energy Transfer (LET)= 81 keV/μm

Ra-223 Decay Chain [α- β- decay]

Four α- particles and two β- particles are emitted

Energies in the α- β- Decay of Ra-223 and its daughters [α- β- decay]

• 95.3% emitted as α-particles Of the total decay energy • 3.6% emitted as β- particles [27.8 MeV emitted per decay] • 1.1% emitted as photons [γ-or x-rays]

Schematic representation of bone surface, bone-marrow & track-lengths

α-emitters The internal bone surface receives a very high radiation dose

though

Glenn Flux, 2015

A significant fraction of the marrow is spared, increasing the survival of marrow cells .

γ-rays of Ra-223 in equilibrium with its progeny allow measurement of Ra-223 Dichloride radioactivity by standard instruments, as Capintec CRC-15R. Capintec-CRC-15R (pure Argon gas ionization chamber) was calibrated for accuracy, constancy, linearity and geometry. s/n158895

Capintec-CRC-15R • was also calibrated with NIST traceable radium-223 standard vials. • Calibration setup in 29-6-2015 determined the calibration number and storage of Ra-223 in calibrator’s memory and a user key was created based on the 3 NIST sources. 2 vial measurements in 2015 & a recalibration vial in 2016 A single dial setting is necessary for accurate Ra-223 activity measurements

Ra-223 γ-Energy Spectrum by γ-camera • Energy spectra of the 3 sources were recorded as γ-rays allow to: • Study the energy distribution, • decide the energy peak selection, • calculate the net area under each γ-ray peak, • consider the full-energy-peak efficiency

SPECT γ-Camera APEX SPS4 ELSCINT- NaI(Tl) crystals 9.5 mm thickness Collimator: MEGP

Ra-223 γ-Energy Spectrum by γ-camera

Energy windows selection: at 154 keV /15% width and 270 keV/ 10% width

Quantitative Imaging protocol SPECT γ-camera calibration to convert Count Rate to Activity

The source was inserted in a 30 cm diameter cylindrical phantom filled with water • SPECT image slices were obtained and • The total measured count rate is assigned to the known activity.

Phantom study by Ra-223 standard source

A calibration factor that converts count rate to activity is obtained.

Quantitative Imaging protocol-Calibration Factor SPECT ROIs processing Counts/slice

Total slices Counts : 106487

Calibration Factor: Activity/Total Counts 1.48/106487= 1.39 * 10-5 MBq/Count

This Calibration Factor of counts to activity should be used in clinical cases measurements by Ra-223-dichloride SPECT scintigraphy 30 / step (120 steps)-10 sec /step - Matrix size : 64x64- 11/4/2016

Voxel absorbed dose calculated from cumulative activity by MatLab We developed an algorithm that calculates absorbed dose at every voxel of the SPECT image.

• A numerical factor was determined to convert the measured count rate from SPECT images to activity. • The SPECT images were imported in MatLab R2015b and converted to 3-D matrices. • Every element of the matrix was assigned with the respective count rate.

• The matrix was multiplied with the conversion factor and the new elements represent the activity at every voxel.

Absorbed doses of Ra223-dichloride • The absorbed dose at every voxel of the cumulative activity matrix was computed with the convolution method. • A 3D convolution matrix was created.

• The elements of this matrix are numerical factors that convert cumulative activity to absorbed dose. examples 1] If all Ra223 activity of our source remains in the spot Absorbed Dose will be : D= 940.8 Gy

In homogeneous distribution 2] If the remaining time of the activity is 1.5 days, then Absorbed Dose will be : D= Δ * Αc = 86.6 Gy

• Ra223 Dose Constant is Δ= 4.51 10-12 Gy*Kg/Bq*s (by Fischer DR &Sgouros G,1996)

The steps of the calibration protocol for Ra-223-dichloride therapy have been completed, in our Institute

Ra-223 with its daughters deliver an intense and localized field of radiation to the bone surfaces, sparing the bone marrow tissue Because of the high-energy deposition of Ra-223, only a low activity is required for therapy, …Radiation protection of the surroundings can be safe.. Thank you for your attention Maria Lyra Georgosopoulou Associate Prof., Med.Physicist