Quantitative Dual-Isotope Planar Imaging of Thorium-227 and Radium-223 Using Defined Energy Windows

Abstract

Introduction: Thorium-227 is an alpha-emitting radioisotope with potential therapeutic applications in targeted alpha therapy. Thorium-227 decays to Radium-223, which may have an independent biodistribution to that of the parent Thorium-227 radiopharmaceutical. Quantitative in vivo imaging with sodium iodide (NaI) detectors is challenging due to cross-talk between neighboring c-photopeaks as well as scattered c-photons. The aim of this work was to validate the use of a spectral analysis technique to estimate the activity of each isotope within a region of interest applied to a pair of conjugate view planar acquisitions, acquired at multiple energy windows. Methods: Energy spectra per unit activity arising from unscattered Thorium-227 photons and Radium-223 photons as well as from scattered photons were modeled. These spectra were scaled until the combination of these component spectra resulted in the closest match to the measured data in four energy windows. Results: Measured estimates of activity followed the known decay curves in phantoms representative of a human torso. The mean errors in estimating Thorium-227 and Radium-223 were 5.1% (range-8.0% to 40.0%) and 3.4% (range-50.0% to 48.7%), respectively. The differences between the integrals of the theoretical and estimated time activity curve were <10% for both Thorium-227 and Radium-223. Conclusion: c-camera quantification of Thorium-227 and Radium-223 can be achieved by using multiple energy window acquisitions.

Practical considerations for quantitative clinical SPECT/CT imaging of alpha particle emitting radioisotopes

“…In the present study, all the 227 Th acquisitions have been performed within 24 h after purification, and further study may be required to evaluate quantification at later timepoints from in-growth of daughter emitters. Larsson et al 48 and Murray et al 34 have proposed a methodology using different energy windows for planar imaging in this context. Li et al 56 proposed a multiple-energy-window projection-domain quantification method that jointly estimates the regional activity uptake of both 227 Th and 223 Ra directly using the SPECT projection data from multiple energy windows.…”

“…227 Th has one principal gamma emission at 236 keV 12 , and is the parent of 223 Ra; thus, its gamma emissions can also be used for imaging. According to the work of Murray et al 34 , planar imaging of 227 Th is achievable using multiple energy windows, and this approach may provide quantitative value. Quantification of a 3 cm diameter sphere in a water-filled cylinder phantom 227 Th filled phantom by SPECT provided values within an error of -12.4 ± 4.9%, using a Symbia Intevo (Siemens) gamma camera equipped with a medium energy-low penetration collimator 35 .…”

Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer

“…Radium-223 is an α-emitting therapeutic radiometal that also offers three possible energy windows for SPECT imaging (Table 7). [190] Radium-223 decays to stable 207 Pb with six intermediate radionuclide progenies ( 223 Ra, t 1/2 = 11.4 d, α! 219 Rn, t 1/2 = 4.0 s, α!…”

“…Thorium-227 is an α-emitting therapeutic radiometal that also offers two energy windows for SPECT imaging (Table 8). 190] Thorium-227 decays to 207 Pb with six intermediate radionuclide progenies. It decays first to 223 Ra by emitting an α-particle with an average energy of 5.9 MeV.…”

“…Quantitative in vivo imaging of 227 Th that accounts for 223 Ra is possible but challenging due to crossevents between neighboring γ-photons, scattering, and relatively small photon abundance. [190,215] An alternative is matching 227 Th with its PET-compatible isotope 89 Zr (Table 8). Like thorium, zirconium exists in a 4 + oxidation state and forms very stable complexes with HOPObased chelators.…”