Estimation of the lower limits for feasible Ra-223 SPECT imaging: a Monte Carlo simulation study

Document Type : Original Article


1 Division of Medical Quantum Science, Department of Health Sciences, Kyushu University, Fukuoka, Japan

2 Chiyoda Technol Corporation, Tokyo, Japan

3 Department of Clinical Radiology, Kyushu University Hospital, Fukuoka, Japan


Objective(s): Ra-223 is a promising radionuclide for the treatment of skeletal metastases in castration-resistant prostate cancer patients. This study aims to estimate the lower limits for feasible Ra-223 single-photon emission computerized tomography (SPECT) imaging using a Monte Carlo simulation study .
Methods: The SPECT images were produced on a homemade code: the Monte Carlo simulation of electrons and photons for SPECT (MCEP-SPECT). The National Electrical Manufacturers Association (NEMA) phantom with six hot spheres of diameters of 37, 28, 22, 17, 13, and 10 mm installed inside, was used. The background activity concentration was 0.6 kBq/mL, and the ratios of hot concentrations to the background (RHB) were 25, 20, 15, 10, and 5. When RHB was 15, the background concentrations of 1.5, 0.9, 0.3, and 0.15 kBq/mL were also tested. The energy window was 84 keV±10%. The number of projections was 60/360°, and the acquisition time was 60 s per projection. Two kinds of collimators: middle-energy general-purpose (MEGP) and high-energy general-purpose (HEGP), were examined. The SPECT images were evaluated based on two quantitative indexes: contrast-to-noise ratio (CNR) for detectability and contrast recovery coefficient (CRC) for quantitative accuracy .
Results: The CRC for the HEGP collimator was 35–40%, while the CRC for the MEGP collimator was 25–30%. The CNRs for the MEGP collimator were larger than those for the HEGP collimator. The CNRs of the hot spheres with diameters less than 22 mm were lower than 5.0 for both collimators, when RHB and the background concentration were 15 and 0.6 kBq/mL, respectively. Based on the obtained results, it was estimated that the lower limit of RHB for the detection of the hot sphere with a diameter of 37 mm would be approximately 20 if the background concentration is 0.05 kBq/mL.
Conclusions: The MEGP collimator is superior in terms of detectability, while the HEGP collimator is superior in terms of quantitative accuracy. When the lesion size is small, the MEGP collimator may be favorable. Based on these results, the estimated lower limit of the activity concentration would be approximately 1 kBq/mL if the background concentration is 0.05 kBq/mL for a large lesion.


1. Nilsson S, Larsen RH, Foss SD, Balteskard L, Borch KW, Westlin J-E, et al. First clinical experience with α-emitting radium-223 in the treatment of skeletal metastases. Clin. Cancer Res. 2005; 12(12):4451-9.
2. Hindorf C, Chittenden S, Aksnes A-K, Parker C, Chris F, Glenn D. Quantitative imaging of 223Ra-chloride (Alpharadin) for targeted alpha-emitting radionuclide therapy of bone metastases. Nucl. Med. Commun. 2012; 33(7):726-32.
3. Carrasquillo JA, O’Donoghue JA, Taskar NP, Humm JL, Rathkopf DE, Slovin SF, et al. Phase I pharmacokinetic and biodistribution study with escalating doses of 223Ra-dichloride in men with castration-resistant metastatic prostate cancer. Eur. J. Nucl. Med. Mol. Imaging 2013; 40(9):1384-93.
4. Lassmann M, Nosske D. Dosimetry of 223Ra-chloride: dose to normal organs and tissues. Eur. J. Nucl. Med. Mol Imaging 2013; 40(2):207-12.
5. Chittenden SJ, Hindorf C, Parker CC, Lewington VJ, Pratt BE, Johnson B, et al. A Phase 1, open-label study of the biodistribution, pharmaco-kinetics, and dosimetry of 223Ra-dichloride in patients with hormone-refractory prostate cancer and skeletal metastases. J. Nucl. Med. 2015; 56(9):1304-9.
6. Pacilio M, Ventroni G, Cassano B, Ialongo P, Lorenzon L, Castro ED, et al. A case report of image-based dosimetry of bone metastases with Alpharadin (223Ra-dichloride) therapy: inter-fraction variability of absorbed dose and follow-up. Ann. Nucl. Med. 2016; 30(2):163-8.
7. Yoshida K, Kaneta T, Takano S, Sugiura M, Kawano T, Hino A, et al. Pharmacokinetics of single dose radium-223 dichloride (BAY 88-8223) in Japanese patients with castration-resistant prostate cancer and bone metastases. Ann. Nucl. Med. 2016; 30(7):453-60.
8. Pacilio M, Ventroni G, De Vincentis G, Cassano B, Pellegrini R, Di Castro E, et al. Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting 223Ra-dichloride. Eur. J. Nucl. Med. Mol. Imaging 2016; 43(1):21-33.
9. Umeda T, Koizumi M, Fukai S, Miyaji N, Motegi K, Nakazawa S, et al. Evaluation of bone metastatic burden by bone SPECT/CT in metastatic prostate cancer patients: defining threshold value for total bone uptake and assessment in radium-223 treated patients. Ann. Nucl. Med. 2018; 32(2):105-13.
10. Pibida L, Zimmerman B, Fitzgerald R, King L, Cessna JT, Bergeron DE. Determination of photon emission probabilities for the main gamma-rays of 223Ra in equilibrium with its progeny. Appl. Radiat. Isot. 2015; 101(1):15-9.
11. Takahashi A, Miwa K, Sasaki M, Baba S. A Monte Carlo study on 223Ra imaging for unsealed radionuclide therapy. Med. Phys. 2016; 43(6):2965-74.
12. Owaki Y, Nakahara T, Kosaka T, Fukada J, Kumabe A, Ichimura A, et al. Ra-223 SPECT for semi-quantitative analysis in comparison with Tc-99m HMDP SPECT: phantom study and initial clinical experience. EJNMMI Research 2017; 7:81.
13. Benabdallah N, Bernardini M, Bianciardi M, de Labriolle-Vaylet C, Franck D, Desbrée A. 223Ra-dichloride therapy of bone metastasis: optimization of SPECT images for quantification. EJNMMI Res. 2019; 9:20
14. Gustafsson J, Rodeño E, Mınguez P. Feasibility and limitations of quantitative SPECT for 223Ra. Phys. Med. Biol. 2020;65(8):085012.
15. Yue J, Hobbs R, Sgouros S, Frey E. Quantitative SPECT Imaging of Ra‐223 in a Phantom. Med. Phys. 2016; 43(Issue 6 Part8):3407.
16. Takahashi A, Baba S, Sasaki M. Assessment of collimators in radium-223 imaging with channelized Hotelling observer: a simulation study. Ann. Nucl. Med. 2018; 32(10): 649-57.
17. Tanaka M, Uehara S, Kojima A, Matsumoto M. Monte Carlo simulation of energy spectra for 123I imaging. Phys. Med. Biol. 2007; 52(15):4409-25.
18. Cherry SR, Sorenson JA, Phelps ME. Physics in Nuclear Medicine. 3rd edition, Pennsylvania: Elsevier; 2003, p263-265.
19. Segars WP, Sturgeon G, Mendonca S, Grimes J, Tsui BMW. 4D XCAT phantom for multimodality imaging research. Med. Phys. 2010; 37(9):4902-15.
20. Cherry SR, Sorenson JA, Phelps ME. Physics in Nuclear Medicine. 3rd edition, Pennsylvania: Elsevier; 2003, p83.