Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting 223Ra-dichloride
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Ra-dichloride is an alpha-emitting radiopharmaceutical used in the treatment of bone metastases from castration-resistant prostate cancer. Image-based dosimetric studies remain challenging because the emitted photons are few. The aim of this study was to implement a methodology for in-vivo quantitative planar imaging, and to assess the absorbed dose to lesions using the MIRD approach.
The study included nine Caucasian patients with 24 lesions (6 humeral head lesions, 4 iliac wing lesions, 2 scapular lesions, 5 trochanter lesions, 3 vertebral lesions, 3 glenoid lesions, 1 coxofemoral lesion). The treatment consisted of six injections (one every 4 weeks) of 50 kBq per kg body weight. Gamma-camera calibrations for 223Ra included measurements of sensitivity and transmission curves. Patients were statically imaged for 30 min, using an MEGP collimator, double-peak acquisition, and filtering to improve the image quality. Lesions were delineated on 99mTc-MDP whole-body images, and the ROIs superimposed on the 223Ra images after image coregistration. The activity was quantified with background, attenuation, and scatter correction. Absorbed doses were assessed deriving the S values from the S factors for soft-tissue spheres of OLINDA/EXM, evaluating the lesion volumes by delineation on the CT images.
In 12 lesions with a wash-in phase the biokinetics were assumed to be biexponential, and to be monoexponential in the remainder. The optimal timing for serial acquisitions was between 1 and 5 h, between 18 and 24 h, between 48 and 60 h, and between 7 and 15 days. The error in cumulated activity neglecting the wash-in phase was between 2 % and 12 %. The mean effective half-life (T 1/2eff) of 223Ra was 8.2 days (range 5.5–11.4 days). The absorbed dose (D) after the first injection was 0.7 Gy (range 0.2–1.9 Gy. Considering the relative biological effectiveness (RBE) of alpha particles (RBE = 5), D RBE = 899 mGy/MBq (range 340–2,450 mGy/MBq). The percent uptake of 99mTc and 223Ra (activity extrapolated to t = 0) were significantly correlated.
The feasibility of in vivo quantitative imaging in 223Ra therapy was confirmed. The lesion uptake of 223Ra-dichloride was significantly correlated with that of 99mTc-MDP. The D RBE to lesions per unit administered activity was much higher than that of other bone-seeking radiopharmaceuticals, but considering a standard administration of 21 MBq (six injections of 50 kBq/kg to a 70-kg patient), the mean cumulative value of D RBE was about 19 Gy, and was therefore in the range of those of other radiopharmaceuticals. The macrodosimetry of bone metastases in treatments with 223Ra-dichloride is feasible, but more work is needed to demonstrate its helpfulness in predicting clinical outcomes.
KeywordsBone metastases 223Ra-dichloride Radionuclide therapy Dosimetry
All patients enrolled in this research were participating to a multicentre study (protocol 88-8223/16216) sponsored by Bayer HealthCare Pharmaceuticals, entitled “Radium-223 chloride in treatment of CRPC/HRPC patients with bone metastasis”.
Compliance with ethical standards
Conflicts of interest
The authors declare that this study complied with the current laws of the country (Italy) where it was performed, and that the clinical ethics committee at each participating centre approved the study.
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