Dosimetry of bone metastases in targeted radionuclide therapy with alpha-emitting ²²³Ra-dichloride

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.