223Ra-dichloride SPECT and planar quantitative images for targeted alpha-emitting therapy of bone metastases.

Objectives 223Ra-dichloride is the first alpha-emitter radiopharmaceutical that has received approval by the US Food and Drug Administration and marketing authorization from European Commission and for the treatment of patients with castration-resistant prostate cancer metastasized to bones. This radiopharmaceutical mimics calcium and forms complexes with the bone mineral hydroxyapatite at areas of increased bone turnover such as bone metastases. To better determine the dose-limiting toxicities to bone marrow due to this new therapy and correlate absorbed dose to therapeutic response, patient-specific dosimetric studies are required. To that aim, it is necessary to compare 223Ra-dichloride uptake to bone lesion locations and its quantitative biodistribution into the bone by 223Ra emission images. Despite a low photon yield, planar imaging of 223Ra-dichloride was shown to be feasible on phantoms and patients allowing determination of biodistribution and pharmacokinetics. But no study has so far explored the feasibility of SPECT images and their optimization in clinics.

Methods The experiments were conducted at the Hôpital Européen Georges Pompidou, in Paris (France), with an Infinia Hawkeye 4 gamma camera, equipped with a medium-energy collimator. The gamma camera imaging parameters were determined by measuring sensibility, spatial resolution and energy spectrum, with a syringe containing 350 kBq of 223Ra. A NEMA Body Phantom and a TORSO Phantom were used to evaluate the possibility of SPECT imaging and to determine the best reconstruction parameters available on clinical software.

Results Images were acquired using three energy windows: 85 keV ± 20%, 154 keV ± 20% and 270 keV ± 10%. Camera sensitivity measured from the phantom study was 42.9, 12.7, and 12.6 cps/MBq for the 85, 154, and 270 keV windows, respectively. The spatial resolution (full-width at half-maximum) was respectively 1.4, 1.7 and 1.5 cm for the three energy windows. The visual quality of the SPECT (60 projections, 360° rotation, and 30s per view) images allows a clinical use. The best reconstruction parameters were determined.

Conclusions This study has demonstrated that it was possible to obtain clinically relevant information from SPECT acquisitions of 223Ra. These results show the added value to acquire 3D images of patients to more precisely localize 223Ra biodistribution and estimate absorbed doses that will permit to establish the proper correlation with tumor response.