Objective: [ 223 Ra]RaCl2 alpha-emitting radiopharmaceutical therapy (αRPT) is approved for treating metastatic castration-resistant prostate cancer (mCRPC), specifically targeting bone metastases (BMs) with short-range alpha particles. This prospective study aimed to quantify absorbed doses (ADs) in target tissues following [ 223 Ra]RaCl2 αRPT in mCRPC patients with symptomatic BMs using quantitative SPECT/CT imaging.
Approach: Four mCRPC patients received [ 223 Ra]RaCl2 intravenously at ~55 kBq/kg every four weeks for up to six cycles. Dosimetry was conducted following the first treatment cycle. Pre-treatment evaluations included 68 Ga-PSMA PET/CT, 99m Tc-MDP bone scan, and laboratory assessments. Serial SPECT/CT scans were acquired at 3-6 h, 18-30 h, and 163-242 h post-injection. Image quantification utilized a calibration phantom, and volumes of interest (VOIs) were segmented for trabecular bone (TB), cortical bone (CB), bone marrow, intestines, liver, and kidneys.A tri-exponential model was applied to derive time-integrated activity coefficients (TIACs). ADs were calculated using the OLINDA/EXM software.
Main results: The liver and kidneys cleared rapidly, while bone compartments retained [²²³Ra]RaCl₂, reflecting its skeletal affinity. Interpatient variability was notable, particularly in the intestines. The highest AD per administered activity was in osteogenic cells (914 mGy/MBq), followed by red marrow (188 mGy/MBq), kidneys (45.90 mGy/MBq), and liver (40.6 mGy/MBq). The total body ADC was 33.4 mGy/MBq, emphasizing selective bone targeting and minimal soft tissue exposure. Quantitative analysis confirmed bone uptake, gastrointestinal transit, rectosigmoid accumulation, and fecal clearance.
Significance: This study analyzed the first Ra-223 quantitative SPECT/CT imaging in mCRPC patients with BMs, demonstrating the feasibility of performing multi-time-point patient-specific dosimetry. Notably, the endosteal bones' highest AD reflects favorable skeletal targeting and controlled off-target radiation in this population. These findings support individualized treatment planning to optimize therapeutic efficacy while minimizing toxicity. Further studies on larger cohorts are warranted to refine dose-escalation strategies and long-term clinical outcomes.
