Safety and Efficacy Study of 225Ac-DOTA-IBA in the Treatment of Bone Metastases

OBJECTIVE: This preliminary study aimed to evaluate the safety and efficacy of 225Ac-DOTA-IBA in the treatment of bone metastases. MATERIALS AND METHODS: Fourteen patients with bone metastases were enrolled and received at least one cycle of 225Ac-DOTA-IBA at a fixed dose of 3.7 MBq per cycle. Treatment-related adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0). Efficacy assessments included Eastern Cooperative Oncology Group (ECOG) performance status, Karnofsky Performance Status (KPS), and pain Numeric Rating Scale (NRS) scores at baseline and 2-4 weeks post-treatment, as well as 68Ga-DOTA-IBA PET/CT scans within 1 week before treatment and 4-8 weeks post-treatment. Imaging responses were categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). RESULTS: 225Ac-DOTA-IBA was well tolerated, with no grade 3/4 AEs. On the basis of NRS scores, the pain relief rate was 92.9% (13/14) after the first cycle and was maintained at this level after subsequent cycles. ECOG performance status remained stable in the majority of patients, with improvement (from grade 2 to 1) observed in 2 cases (14.3%). KPS improved in 71.4% (10/14) of all patients after treatment. 68Ga-DOTA-IBA PET/CT analysis showed PR in 50.0% (7/14), SD in 35.7% (5/14), and PD in 14.2% (2/14). Among 7 patients who had previously received 177Lu-DOTA-IBA, 57.1% (4/7) improved in KPS, and 85.7% (6/7) in NRS. Regarding imaging response in these 7 patients, 42.9% (3/7) achieved PR, 42.9% (3/7) had SD, and 14.3% (1/7) showed PD. Subgroup analysis revealed that patients with bone-only metastases (n=9) had a significantly higher rate of KPS improvement (77.8% vs. 60.0%, P=0.012) and achieved a greater median reduction in pain scores (3.0 vs. 2.0 points, P=0.008). CONCLUSIONS: This study indicated that 225Ac-DOTA-IBA was a promising and well-tolerated therapeutic for bone metastases, demonstrating acceptable toxicity and notable efficacy, including 177Lu-DOTA-IBA-refractory cases. Subgroup analyses indicated that patients with bone-only metastases derived particular clinical benefit.