Dual‑targeted radioligand therapy with [¹⁷⁷Lu]Lu‑DOTATATE plus [¹⁷⁷Lu]Lu‑DOTA‑IBA for bone metastases from neuroendocrine neoplasms: a prospective pilot study.

Abstract

To evaluate the feasibility, safety and preliminary efficacy of dual-targeted radioligand therapy combining [¹⁷⁷Lu]Lu-DOTATATE and [¹⁷⁷Lu]Lu-DOTA-IBA in patients with bone metastases from neuroendocrine neoplasms (NENs). This prospective, single-center, single-arm study enrolled 30 patients with bone metastases from NENs to receive combined [¹⁷⁷Lu]Lu-DOTATATE and [¹⁷⁷Lu]Lu-DOTA-IBA therapy. Treatment response was assessed using RECIST 1.1 and SSTR-PERCIST for all lesions, and modified M.D. Anderson criteria (MDAC) for bone metastases. Pain palliation assessed by the Visual Analogue Scale (VAS). Treatment-related adverse events (TRAEs) were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Progression-free survival (PFS) was performed using the Kaplan-Meier method. A total of 95 treatment cycles were administered. The overall bone pain relief rate was 95.9%, with complete pain resolution in 41.7% of patients. Among 24 evaluable patients, the objective response rates (ORR) were 16.7% by RECIST 1.1, 50% by SSTR-PERCIST, and 29.2% by MDAC. The corresponding disease control rates (DCR) were 79.2%, 79.2%, and 87.5%, respectively. Subgroup analyses revealed comparable ORRs and DCRs between GEP-NENs (n = 14) and non-GEP-NENs (n = 10) across all three criteria. Semi-Quantitative PET/CT parameters, including STV, SUVmax, SUVmean, TLS, TBR, SULpeak, SLD and TBV decreased significantly after treatment (all P < 0.05). Absorbed doses to critical organs remained within safe thresholds. No grade ≥ 4 AEs occurred. No significant difference in PFS was observed between the two subgroups (log-rank P = 0.828). Our findings suggest that dual-targeted radioligand therapy with [¹⁷⁷Lu]Lu-DOTATATE plus [¹⁷⁷Lu]Lu-DOTA-IBA is feasible and well-tolerated, and may provide preliminary antitumor efficacy and pain palliation. However, due to the single-arm design and limited sample size, its definitive anti-tumor efficacy requires confirmation in larger controlled trials.