Preliminary Evaluation of 225Ac/177Lu-DOTATATE PRRT in Progressive Meningiomas

BACKGROUND: Progressive meningiomas present a significant therapeutic challenge; there are few therapeutic options in this scenario. Peptide receptor radionuclide therapy (PRRT) targeting somatostatin receptors (SSTRs) is a promising strategy. This study, for the first time, evaluates the efficacy and safety of a combination or sequential use of alpha- emitting [225Ac]Ac-DOTATATE and beta-emitting [177Lu]Lu-DOTATATE PRRT for patients with advanced, refractory meningiomas. PATIENTS AND METHODS: In this pilot study, 7 patients with inoperable or refractory meningiomas and high SSTR expression on [68Ga]Ga-DOTATATE PET/CT were included. Patients received a median of 4 PRRT cycles, combining [225Ac]Ac-DOTATATE and [177Lu]Lu-DOTATATE. One patient received only 225Ac-DOTATATE. The primary endpoint was progression-free survival (PFS) at 6 months following treatment using Response Assessment in Neuro-Oncology (RANO) criteria. Secondary endpoints included overall survival (OS), clinical response, imaging response, and toxicity. Imaging response was further assessed through semiquantitative analysis of pretreatment and posttreatment MRI and PET images. Single-lesion dosimetry was performed for 1 patient. RESULTS: Our study achieved a PFS-6 rate of 85.7% (95% CI: 42.1%-99.6%). Of the 7 patients, 1 achieved complete clinical remission, 2 had partial remission, and 3 had stable disease. A median OS of 14 months (95% CI: 8-18 mo). At the lesion level (n = 25), responses were heterogeneous; SUVmax revealed partial response in 4 lesions, stable disease in 19, and progressive disease in 2. The therapy was well-tolerated, with only mild, grade 1 hematological toxicities observed. Single-lesion dosimetry calculated a tumor absorbed dose of 3.36 Gy/MBq for [225Ac]Ac-DOTATATE and 2.37 Gy/GBq for [177Lu]Lu-DOTATATE. CONCLUSIONS: Combined PRRT with 225Ac/177Lu-DOTATATE appears feasible and potentially beneficial option in advanced meningiomas. However, given the small sample size, treatment heterogeneity, and lack of controlled comparison, the findings should be interpreted with caution. Larger prospective studies are warranted.