Targeted alpha therapy for recurrent high-grade glioma with [²²⁵Ac]-PSMA: a new theranostic approach
European Journal of Nuclear Medicine and Molecular Imaging, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Basım Tarihi: 2026
- Doi Numarası: 10.1007/s00259-026-08194-6
- Dergi Adı: European Journal of Nuclear Medicine and Molecular Imaging
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, CINAHL, Compendex, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest), Technology Collection (ProQuest)
- Anahtar Kelimeler: Actinium-225, Glioblastoma, Targeted alpha therapy, Theranostics
- İstanbul Üniversitesi-Cerrahpaşa Adresli: Evet
Özet
Purpose: To evaluate the feasibility, safety, and preliminary efficacy of systemic targeted alpha therapy with [²²⁵Ac]-PSMA in patients with recurrent high-grade glioma (HGG). Glioblastoma multiforme (GBM) and HGGs are highly aggressive primary brain tumors with limited treatment options at recurrence. Expression of prostate-specific membrane antigen (PSMA) in the neovasculature of GBM provides a promising target for radioligand therapy using alpha emitters such as Actinium-225. Methods: Four patients with histologically confirmed recurrent HGG received [²²⁵Ac]-PSMA therapy at a dose of 100 kBq/kg per cycle. Diagnoses were established according to the WHO classification available at the time of diagnosis. The cohort included three patients with GBM and one patient with a high-grade diffuse glial tumor, WHO grade III. Treatment cycles were intended at 8–12-week intervals. Baseline and follow-up assessments were performed visually and then semi-quantitave parameters were described on [⁶⁸Ga]-PSMA PET/MRI or PET/CT images also using contrast-enhanced MRI. Clinical status and hematologic parameters were monitored throughout therapy and follow-up. Results: While every patient ultimately developed progressive disease following treatment, the predefined PSMA-avid index lesion regressed in one patient and remained stable in another. No grade ≥ 3 adverse events attributable to [²²⁵Ac]-PSMA or treatment-related mortality were observed. Low-grade toxicity was limited and mainly consisted of mild xerostomia. Conclusion: Systemic [²²⁵Ac]-PSMA therapy appeared feasible and well tolerated, showing preliminary evidence of disease control in recurrent HGGs.