Radioligand therapy for primary brain tumors: a PRISMA-based systematic review of meningiomas and gliomas

There is a critical need for innovative therapies beyond the current standard of care for meningiomas and gliomas. Radioligand therapy (RLT), with its theranostic approach, holds significant promise in this regard. Although several reviews on this topic have been published, none yet have combined the utilization of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology with the Critical Appraisal Skills Programme (CASP) analysis, along with a dedicated subsection specifically addressing ongoing and completed clinical trials. This review aims to fill this gap in the literature by providing a comprehensive assessment of the current evidence on RLT in these tumors.

Published studies were searched through PubMed, Scopus, and Web of Science up to 30 April 2025. Only original articles and clinical studies were included. Following a structured selection process, data extraction was performed. Study quality was critically appraised using CASP analyses. For clinical trials, an additional search was conducted on ClinicalTrials.gov beginning on 12 May 2025.

A total of 30 studies were included in the review: 22 on meningiomas (290 patients) and 8 on gliomas (259 patients). For each study, first author, journal, year of publication, somatostatin receptor imaging, study design, radiopharmaceutical used, main topics, response criteria, toxicity assessment, post-therapy scintigraphy, number of patients, WHO grade, demographics, findings and median follow-up were considered. Among clinical trials, 22 were analyzed, including study site, year of first submission, proposed radiopharmaceutical, study type, primary endpoints and status. Efficacy and toxicity data were the primary focus, and the findings were generally encouraging. Studies on RLT in meningiomas was more robust, while in gliomas remained largely experimental. Nevertheless, the authors' critical appraisal was generally positive. Clinical trials confirmed the more "traditional" nature of research in meningiomas compared to gliomas.

Despite the heterogeneity of the studies, RLT emerges as a promising therapeutic strategy in neuro-oncology. Its theranostic paradigm offers a distinctive advantage, enabling patient selection, treatment personalization, and response monitoring. The development of potentially novel radiopharmaceuticals and the conduct of well-designed multicenter trials with standardized response criteria are needed to further increase the impact and clinical translation of RLT in neuro-oncology.