Radioligand Therapy for Primary Brain Tumors: A PRISMA based Systematic Review of Meningiomas and Gliomas

Ilaria Grassi¹Maddalena Sansovini¹Federica Matteucci¹Irene Marini^1*Paola Caroli¹Monica Celli¹Lorenzo Fantini¹Virginia Rossetti¹Lorena Gurrieri²Nada Riva²Alice Rossi³Ilaria Bronico³Valentina Di Iorio⁴Anna Sarnelli⁵Donatella Arpa⁶Silvia Nicolini¹

• ¹Nuclear Medicine Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" (IRST), Meldola (FC), Italy
• ²Medical Oncology Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" (IRST), Meldola (FC) Italy, Meldola (FC), Italy
• ³Radiology Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" (IRST), Meldola (FC), Italy
• ⁴Radiopharmacy - Pharmacy Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" (IRST) Meldola (FC) Italy, Meldola (FC), Italy
• ⁵Medical Physics Department, IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" (IRST), Meldola (FC), Italy
• ⁶Radiotherapy Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy, Meldola (FC), Italy

IIntroduction 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 context. While several reviews on this topic have been published, none to date have combined the utilization of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, the Critical Appraisal Skills Programme (CASP) analysis and a dedicated subsection specifically addressing ongoing and completed clinical trials. This review aims to fill this gap in the literature, providing a comprehensive assessment of the current evidence on RLT in these tumors. Materials and Methods Published studies were searched up to 30 April 2025 through PubMed, Scopus and Web of Science. Only original articles and clinical studies reporting were included. Following a structured selection process, data extraction was performed. Critical appraisal of study quality was conducted using CASP analyses. For clinical trials, an additional search was performed starting 12 May 2025 on ClinicalTrials.gov. Results A total of 30 studies were included in the review, 22 on meningiomas (290 patients) and 8 on gliomas (259 patients). For each study were considered: 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. 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 generally appeared 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 with gliomas. Conclusion 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.