Glioblastoma (GB) is the most common (50.1%) malignant primary brain tumor in adults. It is typically characterized by extensive invasion of surrounding tissue and rapid proliferation. Despite ongoing advancements in GB treatment, the prognosis remains poor, with a median survival of 12–14 months following diagnosis. This research proposes a novel potential breakthrough therapy, combining radioimmunotherapy with radioligands, blood-brain barrier/blood-tumor barrier (BBB/BTB) opening using focused ultrasound (FUS), and intra-arterial administration of the radioligand via the internal carotid artery.  This concept will be  tested in an in-house developed rat model of glioblastoma tumors, where the efficacy of this therapy is compared to standard treatments and even as an adjuvant approach. Should the results prove promising, this innovative therapy will be advanced to a clinical trial. The ultimate aim is to extend survival, reduce tumor progression, and significantly improve the quality of life for patients.