Focused ultrasound-mediated drug delivery of bevacizumab in treating NF2-related schwannomatosis in an animal model

Abstract Neurofibromatosis type 2 (NF2)-related schwannomatosis is an autosomal dominant genetic disorder characterized by the development of cranial and peripheral nerve schwannomas, including bilateral vestibular schwannomas and dorsal root ganglion schwannomas along the spinal axis, both of which are associated with substantial morbidity. Current therapeutic strategies comprise surgical resection, radiotherapy, and systemic administration of bevacizumab; however, these approaches are frequently limited by high recurrence rates and morbidity. In this study, a transgenic murine model (Postn-Cre;Nf2flox/flox) was employed to investigate the combined effect of intraperitoneally administered human bevacizumab (5 mg/kg b. w.) and focused ultrasound (FUS) on drug delivery and tumor growth in DRG schwannomas. ELISA-based analysis demonstrated a 2.88-fold increase in intratumoral bevacizumab concentration following the combined application of human bevacizumab and FUS, compared to bevacizumab alone. Tumor growth was assessed using 7-tesla MRI of the spine with intravenous gadolinium contrast, and outcomes were compared across five experimental groups: 1) human bevacizumab alone, 2) murine bevacizumab alone, 3) human bevacizumab combined with FUS, 4) FUS alone, and 5) untreated controls. Treatments, including drug administration and FUS exposure, were performed three times at two-week intervals. Notably, the combined treatment group (human bevacizumab + FUS) exhibited a trend toward tumor size reduction.