USPIO enhanced MR imaging in CNS tumors (UMIC): a study protocol

Tumor-associated macrophages (TAMs) are key drivers of brain tumor progression and therapy resistance. Clinically applicable biomarkers capable of evaluating TAM populations in vivo are highly sought, with one potential imaging marker being ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced MRI. Ferumoxytol is a commercially available, now FDA-approved USPIO contrast agent, which circulates for up to 24 hours before undergoing extravasation and TAM-mediated phagocytosis. This study investigates the feasibility of USPIO-enhanced MRI as a noninvasive marker of TAM-associated inflammation in suspected transforming gliomas and vestibular schwannoma (VS). Patients undergo MRI at four timepoints over three days. Following an initial gadolinium-based MRI protocol, participants receive a slow ferumoxytol infusion (5 mg/kg, max 510 mg), with imaging performed immediately post-infusion and at 24 and 48 hours. Tumor tissue obtained at surgery is then analyzed to determine the cellular localization of USPIO internalization. This pilot study aims to characterize USPIO uptake and clearance within the tumor microenvironment, define the distribution and phenotype of USPIO-internalizing TAMs, and identify optimal imaging methods for this TAM quantification. By enabling in vivo characterization of TAM-rich regions, this work may support USPIO-enhanced MRI as a clinical biomarker of inflammation that can inform patient selection for immunomodulatory therapies.Trial Registration Number: NCT06572475.