25 Imaging Tumour-Associated Macrophages in Gliomas and Vestibular Schwannomas Using Ferumoxytol-Enhanced MRI

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Abstract Introduction Tumour-associated macrophages (TAMs) play a central role in brain tumour growth, immune evasion and therapeutic resistance, with a paucity of clinically translatable, non-invasive methods to assess TAM-related inflammation in vivo. One promising approach is ultrasmall superparamagnetic iron oxide nanoparticle (USPIO)-enhanced MRI. Ferumoxytol, a commercially available USPIO, is used off label as an MRI contrast agent and exhibits prolonged intravascular circulation prior to extravasation and subsequent uptake by TAMs. Here, the feasibility of ferumoxytol-enhanced MRI as an imaging biomarker of TAM-associated inflammation in glioma and vestibular schwannoma (VS) was assessed. Methods Participants undergo a longitudinal MRI protocol comprising four imaging sessions, over three days. Following baseline gadolinium-enhanced MRI, ferumoxytol is administered via slow, intravenous infusion (5 mg/kg, maximum dose 510 mg), with MRI performed immediately post-infusion and at 24/48-hour timepoints, with surgical tumour specimens collected/analysed in parallel. This pilot study aims to characterise patterns of USPIO uptake and clearance, define the distribution and phenotype of USPIO-internalising TAMs, and optimise MRI-derived metrics for TAM quantification. Results Across 18 patients imaged to date, ferumoxytol infusion was well tolerated, with no reported adverse events. Longitudinal dynamic changes in tumour T1 relaxivity (R1) between the 1-hour post-ferumoxytol scan and the 48-hour timepoint, indicate temporal redistribution of USPIOs within tumour compartments. At delayed imaging (24/48-hours), susceptibility-weighted imaging changes consistent with USPIO uptake did not consistently co-localise with markers of blood–brain barrier disruption or vascular permeability. Fast-growing vestibular schwannomas exhibited greater and more widespread susceptibility changes than slow-growing tumours, commensurate with increased ferumoxytol uptake and heightened macrophage activity. Conclusion By enabling in vivo visualisation of TAM-enriched regions, this work assesses USPIO-enhanced MRI as a marker of tumour-associated inflammation, to inform patient stratification for immuno-modulatory therapies.