P03.17.B FERUMOXYTOL-ENHANCED MRI IS A FEASIBLE, WELL-TOLERATED POTENTIAL MARKER OF INFLAMMATION IN GLIOMA

Abstract BACKGROUND Immune-mediated inflammation is a key driver of tumour progression in many solid tumours, with tumour-associated macrophages (TAMs) thought to drive tumour infiltration, progression and therapy resistance. Ferumoxytol (FeOx) is an ultrasmall iron oxide nanoparticle (USPIO) preparation used as an off-label contrast agent, which after extravasation, is phagocytosed by TAMs in the tumour microenvironment. This ongoing study investigates the feasibility of FeOx-MRI, as an effective imaging marker of TAM-induced inflammation, in transforming low-grade gliomas (tLGGs) and vestibular schwannoma (VS) cohorts. MATERIAL AND METHODS Patients are recruited from the Greater Manchester Neurosciences Centre, and to date, 9 patients have been successfully imaged following FeOx infusion. Each patient receives a standard gadolinium-based contrast agent (GBCA; Dotarem) followed by FeOx (Feraheme ©; 5 mg/kg, max 510mg), infused over 30 minutes. MRI scanning is conducted at four timepoints over a three-day protocol: post-GBCA (pre-FeOx), 1 hour, 24 hours, and 48 hours post-FeOx. The imaging protocol includes T1/T2/T2* weighted scans, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), and dual-injection dynamic contrast-enhanced MRI (DCE-MRI), processed through validated in-house pipelines. RESULTS Across all 9 patients imaged so far, FeOx infusion was well tolerated, with no adverse events or side effects reported. Analysis of the imaged glioma cohort (n=3) demonstrated dynamic changes in tumour T1 relaxivity (R1) values, between the 1 hour (post-FeOx) and 48hr scan, suggesting dynamic changes in USPIO/FeOx distribution within both the extra/intracellular tumour compartments. At delayed imaging timepoints (24 and 48hr), SWI signal changes consistent with USPIO/FeOx uptake did not always co-localise with regions of blood-brain barrier breakdown on post-GBCA T1-weighted imaging. CONCLUSION Our preliminary findings indicate that USPIO-enhanced MRI, following a slow infusion of FeOx is well-tolerated, with no adverse events in our imaged cohort to date. Demonstrated SWI and R1 changes beyond areas of BBB disruption measured on conventional post-GBCA imaging, suggests that FeOx-MRI may highlight distinct components of the tumour immune microenvironment, and potentially identify TAM-rich regions. Future work, including histological validation, will clarify whether FeOx-MRI signal localises specifically to TAMs - and further inform its utility as a clinical biomarker of TAM-driven inflammation within the tumour microenvironment.