Overview

The immune response or inflammation is known to be a key driver of progression and growth in many solid tumours. Inflammatory cells called macrophages are present in high numbers in many brain tumours and these tumour associated macrophages or TAM are thought to have prognosis and treatment implications in these tumours. A key question, however, is how this inflammation or TAM abundance can be detected, measured and monitored in the clinic. A clinically applicable imaging test that can directly and accurately measure tumour macrophage content would be of considerable value and one technique that may provide this is USPIO enhanced magnetic resonance imaging (MRI). Following intravenous injection, USPIO or ultrasmall superparamagnetic iron oxide nanoparticles, circulate in the bloodstream before being taken up by inflammatory cells/macrophages in tumour tissue, wherein they can be detected by MRI. This pilot study is to evaluate if a commercially available USPIO preparation called ferumoxytol (Feraheme ©) can accurately quantify macrophage abundance in brain tumours, with an exploratory focus on vestibular schwannoma (VS) and suspected transforming low-grade glioma (LGG). Patients with both non-growing (static) and growing VS, and patients with suspected transforming LGG will undergo dedicated MRI sequences before, immediately after (< 2 hours) and at both 24 and 48hrs after ferumoxytol administration. In patients undergoing surgery, acquired imaging will be compared with resected tumour tissue so that markers of inflammation can be compared with USPIO uptake. Through advanced laboratory methods this study will seek to establish within resected VS and LGG specimens: the cellular destination/s of USPIO uptake; the nature of the inflammatory and/or tumour cells containing the USPIO; and the relationship between USPIO uptake and tumour blood vessel permeability or leakiness.

Eligibility

Inclusion Criteria:

• Be at least 16 years old
• Have a CNS tumour suspected to be one of the defined histological types (vestibular scwhannoma or low grade glioma)
• Be able to lie still for up to 1 hour comfortably
• Opinion of the treating clinician is that the patient will be able to successfully complete the research imaging protocol.

Exclusion Criteria:

• Life expectancy less than 1 year
• Previous CNS radiotherapy/ stereotactic radiosurgery (SRS)
• Females who are pregnant/ breastfeeding
• Patients with an eGFR < 30ml/min
• Patients with known and documented history of iron overload/haemosiderosis/ haemochromatosis
• Patients with immune or inflammatory conditions e.g. systemic lupus erythematous, rheumatoid arthritis
• Patients with absolute (e.g. pacemaker) and relative (anxiety or claustrophobia) contraindications to MR scanning
• Patients with a history of allergic reaction to iron or dextran
• Patients with a history of allergic reaction to gadolinium contrast agents, asthma or renal problems
• Patients who are unable to adequately understand verbal explanations or written information given in English.