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[11C](R)-PK11195 positron emission tomography imaging of activated microglia in vivo in Rasmussen's encephalitis
R B Banati1, G W Goerres, R Myers
1MRC Cyclotron Unit, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Abstract:
This study was designed to explore the feasibility of PET using [11C](R)-PK11195 as an in vivo marker of activated microglia/brain macrophages for the assessment of neuroinflammation in Rasmussen's encephalitis (RE). [11C](R)-PK11195 PET was carried out in four normal subjects, two patients with histologically confirmed RE, and three patients with clinically stable hippocampal sclerosis and low seizure frequency. Binding potential maps showing specific binding of [11C](R)-PK11195 were generated for each subject. Regional binding potential values were calculated for anatomically defined regions of interest after coregistration to and spatial transformation into the subjects' own MRI. In one patient with RE who underwent hemispherectomy, the resected, paraffin-embedded brain tissue was stained with an antibody (CR3/43) that labels activated human microglia. Whereas specific binding of [11C](R)-PK11195 in clinically stable hippocampal sclerosis was similar to that in normal brain, patients with RE showed a focal and diffuse increase in binding throughout the affected hemisphere. In RE, [11C](R)-PK11195 PET can reveal in vivo the characteristic, unilateral pattern known from postmortem neuropathologic study. PET imaging of activated microglia/brain macrophages offers a tool for investigation of a range of brain diseases where neuroinflammation is a component and in which conventional MRI does not unequivocally indicate an inflammatory tissue reaction. [11C](R)-PK11195 PET may help in the choice of appropriate biopsy sites and, further, may allow assessment of the efficacy of antiinflammatory disease-modifying treatment.
Insights
Positron emission tomography (PET) with [11C](R)-PK11195 can visualize activated microglia in Rasmussen's encephalitis (RE). This neuroimaging technique reveals the unilateral inflammation characteristic of RE, offering a tool for diagnosing and monitoring neuroinflammatory diseases.
Area of Science:
- Neuroscience
- Radiochemistry
- Medical Imaging
Background:
- Rasmussen's encephalitis (RE) is a rare neurological disorder characterized by chronic inflammation of one brain hemisphere.
- Assessing neuroinflammation in vivo has been challenging, particularly when conventional MRI is inconclusive.
- Activated microglia and brain macrophages are key players in neuroinflammation.
Observation:
- Positron emission tomography (PET) using the tracer [11C](R)-PK11195 was performed in normal subjects, RE patients, and patients with hippocampal sclerosis.
- Binding potential maps were generated to quantify the specific binding of [11C](R)-PK11195, a marker for activated microglia/brain macrophages.
- Histological analysis of resected brain tissue from an RE patient confirmed the presence of activated microglia.
Findings:
- Patients with RE exhibited focal and diffuse increases in [11C](R)-PK11195 binding in the affected hemisphere, consistent with neuropathological findings.
- In contrast, subjects with clinically stable hippocampal sclerosis showed binding levels similar to normal controls.
- [11C](R)-PK11195 PET successfully visualized the unilateral pattern of neuroinflammation characteristic of RE.
Implications:
- [11C](R)-PK11195 PET provides an in vivo method to assess neuroinflammation in RE and potentially other inflammatory brain diseases.
- This imaging modality can aid in selecting biopsy sites and evaluating the effectiveness of anti-inflammatory treatments.
- PET imaging of activated microglia offers a valuable tool for diseases where inflammation is a component and MRI is not definitive.