Quantification of monoamine oxidase B expression with ¹¹C-SL25.1188 for imaging reactive astrocytes in patients with Alzheimer's disease.

Abstract

Astrocyte reactivation can be assessed using positron emission tomography (PET) ligands targeting monoamine oxidase B (MAO-B). ¹¹C-SL25.1188 binds reversibly to MAO-B, allowing precise density measurements, but requires invasive arterial sampling. This study aimed to develop a simplified, noninvasive method to quantify MAO-B with ¹¹C-SL25.1188 PET in Alzheimer's disease (AD). Six patients with mild cognitive impairment (MCI), five patients with AD, and six healthy controls (HCs) underwent ¹¹C-SL25.1188 PET scans. The distribution volume ratios (DVRs) were calculated and compared using two methods: the original multilinear reference tissue model (MRTM_O) and the Logan plot. Changes in MAO-B densities, plasma glial fibrillary acidic protein (GFAP) levels, and abnormal protein aggregation were examined among subjects. A strong agreement was observed between the DVRs estimated using MRTM_O and those obtained with the Logan plot (r² = 0.89), with the cerebellar cortex used as the reference region. This region was selected based on its similar total distribution volume values and comparable MAO-B levels between patients with AD and HCs. Patients with MCI showed higher DVRs in the parietal cortex compared to those with moderate AD. Moreover, patients with moderate AD had higher plasma GFAP levels than HCs but similar levels to patients with MCI. MAO-B density in patients with MCI/AD can be accurately estimated by calculating DVRs using a simplified quantification method that does not require arterial blood sampling. The estimated MAO-B density shows an increase that peaks at the MCI stage, suggesting early astrocyte reactivation in the progression of AD pathology.