Detection of inflammation-related blood-brain barrier dysfunction using PET and MR imaging: a pilot study

The purpose of this study is to non-invasively image subtle blood-brain barrier (BBB) permeability changes in a state of chronic neuroinflammation using radiolabelled human serum albumin (HSA). Although biomarker-based methods for detecting BBB dysfunctions have been established, sensitive spatial and quantitative imaging of low-grade, chronic BBB permeability changes remains limited. This study seeks to establish radiolabelled albumin as a sensitive radiotracer for visualizing and quantifying BBB dysfunction during chronic neuroinflammation. This study evaluated the utility of radiolabeled serum albumin ([⁸⁹Zr]Zr-DFO-HSA) for assessing BBB permeability using co-registered PET and MR imaging in a transgenic mouse model of neuroinflammation mediated by IKK/NF-κB activation. PET and MRI revealed significantly increased radiotracer accumulation in the cerebellum of neuroinflammatory mice, corroborated by ex vivo analyses. Quantitative PET data revealed elevated intracerebral radiotracer concentrations over 24 h, even in the absence of morphological changes in histological evaluations. These findings emphasize the sensitivity of [⁸⁹Zr]Zr-DFO-HSA in detecting early-stage BBB permeability changes prior to the onset of overt morphological damage or clinical symptoms. As a surrogate marker for macromolecular leakage, this non invasive imaging approach shows promise for advancing preclinical research into neuroinflammatory disorders and barrier dysfunctions.