Comparative [18F]Florzolotau and [18F]FDG PET Imaging Patterns in Anti-IgLON5 Disease and Progressive Supranuclear Palsy.

Abstract

Anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease is a rare autoimmune encephalitis that shares clinical features with progressive supranuclear palsy (PSP), complicating differential diagnosis. Here, we sought to investigate whether PET imaging using [18F]Florzolotau and [18F]FDG could distinguish these disorders through characteristic patterns of tau deposition and cerebral glucose metabolism. Eleven patients with serologically confirmed anti-IgLON5 disease, 20 patients with PSP diagnosed according to the 2017 Movement Disorder Society criteria, and 40 age-matched and sex-matched healthy controls were enrolled. Participants underwent [18F]Florzolotau and/or [18F]FDG PET imaging. Visual interpretation and semiquantitative analyses, including voxel-based and region-of-interest approaches, were performed. Anti-IgLON5 patients showed significant [18F]Florzolotau binding in subcortical regions, including the midbrain, pons, caudate, putamen, and thalamus, along with additional involvement of the parietal lobe and cerebellum. PSP patients demonstrated overlapping [18F]Florzolotau uptake in the caudate, putamen, thalamus, midbrain, and pons, but with distinct additional binding in the frontal lobe. [18F]FDG PET revealed contrasting metabolic profiles: anti-IgLON5 disease was associated with diffuse cortical hypometabolism, whereas PSP showed regionally restricted hypometabolism, mainly in the frontal lobe, caudate, putamen, midbrain, and pons. We identified distinct PET signatures that can reliably differentiate anti-IgLON5 disease from PSP. The complementary application of [18F]Florzolotau and [18F]FDG PET imaging may provide valuable biomarkers for differential diagnosis in clinically ambiguous cases, potentially enabling timely immunotherapeutic interventions for patients with imaging patterns suggestive of anti-IgLON5 disease.