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

Purpose: 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 [ 18 F ] Florzolotau and [ 18 F ] FDG could distinguish these disorders through characteristic patterns of tau deposition and cerebral glucose metabolism. Patients and Methods: 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 [ 18 F] Florzolotau and/or [ 18 F] FDG PET imaging. Visual interpretation and semiquantitative analyses, including voxel-based and region-of-interest approaches, were performed. Results: Anti-IgLON5 patients showed significant [ 18 F]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 [ 18 F]Florzolotau uptake in the caudate, putamen, thalamus, midbrain, and pons, but with distinct additional binding in the frontal lobe. [ 18 F]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. Conclusions: We identified distinct PET signatures that can reliably differentiate anti-IgLON5 disease from PSP. The complementary application of [ 18 F ] Florzolotau and [ 18 F ] 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.