[¹⁸F]Fluorodeprenyl-D2 PET as a Tool to Monitor Disease Activity in GAD65-Ab Autoimmune Encephalitis

To evaluate [¹⁸F]fluorodeprenyl-D2 ([¹⁸F]F-DED) positron-emission tomography (PET) imaging as a biomarker of disease activity in autoimmune encephalitis (AIE) associated with glutamic acid decarboxylase 65 (GAD65) antibodies.

[¹⁸F]F-DED PET was performed in 25 GAD65-AIE patients and 8 controls using dynamic (0-60 min) and static (30-60 min) acquisitions. Global astrogliosis was assessed by volumes of distribution (VT; 1-tissue-compartment model with carotid input) and standardized uptake values (SUV). Regional cerebellar and mesiotemporal (MT) uptake was normalized to global uptake (SUVr). PET measures were correlated with clinical phenotypes, MRI findings, and serum biomarkers (neurofilament light chain [sNfL], GAD65-Ab titers, and glial fibrillary acidic protein [sGFAP]).

Clinical phenotypes included limbic encephalitis/temporal lobe epilepsy (LE/TLE; n = 17), stiff-person syndrome (n = 4), and cerebellar ataxia (CA; n = 4), with overlap in nine patients. Global [¹⁸F]F-DED uptake was higher in patients than controls. VT analysis showed increased cortical and MT uptake, while SUVr analysis demonstrated elevated MT uptake across the cohort. LE/TLE patients exhibited increased MT uptake, and CA patients showed higher cerebellar uptake. [¹⁸F]F-DED uptake did not correlate with sNfL or GAD65-Ab titers, but sGFAP showed associations with cerebellar and white-matter uptake. Regional uptake correlated with clinical severity in LE/TLE (MT lobe) and CA (cerebellar white matter).

[¹⁸F]F-DED PET reveals region-specific astrogliosis corresponding to clinical manifestations and disease severity in GAD65-AIE, supporting its potential as a monitoring tool for disease activity.