fluorodeprenyl-D2 PET imaging as a novel tool to monitor disease activity in GAD65-Ab Autoimmune Encephalitis

ObjectivesTo evaluate [18F]fluorodeprenyl-D2 ([18F]F-DED) positron-emission-tomography (PET) imaging for monitoring disease activity in autoimmune encephalitis (AIE) associated with glutamic acid decarboxylase 65 (GAD65) antibodies (Abs). Methods[18F]F-DED PET scans were performed in 22 GAD65-AIE patients and 8 controls. [18F]F-DED uptake was assessed using dynamic (0-60 min post-injection) and static (30-60 min post-injection) acquisition. [18F]F-DED volumes of distribution (VT, 1-tissue-compartment model with carotid input [1TC2k]) and standardized uptake values (SUV) were calculated as a global index of astrogliosis. Furthermore, regional uptake in the cerebellum and mesiotemporal (MT)/ parahippocampal regions was normalized to global cortical/ subcortical uptake (GLM). PET data were correlated with clinical features, MRI findings, and serum biomarkers (neurofilament light chain [sNfL], glial fibrillary acidic protein [sGFAP]). ResultsMain clinical phenotypes included limbic encephalitis (LE)/ temporal lobe epilepsy (TLE) (n=14), stiff-person syndrome (SPS) (n=4), cerebellar ataxia (CA) (n=4), with overlapping features in nine individuals. At the time of PET imaging, median age was 55 years, median disease duration was five years, thirteen patients received immunotherapy, and cranial MRI revealed MT swelling or signal changes in five patients (22.7%), and cerebellar atrophy in one patient (4.5%). Global [18F]F-DED uptake was increased in GAD65-AIE patients compared to controls. VT (1TC2k) and SUVr (GLM) analysis revealed significantly higher MT/ parahippocampal [18F]F-DED uptake in the entire GAD65-AIE cohort compared to controls. MT/ parahippocampal [18F]F-DED uptake was also significantly increased in LE/TLE patients, whereas CA patients showed significantly increased cerebellar [18F]F-DED uptake compared to those without CA. No significant correlation was found between [18F]F-DED uptake and levels of sNfL in GAD65 target regions, whereas sGFAP levels showed a correlation trend with [{superscript 1}F]F-DED uptake in the cerebellum and an association with white matter [{superscript 1}F]F-DED uptake in a voxelwise analysis. [18F]F-DED uptake in MT/ parahippocampal regions and cerebellar white matter correlated with clinical severity in LE/TLE and CA patients, respectively. Discussion[18F]F-DED uptake patterns correspond to clinical phenotypes and track disease severity in GAD65-AIE indicating that [18F]F-DED PET represents a valuable tool for detection and monitoring disease activity in this patient population.