RESUMO
TSPO-PET tracers are sensitive to a single-nucleotide polymorphism (rs6971-SNP), resulting in low-, medium- and high-affinity binders (LABs, MABs and HABS), but the clinical relevance of [18F]GE-180 is still unclear. We evaluated the impact of rs6971-SNP on in vivo [18F]GE-180 binding in a healthy brain and in pseudo-reference tissue in neuro-oncological and neurodegenerative diseases. Standardized uptake values (SUVs) of [18F]GE-180-PET were assessed using a manually drawn region of interest in the frontoparietal and cerebellar hemispheres. The SUVs were compared between the LABs, MABs and HABs in control, glioma, four-repeat tauopathy (4RT) and Alzheimer's disease (AD) subjects. Second, the SUVs were compared between the patients and controls within their rs6971-subgroups. After excluding patients with prior therapy, 24 LABs (7 control, 5 glioma, 6 4RT and 6 AD) were analyzed. Age- and sex-matched MABs (n = 38) and HABs (n = 50) were selected. The LABs had lower frontoparietal and cerebellar SUVs when compared with the MABs and HABs, but no significant difference was observed between the MABs and HABs. Within each rs6971 group, no SUV difference between the patients and controls was detected in the pseudo-reference tissues. The rs6971-SNP affects [18F]GE-180 quantification, revealing lower binding in the LABs when compared to the MABs and HABs. The frontoparietal and cerebellar ROIs were successfully validated as pseudo-reference regions.
RESUMO
Objectives: In recent years several 18F-labeled amyloid PET (Aß-PET) tracers have been developed and have obtained clinical approval. There is evidence that Aß-PET perfusion can provide surrogate information about neuronal injury in neurodegenerative diseases when compared to conventional blood flow and glucose metabolism assessment. However, this paradigm has not yet been tested in neurodegenerative disorders with cortical and subcortical affection. Therefore, we investigated the performance of early acquisition 18F-flutemetamol Aß-PET in comparison to 18F-fluorodeoxyglucose (FDG)-PET in corticobasal syndrome (CBS). Methods: Subjects with clinically possible or probable CBS were recruited within the prospective Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease (ActiGliA) observational study and all CBS cases with an available FDG-PET prior to Aß-PET were selected. Aß-PET was acquired 0-10 min p.i. (early-phase) and 90-110 min p.i. (late-phase) whereas FDG-PET was recorded statically from 30 to 50 min p.i. Semiquantitative regional values and asymmetry indices (AI) were compared between early-phase Aß-PET and FDG-PET. Visual assessments of hypoperfusion and hypometabolism were compared between both methods. Late-phase Aß-PET was evaluated visually for assessment of Aß-positivity. Results: Among 20 evaluated patients with CBS, 5 were Aß-positive. Early-phase Aß-PET and FDG-PET SUVr correlated highly in cortical (mean R = 0.86, range 0.77-0.92) and subcortical brain regions (mean R = 0.84, range 0.79-0.90). Strong asymmetry was observed in FDG-PET for the motor cortex (mean |AI| = 2.9%), the parietal cortex (mean |AI| = 2.9%), and the thalamus (mean |AI| = 5.5%), correlating well with AI of early-phase Aß-PET (mean R = 0.87, range 0.62-0.98). Visual assessments of hypoperfusion and hypometabolism were highly congruent. Conclusion: Early-phase Aß-PET facilitates assessment of neuronal injury in CBS for cortical and subcortical areas. Known asymmetries in CBS are captured by this method, enabling assessment of Aß-status and neuronal injury with a single radiation exposure at a single visit.