In vivo imaging of Tau deposition using a new tracer-¹⁸F-S23 in comparison with ¹⁸F-THK5317 in Alzheimer’s disease

Purpose: To evaluate the effectiveness of a new tau tracer ((S)-1-(4-(6-(dimethylamino) naphthalen-2-yl)phenoxy)-3-fluoropropan-2-ol,¹⁸F-S23) in identifying AD patients from healthy controls (HCs) as compared with ¹⁸F-THK5317.

Methods: The study cohort consisted of 6 AD, 1 FTLD, 1 PSP, 1 DLB, 6 HCs and 2 young volunteers. Dynamic PET was performed over a period of 90 min after injection of tracers in 1 AD patient, 6 HCs and 2 young volunteers. Static data acquisitions with a duration of 20-min from 40 min to 60 min after tracers’ administration were performed in all patients to analyze the standardized uptake value (SUV) and cortical-to-cerebellum SUV ratios (SUVRs). Voxel-based analysis of both tracers was employed to assess their uptake differences between populations.

Results: Both tracers were distributed to the brain of subjects rapidly but the clearance of ¹⁸F-S23 was slower than ¹⁸F-THK5317 within 90 min acquisition. The AD patient showed increased cortical ¹⁸F-S23 binding (e.g., the basal temporal cortex and posterior cingulated cortex); minimal accumulation of tracers was seen in young volunteers. Nonspecific uptake was observed in both tracers in basal ganglia and brain stem, but the radioactive uptake of eyeballs was observed in ¹⁸F-THK5317 only. In comparative studies, the cortical average SUVR of ¹⁸F-THK5317 was 1.32 ± 0.06 for AD versus 1.21 ± 0.03 for HCs (F = 5.73, P < 0.05), and for ¹⁸F-S23, that was 1.20 ± 0.10 versus 1.15 ± 0.06 (F = 3.17, P < 0.05) (Table 1.). In voxelwised analysis, AD patients showed significant increased cortical ¹⁸F-S23 binding in the bilateral basal temporal cortex, hippocampus, prefrontal cortex, insular, ACC and lateral parietal cortex; ¹⁸F-THK5317 displayed increased abnormal radioactive retention in bilateral basal temporal cortex, lateral temporal cortex, prefrontal cortex, PCC/precuneus and lateral parietal cortex (Figure 1.). The patterns of uptake of both tracers were similar in FLTD and PSP patients, which were observed increased radioactive retention in the anterior temporal cortex and in the globus pallidus and midbrain, respectively. No obvious abnormal uptake was found in the DLB patient.

Conclusions: Although the binding intensity and distribution of ¹⁸F-S23 were slightly different with that of ¹⁸F-THK5317 in controls, the significant difference between AD and HCs in cortical regions indicates that ¹⁸F-S23 might be a promising Tau-tracer for PET imaging.

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