Background: The goal of this study was to report a fully automated radiosynthetic procedure of a novel tau tracer [18F]-S16 and its safety, biodistribution and dosimetry evaluation in healthy volunteers. And the potential utility of [18F]-S16 PET imaging in AD tauopathies, as well as to identify the relationship between cerebral tau pathology and hypometablism patterns using both [18F]-S16 and [18F]-FDG were also discussed.
Methods: The automated radiosynthsis of [18F]-S16 was performed on a GE Tracerlab FX2 N module, and the in vitro stability was evaluated. For the biodistribution and radiation dosimetry study, healthy volunteers were underwent a series PET scans acquired at 10, 60, 120 and 240min post-injection. The biodistribution in normal organs and safety were assessed. Radiation dosimetry was calculated using OLINDA/EXM 1.0. For AD diagnosis study, participants with a clinical diagnosis of probable AD and healthy controls (HCs) underwent dynamic [18F]-S16 and static [18F]-FDG PET imaging. [18F]-S16 binding was assessed visually and quantitatively using SUV ratios (SUVRs) measured at different regions of interests (ROIs), with the cerebellar cortex as the reference region. SUVRs of [18F]-FDG in 10 min static data were calculated using mean activity in the pons as the reference region. [18F]-S16 SUVRs were compared between the AD and HCs in different ROIs using the Mann-Whitney U test. In AD patients with all cortical ROI regions, Spearman rank correlation analysis was used to calculate the voxel-wise correlations between [18F]-S16 PET and [18F]-FDG.
Results: The automated radiosynthesis of [18F]-S16 was finished within 45 min, with a radiochemical yield (RCY) of 30 ± 5% (n = 8, non-decay-corrected). The radiochemical purity (RCP) was greater than 98% and the specific activity (SA) was calculated to be 1047 ± 450 GBq/μmol (n = 5), and [18F]-S16 was stable in vitro. In the pilot volunteer study, no adverse effects caused by [18F]-S16 was observed within 24 hours post-injection and no defluorination was observed in vivo. The radiotracer could pass through the blood-brain barrier (BBB) easily, and rapidly cleared from the circulation and excreted mainly through the hepatic system. The absorbed dose of the urinary bladder wall was the highest, 133.7 ± 60.9 μSv/MBq. The whole-body mean effective dose was 15.3 ± 0.3 μSv/MBq. In AD subjects, [18F]-S16 accumulation was identified in cortical regions mainly involving parietal, temporal, precuneus, posterior cingulate and frontal lobes. No specific [18F]-S16 cerebral uptake region was identified visually in HCs. SUVR of AD subjects in these regions was significantly higher than that of HCs. Tracer retention was observed in the substantia nigra and brainstem of both AD subjects and HCs. No specific binding uptake compared with reference region was found in the choroid plexus, venous sinus and white matter. A significant correlation was found between [18F]-S16 binding and hypometabolism across neocortical regions.
Conclusion: [18F]-S16 could be synthesized automatically and it showed favorable biodistribution and safety in human. The dosimetric parameters were safe and comparable to other tau tracers. [18F]-S16 PET indicated a high image quality for imaging tau deposition in AD subjects, and distinguishing AD from HCs.