Novel Tau-PET Tracer ¹⁸F-S16 Combined With Amyloid Deposition And Hypometabolism In Alzheimer's Disease

Part?Spatial Patterns of Hypometabolism and Amyloid Deposition in Variants of Alzheimer's Disease Corresponding to Brain NetworksObjective:To find the most vulnerable network among typical and three variants of AD,and make the links between A?deposition and downstream network dysfunction.Methods:Thirty-eight typical AD,thirteen frontal variants,eight logopenic variants,six posterior variants and twenty normal controls were enrolled.¹¹C-PIB and¹⁸F-FDG PET were obtained.Voxel-wise statistical analysis was used for FDG analysis.Two-sample t tests were performed between each AD group and controls.We assessed the goodness of fit?GOF?of t-maps with brain functional network templates.Then the most vulnerable network in each phenotypic of AD was chosen as VOIs.¹¹C-PIB binding potential(BP_ND)of VOIs were generated by using PMOD.Statistical analysis of BP_ND among four types of AD in each specific network was calculated by using SPSS.Results:The hypometabolism patterns found the most vulnerable network was the left executive-control network?GOF score=4.3,5.0?in typical and frontal variant of AD.For logopenic variant,the highest GOF score?1.9?belonged to auditory network.For posterior variant,the higher visual network was the most vulnerable?GOF score=6.0?.The PIB BP_ND showed that there was no significant difference?p>0.05?among AD groups in the specific network.Conclusion:The phenotypic diversity of AD was correlated with specific functional network failure.But amyloid plagues didn't associate with specific network vulnerability.Part?Novel Tau-PET tracer ¹⁸F-S16 preliminary clinical translational studyPurpose:¹⁸F-?S?-1-?4-?6-?dimethylamino?quinoxalin-2-yl?phenoxy?-3-fluoropropan-2-ol(¹⁸F-S16)as a PET tracer can binds with Tau with high selectivity and sensitivity and provides a potential alternative for the early AD diagnosis compared with other probes.In this study,a fully automated radiosynthetic procedure of ¹⁸F-S16 and its human study were reported.Methods:After synthetic conditions optimization,a multifunctional synthesis module GE Tracerlab FX2 N was employed.The radiosynthesis of ¹⁸F-S16 was started from¹⁸F-fluoride using one-pot reaction followed by semi-preparative HPLC purification.The in vivo and in vitro stability,partition coefficient and biodistribution studies were discussed.As the preclinical behavior of ¹⁸F-S16 as a Tau-PET imaging tracer has been proved in the previous preclinical studies,the first detailed pharmacokinetic and biodistribution parameters obtained from healthy human volunteers were discussed.Tau protein disease were also discussed in this stuty.Results:After the optimized reaction conditions were confirmed,and the automated radiosynthesis of ¹⁸F-S16 was completed.The radiochemical purity of ¹⁸F-S16injection was over 98%and the specific activity was 1047±450 GBq/?mol?n=5?.¹⁸F-S16 was stable both in vivo and in vitro,and it showed high lipophilicity.In the pilot human study,no adverse effects due to ¹⁸F-S16 were observed up to 24 h post-injection.The radiotracer could pass through the blood brain barrier?BBB?easily,and it rapidly cleared from the circulation and excreted mainly through the hepatic system.In Tau protein disese,the specific uptake of ¹⁸F-S16 was consistent with hypometabolism brain regions.Conclusion:We conclude that ¹⁸F-S16 holds a great potential for appropriate and effective imaging of Tau in vivo.These preliminary results indicate that further clinical studies are warranted.