Project Summary/Abstract Title: Development of an Optimized Thermal Deprotection Method for the Synthesis of 18F-based Radiopharmaceuticals. To date, in the process of PET tracer production, there is no method available for deprotection of trityl group under thermal mediated conditions in the absence of acid. Many PET tracers are synthesized on commercially available radiosynthesis modules in good radiochemical yield for preclinical and clinical research studies. In the 18F-labeling, the precursor contains N-trityl (N-Tr) or N-mono-(NMTr) or dimethoxytrityl (DMTr) amine involves a cumbersome, two-step reaction: (i) 18F-fluorination of N-Tr/DMTr amine protected precursor, (ii) treated with HCl for detritylation to afford the corresponding free amine. Generally speaking, when using automated radiosynthetic systems and following current Good Manufacturing Practices (cGMP), Tr/DMTr/MTr protection groups are removed by acid (HCl, H2SO4, or acetic acid) at the last step of synthesis. However, the acid deprotection approach has a number of drawbacks, primarily because of non-homogeneous mixture between various reactive components cause partial deprotection and leads to the low radiochemical yield (RCY) and low radiochemical purity (RCP). Given the commercial availability of N-Tr/DMTr protected precursors, we opted to develop our thermal mediated deprotection route for these precursors, rather than N-Boc because of the longer life-time stability at room temperature. We envision the proposed method to be operationally simple, greener method, effective for the radiosynthesis and purification of the radiotracer that uses a commercial synthesis module without reconfiguration. The importance of PET tau tracers and PET reporter probes are well recognized, and broader research investigation to fully explore and validate the utility of tau tracer-PET is important. Overall, thermal mediated N-Tr deprotection helped to shorten the overall production time, it potentially could increase RCY of the tracers.