Design semi-automated radio-synthesis strategy and synthesis of benzimidazole-based radiotracer 2-(4-(2-(fluoro-18F) ethyl) piperidin-1-yl) benzo imidazo[1,2-a] pyrimidine for Tau as a PET imaging agent

Several studies have reported that benzimidazole-based structures are used in the diagnosis of Alzheimer's disease. Various modified benzimidazole-based structures serve as radiotracers. Among them, 2-(4-(2-(fluoro- 18 F)ethyl)piperidin-1-yl)benzo[4,5]imidazo[1,2- a ]pyrimidine or [ 18 F]T808 is a prominent radiotracer for tau PET tracer. The synthesis was started with trichloroacetyl chloride and ethyl vinyl ether, the precursor synthesis was completed in 9 steps. The precursor facilitated the radiosynthesis of [ 18 F]T808 in excellent yield with higher purity. We explored a radiotracer for diagnosing Alzheimer's disease, specifically a benzimidazole-based tau PET precursor. The goal was to synthesise and develop a semi-automated radiolabelling protocol of 2-(4-(2-(fluoro- 18 F)ethyl)piperidin-1-yl)benzo[4,5] imidazo[1,2- a ]pyrimidine, resulting in a higher yield with shorter radiosynthesis time. The synthesis of the precursor started with Ethyl vinyl ether and trichloroacetyl chloride. All chemically synthesised compounds were characterised by 1 H-NMR, 13 C-NMR, and mass spectrometry. The synthesised precursor was used for the radiosynthesis of tau PET tracer [ 18 F]T808 by the nucleophilic [ 18 F]fluorination with K[ 18 F]F/Kryptofix 2.2.2 in DMSO at 140℃. This transformative process resulted in a crude radiolabeled product being purified through semi-preparative high-performance liquid chromatography (HPLC) and solid phase extraction (SPE) in an isolated desired product. The synthesised radiotracer was analysed using analytical tools such as radio TLC, HPLC, pH, endotoxin, and half-life. The precursor was successfully synthesised in 9 crucial steps with 80% yields, and ˃97% chemical purity. The synthesised precursor was used in the semi-automated radiosynthesis of [ 18 F]T808. The radiolabelled desired product [ 18 F]T808 was successfully achieved. The decay-corrected yield for [ 18 F]T808 was approximately 45–50% at the end of synthesis, 40–45 min Our method resulted in tau PET tracer precursor synthesis of 65% yield with 97% chemical purity. The tau tracer was radiolabeled with 45–50% radiochemical purity of ˃98%. The analytical data match regulatory standards for being used as a PET tracer for clinical studies.