타우 PET영상을 위한 18F-THK5351의 표지방법 개발

Abstract

Purmose: 18F-THK5351 is the newly developed PET probe for tau imaging in alzheimer's disease. The purpose of study was to establish the automated production of 18F-THK5351 on a commercial module. Materials and Methods: Two different approaches were evaluated for the synthesis of 18F-THK5351. The first approach (method I) included the nucleophilic 18F-fluorination of the tosylate precursor, subsequently followed by pre-HPLC purification of crude reaction mixture with SPE cartridge. In the second approach (method II), the crude reaction mixture was directly introduced to a semi-preparative HPLC without SPE purification. The radiosynthesis of 18F-THK5351 was performed on a commercial GE TRACERlabTM FX-FN module. Quality control of 18F-THK5351 was carried out to meet the criteria guidelined in USP for PET radiopharmaceuticals. Results: The overall radiochemical yield of method I was 23.8±1.9% (n=4) as the decay-corrected yield (end of synthesis, EOS) and the total synthesis time was 75±3 min. The radiochemical yield of method II was 31.9±6.7% (decay-corrected, n=10) and the total preparation time was 70±2 min. The radiochemical purity was>98%. Conclusion: This study shows that method II provides higher radiochemical yield and shorter production time compared to the pre-SPE purification described in method I. The 18F-THK5351 synthesis by method II will be ideal for routine clinical application, considering short physical half-life of fluorine-18 (t1/2=110 min).