Authors: Sang Hee Lee1,2,3, Hyunho An2, Ji Hyeon Kim2, Byung Chul Lee2,3, Sang Eun Kim1,2,3
1Department of Molecular and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Suwon, South Korea
2Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea
3Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon, South Korea
Background
TSPO PET imaging can provide the pathological information related to neuroinflammatory brain disorders1. Recently, we developed a novel TSPO-binding radiotracer, [18F]BS224 which shows high TSPO-binding affinity, a clearly visibility of the inflammatory lesion and less sensitivity to TSPO polymorphism rs6971 in preclinical studies2.
Aims
High radiochemical yields and a reproducible synthesis of [18F]BS224 is urgently needed for clinical studies. Therefore, we have synthesized two different precursors (diaryliodonium tosylate and pinacol boronic ester forms) and attempted to optimize the reaction conditions based on the reactivity in the fluorine-18 incorporation environment using the automated module.
Methods
Radiosynthesis of [18F]BS224 was performed by using two different precursors (Figure). Fluorine-18 incorporation condition from diaryliodonium tosylate or pinacol boronate ester precursor were optimized in the presence of different PTC complexs, solvents, temperatures and catalysts, respectively. The obtained radiochemical yields of [18F]BS224 were measured by radio-TLC and semi-preparative HPLC.
Results and Conclusion
[18F]BS224 was prepared in RCY 25% and 63% from diaryliodonium tosylate and pinacol boronic ester precursor, respectively, based on radio-TLC analysis. The condition (B) of [18F]BS224 resulted in RCY 39 % (n=10) with high AM (127 GBq/µmol) and RCY (>99 %). The reliable fully automated method for [18F]BS224 is ongoing.
References
1. Banati RB et al. PK (‘peripheral benzodiazepine’) – binding sites in the CNS indicate early and discrete brain lesions: microautoradiographic detection of [3H]PK 11195 binding to activated microglia. J Neurophysiol. 1997;26:77-82
2. Owen DR et al. An 18-kDa Translocator Protein (TSPO) Polymorphism Explains Differences in Binding Affinity of the PET Radioligand PBR28. J Cerebr Blood F Met. 2012;32:1-5