9-(4-[¹⁸F] Fluoro-3-hydroxymethylbutyl) guanine 합성의 자동화와 최적화에 관한 연구

A Study on the Automation and Optimization of 9-(4-[¹⁸F] Fluoro-3-hydroxymethylbutyl) Guanine Synthesis

Purpose: The HSV1-tk reporter gene system is the most widely used system because of its advantage is that it is possible to monitor directly without the introduction of a separate reporter gene in case of HSV1-tk suicide gene therapy. This study was performed to automate 9-(4-[¹⁸F] Fluoro-3-hydroxymethylbutyl) guanine ([¹⁸F] FHBG) that are widely used as substrate for the HSV1-tk reporter gene in living organisms with positron emission tomography (PET) and find the optimized conditions of synthesis. Materials and Methods: Fully automated synthesis of [¹⁸F] FHBG was performed using Explora-RN (CTI, USA) module. We have changed of reaction time (3, 5, 10 min) and temperature (110, 120, 130°C) for the optimized conditions of synthesis. Also we experimented to find the optimal concentration of precursor (5, 7, 10 mg). Results: [¹⁸F] FHBG was purified by HPLC system and collected at around 10-12 min. Synthesis using Explora-RN module showed a 32.0±1.2% yield of radiochemical (decay corrected), the purity was greater than 98%. And the entire synthesis time was less than 48 min. Temperature of the highest synthesis yield was 130°C, reaction time was 5 minutes and concentration of precursor was 10 mg (recommended volume in manual) (n=36). In contrast to radiochemical yield of precursor 10 mg (32±1.2%), yield of 5 and 7 mg precursor was unstable. Conclusion: Automation of [¹⁸F] FHBG synthesis at Explora-RN module has been completed. In addition, we were able to obtain optimized reaction time, temperature and concentration of precursor. Therefore this study would be provided more rapid synthesis and higher radiochemical yield.