Korean Journal of Clinical Laboratory Science (대한임상검사과학회지)

Korean Society for Clinical Laboratory Science (대한임상검사과학회)
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Optimization of Automated Solid Phase Extraction-based Synthesis of [18F]Fluorocholine

고체상 추출법을 기반으로 한 [18F]Fluorocholine 합성법의 최적화 연구

  • Jun Young PARK (Nuclear Medicine Laboratory, Yonsei University Severance Hospital) ;
  • Jeongmin SON (Nuclear Medicine Laboratory, Yonsei University Severance Hospital) ;
  • Won Jun KANG (Department of Nuclear Medicine, Yonsei University Severance Hospital)
  • 박준영 (연세대학교 세브란스병원 핵의학검사실) ;
  • 손정민 (연세대학교 세브란스병원 핵의학검사실) ;
  • 강원준 (연세대학교 세브란스병원 핵의학과)
  • Received : 2023.10.30
  • Accepted : 2023.11.14
  • Published : 2023.12.31
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Abstract

[18F]Fluorocholine is a radiopharmaceutical used non-invasively in positron emission tomography to diagnose parathyroid adenoma, prostate cancer, and hepatocellular carcinoma by evaluating the choline metabolism. In this study, a radiolabeling method for [18F]fluorocholine was optimized using a solid phase extraction (SPE) cartridge. [18F]Fluorocholine was labeled in two steps using an automated synthesizer. In the first step, dibromomethane was reacted with [18F]KF/K2.2.2/K2CO3 to obtain the intermediate [18F]fluorobromomethane. In the second step, [18F]fluorobromomethane was passed through a Sep-PakⓇ Silica SPE cartridge to remove the impurities and then reacted with N,N-dimethylaminoethanol (DMAE) in a Sep-PakⓇ C18 SPE cartridge to label [18F]fluorocholine. The reaction conditions of [18F]fluorocholine were optimized. The synthesis yield was confirmed according to the number of silica cartridges and DMAE concentration. No statistically significant difference in the synthesis yield of [18F]fluorocholine was observed when using four or three silica cartridges (P>0.05). The labeling yield was 11.5±0.5% (N=4) when DMAE was used as its original solution. On the other hand, when diluted to 10% with dimethyl sulfoxide, the radiochemical yield increased significantly to 30.1±5.2% (N=20). In conclusion, [18F]Fluorocholine for clinical use can be synthesized stably in high yield by applying an optimized synthesis method.

[18F]Fluorocholine은 임상에서 부갑상선 선종, 전립선암 및 간세포암 진단 등에 사용되는 PET용 콜린 방사성의약품이다. 본 연구에서는 고체상 추출 카트리지법을 방사성의약품 자동합성장치에 적용하여 [18F]fluorocholine을 제조하는 방법을 최적화하였다. [18F]Fluorocholine은 하나의 반응용기를 사용하여 두 단계 표지반응으로 합성하였으며, [18F]fluorocholine 합성과정 중 생성되는 불순물을 제거하기 위해 사용하는 SepPakⓇ Silica 카트리지의 개수를 3개로 최적화하였고, 전구 물질인 DMAE를 10%로 희석하였을 때 가장 높은 방사화학적 수율을 획득 할 수 있었다. 또한 최종 생산된 [18F] fluorocholine 주사액은 유럽약전에 명시된 품질관리기준을 모두 만족하였다. 본 연구를 통해 쉽고 간편하게 사용할 수 있는 고체상 추출 카트리지를 사용하여 방사성의약품 자동합성장치에 최적화한 [18F]fluorocholine의 합성법은 임상 현장에 안정적으로 [18F]fluorocholine을 공급하는데 유용하게 사용될 것으로 사료된다.

Keywords

References

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