대한임상검사과학회지 (Korean Journal of Clinical Laboratory Science)

  • 제56권1호
  • /
  • Pages.43-51
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  • 2024
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  • 1738-3544(pISSN)
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  • 2288-1662(eISSN)
대한임상검사과학회 (Korean Society for Clinical Laboratory Science)
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카세트 기반 자동합성장치를 사용한 [68Ga]Ga-FAPI-04의 합성방법 연구

Development of a Synthetic Method for [68Ga]Ga-FAPI-04 Using a Cassette-based Synthesizer

  • 박준영 (연세대학교 의과대학 세브란스병원 핵의학과) ;
  • 강원준 (연세대학교 의과대학 세브란스병원 핵의학과)
  • Jun Young PARK (Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine) ;
  • Won Jun KANG (Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine)
  • 투고 : 2024.01.31
  • 심사 : 2024.02.25
  • 발행 : 2024.03.31
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초록

[68Ga]Ga-FAPI-04는 암세포에 과발현 되어 있는 fibroblast activation protein (FAP)에 특이적으로 결합하는 FAP 저해제(FAP inhibitor, FAPI)에 방사성동위원소 68Ga을 표지한 방사성의약품이다. 본 연구에서는 국내에서 제작된 카세트기반 자동합성장치를 사용하여 [68Ga]Ga-FAPI-04를 제조하는 방법을 개발하였다. [68Ga]Ga-FAPI-04의 합법을 개발하기 위해 완충액 HEPES의 농도, 반응시간, FAPI-04 전구체 양, 반응온도에 따른 표지효율을 확인하였다. [68Ga]Ga-FAPI-04는 2 M HEPES를 사용하여 pH 3.85에서 반응할 경우 가장 높은 표지효율을 획득할 수 있었고, 반응시간이 10분일 경우와 25 ㎍의 FAPI-04 전구체를 사용할 경우 및 100℃에서 반응할 경우 가장 높은 표지효율을 획득할 수 있었다. 또한 최종 합성된 [68Ga]Ga-FAPI-04는 모든 품질기준을 만족하여 본 연구를 통해 개발된 [68Ga]Ga-FAPI-04의 합성법은 FAPI 기반 방사성의 약품생산에 활용도가 높을 것으로 예상된다.

[68Ga]Ga-FAPI-04 is a promising radiopharmaceutical that binds specifically to fibroblast activation protein, which is overexpressed in more than 90% of malignant epithelial tumors but not in normal healthy tissue. This study aimed to develop an efficient method for producing 68Ga-labelled FAPI-04 using a cassette-based automated synthesizer. [68Ga]GaCl3 was eluted from an Eckert & Ziegler Medical germanium-68/gallium-68 generator using 2.5 mL of 0.1 M HCl. The synthesis of the [68Ga]Ga-FAPI-04 was performed using different concentrations of HEPES (1~2.5 M; 4-(2-hydroxyethyl) piperazine-1-ethanesulfonic acid) in 3~10 minutes; amounts of FAPI-04 precursor (5~50 ㎍) and reaction temperature (25℃~100℃) were optimized on the BIKBox® synthesizer. The labeling efficiency of [68Ga]Ga-FAPI-04 was greater than 96% (decay corrected) using 25 ㎍ FAPI-04 synthesized in 10 minutes at 100℃ in 2 M HEPES (pH 3.85), and its stability was greater than 99% at 6 hours. The total synthesis time of [68Ga]Ga-FAPI-04 was 32.4 minutes, and the product met all quality control criteria. In this study, we developed and optimized a labeling method using [68Ga]Ga-FAPI-04 using a cassette-based synthesizer. The devised method is expected to be useful for supplying [68Ga]Ga-FAPI-04 for diagnosis in clinical practice.

키워드

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