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  • [Int J Mol Sci.] Glucose-Thymidine Ratio as a Metabolism Index Using 18 F-FDG and 18 F-FLT PET Uptake as a Potential Imaging Biomarker for Evaluating Immune Checkpoint Inhibitor Therapy

    2022년 10월호
    [Int J Mol Sci.] Glucose-Thymidine Ratio as a Metabolism Index Using 18 F-FDG and 18 F-FLT PET Uptake as a Potential Imaging Biomarker for Evaluating Immune Checkpoint Inhibitor Therapy

    서울의대 / 오세라, 윤혜원*, 팽진철*

  • 출처
    Int J Mol Sci.
  • 등재일
    2022 Aug 17
  • 저널이슈번호
    23(16):9273. doi: 10.3390/ijms23169273.
  • 내용

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    Abstract
    Immune checkpoint inhibitors (ICIs) are widely used in cancer immunotherapy, requiring effective methods for response monitoring. This study evaluated changes in 18F-2-fluoro-2-deoxy-D-glucose (FDG) and 18F-fluorothymidine (FLT) uptake by tumors following ICI treatment as potential imaging biomarkers in mice. Tumor uptakes of 18F-FDG and 18F-FLT were measured and compared between the ICI treatment and control groups. A combined imaging index of glucose-thymidine uptake ratio (GTR) was defined and compared between groups. In the ICI treatment group, tumor growth was effectively inhibited, and higher proportions of immune cells were observed. In the early phase, 18F-FDG uptake was higher in the treatment group, whereas 18F-FLT uptake was not different. There was no difference in 18F-FDG uptake between the two groups in the late phase. However, 18F-FLT uptake of the control group was markedly increased compared with the ICI treatment group. GTR was consistently higher in the ICI treatment group in the early and late phases. After ICI treatment, changes in tumor cell proliferation were observed with 18F-FLT, whereas 18F-FDG showed altered metabolism in both tumor and immune cells. A combination of 18F-FLT and 18F-FDG PET, such as GTR, is expected to serve as a potentially effective imaging biomarker for monitoring ICI treatment.

     

     

    Affiliations

    Sera Oh  1   2   3 , Hyewon Youn  1   3   4 , Jin Chul Paeng  1   3 , Young-Hwa Kim  1   3 , Chul-Hee Lee  1   3 , Hongyoon Choi  1   3 , Keon Wook Kang  1   2   3   5 , June-Key Chung  1   3 , Gi Jeong Cheon  1   3
    1 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
    2 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea.
    3 Laboratory of Molecular Imaging and Therapy, Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
    4 Cancer Imaging Center, Seoul National University Hospital, Seoul 03080, Korea.
    5 Bio-MAX Institute, Seoul National University, Seoul 03080, Korea.

  • 키워드
    18F-FDG; 18F-FLT; glucose–thymidine ratio(GTR); immune checkpoint therapy; metabolism index.
  • 연구소개
    면역관문억제제 (Immunce checkpoint inhibitor, ICI) 는 암 면역치료의 타겟으로 널리 사용되고 있으며 효과적인 항암요법의 한 방법으로써 현재 임상 약제로 쓰이고 있습니다. 하지만 면역관문억제제를 이용한 치료 반응이 굉장히 제한적이기 때문에 치료 반응을 예측하기가 어렵다는 단점이 있습니다. 따라서 면역치료 요법의 효과적인 모니터링 방법이 필요합니다. 본 연구는 핵의학에서 널리 쓰이는 18F-FDG (18F-2-fluoro-2-deoxy-D-glucose) 및 18F-FLT (18F-fluorothymidine) PET 을 이용하여 ICI 치료에 따른 포도당과 티미딘 (핵산) 대사의 변화를 비교한 내용입니다. 포도당-티미딘 대사 지수 (GTR)를 이용하여 ICI 치료 모니터링을 비교했을 때 ICI 치료군에서 높은 GTR를 보였고 이는 잠재적인 이미징 바이오마커로 가능성을 제시할 수 있다고 생각합니다.
  • 편집위원

    면역관문억제제는 면역치료에 있어 중요한 부분을 차지하고 있으며 GTR 등의 새로운 biomarker를 제시하여 FDG에 국한되지 않고 더 우수한 치료반응 모니터링이 임상에 적용될 수 있을 것이라 기대됩니다.

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