분자영상 및 방사화학

  • [J Nucl Med.] 미분화갑상선암의 방사선요오드치료 불응을 극복할 수 있는 새로운 clue를 제공MEK inhibition induces therapeutic iodine uptake in a murine model of anaplastic thyroid cancer.

    University of Bern / ElMokh O*

  • 출처
    J Nucl Med.
  • 등재일
    2018 Nov 21. pii: jnumed.118.216721. doi: 10.2967/
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  • 내용

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    Abstract
    Anaplastic thyroid carcinoma (ATC) is refractory to radioiodine therapy in part due to impaired iodine metabolism. We targeted the MAPK and PI3'K pathways with the intent to induce radioiodine uptake for radioiodine treatment of ATC. Methods: Human ATC cells were used to evaluate the ability of pharmacological inhibition of the mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways to induce radioiodine uptake. Thyrocyte-specific double mutant BRAFV600E PIK3CAH1047R mice were treated with a MEK inhibitor followed by radioiodine treatment and tumor burden was monitored by ultrasound imaging. Results: ATC cell lines showed an increase in sodium-iodine symporter transcription when treated with a MEK or BRAFV600E inhibitor alone and in combination with PI3'K inhibitor. This translated into a dose-dependent elevation of iodine uptake following treatment with a MEK inhibitor alone and in combination with a PI3'K inhibitor. In vivo, MEK inhibition but not BRAF nor PI3'K inhibition upregulated sodium-iodine symporter transcription. This translated into a stable reduction of tumor burden when mice were treated with a MEK inhibitor prior to radioiodine administration. Conclusion: This study confirms the ability of MEK inhibition to induce iodine uptake in in vitro and in vivo models of ATC. The approach of using a MEK inhibitor before radioiodine treatment could readily be translated into clinical practice and provide a much-needed therapeutic option for patients with ATC.

     


    Author information

    ElMokh O1, Taelmann V2, Radojewski P2, Roelli MA1, Stooss A1, Dumont RA3, Dettmer M1, Phillips W4, Walter MA2, Charles RR1.
    1
    University of Bern, Switzerland.
    2
    University of Geneva, Switzerland.
    3
    UCSF, United States.
    4
    Peter Mac Institute, Melbourne, Australia.

  • 키워드
    Differentiation; Drug resistance; Endocrine; Molecular Biology; NIS; Oncology: Head and neck; Radionuclide Therapy; Targeted therapy
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