Synthesis, preclinical assessment, and first-in-human study of [18F]d4-FET for brain tumor imaging.

Purpose: Tumor-to-background ratio (TBR) is a critical metric in oncologic PET imaging. This study aims to enhance the TBR of [18F]FET in brain tumor imaging by substituting deuterium ("D") for hydrogen ("H"), thereby improving the diagnostic sensitivity and accuracy. Methods: [18F]d4-FET was synthe...

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Published in:European Journal of Nuclear Medicine & Molecular Imaging Vol. 52; no. 3; pp. 864 - 876
Main Authors: Hou, Lu, Chen, Zhiyong, Chen, Fanfan, Sheng, Lianghe, Ye, Weijian, Dai, Yingchu, Guo, Xiaoyu, Dong, Chenchen, Li, Guocong, Liao, Kai, Li, Yinlong, Ma, Jie, Wei, Huiyi, Ran, Wenqing, Shang, Jingjie, Ling, Xueying, Patel, Jimmy S., Liang, Steven H., Xu, Hao, Wang, Lu
Format: Journal Article
Published: Springer Nature Feb2025
Online Access:View this record in EBSCOhost
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      dt: Feb2025
      vid: 52
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      pub: Springer Nature
      place: New York, New York
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        182409450
        180572854
        10.1007/s00259-024-06964-8
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        atl: Synthesis, preclinical assessment, and first-in-human study of [18F]d4-FET for brain tumor imaging.
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        au:
          Hou, Lu
          Chen, Zhiyong
          Chen, Fanfan
          Sheng, Lianghe
          Ye, Weijian
          Dai, Yingchu
          Guo, Xiaoyu
          Dong, Chenchen
          Li, Guocong
          Liao, Kai
          Li, Yinlong
          Ma, Jie
          Wei, Huiyi
          Ran, Wenqing
          Shang, Jingjie
          Ling, Xueying
          Patel, Jimmy S.
          Liang, Steven H.
          Xu, Hao
          Wang, Lu
        affil: https://ror.org/05d5vvz89 Center of Cyclotron and PET Radiopharmaceuticals, Department of Nuclear Medicine, & Key Laboratory of Basic and Translational Research On Radiopharmaceuticals, The First Affiliated Hospital of Jinan University, 510630, Guangzhou, China
      sug:
      ab: Purpose: Tumor-to-background ratio (TBR) is a critical metric in oncologic PET imaging. This study aims to enhance the TBR of [18F]FET in brain tumor imaging by substituting deuterium ("D") for hydrogen ("H"), thereby improving the diagnostic sensitivity and accuracy. Methods: [18F]d4-FET was synthesised by two automated radiochemistry modules. Biodistribution studies and imaging efficacy were evaluated in vivo and ex vivo in rodent models, while metabolic stability and radiation dosimetry were assessed in non-human primates. Additionally, preliminary imaging evaluations were carried out in five brain tumor patients: three glioma patients underwent imaging with both [18F]d4-FET and [18F]FET, and two patients with brain metastases were imaged using [18F]d4-FET and [18F]FDG. Results: [18F]d4-FET demonstrated high radiochemical purity and yield. PET/MRI in rodent models demonstrated superior TBR for [18F]d4-FET compared to [18F]FET, and autoradiography showed tumor margins that correlated well with pathological extents. Studies in cynomolgus monkeys indicated comparable in vivo stability and effective dose with [18F]FET. In glioma patients, [18F]d4-FET showed enhanced TBR, while in patients with brain metastases, [18F]d4-FET displayed superior lesion delineation compared to [18F]FDG, especially in smaller metastatic sites. Conclusion: We successfully synthesized the novel PET radiotracer [18F]d4-FET, which retains the advantageous properties of [18F]FET while potentially enhancing TBR for glioma imaging. Preliminary studies indicate excellent stability, efficacy, and sensitivity of [18F]d4-FET, suggesting its potential in clinical evaluations of brain tumors. Trial registration: ChiCTR2400081576, registration date: 2024–03-05, https://www.chictr.org.cn/bin/project/edit?pid=206162
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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