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A bis-boron boramino acid PET tracer for brain tumor diagnosis

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

A Correction to this article was published on 22 March 2024

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Abstract

Purpose

Boramino acids are a class of amino acid biomimics that replace the carboxylate group with trifluoroborate and can achieve the 18F-labeled positron emission tomography (PET) and boron neutron capture therapy (BNCT) with identical chemical structure.

Methods

This study reports a trifluoroborate-derived boronophenylalanine (BBPA), a derived boronophenylalanine (BPA) for BNCT, as a promising PET tracer for tumor imaging.

Results

Competition inhibition assays in cancer cells suggested the cell accumulation of [18F]BBPA is through large neutral amino acid transporter type-1 (LAT-1). Of note, [18F]BBPA is a pan-cancer probe that shows notable tumor uptake in B16-F10 tumor-bearing mice. In the patients with gliomas and metastatic brain tumors, [18F]BBPA-PET shows good tumor uptake and notable tumor-to-normal brain ratio (T/N ratio, 18.7 ± 5.5, n = 11), higher than common amino acid PET tracers. The [18F]BBPA-PET quantitative parameters exhibited no difference in diverse contrast-enhanced status (P = 0.115–0.687) suggesting the [18F]BBPA uptake was independent from MRI contrast-enhancement.

Conclusion

This study outlines a clinical trial with [18F]BBPA to achieve higher tumor-specific accumulation for PET, provides a potential technique for brain tumor diagnosis, and might facilitate the BNCT of brain tumors.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by National Natural Science Foundation of China (Grant No. 22225603), Ministry of Science and Technology of the People’s Republic of China (Grant No. 2021YFA1601400), Beijing Municipal Natural Science Foundation (Grant No. Z200018), and Changping Laboratory to Zhibo Liu, Science Foundation of Peking University Cancer Hospital (Grant No. PY202309) to Zhu Li, Beijing Municipal Natural Science Foundation (Grant No.7232351), Special Research Fund for Central Universities, and Peking Union Medical College (Grant No. 3332022024), and National Natural Science Foundation of China (Grant No. 32301152) to Ziren Kong, and the National High Level Hospital Clinical Research Funding(Grant No. 2022-PUMCH-A-019) to Yu Wang. We thank the facility support from the Analytical Instrumentation Center of Peking University.

Author information

Author notes

  1. Zhu Li and Junyi Chen contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China

    Zhu Li, Nan Li, Zhi Yang & Zhibo Liu

  2. Beijing National Laboratory for Molecular Sciences, Radiochemistry and Radiation Chemistry Key Laboratory of Fundamental Science, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, NMPA Key Laboratory for Research and Evaluation of Radiopharmaceuticals, Peking University, Beijing, China

    Junyi Chen, Mengxin Xu, Bo-Shuai Mu & Zhibo Liu

  3. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Ziren Kong, Yixin Shi, Wenbin Ma & Yu Wang

  4. Department of Head and Neck Surgery, National Clinical Research Center for Cancer/Cancer Hospital, National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Ziren Kong

  5. Peking University-Tsinghua University Center for Life Sciences, Beijing, China

    Zhibo Liu

  6. Changping Laboratory, Beijing, China

    Zhibo Liu

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  1. Zhu Li
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Contributions

Zhibo Liu and Yu Wang conceived the study; Junyi Chen performed material synthesis, characterization and chemical analysis; Zhu Li, Junyi Chen and Yixin Shi assisted by Mengxin Xu performed most of the experiments; Nan Li, Wenbin Ma, Bo-Shuai Mu and Zhi Yang provided technical assistance and suggestions. Yu Wang, Zhi Yang, Ziren Kong and Zhibo Liu analysed the data. Ziren Kong, Junyi Chen and Zhibo Liu wrote the manuscript with input from all authors. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Yu Wang or Zhibo Liu.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki, approved by the Institutional Review Board of the Peking University Cancer Hospital (ID 2021KT38), and registered at clinicaltrials.gov (NCT05987098). Written informed consent was obtained from all participants.

Competing Interests

Junyi Chen, Mengxin Xu, and Zhibo Liu are consultants of Boomray Pharmaceuticals (Beijing) Co., Ltd. No other potential conflicts of interest relevant to this article exist.

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The authors regret that the version of Figure 3 that appears in the original published article is incorrect. The correct and incorrect versions of the figure is provided in the erratum article.

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Li, Z., Chen, J., Kong, Z. et al. A bis-boron boramino acid PET tracer for brain tumor diagnosis. Eur J Nucl Med Mol Imaging 51, 1703–1712 (2024). https://doi.org/10.1007/s00259-024-06600-5

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