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

Zhu Li1, Junyi Chen2, Ziren Kong3,4, Yixin Shi3, Mengxin Xu2, Bo-Shuai Mu2, Nan Li1, Wenbin Ma3, Zhi Yang1, Yu Wang3, Zhibo Liu1,2,5,6
1Key Laboratory of Carcinogenesis and Translational Research, Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, China
2Beijing 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
3Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
4Department 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
5Peking University-Tsinghua University Center for Life Sciences, Beijing, China
6Changping Laboratory, Beijing, China

Tóm tắt

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

Tài liệu tham khảo

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