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

Abstract

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.