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

Eur J Nucl Med Mol Imaging. 2024 May;51(6):1703-1712. doi: 10.1007/s00259-024-06600-5. Epub 2024 Jan 9.

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.

Keywords: Boramino acid; Brain tumor; Positron emission tomography.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Boron Compounds / pharmacokinetics
  • Brain Neoplasms* / diagnostic imaging
  • Cell Line, Tumor
  • Female
  • Humans
  • Large Neutral Amino Acid-Transporter 1 / metabolism
  • Male
  • Mice
  • Middle Aged
  • Positron-Emission Tomography* / methods
  • Radioactive Tracers
  • Radiopharmaceuticals / pharmacokinetics

Substances

  • Boron Compounds
  • Radioactive Tracers
  • Large Neutral Amino Acid-Transporter 1
  • Radiopharmaceuticals