Boronotyrosine, a Borylated Amino Acid Mimetic with Enhanced Solubility, Tumor Boron Delivery, and Retention for the Re-emerging Boron Neutron Capture Therapy Field

J Med Chem. 2023 Oct 12;66(19):13809-13820. doi: 10.1021/acs.jmedchem.3c01265. Epub 2023 Sep 20.

Abstract

Boron neutron capture therapy (BNCT) is a re-emerging binary cellular level cancer intervention that occurs through the interaction of a cancer-specific 10boron (10B) drug and neutrons. We created a new 10B drug, 3-borono-l-tyrosine (BTS), that improves on the characteristics of the main historical BNCT drug 4-borono-l-phenylalanine (BPA). BTS has up to 4 times greater uptake in vitro than BPA and increased cellular retention. Like BPA, BTS uptake is mediated by the l-type amino acid transporter-1 (LAT1) but is less sensitive to natural amino acid competition. BTS can be formulated and bolus dosed at much higher levels than BPA, resulting in 2-3 times greater boron delivery in vivo. Fast blood clearance and greater tumor boron delivery result in superior tumor-to-blood ratios. BTS boron delivery appears to correlate with LAT1 expression. BTS is a promising boron delivery drug that has the potential to improve modern BNCT interventions.

MeSH terms

  • Amino Acids*
  • Boron
  • Boron Compounds / chemistry
  • Boron Neutron Capture Therapy* / methods
  • Cell Line, Tumor
  • Phenylalanine / chemistry
  • Solubility

Substances

  • Amino Acids
  • Boron
  • Phenylalanine
  • Boron Compounds