RRC ID 77385
Author Hirano F, Kondo N, Murata Y, Sudani A, Temma T.
Title Assessing the effectiveness of fluorinated and α-methylated 3-boronophenylalanine for improved tumor-specific boron delivery in boron neutron capture therapy.
Journal Bioorg Chem
Abstract A [10B]boron agent and a nuclear imaging probe for pharmacokinetic estimation form the fundamental pair in successful boron neutron capture therapy (BNCT). However, 4-[10B]borono-l-phenylalanine (BPA), used in clinical BNCT, has undesirable water solubility and tumor selectivity. Therefore, we synthesized fluorinated and α-methylated 3-borono-l-phenylalanine (3BPA) derivatives to realize improved water solubility, tumor targetability, and biodistribution. All 3BPA derivatives exhibited over 10 times higher water solubility than BPA. Treatment with α-methylated 3BPA derivatives resulted in decreased cell uptake via l-type amino acid transporter (LAT) 2 while maintaining LAT1 recognition, thereby significantly improving LAT1/LAT2 selectivity. Biodistribution studies showed that fluorinated α-methyl 3BPA derivatives exhibited reduced boron accumulation in nontarget tissues, including muscle, skin, and plasma. Consequently, these derivatives demonstrated significantly improved tumor-to-normal tissue ratios compared to 3BPA and BPA. Overall, fluorinated α-methyl 3BPA derivatives with the corresponding radiofluorinated compounds hold potential as promising agents for future BNCT/PET theranostics.
Volume 142
Pages 106940
Published 2023-11-2
DOI 10.1016/j.bioorg.2023.106940
PII S0045-2068(23)00601-6
PMID 37939508
IF 4.831
Human and Animal Cells T3M-4(RCB1021)