Send to

Choose Destination
Cancer Res. 2009 Mar 1;69(5):2126-32. doi: 10.1158/0008-5472.CAN-08-2345. Epub 2009 Feb 24.

L-amino acid transporter-1 and boronophenylalanine-based boron neutron capture therapy of human brain tumors.

Author information

Department of Neurosurgery, Molecular Neurooncology Laboratory, The University of Birmingham, Queen Elizabeth Hospital Neuroscience Centre, Edgbaston, Birmingham, United Kingdom.


The system l-amino acid transporter-1 (LAT-1) imports p-boronophenylalanine (BPA) into cells and may play a major role in the effectiveness of BPA-based boron neutron capture therapy. The functional status of LAT-1 and its relationship to cell proliferation were simultaneously examined in the same section of human tumor material using a dual-labeling technique. The uptake of BPA (boron inductively coupled plasma mass spectrometry) was profiled in the presence of agonists and antagonists in fresh tumor explants. The number of LAT-1-expressing cells (mean +/- SD) was three times higher than that of proliferating cell nuclear antigen (PCNA)-expressing cells (71.5 +/- 17.02% versus 23.8 +/- 16.5%; P < 0.0001; n = 38 glioblastoma and metastatic tumors). There was no correlation between PCNA cells and the number of LAT-1/PCNA double-stained cells, and not all PCNA-expressing cells coexpressed LAT-1. Boron uptake reached 30 +/- 15 mug/g of wet weight of tissue by 4 hours both in tumor and brain around tumor tissue containing tumor cells compared with time 0 (P < 0.005; n = 4 glioblastoma tumors). This uptake was inhibited by both phenylalanine and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. These LAT-1 data indicate that BPA-based boron neutron capture therapy might affect up to 70% of tumor cells, representing a three times higher proportion of tumor cells than their cell cycle status might suggest. Cells expressing PCNA, but not LAT-1, will require a different therapeutic strategy.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center