Abstract 4543: Uptake of 18F-FDOPA analogue 3H-L-DOPA is mediated by large neutral amino acid transporter LAT1 in human glioblastoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.4543-4543
• Main Authors: Youland, Ryan S., Kitange, Gaspar J., Pokorny, Jenny L., Sarkaria, Jann N.
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-4543

INTRODUCTION: The L-Type amino acid transporter 1 (LAT1) transports large neutral amino acids across the plasma membrane in a variety of cells. Positron emission tomography (PET) imaging with the amino acid tracer 6-18F-fluoro-L-dopa (18F-FDOPA) provides useful histological information in human gliomas in addition to providing better localizing information then CT or MRI alone. This study is the first to correlate LAT1 expression with uptake of the 18F-FDOPA analog, 3H-L-DOPA in human glioblastomas. METHODS: Endogenous expression of LAT1 was evaluated in two established glioblastoma multiforme (GBM) cell lines and three primary GBM xenografts using Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Uptake of FDOPA was assessed in vitro using 3H-L-DOPA as an analog to 18F-FDOPA. Knockdown of LAT1 expression was achieved by lentiviral expression of anti-LAT1 shRNA in GBM lines with high LAT1 expression. The effect of LAT1 knockdown on 3H-L-DOPA uptake was then quantified. RESULTS: Results from Western blotting and qRT-PCR demonstrate that LAT1 is variably expressed in GBM. Levels of 3H-L-DOPA uptake were directly related to LAT1 expression (p