Comparison of L-type amino acid transporter 1 expression and L-[3-18F]-α-methyl tyrosine uptake in outcome of non-small cell lung cancer.
OBJECTIVE
L-Type amino acid transporter 1 (LAT1) has associated with tumor growth and poor outcome of patients with non-small cell lung cancer (NSCLC). L-[3-(18)F]-α-methyl tyrosine ((18)F-FAMT) is an amino acid tracer for positron emission tomography (PET) imaging, and (18)F-FAMT uptake is mediated by LAT1. The purpose of this study is to compare the prognostic significance of (18)F-FAMT uptake in the primary tumors with that of LAT1 expression in patients with NSCLC.


METHODS
Fifty-nine patients with NSCLC were enrolled in this study. All patients underwent (18)F-FAMT PET prior to resection of the tumor, and immunohistochemical staining of the resected tumors were performed to compare the (18)F-FAMT uptake and LAT1 expression. Uptake of (18)F-FAMT was evaluated using semiquantitative standardized uptake value (SUV(max)), and the cutoff value was determined to discriminate patients with high SUV(max) from those with low SUV(max). Expression of LAT1 was evaluated by the score of staining intensity through 1 to 4. SUV(max) and LAT1 expression were compared according to the clinicopathological variables.


RESULTS
The best discriminative cutoff value of (18)F-FAMT SUV(max) within the primary tumors was 1.6. The high SUV(max) (>1.6) in (18)F-FAMT PET was significantly associated with male, and positive LAT1 expression was significantly associated with male and nonadenocarcinoma. In the univariate analysis, high SUV(max) (>1.6) in (18)F-FAMT PET and positive LAT1 expression were significant predictor of the poor outcome. Multivariate analysis confirmed that positive LAT1 expression was an independent and significant factor for predicting poor prognosis in NSCLC (P=.035).


CONCLUSIONS
LAT1 expression is a stronger prognostic factor than (18)F-FAMT uptake in surgically resected NSCLC.
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Showa-machi, Maebashi, Gunma 371-8511, Japan. kkaira1970@yahoo.co.jp
Kyoichi
K
Kaira
Noboru
N
Oriuchi
Kimihiro
K
Shimizu
Hisao
H
Imai
Hideyuki
H
Tominaga
Noriko
N
Yanagitani
Noriaki
N
Sunaga
Takeshi
T
Hisada
Tamotsu
T
Ishizuka
Yoshikatsu
Y
Kanai
Tetsunari
T
Oyama
Masatomo
M
Mori
Keigo
K
Endo
D000328:Adult; D000368:Aged; D001692:Biological Transport; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D027283:Large Neutral Amino Acid-Transporter 1 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008781:Methyltyrosines / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
C105991:3-fluoro-alpha-methyltyrosine; D027283:Large Neutral Amino Acid-Transporter 1; D008781:Methyltyrosines