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3‐ 18 F‐ l ‐α‐methyl‐tyrosine ([ 18 F] FAMT ), a  PET  probe for tumor imaging, has advantages of high cancer‐specificity and lower physiologic background.  FAMT ‐ PET  has been proved useful in clinical studies for the prediction of prognosis, the assessment of therapy response and the differentiation of malignant tumors from inflammation and benign lesions. The tumor uptake of [ 18 F] FAMT  in  PET  is strongly correlated with the expression of L‐type amino acid transporter 1 ( LAT 1), an isoform of system L upregulated in cancers. In this study, to assess the transporter‐mediated mechanisms in  FAMT  uptake by tumors, we examined amino acid transporters for  FAMT  transport. We synthesized [ 14 C] FAMT  and measured its transport by human amino acid transporters expressed in  Xenopus  oocytes. The transport of  FAMT  was compared with that of  l ‐methionine, a well‐studied amino acid  PET  probe. The significance of  LAT 1 in  FAMT  uptake by tumor cells was confirmed by si RNA  knockdown. Among amino acid transporters, [ 14 C] FAMT  was specifically transported by  LAT 1, whereas  l ‐[ 14 C]methionine was taken up by most of the transporters. K m  of  LAT 1‐mediated [ 14 C] FAMT  transport was 72.7 μM, similar to that for endogenous substrates. Knockdown of  LAT 1 resulted in the marked reduction of [ 14 C] FAMT  transport in HeLa S3 cells, confirming the contribution of  LAT 1 in  FAMT  uptake by tumor cells.  FAMT  is highly specific to cancer‐type amino acid transporter  LAT 1, which explains the cancer‐specific accumulation of [ 18 F] FAMT  in  PET . This,  vice versa , further supports the cancer‐specific expression of  LAT 1. This study has established  FAMT  as a  LAT 1‐specific molecular probe to monitor the expression of a potential tumor biomarker  LAT 1.

Specific transport of 3‐fluoro‐ l ‐α‐methyl‐tyrosine by LAT 1 explains its specificity to malignant tumors in imaging