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Correlation of l-methyl-11C-methionine (MET) uptake with l-type amino acid transporter 1 in human gliomas

  • Clinical Study - Patient Study
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Abstract

l-Type amino acid transporter 1 (LAT1) is a neutral amino acid transport system and is a major route for the transport of large neutral amino acids, including methionine, through the plasma membrane. LAT1 requires the heavy chain of 4F2 cell surface antigen (4F2hc) for its functional expression. Positron emission tomography (PET) with l-[methyl-11C] methionine (MET) provides information about amino acid metabolism in brain tumors. We conducted a clinicopathologic study to elucidate the correlation of LAT1 and 4F2hc expression with MET uptake in patients with newly diagnosed human gliomas. Thirty-three newly diagnosed glioma patients were enrolled in this study. Uptake of MET in the tumor was evaluated with the maximum standardized uptake value (SUVmax). Expression of the LAT1, 4F2hc, and CD34, and Ki-67 labeling index of the tumor were analyzed by immunohistochemical staining, and the correlation with the SUVmax in the tumors was examined. Expression of LAT1 and 4F2hc was higher in high-grade gliomas than in low-grade gliomas. The grade of LAT1 immunostaining increased with glioma grade. LAT1 was mainly expressed in the tumor cytoplasm and vascular endothelium and 4F2hc was mainly expressed in the tumor cytoplasm and plasma membrane. Expression of LAT1 but not 4F2hc was significantly correlated with MET SUVmax. Expression of LAT1 in the tumor vascular endothelium is significantly correlated with CD34 positive microvessel density. In conclusion, MET SUVmax correlates with LAT1 expression in the tumor in newly diagnosed gliomas. MET transport may be increased by an increased number of microvessels combined with a higher density or activity of LAT1 in the tumor endothelial cells in high-grade gliomas. Use of MET-PET as a molecular target combined with anti-angiogenesis in glioma therapy should be addressed in future studies.

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Acknowledgment

Shuichi Okubo and Hai-Ning Zhen contributed equally to this study. The authors appreciate the excellent technical support of the radiological technologist at our institution.

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Authors and Affiliations

  1. Department of Neurological Surgery, Faculty of Medicine, Kagawa University, 1750-1 Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Shuichi Okubo, Hai-Ning Zhen, Nobuyuki Kawai & Takashi Tamiya

  2. Department of Radiology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Yoshihiro Nishiyama

  3. Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Reiji Haba

  4. Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China

    Hai-Ning Zhen

Authors
  1. Shuichi Okubo
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  2. Hai-Ning Zhen
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  3. Nobuyuki Kawai
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  4. Yoshihiro Nishiyama
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  5. Reiji Haba
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  6. Takashi Tamiya
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Correspondence to Nobuyuki Kawai.

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Okubo, S., Zhen, HN., Kawai, N. et al. Correlation of l-methyl-11C-methionine (MET) uptake with l-type amino acid transporter 1 in human gliomas. J Neurooncol 99, 217–225 (2010). https://doi.org/10.1007/s11060-010-0117-9

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  • DOI: https://doi.org/10.1007/s11060-010-0117-9

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