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Increased tryptophan transport in epileptogenic dysembryoplastic neuroepithelial tumors

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Abstract

Dysembryoplastic neuroepithelial tumors (DNTs) are typically hypometabolic but can show increased amino acid uptake on positron emission tomography (PET). To better understand mechanisms of amino acid accumulation in epileptogenic DNTs, we combined quantitative α-[11C]methyl-l-tryptophan (AMT) PET with tumor immunohistochemistry. Standardized uptake values (SUVs) of AMT and glucose were measured in 11 children with temporal lobe DNT. Additional quantification for AMT transport and metabolism was performed in 9 DNTs. Tumor specimens were immunostained for the l-type amino acid transporter 1 (LAT1) and indoleamine 2,3-dioxygenase (IDO), a key enzyme of the immunomodulatory kynurenine pathway. All 11 tumors showed glucose hypometabolism, while mean AMT SUVs were higher than normal cortex in eight DNTs. Further quantification showed increased AMT transport in seven and high AMT metabolic rates in three DNTs. Two patients showing extratumoral cortical increases of AMT SUV had persistent seizures despite complete tumor resection. Resected DNTs showed moderate to strong LAT1 and mild to moderate IDO immunoreactivity, with the strongest expression in tumor vessels. These results indicate that accumulation of tryptophan in DNTs is driven by high amino acid transport, mediated by LAT1, which can provide the substrate for tumoral tryptophan metabolism through the kynurenine pathway, that can produce epileptogenic metabolites. Increased AMT uptake can extend to extratumoral cortex, and presence of such cortical regions may increase the likelihood of recurrent seizures following surgical excision of DNTs.

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Acknowledgments

The study was supported by a grant from the National Institutes of Health (NIH, CA123451 to C.J.) and Start-up Funds (Wayne State University School of Medicine to S.M.). We thank Pulak Chakraborty, PhD, for AMT radiochemistry and Sam Kiousis, BS, for skilled technical assistance with immunohistochemistry. We are grateful to the entire staff at the PET Center, Children’s Hospital of Michigan, who provided invaluable technical help in performing the PET scans.

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Authors and Affiliations

  1. PET Center, Children’s Hospital of Michigan, 3901 Beaubien Blvd, Detroit, MI, 48201, USA

    Bálint Alkonyi, Diane C. Chugani, Otto Muzik, Harry T. Chugani & Csaba Juhász

  2. Departments of Pediatrics, Wayne State University, Detroit, MI, USA

    Bálint Alkonyi, Otto Muzik, Harry T. Chugani & Csaba Juhász

  3. Departments of Neurology, Wayne State University, Detroit, MI, USA

    Harry T. Chugani & Csaba Juhász

  4. Departments of Neurosurgery, Wayne State University, Detroit, MI, USA

    Sandeep Mittal & Sandeep Sood

  5. Departments of Radiology, Wayne State University, Detroit, MI, USA

    Diane C. Chugani & Otto Muzik

  6. Departments of Pathology, Wayne, State University, Detroit, MI, USA

    William J. Kupsky

  7. The Barbara Ann Karmanos Cancer Institute, Detroit, MI, USA

    Sandeep Mittal, Ian Zitron, William J. Kupsky & Csaba Juhász

Authors
  1. Bálint Alkonyi
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  2. Sandeep Mittal
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Correspondence to Csaba Juhász.

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Alkonyi, B., Mittal, S., Zitron, I. et al. Increased tryptophan transport in epileptogenic dysembryoplastic neuroepithelial tumors. J Neurooncol 107, 365–372 (2012). https://doi.org/10.1007/s11060-011-0750-y

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  • DOI: https://doi.org/10.1007/s11060-011-0750-y

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