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Imaging Correlates of Differential Expression of Indoleamine 2,3-Dioxygenase in Human Brain Tumors

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Abstract

Background

Tryptophan catabolism via the kynurenine pathway, mediated by indoleamine 2,3-dioxygenase (IDO), is a mechanism involved in tumor immunoresistance. Positron emission tomography (PET) with α-[11C]methyl-L-tryptophan (AMT) can quantify transport and metabolism of tryptophan in infiltrating gliomas and glioneuronal tumors. In the present study, we investigated whether increased tryptophan metabolism in brain tumors measured by PET is related to expression of IDO in resected brain tumor specimens.

Methods

IDO expression was assessed by immunohistochemistry in tumor specimens from 15 patients (median age, 34 years) with primary brain tumors who underwent AMT PET scanning before tumor resection. Patterns of IDO expression were compared between low- and high-grade tumors and also to AMT transport and metabolism measured on PET.

Results

IDO immunoreactivity was seen in tumor cells in six of seven low-grade tumors but only in one of eight high-grade tumors (p = 0.01); three of these latter tumors showed endothelial staining only. Low-grade neoplasms showed lower transport rate (p < 0.01) but higher metabolic rate (p = 0.003) for AMT as compared to high-grade tumors. AMT metabolic rates were lower in tumor samples with no or minimal IDO expression as compared to those with widespread IDO staining (p = 0.017).

Conclusion

Low-grade tumors show widespread IDO expression, while IDO expression in high-grade brain tumors can be absent or largely confined to endothelial cells. AMT PET can be useful to identify brain tumors with different profiles of IDO expression, thus providing a useful imaging marker for emerging treatments targeting tumor IDO activity.

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Acknowledgement

The authors thank Galina Rabkin, CNMT, Angela Wigeluk, CNMT, and Mei-li Lee, MS, for their technical assistance in performing the PET studies. They also thank Ms. Barbara Pruetz from the Department of Pathology for her expert assistance in the immunohistochemistry studies. The study was supported by a grant from the National Cancer Institute (CA-12341, to C. Juhasz).

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Authors and Affiliations

  1. Carman and Ann Adams Department of Pediatrics, School of Medicine, Wayne State University, Detroit, MI, USA

    Carlos E. A. Batista, Csaba Juhász, Otto Muzik, Harry T. Chugani, Sandeep Sood & Diane C. Chugani

  2. Department of Neurology, School of Medicine, Wayne State University, Detroit, MI, USA

    Csaba Juhász, Geoffrey Barger & Harry T. Chugani

  3. Department of Radiology, School of Medicine, Wayne State University, Detroit, MI, USA

    Otto Muzik, Harry T. Chugani & Diane C. Chugani

  4. Department of Pathology, School of Medicine, Wayne State University, Detroit, MI, USA

    William J. Kupsky

  5. Department of Neurosurgery, School of Medicine, Wayne State University, Detroit, MI, USA

    Sandeep Mittal & Sandeep Sood

  6. Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI, USA

    Csaba Juhász, Geoffrey Barger & Sandeep Mittal

  7. PET Center, Children’s Hospital of Michigan, Detroit, MI, USA

    Carlos E. A. Batista, Csaba Juhász, Otto Muzik, Harry T. Chugani, Pulak K. Chakraborty & Diane C. Chugani

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  1. Carlos E. A. Batista
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  2. Csaba Juhász
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Correspondence to Csaba Juhász.

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Batista, C.E.A., Juhász, C., Muzik, O. et al. Imaging Correlates of Differential Expression of Indoleamine 2,3-Dioxygenase in Human Brain Tumors. Mol Imaging Biol 11, 460–466 (2009). https://doi.org/10.1007/s11307-009-0225-0

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  • DOI: https://doi.org/10.1007/s11307-009-0225-0

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