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Journal of Neuro-Oncology

, Volume 102, Issue 3, pp 409–415 | Cite as

Differential kinetics of α-[11C]methyl-l-tryptophan on PET in low-grade brain tumors

  • Csaba Juhász
  • Otto Muzik
  • Diane C. Chugani
  • Harry T. Chugani
  • Sandeep Sood
  • Pulak K. Chakraborty
  • Geoffrey R. Barger
  • Sandeep Mittal
Clinical Study – Patient Study

Abstract

Increased tryptophan metabolism via the kynurenine pathway is a major mechanism of tumor immuno-resistance. α-[11C]Methyl-l-tryptophan (AMT) is a positron emission tomography (PET) tracer for tryptophan catabolism, and increased AMT uptake has been demonstrated in brain tumors. In this study we evaluated the use of AMT PET for detection of low-grade gliomas and glioneuronal tumors, and determined if kinetic parameters of AMT uptake can differentiate among tumor types. AMT PET images were obtained in 23 patients with newly diagnosed low-grade brain tumors (WHO grade II gliomas and WHO grade I dysembryoplastic neuroepithelial tumors [DNETs]). Kinetic variables, including the unidirectional uptake rate (K-complex) and volume of distribution (VD; which characterizes tracer transport), were measured using a graphical approach from tumor dynamic PET and blood-input data, and metabolic rates (\( k^{\prime}_{3} \)) were also calculated. These values as well as tumor/cortex ratios were compared across tumor types. AMT PET showed increased tumor/cortex K-complex (n = 16) and/or VD ratios (n = 15) in 21/23 patients (91%), including 11/13 tumors with no gadolinium enhancement on MRI. No increases in AMT were seen in an oligodendroglioma and a DNET. Astrocytomas and oligoastrocytomas showed higher \( k^{\prime}_{3} \) tumor/cortex ratios (1.66 ± 0.46) than oligodendrogliomas (0.96 ± 0.21; P = 0.001) and DNETs (0.75 ± 0.39; P < 0.001). These results demonstrate that AMT PET identifies most low-grade gliomas and DNETs by high uptake, even if these tumors are not contrast-enhancing on MRI. Kinetic analysis of AMT uptake shows significantly higher tumor/cortex tryptophan metabolic ratios in astrocytomas and oligoastrocytomas in comparison with oligodendrogliomas and DNETs.

Keywords

Gliomas Astrocytoma Low-grade Positron emission tomography Tryptophan Metabolism 

Notes

Acknowledgments

The study was supported by a grant from the National Cancer Institute (#CA123451, to C. Juhász). The authors thank Cathie Germain, MA, Angela Wigeluk, CNMT, Carole Clapko, CNMT, Galina Rabkin, CNMT, Melissa Burkett, CNMT, Andrew Mosqueda, CNMT, Anna DeBoard, RN, Jane Cornett, RN, and Mei-li Lee, MS, for their assistance in patient recruitment and preparation, as well as performing the PET studies.

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Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Csaba Juhász
    • 1
    • 2
    • 3
    • 6
  • Otto Muzik
    • 1
    • 2
    • 3
    • 4
  • Diane C. Chugani
    • 1
    • 2
    • 4
  • Harry T. Chugani
    • 1
    • 2
    • 3
  • Sandeep Sood
    • 2
    • 5
  • Pulak K. Chakraborty
    • 1
    • 4
  • Geoffrey R. Barger
    • 3
    • 6
  • Sandeep Mittal
    • 5
    • 6
  1. 1.PET Center, Children’s Hospital of MichiganWayne State University School of MedicineDetroitUSA
  2. 2.Carman and Ann Adams Department of PediatricsWayne State University School of MedicineDetroitUSA
  3. 3.Department of NeurologyWayne State University School of MedicineDetroitUSA
  4. 4.Department of RadiologyWayne State University School of MedicineDetroitUSA
  5. 5.Department of NeurosurgeryWayne State University School of MedicineDetroitUSA
  6. 6.The Barbara Ann Karmanos Cancer InstituteDetroitUSA

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