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Tryptophan PET in pretreatment delineation of newly-diagnosed gliomas: MRI and histopathologic correlates

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Abstract

Pretreatment delineation of infiltrating glioma volume remains suboptimal with current neuroimaging techniques. Gadolinium-enhanced T1-weighted (T1-Gad) MR images often underestimate the true extent of the tumor, while T2-weighted images preferentially highlight peritumoral edema. Accumulation of α-[11C]methyl-l-tryptophan (AMT) on positron emission tomography (PET) has been shown in gliomas. To determine whether increased uptake on AMT–PET would detect tumor-infiltrated brain tissue outside the contrast-enhancing region and differentiate it from peritumoral vasogenic edema, volumes and spatial concordance of T1-Gad and T2 MRI abnormalities as well as AMT–PET abnormalities were analyzed in 28 patients with newly-diagnosed WHO grade II–IV gliomas. AMT-accumulating grade I meningiomas were used to define an AMT uptake cutoff threshold that detects the tumor but excludes peri-meningioma vasogenic edema. Tumor infiltration in AMT-accumulating areas was studied in stereotactically-resected specimens from patients with glioblastoma. In the 28 gliomas, mean AMT–PET-defined tumor volumes were greater than the contrast-enhancing volume, but smaller than T2 abnormalities. Volume of AMT-accumulating tissue outside MRI abnormalities increased with higher tumor proliferative index and was the largest in glioblastomas. Tumor infiltration was confirmed by histopathology from AMT-positive regions outside contrast-enhancing glioblastoma mass, while no or minimal tumor cells were found in AMT-negative specimens. These results demonstrate that increased AMT accumulation on PET detects glioma-infiltrated brain tissue extending beyond the contrast-enhanced tumor mass. While tryptophan uptake is low in peritumoral vasogenic edema, AMT–PET can detect tumor-infiltrated brain outside T2-lesions. Thus, AMT–PET may assist pretreatment delineation of tumor infiltration, particularly in high-grade gliomas.

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Acknowledgments

The study was supported by a grant (R01 CA123451 to C.J.) from the National Cancer Institute, Start-up Funds (Wayne State University School of Medicine to S.M.) and a Strategic Research Initiative Grant from the Karmanos Cancer Institute (to S.M. and C.J.). We thank Hancheng Cai, PhD and Thomas Mangner, PhD, for assistance in PET radiochemistry. We thank Janet Barger, RN, Kelly Forcucci, RN, and Cathie Germain, MA for assisting patient recruitment and scheduling, as well as Natasha L. Robinette, MD, and Alit Yousif, MD, for reviewing the clinical MRI scans. 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.

Conflict of interest

None of the authors report any conflict of interest or financial disclosure.

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Authors and Affiliations

  1. PET Center and Translational Imaging Laboratory, Children’s Hospital of Michigan, Detroit, MI, USA

    David O. Kamson, Csaba Juhász, Pulak K. Chakraborty & Otto Muzik

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

    Csaba Juhász & Geoffrey R. Barger

  3. Department of Pediatrics, Wayne State University, Detroit, MI, USA

    Csaba Juhász & Otto Muzik

  4. The Karmanos Cancer Institute, Detroit, MI, USA

    Csaba Juhász, William J. Kupsky, Geoffrey R. Barger & Sandeep Mittal

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

    Amy Buth & Sandeep Mittal

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

    William J. Kupsky

  7. Department of Radiology, Wayne State University, Detroit, MI, USA

    Pulak K. Chakraborty & Otto Muzik

  8. Departments of Neurology and Pediatrics, Wayne State University School of Medicine, PET Center and Translational Imaging Laboratory, Children’s Hospital of Michigan, 3901 Beaubien Street, Detroit, MI, 48201, USA

    Csaba Juhász

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  1. David O. Kamson
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Correspondence to Csaba Juhász.

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Kamson, D.O., Juhász, C., Buth, A. et al. Tryptophan PET in pretreatment delineation of newly-diagnosed gliomas: MRI and histopathologic correlates. J Neurooncol 112, 121–132 (2013). https://doi.org/10.1007/s11060-013-1043-4

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