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01-01-2019 | Clinical Study

Imaging tryptophan uptake with positron emission tomography in glioblastoma patients treated with indoximod

Authors: Rimas V. Lukas, Csaba Juhász, Derek A. Wainwright, Charles David James, Eugene Kennedy, Roger Stupp, Maciej S. Lesniak

Published in: Journal of Neuro-Oncology | Issue 1/2019

Abstract

Introduction

Glioblastoma (GBM) is the most frequent and aggressive primary tumor of the central nervous system, accounting for over 50% of all primary malignant gliomas arising in the adult brain. Even after surgical resection, adjuvant radiotherapy (RT) and temozolomide (TMZ) chemotherapy, as well as tumor-treating fields, the median survival is only 15–20 months. We have identified a pathogenic mechanism that contributes to the tumor-induced immunosuppression in the form of increased indoleamine 2,3 dioxygenase 1 (IDO1) expression; an enzyme that metabolizes the essential amino acid, tryptophan (Trp), into kynurenine (Kyn). However, real-time measurements of IDO1 activity has yet to become mainstream in clinical protocols for assessing IDO1 activity in GBM patients.

Methods

Pre-treatment and on-treatment α-[¹¹C]-methyl-l-Trp (AMT) positron emission tomography (PET) with co-registered MRI was performed on patients with recurrent GBM treated with the IDO1 pathway inhibitor indoximod (D1-MT) and TMZ.

Results

Regional intratumoral variability of AMT within enhancing and non-enhancing tumor was noted at baseline. On treatment imaging revealed decreased regional uptake suggesting IDO1 pathway modulation with treatment.

Conclusions

Here, we have validated the ability to use PET of the Trp probe, AMT, for use in visualizing and quantifying intratumoral Trp uptake in GBM patients treated with an IDO1 pathway inhibitor. These data serve as rationale to utilize AMT-PET imaging in the future evaluation of GBM patients treated with IDO1 enzyme inhibitors.

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Title: Imaging tryptophan uptake with positron emission tomography in glioblastoma patients treated with indoximod
Authors: Rimas V. Lukas
Csaba Juhász
Derek A. Wainwright
Charles David James
Eugene Kennedy
Roger Stupp
Maciej S. Lesniak
Publication date: 01-01-2019
Publisher: Springer US
Published in: Journal of Neuro-Oncology / Issue 1/2019
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-018-03013-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Imaging tryptophan uptake with positron emission tomography in glioblastoma patients treated with indoximod

Abstract

Introduction

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

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