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J Neurooncol. 2019 Jan;141(1):111-120. doi: 10.1007/s11060-018-03013-x. Epub 2018 Nov 10.

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

Lukas RV1,2,3, Juhász C4,5, Wainwright DA6,7,8, James CD6,7,8, Kennedy E9, Stupp R10,6,7,8, Lesniak MS6,7,8.

Author information

1
Department of Neurology, Northwestern University, 710 N. Lake Shore Drive, Abbott Hall 1114, Chicago, IL, 60611, USA. rimas.lukas@nm.org.
2
Lurie Cancer Center, Northwestern University, Chicago, USA. rimas.lukas@nm.org.
3
Lou & Jean Malnati Brain Tumor Institute, Northwestern University, Chicago, USA. rimas.lukas@nm.org.
4
Neurology, and Neurosurgery, Department of Pediatrics, Wayne State University, Detroit, USA.
5
Karmanos Cancer Institute, Wayne State University, Detroit, USA.
6
Department of Neurosurgery, Northwestern University, Chicago, USA.
7
Lurie Cancer Center, Northwestern University, Chicago, USA.
8
Lou & Jean Malnati Brain Tumor Institute, Northwestern University, Chicago, USA.
9
NewLink Genetics, Ames, USA.
10
Department of Neurology, Northwestern University, 710 N. Lake Shore Drive, Abbott Hall 1114, Chicago, IL, 60611, USA.

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.

KEYWORDS:

1-MT; AMT; Biomarker; Glioblastoma; IDO; Indoximod; PET

PMID:
30415456
PMCID:
PMC6414051
[Available on 2020-01-01]
DOI:
10.1007/s11060-018-03013-x
[Indexed for MEDLINE]

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