Amino Acid PET Imaging of the Early Metabolic Response During Tumor-Treating Fields (TTFields) Therapy in Recurrent Glioblastoma

Bosnyák, Edit; Barger, Geoffrey; Michelhaugh, Sharon K.; Robinette, Natasha; Amit-Yousif, Alit; Mittal, Sandeep; Juhász, Csaba

doi:10.1097/rlu.0000000000001942

Cited by 10 publications

(12 citation statements)

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“…In this case, [ 11 C]-AMT imaging before and after treatment allowed monitoring of tumor metabolism with higher sensitivity to tumor growth or regression than MRI alone. Amino acid PET has previously monitored treatment efficacy during bevacizumab and TTFields therapy in glioblastomas (20,28). TTFields has also been successful at reducing tumor burden and symptoms in glioblastoma (29).…”

Section: Discussionmentioning

confidence: 99%

“…In our center, the amino acid radiotracer alpha-[ 11 C] methyl-L-tryptophan ([ 11 C]-AMT) has been successfully used to identify and monitor epileptic and tumorous lesions in the brain (15)(16)(17)(18)(19)(20)(21)(22)(23). Tryptophan is an essential amino acid for protein synthesis; however, within the brain most of the tryptophan enters alternative pathways to produce serotonin, melatonin, tryptamine, and kynurenine (KYN).…”

Section: Introductionmentioning

confidence: 99%

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Multimodal neuroimaging of gliomatosis cerebri: a case series of four patients

Bonomi

John

Patel

et al. 2020

Acta Radiologica Open

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In the latest World Health Organization classification of brain tumors, gliomatosis cerebri has been redefined to varying subsets of diffuse gliomas; however, the term is still used to describe gliomas with infiltrative growth into three or more cerebral lobes. These tumors are frequently misdiagnosed and difficult to treat due to their atypical presentation using structural imaging modalities including computed tomography and T1/T2-weighted magnetic resonance imaging (MRI). In this retrospective case series, we compared clinical MRI to amino acid positron emission tomography (PET) to assess the potential value of PET in the assessment of the extent of tumor involvement and in monitoring disease progression. We report the clinical course and serial multimodal imaging findings of four patients. Each patient presented at varying points in disease progression with widespread glioma brain involvement and was evaluated at least once by amino acid PET using alpha-[11C]methyl-L-tryptophan ([11C]-AMT). Increased uptake of [11C]-AMT was detected in a subset of non-enhancing brain lesions and detected tumor invasion before MRI signs of tumor in some regions. Increased uptake of [11C]-AMT was also detected in tumorous regions not detected by perfusion MRI or MR spectroscopy. Metabolic response to treatment was also observed in two patients. Overall, these data are consistent with and expand upon previous reports using other amino acid PET tracers in gliomatosis and show the potential added value of this imaging modality to clinical MRI in the detection and monitoring of these diffusely infiltrative tumors.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Multimodal neuroimaging of gliomatosis cerebri: a case series of four patients

Bonomi

John

Patel

et al. 2020

Acta Radiologica Open

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“…Serial AMT-PET imaging has also been performed in several patients with recurrent GBM, prior to- and actively receiving-tumor treating fields therapy, and has demonstrated an interval decrease in intratumoral AMT uptake as a potential indication of a response to treatment. Some of the AMT-PET changes occurred prior to responses observed by conventional MRI imaging [35]. Thus, an interval decrease in AMT uptake ratios during indoximod treatment is unlikely to be associated with tumor progression, even if MRI showed progressive contrast enhancement.…”

Section: Discussionmentioning

confidence: 99%

“…In progressive GBM patients evaluated with the AMT-PET method, a higher intratumoral AMT rate of uptake was associated with shorter survival [34]. The conclusions of Kamson et al are based on the analysis of a single time point for each patient, although serial imaging of tumor for assessing the response to therapy has been reported in a limited number of patients [35]. Here, we report the initial results from a multi-time point AMT-PET imaging study for three GBM patients, with imaging prior to- and while on-treatment with the IDO1 pathway inhibitor, indoximod.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

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Introduction: Glioblastoma (GBM) is the most frequent and aggressive primary tumor of the central nervous system (CNS), 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 temozolomide. 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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“…After chemoradiation completion, newly diagnosed glioblastoma patients can be treated with tumor-treating fields therapy in addition to adjuvant temozolomide chemotherapy [105]. Initial studies suggest that amino acid PET might identify responding patients undergoing tumor-treating fields therapy, but it has to be considered that the response can also be related to the concurrently applied chemotherapy or delayed chemoradiation effects [106,107].…”

Section: Value Of Amino Acid Pet Tracers For Brain Tumor Patientsmentioning

confidence: 99%

Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors

et al. 2020

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The number of positron-emission tomography (PET) tracers used to evaluate patients with brain tumors has increased substantially over the last years. For the management of patients with brain tumors, the most important indications are the delineation of tumor extent (e.g., for planning of resection or radiotherapy), the assessment of treatment response to systemic treatment options such as alkylating chemotherapy, and the differentiation of treatment-related changes (e.g., pseudoprogression or radiation necrosis) from tumor progression. Furthermore, newer PET imaging approaches aim to address the need for noninvasive assessment of tumoral immune cell infiltration and response to immunotherapies (e.g., T-cell imaging). This review summarizes the clinical value of the landscape of tracers that have been used in recent years for the above-mentioned indications and also provides an overview of promising newer tracers for this group of patients.

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Amino Acid PET Imaging of the Early Metabolic Response During Tumor-Treating Fields (TTFields) Therapy in Recurrent Glioblastoma

Cited by 10 publications

References 10 publications

Multimodal neuroimaging of gliomatosis cerebri: a case series of four patients

Multimodal neuroimaging of gliomatosis cerebri: a case series of four patients

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

Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors

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