Comparison of 18F-GE-180 and dynamic 18F-FET PET in high grade glioma: a double-tracer pilot study

Unterrainer, Marcus; Fleischmann, Daniel; Diekmann, Caroline; Vomacka, Lena; Lindner, Simon; Vettermann, Franziska; Brendel, Matthias; Wenter, Vera; Ertl‐Wagner, Birgit; Herms, Jochen; Wetzel, Christian H.; Rupprecht, Rainer; Tonn, Joerg‐Christian; Belka, Claus; Bartenstein, Peter; Niyazi, Maximilian; Albert, Nathalie L.

doi:10.1007/s00259-018-4166-1

Cited by 56 publications

(78 citation statements)

References 45 publications

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“…Additionally, in almost all types of CNS pathologies, TSPO levels are increased, and in some psychiatric disorders, such as schizophrenia, the TSPO signal in PET is decreased [34]. Although TSPO ligands are widely used in molecular imaging in all sorts of CNS pathologies, little is known about the role of TSPO expression and neuroinflammation in glioblastoma patients and PET imaging with TSPO radioligands is not yet standard for the imaging of brain tumor patients [18,19,[35][36][37]. In this study, we could show that the expression of TSPO is higher in brain tumor samples compared to those from epilepsy patients.…”

Section: Discussionmentioning

confidence: 99%

Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells

Cai

Kirchleitner

Zhao

et al. 2020

IJMS

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Molecular imaging is essential for diagnosis and treatment planning for glioblastoma patients. Positron emission tomography (PET) with tracers for the detection of the solute carrier family 7 member 5 (SLC7A5; also known as the amino acid transporter light chain L system, LAT1) and for the mitochondrial translocator protein (TSPO) is successfully used to provide additional information on tumor volume and prognosis. The current approaches for TSPO-PET and the visualization of tracer ([18F] Fluoroethyltyrosine, FET) uptake by LAT1 (FET-PET) do not yet exploit the full diagnostic potential of these molecular imaging techniques. Therefore, we investigated the expression of TSPO and LAT1 in patient glioblastoma (GBM) samples, as well as in various GBM mouse models representing patient GBMs of different genetic subtypes. By immunohistochemistry, we found that TSPO and LAT1 are upregulated in human GBM samples compared to normal brain tissue. Next, we orthotopically implanted patient-derived GBM cells, as well as genetically engineered murine GBM cells, representing different genetic subtypes of the disease. To determine TSPO and LAT1 expression, we performed immunofluorescence staining. We found that both TSPO and LAT1 expression was increased in tumor regions of the implanted human or murine GBM cells when compared to the neighboring mouse brain tissue. While LAT1 was largely restricted to tumor cells, we found that TSPO was also expressed by microglia, tumor-associated macrophages, endothelial cells, and pericytes. The Cancer Genome Atlas (TCGA)-data analysis corroborates the upregulation of TSPO in a bigger cohort of GBM patient samples compared to tumor-free brain tissue. In addition, AIF1 (the gene encoding for the myeloid cell marker Iba1) was also upregulated in GBM compared to the control. Interestingly, TSPO, as well as AIF1, showed significantly different expression levels depending on the GBM genetic subtype, with the highest expression being exhibited in the mesenchymal subtype. High TSPO and AIF1 expression also correlated with a significant decrease in patient survival compared to low expression. In line with this finding, the expression levels for TSPO and AIF1 were also significantly higher in (isocitrate-dehydrogenase wild-type) IDHWT compared to IDH mutant (IDHMUT) GBM. LAT1 expression, on the other hand, was not different among the individual GBM subtypes. Therefore, we could conclude that FET- and TSPO-PET confer different information on pathological features based on different genetic GBM subtypes and may thus help in planning individualized strategies for brain tumor therapy in the future. A combination of TSPO-PET and FET-PET could be a promising way to visualize tumor-associated myeloid cells and select patients for treatment strategies targeting the myeloid compartment.

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Section: Discussionmentioning

confidence: 99%

Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells

Cai

Kirchleitner

Zhao

et al. 2020

IJMS

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“…The recently introduced TSPO ligand GE-180 labeled with [ 18 F] offers an increased binding specificity and was tested in patients with gliomas [113] and neuroinflammatory diseases such as multiple sclerosis [114][115][116]. Regarding the delineation of glioma extent, it has been demonstrated that the [ 18 F]GE-180 uptake volume is significantly larger than the volume of contrast enhancement [113,117]. However, when comparing [ 18 F]FET with [ 18 F]GE-180 uptake volumes intraindividually in terms of spatial distribution, the overlap is only moderate (Dice similarity coefficient, 0.55) despite comparable tumor volumes [117].…”

Section: Pet Imaging Of the Mitochondrial Translocator Proteinmentioning

confidence: 99%

“…Regarding the delineation of glioma extent, it has been demonstrated that the [ 18 F]GE-180 uptake volume is significantly larger than the volume of contrast enhancement [113,117]. However, when comparing [ 18 F]FET with [ 18 F]GE-180 uptake volumes intraindividually in terms of spatial distribution, the overlap is only moderate (Dice similarity coefficient, 0.55) despite comparable tumor volumes [117]. These differences might help to characterize glioma heterogeneity and warrant further studies with spatial correlation of imaging findings of [ 18 F]FET uptake to [ 18 F]GE-180 uptake with neuropathology.…”

Section: Pet Imaging Of the Mitochondrial Translocator Proteinmentioning

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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“…LGG and HGG of different subtypes (mainly astrocytoma and oligodendroglioma), showed that dynamic PET imaging using R-[ 11 C]PK11195 can discriminate between low-grade astrocytoma and oligodendrogliomas [94]. Due to the short half-life of carbon-11 and the relatively low TBR provided by R-[ 11 C]PK11195, a novel third generation 18 F-labeled TSPO targeting ligand named [ 18 F]GE-180 has been developed, which showed improved contrast in HGG patients [101,102].…”

Section: Diagnostic Imaging Of Upregulated (Membrane) Receptorsmentioning

confidence: 99%

The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors

Pruis

Dongen

Zanten

2020

IJMS

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This review highlights the added value of PET imaging in Central Nervous System (CNS) tumors, which is a tool that has rapidly evolved from a merely diagnostic setting to multimodal molecular diagnostics and the guidance of targeted therapy. PET is the method of choice for studying target expression and target binding behind the assumedly intact blood–brain barrier. Today, a variety of diagnostic PET tracers can be used for the primary staging of CNS tumors and to determine the effect of therapy. Additionally, theranostic PET tracers are increasingly used in the context of pharmaceutical and radiopharmaceutical drug development and application. In this approach, a single targeted drug is used for PET diagnosis, upon the coupling of a PET radionuclide, as well as for targeted (nuclide) therapy. Theranostic PET tracers have the potential to serve as a non-invasive whole body navigator in the selection of the most effective drug candidates and their most optimal dose and administration route, together with the potential to serve as a predictive biomarker in the selection of patients who are most likely to benefit from treatment. PET imaging supports the transition from trial and error medicine to predictive, preventive, and personalized medicine, hopefully leading to improved quality of life for patients and more cost-effective care.

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Comparison of 18F-GE-180 and dynamic 18F-FET PET in high grade glioma: a double-tracer pilot study

Cited by 56 publications

References 45 publications

Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells

Glioblastoma Exhibits Inter-Individual Heterogeneity of TSPO and LAT1 Expression in Neoplastic and Parenchymal Cells

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

The Added Value of Diagnostic and Theranostic PET Imaging for the Treatment of CNS Tumors

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