Approaches to PET Imaging of Glioblastoma

Abstract

Glioblastoma multiforme (GBM) is the deadliest type of brain tumor, affecting approximately three in 100,000 adults annually. Positron emission tomography (PET) imaging provides an important non-invasive method of measuring biochemically specific targets at GBM lesions. These powerful data can characterize tumors, predict treatment effectiveness, and monitor treatment. This review will discuss the PET imaging agents that have already been evaluated in GBM patients so far, and new imaging targets with promise for future use. Previously used PET imaging agents include the tracers for markers of proliferation ([11C]methionine; [18F]fluoro-ethyl-L-tyrosine, [18F]Fluorodopa, [18F]fluoro-thymidine, and [18F]clofarabine), hypoxia sensing ([18F]FMISO, [18F]FET-NIM, [18F]EF5, [18F]HX4, and [64Cu]ATSM), and ligands for inflammation. As cancer therapeutics evolve toward personalized medicine and therapies centered on tumor biomarkers, the development of complimentary selective PET agents can dramatically enhance these efforts. Newer biomarkers for GBM PET imaging are discussed, with some already in use for PET imaging other cancers and neurological disorders. These targets include Sigma 1, Sigma 2, programmed death ligand 1, poly-ADP-ribose polymerase, and isocitrate dehydrogenase. For GBM, these imaging agents come with additional considerations such as blood–brain barrier penetration, quantitative modeling approaches, and nonspecific binding.

Deficiency of G9a Inhibits Cell Proliferation and Activates Autophagy via Transcriptionally Regulating c-Myc Expression in Glioblastoma

“…Currently, standard care includes maximum surgical resection, followed by radiotherapy and simultaneous chemotherapy with temozolomide (TMZ) (Ozdemir-Kaynak et al, 2018). Although great advances have been obtained in diagnostic technology (Drake et al, 2020), surgery technique, and radio-/chemotherapy (Oberheim Bush et al, 2019), long-term survivors are very rare and tumors usually recur within a short period of time (Silantyev et al, 2019), and the 5-year survival is still lower than 6% (Shergalis et al, 2018). Therefore, novel therapeutic strategies of glioblastoma are urgently needed, and gaining a comprehensive understanding of the molecular mechanisms of glioblastoma initiation and progression is very important.…”

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

“…Radiolabeled amino acid tracers ( Figure 1) are of great interest in brain tumor imaging because of the high tumor-to-brain contrast based on the relatively high specificity for neoplastic tissue and the low uptake in healthy brain tissue [7,8,21,[31][32][33].…”

“…Radiolabeled amino acid tracers ( Figure 1) are of great interest in brain tumor imaging because of the high tumor-to-brain contrast based on the relatively high specificity for neoplastic tissue and the low uptake in healthy brain tissue [7,8,21,[31][32][33]. is mainly based on the increased expression of large neutral amino acid transporters of the l-type (LAT) in gliomas and brain metastases (i.e., subtypes LAT1 and LAT2) [7,[34][35][36][37].…”

Sigma-1 Receptor Positron Emission Tomography: A New Molecular Imaging Approach Using (S)-(−)-[18F]Fluspidine in Glioblastoma

“…By application of suitable radiolabeled molecules, positron emission tomography (PET) in particular can assess such alterations with high sensitivity. Imaging agents for the investigation of the catabolic and anabolic metabolism can detect cancer-specific alterations in high-capacity processes such as glycolysis (by [ 18 F]FDG), amino acid transport (by [ 11 C]MET or [ 18 F]FET), and membrane turnover (by [ 18 F]FMC) [13,14]. They are currently utilized to improve the clinical management of brain cancer patients.…”

“…Furthermore, the PET technology offers the principal possibility to investigate differences in the expression pattern and activity of diagnostically and therapeutically relevant proteins, such as receptors or enzymes, and to correlate them with tumour heterogeneity and aggressiveness. The current development of radiolabelled probes to image e.g., isocitrate dehydrogenase mutations (IDH1R132H) [15], or the glutamate carboxypeptidase II (prostate-specific membrane antigen, PSMA) [16], reflects the interest in preclinical and clinical research on detailed and targeted molecular characterisation of malignancies in the brain, which is a prerequisite to define the role of nuclear medicine imaging for the individualized treatment of patients with GBM [14,17].…”