PET Imaging in Glioblastoma: Use in Clinical Practice

Abstract

Positron emission tomography (PET) is a nuclear medicine imaging method with increasing relevance for the diagnosis, prognostication, and monitoring of glioblastomas. PET provides additional insight beyond magnetic resonance imaging (MRI) into the biology of gliomas, which can be used for noninvasive grading, differential diagnosis, delineation of tumor extent, planning of surgery, and radiotherapy and post-treatment monitoring. In clinical practice, two classes of radiotracers have been used predominantly for imaging purposes, namely glucose metabolism tracers and amino acid transport tracers. Both classes of tracers can provide information on grading and prognosis of gliomas, but amino acid tracers, which exhibit lower uptake in normal brain tissue, are better suited for delineation of tumor extent, treatment planning, or follow-up than 18 F-2-fluoro-2-deoxy-D-glucose ( 18 F-FDG). Owing to the progress in PET imaging using radiolabeled amino acids in recent years, the Response Assessment in Neuro-Oncology (RANO) working group, an international effort to develop new standardized response criteria for clinical trials in brain tumors, has recently recommended amino acid PET as an additional tool in the diagnostic assessment of brain tumors. PET Imaging in Glioblastomas 156These developments as well as multimodality imaging should improve the diagnostic assessment of these tumors.

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

“…With applying these procedures, [ 18 F]FDG has shown acceptable sensitivity for the identification of anaplastic abnormalities in patients with low-grade glioma (LGG), high-grade glioma (HGG; Figure 1a [24]), CNS lymphoma, brain metastases, and meningioma [25][26][27]. Moreover, higher [ 18 F]FDG uptake has shown a positive correlation with higher histologic grade and worse prognosis [26,28], making [ 18 F]FDG PET a suitable tool for the prediction of progression-free survival (PFS) and overall survival (OS) [29]. [ 18 F]FDG PET has shown not to be suited for radiation treatment planning, since the region of increased uptake generally covers a smaller volume than what was defined as malignant on T1-weighted gadolinium and T2-weighted MR-images [30].…”

“…Subsequent studies showed a correlation between both uptake intensity and uptake volume and survival after radiotherapy, where higher intensity and larger volumes corresponded with worse survival [62][63][64] (Figure 1e) [69,76]. Most studies found [ 18 F]FLT uptake only in areas of contrast enhancement on MRI, suggesting a dependency on BBB disruption [21,29]. One study by Jacobs et al, on the other hand, showed an uptake of [ 18 F]FLT also in non-enhancing tumor areas and in LGG.…”

“…To date, hypoxia tracers that contain therapeutic compounds have not yet been developed. Finally, less routinely used diagnostic tracers that make use of abnormal metabolic processes include 3 -deoxy-3 -[ 18 F]fluorothymidine ([ 18 F]FLT), [ 11 C]choline or [ 18 F]fluorocholine, [ 11 C]acetate, and62 Cu-or64 Cu-labeled tracers, which all show promising results for diagnosing patients with CNS tumors(Table 1)[21,22,29,[69][70][71][72][73][74][75]. [ 18 F]FLT displays the activity of thymidine kinase 1 (TK1), which is a cytosolic enzyme that is active during S and G2 cell cycle phases[21].…”

pH as a potential therapeutic target to improve temozolomide antitumor efficacy : A mechanistic modeling study

“…21 Positron emission tomography (PET scan) is now standardly used to highlight the tumor sites thanks to this specific signature. 22,23 The increased glycolytic metabolism is related to hypoxia: as the tumor grow the increased cell population increases oxygen consumption and contribute to the local vascular disruption that together result in a local deficit of oxygen. To survive, the cells switch their metabolism to glycolysis.…”

Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study

“…Another important technique for therapeutic follow up analysis in glioma models is the PET that display functional and biological information, such as metastatic lesion and tumor level staging of III and IV [49,[58][59][60][61][62]. PET has high diagnostic, prognostic, and therapeutic evaluation value when integrating with CT or MRI informations [61,62] for drug metabolism and PET radiotracers as 18 F-2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) which evaluates glucose metabolism. High-grade gliomas, such as GBM, are known to consume high glucose levels.…”