Molecular imaging of gliomas with PET: Opportunities and limitations

Abstract

Neuroimaging enables the noninvasive evaluation of glioma and is considered to be one of the key factors for individualized therapy and patient management, since accurate diagnosis and demarcation of viable tumor tissue is required for treatment planning as well as assessment of treatment response. Conventional imaging techniques like MRI and CT reveal morphological information but are of limited value for the assessment of more specific and reproducible information about biology and activity of the tumor. Molecular imaging with PET is increasingly implemented in neuro-oncology, since it provides additional metabolic information of the tumor, both for patient management as well as for evaluation of newly developed therapeutics. Different molecular processes have been proposed to be useful, like glucose consumption, expression of amino acid transporters, proliferation rate, membrane biosynthesis, and hypoxia. Thus, PET might help neuro-oncologists gain further insights into tumor biology by "true molecular imaging" as well as understand treatment-related phenomena. This review describes the method of PET acquisition as well as the tracers used to image biological processes in gliomas. Furthermore, it considers the clinical impact of PET on the use of currently available radiotracers, which were shown to be potentially valuable for discrimination between neoplastic and nonneoplastic tissue, as well as on tumor grading, determinination of treatment response, and providing an outlook toward further developments.

Diagnostic Accuracy of PET for Recurrent Glioma Diagnosis: A Meta-Analysis

“…Amino acid tracers such as 11 C-MET and 18 F-FET offer higher contrast than 18 F-FDG based on the increased intracellular amino acid use and extracellular matrix production of tumor cells. 8,10 Further, uptake of 18 F-FLT correlates well with thymidine kinase-1 activity, a cytosolic enzyme with high concentration in proliferating cells but low in resting cells. 8,10 Because cell proliferation rates are higher in malignant glioma cells compared with scar tissue, 18 F-FLT can also differentiate tumor recurrence from treatment-induced necrosis.…”

“…PET is a promising molecular neuroimaging technique that provides metabolic tumor information complementing the CT and MR imaging examinations. 8 Several studies have evaluated PET by using various tracers (eg, 18 F-FDG, 11 C-MET, 18 F-FET, or 18 F-FLT) as a test for aiding the differential diagnosis of suspected glioma recurrence. 18 F-FDG is the most widely used tracer; its uptake correlates with the amount of glucose consumption and the local metabolic rate within the glioma lesion.…”

“…9 Uptake of 18 F-FDG in high-grade glioma is typically similar to or less than that in normal gray matter; uptake in low-grade glioma is similar to that in white matter. 8,10 Due to the low contrast between tumor and healthy brain tissue with 18 F-FDG, however, more specific tracers have been developed. Amino acid tracers such as 11 C-MET and 18 F-FET offer higher contrast than 18 F-FDG based on the increased intracellular amino acid use and extracellular matrix production of tumor cells.…”

Correlation of 4′-[methyl-11C]-Thiothymidine Uptake with Ki-67 Immunohistochemistry in Patients with Newly Diagnosed and Recurrent Gliomas

“…Increased cell proliferation and DNA replication is a characteristic of malignant transformation [12]. The assessment of cellular proliferation rate by means of PET is useful as a noninvasive clinical approach.…”

Diagnostic accuracy of F-18-fluoroethyltyrosine PET and PET/CT in patients with brain tumor

“…Magnetic resonance spectroscopy (MRS), to increase specificity, investigates the presence of neuronal and membrane metabolites, such as N-acetylaspartate, choline, creatine, inositol or lactates, but it is limited by poor spatial resolution and frequent artifacts due to proximity with spinal fluid or skull bone. On the contrary, molecular imaging with positron-emission tomography (PET) provides information on tumor metabolism and grade, and helps to identify and delineate tumor zones with increased growth activity [3]. As PET with 18 Ffluorodeoxyglucose (FDG) is not able to reliably predict the tumoral nature of a lesion due to high uptake in normal brain and unspecific uptake in inflammatory or benign lesions, amino acid tracers have been developed in recent decades.…”