Amino acid tracers in PET imaging of diffuse low-grade gliomas: a systematic review of preoperative applications

Abstract

Positron emission tomography (PET) imaging using amino acid tracers has in recent years become widely used in the diagnosis and prediction of disease course in diffuse low-grade gliomas (LGG). However, implications of preoperative PET for treatment and prognosis in this patient group have not been systematically studied. The aim of this systematic review was to evaluate the preoperative diagnostic and prognostic value of amino acid PET in suspected diffuse LGG. Medline, Cochrane Library, and Embase databases were systematically searched using keywords “PET,” “low-grade glioma,” and “amino acids tracers” with their respective synonyms. Out of 2137 eligible studies, 28 met the inclusion criteria. Increased amino acid uptake (lesion/brain) was consistently reported among included studies; in 25–92% of subsequently histopathology-verified LGG, in 83–100% of histopathology-verified HGG, and also in some non-neoplastic lesions. No consistent results were found in studies reporting hot spot areas on PET in MRI-suspected LGG. Thus, the diagnostic value of amino acid PET imaging in suspected LGG has proven difficult to interpret, showing clear overlap and inconsistencies among reported results. Similarly, the results regarding the prognostic value of PET in suspected LGG and the correlation between uptake ratios and the molecular tumor status of LGG were conflicting. This systematic review illustrates the difficulties with prognostic studies presenting data on group-level without adjustment for established clinical prognostic factors, leading to a loss of additional prognostic information. We conclude that the prognostic value of PET is limited to analysis of histological subgroups of LGG and is probably strongest when using kinetic analysis of dynamic FET uptake parameters.Electronic supplementary materialThe online version of this article (10.1007/s00701-018-3563-3) contains supplementary material, which is available to authorized users.

Clinical Management of Diffuse Low-Grade Gliomas

“…Positron emission tomography (PET) imaging reflects fundamental metabolic patterns in brain gliomas [ 56 ]. In particular, PET with radiolabeled amino acids such as [ 11 C-methyl]-methionine ( 11 C-MET), O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ( 18 F-FET), and 3,4-dihydroxy-6-[ 18 F]-fluoro-L-phenylalanine ( 18 F-FDOPA) has been proven to have a moderately high diagnostic accuracy to discriminate high and low-grade gliomas, but the overlap between tumor subtypes hampers clear separation [ 57 , 58 ]. Nonetheless, a clear role as independent prognostic tool is still not demonstrated, since studies are few and with conflicting results [ 58 ].…”

“…In particular, PET with radiolabeled amino acids such as [ 11 C-methyl]-methionine ( 11 C-MET), O-(2-[ 18 F]-fluoroethyl)-L-tyrosine ( 18 F-FET), and 3,4-dihydroxy-6-[ 18 F]-fluoro-L-phenylalanine ( 18 F-FDOPA) has been proven to have a moderately high diagnostic accuracy to discriminate high and low-grade gliomas, but the overlap between tumor subtypes hampers clear separation [ 57 , 58 ]. Nonetheless, a clear role as independent prognostic tool is still not demonstrated, since studies are few and with conflicting results [ 58 ]. Amino acid PET can be performed to detect aggressive disease foci in anatomical MRI findings suggestive of WHO grade II glioma, hence possibly guiding biopsy and tumor resection, as well as radiation dose boosting [ 59 ].…”

Ischemic Brain Injury and Regulatory T Cells

“…To secrete mature IL-1β, inflammasome must be activated in macrophages. We and others have shown that inhibition of inflammasome is one way to reduce neuroinflammation and infarct volume growth after stroke [14,15] (Figure 1 and 2).…”

Contribution of PET Imaging to Clinical Management of Gliomas

“…MET-PET can help determine prognosis in gliomas and is superior than FDG-PET and MRI in predicting survival in lowgrade gliomas [48]. Recent reviews have summarized the value of MET-PET for imaging of gliomas [4,[49][50][51]. MET uptake differs with tumor type: in oligodendrogliomas, uptake tends to be higher than in astrocytomas of the same histological grade, although they are less aggressive [52].…”

“…Dynamic FET studies with inclusion of early and late scans therefore improved differentiation and grading performance [69][70][71][72]. Kinetic analysis of dynamic FET uptake parameters is of special prognostic value in diffuse low-grade gliomas [51].…”