The Utility of Conventional Amino Acid PET Radiotracers in the Evaluation of Glioma Recurrence also in Comparison with MRI

Abstract

Aim: In this comprehensive review we present an update on the most relevant studies evaluating the utility of amino acid PET radiotracers for the evaluation of glioma recurrence as compared to magnetic resonance imaging (MRI). Methods: A literature search extended until June 2020 on the PubMed/MEDLINE literature database was conducted using the terms “high-grade glioma”, “glioblastoma”, “brain tumors”, “positron emission tomography”, “PET”, “amino acid PET”, “[11C]methyl-l-methionine”, “[18F]fluoroethyl-tyrosine”, “[18F]fluoro-l-dihydroxy-phenylalanine”, “MET”, “FET”, “DOPA”, “magnetic resonance imaging”, “MRI”, “advanced MRI”, “magnetic resonance spectroscopy”, “perfusion-weighted imaging”, “diffusion-weighted imaging”, “MRS”, “PWI”, “DWI”, “hybrid PET/MR”, “glioma recurrence”, “pseudoprogression”, “PSP”, “treatment-related change”, and “radiation necrosis” alone and in combination. Only original articles edited in English and about humans with at least 10 patients were included. Results: Forty-four articles were finally selected. Conventional amino acid PET tracers were demonstrated to be reliable diagnostic techniques in differentiating tumor recurrence thanks to their high uptake from tumor tissue and low background in normal grey matter, giving additional and early information to standard modalities. Among them, MET–PET seems to present the highest diagnostic value but its use is limited to on-site cyclotron facilities. [18F]labelled amino acids, such as FDOPA and FET, were developed to provide a more suitable PET tracer for routine clinical applications, and demonstrated similar diagnostic performance. When compared to the gold standard MRI, amino acid PET provides complementary and comparable information to standard modalities and seems to represent an essential tool in the differentiation between tumor recurrence and other entities such as pseudoprogression, radiation necrosis, and pseudoresponse. Conclusions: Despite the introduction of new advanced imaging techniques, the diagnosis of glioma recurrence remains challenging. In this scenario, the growing knowledge about imaging techniques and analysis, such as the combined PET/MRI and the application of artificial intelligence (AI) and machine learning (ML), could represent promising tools to face this difficult and debated clinical issue.

PET Criteria by Cancer Type from Imaging Interpretation to Treatment Response Assessment: Beyond FDG PET Score

“…It is known that postoperative assessment in glioma patients is crucial in the imaging follow-up and for prognostic considerations [ 82 ]. Even for the evaluation of recurrence, PET imaging demonstrated its added value over MRI, given its ability to assess tumor metabolism and reduce pseudo-progression pitfalls [ 83 ]. However, [ 18 F]Fluorocholine is not the standard of choice because amino acid tracers (such as [ 11 C]MET, [ 18 F]FET) demonstrated better diagnostic performance.…”

Posttherapy technetium-99m pentavalent dimercaptosuccinic acid brain single-photon emission computed tomography/computed tomography: diagnostic and prognostic values in patients with glioma

“…For example, PET can help distinguish between true and pseudoresponse to antiangiogenic agents in recurrent glioma and determine treatment failures earlier than MRI in recurrent glioma [21][22][23]. Though it is clear that PET has several advantages over SPECT, given its inherent quantitative nature, better resolution, and multitude of radiotracers; however, it is far more expensive and not widely available, especially in developing countries [24]. The reported diagnostic accuracy of amino acid tracers in the literature ranged from 81 to 99% [25][26][27][28].…”

Radiomics: The New Promise for Differentiating Progression, Recurrence, Pseudoprogression, and Radionecrosis in Glioma and Glioblastoma Multiforme

“…This modality can also differentiate between true progression and pseudoprogression, with higher Tbrmax and mean tumor-to-brain ratio (tbrmean) favoring true progression [ 60 ], while pseudoprogression manifests with a relatively lower uptake of the radioactive tracer [ 61 ]. Nevertheless, amino acid PET requires longer acquisition times than other PET imaging modalities [ 62 ]. Additionally, both progression and pseudoprogression can increase metabolic activity on PET scans, making it difficult to differentiate between them [ 63 ].…”