Abstract
BackgroundThe ability to accurately and non-invasively distinguish high-grade glioma from low-grade glioma remains a challenge despite advances in molecular and magnetic resonance imaging. We investigated the ability of fluciclovine (18F) PET as a means to identify and distinguish these lesions in patients with known gliomas and to correlate uptake with Ki-67.ResultsSixteen patients with a total of 18 newly diagnosed low-grade gliomas (n = 6) and high grade gliomas (n = 12) underwent fluciclovine PET imaging after histopathologic assessment. Fluciclovine PET analysis comprised tumor SUVmax and SUVmean, as well as metabolic tumor thresholds (1.3*, 1.6*, 1.9*) to normal brain background (TBmax, and TBmean). Comparison was additionally made to the proliferative status of the tumor as indicated by Ki-67 values.Fluciclovine uptake greater than normal brain parenchyma was found in all lesions studied. Time activity curves demonstrated statistically apparent flattening of the curves for both high-grade gliomas and low-grade gliomas starting 30 min after injection, suggesting an influx/efflux equilibrium. The best semiquantitative metric in discriminating HGG from LGG was obtained utilizing a metabolic 1 tumor threshold of 1.3* contralateral normal brain parenchyma uptake to create a tumor: background (TBmean1.3) cutoff of 2.15 with an overall sensitivity of 97.5% and specificity of 95.5%. Additionally, using a SUVmax > 4.3 cutoff gave a sensitivity of 90.9% and specificity of 97.5%. Tumor SUVmean and tumor SUVmax as a ratio to mean normal contralateral brain were both found to be less relevant predictors of tumor grade. Both SUVmax (R = 0.71, p = 0.0227) and TBmean (TBmean1.3: R = 0.81, p = 0.00081) had a high correlation with the tumor proliferative index Ki-67.ConclusionsFluciclovine PET produces high-contrast images between both low-grade and high grade gliomas and normal brain by visual and semiquantitative analysis. Fluciclovine PET appears to discriminate between low-grade glioma and high-grade glioma, but must be validated with a larger sample size.
Highlights
The ability to accurately and non-invasively distinguish high-grade glioma from low-grade glioma remains a challenge despite advances in molecular and magnetic resonance imaging
In distinction to other amino acid positron emission tomography (PET) tracers, such as L-[methyl-11C]-methionine (MET), 18F fluoro-ethyltyrosine fluoroethyltyrosine (FET), and 3,4-dihydroxy-6-[18F] fluoro-L-phenylalanine (FDOPA) which are predominantly transported via system L amino acid transporters, fluciclovine undergoes cellular transport by both system L and system alanine-serine-cysteine (ASC), ASCT2, in human astrocytes and glioma cells [11]
One of the multifocal glioblastoma patients previously had a known oligodendroglioma which had been treated with external radiation 2 years prior to the fluciclovine PET
Summary
The ability to accurately and non-invasively distinguish high-grade glioma from low-grade glioma remains a challenge despite advances in molecular and magnetic resonance imaging. In distinction to other amino acid PET tracers, such as L-[methyl-11C]-methionine (MET), 18F fluoro-ethyltyrosine fluoroethyltyrosine (FET), and 3,4-dihydroxy-6-[18F] fluoro-L-phenylalanine (FDOPA) which are predominantly transported via system L amino acid transporters, fluciclovine undergoes cellular transport by both system L and system alanine-serine-cysteine (ASC), ASCT2, in human astrocytes and glioma cells [11]. Both system L and ASCT2 are known to be obligate amino acid exchanges with intracellular and extracellular substrates exchanged in a 1:1 manner [12]. ASCT2 is not expressed at the luminal side of the blood-brain-barrier (BBB) and is likely not involved with the transport of fluciclovine into the normal brain and in tumors with an intact BBB [13]
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