[18F]Fluciclovine PET discrimination between high- and low-grade gliomas

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.Electronic supplementary materialThe online version of this article (10.1186/s13550-018-0415-3) contains supplementary material, which is available to authorized users.

18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors

“…F-Fluciclovine images showed high contrast, confirmed by the high tumor-to-brain ratios (tumor SUVmax-to-SUVmean of a reference normal-brain region), concordant with the first clinical studies [10][11][12][13][14]. Our results showed that the two ratios calculated with two different reference regions (either the contralateral normal brain tissue or the cerebellum) are highly correlated, as was previously described by Kondo et al [10].…”

“…All 18 F-Fluciclovine and 11 C-Methionine visual and SUV analyses were conducted using the Hermes HybridViewer imaging software (Hermes Medical Solutions, Stockholm, Sweden) based on a summed 25-45 min PET static image set registered to a contrast-enhanced MR (or in one case CT) image acquired within 30 days of the PET image. We chose to base our analysis upon a summed 25-45 min image because the uptake was relatively stable over this time period; it was the latest time consistently acquired across patients for both 18 F-Fluciclovine and 11 C-Methionine and it was similar to time points used in other studies of 18 F-Fluciclovine uptake into brain tumors [10,12].…”

“…Pre-clinical studies have shown that 18 F-Fluciclovine could be a potential PET tracer for brain tumor imaging [9], and the results from clinical studies evaluating 18 F-Fluciclovine PET for primary staging of gliomas are encouraging [10][11][12]. Recently, Tsuyuguchi et al showed in a preliminary study of six patients that 18 F-Fluciclovine may provide better assessment than 11 C-Methionine for the initial detection of glioma [13].…”

“…It has been reported that most amino acid tracers (e.g., FET, MET, FACBC) do not accurately separate tumor grades based on histological subtypes [2]. Nevertheless, Parent et al recently showed that 18 F-Fluciclovine PET may discriminate highand low-grade gliomas [12]. In our study we chose not to test the correlation between tumor grading and Fluciclovine uptake because the overwhelming majority of patients presented with high-grade glioma, as one might expect in a recurrent/ progressive disease setting.…”

Incidental detection of oropharyngeal cancer with fluciclovine PET

“…In its first application of a single test patient with residual glioblastoma, fluciclovine demonstrated rapid uptake in tumor compared to normal brain tissue, suggesting its potential value as an imaging agent . Subsequent clinical trials then confirmed its utility in distinguishing high‐grade from low‐grade gliomas compared to established radiopharmaceuticals . Its efficacy was attributed to an affinity for tumor tissue as well as a hypothesized resistance to metabolism during cellular uptake…”