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

Abstract

The aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection. Twenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI. 18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5\u2009±\u20092.3), while 11C-Methionine’s tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0\u2009±\u20092.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p\u2009<\u20090.0001). This was due to 18F-Fluciclovine’s lower background in normal brain tissue (0.5\u2009±\u20090.2 compared to 1.3\u2009±\u20090.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7\u2009±\u20092.3 h), and achieving a consistent final distribution volume averaging 1.4\u2009±\u20090.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57\u2009±\u200951 min), with an average distribution volume of 3.2\u2009±\u20091.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine. Tumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.