18F-Fluciclovine (18F-FACBC) PET imaging of recurrent brain tumors
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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 ± 2.3), while 11C-Methionine’s tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0 ± 2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p < 0.0001). This was due to 18F-Fluciclovine’s lower background in normal brain tissue (0.5 ± 0.2 compared to 1.3 ± 0.4 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 ± 2.3 h), and achieving a consistent final distribution volume averaging 1.4 ± 0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57 ± 51 min), with an average distribution volume of 3.2 ± 1.1 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.
KeywordsGlioma PET 18F-FACBC 18F-Fluciclovine 11C-methionine
We are grateful to Blue Earth Diagnostics for providing support for the data analysis and publication costs.
Funding was provided by grant R21 CA093501 and Dr. A.B. Lassman’s grants.
Compliance with ethical standards
Conflict of interest
Blue Earth Diagnostics provided support for the data analysis and paid for a part of Dr. L. Michaud salary.
This research was funded in part by Dr. A.B. Lassman’s grants from Dana Foundation, Brain Tumor Funders’ Collaborative, The Society of Memorial Sloan-Kettering Cancer Center, Brain Tumor Center of Memorial Sloan Kettering Cancer Center, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Foundation for Cancer Research and The Experimental Therapeutics Center of Memorial Sloan Kettering Cancer Center. In the last 12 months, outside the submitted work, Dr. A.B. Lassman received: Personal fees/honoraria from Orbus, Karyopharm, NW Bio, AbbVie, Agios, Bioclinica as an expert blinded independent reviewer of clinical and imaging data for a BMS-sponsored trial, Sapience, Physicians’ Education Resource/Chemotherapy Foundation Symposium; Research support from Genentech/Roche, Amgen, AbbVie, Millenium, Celldex, Novartis, Pfizer, Aeterna Zenaris, Karyopharm, RTOG-Foundation, Kadmon, VBI Vaccines, Beigene, Oncoceutics; and Travel/in-kind support from Orbus, Karyopharm, NW Bio, Oncoceutics, GCAR, Agios, AbbVie, Celgene, Novocure, Tocagen.
Dr. H. Schoder has no actual conflict of interest. He was a consultant for Aileron Pharmaceuticals until June 30, 2018.
Dr. WA. Weber is on advisory boards and receives compensation from Bayer, Blue Earth Diagnostics, Endocyte and Pentixapharm. He has received research support from BMS, Imaginab, Ipsen and Piramal.
B.J. Beattie, Dr. T. Akhurst, P. Zanzonico, Dr. M. Dunphy, Dr. R. Finn, A. Mauguen, and Dr. R. Blasberg declare they have no conflict of interest.
All procedures performed in this study were in accordance with the ethical standards of our institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
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