RT Journal Article SR Electronic T1 Preclinical Evaluation and Quantification of 18F-FPEB as a Radioligand for PET Imaging of the Metabotropic Glutamate Receptor 5 JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 1954 OP 1959 DO 10.2967/jnumed.115.162636 VO 56 IS 12 A1 Bart de Laat A1 Gil Leurquin-Sterk A1 Sofie Celen A1 Guy Bormans A1 Michel Koole A1 Koen Van Laere A1 Cindy Casteels YR 2015 UL http://jnm.snmjournals.org/content/56/12/1954.abstract AB The metabotropic glutamate receptor 5 (mGluR5) is a high-interest target for PET imaging because it plays a role in several pathologies, including addiction, schizophrenia, and fragile X syndrome. Methods: We studied the pharmacokinetics of 18F-FPEB (3-18F-fluoro-5-(2-pyridinylethynyl)benzonitrile), a selective PET radioligand for mGluR5, and used it to quantify mGluR5 in rat brain. Quantification was performed using both arterial sampling in combination with compartment models and simplified reference methods. The simplified reference tissue model (SRTM), Ichise's original multi-linear reference tissue model (MRTMO), and Logan noninvasive were tested as reference models with nondisplaceable binding (BPND) as outcome parameter. Additionally, test–retest scans were obtained in 6 animals. Results: 18F-FPEB uptake in rat brain was consistent with its known distribution. No radiometabolites were present in the brain, and binding was specific as shown in blocking experiments, which also confirmed the cerebellum as a viable reference region. A 2-tissue-compartment model was used to determine BPND for the striatum (11.7 ± 1.5), nucleus accumbens (10.6 ± 2.0), hippocampus (9.0 ± 1.2), cortex (7.2 ± 1.0), and thalamus (4.0 ± 0.9). Reference methods were able to estimate these values with small bias (<2%). Test–retest analysis showed high repeatability between scans below 6%, also for shorter scan durations of 30 and 60 min. Conclusion: Because of its favorable reversible kinetics, high specificity, and absence of brain radiometabolites 18F-FPEB proves a highly useful tracer for in vivo visualization of the mGluR5 in rat brain. Moreover, reference tissue models allow noninvasive, rapid scanning with good test–retest.