Test–retest reproducibility of the metabotropic glutamate receptor 5 ligand [18F]FPEB with bolus plus constant infusion in humans
- 624 Downloads
[18F]FPEB is a promising PET radioligand for the metabotropic glutamate receptor 5 (mGluR5), a potential target for the treatment of neuropsychiatric diseases. The purpose of this study was to evaluate the test–retest reproducibility of [18F]FPEB in the human brain.
Seven healthy male subjects were scanned twice, 3 – 11 weeks apart. Dynamic data were acquired using bolus plus infusion of 162 ± 32 MBq [18F]FPEB. Four methods were used to estimate volume of distribution (V T): equilibrium analysis (EQ) using arterial (EQA) or venous input data (EQV), MA1, and a two-tissue compartment model (2 T). Binding potential (BP ND) was also estimated using cerebellar white matter (CWM) or gray matter (CGM) as the reference region using EQ, 2 T and MA1. Absolute test–retest variability (aTRV) of V T and BP ND were calculated for each method. Venous blood measurements (C V) were compared with arterial input (C A) to examine their usability in EQ analysis.
Regional V T estimated by the four methods displayed a high degree of agreement (r 2 ranging from 0.83 to 0.99 among the methods), although EQA and EQV overestimated V T by a mean of 9 % and 7 %, respectively, compared to 2 T. Mean values of aTRV of V T were 11 % by EQA, 12 % by EQV, 14 % by MA1 and 14 % by 2 T. Regional BP ND also agreed well among the methods and mean aTRV of BP ND was 8 – 12 % (CWM) and 7 – 9 % (CGM). Venous and arterial blood concentrations of [18F]FPEB were well matched during equilibrium (C V = 1.01 · C A, r 2 = 0.95).
[18F]FPEB binding shows good TRV with minor differences among analysis methods. Venous blood can be used as an alternative for input function measurement instead of arterial blood in EQ analysis. Thus, [18F]FPEB is an excellent PET imaging tracer for mGluR5 in humans.
Keywords[18F]FPEB Human Metabotropic glutamate receptor 5 Positron emission tomography Reproducibility
The authors thank the staff of the Yale University PET Center for their technical expertise and support.
Compliance with ethical standards
This study was supported by the Yale Pfizer Bioimaging Alliance. This study was also made possible by CTSA grant number UL1 RR024139 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH roadmap for Medical Research.
Conflicts of interest
- 10.Patel S, Ndubizu O, Hamill T, Chaudhary A, Burns HD, Hargreaves R, et al. Screening cascade and development of potential positron emission tomography radiotracers for mGluR5: in vitro and in vivo characterization. Mol Imaging Biol. 2005;7:314–23. doi: 10.1007/s11307-005-0005-4.PubMedCrossRefGoogle Scholar
- 11.Wang JQ, Tueckmantel W, Zhu A, Pellegrino D, Brownell AL. Synthesis and preliminary biological evaluation of 3-[(18)F]fluoro-5-(2-pyridinylethynyl)benzonitrile as a PET radiotracer for imaging metabotropic glutamate receptor subtype 5. Synapse. 2007;61:951–61. doi: 10.1002/syn.20445.PubMedCrossRefGoogle Scholar
- 12.First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV axis I disorders, clinician version (SCID-CV). Washington: American Psychiatric Press; 1996.Google Scholar
- 13.Lim K, Labaree D, Li S, Huang Y. Preparation of the metabotropic glutamate receptor 5 (mGluR5) PET tracer [(18)F]FPEB for human use: an automated radiosynthesis and a novel one-pot synthesis of its radiolabeling precursor. Appl Radiat Isot. 2014;94C:349–54. doi: 10.1016/j.apradiso.2014.09.006.CrossRefGoogle Scholar
- 14.Sullivan JM, Lim K, Labaree D, Lin SF, McCarthy TJ, Seibyl JP, et al. Kinetic analysis of the metabotropic glutamate subtype 5 tracer [(18)F]FPEB in bolus and bolus-plus-constant-infusion studies in humans. J Cereb Blood Flow Metab. 2013;33:532–41. doi: 10.1038/jcbfm.2012.195.PubMedCentralPubMedCrossRefGoogle Scholar
- 15.Carson RE, Barker WC, Liow JS, Johnson CA. Design of a motion-compensation OSEM list-mode algorithm for resolution-recovery reconstruction for the HRRT. IEEE Nucl Sci Symp Conf Rec. 2003;5:3281–5Google Scholar
- 20.DeLorenzo C, Milak MS, Brennan KG, Kumar JS, Mann JJ, Parsey RV. In vivo positron emission tomography imaging with [11C]ABP688: binding variability and specificity for the metabotropic glutamate receptor subtype 5 in baboons. Eur J Nucl Med Mol Imaging. 2011;38:1083–94. doi: 10.1007/s00259-010-1723-7.PubMedCentralPubMedCrossRefGoogle Scholar
- 21.Wong DF, Waterhouse R, Kuwabara H, Kim J, Brasic JR, Chamroonrat W, et al. 18F-FPEB, a PET radiopharmaceutical for quantifying metabotropic glutamate 5 receptors: a first-in-human study of radiochemical safety, biokinetics, and radiation dosimetry. J Nucl Med. 2013;54:388–96. doi: 10.2967/jnumed.112.107995.PubMedCrossRefGoogle Scholar
- 22.Kuwabara H, Chamroonrat W, Mathews W, Waterhouse R, Brasic J, Guevara MR, et al. Evaluation of 11C-ABP688 and 18F-FPEB for imaging mGluR5 receptors in the human brain. J Nucl Med. 2011;52 Suppl 1:390.Google Scholar
- 24.Martinez D, Slifstein M, Nabulsi N, Grassetti A, Urban NB, Perez A, et al. Imaging glutamate homeostasis in cocaine addiction with the metabotropic glutamate receptor 5 positron emission tomography radiotracer [11C]ABP688 and magnetic resonance spectroscopy. Biol Psychiatry. 2014;75:165–71. doi: 10.1016/j.biopsych.2013.06.026.PubMedCentralPubMedCrossRefGoogle Scholar
- 26.Deschwanden A, Karolewicz B, Feyissa AM, Treyer V, Ametamey SM, Johayem A, et al. Reduced metabotropic glutamate receptor 5 density in major depression determined by [11C]ABP688 PET and postmortem study. Am J Psychiatry. 2011;168:727–34. doi: 10.1176/appi.ajp.2011.09111607.PubMedCentralPubMedCrossRefGoogle Scholar
- 27.DeLorenzo C, DellaGioia N, Bloch M, Sanacora G, Nabulsi N, Abdallah C, et al. In vivo ketamine-induced changes in [11C]ABP688 binding to metabotropic glutamate receptor subtype 5. Biol Psychiatry. 2015;77:266–75. doi: 10.1016/j.biopsych.2014.06.024.
- 28.Kagedal M, Cselenyi Z, Nyberg S, Raboisson P, Stahle L, Stenkrona P, et al. A positron emission tomography study in healthy volunteers to estimate mGluR5 receptor occupancy of AZD2066 – estimating occupancy in the absence of a reference region. Neuroimage. 2013;82:160–9. doi: 10.1016/j.neuroimage.2013.05.006.PubMedCrossRefGoogle Scholar