Comparison of two PET radioligands, [11C]FPEB and [11C]SP203, for quantification of metabotropic glutamate receptor 5 in human brain

Talakad G. Lohith, Tetsuya Tsujikawa, Fabrice G. Siméon, Mattia Veronese, Sami S. Zoghbi, Chul Hyoung Lyoo, Yasuyuki Kimura, Cheryl L. Morse, Victor W. Pike, Masahiro Fujita, Robert B. Innis

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Abstract

Of the two 18F-labeled PET ligands currently available to image metabotropic glutamate receptor 5 (mGluR5), [18F]FPEB is reportedly superior because [18F]SP203 undergoes glutathionlyation, generating [18F]-fluoride ion that accumulates in brain and skull. To allow multiple PET studies on the same day with lower radiation exposure, we prepared [11C]FPEB and [11C]SP203 from [11C]hydrogen cyanide and compared their abilities to accurately quantify mGluR5 in human brain, especially as regards radiometabolite accumulation. Genomic plot was used to estimate the ratio of specific-to-nondisplaceable uptake (BPND) without using a receptor blocking drug. Both tracers quantified mGluR5; however [11C]SP203, like [18F]SP203, had radiometabolite accumulation in brain, as evidenced by increased distribution volume (VT) over the scan period. Absolute VT values were ∼30% lower for 11C-labeled compared with 18F-labeled radioligands, likely caused by the lower specific activities (and high receptor occupancies) of the 11C radioligands. The genomic plot indicated ∼60% specific binding in cerebellum, which makes it inappropriate as a reference region. Whole-body scans performed in healthy subjects demonstrated a low radiation burden typical for 11C-ligands. Thus, the evidence suggests that [11C]FPEB is superior to [11C]SP203. If prepared in higher specific activity, [11C]FPEB would presumably be as effective as [18F]FPEB for quantifying mGluR5 in human brain.

Original languageEnglish
Pages (from-to)2458-2470
Number of pages13
JournalJournal of Cerebral Blood Flow and Metabolism
Volume37
Issue number7
DOIs
Publication statusPublished - 2017 Jul 1

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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    Lohith, T. G., Tsujikawa, T., Siméon, F. G., Veronese, M., Zoghbi, S. S., Lyoo, C. H., Kimura, Y., Morse, C. L., Pike, V. W., Fujita, M., & Innis, R. B. (2017). Comparison of two PET radioligands, [11C]FPEB and [11C]SP203, for quantification of metabotropic glutamate receptor 5 in human brain. Journal of Cerebral Blood Flow and Metabolism, 37(7), 2458-2470. https://doi.org/10.1177/0271678X16668891