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

• Published in: Journal of cerebral blood flow and metabolism Vol. 37; no. 7; pp. 2458 - 2470
• Main Authors: Lohith, Talakad G, Tsujikawa, Tetsuya, Siméon, Fabrice G, Veronese, Mattia, Zoghbi, Sami S, Lyoo, Chul Hyoung, Kimura, Yasuyuki, Morse, Cheryl L, Pike, Victor W, Fujita, Masahiro, Innis, Robert B
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.07.2017
• Subjects: Adult; Brain - diagnostic imaging; Brain - metabolism; Carbon Radioisotopes; Female; Healthy Volunteers; Humans; Image Processing, Computer-Assisted; Ligands; Male; Models, Biological; Nitriles - blood; Nitriles - pharmacokinetics; Original; Positron-Emission Tomography - methods; Pyridines - blood; Pyridines - pharmacokinetics; Radionuclide Imaging; Radiopharmaceuticals - pharmacokinetics; Receptor, Metabotropic Glutamate 5 - genetics; Receptor, Metabotropic Glutamate 5 - metabolism; RNA, Messenger - genetics; Thiazoles - blood; Thiazoles - pharmacokinetics; Tissue Distribution; Whole Body Imaging; PET imaging; genomic plot; mGluR5; FPEB; SP203
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1177/0271678X16668891

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.