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

Of the two F-labeled PET ligands currently available to image metabotropic glutamate receptor 5 (mGluR5), [F]FPEB is reportedly superior because [F]SP203 undergoes glutathionlyation, generating [F]-fluoride ion that accumulates in brain and skull. To allow multiple PET studies on the same day with lower radiation exposure, we prepared [C]FPEB and [C]SP203 from [C]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 ( BP) without using a receptor blocking drug. Both tracers quantified mGluR5; however [C]SP203, like [F]SP203, had radiometabolite accumulation in brain, as evidenced by increased distribution volume ( V) over the scan period. Absolute V values were ∼30% lower for C-labeled compared with F-labeled radioligands, likely caused by the lower specific activities (and high receptor occupancies) of the C 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 C-ligands. Thus, the evidence suggests that [C]FPEB is superior to [C]SP203. If prepared in higher specific activity, [C]FPEB would presumably be as effective as [F]FPEB for quantifying mGluR5 in human brain.