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Of the two  18 F-labeled PET ligands currently available to image metabotropic glutamate receptor 5 (mGluR5), [ 18 F]FPEB is reportedly superior because [ 18 F]SP203 undergoes glutathionlyation, generating [ 18 F]-fluoride ion that accumulates in brain and skull. To allow multiple PET studies on the same day with lower radiation exposure, we prepared [ 11 C]FPEB and [ 11 C]SP203 from [ 11 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 ND ) without using a receptor blocking drug. Both tracers quantified mGluR5; however [ 11 C]SP203, like [ 18 F]SP203, had radiometabolite accumulation in brain, as evidenced by increased distribution volume ( V T ) over the scan period. Absolute V T  values were ∼30% lower for  11 C-labeled compared with  18 F-labeled radioligands, likely caused by the lower specific activities (and high receptor occupancies) of the  11 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  11 C-ligands. Thus, the evidence suggests that [ 11 C]FPEB is superior to [ 11 C]SP203. If prepared in higher specific activity, [ 11 C]FPEB would presumably be as effective as [ 18 F]FPEB for quantifying mGluR5 in human brain.

journal of cerebral blood flow and metabolism

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

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

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