Comparison of two PET radioligands, [11C]FPEB and [11C]SP203, for quantification of metabotropic glutamate receptor 5 in human brain. Issue 7 (July 2017)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 37:Issue 7(2017)
• Page Start: 2458
• Page End: 2470
• Publication Date: 2017-07
• Subjects: FPEB -- genomic plot -- mGluR5 -- SP203 -- PET imaging; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X16668891
• Languages: English
• ISSNs: 0271-678X

Abstract

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.