Research ArticleNeurology

Evaluation of a PET Radioligand to Image O-GlcNAcase in Brain and Periphery of Rhesus Monkey and Knock-Out Mouse

Soumen Paul, Mohammad B. Haskali, Jeih-San Liow, Sami S. Zoghbi, Vanessa N. Barth, Marcy Comly Kolodrubetz, Michelle R. Bond, Cheryl L. Morse, Robert L. Gladding, Michael P. Frankland, Nancy Kant, Lawrence Slieker, Sergey Shcherbinin, Hugh N. Nuthall, Paolo Zanotti-Fregonara, John A. Hanover, Cynthia Jesudason, Victor W. Pike and Robert B. Innis
Journal of Nuclear Medicine January 2019, 60 (1) 129-134; DOI: https://doi.org/10.2967/jnumed.118.213231

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Structure of 18F-LSN3316612.

  • FIGURE 2.
    FIGURE 2.

    Concentration of radioactivity in brain at baseline (A) and after blockade (B) and concentration of parent radioligand in plasma (C). In baseline graph, symbols represent mean ± SD from 4 monkeys. The other 2 graphs show results from 1 animal. For blockade, thiamet-G (10 mg/kg intravenously) was injected 45 min before radioligand.

  • FIGURE 3.
    FIGURE 3.

    Parametric images of VT in rhesus monkey brain at baseline and after thiamet-G blockade. Uptake at baseline was especially high in striatum, hippocampus, frontal cortex, amygdala, and pituitary (arrows). Thiamet-G (10 mg/kg intravenously) decreased uptake by >90% in all regions. Skull shows negligible uptake of radioactivity. These parametric images quantified VT at voxel level using Logan plot.

  • FIGURE 4.
    FIGURE 4.

    Uptake of radioactivity in corpus callosum (white matter region) of rhesus macaque brain. Uptake at baseline (○) was significantly blocked by nonradioactive LSN3316612 (●), 1 mg/kg intravenously, administered 45 min before radioligand.

  • FIGURE 5.
    FIGURE 5.

    Time stability curves of total VT for 2 regions: striatum (□), which had high uptake, and cerebellum (●), which had lowest uptake. VT was calculated using unconstrained 2-tissue-compartment model with increasingly truncated acquisition times. All values of VT were normalized as percentage of terminal value attained from 120 min of imaging. Data represent mean ± SD of 4 monkeys.

  • FIGURE 6.
    FIGURE 6.

    Uptake of radioactivity in whole brain from 2 controls (○) and 2 Oga∆Br (●) mice. Uptake in control mice preblocked with thiamet-G (△) (10 mg/kg intravenously) was similar to that in Oga∆Br mice.

  • FIGURE 7.
    FIGURE 7.

    Whole-body distribution of radioactivity in male monkey after injection of 18F- LSN3316612 at baseline and with thiamet-G blockade (10 mg/kg, intravenously). Images were averaged for entire 120-min scan and presented as maximal-intensity projection, which enhances contrast and allows easier visualization of organs. Clear blocking effect was seen in brain, heart, kidneys, small intestine, spleen, testes, and seminal vesicle. In blocked scan, radioactivity below pelvis was due to urine excreted into animal’s diaper.

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