Journal: Acta Pharmaceutica Sinica. B

Article Title: Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

doi: 10.1016/j.apsb.2022.05.017

Figure Lengend Snippet: Full of 11 HDAC isoforms profiling of synthetic compounds a .

Article Snippet: The concentrations of PB118 in n -octanol and water were measured by LC–MS (Agilent 6310 ion trap mass spectrometer).

Techniques:

Journal: Acta Pharmaceutica Sinica. B

Article Title: Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

doi: 10.1016/j.apsb.2022.05.017

Figure Lengend Snippet: Molecular Modeling and Stimulation of PB118. (A) Chemical structure of PB118 and (B) its inhibitory activities against HDAC1–11. (C) Molecular docking study results of PB118 based on the zHDAC6 crystal complex (PDB entry 6THV). Zn ion is shown as a purple sphere and hydrogen bonds as yellow dotted lines; key amino acid residues that create the specific pocket in HDAC6 are represented as a stick and labeled as shown. (D) Surface poses of PB118 in the HDAC6 binding pocket.

Article Snippet: The concentrations of PB118 in n -octanol and water were measured by LC–MS (Agilent 6310 ion trap mass spectrometer).

Techniques: Labeling, Binding Assay

Journal: Acta Pharmaceutica Sinica. B

Article Title: Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

doi: 10.1016/j.apsb.2022.05.017

Figure Lengend Snippet: ADME/PK studies of PB118 a .

Article Snippet: The concentrations of PB118 in n -octanol and water were measured by LC–MS (Agilent 6310 ion trap mass spectrometer).

Techniques: In Vitro, Inhibition, Protein Binding, In Vivo

Journal: Acta Pharmaceutica Sinica. B

Article Title: Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

doi: 10.1016/j.apsb.2022.05.017

Figure Lengend Snippet: Radiosynthesis of [ 18 F]PB118. Reagents and conditions: (i) K 222 /[ 18 F]KF, Cu 2 (OTf) 2 (py) 4 , DMA, 120 °C, 20 min. RCY: 14%–16% (non-decay-corrected, n = 6); (ii) 0.6 mol/L NaOH, NH 2 OH (50% ( w / w ) in H 2 O), MeOH/THF (1:1), 10 min. RCY: 66%–70% (non-decay-corrected). Molar activity: 110 GBq/μmol (EOB).

Article Snippet: The concentrations of PB118 in n -octanol and water were measured by LC–MS (Agilent 6310 ion trap mass spectrometer).

Techniques: Activity Assay

Journal: Acta Pharmaceutica Sinica. B

Article Title: Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

doi: 10.1016/j.apsb.2022.05.017

Figure Lengend Snippet: PET imaging studies of [ 18 F]PB118 in WT mice. (A) Representative PET images of [ 18 F]PB118 focus on the mice brain (0–60 min; midbrain axial); (B) the baseline and blocking (2.0 mg/kg unlabeled PB118 and 2.0 mg/kg HDAC6 selective inhibitor tubastatin A) time–activity curves of [ 18 F]PB118 in the mice whole brain ( n = 4). The data were expressed as mean ± SD, n = 4.

Article Snippet: The concentrations of PB118 in n -octanol and water were measured by LC–MS (Agilent 6310 ion trap mass spectrometer).

Techniques: Imaging, Blocking Assay, Activity Assay

Journal: Acta Pharmaceutica Sinica. B

Article Title: Development of a potential PET probe for HDAC6 imaging in Alzheimer's disease

doi: 10.1016/j.apsb.2022.05.017

Figure Lengend Snippet: PET imaging studies of [ 18 F]PB118. (A) Representative summed PET/CT images (0–60 min, show as sagittal slices, coronal slices, and midbrain axial) focus on the brain of WT mice and (B) 5xFAD mice. (C) TACs of [ 18 F]PB118 in the whole brain of WT and 5xFAD mice. (D) the area under the curve (AUC) of TACs in (C) shows a statistically significant difference in [ 18 F]PB118 brain uptake in WT and 5xFAD mice. (E) Regional brain biodistribution of [ 18 F]PB118 in cortex, cerebellum, thalamus, hypothalamus, striatum, hippocampus, and amygdala in WT and 5xFAD mice. (F)–(G) Representative PET/MR baseline and blocking SUV images of a rhesus monkey brain, averaged from 90 to 120 min, after intravenous injection of [ 18 F]PB118. (H)–(I) TACs of [ 18 F]PB118 in the regions of interest in baseline and blocking studies. All data are expressed as mean ± SD, n = 4; Asterisks indicate statistical significance. ∗ P < 0.05, ∗∗ P ≤ 0.01, and ∗∗∗ P ≤ 0.001.

Article Snippet: The concentrations of PB118 in n -octanol and water were measured by LC–MS (Agilent 6310 ion trap mass spectrometer).

Techniques: Imaging, Positron Emission Tomography-Computed Tomography, Positron Emission Tomography-Magnetic Resonance Imaging, Blocking Assay, Injection