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. 2023 Sep;43(9):1612-1624.
doi: 10.1177/0271678X231173185. Epub 2023 Apr 27.

Isoflurane and ketamine-xylazine modify pharmacokinetics of [18F]SynVesT-1 in the mouse brain

Alan Miranda  1 , Daniele Bertoglio  1 , Caro De Weerdt  1 , Steven Staelens  1 , Jeroen Verhaeghe  1
Affiliations

Isoflurane and ketamine-xylazine modify pharmacokinetics of [18F]SynVesT-1 in the mouse brain

Alan Miranda et al. J Cereb Blood Flow Metab. 2023 Sep.

Abstract

We investigated the effect of isoflurane and ketamine-xylazine anesthesia on the positron emission tomography (PET) tracer [18F]SynVesT-1 in the mouse brain. [18F]SynVesT-1 PET scans were performed in C57BL/6J mice in five conditions: isoflurane anesthesia (ANISO), ketamine-xylazine (ANKX), awake freely moving (AW), awake followed by isoflurane administration (AW/ANISO) or followed by ketamine-xylazine (AW/ANKX) 20 min post tracer injection. ANISO, ANKX and AW scans were also performed in mice administered with levetiracetam (LEV, 200 mg/kg) to assess non-displaceable binding. Metabolite analysis was performed in ANISO, ANKX and AW mice. Finally, in vivo autoradiography in ANISO, ANKX and AW mice at 30 min post-injection was performed for validation. Kinetic modeling, with a metabolite corrected image derived input function, was performed to calculate total and non-displaceable volume of distribution (VT(IDIF)). VT(IDIF) was higher in ANISO compared to AW (p < 0.0001) while VT(IDIF) in ANKX was lower compared with AW (p < 0.0001). Non-displaceable VT(IDIF) was significantly different between ANISO and AW, but not between ANKX and AW. Change in the TAC washout was observed after administration of either isoflurane or ketamine-xylazine. Observed changes in tracer kinetics and volume of distribution might be explained by physiological changes due to anesthesia, as well as by induced cellular effects.

Keywords: [18F]SynVesT-1; isoflurane; ketamine-xylazine; mouse brain; positron emission tomography.

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Conflict of interest statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Regional [18F]SynVesT-1 volume of distribution (VT(IDIF)) in mice from (a) group 1 (ANISO, AW), (b) group 2 (ANISO, AW, with LEV blocking 200 mg/kg), (c) group 3 (ANKX, AW) and (d) group 4 (ANKX,AW, with LEV blocking 200 mg/kg), calculated with Logan plot. Plots y-axis scale is different.
Figure 2.
Figure 2.
Average brain [18F]SynVesT-1 VT(IDIF) maps in isoflurane anesthetized and awake mice without (a group 1) and with (b, group 2) levetiracetam (LEV) blocking (200 mg/kg). (c) Relative (to the whole brain) VT(IDIF) in mice without LEV blocking. The red arrow points to medulla region and (d) Magnetic resonance for anatomical reference.
Figure 3.
Figure 3.
Average brain [18F]SynVesT-1 VT(IDIF) maps in ketamine-xylazine anesthetized and awake mice without (a group 3) and with (b, group 4) levetiracetam (LEV) blocking (200 mg/kg). (c) Relative (to the whole brain) VT(IDIF) in mice without LEV blocking. Red arrows points to cortex and medulla and (d) Magnetic resonance for anatomical reference.
Figure 4.
Figure 4.
(a) Mean regional SUV time activity curves for ANISO, AW, and AW/ANISO conditions during 2 hours scans. (b) Mean regional SUV time activity curves for ANKX, AW, and AW/ANKX conditions during 1 hour scans. Time axis is different in column (a) and (b). CTX: cortex; CP: caudate putamen; TH: thalamus; HC: hippocampus; CB: cerebellum.
Figure 5.
Figure 5.
(a) Autoradiography regional brain quantification in animals under isoflurane, and ketamine-xylazine anesthesia, as well as in awake animals, in animals sacrificed 30 min tracer post-injection. (b) Regional brain quantification in brain PET images in ANISO, ANKX, and AW conditions, at 30 min tracer post-injection. (c) Correlation, and regression line, between brain mean regional quantification values (every point is a region), in ARG and PET at 30 min post-tracer injection, considering animals in the 3 conditions and (d) Example of brain autoradiography image and the different regions used for quantification.
See this image and copyright information in PMC

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