Influence of P-Glycoprotein Inhibition or Deficiency at the Blood–Brain Barrier on 18F-2-Fluoro-2-Deoxy-d-glucose (18F-FDG) Brain Kinetics

Abstract

ABSTRACT. The fluorinated D-glucose analog 18 F-2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact 18 F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate 18 F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1 , k 2 , k 3 , V T , and CMR Glc . The lack of P-gp effect on in vivo 18 F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates 18 F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. 18F-FDG is not a P-gp substrate at the BBB and 18 F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

Differential influence of propofol and isoflurane anesthesia in a non‐human primate on the brain kinetics and binding of [18F]DPA‐714, a positron emission tomography imaging marker of glial activation

“…Non‐human primates are widely used for neuroscience studies because they provide relevant data regarding brain function and allow fast translation of preclinical concepts to humans (Roelfsema & Treue, ). Baboons are widely used for PET imaging, given the size of the brain compared with PET imaging spatial resolution (Tournier et al ., ). Moreover, baboons allow suitable blood sampling for accurate measure of metabolite‐corrected input function to test the hypothesis of a differential influence of anesthetic protocols on [ 18 F]DPA‐714 plasma kinetics.…”

Imaging the impact of cyclosporin A and dipyridamole on P-glycoprotein (ABCB1) function at the blood-brain barrier: A [11C]-N-desmethyl-loperamide PET study in nonhuman primates

“…After being intubated, baboons were artificially ventilated, maintained anesthetized with 66% N 2 O/1% isoflurane. PET data were acquired as previously described (Tournier et al, 2015).…”

Comparative test-retest variability of outcome parameters derived from brain [18F]FDG PET studies in non-human primates

“…Over the last four decades, [ 18 F]FDG brain PET has mostly been used in the context of neurodegenerative diseases and brain tumor research [2]. As non-invasive technique, [ 18 F]FDG PET has also been used to monitor the regional effects of potential CNS drugs and/or pharmacological challenges with repeated scans [3][4][5][6]. More recently, [ 18 F]FDG brain PET was also applied to unravel brain networks in healthy and diseased brains [7].…”