Abstract CT013: Osimertinib displays high brain exposure in healthy subjects with intact blood-brain barrier: a microdose positron emission tomography (PET) study with11C-labelled osimertinib

2018 ◽  
Author(s):  
Karthick Vishwanathan ◽  
Andrea Varrone ◽  
Katarina Varnas ◽  
Aurelija Jucaite ◽  
Zsolt Cselenyi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Healthy Subjects ◽  
Emission Tomography ◽  
Brain Barrier ◽  
High Brain ◽  
Blood Brain ◽  
Positron Emission ◽  
Brain Exposure

Hyperosmolar blood-brain barrier disruption in baboons: an in vivo study using positron emission tomography and rubidium-82

1996 ◽  
Vol 84 (3) ◽  
pp. 494-502 ◽  
Author(s):  
Bernhard Zünkeler ◽  
Richard E. Carson ◽  
Jeffrey Olson ◽  
Ronald G. Blasberg ◽  
Mary Girton ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Brain Tumors ◽  
Blood Brain Barrier ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Blood Brain ◽  
Positron Emission ◽  
The Mean ◽  
Rubidium 82

✓ Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (82Rb, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8- to 15-minute intervals after BBB disruption. The mean influx constant (K1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray- and white-matter brain regions was 4.9 ± 2.4 µl/min/ml (± standard deviation) at baseline and increased more than 100% (ΔK1 = 9.4 ± 5.1 µl/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K1 correlated directly with the total amount of mannitol administered (p < 0.005). Vascular permeability returned to baseline with a halftime of 24.0 ± 14.3 minutes. The mean brain plasma volume rose by 0.57 ± 0.34 ml/100 ml in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors.

scholarly journals Approaching Complete Inhibition of P-Glycoprotein at the Human Blood–Brain Barrier: An (R)-[11C]Verapamil PET Study

2015 ◽  
Vol 35 (5) ◽  
pp. 743-746 ◽  
Author(s):  
Martin Bauer ◽  
Rudolf Karch ◽  
Markus Zeitlinger ◽  
Cécile Philippe ◽  
Kerstin Römermann ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Distribution Volume ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Whole Brain ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Positron Emission ◽  
Pet Scans

As P-glycoprotein (Pgp) inhibition at the blood–brain barrier (BBB) after administration of a single dose of tariquidar is transient, we performed positron emission tomography (PET) scans with the Pgp substrate ( R)-[11C]verapamil in five healthy volunteers during continuous intravenous tariquidar infusion. Total distribution volume ( VT) of ( R)-[11C]verapamil in whole-brain gray matter increased by 273 ± 78% relative to baseline scans without tariquidar, which was higher than previously reported VT increases. During tariquidar infusion whole-brain VT was comparable to VT in the pituitary gland, a region not protected by the BBB, which suggested that we were approaching complete Pgp inhibition at the human BBB.

P-glycoprotein at the Blood-Brain Barrier and Analysis of Drug Transport with Positron-Emission Tomography

2001 ◽  
Vol 41 (7) ◽  
pp. 48-54 ◽  
Author(s):  
N. H. Hendrikse ◽  
J. Bart ◽  
E.G.E. de Vries ◽  
H.J.M. Groen ◽  
W.T.A. van der Graaf ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Drug Transport ◽  
Emission Tomography ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Positron Emission

scholarly journals Diphenhydramine as a selective probe to study H+-antiporter function at the blood–brain barrier: Application to [11C]diphenhydramine positron emission tomography imaging

2016 ◽  
Vol 37 (6) ◽  
pp. 2185-2195 ◽  
Author(s):  
Sylvain Auvity ◽  
Hélène Chapy ◽  
Sébastien Goutal ◽  
Fabien Caillé ◽  
Benoit Hosten ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Positron Emission Tomography Imaging ◽  
Emission Tomography ◽  
Brain Barrier ◽  
Tomography Imaging ◽  
Blood Brain ◽  
Positron Emission ◽  
The Brain

Diphenhydramine, a sedative histamine H1-receptor (H1R) antagonist, was evaluated as a probe to measure drug/H+-antiporter function at the blood–brain barrier. In situ brain perfusion experiments in mice and rats showed that diphenhydramine transport at the blood–brain barrier was saturable, following Michaelis–Menten kinetics with a Km = 2.99 mM and Vmax = 179.5 nmol s−1 g−1. In the pharmacological plasma concentration range the carrier-mediated component accounted for 77% of diphenhydramine influx while passive diffusion accounted for only 23%. [14C]Diphenhydramine blood–brain barrier transport was proton and clonidine sensitive but was influenced by neither tetraethylammonium, a MATE1 (SLC47A1), and OCT/OCTN (SLC22A1-5) modulator, nor P-gp/Bcrp (ABCB1a/1b/ABCG2) deficiency. Brain and plasma kinetics of [11C]diphenhydramine were measured by positron emission tomography imaging in rats. [11C]Diphenhydramine kinetics in different brain regions were not influenced by displacement with 1 mg kg−1 unlabeled diphenhydramine, indicating the specificity of the brain positron emission tomography signal for blood–brain barrier transport activity over binding to any central nervous system target in vivo. [11C]Diphenhydramine radiometabolites were not detected in the brain 15 min after injection, allowing for the reliable calculation of [11C]diphenhydramine brain uptake clearance (Clup = 0.99 ± 0.18 mL min−1 cm−3). Diphenhydramine is a selective and specific H+-antiporter substrate. [11C]Diphenhydramine positron emission tomography imaging offers a reliable and noninvasive method to evaluate H+-antiporter function at the blood–brain barrier.

scholarly journals Factors Governing P-Glycoprotein-Mediated Drug–Drug Interactions at the Blood–Brain Barrier Measured with Positron Emission Tomography

2015 ◽  
Vol 12 (9) ◽  
pp. 3214-3225 ◽  
Author(s):  
Thomas Wanek ◽  
Kerstin Römermann ◽  
Severin Mairinger ◽  
Johann Stanek ◽  
Michael Sauberer ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Drug Interactions ◽  
Blood Brain Barrier ◽  
Emission Tomography ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Positron Emission

P-glycoprotein at the Blood-Brain Barrier and Analysis of Drug Transport with Positron-Emission Tomography

2001 ◽  
Vol 41 (99) ◽  
pp. 48-54 ◽  
Author(s):  
N.H. Hendrikse ◽  
J. Bart ◽  
E.G.E. de Vries ◽  
H.J.M. Groen ◽  
W.T.A. van der Graaf ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Blood Brain Barrier ◽  
Drug Transport ◽  
Emission Tomography ◽  
Brain Barrier ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Positron Emission
Sign in / Sign up

Export Citation Format

Share Document